Pulmonology

A blood test for elevated carbon dioxide may be used in screening adults for obesity hypoventilation syndrome, according to new guidelines.

Obese adults with sleep-disordered breathing and increased blood carbon dioxide levels during the day are likely to have obesity hypoventilation syndrome (OHS), a result of shallow or slow breathing that can lead to respiratory failure, heart failure, pulmonary hypertension, and death. Pulmonologists and sleep specialists may be the first to see and diagnose patients with OHS in the outpatient setting, while other cases are diagnosed in the hospital when patients present with hypercapnic respiratory failure.

Screening for OHS usually involves measuring arterial blood gases, which is not standard practice in outpatient clinics. Patients often remain undiagnosed and untreated until late in the course of the disease, according to the American Thoracic Society, which in August published a new diagnosis and management guideline aiming to boost early diagnosis and reduce variability in treatment (Am J Respir Crit Care Med. 2019;200:3,e6–e24).

The guideline authors, led by Babak Mokhlesi, MD, of the University of Chicago, recommend a simpler screening method – measuring serum bicarbonate only – to rule out OHS in obese patients with nighttime breathing problems.

Serum bicarbonate should be measured in obese patients with sleep-disordered breathing and a low likelihood of OHS, Dr. Mokhlesi and colleagues recommend in the guideline. If serum bicarbonate is below 27 mmol/L, it is not necessary to conduct further testing as the patient is unlikely to have OHS.

In patients whose serum bicarbonate is higher than 27 mmol/L, or who are strongly suspected of having OHS at presentation because of severe obesity or other symptoms, arterial blood gases should be measured and a sleep study conducted. The guideline authors said that there is insufficient evidence to recommend that pulse oximetry be used in the diagnostic pathway for OHS.

First-line treatment for stable, ambulatory patients with OHS should be positive airway pressure during sleep, rather than noninvasive ventilation, Dr. Mokhlesi and colleagues concluded. For patients with comorbid obstructive sleep apnea – as many as 70% of OHS patients also have OSA – the first-line treatment should be continuous positive airway pressure (CPAP) at night, the guideline states.

Patients hospitalized with respiratory failure and suspected of having OHS should be discharged with noninvasive ventilation until diagnostic procedures can be performed, along with PAP titration in a sleep lab.

In patients initially treated with CPAP who remain symptomatic or whose blood carbon dioxide does not improve, noninvasive ventilation can be tried, the guidelines say. Finally, patients diagnosed with OHS should be guided to weight loss interventions with the aim of reducing body weight by 25%-30%. This can include referral for bariatric surgery in patients without contraindications.

Dr. Mokhlesi and colleagues acknowledged that all of the recommendations contained in the guideline are classed as “conditional,” based on the quality of evidence assessed.

The American Thoracic Society funded the study. Dr. Mokhlesi and 7 coauthors disclosed financial conflicts of interest, while an additional 13 coauthors had none. Disclosures can be found on the AJRCCM website.

SOURCE: Mokhlesi B et al. Am J Respir Crit Care Med. 2019;200:3,e6-e24

A blood test for elevated carbon dioxide may be used in screening adults for obesity hypoventilation syndrome, according to new guidelines.

Obese adults with sleep-disordered breathing and increased blood carbon dioxide levels during the day are likely to have obesity hypoventilation syndrome (OHS), a result of shallow or slow breathing that can lead to respiratory failure, heart failure, pulmonary hypertension, and death. Pulmonologists and sleep specialists may be the first to see and diagnose patients with OHS in the outpatient setting, while other cases are diagnosed in the hospital when patients present with hypercapnic respiratory failure.

Screening for OHS usually involves measuring arterial blood gases, which is not standard practice in outpatient clinics. Patients often remain undiagnosed and untreated until late in the course of the disease, according to the American Thoracic Society, which in August published a new diagnosis and management guideline aiming to boost early diagnosis and reduce variability in treatment (Am J Respir Crit Care Med. 2019;200:3,e6–e24).

The guideline authors, led by Babak Mokhlesi, MD, of the University of Chicago, recommend a simpler screening method – measuring serum bicarbonate only – to rule out OHS in obese patients with nighttime breathing problems.

Serum bicarbonate should be measured in obese patients with sleep-disordered breathing and a low likelihood of OHS, Dr. Mokhlesi and colleagues recommend in the guideline. If serum bicarbonate is below 27 mmol/L, it is not necessary to conduct further testing as the patient is unlikely to have OHS.

In patients whose serum bicarbonate is higher than 27 mmol/L, or who are strongly suspected of having OHS at presentation because of severe obesity or other symptoms, arterial blood gases should be measured and a sleep study conducted. The guideline authors said that there is insufficient evidence to recommend that pulse oximetry be used in the diagnostic pathway for OHS.

First-line treatment for stable, ambulatory patients with OHS should be positive airway pressure during sleep, rather than noninvasive ventilation, Dr. Mokhlesi and colleagues concluded. For patients with comorbid obstructive sleep apnea – as many as 70% of OHS patients also have OSA – the first-line treatment should be continuous positive airway pressure (CPAP) at night, the guideline states.

Patients hospitalized with respiratory failure and suspected of having OHS should be discharged with noninvasive ventilation until diagnostic procedures can be performed, along with PAP titration in a sleep lab.

In patients initially treated with CPAP who remain symptomatic or whose blood carbon dioxide does not improve, noninvasive ventilation can be tried, the guidelines say. Finally, patients diagnosed with OHS should be guided to weight loss interventions with the aim of reducing body weight by 25%-30%. This can include referral for bariatric surgery in patients without contraindications.

Dr. Mokhlesi and colleagues acknowledged that all of the recommendations contained in the guideline are classed as “conditional,” based on the quality of evidence assessed.

The American Thoracic Society funded the study. Dr. Mokhlesi and 7 coauthors disclosed financial conflicts of interest, while an additional 13 coauthors had none. Disclosures can be found on the AJRCCM website.

SOURCE: Mokhlesi B et al. Am J Respir Crit Care Med. 2019;200:3,e6-e24

A blood test for elevated carbon dioxide may be used in screening adults for obesity hypoventilation syndrome, according to new guidelines.

Obese adults with sleep-disordered breathing and increased blood carbon dioxide levels during the day are likely to have obesity hypoventilation syndrome (OHS), a result of shallow or slow breathing that can lead to respiratory failure, heart failure, pulmonary hypertension, and death. Pulmonologists and sleep specialists may be the first to see and diagnose patients with OHS in the outpatient setting, while other cases are diagnosed in the hospital when patients present with hypercapnic respiratory failure.

Screening for OHS usually involves measuring arterial blood gases, which is not standard practice in outpatient clinics. Patients often remain undiagnosed and untreated until late in the course of the disease, according to the American Thoracic Society, which in August published a new diagnosis and management guideline aiming to boost early diagnosis and reduce variability in treatment (Am J Respir Crit Care Med. 2019;200:3,e6–e24).

The guideline authors, led by Babak Mokhlesi, MD, of the University of Chicago, recommend a simpler screening method – measuring serum bicarbonate only – to rule out OHS in obese patients with nighttime breathing problems.

Serum bicarbonate should be measured in obese patients with sleep-disordered breathing and a low likelihood of OHS, Dr. Mokhlesi and colleagues recommend in the guideline. If serum bicarbonate is below 27 mmol/L, it is not necessary to conduct further testing as the patient is unlikely to have OHS.

In patients whose serum bicarbonate is higher than 27 mmol/L, or who are strongly suspected of having OHS at presentation because of severe obesity or other symptoms, arterial blood gases should be measured and a sleep study conducted. The guideline authors said that there is insufficient evidence to recommend that pulse oximetry be used in the diagnostic pathway for OHS.

First-line treatment for stable, ambulatory patients with OHS should be positive airway pressure during sleep, rather than noninvasive ventilation, Dr. Mokhlesi and colleagues concluded. For patients with comorbid obstructive sleep apnea – as many as 70% of OHS patients also have OSA – the first-line treatment should be continuous positive airway pressure (CPAP) at night, the guideline states.

Patients hospitalized with respiratory failure and suspected of having OHS should be discharged with noninvasive ventilation until diagnostic procedures can be performed, along with PAP titration in a sleep lab.

In patients initially treated with CPAP who remain symptomatic or whose blood carbon dioxide does not improve, noninvasive ventilation can be tried, the guidelines say. Finally, patients diagnosed with OHS should be guided to weight loss interventions with the aim of reducing body weight by 25%-30%. This can include referral for bariatric surgery in patients without contraindications.

Dr. Mokhlesi and colleagues acknowledged that all of the recommendations contained in the guideline are classed as “conditional,” based on the quality of evidence assessed.

The American Thoracic Society funded the study. Dr. Mokhlesi and 7 coauthors disclosed financial conflicts of interest, while an additional 13 coauthors had none. Disclosures can be found on the AJRCCM website.

SOURCE: Mokhlesi B et al. Am J Respir Crit Care Med. 2019;200:3,e6-e24

Vitamin E acetate is one possible culprit in the mysterious vaping-associated lung disease that has killed three patients, sickened 450, and baffled clinicians and investigators all summer.

mauro grigollo/Thinkstock

Another death may be linked to the disorder, officials said during a joint press briefing held by the Centers for Disease Control and Prevention and the Food and Drug Administration. In all, 450 potential cases have been reported and e-cigarette use confirmed in 215. Cases have occurred in 33 states and one territory. A total of 84% of the patients reported having used tetrahydrocannabinol (THC) products in e-cigarette devices.

A preliminary report on the situation by Jennifer Layden, MD, of the department of public health in Illinois and colleagues – including a preliminary case definition – was simultaneously released in the New England Journal of Medicine (2019 Sep 6. doi: 10.1056/NEJMoa1911614).

No single device or substance was common to all the cases, leading officials to issue a blanket warning against e-cigarettes, especially those containing THC.

“We believe a chemical exposure is likely related, but more information is needed to determine what substances. Some labs have identified vitamin E acetate in some samples,” said Dana Meaney-Delman, MD, MPH, incident manager, CDC 2019 Lung Injury Response. “Continued investigation is needed to identify the risk associated with a specific product or substance.”

Besides vitamin E acetate, federal labs are looking at other cannabinoids, cutting agents, diluting agents, pesticides, opioids, and toxins.

Officials also issued a general warning about the products. Youths, young people, and pregnant women should never use e-cigarettes, they cautioned, and no one should buy them from a noncertified source, a street vendor, or a social contact. Even cartridges originally obtained from a certified source should never have been altered in any way.

Dr. Layden and colleagues reported that bilateral lung infiltrates was characterized in 98% of the 53 patients hospitalized with the recently reported e-cigarette–induced lung injury. Nonspecific constitutional symptoms, including fever, chills, weight loss, and fatigue, were present in all of the patients.

Patients may show some symptoms days or even weeks before acute respiratory failure develops, and many had sought medical help before that. All presented with bilateral lung infiltrates, part of an evolving case definition. Many complained of nonspecific constitutional symptoms, including fever, chills, gastrointestinal symptoms, and weight loss. Of the patients who underwent bronchoscopy, many were diagnosed as having lipoid pneumonia, a rare condition characterized by lipid-laden macrophages.

“We don’t know the significance of the lipid-containing macrophages, and we don’t know if the lipids are endogenous or exogenous,” Dr. Meaney-Delman said.

The incidence of such cases appears to be rising rapidly, Dr. Layden noted. An epidemiologic review of cases in Illinois found that the mean monthly rate of visits related to severe respiratory illness in June-August was twice that observed during the same months last year.
 

msullivan@mdedge.com

SOURCE: Layden JE et al. N Engl J Med. 2019 Sep 6. doi: 1 0.1056/NEJMoa1911614.

Vitamin E acetate is one possible culprit in the mysterious vaping-associated lung disease that has killed three patients, sickened 450, and baffled clinicians and investigators all summer.

mauro grigollo/Thinkstock

Another death may be linked to the disorder, officials said during a joint press briefing held by the Centers for Disease Control and Prevention and the Food and Drug Administration. In all, 450 potential cases have been reported and e-cigarette use confirmed in 215. Cases have occurred in 33 states and one territory. A total of 84% of the patients reported having used tetrahydrocannabinol (THC) products in e-cigarette devices.

A preliminary report on the situation by Jennifer Layden, MD, of the department of public health in Illinois and colleagues – including a preliminary case definition – was simultaneously released in the New England Journal of Medicine (2019 Sep 6. doi: 10.1056/NEJMoa1911614).

No single device or substance was common to all the cases, leading officials to issue a blanket warning against e-cigarettes, especially those containing THC.

“We believe a chemical exposure is likely related, but more information is needed to determine what substances. Some labs have identified vitamin E acetate in some samples,” said Dana Meaney-Delman, MD, MPH, incident manager, CDC 2019 Lung Injury Response. “Continued investigation is needed to identify the risk associated with a specific product or substance.”

Besides vitamin E acetate, federal labs are looking at other cannabinoids, cutting agents, diluting agents, pesticides, opioids, and toxins.

Officials also issued a general warning about the products. Youths, young people, and pregnant women should never use e-cigarettes, they cautioned, and no one should buy them from a noncertified source, a street vendor, or a social contact. Even cartridges originally obtained from a certified source should never have been altered in any way.

Dr. Layden and colleagues reported that bilateral lung infiltrates was characterized in 98% of the 53 patients hospitalized with the recently reported e-cigarette–induced lung injury. Nonspecific constitutional symptoms, including fever, chills, weight loss, and fatigue, were present in all of the patients.

Patients may show some symptoms days or even weeks before acute respiratory failure develops, and many had sought medical help before that. All presented with bilateral lung infiltrates, part of an evolving case definition. Many complained of nonspecific constitutional symptoms, including fever, chills, gastrointestinal symptoms, and weight loss. Of the patients who underwent bronchoscopy, many were diagnosed as having lipoid pneumonia, a rare condition characterized by lipid-laden macrophages.

“We don’t know the significance of the lipid-containing macrophages, and we don’t know if the lipids are endogenous or exogenous,” Dr. Meaney-Delman said.

The incidence of such cases appears to be rising rapidly, Dr. Layden noted. An epidemiologic review of cases in Illinois found that the mean monthly rate of visits related to severe respiratory illness in June-August was twice that observed during the same months last year.
 

msullivan@mdedge.com

SOURCE: Layden JE et al. N Engl J Med. 2019 Sep 6. doi: 1 0.1056/NEJMoa1911614.

Vitamin E acetate is one possible culprit in the mysterious vaping-associated lung disease that has killed three patients, sickened 450, and baffled clinicians and investigators all summer.

mauro grigollo/Thinkstock

Another death may be linked to the disorder, officials said during a joint press briefing held by the Centers for Disease Control and Prevention and the Food and Drug Administration. In all, 450 potential cases have been reported and e-cigarette use confirmed in 215. Cases have occurred in 33 states and one territory. A total of 84% of the patients reported having used tetrahydrocannabinol (THC) products in e-cigarette devices.

A preliminary report on the situation by Jennifer Layden, MD, of the department of public health in Illinois and colleagues – including a preliminary case definition – was simultaneously released in the New England Journal of Medicine (2019 Sep 6. doi: 10.1056/NEJMoa1911614).

No single device or substance was common to all the cases, leading officials to issue a blanket warning against e-cigarettes, especially those containing THC.

“We believe a chemical exposure is likely related, but more information is needed to determine what substances. Some labs have identified vitamin E acetate in some samples,” said Dana Meaney-Delman, MD, MPH, incident manager, CDC 2019 Lung Injury Response. “Continued investigation is needed to identify the risk associated with a specific product or substance.”

Besides vitamin E acetate, federal labs are looking at other cannabinoids, cutting agents, diluting agents, pesticides, opioids, and toxins.

Officials also issued a general warning about the products. Youths, young people, and pregnant women should never use e-cigarettes, they cautioned, and no one should buy them from a noncertified source, a street vendor, or a social contact. Even cartridges originally obtained from a certified source should never have been altered in any way.

Dr. Layden and colleagues reported that bilateral lung infiltrates was characterized in 98% of the 53 patients hospitalized with the recently reported e-cigarette–induced lung injury. Nonspecific constitutional symptoms, including fever, chills, weight loss, and fatigue, were present in all of the patients.

Patients may show some symptoms days or even weeks before acute respiratory failure develops, and many had sought medical help before that. All presented with bilateral lung infiltrates, part of an evolving case definition. Many complained of nonspecific constitutional symptoms, including fever, chills, gastrointestinal symptoms, and weight loss. Of the patients who underwent bronchoscopy, many were diagnosed as having lipoid pneumonia, a rare condition characterized by lipid-laden macrophages.

“We don’t know the significance of the lipid-containing macrophages, and we don’t know if the lipids are endogenous or exogenous,” Dr. Meaney-Delman said.

The incidence of such cases appears to be rising rapidly, Dr. Layden noted. An epidemiologic review of cases in Illinois found that the mean monthly rate of visits related to severe respiratory illness in June-August was twice that observed during the same months last year.
 

msullivan@mdedge.com

SOURCE: Layden JE et al. N Engl J Med. 2019 Sep 6. doi: 1 0.1056/NEJMoa1911614.

Michigan Governor Gretchen Whitmer (D) has ordered the state Department of Health and Human Services to issue emergency rules banning the sale of flavored nicotine vaping products in retail stores and online.

VlaDee/Getty Images

The state health agency is expected to issue rules outlining the ban within the next 30 days. The emergency ban will be in effect for 6 months, with the possibility of a 6-month extension while state health regulators craft rules to set in place a permanent ban.

The ban will also prohibit “misleading marketing of vaping products, including the use of terms like ‘clean,’ ‘safe,’ and ‘healthy,’ that perpetuate beliefs that these products are harmless,” according to a statement issued by Gov. Whitmer.

Companies selling vaping products “are using candy flavors to hook children on nicotine and misleading claims to promote the belief that these products are safe,” she said in a statement. “That ends today. Our kids deserve leaders who are going to fight to protect them. These bold steps will finally put an end to these irresponsible and deceptive practices and protect Michiganders’ public health.”

The ban also will cover mint- and menthol-flavors in addition to sweet flavors but will not ban tobacco-flavored e-cigarette products.

The American Academy of Pediatrics, American Heart Association, American Lung Association, American Cancer Society Cancer Action Network and other organizations praised the action taken by the state, calling the steps “necessary and appropriate.”

“The need for action is even more urgent in light of the recent outbreak of severe lung illness associated with e-cigarette use and the failure of the U.S. Food and Drug Administration to take strong regulatory action such as prohibiting the sale of the flavored products nationwide that have attracted shocking numbers of our nation’s youth,” the organizations said in a statement.

The groups noted that “health authorities are investigating reports of severe respiratory illness associated with e-cigarette use in at least 215 people ... in 25 states,” adding that many are youth and young adults.

The U.S. Department of Health & Human Services Secretary Alex Azar said in an Aug. 30 statement that the federal government is “using every tool we have to get to the bottom of this deeply concerning outbreak of illness in Americans who use e-cigarettes. More broadly, we will continue using every regulatory and enforcement power we have to stop the epidemic of youth e-cigarette use.”

HHS noted that no single substance or e-cigarette product has been consistently associated with the reports of illness. The agency called upon clinicians to report any new cases as appropriate to their state and local health departments.

Gov. Whitmer earlier this year signed bills that clarify that it is illegal to sell nontraditional nicotine products to minors, but the governor’s statement notes her criticism that the bills did not go far enough to protect the state’s youth, necessitating this further action.

gtwachtman@mdedge.com

Michigan Governor Gretchen Whitmer (D) has ordered the state Department of Health and Human Services to issue emergency rules banning the sale of flavored nicotine vaping products in retail stores and online.

VlaDee/Getty Images

The state health agency is expected to issue rules outlining the ban within the next 30 days. The emergency ban will be in effect for 6 months, with the possibility of a 6-month extension while state health regulators craft rules to set in place a permanent ban.

The ban will also prohibit “misleading marketing of vaping products, including the use of terms like ‘clean,’ ‘safe,’ and ‘healthy,’ that perpetuate beliefs that these products are harmless,” according to a statement issued by Gov. Whitmer.

Companies selling vaping products “are using candy flavors to hook children on nicotine and misleading claims to promote the belief that these products are safe,” she said in a statement. “That ends today. Our kids deserve leaders who are going to fight to protect them. These bold steps will finally put an end to these irresponsible and deceptive practices and protect Michiganders’ public health.”

The ban also will cover mint- and menthol-flavors in addition to sweet flavors but will not ban tobacco-flavored e-cigarette products.

The American Academy of Pediatrics, American Heart Association, American Lung Association, American Cancer Society Cancer Action Network and other organizations praised the action taken by the state, calling the steps “necessary and appropriate.”

“The need for action is even more urgent in light of the recent outbreak of severe lung illness associated with e-cigarette use and the failure of the U.S. Food and Drug Administration to take strong regulatory action such as prohibiting the sale of the flavored products nationwide that have attracted shocking numbers of our nation’s youth,” the organizations said in a statement.

The groups noted that “health authorities are investigating reports of severe respiratory illness associated with e-cigarette use in at least 215 people ... in 25 states,” adding that many are youth and young adults.

The U.S. Department of Health & Human Services Secretary Alex Azar said in an Aug. 30 statement that the federal government is “using every tool we have to get to the bottom of this deeply concerning outbreak of illness in Americans who use e-cigarettes. More broadly, we will continue using every regulatory and enforcement power we have to stop the epidemic of youth e-cigarette use.”

HHS noted that no single substance or e-cigarette product has been consistently associated with the reports of illness. The agency called upon clinicians to report any new cases as appropriate to their state and local health departments.

Gov. Whitmer earlier this year signed bills that clarify that it is illegal to sell nontraditional nicotine products to minors, but the governor’s statement notes her criticism that the bills did not go far enough to protect the state’s youth, necessitating this further action.

gtwachtman@mdedge.com

Michigan Governor Gretchen Whitmer (D) has ordered the state Department of Health and Human Services to issue emergency rules banning the sale of flavored nicotine vaping products in retail stores and online.

VlaDee/Getty Images

The state health agency is expected to issue rules outlining the ban within the next 30 days. The emergency ban will be in effect for 6 months, with the possibility of a 6-month extension while state health regulators craft rules to set in place a permanent ban.

The ban will also prohibit “misleading marketing of vaping products, including the use of terms like ‘clean,’ ‘safe,’ and ‘healthy,’ that perpetuate beliefs that these products are harmless,” according to a statement issued by Gov. Whitmer.

Companies selling vaping products “are using candy flavors to hook children on nicotine and misleading claims to promote the belief that these products are safe,” she said in a statement. “That ends today. Our kids deserve leaders who are going to fight to protect them. These bold steps will finally put an end to these irresponsible and deceptive practices and protect Michiganders’ public health.”

The ban also will cover mint- and menthol-flavors in addition to sweet flavors but will not ban tobacco-flavored e-cigarette products.

The American Academy of Pediatrics, American Heart Association, American Lung Association, American Cancer Society Cancer Action Network and other organizations praised the action taken by the state, calling the steps “necessary and appropriate.”

“The need for action is even more urgent in light of the recent outbreak of severe lung illness associated with e-cigarette use and the failure of the U.S. Food and Drug Administration to take strong regulatory action such as prohibiting the sale of the flavored products nationwide that have attracted shocking numbers of our nation’s youth,” the organizations said in a statement.

The groups noted that “health authorities are investigating reports of severe respiratory illness associated with e-cigarette use in at least 215 people ... in 25 states,” adding that many are youth and young adults.

The U.S. Department of Health & Human Services Secretary Alex Azar said in an Aug. 30 statement that the federal government is “using every tool we have to get to the bottom of this deeply concerning outbreak of illness in Americans who use e-cigarettes. More broadly, we will continue using every regulatory and enforcement power we have to stop the epidemic of youth e-cigarette use.”

HHS noted that no single substance or e-cigarette product has been consistently associated with the reports of illness. The agency called upon clinicians to report any new cases as appropriate to their state and local health departments.

Gov. Whitmer earlier this year signed bills that clarify that it is illegal to sell nontraditional nicotine products to minors, but the governor’s statement notes her criticism that the bills did not go far enough to protect the state’s youth, necessitating this further action.

gtwachtman@mdedge.com

According to World Health Organization estimates, 65 million people have moderate-to-severe chronic obstructive pulmonary disease (COPD) globally, and > 20 million patients with COPD are living in the US.¹ COPD is a progressive respiratory disease with a poor prognosis and a significant cause of morbidity and mortality in the US, especially within the Veterans Health Administration (VHA).² The prevalence of COPD is higher in veterans than it is in the general population. COPD prevalence in the adult US population has been estimated to be between 5% and 15%, whereas in veterans, prevalence estimates have ranged from about 5% to 43%.^3-5

COPD is associated with disabling dyspnea, muscle weakness, exercise intolerance, morbidity, and mortality. These symptoms and complications gradually and progressively compromise mobility, ability to perform daily functions, and decrease quality of life (QOL). Dyspnea, fatigue, and discomfort are the principal symptoms that negatively impact exercise tolerance.^6,7 Therefore, patients often intentionally limit their activities to avoid these uncomfortable feelings and adopt a more sedentary behavior. As the disease progresses, individuals with COPD will gradually need assistance in performing activities of daily living, which eventually leads to functional dependence.

Pulmonary rehabilitation (PR) is an essential component of the management of symptomatic patients with COPD. PR is an evidence-based, multidisciplinary, comprehensive intervention that includes exercise and education for patients with chronic respiratory disease.⁸ The key benefits of PR are clinical improvements in dyspnea, physical capacity, QOL, and reduced disability in patients with COPD and other respiratory diseases.^9-11 PR was found to improve respiratory health in veterans with COPD and decrease respiratory-related health care utilization.¹²

Despite the known benefits of PR, many patients with chronic respiratory diseases are not referred or do not have access to rehabilitation. Also, uptake of PR is low due to patient frailty, transportation issues, and other health care access problems.^13-15 Unfortunately, in the US health care system, access to PR and other nonpharmacologic treatments can be challenging due to a shortage of available PR programs, limited physician referral to existing programs, and lack of family and social support.¹⁶

There are only a few accredited PR programs in VHA facilities, and they tend to be located in urban areas.^12,17 Many patients have limited access to the PR programs due to geographic distance to the programs and transportation challenges (eg, limited ability to drive, cost of transportation). Moreover, veterans with COPD are likely to have limited mobility or are homebound due to experiencing shortness of breath with minimal exertion. Given the clear benefits of PR and the increasing impact of COPD on morbidity and mortality of the patients with COPD, strategies to improve the access and capacity of PR are needed. VA telehealth services allow for distribution of health care services in different geographic locations by providing access for the veterans who live in rural and highly rural areas. The most recent implementation of VA Video Connect (VVC) by the VHA provides a new avenue for clinicians to deliver much needed medical care into the veterans’ home.

COPD Telehealth Program

In this article, we describe the processes for developing and delivering an in-home, interactive, supervised PR program for veterans with severe COPD through VA telehealth service. The program consists of 18 sessions delivered over 6 weeks by a licensed physical therapist (PT) and a respiratory therapist (RT). The aims of the telehealth PR are to improve exercise tolerance, reduce dyspnea and fatigue, improve QOL, improve accessibility, and decrease costs and transportation burdens for patients with COPD. The program was developed, implemented and delivered by an interdisciplinary team, including a pulmonologist, PT, RT, physiatrist, and nonclinical supporting staff.

 

 

Patient Assessment

To be eligible to participate in the program the patient must: (1) have a forced expiratory volume (FEV₁) < 60%; ( 2) be medically stable and be receiving optimal medical management; (3) have no severe cognitive impairments; (4) be able to use a computer and e-mail; (5) be able to ambulate with or without a walking device; (6) be willing to enroll in a smoking cessation program or to stop smoking; (7) be willing to participate without prolonged interruption; and (8) have all visual and auditory impairments corrected with medical devices.

After referral and enrollment, patients receive medical and physical examinations by the PR team, including a pulmonologist, a PT, and a RT, to ensure that the patients are medically stable to undergo rehabilitation and to develop a tailored exercise program while being mindful of the comorbidities, limitations, and precautions, (eg, loss of balance, risk of fall, limited range of motion). The preprogram assessment includes a pulmonary function test, arterial blood gas test, Montreal Cognitive Assessment, Modified Medical Research Council Scale, St. George Respiratory Questionnaire, the COPD Assessment Test, Patient Health Questionnaire-9,Generalized Anxiety Disorder Assessment-7, Epworth Sleepiness Scale, Katz Index of Independence of Activities of Daily Living, medications and inhaler use, oxygen use, breathing pattern, coughing, 6-minute walk test, Modified Borg Dyspnea Scale, grip strength, 5 Times Sit to Stand Test, manual muscle test, gait measure, Timed Up & Go test, clinical balance tests, range of motion, flexibility, sensation, pain, and fall history.^18-32 Educational needs (eg, respiratory hygiene, nutrition, infection control, sleep, disease/symptom management) also are evaluated.

This thorough assessment is performed in a face-to-face outpatient visit. During the program participation, a physiatrist may be consulted for additional needs (eg, wheelchair assessment, home safety evaluation/ modifications, and mobility/disability issues). After completing the 6-week program, patients are scheduled for the postprogram evaluation in a face-to-face outpatient visit with the clinicians.

Equipment

Both clinician and the patient are equipped with a computer with Wi-Fi connectivity, a webcam, and a microphone. Patients are provided an exercise pictorial booklet, an exercise compact disk (audio and video), small exercise apparatuses (eg, assorted colors of resistance bands, hand grip exerciser, hand putty, ergometer, harmonica, and pedometer), incentive spirometer, pulse oximeter, cough assistive device (as needed), blood pressure monitor, COPD information booklets, and a diary to use at home during the program.³³

Technology Preparation

Prior to starting the telehealth program, the patient is contacted 1 or 2 days before the first session for technical preparation and familiarization of the VA telehealth connection process. Either the PT or RT provides step-by-step instructions for the patient to practice connecting through VVC during this preparatory phone call. The patient also practices using the computer webcam, speaker, and microphone; checks the telehealth scheduling e-mail; and learns how to solve possible common technical issues (eg, adjusting volume and position of webcam). The patient is asked to set up a table close to the computer and to place all exercise apparatuses and respiratory devices on the table surface.

Program Delivery

A secure online VVC is used for connection during the telehealth session. The patient received an e-mail from the telehealth scheduling system with a link for VVC before each session. During the 6-week program, each telehealth session is conducted by a PT and a RT concurrently for 120 minutes, 3 days per week. The PT provides exercises for the patient to attempt, and the RT provides breathing training and monitoring during the session. After a successful connection to VVC, the therapist verifies the patient’s identity and confirms patient consent for the telehealth session.

After this check-in process, the patient performs a self-measure of resting blood pressure (BP), heart rate, respiratory rate, and blood oxygen saturation and reports to the therapists. During the exercise session, fatigue/exertion, dyspnea (Modified Borg Dyspnea Scale; Borg CR10 Scale), BP, heart rate, oxygen saturation, and other clinical symptoms and responses to exercise are monitored by the therapists, using both patient-reported measures and clinical observation by the therapists.^34,35 Any medical emergency during the session is reported immediately to the pulmonologist for further management.

Structure

Prior to each exercise session, exercise precautions, fall prevention, good posture, pursed-lip breathing, pacing, and coordinated breathing are discussed with the patient. The PT demonstrates stretching and warm-up exercises in front of the webcam for the patient to follow. Then the patient performs all exercises in view of the webcam during the session (Figure 1). A RT monitors breathing patterns and corrects with verbal instructions if not properly performed.

Loss of skeletal muscle mass and cachexia are highly prevalent comorbidities of COPD and have been associated with breathlessness, functional limitation, and poor prognosis.³⁶ To address these comorbidities, our program consists of progressive strengthening, aerobic, balance, and flexibility exercises. Resistance bands and tubes are used for strengthening exercises. Callisthenic exercises (eg, chair squat, chair stand, knee marching, bridging, single limb stances, and lunge) are used for progressive strengthening and balance exercises. Progression of strengthening and balance exercises are done through increasing the volume of exercise (ie, numbers of sets and repetitions) and increased load and level of difficulty based on the patient’s progress and comorbidity. The exercise program focuses on strengthening muscles, especially large muscle groups, to improve overall muscle strength and performance of functional activities.³⁷

Arm/pedal ergometer and daily walking are used for daily aerobic exercise. In a study of patients with COPD by the PAC-COPD Study Group, step counter use was found to increase physical activity and improve exercise capacity, which supports its use in COPD management.³⁸ During program participation, the patient is asked to wear a pedometer to monitor the number of steps taken per day and to report step data to the therapists during the telehealth session. The pedometer stores the previous 41 calendar days of data and displays the most recent 7 calendar days of data.

The patient is encouraged to set a realistic daily step goal. The general program goal is to increase at least 1000 steps per day. However, this goal can be adjusted depending on the patient’s health status and comorbid conditions. The PAC-COPD Study Group found that for every additional 1000 daily steps at low intensity, COPD hospitalization risk decreased by 20%.³⁹ A magnitude of 2000 steps or about 1 mile of walking per day was found to be associated with increased physical activity and health benefits in the general population.⁴⁰

Respiratory muscle training and breathing exercise are provided by the RT, using breathing and incentive spirometer techniques (Figure 2). Huff coughing, diaphragmatic deep breathing, and pursed-lip breathing are instructed by the RT during the session. Effective coughing technique with a cough assistive device is also provided during breathing training if needed.

Patient Education

In patients with COPD, there are numerous positive health benefits associated with education, including assisting the patients to become active participants in the PR program leading to satisfying outcomes; assisting the patients to better understand the lung health, disease processes, physical and psychological changes that occur with COPD; assisting the patients to explore coping strategies for those changes; building lifelong behavioral changes; and developing the self-management skills for sustainability. Through the educational process, patients with COPD can become more skilled at collaborative self-management and improve adherence to their treatment plan, which in turn can result in a reduction in hospital admissions and reduced health care costs.^8,41

Education is provided with every session after the patient completes the exercise. Patients are required to record their COPD symptoms, daily activity, home exercise program, sleep, food intake, and additional physical or social activity in their COPD diary and to report during the session (Figure 3). A COPD diary assists patients in self-monitoring their COPD symptoms and provides the therapists with information about clinical changes, behavioral changes, and/or specific unmet needs for education. Several topics related to COPD are included in the education session: lung or respiratory disease/condition and self-management; smoking cessation; physical activity; energy-conserving techniques; breathing and coughing techniques; smoking cessation; nutrition/healthy eating and weight counseling; sex and intimacy; psychological counseling and/or group support; emergency planning (eg, medical, travel, and inclement weather); correct use of inhaler and medications; home oxygen; sleep and sleep hygiene; palliative care and advanced directive; infection control; and sputum clearance.^42,43

Program Maintenance

After successfully completing the 6-week program, patients are referred to the VA TeleMOVE! Program or MOVE! Weight Management Program for continuous, long-term management of weight, nutrition, physical activity/exercise, and social activity needs or goals. The patients are scheduled for monthly follow-up phone visits for 6 months with the telerehabilitation team for enforcing sustainability. The phone call visit consists of reviewing breathing techniques, exercise program, physical activity, education, encouragement, and addressing any issues that arise during the self-maintained period.

Limitations

There are several issues of concern and precautions when delivering PR through telehealth into the home. First, the patient performs exercises independently without being manually guarded by the therapists. Risk of falls are a major concern due to impaired balance, poor vision, and other possible unusual physiologic responses to exercise (eg, drop in BP, dizziness, loss of balance). The area in front of the computer needs to be cleared of fall hazards (ie, area rug, wires, objects on the floor). The patient also needs to be educated on self-measurements of BP and oxygen saturation and reports to the therapists. The therapists provide detailed instructions on how to obtain these measures correctly; otherwise, the values may not be valid for a clinical judgment during the exercise session or for other clinical management. In a home environment, there is a limited use of exercise apparatuses. For this program, we only used resistance bands/tubes, small arm/leg ergometer, hand grip, and hand putty for the exercise program. We feel that dumbbell and weight plates are not suitable due to a possible risk of injury if the patient accidently drops them.

Advanced balance training is not suitable due to an increased risk for falls. Without the presence of the PT, level of challenge/difficulty is somewhat limited for this telehealth supervision exercise program. In addition, visual and audio quality are necessary for the session. The patient and the therapists need to see each other clearly to ensure correct methods and forms of each exercise. Furthermore, rehearsal of technical skills with the therapists is very important because this population is older and often has limited computer skills. Any technical difficulty or failure can lead to undesirable situations (eg, anxiety episodes, worries, shortness of breath, upset), which compromise exercise performance during the session. Finally, a phone is needed as an alternative in case of a poor VVC connection.

Conclusion

COPD symptoms and complications greatly affect patients’ ability to perform daily activities, decrease QOL and functional ability, and result in extensive use of health services. Many patients have limited access to a PR program at hospitals or rehabilitation centers due to health conditions, lack of transportation, and/or family support. This home-based, interactive telehealth PR program can break down the geographic barriers, solve poor program accessibility, potentially increase the utilization of PR, and reduce the cost and travel required by the patients.

Acknowledgments
The Telehealth Pulmonary Rehabilitation Program was originally funded by the Veterans Health Administration VA ACCESS Program (AS, CL, HKH). We thank all the veterans for their time and effort in participating in this newly developed rehabilitation program.

According to World Health Organization estimates, 65 million people have moderate-to-severe chronic obstructive pulmonary disease (COPD) globally, and > 20 million patients with COPD are living in the US.¹ COPD is a progressive respiratory disease with a poor prognosis and a significant cause of morbidity and mortality in the US, especially within the Veterans Health Administration (VHA).² The prevalence of COPD is higher in veterans than it is in the general population. COPD prevalence in the adult US population has been estimated to be between 5% and 15%, whereas in veterans, prevalence estimates have ranged from about 5% to 43%.^3-5

COPD is associated with disabling dyspnea, muscle weakness, exercise intolerance, morbidity, and mortality. These symptoms and complications gradually and progressively compromise mobility, ability to perform daily functions, and decrease quality of life (QOL). Dyspnea, fatigue, and discomfort are the principal symptoms that negatively impact exercise tolerance.^6,7 Therefore, patients often intentionally limit their activities to avoid these uncomfortable feelings and adopt a more sedentary behavior. As the disease progresses, individuals with COPD will gradually need assistance in performing activities of daily living, which eventually leads to functional dependence.

Pulmonary rehabilitation (PR) is an essential component of the management of symptomatic patients with COPD. PR is an evidence-based, multidisciplinary, comprehensive intervention that includes exercise and education for patients with chronic respiratory disease.⁸ The key benefits of PR are clinical improvements in dyspnea, physical capacity, QOL, and reduced disability in patients with COPD and other respiratory diseases.^9-11 PR was found to improve respiratory health in veterans with COPD and decrease respiratory-related health care utilization.¹²

Despite the known benefits of PR, many patients with chronic respiratory diseases are not referred or do not have access to rehabilitation. Also, uptake of PR is low due to patient frailty, transportation issues, and other health care access problems.^13-15 Unfortunately, in the US health care system, access to PR and other nonpharmacologic treatments can be challenging due to a shortage of available PR programs, limited physician referral to existing programs, and lack of family and social support.¹⁶

There are only a few accredited PR programs in VHA facilities, and they tend to be located in urban areas.^12,17 Many patients have limited access to the PR programs due to geographic distance to the programs and transportation challenges (eg, limited ability to drive, cost of transportation). Moreover, veterans with COPD are likely to have limited mobility or are homebound due to experiencing shortness of breath with minimal exertion. Given the clear benefits of PR and the increasing impact of COPD on morbidity and mortality of the patients with COPD, strategies to improve the access and capacity of PR are needed. VA telehealth services allow for distribution of health care services in different geographic locations by providing access for the veterans who live in rural and highly rural areas. The most recent implementation of VA Video Connect (VVC) by the VHA provides a new avenue for clinicians to deliver much needed medical care into the veterans’ home.

COPD Telehealth Program

In this article, we describe the processes for developing and delivering an in-home, interactive, supervised PR program for veterans with severe COPD through VA telehealth service. The program consists of 18 sessions delivered over 6 weeks by a licensed physical therapist (PT) and a respiratory therapist (RT). The aims of the telehealth PR are to improve exercise tolerance, reduce dyspnea and fatigue, improve QOL, improve accessibility, and decrease costs and transportation burdens for patients with COPD. The program was developed, implemented and delivered by an interdisciplinary team, including a pulmonologist, PT, RT, physiatrist, and nonclinical supporting staff.

 

 

Patient Assessment

To be eligible to participate in the program the patient must: (1) have a forced expiratory volume (FEV₁) < 60%; ( 2) be medically stable and be receiving optimal medical management; (3) have no severe cognitive impairments; (4) be able to use a computer and e-mail; (5) be able to ambulate with or without a walking device; (6) be willing to enroll in a smoking cessation program or to stop smoking; (7) be willing to participate without prolonged interruption; and (8) have all visual and auditory impairments corrected with medical devices.

After referral and enrollment, patients receive medical and physical examinations by the PR team, including a pulmonologist, a PT, and a RT, to ensure that the patients are medically stable to undergo rehabilitation and to develop a tailored exercise program while being mindful of the comorbidities, limitations, and precautions, (eg, loss of balance, risk of fall, limited range of motion). The preprogram assessment includes a pulmonary function test, arterial blood gas test, Montreal Cognitive Assessment, Modified Medical Research Council Scale, St. George Respiratory Questionnaire, the COPD Assessment Test, Patient Health Questionnaire-9,Generalized Anxiety Disorder Assessment-7, Epworth Sleepiness Scale, Katz Index of Independence of Activities of Daily Living, medications and inhaler use, oxygen use, breathing pattern, coughing, 6-minute walk test, Modified Borg Dyspnea Scale, grip strength, 5 Times Sit to Stand Test, manual muscle test, gait measure, Timed Up & Go test, clinical balance tests, range of motion, flexibility, sensation, pain, and fall history.^18-32 Educational needs (eg, respiratory hygiene, nutrition, infection control, sleep, disease/symptom management) also are evaluated.

This thorough assessment is performed in a face-to-face outpatient visit. During the program participation, a physiatrist may be consulted for additional needs (eg, wheelchair assessment, home safety evaluation/ modifications, and mobility/disability issues). After completing the 6-week program, patients are scheduled for the postprogram evaluation in a face-to-face outpatient visit with the clinicians.

Equipment

Both clinician and the patient are equipped with a computer with Wi-Fi connectivity, a webcam, and a microphone. Patients are provided an exercise pictorial booklet, an exercise compact disk (audio and video), small exercise apparatuses (eg, assorted colors of resistance bands, hand grip exerciser, hand putty, ergometer, harmonica, and pedometer), incentive spirometer, pulse oximeter, cough assistive device (as needed), blood pressure monitor, COPD information booklets, and a diary to use at home during the program.³³

Technology Preparation

Prior to starting the telehealth program, the patient is contacted 1 or 2 days before the first session for technical preparation and familiarization of the VA telehealth connection process. Either the PT or RT provides step-by-step instructions for the patient to practice connecting through VVC during this preparatory phone call. The patient also practices using the computer webcam, speaker, and microphone; checks the telehealth scheduling e-mail; and learns how to solve possible common technical issues (eg, adjusting volume and position of webcam). The patient is asked to set up a table close to the computer and to place all exercise apparatuses and respiratory devices on the table surface.

Program Delivery

A secure online VVC is used for connection during the telehealth session. The patient received an e-mail from the telehealth scheduling system with a link for VVC before each session. During the 6-week program, each telehealth session is conducted by a PT and a RT concurrently for 120 minutes, 3 days per week. The PT provides exercises for the patient to attempt, and the RT provides breathing training and monitoring during the session. After a successful connection to VVC, the therapist verifies the patient’s identity and confirms patient consent for the telehealth session.

After this check-in process, the patient performs a self-measure of resting blood pressure (BP), heart rate, respiratory rate, and blood oxygen saturation and reports to the therapists. During the exercise session, fatigue/exertion, dyspnea (Modified Borg Dyspnea Scale; Borg CR10 Scale), BP, heart rate, oxygen saturation, and other clinical symptoms and responses to exercise are monitored by the therapists, using both patient-reported measures and clinical observation by the therapists.^34,35 Any medical emergency during the session is reported immediately to the pulmonologist for further management.

Structure

Prior to each exercise session, exercise precautions, fall prevention, good posture, pursed-lip breathing, pacing, and coordinated breathing are discussed with the patient. The PT demonstrates stretching and warm-up exercises in front of the webcam for the patient to follow. Then the patient performs all exercises in view of the webcam during the session (Figure 1). A RT monitors breathing patterns and corrects with verbal instructions if not properly performed.

Loss of skeletal muscle mass and cachexia are highly prevalent comorbidities of COPD and have been associated with breathlessness, functional limitation, and poor prognosis.³⁶ To address these comorbidities, our program consists of progressive strengthening, aerobic, balance, and flexibility exercises. Resistance bands and tubes are used for strengthening exercises. Callisthenic exercises (eg, chair squat, chair stand, knee marching, bridging, single limb stances, and lunge) are used for progressive strengthening and balance exercises. Progression of strengthening and balance exercises are done through increasing the volume of exercise (ie, numbers of sets and repetitions) and increased load and level of difficulty based on the patient’s progress and comorbidity. The exercise program focuses on strengthening muscles, especially large muscle groups, to improve overall muscle strength and performance of functional activities.³⁷

Arm/pedal ergometer and daily walking are used for daily aerobic exercise. In a study of patients with COPD by the PAC-COPD Study Group, step counter use was found to increase physical activity and improve exercise capacity, which supports its use in COPD management.³⁸ During program participation, the patient is asked to wear a pedometer to monitor the number of steps taken per day and to report step data to the therapists during the telehealth session. The pedometer stores the previous 41 calendar days of data and displays the most recent 7 calendar days of data.

The patient is encouraged to set a realistic daily step goal. The general program goal is to increase at least 1000 steps per day. However, this goal can be adjusted depending on the patient’s health status and comorbid conditions. The PAC-COPD Study Group found that for every additional 1000 daily steps at low intensity, COPD hospitalization risk decreased by 20%.³⁹ A magnitude of 2000 steps or about 1 mile of walking per day was found to be associated with increased physical activity and health benefits in the general population.⁴⁰

Respiratory muscle training and breathing exercise are provided by the RT, using breathing and incentive spirometer techniques (Figure 2). Huff coughing, diaphragmatic deep breathing, and pursed-lip breathing are instructed by the RT during the session. Effective coughing technique with a cough assistive device is also provided during breathing training if needed.

Patient Education

In patients with COPD, there are numerous positive health benefits associated with education, including assisting the patients to become active participants in the PR program leading to satisfying outcomes; assisting the patients to better understand the lung health, disease processes, physical and psychological changes that occur with COPD; assisting the patients to explore coping strategies for those changes; building lifelong behavioral changes; and developing the self-management skills for sustainability. Through the educational process, patients with COPD can become more skilled at collaborative self-management and improve adherence to their treatment plan, which in turn can result in a reduction in hospital admissions and reduced health care costs.^8,41

Education is provided with every session after the patient completes the exercise. Patients are required to record their COPD symptoms, daily activity, home exercise program, sleep, food intake, and additional physical or social activity in their COPD diary and to report during the session (Figure 3). A COPD diary assists patients in self-monitoring their COPD symptoms and provides the therapists with information about clinical changes, behavioral changes, and/or specific unmet needs for education. Several topics related to COPD are included in the education session: lung or respiratory disease/condition and self-management; smoking cessation; physical activity; energy-conserving techniques; breathing and coughing techniques; smoking cessation; nutrition/healthy eating and weight counseling; sex and intimacy; psychological counseling and/or group support; emergency planning (eg, medical, travel, and inclement weather); correct use of inhaler and medications; home oxygen; sleep and sleep hygiene; palliative care and advanced directive; infection control; and sputum clearance.^42,43

Program Maintenance

After successfully completing the 6-week program, patients are referred to the VA TeleMOVE! Program or MOVE! Weight Management Program for continuous, long-term management of weight, nutrition, physical activity/exercise, and social activity needs or goals. The patients are scheduled for monthly follow-up phone visits for 6 months with the telerehabilitation team for enforcing sustainability. The phone call visit consists of reviewing breathing techniques, exercise program, physical activity, education, encouragement, and addressing any issues that arise during the self-maintained period.

Limitations

There are several issues of concern and precautions when delivering PR through telehealth into the home. First, the patient performs exercises independently without being manually guarded by the therapists. Risk of falls are a major concern due to impaired balance, poor vision, and other possible unusual physiologic responses to exercise (eg, drop in BP, dizziness, loss of balance). The area in front of the computer needs to be cleared of fall hazards (ie, area rug, wires, objects on the floor). The patient also needs to be educated on self-measurements of BP and oxygen saturation and reports to the therapists. The therapists provide detailed instructions on how to obtain these measures correctly; otherwise, the values may not be valid for a clinical judgment during the exercise session or for other clinical management. In a home environment, there is a limited use of exercise apparatuses. For this program, we only used resistance bands/tubes, small arm/leg ergometer, hand grip, and hand putty for the exercise program. We feel that dumbbell and weight plates are not suitable due to a possible risk of injury if the patient accidently drops them.

Advanced balance training is not suitable due to an increased risk for falls. Without the presence of the PT, level of challenge/difficulty is somewhat limited for this telehealth supervision exercise program. In addition, visual and audio quality are necessary for the session. The patient and the therapists need to see each other clearly to ensure correct methods and forms of each exercise. Furthermore, rehearsal of technical skills with the therapists is very important because this population is older and often has limited computer skills. Any technical difficulty or failure can lead to undesirable situations (eg, anxiety episodes, worries, shortness of breath, upset), which compromise exercise performance during the session. Finally, a phone is needed as an alternative in case of a poor VVC connection.

Conclusion

COPD symptoms and complications greatly affect patients’ ability to perform daily activities, decrease QOL and functional ability, and result in extensive use of health services. Many patients have limited access to a PR program at hospitals or rehabilitation centers due to health conditions, lack of transportation, and/or family support. This home-based, interactive telehealth PR program can break down the geographic barriers, solve poor program accessibility, potentially increase the utilization of PR, and reduce the cost and travel required by the patients.

Acknowledgments
The Telehealth Pulmonary Rehabilitation Program was originally funded by the Veterans Health Administration VA ACCESS Program (AS, CL, HKH). We thank all the veterans for their time and effort in participating in this newly developed rehabilitation program.

According to World Health Organization estimates, 65 million people have moderate-to-severe chronic obstructive pulmonary disease (COPD) globally, and > 20 million patients with COPD are living in the US.¹ COPD is a progressive respiratory disease with a poor prognosis and a significant cause of morbidity and mortality in the US, especially within the Veterans Health Administration (VHA).² The prevalence of COPD is higher in veterans than it is in the general population. COPD prevalence in the adult US population has been estimated to be between 5% and 15%, whereas in veterans, prevalence estimates have ranged from about 5% to 43%.^3-5

COPD is associated with disabling dyspnea, muscle weakness, exercise intolerance, morbidity, and mortality. These symptoms and complications gradually and progressively compromise mobility, ability to perform daily functions, and decrease quality of life (QOL). Dyspnea, fatigue, and discomfort are the principal symptoms that negatively impact exercise tolerance.^6,7 Therefore, patients often intentionally limit their activities to avoid these uncomfortable feelings and adopt a more sedentary behavior. As the disease progresses, individuals with COPD will gradually need assistance in performing activities of daily living, which eventually leads to functional dependence.

Pulmonary rehabilitation (PR) is an essential component of the management of symptomatic patients with COPD. PR is an evidence-based, multidisciplinary, comprehensive intervention that includes exercise and education for patients with chronic respiratory disease.⁸ The key benefits of PR are clinical improvements in dyspnea, physical capacity, QOL, and reduced disability in patients with COPD and other respiratory diseases.^9-11 PR was found to improve respiratory health in veterans with COPD and decrease respiratory-related health care utilization.¹²

Despite the known benefits of PR, many patients with chronic respiratory diseases are not referred or do not have access to rehabilitation. Also, uptake of PR is low due to patient frailty, transportation issues, and other health care access problems.^13-15 Unfortunately, in the US health care system, access to PR and other nonpharmacologic treatments can be challenging due to a shortage of available PR programs, limited physician referral to existing programs, and lack of family and social support.¹⁶

There are only a few accredited PR programs in VHA facilities, and they tend to be located in urban areas.^12,17 Many patients have limited access to the PR programs due to geographic distance to the programs and transportation challenges (eg, limited ability to drive, cost of transportation). Moreover, veterans with COPD are likely to have limited mobility or are homebound due to experiencing shortness of breath with minimal exertion. Given the clear benefits of PR and the increasing impact of COPD on morbidity and mortality of the patients with COPD, strategies to improve the access and capacity of PR are needed. VA telehealth services allow for distribution of health care services in different geographic locations by providing access for the veterans who live in rural and highly rural areas. The most recent implementation of VA Video Connect (VVC) by the VHA provides a new avenue for clinicians to deliver much needed medical care into the veterans’ home.

COPD Telehealth Program

In this article, we describe the processes for developing and delivering an in-home, interactive, supervised PR program for veterans with severe COPD through VA telehealth service. The program consists of 18 sessions delivered over 6 weeks by a licensed physical therapist (PT) and a respiratory therapist (RT). The aims of the telehealth PR are to improve exercise tolerance, reduce dyspnea and fatigue, improve QOL, improve accessibility, and decrease costs and transportation burdens for patients with COPD. The program was developed, implemented and delivered by an interdisciplinary team, including a pulmonologist, PT, RT, physiatrist, and nonclinical supporting staff.

 

 

Patient Assessment

To be eligible to participate in the program the patient must: (1) have a forced expiratory volume (FEV₁) < 60%; ( 2) be medically stable and be receiving optimal medical management; (3) have no severe cognitive impairments; (4) be able to use a computer and e-mail; (5) be able to ambulate with or without a walking device; (6) be willing to enroll in a smoking cessation program or to stop smoking; (7) be willing to participate without prolonged interruption; and (8) have all visual and auditory impairments corrected with medical devices.

After referral and enrollment, patients receive medical and physical examinations by the PR team, including a pulmonologist, a PT, and a RT, to ensure that the patients are medically stable to undergo rehabilitation and to develop a tailored exercise program while being mindful of the comorbidities, limitations, and precautions, (eg, loss of balance, risk of fall, limited range of motion). The preprogram assessment includes a pulmonary function test, arterial blood gas test, Montreal Cognitive Assessment, Modified Medical Research Council Scale, St. George Respiratory Questionnaire, the COPD Assessment Test, Patient Health Questionnaire-9,Generalized Anxiety Disorder Assessment-7, Epworth Sleepiness Scale, Katz Index of Independence of Activities of Daily Living, medications and inhaler use, oxygen use, breathing pattern, coughing, 6-minute walk test, Modified Borg Dyspnea Scale, grip strength, 5 Times Sit to Stand Test, manual muscle test, gait measure, Timed Up & Go test, clinical balance tests, range of motion, flexibility, sensation, pain, and fall history.^18-32 Educational needs (eg, respiratory hygiene, nutrition, infection control, sleep, disease/symptom management) also are evaluated.

This thorough assessment is performed in a face-to-face outpatient visit. During the program participation, a physiatrist may be consulted for additional needs (eg, wheelchair assessment, home safety evaluation/ modifications, and mobility/disability issues). After completing the 6-week program, patients are scheduled for the postprogram evaluation in a face-to-face outpatient visit with the clinicians.

Equipment

Both clinician and the patient are equipped with a computer with Wi-Fi connectivity, a webcam, and a microphone. Patients are provided an exercise pictorial booklet, an exercise compact disk (audio and video), small exercise apparatuses (eg, assorted colors of resistance bands, hand grip exerciser, hand putty, ergometer, harmonica, and pedometer), incentive spirometer, pulse oximeter, cough assistive device (as needed), blood pressure monitor, COPD information booklets, and a diary to use at home during the program.³³

Technology Preparation

Prior to starting the telehealth program, the patient is contacted 1 or 2 days before the first session for technical preparation and familiarization of the VA telehealth connection process. Either the PT or RT provides step-by-step instructions for the patient to practice connecting through VVC during this preparatory phone call. The patient also practices using the computer webcam, speaker, and microphone; checks the telehealth scheduling e-mail; and learns how to solve possible common technical issues (eg, adjusting volume and position of webcam). The patient is asked to set up a table close to the computer and to place all exercise apparatuses and respiratory devices on the table surface.

Program Delivery

A secure online VVC is used for connection during the telehealth session. The patient received an e-mail from the telehealth scheduling system with a link for VVC before each session. During the 6-week program, each telehealth session is conducted by a PT and a RT concurrently for 120 minutes, 3 days per week. The PT provides exercises for the patient to attempt, and the RT provides breathing training and monitoring during the session. After a successful connection to VVC, the therapist verifies the patient’s identity and confirms patient consent for the telehealth session.

After this check-in process, the patient performs a self-measure of resting blood pressure (BP), heart rate, respiratory rate, and blood oxygen saturation and reports to the therapists. During the exercise session, fatigue/exertion, dyspnea (Modified Borg Dyspnea Scale; Borg CR10 Scale), BP, heart rate, oxygen saturation, and other clinical symptoms and responses to exercise are monitored by the therapists, using both patient-reported measures and clinical observation by the therapists.^34,35 Any medical emergency during the session is reported immediately to the pulmonologist for further management.

Structure

Prior to each exercise session, exercise precautions, fall prevention, good posture, pursed-lip breathing, pacing, and coordinated breathing are discussed with the patient. The PT demonstrates stretching and warm-up exercises in front of the webcam for the patient to follow. Then the patient performs all exercises in view of the webcam during the session (Figure 1). A RT monitors breathing patterns and corrects with verbal instructions if not properly performed.

Loss of skeletal muscle mass and cachexia are highly prevalent comorbidities of COPD and have been associated with breathlessness, functional limitation, and poor prognosis.³⁶ To address these comorbidities, our program consists of progressive strengthening, aerobic, balance, and flexibility exercises. Resistance bands and tubes are used for strengthening exercises. Callisthenic exercises (eg, chair squat, chair stand, knee marching, bridging, single limb stances, and lunge) are used for progressive strengthening and balance exercises. Progression of strengthening and balance exercises are done through increasing the volume of exercise (ie, numbers of sets and repetitions) and increased load and level of difficulty based on the patient’s progress and comorbidity. The exercise program focuses on strengthening muscles, especially large muscle groups, to improve overall muscle strength and performance of functional activities.³⁷

Arm/pedal ergometer and daily walking are used for daily aerobic exercise. In a study of patients with COPD by the PAC-COPD Study Group, step counter use was found to increase physical activity and improve exercise capacity, which supports its use in COPD management.³⁸ During program participation, the patient is asked to wear a pedometer to monitor the number of steps taken per day and to report step data to the therapists during the telehealth session. The pedometer stores the previous 41 calendar days of data and displays the most recent 7 calendar days of data.

The patient is encouraged to set a realistic daily step goal. The general program goal is to increase at least 1000 steps per day. However, this goal can be adjusted depending on the patient’s health status and comorbid conditions. The PAC-COPD Study Group found that for every additional 1000 daily steps at low intensity, COPD hospitalization risk decreased by 20%.³⁹ A magnitude of 2000 steps or about 1 mile of walking per day was found to be associated with increased physical activity and health benefits in the general population.⁴⁰

Respiratory muscle training and breathing exercise are provided by the RT, using breathing and incentive spirometer techniques (Figure 2). Huff coughing, diaphragmatic deep breathing, and pursed-lip breathing are instructed by the RT during the session. Effective coughing technique with a cough assistive device is also provided during breathing training if needed.

Patient Education

In patients with COPD, there are numerous positive health benefits associated with education, including assisting the patients to become active participants in the PR program leading to satisfying outcomes; assisting the patients to better understand the lung health, disease processes, physical and psychological changes that occur with COPD; assisting the patients to explore coping strategies for those changes; building lifelong behavioral changes; and developing the self-management skills for sustainability. Through the educational process, patients with COPD can become more skilled at collaborative self-management and improve adherence to their treatment plan, which in turn can result in a reduction in hospital admissions and reduced health care costs.^8,41

Education is provided with every session after the patient completes the exercise. Patients are required to record their COPD symptoms, daily activity, home exercise program, sleep, food intake, and additional physical or social activity in their COPD diary and to report during the session (Figure 3). A COPD diary assists patients in self-monitoring their COPD symptoms and provides the therapists with information about clinical changes, behavioral changes, and/or specific unmet needs for education. Several topics related to COPD are included in the education session: lung or respiratory disease/condition and self-management; smoking cessation; physical activity; energy-conserving techniques; breathing and coughing techniques; smoking cessation; nutrition/healthy eating and weight counseling; sex and intimacy; psychological counseling and/or group support; emergency planning (eg, medical, travel, and inclement weather); correct use of inhaler and medications; home oxygen; sleep and sleep hygiene; palliative care and advanced directive; infection control; and sputum clearance.^42,43

Program Maintenance

After successfully completing the 6-week program, patients are referred to the VA TeleMOVE! Program or MOVE! Weight Management Program for continuous, long-term management of weight, nutrition, physical activity/exercise, and social activity needs or goals. The patients are scheduled for monthly follow-up phone visits for 6 months with the telerehabilitation team for enforcing sustainability. The phone call visit consists of reviewing breathing techniques, exercise program, physical activity, education, encouragement, and addressing any issues that arise during the self-maintained period.

Limitations

There are several issues of concern and precautions when delivering PR through telehealth into the home. First, the patient performs exercises independently without being manually guarded by the therapists. Risk of falls are a major concern due to impaired balance, poor vision, and other possible unusual physiologic responses to exercise (eg, drop in BP, dizziness, loss of balance). The area in front of the computer needs to be cleared of fall hazards (ie, area rug, wires, objects on the floor). The patient also needs to be educated on self-measurements of BP and oxygen saturation and reports to the therapists. The therapists provide detailed instructions on how to obtain these measures correctly; otherwise, the values may not be valid for a clinical judgment during the exercise session or for other clinical management. In a home environment, there is a limited use of exercise apparatuses. For this program, we only used resistance bands/tubes, small arm/leg ergometer, hand grip, and hand putty for the exercise program. We feel that dumbbell and weight plates are not suitable due to a possible risk of injury if the patient accidently drops them.

Advanced balance training is not suitable due to an increased risk for falls. Without the presence of the PT, level of challenge/difficulty is somewhat limited for this telehealth supervision exercise program. In addition, visual and audio quality are necessary for the session. The patient and the therapists need to see each other clearly to ensure correct methods and forms of each exercise. Furthermore, rehearsal of technical skills with the therapists is very important because this population is older and often has limited computer skills. Any technical difficulty or failure can lead to undesirable situations (eg, anxiety episodes, worries, shortness of breath, upset), which compromise exercise performance during the session. Finally, a phone is needed as an alternative in case of a poor VVC connection.

Conclusion

COPD symptoms and complications greatly affect patients’ ability to perform daily activities, decrease QOL and functional ability, and result in extensive use of health services. Many patients have limited access to a PR program at hospitals or rehabilitation centers due to health conditions, lack of transportation, and/or family support. This home-based, interactive telehealth PR program can break down the geographic barriers, solve poor program accessibility, potentially increase the utilization of PR, and reduce the cost and travel required by the patients.

Acknowledgments
The Telehealth Pulmonary Rehabilitation Program was originally funded by the Veterans Health Administration VA ACCESS Program (AS, CL, HKH). We thank all the veterans for their time and effort in participating in this newly developed rehabilitation program.

An 83-year-old woman with hypertension, hypothyroidism, and a history of depression presented to the emergency department with acute shortness of breath and hypoxia. She was found to have submassive pulmonary embolism, and a heparin infusion was started immediately.

Urgent nasopharyngeal laryngoscopy revealed a hematoma at the base of her tongue that extended into the vallecula, piriform sinuses, and aryepiglottic fold, causing acute airway obstruction. These features combined with the supratherapeutic aPTT led to the diagnosis of pseudo-Ludwig angina.

DANGER OF RAPID AIRWAY COMPROMISE

Pseudo-Ludwig angina is a rare condition in which over-anticoagulation causes sublingual swelling leading to airway obstruction, whereas true Ludwig angina is an infectious regional suppuration of the neck.

Most reported cases of pseudo-Ludwig angina have resulted from overanticogulation with warfarin or warfarin-like substances (rodenticides), or from coagulopathy due to liver disease.^1–3 Early recognition is essential to avoid airway compromise.

In our patient, all anticoagulation was discontinued, and she was intubated until the hematoma began to resolve, the aPTT returned to normal, and respiratory compromise improved. At follow-up 2 months later, the sublingual hematoma had completely resolved (Figure 1). And at a 6-month follow-up visit, the pulmonary embolism had resolved, and pulmonary pressures by 2-dimensional echocardiography were normal.

An 83-year-old woman with hypertension, hypothyroidism, and a history of depression presented to the emergency department with acute shortness of breath and hypoxia. She was found to have submassive pulmonary embolism, and a heparin infusion was started immediately.

Urgent nasopharyngeal laryngoscopy revealed a hematoma at the base of her tongue that extended into the vallecula, piriform sinuses, and aryepiglottic fold, causing acute airway obstruction. These features combined with the supratherapeutic aPTT led to the diagnosis of pseudo-Ludwig angina.

DANGER OF RAPID AIRWAY COMPROMISE

Pseudo-Ludwig angina is a rare condition in which over-anticoagulation causes sublingual swelling leading to airway obstruction, whereas true Ludwig angina is an infectious regional suppuration of the neck.

Most reported cases of pseudo-Ludwig angina have resulted from overanticogulation with warfarin or warfarin-like substances (rodenticides), or from coagulopathy due to liver disease.^1–3 Early recognition is essential to avoid airway compromise.

In our patient, all anticoagulation was discontinued, and she was intubated until the hematoma began to resolve, the aPTT returned to normal, and respiratory compromise improved. At follow-up 2 months later, the sublingual hematoma had completely resolved (Figure 1). And at a 6-month follow-up visit, the pulmonary embolism had resolved, and pulmonary pressures by 2-dimensional echocardiography were normal.

An 83-year-old woman with hypertension, hypothyroidism, and a history of depression presented to the emergency department with acute shortness of breath and hypoxia. She was found to have submassive pulmonary embolism, and a heparin infusion was started immediately.

Urgent nasopharyngeal laryngoscopy revealed a hematoma at the base of her tongue that extended into the vallecula, piriform sinuses, and aryepiglottic fold, causing acute airway obstruction. These features combined with the supratherapeutic aPTT led to the diagnosis of pseudo-Ludwig angina.

DANGER OF RAPID AIRWAY COMPROMISE

Pseudo-Ludwig angina is a rare condition in which over-anticoagulation causes sublingual swelling leading to airway obstruction, whereas true Ludwig angina is an infectious regional suppuration of the neck.

Most reported cases of pseudo-Ludwig angina have resulted from overanticogulation with warfarin or warfarin-like substances (rodenticides), or from coagulopathy due to liver disease.^1–3 Early recognition is essential to avoid airway compromise.

In our patient, all anticoagulation was discontinued, and she was intubated until the hematoma began to resolve, the aPTT returned to normal, and respiratory compromise improved. At follow-up 2 months later, the sublingual hematoma had completely resolved (Figure 1). And at a 6-month follow-up visit, the pulmonary embolism had resolved, and pulmonary pressures by 2-dimensional echocardiography were normal.

A 50-year-old man with Crohn disease and psoriatic arthritis treated with infliximab and methotrexate presented to a tertiary care hospital with fever, cough, and chest discomfort. The symptoms had first appeared 2 weeks earlier, and he had gone to an urgent care center, where he was prescribed a 5-day course of azithromycin and a corticosteroid, but this had not relieved his symptoms.

Bronchoscopy revealed edematous mucosa throughout, with minimal secretion. Specimens for bacterial, acid-fast bacillus, and fungal cultures were obtained from bronchoalveolar lavage. Endobronchial lymph node biopsy with ultrasonographic guidance revealed nonnecrotizing granuloma.

Bronchoalveolar lavage cultures showed no growth, but the patient’s serum histoplasma antigen was positive at 5.99 ng/dL (reference range: none detected), leading to the diagnosis of mediastinal granuloma due to histoplasmosis with possible dissemination. His immunosuppressant drugs were stopped, and oral itraconazole was started.

At a follow-up visit 2 months later, his serum antigen level had decreased to 0.68 ng/dL, and he had no symptoms whatsoever. At a visit 1 month after that, infliximab and methotrexate were restarted because of an exacerbation of Crohn disease. His oral itraconazole treatment was to be continued for at least 12 months, given the high suspicion for disseminated histoplasmosis while on immunosuppressant therapy.

DIFFERENTIAL DIAGNOSIS OF GRANULOMATOUS LUNG DISEASE AND LYMPHADENOPATHY

The differential diagnosis of granulomatous lung disease and lymphadenopathy is broad and includes noninfectious and infectious conditions.¹

Noninfectious causes include lymphoma, sarcoidosis, inflammatory bowel disease, hypersensitivity pneumonia, side effects of drugs (eg, methotrexate, etanercept), rheumatoid nodules, vasculitis (eg, Churg-Strauss syndrome, granulomatosis with polyangiitis, primary amyloidosis, pneumoconiosis (eg, beryllium, cobalt), and Castleman disease.

There is concern that tumor necrosis factor antagonists may increase the risk of lymphoma, but a 2017 study found no evidence of this.²

Infectious conditions associated with granulomatous lung disease include tuberculosis, nontuberculous mycobacterial infection, fungal infection (eg, Cryptococcus, Coccidioides, Histoplasma, Blastomyces), brucellosis, tularemia (respiratory type B), parasitic infection (eg, Toxocara, Leishmania, Echinococcus, Schistosoma), and Whipple disease.

HISTOPLASMOSIS

Histoplasmosis, caused by infection with Histoplasma capsulatum, is the most prevalent endemic mycotic disease in the United States.³ The fungus is commonly found in the Ohio and Mississippi River valleys in the United States, and also in Central and South America and Asia.

Risk factors for histoplasmosis include living in or traveling to an endemic area, exposure to aerosolized soil that contains spores, and exposure to bats or birds and their droppings.⁴

Fewer than 5% of exposed individuals develop symptoms, which include fever, chills, headache, myalgia, anorexia, cough, and chest pain.⁵ Patients may experience symptoms shortly after exposure or may remain free of symptoms for years, with intermittent relapses of symptoms.⁶ Hilar or mediastinal lymphadenopathy is common in acute pulmonary histoplasmosis.⁷

The risk of disseminated histoplasmosis is greater in patients with reduced cell-mediated immunity, such as in human immunodeficiency virus infection, acquired immunodeficiency syndrome, solid-organ or bone marrow transplant, hematologic malignancies, immunosuppression (corticosteroids, disease-modifying antirheumatic drugs, and tumor necrosis factor antagonists), and congenital T-cell deficiencies.⁸

In a retrospective study, infliximab was the tumor necrosis factor antagonist most commonly associated with histoplasmosis.⁹ In a study of patients with rheumatoid arthritis, the disease-modifying drug most commonly associated was methotrexate.¹⁰

 

 

GOLD STANDARD FOR DIAGNOSIS

Isolation of H capsulatum from clinical specimens remains the gold standard for confirmation of histoplasmosis. The sensitivity of culture to detect H capsulatum depends on the clinical manifestations: it is 74% in patients with disseminated histoplasmosis, but only 42% in patients with acute pulmonary histoplasmosis.¹¹ The serum histoplasma antigen test has a sensitivity of 91.8% in disseminated histoplasmosis, 87.5% in chronic pulmonary histoplasmosis, and 83% in acute pulmonary histoplasmosis.¹²

Urine testing for histoplasma antigen has generally proven to be slightly more sensitive than serum testing in all manifestations of histoplasmosis.¹³ Combining urine and serum testing increases the likelihood of antigen detection.

TREATMENT

Asymptomatic patients with mediastinal histoplasmosis do not require treatment. (Note: in some cases, lymphadenopathy is found incidentally, and biopsy is done to rule out malignancy.)

Standard treatment of symptomatic mediastinal histoplasmosis is oral itraconazole 200 mg, 3 times daily for 3 days, followed by 200 mg orally once or twice daily for 6 to 12 weeks.¹⁴

Although stopping immunosuppressant drugs is considered the standard of care in treating histoplasmosis in immunocompromised patients, there are no guidelines on when to resume them. However, a retrospective study of 98 cases of histoplasmosis in patients on tumor necrosis factor antagonists found that resuming immunosuppressants might be safe with close monitoring during the course of antifungal therapy.⁹ The role of long-term suppressive therapy with antifungal agents in patients on chronic immunosuppressive therapy is still unknown and needs further study.

TAKE-HOME MESSAGES

• Histoplasmosis is the most prevalent endemic mycotic disease in the United States, and mediastinal lymphadenopathy is commonly seen in acute pulmonary histoplasmosis.
• Histoplasmosis should be included in the differential diagnosis of granulomatous lung disease in patients from an endemic area or with a history of travel to an endemic area.
• Immunosuppressive agents such as tumor necrosis factor antagonists and disease-modifying antirheumatic drugs can predispose to invasive fungal infection, including histoplasmosis.
• While isolation of H capsulatum from culture remains the gold standard for the diagnosis of histoplasmosis, the histoplasma antigen tests (serum and urine) is more sensitive than culture.

A 50-year-old man with Crohn disease and psoriatic arthritis treated with infliximab and methotrexate presented to a tertiary care hospital with fever, cough, and chest discomfort. The symptoms had first appeared 2 weeks earlier, and he had gone to an urgent care center, where he was prescribed a 5-day course of azithromycin and a corticosteroid, but this had not relieved his symptoms.

Bronchoscopy revealed edematous mucosa throughout, with minimal secretion. Specimens for bacterial, acid-fast bacillus, and fungal cultures were obtained from bronchoalveolar lavage. Endobronchial lymph node biopsy with ultrasonographic guidance revealed nonnecrotizing granuloma.

Bronchoalveolar lavage cultures showed no growth, but the patient’s serum histoplasma antigen was positive at 5.99 ng/dL (reference range: none detected), leading to the diagnosis of mediastinal granuloma due to histoplasmosis with possible dissemination. His immunosuppressant drugs were stopped, and oral itraconazole was started.

At a follow-up visit 2 months later, his serum antigen level had decreased to 0.68 ng/dL, and he had no symptoms whatsoever. At a visit 1 month after that, infliximab and methotrexate were restarted because of an exacerbation of Crohn disease. His oral itraconazole treatment was to be continued for at least 12 months, given the high suspicion for disseminated histoplasmosis while on immunosuppressant therapy.

DIFFERENTIAL DIAGNOSIS OF GRANULOMATOUS LUNG DISEASE AND LYMPHADENOPATHY

The differential diagnosis of granulomatous lung disease and lymphadenopathy is broad and includes noninfectious and infectious conditions.¹

Noninfectious causes include lymphoma, sarcoidosis, inflammatory bowel disease, hypersensitivity pneumonia, side effects of drugs (eg, methotrexate, etanercept), rheumatoid nodules, vasculitis (eg, Churg-Strauss syndrome, granulomatosis with polyangiitis, primary amyloidosis, pneumoconiosis (eg, beryllium, cobalt), and Castleman disease.

There is concern that tumor necrosis factor antagonists may increase the risk of lymphoma, but a 2017 study found no evidence of this.²

Infectious conditions associated with granulomatous lung disease include tuberculosis, nontuberculous mycobacterial infection, fungal infection (eg, Cryptococcus, Coccidioides, Histoplasma, Blastomyces), brucellosis, tularemia (respiratory type B), parasitic infection (eg, Toxocara, Leishmania, Echinococcus, Schistosoma), and Whipple disease.

HISTOPLASMOSIS

Histoplasmosis, caused by infection with Histoplasma capsulatum, is the most prevalent endemic mycotic disease in the United States.³ The fungus is commonly found in the Ohio and Mississippi River valleys in the United States, and also in Central and South America and Asia.

Risk factors for histoplasmosis include living in or traveling to an endemic area, exposure to aerosolized soil that contains spores, and exposure to bats or birds and their droppings.⁴

Fewer than 5% of exposed individuals develop symptoms, which include fever, chills, headache, myalgia, anorexia, cough, and chest pain.⁵ Patients may experience symptoms shortly after exposure or may remain free of symptoms for years, with intermittent relapses of symptoms.⁶ Hilar or mediastinal lymphadenopathy is common in acute pulmonary histoplasmosis.⁷

The risk of disseminated histoplasmosis is greater in patients with reduced cell-mediated immunity, such as in human immunodeficiency virus infection, acquired immunodeficiency syndrome, solid-organ or bone marrow transplant, hematologic malignancies, immunosuppression (corticosteroids, disease-modifying antirheumatic drugs, and tumor necrosis factor antagonists), and congenital T-cell deficiencies.⁸

In a retrospective study, infliximab was the tumor necrosis factor antagonist most commonly associated with histoplasmosis.⁹ In a study of patients with rheumatoid arthritis, the disease-modifying drug most commonly associated was methotrexate.¹⁰

 

 

GOLD STANDARD FOR DIAGNOSIS

Isolation of H capsulatum from clinical specimens remains the gold standard for confirmation of histoplasmosis. The sensitivity of culture to detect H capsulatum depends on the clinical manifestations: it is 74% in patients with disseminated histoplasmosis, but only 42% in patients with acute pulmonary histoplasmosis.¹¹ The serum histoplasma antigen test has a sensitivity of 91.8% in disseminated histoplasmosis, 87.5% in chronic pulmonary histoplasmosis, and 83% in acute pulmonary histoplasmosis.¹²

Urine testing for histoplasma antigen has generally proven to be slightly more sensitive than serum testing in all manifestations of histoplasmosis.¹³ Combining urine and serum testing increases the likelihood of antigen detection.

TREATMENT

Asymptomatic patients with mediastinal histoplasmosis do not require treatment. (Note: in some cases, lymphadenopathy is found incidentally, and biopsy is done to rule out malignancy.)

Standard treatment of symptomatic mediastinal histoplasmosis is oral itraconazole 200 mg, 3 times daily for 3 days, followed by 200 mg orally once or twice daily for 6 to 12 weeks.¹⁴

Although stopping immunosuppressant drugs is considered the standard of care in treating histoplasmosis in immunocompromised patients, there are no guidelines on when to resume them. However, a retrospective study of 98 cases of histoplasmosis in patients on tumor necrosis factor antagonists found that resuming immunosuppressants might be safe with close monitoring during the course of antifungal therapy.⁹ The role of long-term suppressive therapy with antifungal agents in patients on chronic immunosuppressive therapy is still unknown and needs further study.

TAKE-HOME MESSAGES

• Histoplasmosis is the most prevalent endemic mycotic disease in the United States, and mediastinal lymphadenopathy is commonly seen in acute pulmonary histoplasmosis.
• Histoplasmosis should be included in the differential diagnosis of granulomatous lung disease in patients from an endemic area or with a history of travel to an endemic area.
• Immunosuppressive agents such as tumor necrosis factor antagonists and disease-modifying antirheumatic drugs can predispose to invasive fungal infection, including histoplasmosis.
• While isolation of H capsulatum from culture remains the gold standard for the diagnosis of histoplasmosis, the histoplasma antigen tests (serum and urine) is more sensitive than culture.

A 50-year-old man with Crohn disease and psoriatic arthritis treated with infliximab and methotrexate presented to a tertiary care hospital with fever, cough, and chest discomfort. The symptoms had first appeared 2 weeks earlier, and he had gone to an urgent care center, where he was prescribed a 5-day course of azithromycin and a corticosteroid, but this had not relieved his symptoms.

Bronchoscopy revealed edematous mucosa throughout, with minimal secretion. Specimens for bacterial, acid-fast bacillus, and fungal cultures were obtained from bronchoalveolar lavage. Endobronchial lymph node biopsy with ultrasonographic guidance revealed nonnecrotizing granuloma.

Bronchoalveolar lavage cultures showed no growth, but the patient’s serum histoplasma antigen was positive at 5.99 ng/dL (reference range: none detected), leading to the diagnosis of mediastinal granuloma due to histoplasmosis with possible dissemination. His immunosuppressant drugs were stopped, and oral itraconazole was started.

At a follow-up visit 2 months later, his serum antigen level had decreased to 0.68 ng/dL, and he had no symptoms whatsoever. At a visit 1 month after that, infliximab and methotrexate were restarted because of an exacerbation of Crohn disease. His oral itraconazole treatment was to be continued for at least 12 months, given the high suspicion for disseminated histoplasmosis while on immunosuppressant therapy.

DIFFERENTIAL DIAGNOSIS OF GRANULOMATOUS LUNG DISEASE AND LYMPHADENOPATHY

The differential diagnosis of granulomatous lung disease and lymphadenopathy is broad and includes noninfectious and infectious conditions.¹

Noninfectious causes include lymphoma, sarcoidosis, inflammatory bowel disease, hypersensitivity pneumonia, side effects of drugs (eg, methotrexate, etanercept), rheumatoid nodules, vasculitis (eg, Churg-Strauss syndrome, granulomatosis with polyangiitis, primary amyloidosis, pneumoconiosis (eg, beryllium, cobalt), and Castleman disease.

There is concern that tumor necrosis factor antagonists may increase the risk of lymphoma, but a 2017 study found no evidence of this.²

Infectious conditions associated with granulomatous lung disease include tuberculosis, nontuberculous mycobacterial infection, fungal infection (eg, Cryptococcus, Coccidioides, Histoplasma, Blastomyces), brucellosis, tularemia (respiratory type B), parasitic infection (eg, Toxocara, Leishmania, Echinococcus, Schistosoma), and Whipple disease.

HISTOPLASMOSIS

Histoplasmosis, caused by infection with Histoplasma capsulatum, is the most prevalent endemic mycotic disease in the United States.³ The fungus is commonly found in the Ohio and Mississippi River valleys in the United States, and also in Central and South America and Asia.

Risk factors for histoplasmosis include living in or traveling to an endemic area, exposure to aerosolized soil that contains spores, and exposure to bats or birds and their droppings.⁴

Fewer than 5% of exposed individuals develop symptoms, which include fever, chills, headache, myalgia, anorexia, cough, and chest pain.⁵ Patients may experience symptoms shortly after exposure or may remain free of symptoms for years, with intermittent relapses of symptoms.⁶ Hilar or mediastinal lymphadenopathy is common in acute pulmonary histoplasmosis.⁷

The risk of disseminated histoplasmosis is greater in patients with reduced cell-mediated immunity, such as in human immunodeficiency virus infection, acquired immunodeficiency syndrome, solid-organ or bone marrow transplant, hematologic malignancies, immunosuppression (corticosteroids, disease-modifying antirheumatic drugs, and tumor necrosis factor antagonists), and congenital T-cell deficiencies.⁸

In a retrospective study, infliximab was the tumor necrosis factor antagonist most commonly associated with histoplasmosis.⁹ In a study of patients with rheumatoid arthritis, the disease-modifying drug most commonly associated was methotrexate.¹⁰

 

 

GOLD STANDARD FOR DIAGNOSIS

Isolation of H capsulatum from clinical specimens remains the gold standard for confirmation of histoplasmosis. The sensitivity of culture to detect H capsulatum depends on the clinical manifestations: it is 74% in patients with disseminated histoplasmosis, but only 42% in patients with acute pulmonary histoplasmosis.¹¹ The serum histoplasma antigen test has a sensitivity of 91.8% in disseminated histoplasmosis, 87.5% in chronic pulmonary histoplasmosis, and 83% in acute pulmonary histoplasmosis.¹²

Urine testing for histoplasma antigen has generally proven to be slightly more sensitive than serum testing in all manifestations of histoplasmosis.¹³ Combining urine and serum testing increases the likelihood of antigen detection.

TREATMENT

Asymptomatic patients with mediastinal histoplasmosis do not require treatment. (Note: in some cases, lymphadenopathy is found incidentally, and biopsy is done to rule out malignancy.)

Standard treatment of symptomatic mediastinal histoplasmosis is oral itraconazole 200 mg, 3 times daily for 3 days, followed by 200 mg orally once or twice daily for 6 to 12 weeks.¹⁴

Although stopping immunosuppressant drugs is considered the standard of care in treating histoplasmosis in immunocompromised patients, there are no guidelines on when to resume them. However, a retrospective study of 98 cases of histoplasmosis in patients on tumor necrosis factor antagonists found that resuming immunosuppressants might be safe with close monitoring during the course of antifungal therapy.⁹ The role of long-term suppressive therapy with antifungal agents in patients on chronic immunosuppressive therapy is still unknown and needs further study.

TAKE-HOME MESSAGES

• Histoplasmosis is the most prevalent endemic mycotic disease in the United States, and mediastinal lymphadenopathy is commonly seen in acute pulmonary histoplasmosis.
• Histoplasmosis should be included in the differential diagnosis of granulomatous lung disease in patients from an endemic area or with a history of travel to an endemic area.
• Immunosuppressive agents such as tumor necrosis factor antagonists and disease-modifying antirheumatic drugs can predispose to invasive fungal infection, including histoplasmosis.
• While isolation of H capsulatum from culture remains the gold standard for the diagnosis of histoplasmosis, the histoplasma antigen tests (serum and urine) is more sensitive than culture.

SEATTLE – ICU transfers for acute bronchiolitis dropped 63% at Johns Hopkins All Children’s Hospital in St. Petersburg, Fla., after the high-flow nasal cannula limit on the floor was raised from 6 L/min to 12 L/min, and treatment was started in the emergency department, according to a presentation at Pediatric Hospital Medicine.

A year before the change was made in April 2018, there were 17 transfers among 249 bronchiolitis patients treated on the floor, a transfer rate of 6.8%. In the year after the change, there were eight among 319 patients, a transfer rate of 2.5%. Raising the limit to 12 L/min prevented an estimated 14 transfers, for a total savings of almost $250,000, said pediatric hospitalist and assistant professor Shaila Siraj, MD.

“As hospitalists, we felt we could safely take care of these patients,” Dr. Siraj said.

So she and her colleague pediatric critical care specialist Anthony Sochet, MD, also an assistant professor of pediatrics, reviewed over a year’s worth of data at All Children’s. They found that 12 L/min – roughly 1.5 L/kg/min – was the cutoff that best discriminated between patients who needed intubation and those who did not, “so that’s what we chose,” Dr. Sochet said.

For simplicity, they broke limits down by age: A maximum flow rate of 8 L/min for children up to 6 months old; 10 L for children aged 6-12 months; and up to 12 L/min for children age 12-24 months. The fraction of inspired oxygen remained the same at 50%. Children were started at maximum flows, then weaned down as they improved. Respiratory assessments were made at least every 4 hours.

The changes were part of a larger revision of the hospital’s pathway for uncomplicated bronchiolitis in children up to 2 years old; it was a joint effort involving nurses, respiratory therapists, and pediatric hospitalists, and ED and ICU teams.

Early initiation in the ED was “probably one of the most important” changes; it kept children from wearing out as they struggled to breath. Kids often start to improve right away, but when then don’t after 30-60 minutes, it’s an indication that they should probably be triaged to the ICU for possible intubation, Dr. Siraj said.

Dr. Sochet was careful to note that institutions have to assess their own situations before taking similar steps. “Not everyone has a tertiary care ICU staffed 24 and 7,” he said.

“You have to ask what floor resources you have, what’s your ability to escalate when you need to. Use data from your own institution to guide where you pick your cutoffs. Adequate staffing is really about respiratory [therapist]/nursing ratios, not the physicians,” he said.

In addition, “in an otherwise healthy child that just has [HFNC] for bronchiolitis, there is absolutely no reason why you should be withholding feeds.” Fed children will feel better and do better, he said.

The presenters had no disclosures.

aotto@mdedge.com

SEATTLE – ICU transfers for acute bronchiolitis dropped 63% at Johns Hopkins All Children’s Hospital in St. Petersburg, Fla., after the high-flow nasal cannula limit on the floor was raised from 6 L/min to 12 L/min, and treatment was started in the emergency department, according to a presentation at Pediatric Hospital Medicine.

A year before the change was made in April 2018, there were 17 transfers among 249 bronchiolitis patients treated on the floor, a transfer rate of 6.8%. In the year after the change, there were eight among 319 patients, a transfer rate of 2.5%. Raising the limit to 12 L/min prevented an estimated 14 transfers, for a total savings of almost $250,000, said pediatric hospitalist and assistant professor Shaila Siraj, MD.

“As hospitalists, we felt we could safely take care of these patients,” Dr. Siraj said.

So she and her colleague pediatric critical care specialist Anthony Sochet, MD, also an assistant professor of pediatrics, reviewed over a year’s worth of data at All Children’s. They found that 12 L/min – roughly 1.5 L/kg/min – was the cutoff that best discriminated between patients who needed intubation and those who did not, “so that’s what we chose,” Dr. Sochet said.

For simplicity, they broke limits down by age: A maximum flow rate of 8 L/min for children up to 6 months old; 10 L for children aged 6-12 months; and up to 12 L/min for children age 12-24 months. The fraction of inspired oxygen remained the same at 50%. Children were started at maximum flows, then weaned down as they improved. Respiratory assessments were made at least every 4 hours.

The changes were part of a larger revision of the hospital’s pathway for uncomplicated bronchiolitis in children up to 2 years old; it was a joint effort involving nurses, respiratory therapists, and pediatric hospitalists, and ED and ICU teams.

Early initiation in the ED was “probably one of the most important” changes; it kept children from wearing out as they struggled to breath. Kids often start to improve right away, but when then don’t after 30-60 minutes, it’s an indication that they should probably be triaged to the ICU for possible intubation, Dr. Siraj said.

Dr. Sochet was careful to note that institutions have to assess their own situations before taking similar steps. “Not everyone has a tertiary care ICU staffed 24 and 7,” he said.

“You have to ask what floor resources you have, what’s your ability to escalate when you need to. Use data from your own institution to guide where you pick your cutoffs. Adequate staffing is really about respiratory [therapist]/nursing ratios, not the physicians,” he said.

In addition, “in an otherwise healthy child that just has [HFNC] for bronchiolitis, there is absolutely no reason why you should be withholding feeds.” Fed children will feel better and do better, he said.

The presenters had no disclosures.

aotto@mdedge.com

SEATTLE – ICU transfers for acute bronchiolitis dropped 63% at Johns Hopkins All Children’s Hospital in St. Petersburg, Fla., after the high-flow nasal cannula limit on the floor was raised from 6 L/min to 12 L/min, and treatment was started in the emergency department, according to a presentation at Pediatric Hospital Medicine.

A year before the change was made in April 2018, there were 17 transfers among 249 bronchiolitis patients treated on the floor, a transfer rate of 6.8%. In the year after the change, there were eight among 319 patients, a transfer rate of 2.5%. Raising the limit to 12 L/min prevented an estimated 14 transfers, for a total savings of almost $250,000, said pediatric hospitalist and assistant professor Shaila Siraj, MD.

“As hospitalists, we felt we could safely take care of these patients,” Dr. Siraj said.

So she and her colleague pediatric critical care specialist Anthony Sochet, MD, also an assistant professor of pediatrics, reviewed over a year’s worth of data at All Children’s. They found that 12 L/min – roughly 1.5 L/kg/min – was the cutoff that best discriminated between patients who needed intubation and those who did not, “so that’s what we chose,” Dr. Sochet said.

For simplicity, they broke limits down by age: A maximum flow rate of 8 L/min for children up to 6 months old; 10 L for children aged 6-12 months; and up to 12 L/min for children age 12-24 months. The fraction of inspired oxygen remained the same at 50%. Children were started at maximum flows, then weaned down as they improved. Respiratory assessments were made at least every 4 hours.

The changes were part of a larger revision of the hospital’s pathway for uncomplicated bronchiolitis in children up to 2 years old; it was a joint effort involving nurses, respiratory therapists, and pediatric hospitalists, and ED and ICU teams.

Early initiation in the ED was “probably one of the most important” changes; it kept children from wearing out as they struggled to breath. Kids often start to improve right away, but when then don’t after 30-60 minutes, it’s an indication that they should probably be triaged to the ICU for possible intubation, Dr. Siraj said.

Dr. Sochet was careful to note that institutions have to assess their own situations before taking similar steps. “Not everyone has a tertiary care ICU staffed 24 and 7,” he said.

“You have to ask what floor resources you have, what’s your ability to escalate when you need to. Use data from your own institution to guide where you pick your cutoffs. Adequate staffing is really about respiratory [therapist]/nursing ratios, not the physicians,” he said.

In addition, “in an otherwise healthy child that just has [HFNC] for bronchiolitis, there is absolutely no reason why you should be withholding feeds.” Fed children will feel better and do better, he said.

The presenters had no disclosures.

aotto@mdedge.com

Initial management decisions for patients with community-acquired pneumonia (CAP) will depend on severity of infection, with need for hospitalization being one of the first decisions. Because empiric antibiotics are the mainstay of treatment and the causative organisms are seldom identified, underlying medical conditions and epidemiologic risk factors are considered when selecting an empiric regimen. As with other infections, duration of therapy is not standardized, but rather is guided by clinical improvement. Prevention of pneumonia centers around vaccination and smoking cessation. This article, the second in a 2-part review of CAP in adults, focuses on site of care decision, empiric and directed therapies, length of treatment, and prevention strategies. Evaluation and diagnosis of CAP are discussed in a separate article.

Site of Care Decision

For patients diagnosed with CAP, the clinician must decide whether treatment will be done in an outpatient or inpatient setting, and for those in the inpatient setting, whether they can safely be treated on the general medical ward or in the intensive care unit (ICU). Two common scoring systems that can be used to aid the clinician in determining severity of the infection and guide site-of-care decisions are the Pneumonia Severity Index (PSI) and CURB-65 scores.

The PSI score uses 20 different parameters, including comorbidities, laboratory parameters, and radiographic findings, to stratify patients into 5 mortality risk classes.¹ On the basis of associated mortality rates, it has been suggested that risk class I and II patients should be treated as outpatients, risk class III patients should be treated in an observation unit or with a short hospitalization, and risk class IV and V patients should be treated as inpatients.¹

The CURB-65 method of risk stratification is based on 5 clinical parameters: confusion, urea level, respiratory rate, systolic blood pressure, and age ≥ 65 years (Table 1).^2,3 A modification to the CURB-65 algorithm tool was CRB-65, which excludes urea nitrogen, making it optimal for making determinations in a clinic-based setting. It should be emphasized that these tools do not take into account other factors that should be used in determining location of treatment, such as stable home, mental illness, or concerns about compliance with medications. In many instances, it is these factors that preclude low-risk patients from being treated as outpatients.^4,5 Similarly, these scoring systems have not been validated for immunocompromised patients or those who would qualify as having health care–associated pneumonia.

Patients with CURB-65 scores of 4 or 5 are considered to have severe pneumonia, and admission to the ICU should be considered for these patients. Aside from the CURB-65 score, anyone requiring vasopressor support or mechanical ventilation merits admission to the ICU.⁶ American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) guidelines also recommend the use of “minor criteria” for making ICU admission decisions; these include respiratory rate ≥ 30 breaths/minute, PaO₂ fraction ≤ 250 mm Hg, multilobar infiltrates, confusion, blood urea nitrogen ≥ 20 mg/dL, leukopenia, thrombocytopenia, hypothermia, and hypotension.⁶ These factors are associated with increased mortality due to CAP, and ICU admission is indicated if 3 of the minor criteria for severe CAP are present.

Another clinical calculator that can be used for assessing severity of CAP is SMART-COP (systolic blood pressure, multilobar chest radiography involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation and arterial pH).⁷ This scoring system uses 8 weighted criteria to predict which patients will require intensive respiratory or vasopressor support. SMART-COP has a sensitivity of 79% and a specificity of 64% in predicting ICU admission, whereas CURB-65 has a pooled sensitivity of 57.2% and specificity of 77.2%.⁸

Antibiotic Therapy

Antibiotics are the mainstay of treatment for CAP, with the majority of patients with CAP treated empirically taking into account the site of care, likely pathogen, and antimicrobial resistance issues. Patients with pneumonia who are treated as outpatients usually respond well to empiric antibiotic treatment, and a causative pathogen is not usually sought. Patients who are hospitalized for treatment of CAP usually receive empiric antibiotic on admission. Once the etiology has been determined by microbiologic or serologic means, antimicrobial therapy should be adjusted accordingly. A CDC study found that the burden of viral etiologies was higher than previously thought, with rhinovirus and influenza accounting for 15% of cases and Streptococcus pneumoniae for only 5%.⁹ This study highlighted the fact that despite advances in molecular techniques, no pathogen is identified for most patients with pneumonia.⁹ Given the lack of discernable pathogens in the majority of cases, patients should continue to be treated with antibiotics unless a nonbacterial etiology is found.

Outpatients without comorbidities or risk factors for drug-resistant S. pneumoniae (Table 2)¹⁰ can be treated with monotherapy. Hospitalized patients are usually treated with combination intravenous therapy, although non-ICU patients who receive a respiratory fluoroquinolone can be treated orally.

As previously mentioned, antibiotic therapy is typically empiric, since neither clinical features nor radiographic features are sufficient to include or exclude infectious etiologies. Epidemiologic risk factors should be considered and, in certain cases, antimicrobial coverage should be expanded to include those entities; for example, treatment of anaerobes in the setting of lung abscess and antipseudomonal antibiotics for patients with bronchiectasis.

Of concern in the treatment of CAP is the increased prevalence of antimicrobial resistance among S. pneumoniae. The IDSA guidelines report that drug-resistant S. pneumoniae is more common in persons aged < 2 or > 65 years, and those with β-lactam therapy within the previous 3 months, alcoholism, medical comorbidities, immunosuppressive illness or therapy, or exposure to a child who attends a day care center.⁶

Staphylococcus aureus should be considered during influenza outbreaks, with either vancomycin or linezolid being the recommended agents in the setting of methicillin-resistant S. aureus (MRSA). In a study comparing vancomycin versus linezolid for nosocomial pneumonia, the all-cause 60-day mortality was similar for both agents.¹¹ Daptomycin, another agent used against MRSA, is not indicated in the setting of pneumonia because daptomycin binds to surfactant, yielding it ineffective in the treatment of pneumonia.¹² Ceftaroline is a newer cephalosporin with activity against MRSA; its role in treatment of community-acquired MRSA pneumonia has not been fully elucidated, but it appears to be a useful agent for this indication.^13,14 Similarly, other agents known to have antibacterial properties against MRSA, such as trimethoprim/sulfamethoxazole and doxycycline, have not been studied for this indication. Clindamycin has been used to treat MRSA in children, and IDSA guidelines on the treatment of MRSA list clindamycin as an alternative¹⁵ if MRSA is known to be sensitive.

A summary of recommended empiric antibiotic therapy is presented in Table 3.¹⁶

Three antibiotics were approved by the US Food and Drug Administration (FDA) for the treatment of CAP after the release of the IDSA/ATS guidelines in 2007. Ceftaroline fosamil is a fifth-generation cephalosporin that has coverage for MRSA and was approved in November 2010.¹⁷ It can only be administered intravenously and needs dose adjustment for renal function. Omadacycline is a new tetracycline that was approved by the FDA in October 2018.¹⁸ It is available in both intravenous injectable and oral forms. No dose adjustment is needed for renal function. Lefamulin is a first-in-class novel pleuromutilin antibiotic which was FDA-approved in August 2019. It can be administered intravenously or orally, with no dosage adjustment necessary in patients with renal impairment.¹⁹

Antibiotic Therapy for Selected Pathogens

Streptococcus pneumoniae

Patients with pneumococcal pneumonia who have penicillin-susceptible strains can be treated with intravenous penicillin (2 or 3 million units every 4 hours) or ceftriaxone. Once a patient meets criteria of stability, they can then be transitioned to oral penicillin, amoxicillin, or clarithromycin. Those with strains with reduced susceptibility can still be treated with penicillin, but at a higher dose (4 million units intravenously [IV] every 4 hours), or a third-generation cephalosporin. Those whose pneumococcal pneumonia is complicated by bacteremia will benefit from dual therapy if severely ill, requiring ICU monitoring. Those not severely ill can be treated with monotherapy.²⁰

Staphylococcus aureus

Staphylococcus aureus is more commonly associated with hospital-acquired pneumonia, but it may also be seen during the influenza season and in those with severe necrotizing CAP. Both linezolid and vancomycin can be used to treat MRSA CAP. As noted, ceftaroline has activity against MRSA and is approved for treatment of CAP, but is not approved by the FDA for MRSA CAP treatment. Similarly, tigecycline is approved for CAP and has activity against MRSA, but is not approved for MRSA CAP. Moreover, the FDA has warned of increased risk of death with tigecycline and has a black box warning to that effect.²¹

Legionella

Legionellosis can be treated with tetra¬cyclines, macrolides, or fluoroquinolones. For non-immunocompromised patients with mild pneumonia, any of the listed antibiotics is considered appropriate. However, patients with severe infection or those with immunosuppression should be treated with either levofloxacin or azithromycin for 7 to 10 days.²²

Chlamydophila pneumoniae

As with other atypical organisms, Chlamydophila pneumoniae can be treated with doxycycline, a macrolide, or respiratory fluoroquinolones. However, length of therapy varies by regimen used; treating with doxycycline 100 mg twice daily generally requires 14 to 21 days, whereas moxifloxacin 400 mg daily requires 10 days.²³

Mycoplasma pneumoniae

As with C. pneumoniae, length of therapy of Mycoplasma pneumoniae varies by which antimicrobial regimen is used. Shortest courses are seen with the use of macrolides for 5 days, whereas 14 days is considered standard for doxycycline or a respiratory fluoroquinolone.²⁴ It should be noted that there has been increasingly documented resistance to macrolides, with known resistance of 8.2% in the United States.²⁵

Duration of Treatment

Most patients with CAP respond to appropriate therapy within 72 hours. IDSA/ATS guidelines recommend that patients with routine cases of CAP be treated for a minimum of 5 days. Despite this, many patients are treated for an excessive amount of time, with over 70% of patients reported to have received antibiotics for more than 10 days for uncomplicated CAP.²⁶ There are instances that require longer courses of antibiotics, including cases caused by Pseudomonas aeruginosa, S. aureus, and Legionella species and patients with lung abscesses or necrotizing infections, among others.²⁷

Hospitalized patients do not need to be monitored for an additional day once they have reached clinical stability (Table 4), are able to maintain oral intake, and have normal mentation, provided that other comorbidities are stable and social needs have been met.⁶ C-reactive protein (CRP) level has been postulated as an additional measure of stability, specifically monitoring for a greater than 50% reduction in CRP; however, this was validated only for those with complicated pneumonia.²⁸ Patients discharged from the hospital with instability have higher risk of readmission or death.²⁹

Transition to Oral Therapy

IDSA/ATS guidelines⁶ recommend that patients should be transitioned from intravenous to oral antibiotics when they are improving clinically, have stable vital signs, and are able to ingest food/fluids and medications.

Management of Nonresponders

Although the majority of patients respond to antibiotics within 72 hours, treatment failure occurs in up to 15% of patients.¹⁵ Nonresponding pneumonia is generally seen in 2 patterns: worsening of clinical status despite empiric antibiotics or delay in achieving clinical stability, as defined in Table 4, after 72 hours of treatment.³⁰ Risk factors associated with nonresponding pneumonia³¹ are:

• Radiographic: multilobar infiltrates, pleural effusion, cavitation
• Bacteriologic: MRSA, gram-negative or Legionella pneumonia
• Severity index: PSI > 90
• Pharmacologic: incorrect antibiotic choice based on susceptibility

Patients with acute deterioration of clinical status require prompt transfer to a higher level of care and may require mechanical ventilator support. In those with delay in achieving clinical stability, a question centers on whether the same antibiotics can be continued while doing further radiographic/microbiologic work-up and/or changing antibiotics. History should be reviewed, with particular attention to exposures, travel history, and microbiologic and radiographic data. Clinicians should recall that viruses account for up to 20% of pneumonias and that there are also noninfectious causes that can mimic pyogenic infections.³² If adequate initial cultures were not obtained, they should be obtained; however, care must be taken in reviewing new sets of cultures while on antibiotics, as they may reveal colonization selected out by antibiotics and not a true pathogen. If repeat evaluation is unrevealing, then further evaluation with computed tomography (CT) scan and bronchoscopy with bronchoalveolar lavage and biopsy is warranted. CT scans can show pleural effusions, bronchial obstructions, or a pattern suggestive of cryptogenic pneumonia. A bronchoscopy might yield a microbiologic diagnosis and, when combined with biopsy, can also evaluate for noninfectious causes.

As with other infections, if escalation of antibiotics is undertaken, clinicians should try to determine the reason for nonresponse. To simply broaden antimicrobial therapy without attempts at establishing a microbiologic or radiographic cause for nonresponse may lead to inappropriate treatment and recurrence of infection. Aside from patients who have bacteremic pneumococcal pneumonia in an ICU setting, there are no published reports pointing to superiority of combination antibiotics.²⁰

Other Treatment

Several agents have been evaluated as adjunctive treatment of pneumonia to decrease the inflammatory response associated with pneumonia; namely, steroids, macrolide antibiotics, and statins. To date, only the use of steroids (methylprednisolone 0.5 mg/kg every 12 hours for 5 days) in those with severe CAP and high initial anti-inflammatory response (CRP > 150) has been shown to decrease treatment failure, decrease risk of acute respiratory distress syndrome, and possibly reduce length of stay and duration of intravenous antibiotics, without effect on mortality or adverse side effects.^33,34 However, a recent double-blind randomized study conducted in Australia in which patients admitted with CAP were prescribed prednisolone acetate (50 mg/day for 7 days) and de-escalated from parenteral to oral antibiotics according to standardized criteria revealed no difference in mortality, length of stay, or readmission rates between the corticosteroids group and the control group at 90-day follow-up.³⁵ At this point, corticosteroid as an adjunctive treatment for CAP is still controversial and the new 2019 ATS/IDSA guidelines recommend not routinely using corticosteroids in all patients with CAP.³⁶ Other adjunctive methods have not been found to have significant impact.⁶

Prevention of Pneumonia

Prevention of pneumococcal pneumonia involves vaccinations to prevent infection caused by S. pneumoniae and influenza viruses. As influenza is a risk factor for bacterial infection, specifically with S. pneumoniae, influenza vaccination can help prevent bacterial pneumonia.³⁷ In their most recent recommendations, the CDC continues to recommend routine influenza vaccination for all persons older than age 6 months, unless otherwise contraindicated.³⁸

There are 2 vaccines for prevention of pneumococcal disease: the pneumococcal polysaccharide vaccine (PPSV23) and a conjugate vaccine (PCV13). Following vaccination with PPSV23, 80% of adults develop antibodies against at least 18 of the 23 serotypes.³⁹ PPSV23 is reported to be protective against invasive pneumococcal infection, although there is no consensus regarding whether PPSV23 leads to decreased rates of pneumonia.⁴⁰ On the other hand, PCV13 vaccination was associated with prevention of both invasive disease and CAP in adults aged 65 years or older.⁴¹ The CDC recommends that all children aged 2 years or younger receive PCV13, and those aged 65 or older receive PCV13 followed by a dose of PPSV23.^42,43 The dose of PPSV23 should be given at least 1 year after the dose of PCV13 is administered.⁴⁴ Persons younger than 65 years with immunocompromising and certain other conditions should also receive vaccination (Table 5).⁴⁴ Full recommendations, many scenarios, and details on timing of vaccinations can be found at the CDC’s website.

Cigarette smoking increases the risk of respiratory infections, as evidenced by smokers accounting for almost half of all patients with invasive pneumococcal disease.¹¹ As this is a modifiable risk factor, smoking cessation should be part of a comprehensive approach toward prevention of pneumonia.

Summary

Most patients with CAP are treated empirically with antibiotics, with therapy selection based on the site of care, likely pathogen, and antimicrobial resistance issues. Those treated as outpatients usually respond well to empiric antibiotic treatment, and a causative pathogen is not usually sought. Patients who are hospitalized for treatment usually receive empiric antibiotic on admission, and antimicrobial therapy is adjusted accordingly once the etiology has been determined by microbiologic or serologic means. At this time, the use of corticosteroid as an adjunctive treatment for CAP is still controversial, so not all patients with CAP should routinely receive corticosteroids. Because vaccination (PPSV23, PCV13, and influenza vaccine) remains the most effective tool in preventing the development of CAP, clinicians should strive for 100% vaccination rates in persons without contraindications.

Initial management decisions for patients with community-acquired pneumonia (CAP) will depend on severity of infection, with need for hospitalization being one of the first decisions. Because empiric antibiotics are the mainstay of treatment and the causative organisms are seldom identified, underlying medical conditions and epidemiologic risk factors are considered when selecting an empiric regimen. As with other infections, duration of therapy is not standardized, but rather is guided by clinical improvement. Prevention of pneumonia centers around vaccination and smoking cessation. This article, the second in a 2-part review of CAP in adults, focuses on site of care decision, empiric and directed therapies, length of treatment, and prevention strategies. Evaluation and diagnosis of CAP are discussed in a separate article.

Site of Care Decision

For patients diagnosed with CAP, the clinician must decide whether treatment will be done in an outpatient or inpatient setting, and for those in the inpatient setting, whether they can safely be treated on the general medical ward or in the intensive care unit (ICU). Two common scoring systems that can be used to aid the clinician in determining severity of the infection and guide site-of-care decisions are the Pneumonia Severity Index (PSI) and CURB-65 scores.

The PSI score uses 20 different parameters, including comorbidities, laboratory parameters, and radiographic findings, to stratify patients into 5 mortality risk classes.¹ On the basis of associated mortality rates, it has been suggested that risk class I and II patients should be treated as outpatients, risk class III patients should be treated in an observation unit or with a short hospitalization, and risk class IV and V patients should be treated as inpatients.¹

The CURB-65 method of risk stratification is based on 5 clinical parameters: confusion, urea level, respiratory rate, systolic blood pressure, and age ≥ 65 years (Table 1).^2,3 A modification to the CURB-65 algorithm tool was CRB-65, which excludes urea nitrogen, making it optimal for making determinations in a clinic-based setting. It should be emphasized that these tools do not take into account other factors that should be used in determining location of treatment, such as stable home, mental illness, or concerns about compliance with medications. In many instances, it is these factors that preclude low-risk patients from being treated as outpatients.^4,5 Similarly, these scoring systems have not been validated for immunocompromised patients or those who would qualify as having health care–associated pneumonia.

Patients with CURB-65 scores of 4 or 5 are considered to have severe pneumonia, and admission to the ICU should be considered for these patients. Aside from the CURB-65 score, anyone requiring vasopressor support or mechanical ventilation merits admission to the ICU.⁶ American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) guidelines also recommend the use of “minor criteria” for making ICU admission decisions; these include respiratory rate ≥ 30 breaths/minute, PaO₂ fraction ≤ 250 mm Hg, multilobar infiltrates, confusion, blood urea nitrogen ≥ 20 mg/dL, leukopenia, thrombocytopenia, hypothermia, and hypotension.⁶ These factors are associated with increased mortality due to CAP, and ICU admission is indicated if 3 of the minor criteria for severe CAP are present.

Another clinical calculator that can be used for assessing severity of CAP is SMART-COP (systolic blood pressure, multilobar chest radiography involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation and arterial pH).⁷ This scoring system uses 8 weighted criteria to predict which patients will require intensive respiratory or vasopressor support. SMART-COP has a sensitivity of 79% and a specificity of 64% in predicting ICU admission, whereas CURB-65 has a pooled sensitivity of 57.2% and specificity of 77.2%.⁸

Antibiotic Therapy

Antibiotics are the mainstay of treatment for CAP, with the majority of patients with CAP treated empirically taking into account the site of care, likely pathogen, and antimicrobial resistance issues. Patients with pneumonia who are treated as outpatients usually respond well to empiric antibiotic treatment, and a causative pathogen is not usually sought. Patients who are hospitalized for treatment of CAP usually receive empiric antibiotic on admission. Once the etiology has been determined by microbiologic or serologic means, antimicrobial therapy should be adjusted accordingly. A CDC study found that the burden of viral etiologies was higher than previously thought, with rhinovirus and influenza accounting for 15% of cases and Streptococcus pneumoniae for only 5%.⁹ This study highlighted the fact that despite advances in molecular techniques, no pathogen is identified for most patients with pneumonia.⁹ Given the lack of discernable pathogens in the majority of cases, patients should continue to be treated with antibiotics unless a nonbacterial etiology is found.

Outpatients without comorbidities or risk factors for drug-resistant S. pneumoniae (Table 2)¹⁰ can be treated with monotherapy. Hospitalized patients are usually treated with combination intravenous therapy, although non-ICU patients who receive a respiratory fluoroquinolone can be treated orally.

As previously mentioned, antibiotic therapy is typically empiric, since neither clinical features nor radiographic features are sufficient to include or exclude infectious etiologies. Epidemiologic risk factors should be considered and, in certain cases, antimicrobial coverage should be expanded to include those entities; for example, treatment of anaerobes in the setting of lung abscess and antipseudomonal antibiotics for patients with bronchiectasis.

Of concern in the treatment of CAP is the increased prevalence of antimicrobial resistance among S. pneumoniae. The IDSA guidelines report that drug-resistant S. pneumoniae is more common in persons aged < 2 or > 65 years, and those with β-lactam therapy within the previous 3 months, alcoholism, medical comorbidities, immunosuppressive illness or therapy, or exposure to a child who attends a day care center.⁶

Staphylococcus aureus should be considered during influenza outbreaks, with either vancomycin or linezolid being the recommended agents in the setting of methicillin-resistant S. aureus (MRSA). In a study comparing vancomycin versus linezolid for nosocomial pneumonia, the all-cause 60-day mortality was similar for both agents.¹¹ Daptomycin, another agent used against MRSA, is not indicated in the setting of pneumonia because daptomycin binds to surfactant, yielding it ineffective in the treatment of pneumonia.¹² Ceftaroline is a newer cephalosporin with activity against MRSA; its role in treatment of community-acquired MRSA pneumonia has not been fully elucidated, but it appears to be a useful agent for this indication.^13,14 Similarly, other agents known to have antibacterial properties against MRSA, such as trimethoprim/sulfamethoxazole and doxycycline, have not been studied for this indication. Clindamycin has been used to treat MRSA in children, and IDSA guidelines on the treatment of MRSA list clindamycin as an alternative¹⁵ if MRSA is known to be sensitive.

A summary of recommended empiric antibiotic therapy is presented in Table 3.¹⁶

Three antibiotics were approved by the US Food and Drug Administration (FDA) for the treatment of CAP after the release of the IDSA/ATS guidelines in 2007. Ceftaroline fosamil is a fifth-generation cephalosporin that has coverage for MRSA and was approved in November 2010.¹⁷ It can only be administered intravenously and needs dose adjustment for renal function. Omadacycline is a new tetracycline that was approved by the FDA in October 2018.¹⁸ It is available in both intravenous injectable and oral forms. No dose adjustment is needed for renal function. Lefamulin is a first-in-class novel pleuromutilin antibiotic which was FDA-approved in August 2019. It can be administered intravenously or orally, with no dosage adjustment necessary in patients with renal impairment.¹⁹

Antibiotic Therapy for Selected Pathogens

Streptococcus pneumoniae

Patients with pneumococcal pneumonia who have penicillin-susceptible strains can be treated with intravenous penicillin (2 or 3 million units every 4 hours) or ceftriaxone. Once a patient meets criteria of stability, they can then be transitioned to oral penicillin, amoxicillin, or clarithromycin. Those with strains with reduced susceptibility can still be treated with penicillin, but at a higher dose (4 million units intravenously [IV] every 4 hours), or a third-generation cephalosporin. Those whose pneumococcal pneumonia is complicated by bacteremia will benefit from dual therapy if severely ill, requiring ICU monitoring. Those not severely ill can be treated with monotherapy.²⁰

Staphylococcus aureus

Staphylococcus aureus is more commonly associated with hospital-acquired pneumonia, but it may also be seen during the influenza season and in those with severe necrotizing CAP. Both linezolid and vancomycin can be used to treat MRSA CAP. As noted, ceftaroline has activity against MRSA and is approved for treatment of CAP, but is not approved by the FDA for MRSA CAP treatment. Similarly, tigecycline is approved for CAP and has activity against MRSA, but is not approved for MRSA CAP. Moreover, the FDA has warned of increased risk of death with tigecycline and has a black box warning to that effect.²¹

Legionella

Legionellosis can be treated with tetra¬cyclines, macrolides, or fluoroquinolones. For non-immunocompromised patients with mild pneumonia, any of the listed antibiotics is considered appropriate. However, patients with severe infection or those with immunosuppression should be treated with either levofloxacin or azithromycin for 7 to 10 days.²²

Chlamydophila pneumoniae

As with other atypical organisms, Chlamydophila pneumoniae can be treated with doxycycline, a macrolide, or respiratory fluoroquinolones. However, length of therapy varies by regimen used; treating with doxycycline 100 mg twice daily generally requires 14 to 21 days, whereas moxifloxacin 400 mg daily requires 10 days.²³

Mycoplasma pneumoniae

As with C. pneumoniae, length of therapy of Mycoplasma pneumoniae varies by which antimicrobial regimen is used. Shortest courses are seen with the use of macrolides for 5 days, whereas 14 days is considered standard for doxycycline or a respiratory fluoroquinolone.²⁴ It should be noted that there has been increasingly documented resistance to macrolides, with known resistance of 8.2% in the United States.²⁵

Duration of Treatment

Most patients with CAP respond to appropriate therapy within 72 hours. IDSA/ATS guidelines recommend that patients with routine cases of CAP be treated for a minimum of 5 days. Despite this, many patients are treated for an excessive amount of time, with over 70% of patients reported to have received antibiotics for more than 10 days for uncomplicated CAP.²⁶ There are instances that require longer courses of antibiotics, including cases caused by Pseudomonas aeruginosa, S. aureus, and Legionella species and patients with lung abscesses or necrotizing infections, among others.²⁷

Hospitalized patients do not need to be monitored for an additional day once they have reached clinical stability (Table 4), are able to maintain oral intake, and have normal mentation, provided that other comorbidities are stable and social needs have been met.⁶ C-reactive protein (CRP) level has been postulated as an additional measure of stability, specifically monitoring for a greater than 50% reduction in CRP; however, this was validated only for those with complicated pneumonia.²⁸ Patients discharged from the hospital with instability have higher risk of readmission or death.²⁹

Transition to Oral Therapy

IDSA/ATS guidelines⁶ recommend that patients should be transitioned from intravenous to oral antibiotics when they are improving clinically, have stable vital signs, and are able to ingest food/fluids and medications.

Management of Nonresponders

Although the majority of patients respond to antibiotics within 72 hours, treatment failure occurs in up to 15% of patients.¹⁵ Nonresponding pneumonia is generally seen in 2 patterns: worsening of clinical status despite empiric antibiotics or delay in achieving clinical stability, as defined in Table 4, after 72 hours of treatment.³⁰ Risk factors associated with nonresponding pneumonia³¹ are:

• Radiographic: multilobar infiltrates, pleural effusion, cavitation
• Bacteriologic: MRSA, gram-negative or Legionella pneumonia
• Severity index: PSI > 90
• Pharmacologic: incorrect antibiotic choice based on susceptibility

Patients with acute deterioration of clinical status require prompt transfer to a higher level of care and may require mechanical ventilator support. In those with delay in achieving clinical stability, a question centers on whether the same antibiotics can be continued while doing further radiographic/microbiologic work-up and/or changing antibiotics. History should be reviewed, with particular attention to exposures, travel history, and microbiologic and radiographic data. Clinicians should recall that viruses account for up to 20% of pneumonias and that there are also noninfectious causes that can mimic pyogenic infections.³² If adequate initial cultures were not obtained, they should be obtained; however, care must be taken in reviewing new sets of cultures while on antibiotics, as they may reveal colonization selected out by antibiotics and not a true pathogen. If repeat evaluation is unrevealing, then further evaluation with computed tomography (CT) scan and bronchoscopy with bronchoalveolar lavage and biopsy is warranted. CT scans can show pleural effusions, bronchial obstructions, or a pattern suggestive of cryptogenic pneumonia. A bronchoscopy might yield a microbiologic diagnosis and, when combined with biopsy, can also evaluate for noninfectious causes.

As with other infections, if escalation of antibiotics is undertaken, clinicians should try to determine the reason for nonresponse. To simply broaden antimicrobial therapy without attempts at establishing a microbiologic or radiographic cause for nonresponse may lead to inappropriate treatment and recurrence of infection. Aside from patients who have bacteremic pneumococcal pneumonia in an ICU setting, there are no published reports pointing to superiority of combination antibiotics.²⁰

Other Treatment

Several agents have been evaluated as adjunctive treatment of pneumonia to decrease the inflammatory response associated with pneumonia; namely, steroids, macrolide antibiotics, and statins. To date, only the use of steroids (methylprednisolone 0.5 mg/kg every 12 hours for 5 days) in those with severe CAP and high initial anti-inflammatory response (CRP > 150) has been shown to decrease treatment failure, decrease risk of acute respiratory distress syndrome, and possibly reduce length of stay and duration of intravenous antibiotics, without effect on mortality or adverse side effects.^33,34 However, a recent double-blind randomized study conducted in Australia in which patients admitted with CAP were prescribed prednisolone acetate (50 mg/day for 7 days) and de-escalated from parenteral to oral antibiotics according to standardized criteria revealed no difference in mortality, length of stay, or readmission rates between the corticosteroids group and the control group at 90-day follow-up.³⁵ At this point, corticosteroid as an adjunctive treatment for CAP is still controversial and the new 2019 ATS/IDSA guidelines recommend not routinely using corticosteroids in all patients with CAP.³⁶ Other adjunctive methods have not been found to have significant impact.⁶

Prevention of Pneumonia

Prevention of pneumococcal pneumonia involves vaccinations to prevent infection caused by S. pneumoniae and influenza viruses. As influenza is a risk factor for bacterial infection, specifically with S. pneumoniae, influenza vaccination can help prevent bacterial pneumonia.³⁷ In their most recent recommendations, the CDC continues to recommend routine influenza vaccination for all persons older than age 6 months, unless otherwise contraindicated.³⁸

There are 2 vaccines for prevention of pneumococcal disease: the pneumococcal polysaccharide vaccine (PPSV23) and a conjugate vaccine (PCV13). Following vaccination with PPSV23, 80% of adults develop antibodies against at least 18 of the 23 serotypes.³⁹ PPSV23 is reported to be protective against invasive pneumococcal infection, although there is no consensus regarding whether PPSV23 leads to decreased rates of pneumonia.⁴⁰ On the other hand, PCV13 vaccination was associated with prevention of both invasive disease and CAP in adults aged 65 years or older.⁴¹ The CDC recommends that all children aged 2 years or younger receive PCV13, and those aged 65 or older receive PCV13 followed by a dose of PPSV23.^42,43 The dose of PPSV23 should be given at least 1 year after the dose of PCV13 is administered.⁴⁴ Persons younger than 65 years with immunocompromising and certain other conditions should also receive vaccination (Table 5).⁴⁴ Full recommendations, many scenarios, and details on timing of vaccinations can be found at the CDC’s website.

Cigarette smoking increases the risk of respiratory infections, as evidenced by smokers accounting for almost half of all patients with invasive pneumococcal disease.¹¹ As this is a modifiable risk factor, smoking cessation should be part of a comprehensive approach toward prevention of pneumonia.

Summary

Most patients with CAP are treated empirically with antibiotics, with therapy selection based on the site of care, likely pathogen, and antimicrobial resistance issues. Those treated as outpatients usually respond well to empiric antibiotic treatment, and a causative pathogen is not usually sought. Patients who are hospitalized for treatment usually receive empiric antibiotic on admission, and antimicrobial therapy is adjusted accordingly once the etiology has been determined by microbiologic or serologic means. At this time, the use of corticosteroid as an adjunctive treatment for CAP is still controversial, so not all patients with CAP should routinely receive corticosteroids. Because vaccination (PPSV23, PCV13, and influenza vaccine) remains the most effective tool in preventing the development of CAP, clinicians should strive for 100% vaccination rates in persons without contraindications.

Initial management decisions for patients with community-acquired pneumonia (CAP) will depend on severity of infection, with need for hospitalization being one of the first decisions. Because empiric antibiotics are the mainstay of treatment and the causative organisms are seldom identified, underlying medical conditions and epidemiologic risk factors are considered when selecting an empiric regimen. As with other infections, duration of therapy is not standardized, but rather is guided by clinical improvement. Prevention of pneumonia centers around vaccination and smoking cessation. This article, the second in a 2-part review of CAP in adults, focuses on site of care decision, empiric and directed therapies, length of treatment, and prevention strategies. Evaluation and diagnosis of CAP are discussed in a separate article.

Site of Care Decision

For patients diagnosed with CAP, the clinician must decide whether treatment will be done in an outpatient or inpatient setting, and for those in the inpatient setting, whether they can safely be treated on the general medical ward or in the intensive care unit (ICU). Two common scoring systems that can be used to aid the clinician in determining severity of the infection and guide site-of-care decisions are the Pneumonia Severity Index (PSI) and CURB-65 scores.

The PSI score uses 20 different parameters, including comorbidities, laboratory parameters, and radiographic findings, to stratify patients into 5 mortality risk classes.¹ On the basis of associated mortality rates, it has been suggested that risk class I and II patients should be treated as outpatients, risk class III patients should be treated in an observation unit or with a short hospitalization, and risk class IV and V patients should be treated as inpatients.¹

The CURB-65 method of risk stratification is based on 5 clinical parameters: confusion, urea level, respiratory rate, systolic blood pressure, and age ≥ 65 years (Table 1).^2,3 A modification to the CURB-65 algorithm tool was CRB-65, which excludes urea nitrogen, making it optimal for making determinations in a clinic-based setting. It should be emphasized that these tools do not take into account other factors that should be used in determining location of treatment, such as stable home, mental illness, or concerns about compliance with medications. In many instances, it is these factors that preclude low-risk patients from being treated as outpatients.^4,5 Similarly, these scoring systems have not been validated for immunocompromised patients or those who would qualify as having health care–associated pneumonia.

Patients with CURB-65 scores of 4 or 5 are considered to have severe pneumonia, and admission to the ICU should be considered for these patients. Aside from the CURB-65 score, anyone requiring vasopressor support or mechanical ventilation merits admission to the ICU.⁶ American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) guidelines also recommend the use of “minor criteria” for making ICU admission decisions; these include respiratory rate ≥ 30 breaths/minute, PaO₂ fraction ≤ 250 mm Hg, multilobar infiltrates, confusion, blood urea nitrogen ≥ 20 mg/dL, leukopenia, thrombocytopenia, hypothermia, and hypotension.⁶ These factors are associated with increased mortality due to CAP, and ICU admission is indicated if 3 of the minor criteria for severe CAP are present.

Another clinical calculator that can be used for assessing severity of CAP is SMART-COP (systolic blood pressure, multilobar chest radiography involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation and arterial pH).⁷ This scoring system uses 8 weighted criteria to predict which patients will require intensive respiratory or vasopressor support. SMART-COP has a sensitivity of 79% and a specificity of 64% in predicting ICU admission, whereas CURB-65 has a pooled sensitivity of 57.2% and specificity of 77.2%.⁸

Antibiotic Therapy

Antibiotics are the mainstay of treatment for CAP, with the majority of patients with CAP treated empirically taking into account the site of care, likely pathogen, and antimicrobial resistance issues. Patients with pneumonia who are treated as outpatients usually respond well to empiric antibiotic treatment, and a causative pathogen is not usually sought. Patients who are hospitalized for treatment of CAP usually receive empiric antibiotic on admission. Once the etiology has been determined by microbiologic or serologic means, antimicrobial therapy should be adjusted accordingly. A CDC study found that the burden of viral etiologies was higher than previously thought, with rhinovirus and influenza accounting for 15% of cases and Streptococcus pneumoniae for only 5%.⁹ This study highlighted the fact that despite advances in molecular techniques, no pathogen is identified for most patients with pneumonia.⁹ Given the lack of discernable pathogens in the majority of cases, patients should continue to be treated with antibiotics unless a nonbacterial etiology is found.

Outpatients without comorbidities or risk factors for drug-resistant S. pneumoniae (Table 2)¹⁰ can be treated with monotherapy. Hospitalized patients are usually treated with combination intravenous therapy, although non-ICU patients who receive a respiratory fluoroquinolone can be treated orally.

As previously mentioned, antibiotic therapy is typically empiric, since neither clinical features nor radiographic features are sufficient to include or exclude infectious etiologies. Epidemiologic risk factors should be considered and, in certain cases, antimicrobial coverage should be expanded to include those entities; for example, treatment of anaerobes in the setting of lung abscess and antipseudomonal antibiotics for patients with bronchiectasis.

Of concern in the treatment of CAP is the increased prevalence of antimicrobial resistance among S. pneumoniae. The IDSA guidelines report that drug-resistant S. pneumoniae is more common in persons aged < 2 or > 65 years, and those with β-lactam therapy within the previous 3 months, alcoholism, medical comorbidities, immunosuppressive illness or therapy, or exposure to a child who attends a day care center.⁶

Staphylococcus aureus should be considered during influenza outbreaks, with either vancomycin or linezolid being the recommended agents in the setting of methicillin-resistant S. aureus (MRSA). In a study comparing vancomycin versus linezolid for nosocomial pneumonia, the all-cause 60-day mortality was similar for both agents.¹¹ Daptomycin, another agent used against MRSA, is not indicated in the setting of pneumonia because daptomycin binds to surfactant, yielding it ineffective in the treatment of pneumonia.¹² Ceftaroline is a newer cephalosporin with activity against MRSA; its role in treatment of community-acquired MRSA pneumonia has not been fully elucidated, but it appears to be a useful agent for this indication.^13,14 Similarly, other agents known to have antibacterial properties against MRSA, such as trimethoprim/sulfamethoxazole and doxycycline, have not been studied for this indication. Clindamycin has been used to treat MRSA in children, and IDSA guidelines on the treatment of MRSA list clindamycin as an alternative¹⁵ if MRSA is known to be sensitive.

A summary of recommended empiric antibiotic therapy is presented in Table 3.¹⁶

Three antibiotics were approved by the US Food and Drug Administration (FDA) for the treatment of CAP after the release of the IDSA/ATS guidelines in 2007. Ceftaroline fosamil is a fifth-generation cephalosporin that has coverage for MRSA and was approved in November 2010.¹⁷ It can only be administered intravenously and needs dose adjustment for renal function. Omadacycline is a new tetracycline that was approved by the FDA in October 2018.¹⁸ It is available in both intravenous injectable and oral forms. No dose adjustment is needed for renal function. Lefamulin is a first-in-class novel pleuromutilin antibiotic which was FDA-approved in August 2019. It can be administered intravenously or orally, with no dosage adjustment necessary in patients with renal impairment.¹⁹

Antibiotic Therapy for Selected Pathogens

Streptococcus pneumoniae

Patients with pneumococcal pneumonia who have penicillin-susceptible strains can be treated with intravenous penicillin (2 or 3 million units every 4 hours) or ceftriaxone. Once a patient meets criteria of stability, they can then be transitioned to oral penicillin, amoxicillin, or clarithromycin. Those with strains with reduced susceptibility can still be treated with penicillin, but at a higher dose (4 million units intravenously [IV] every 4 hours), or a third-generation cephalosporin. Those whose pneumococcal pneumonia is complicated by bacteremia will benefit from dual therapy if severely ill, requiring ICU monitoring. Those not severely ill can be treated with monotherapy.²⁰

Staphylococcus aureus

Staphylococcus aureus is more commonly associated with hospital-acquired pneumonia, but it may also be seen during the influenza season and in those with severe necrotizing CAP. Both linezolid and vancomycin can be used to treat MRSA CAP. As noted, ceftaroline has activity against MRSA and is approved for treatment of CAP, but is not approved by the FDA for MRSA CAP treatment. Similarly, tigecycline is approved for CAP and has activity against MRSA, but is not approved for MRSA CAP. Moreover, the FDA has warned of increased risk of death with tigecycline and has a black box warning to that effect.²¹

Legionella

Legionellosis can be treated with tetra¬cyclines, macrolides, or fluoroquinolones. For non-immunocompromised patients with mild pneumonia, any of the listed antibiotics is considered appropriate. However, patients with severe infection or those with immunosuppression should be treated with either levofloxacin or azithromycin for 7 to 10 days.²²

Chlamydophila pneumoniae

As with other atypical organisms, Chlamydophila pneumoniae can be treated with doxycycline, a macrolide, or respiratory fluoroquinolones. However, length of therapy varies by regimen used; treating with doxycycline 100 mg twice daily generally requires 14 to 21 days, whereas moxifloxacin 400 mg daily requires 10 days.²³

Mycoplasma pneumoniae

As with C. pneumoniae, length of therapy of Mycoplasma pneumoniae varies by which antimicrobial regimen is used. Shortest courses are seen with the use of macrolides for 5 days, whereas 14 days is considered standard for doxycycline or a respiratory fluoroquinolone.²⁴ It should be noted that there has been increasingly documented resistance to macrolides, with known resistance of 8.2% in the United States.²⁵

Duration of Treatment

Most patients with CAP respond to appropriate therapy within 72 hours. IDSA/ATS guidelines recommend that patients with routine cases of CAP be treated for a minimum of 5 days. Despite this, many patients are treated for an excessive amount of time, with over 70% of patients reported to have received antibiotics for more than 10 days for uncomplicated CAP.²⁶ There are instances that require longer courses of antibiotics, including cases caused by Pseudomonas aeruginosa, S. aureus, and Legionella species and patients with lung abscesses or necrotizing infections, among others.²⁷

Hospitalized patients do not need to be monitored for an additional day once they have reached clinical stability (Table 4), are able to maintain oral intake, and have normal mentation, provided that other comorbidities are stable and social needs have been met.⁶ C-reactive protein (CRP) level has been postulated as an additional measure of stability, specifically monitoring for a greater than 50% reduction in CRP; however, this was validated only for those with complicated pneumonia.²⁸ Patients discharged from the hospital with instability have higher risk of readmission or death.²⁹

Transition to Oral Therapy

IDSA/ATS guidelines⁶ recommend that patients should be transitioned from intravenous to oral antibiotics when they are improving clinically, have stable vital signs, and are able to ingest food/fluids and medications.

Management of Nonresponders

Although the majority of patients respond to antibiotics within 72 hours, treatment failure occurs in up to 15% of patients.¹⁵ Nonresponding pneumonia is generally seen in 2 patterns: worsening of clinical status despite empiric antibiotics or delay in achieving clinical stability, as defined in Table 4, after 72 hours of treatment.³⁰ Risk factors associated with nonresponding pneumonia³¹ are:

• Radiographic: multilobar infiltrates, pleural effusion, cavitation
• Bacteriologic: MRSA, gram-negative or Legionella pneumonia
• Severity index: PSI > 90
• Pharmacologic: incorrect antibiotic choice based on susceptibility

Patients with acute deterioration of clinical status require prompt transfer to a higher level of care and may require mechanical ventilator support. In those with delay in achieving clinical stability, a question centers on whether the same antibiotics can be continued while doing further radiographic/microbiologic work-up and/or changing antibiotics. History should be reviewed, with particular attention to exposures, travel history, and microbiologic and radiographic data. Clinicians should recall that viruses account for up to 20% of pneumonias and that there are also noninfectious causes that can mimic pyogenic infections.³² If adequate initial cultures were not obtained, they should be obtained; however, care must be taken in reviewing new sets of cultures while on antibiotics, as they may reveal colonization selected out by antibiotics and not a true pathogen. If repeat evaluation is unrevealing, then further evaluation with computed tomography (CT) scan and bronchoscopy with bronchoalveolar lavage and biopsy is warranted. CT scans can show pleural effusions, bronchial obstructions, or a pattern suggestive of cryptogenic pneumonia. A bronchoscopy might yield a microbiologic diagnosis and, when combined with biopsy, can also evaluate for noninfectious causes.

As with other infections, if escalation of antibiotics is undertaken, clinicians should try to determine the reason for nonresponse. To simply broaden antimicrobial therapy without attempts at establishing a microbiologic or radiographic cause for nonresponse may lead to inappropriate treatment and recurrence of infection. Aside from patients who have bacteremic pneumococcal pneumonia in an ICU setting, there are no published reports pointing to superiority of combination antibiotics.²⁰

Other Treatment

Several agents have been evaluated as adjunctive treatment of pneumonia to decrease the inflammatory response associated with pneumonia; namely, steroids, macrolide antibiotics, and statins. To date, only the use of steroids (methylprednisolone 0.5 mg/kg every 12 hours for 5 days) in those with severe CAP and high initial anti-inflammatory response (CRP > 150) has been shown to decrease treatment failure, decrease risk of acute respiratory distress syndrome, and possibly reduce length of stay and duration of intravenous antibiotics, without effect on mortality or adverse side effects.^33,34 However, a recent double-blind randomized study conducted in Australia in which patients admitted with CAP were prescribed prednisolone acetate (50 mg/day for 7 days) and de-escalated from parenteral to oral antibiotics according to standardized criteria revealed no difference in mortality, length of stay, or readmission rates between the corticosteroids group and the control group at 90-day follow-up.³⁵ At this point, corticosteroid as an adjunctive treatment for CAP is still controversial and the new 2019 ATS/IDSA guidelines recommend not routinely using corticosteroids in all patients with CAP.³⁶ Other adjunctive methods have not been found to have significant impact.⁶

Prevention of Pneumonia

Prevention of pneumococcal pneumonia involves vaccinations to prevent infection caused by S. pneumoniae and influenza viruses. As influenza is a risk factor for bacterial infection, specifically with S. pneumoniae, influenza vaccination can help prevent bacterial pneumonia.³⁷ In their most recent recommendations, the CDC continues to recommend routine influenza vaccination for all persons older than age 6 months, unless otherwise contraindicated.³⁸

There are 2 vaccines for prevention of pneumococcal disease: the pneumococcal polysaccharide vaccine (PPSV23) and a conjugate vaccine (PCV13). Following vaccination with PPSV23, 80% of adults develop antibodies against at least 18 of the 23 serotypes.³⁹ PPSV23 is reported to be protective against invasive pneumococcal infection, although there is no consensus regarding whether PPSV23 leads to decreased rates of pneumonia.⁴⁰ On the other hand, PCV13 vaccination was associated with prevention of both invasive disease and CAP in adults aged 65 years or older.⁴¹ The CDC recommends that all children aged 2 years or younger receive PCV13, and those aged 65 or older receive PCV13 followed by a dose of PPSV23.^42,43 The dose of PPSV23 should be given at least 1 year after the dose of PCV13 is administered.⁴⁴ Persons younger than 65 years with immunocompromising and certain other conditions should also receive vaccination (Table 5).⁴⁴ Full recommendations, many scenarios, and details on timing of vaccinations can be found at the CDC’s website.

Cigarette smoking increases the risk of respiratory infections, as evidenced by smokers accounting for almost half of all patients with invasive pneumococcal disease.¹¹ As this is a modifiable risk factor, smoking cessation should be part of a comprehensive approach toward prevention of pneumonia.

Summary

Most patients with CAP are treated empirically with antibiotics, with therapy selection based on the site of care, likely pathogen, and antimicrobial resistance issues. Those treated as outpatients usually respond well to empiric antibiotic treatment, and a causative pathogen is not usually sought. Patients who are hospitalized for treatment usually receive empiric antibiotic on admission, and antimicrobial therapy is adjusted accordingly once the etiology has been determined by microbiologic or serologic means. At this time, the use of corticosteroid as an adjunctive treatment for CAP is still controversial, so not all patients with CAP should routinely receive corticosteroids. Because vaccination (PPSV23, PCV13, and influenza vaccine) remains the most effective tool in preventing the development of CAP, clinicians should strive for 100% vaccination rates in persons without contraindications.

Despite advances in medical science, pneumonia remains a major cause of morbidity and mortality. In 2017, 49,157 patients in the United States died from the disease.¹ Pneumonia can be classified as community-acquired, hospital-acquired, or ventilator-associated. Another category, healthcare-associated pneumonia, was included in an earlier Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guideline but was removed from the 2016 guideline because there was no clear evidence that patients diagnosed with healthcare-associated pneumonia were at higher risk for harboring multidrug-resistant pathogens.² This review is the first of 2 articles focusing on the management of community-acquired pneumonia (CAP). Here, we review CAP epidemiology, microbiology, predisposing factors, and diagnosis; current treatment and prevention of CAP are reviewed in a separate article.

Definition and Epidemiology

CAP is defined as an acute infection of the lungs that develops in patients who have not been hospitalized recently and have not had regular exposure to the health care system.³ A previously ambulatory patient who is diagnosed with pneumonia within 48 hours after admission also meets the criteria for CAP. Approximately 4 to 5 million cases of CAP are diagnosed in the United States annually.⁴ About 25% of CAP patients require hospitalization, and about 5% to 10% of these patients are admitted to the intensive care unit (ICU).⁵ In-hospital mortality is considerable (~10% in population-based studies),⁶ and 30-day mortality was found to be as high as 23% in a review by File and Marrie.⁷ CAP also confers a high risk of long-term morbidity and mortality compared with the general population who have never had CAP, irrespective of age.⁸

Causative Organisms

Numerous microorganisms can cause CAP. Common causes and less common causes are delineated in Table 1. Until recently, many studies had demonstrated that pneumococcus was the most common cause of CAP. However, in the CDC Etiology of Pneumonia in the Community (EPIC) study team’s 2015 prospective, multicenter, population-based study, no pathogen was detected in the majority of patients diagnosed with CAP requiring hospitalization. The most common pathogens they detected were rhinovirus (9%), followed by influenza virus (6%) and pneumococcus (5%).⁹ Factors considered to be contributing to the decrease in the percentage of pneumococcus in patients diagnosed with CAP are the widespread use of pneumococcal vaccine and reduced rates of smoking.^10,11

Predisposing Factors

Most people diagnosed with CAP have 1 or more predisposing factors (Table 2).^12,13 Patients who develop CAP typically have a combination of these predisposing factors rather than a single factor. Aging, in combination with other risk factors, increases the susceptibility of a person to pneumonia.

Clinical Signs and Symptoms

Symptoms of CAP include fever, chills, rigors, fatigue, anorexia, diaphoresis, dyspnea, cough (with or without sputum production), and pleuritic chest pain. There is no individual symptom or cluster of symptoms that can absolutely differentiate pneumonia from other acute respiratory diseases, including upper and lower respiratory infections. However, patients presenting with the constellation of symptoms of fever ≥ 100°F (37.8°C), productive cough, and tachycardia is more suggestive of pneumonia.¹⁴ Abnormal vital signs include fever, hypothermia, tachypnea, tachycardia, and oxygen desaturation. Auscultation of the chest reveals crackles or other adventitious breath sounds. Elderly patients with pneumonia report a significantly lower number of both respiratory and nonrespiratory symptoms compared with younger patients. Clinicians should be aware of this phenomenon to avoid delayed diagnosis and treatment.¹⁵

Imaging Evaluation

The presence of a pulmonary consolidation or an infiltrate on chest radiograph is required to diagnose CAP, and a chest radiograph should be obtained when CAP is suspected.¹⁶ However, there is no pattern of radiographic abnormalities reliable enough to differentiate infectious pneumonia from noninfectious causes.¹⁷

There are case reports and case series demonstrating false-negative plain chest radiographs in dehydrated patients¹⁸ or in patients in a neutropenic state. However, animal studies have shown that dogs challenged with pneumococcus showed abnormal pulmonary shadow, suggestive of pneumonia, regardless of hydration status.¹⁹ There is also no reliable scientific evidence to support the notion that severe neutropenia can cause false-negative radiographs because of the inability to develop an acute inflammatory reaction in the lungs.²⁰

A chest computed tomography (CT) scan is more sensitive than a plain chest radiograph in detecting pneumonia. Therefore, a chest CT should be performed in a patient with negative plain chest radiograph when pneumonia is still highly suspected.²¹ A chest CT scan is also more sensitive in detecting cavitation, adenopathy, interstitial disease, and empyema. It also has the advantage of better defining anatomical changes than plain films.²²

Because improvement of pulmonary opacities in patients with CAP lags behind clinical improvement, repeating chest imaging studies is not recommended in patients who demonstrate clinical improvement. Clearing of pulmonary infiltrate or consolidation sometimes can take 6 weeks or longer.²³

Laboratory Evaluation

Generally, the etiologic agent of CAP cannot be determined solely on the basis of clinical signs and symptoms or imaging studies. Although routine microbiological testing for patients suspicious for CAP is not necessary for empirical treatment, determining the etiologic agent of the pneumonia allows the clinician to narrow the antibiotics from a broad-spectrum empirical regimen to specific pathogen-directed therapy. Determination of certain etiologic agents causing the pneumonia can have important public health implications (eg, Mycobacterium tuberculosis and influenza virus).²⁴

Sputum Gram Stain and Culture

Sputum Gram stain is an inexpensive test that may identify pathogens that cause CAP (eg, Streptococcus pneumoniae and Haemophilus influenzae). A quality specimen is required. A sputum sample must contain more than 25 neutrophils and less than 10 squamous epithelial cells/low power field on Gram stain to be considered suitable for culture. The sensitivity and specificity of sputum Gram stain and culture are highly variable in different clinical settings (eg, outpatient setting, nursing home, ICU). Reed et al’s meta-analysis of patients diagnosed with CAP in the United States showed the sensitivity and specificity of sputum Gram stain (compared with sputum culture) ranged from 15% to 100% and 11% to 100%, respectively.²⁴ In cases of proven bacteremic pneumococcal pneumonia, positive cultures from sputum samples were positive less than 50% of the time.²⁵

For patients who cannot provide sputum samples or are intubated, deep-suction aspirate or bronchoalveolar lavage through a bronchoscopic procedure may be necessary to obtain pulmonary secretion for Gram stain and culture. Besides bacterial culture, sputum samples can also be sent for fungal and mycobacterial cultures and acid-fast stain, if deemed clinically necessary.

The 2019 ATS/IDSA guidelines for diagnosis and treatment of adults with CAP recommend sputum culture in patients with severe disease and in all inpatients empirically treated for MRSA or Pseudomonas aeruginosa.²⁶

 

 

Blood Culture

Because the positivity rate of blood culture in patients who are suspected to have pneumonia but not exposed to antimicrobial agents is low (5%–14%), blood cultures are not recommended for all patients with CAP. Another reason for not recommending blood culture is positive culture rarely leads to changes in antibiotic regimen in patients without underlying diseases.²⁷ However, the 2019 ATS/IDSA guidelines recommend blood culture in patients with severe disease and in all inpatients treated empirically for MRSA or P. aeruginosa.²⁶

A multinational study published in 2008 examined 125 patients with pneumococcal bacteremic CAP versus 1847 patients with non-bacteremic CAP.²⁸ Analysis of the data demonstrated no association between pneumococcal bacteremic CAP and time to clinical stability, length of hospital stay, all-cause mortality, or CAP-related mortality. The authors concluded that pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP compared to non-bacteremic patients, and the presence of pneumococcal bacteremia should not deter de-escalation of therapy in clinically stable patients.

Urinary Antigen Tests

Urinary antigen tests may assist clinicians in narrowing antibiotic therapy when test results are positive. There are 2 US Food and Drug Administration–approved tests available to clinicians for detecting pneumococcal and Legionella antigen in urine. The test for Legionella pneumophila detects disease due to serogroup 1 only, which accounts for 80% of community-acquired Legionnaires’ disease. The sensitivity and specificity of the Legionella urine antigen test are 90% and 99%, respectively. The pneumococcal urine antigen test is less sensitive and specific than the Legionella urine antigen test (sensitivity 80% and specificity > 90%).^29,30

Advantages of the urinary antigen tests are that they are easily performed, results are available in less than an hour if done in-house, and results are not affected by prior exposure to antibiotics. However, the tests do not meet Clinical Laboratory Improvements Amendments criteria for waiver and must be performed by a technician in the laboratory. A multicenter, prospective surveillance study of hospitalized patients with CAP showed that the 2007 IDSA/ATS guidelines’ recommended indications for S. pneumoniae and L. pneumophila urinary antigen tests do not have sufficient sensitivity and specificity to identify patients with positive tests.³¹

Polymerase Chain Reaction

There are several FDA-approved polymerase chain reaction (PCR) tests commercially available to assist clinicians in diagnosing pneumonia. PCR testing of nasopharyngeal swabs for diagnosis of influenza has become standard in many US medical facilities. The great advantages of using PCR to diagnose influenza are its high sensitivity and specificity and rapid turnaround time. PCR can also be used to detect Legionella species, S. pneumonia, Mycoplasma pneumoniae, Chlamydophila pneumonia, and mycobacterial species.²⁴

One limitation of using PCR tests on respiratory specimens is that specimens can be contaminated with oral or upper airway flora, so the results must be interpreted with caution, bearing in mind that some of the pathogens isolated may be colonizers of the oral or upper airway flora.³²

Biologic Markers

Two biologic markers—procalcitonin and C-reactive protein (CRP)—can be used in conjunction with history, physical examination, laboratory tests, and imaging studies to assist in the diagnosis and treatment of CAP.²⁴ Procalcitonin is a peptide precursor of the hormone calcitonin that is released by parenchymal cells into the bloodstream, resulting in increased serum level in patients with bacterial infections. In contrast, there is no remarkable procalcitonin level increase with viral or noninfectious inflammation. The reference value of procalcitonin in the blood of an adult individual without infection or inflammation is < 0.15 ng/mL. In the blood, procalcitonin has a half-life of 25 to 30 hours. The quantitative immunoluminometric method (LUMI test, Brahms PCT, Berlin, Germany) is the preferred test to use because of its high sensitivity.³³ A meta-analysis of 12 studies involving more than 2400 patients with CAP demonstrated that serum procalcitonin does not have sufficient sensitivity or specificity to distinguish between bacterial and nonbacterial pneumonia. The authors concluded that procalcitonin level cannot be used to decide whether an antibiotic should be administered.³⁴

A 2012 Cochrane meta-analysis that involved 4221 patients with acute respiratory infections (with half of the patients diagnosed with CAP) from 14 prospective trials found the use of procalcitonin test for antibiotic use significantly decreased median antibiotic exposure from 8 to 4 days without an increase in treatment failure, mortality rates in any clinical setting (eg, outpatient clinic, emergency room), or length of hospitalization.³⁵ An update of the 2012 Cochrane review that examined the safety and efficacy of using procalcitonin for starting or stopping antibiotics again demonstrated procalcitonin use was associated with a reduction of antibiotic use (2.4 days).³⁶ A prospective study conducted in France on 100 ICU patients showed that increased procalcitonin from day 1 to day 3 has a poor prognosis factor for severe CAP, whereas decreasing procalcitonin levels is associated with a favorable outcome.³⁷

Because of conflicting data, the 2019 ATS/IDSA guidelines do not recommend using procalcitonin to determine need for initial antibacterial therapy.²⁶

CRP is an acute phase protein produced by the liver. CRP level in the blood increases in response to acute infection or inflammation. Use of CRP in assisting diagnosis and guiding treatment of CAP is more limited in part due to its poor specificity. A prospective study conducted on 168 consecutive patients who presented with cough showed that a CRP level > 40 mg/L had a sensitivity and specificity of 70% and 90%, respectively.³⁸

Summary

CAP remains a leading cause of hospitalization and death in the 21st century. Traditionally, pneumococcus has been considered the major pathogen causing CAP; however, the 2015 EPIC study found that S. pneumoniae was detected in only 5% of patients diagnosed with CAP. Despite the new findings, it is still recommended that empiric treatment for CAP target common typical bacteria (pneumococcus, H. influenzae, Moraxella catarrhalis) and atypical bacteria (M. pneumonia, C. pneumoniae, L. pneumophila).

Because diagnosing pneumonia through history and clinical examination is less than 50% sensitive, a chest imaging study (a plain chest radiograph or a chest CT scan) is usually required to make the diagnosis. Laboratory tests, such as sputum Gram stain/culture, blood culture, urinary antigen tests, PCR test, procalcitonin, and CRP are important adjunctive diagnostic modalities to assist in the diagnosis and management of CAP. However, because no single test is sensitive and specific enough to be a stand-alone test, they should be used in conjunction with history, physical examination, and imaging studies.

Despite advances in medical science, pneumonia remains a major cause of morbidity and mortality. In 2017, 49,157 patients in the United States died from the disease.¹ Pneumonia can be classified as community-acquired, hospital-acquired, or ventilator-associated. Another category, healthcare-associated pneumonia, was included in an earlier Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guideline but was removed from the 2016 guideline because there was no clear evidence that patients diagnosed with healthcare-associated pneumonia were at higher risk for harboring multidrug-resistant pathogens.² This review is the first of 2 articles focusing on the management of community-acquired pneumonia (CAP). Here, we review CAP epidemiology, microbiology, predisposing factors, and diagnosis; current treatment and prevention of CAP are reviewed in a separate article.

Definition and Epidemiology

CAP is defined as an acute infection of the lungs that develops in patients who have not been hospitalized recently and have not had regular exposure to the health care system.³ A previously ambulatory patient who is diagnosed with pneumonia within 48 hours after admission also meets the criteria for CAP. Approximately 4 to 5 million cases of CAP are diagnosed in the United States annually.⁴ About 25% of CAP patients require hospitalization, and about 5% to 10% of these patients are admitted to the intensive care unit (ICU).⁵ In-hospital mortality is considerable (~10% in population-based studies),⁶ and 30-day mortality was found to be as high as 23% in a review by File and Marrie.⁷ CAP also confers a high risk of long-term morbidity and mortality compared with the general population who have never had CAP, irrespective of age.⁸

Causative Organisms

Numerous microorganisms can cause CAP. Common causes and less common causes are delineated in Table 1. Until recently, many studies had demonstrated that pneumococcus was the most common cause of CAP. However, in the CDC Etiology of Pneumonia in the Community (EPIC) study team’s 2015 prospective, multicenter, population-based study, no pathogen was detected in the majority of patients diagnosed with CAP requiring hospitalization. The most common pathogens they detected were rhinovirus (9%), followed by influenza virus (6%) and pneumococcus (5%).⁹ Factors considered to be contributing to the decrease in the percentage of pneumococcus in patients diagnosed with CAP are the widespread use of pneumococcal vaccine and reduced rates of smoking.^10,11

Predisposing Factors

Most people diagnosed with CAP have 1 or more predisposing factors (Table 2).^12,13 Patients who develop CAP typically have a combination of these predisposing factors rather than a single factor. Aging, in combination with other risk factors, increases the susceptibility of a person to pneumonia.

Clinical Signs and Symptoms

Symptoms of CAP include fever, chills, rigors, fatigue, anorexia, diaphoresis, dyspnea, cough (with or without sputum production), and pleuritic chest pain. There is no individual symptom or cluster of symptoms that can absolutely differentiate pneumonia from other acute respiratory diseases, including upper and lower respiratory infections. However, patients presenting with the constellation of symptoms of fever ≥ 100°F (37.8°C), productive cough, and tachycardia is more suggestive of pneumonia.¹⁴ Abnormal vital signs include fever, hypothermia, tachypnea, tachycardia, and oxygen desaturation. Auscultation of the chest reveals crackles or other adventitious breath sounds. Elderly patients with pneumonia report a significantly lower number of both respiratory and nonrespiratory symptoms compared with younger patients. Clinicians should be aware of this phenomenon to avoid delayed diagnosis and treatment.¹⁵

Imaging Evaluation

The presence of a pulmonary consolidation or an infiltrate on chest radiograph is required to diagnose CAP, and a chest radiograph should be obtained when CAP is suspected.¹⁶ However, there is no pattern of radiographic abnormalities reliable enough to differentiate infectious pneumonia from noninfectious causes.¹⁷

There are case reports and case series demonstrating false-negative plain chest radiographs in dehydrated patients¹⁸ or in patients in a neutropenic state. However, animal studies have shown that dogs challenged with pneumococcus showed abnormal pulmonary shadow, suggestive of pneumonia, regardless of hydration status.¹⁹ There is also no reliable scientific evidence to support the notion that severe neutropenia can cause false-negative radiographs because of the inability to develop an acute inflammatory reaction in the lungs.²⁰

A chest computed tomography (CT) scan is more sensitive than a plain chest radiograph in detecting pneumonia. Therefore, a chest CT should be performed in a patient with negative plain chest radiograph when pneumonia is still highly suspected.²¹ A chest CT scan is also more sensitive in detecting cavitation, adenopathy, interstitial disease, and empyema. It also has the advantage of better defining anatomical changes than plain films.²²

Because improvement of pulmonary opacities in patients with CAP lags behind clinical improvement, repeating chest imaging studies is not recommended in patients who demonstrate clinical improvement. Clearing of pulmonary infiltrate or consolidation sometimes can take 6 weeks or longer.²³

Laboratory Evaluation

Generally, the etiologic agent of CAP cannot be determined solely on the basis of clinical signs and symptoms or imaging studies. Although routine microbiological testing for patients suspicious for CAP is not necessary for empirical treatment, determining the etiologic agent of the pneumonia allows the clinician to narrow the antibiotics from a broad-spectrum empirical regimen to specific pathogen-directed therapy. Determination of certain etiologic agents causing the pneumonia can have important public health implications (eg, Mycobacterium tuberculosis and influenza virus).²⁴

Sputum Gram Stain and Culture

Sputum Gram stain is an inexpensive test that may identify pathogens that cause CAP (eg, Streptococcus pneumoniae and Haemophilus influenzae). A quality specimen is required. A sputum sample must contain more than 25 neutrophils and less than 10 squamous epithelial cells/low power field on Gram stain to be considered suitable for culture. The sensitivity and specificity of sputum Gram stain and culture are highly variable in different clinical settings (eg, outpatient setting, nursing home, ICU). Reed et al’s meta-analysis of patients diagnosed with CAP in the United States showed the sensitivity and specificity of sputum Gram stain (compared with sputum culture) ranged from 15% to 100% and 11% to 100%, respectively.²⁴ In cases of proven bacteremic pneumococcal pneumonia, positive cultures from sputum samples were positive less than 50% of the time.²⁵

For patients who cannot provide sputum samples or are intubated, deep-suction aspirate or bronchoalveolar lavage through a bronchoscopic procedure may be necessary to obtain pulmonary secretion for Gram stain and culture. Besides bacterial culture, sputum samples can also be sent for fungal and mycobacterial cultures and acid-fast stain, if deemed clinically necessary.

The 2019 ATS/IDSA guidelines for diagnosis and treatment of adults with CAP recommend sputum culture in patients with severe disease and in all inpatients empirically treated for MRSA or Pseudomonas aeruginosa.²⁶

 

 

Blood Culture

Because the positivity rate of blood culture in patients who are suspected to have pneumonia but not exposed to antimicrobial agents is low (5%–14%), blood cultures are not recommended for all patients with CAP. Another reason for not recommending blood culture is positive culture rarely leads to changes in antibiotic regimen in patients without underlying diseases.²⁷ However, the 2019 ATS/IDSA guidelines recommend blood culture in patients with severe disease and in all inpatients treated empirically for MRSA or P. aeruginosa.²⁶

A multinational study published in 2008 examined 125 patients with pneumococcal bacteremic CAP versus 1847 patients with non-bacteremic CAP.²⁸ Analysis of the data demonstrated no association between pneumococcal bacteremic CAP and time to clinical stability, length of hospital stay, all-cause mortality, or CAP-related mortality. The authors concluded that pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP compared to non-bacteremic patients, and the presence of pneumococcal bacteremia should not deter de-escalation of therapy in clinically stable patients.

Urinary Antigen Tests

Urinary antigen tests may assist clinicians in narrowing antibiotic therapy when test results are positive. There are 2 US Food and Drug Administration–approved tests available to clinicians for detecting pneumococcal and Legionella antigen in urine. The test for Legionella pneumophila detects disease due to serogroup 1 only, which accounts for 80% of community-acquired Legionnaires’ disease. The sensitivity and specificity of the Legionella urine antigen test are 90% and 99%, respectively. The pneumococcal urine antigen test is less sensitive and specific than the Legionella urine antigen test (sensitivity 80% and specificity > 90%).^29,30

Advantages of the urinary antigen tests are that they are easily performed, results are available in less than an hour if done in-house, and results are not affected by prior exposure to antibiotics. However, the tests do not meet Clinical Laboratory Improvements Amendments criteria for waiver and must be performed by a technician in the laboratory. A multicenter, prospective surveillance study of hospitalized patients with CAP showed that the 2007 IDSA/ATS guidelines’ recommended indications for S. pneumoniae and L. pneumophila urinary antigen tests do not have sufficient sensitivity and specificity to identify patients with positive tests.³¹

Polymerase Chain Reaction

There are several FDA-approved polymerase chain reaction (PCR) tests commercially available to assist clinicians in diagnosing pneumonia. PCR testing of nasopharyngeal swabs for diagnosis of influenza has become standard in many US medical facilities. The great advantages of using PCR to diagnose influenza are its high sensitivity and specificity and rapid turnaround time. PCR can also be used to detect Legionella species, S. pneumonia, Mycoplasma pneumoniae, Chlamydophila pneumonia, and mycobacterial species.²⁴

One limitation of using PCR tests on respiratory specimens is that specimens can be contaminated with oral or upper airway flora, so the results must be interpreted with caution, bearing in mind that some of the pathogens isolated may be colonizers of the oral or upper airway flora.³²

Biologic Markers

Two biologic markers—procalcitonin and C-reactive protein (CRP)—can be used in conjunction with history, physical examination, laboratory tests, and imaging studies to assist in the diagnosis and treatment of CAP.²⁴ Procalcitonin is a peptide precursor of the hormone calcitonin that is released by parenchymal cells into the bloodstream, resulting in increased serum level in patients with bacterial infections. In contrast, there is no remarkable procalcitonin level increase with viral or noninfectious inflammation. The reference value of procalcitonin in the blood of an adult individual without infection or inflammation is < 0.15 ng/mL. In the blood, procalcitonin has a half-life of 25 to 30 hours. The quantitative immunoluminometric method (LUMI test, Brahms PCT, Berlin, Germany) is the preferred test to use because of its high sensitivity.³³ A meta-analysis of 12 studies involving more than 2400 patients with CAP demonstrated that serum procalcitonin does not have sufficient sensitivity or specificity to distinguish between bacterial and nonbacterial pneumonia. The authors concluded that procalcitonin level cannot be used to decide whether an antibiotic should be administered.³⁴

A 2012 Cochrane meta-analysis that involved 4221 patients with acute respiratory infections (with half of the patients diagnosed with CAP) from 14 prospective trials found the use of procalcitonin test for antibiotic use significantly decreased median antibiotic exposure from 8 to 4 days without an increase in treatment failure, mortality rates in any clinical setting (eg, outpatient clinic, emergency room), or length of hospitalization.³⁵ An update of the 2012 Cochrane review that examined the safety and efficacy of using procalcitonin for starting or stopping antibiotics again demonstrated procalcitonin use was associated with a reduction of antibiotic use (2.4 days).³⁶ A prospective study conducted in France on 100 ICU patients showed that increased procalcitonin from day 1 to day 3 has a poor prognosis factor for severe CAP, whereas decreasing procalcitonin levels is associated with a favorable outcome.³⁷

Because of conflicting data, the 2019 ATS/IDSA guidelines do not recommend using procalcitonin to determine need for initial antibacterial therapy.²⁶

CRP is an acute phase protein produced by the liver. CRP level in the blood increases in response to acute infection or inflammation. Use of CRP in assisting diagnosis and guiding treatment of CAP is more limited in part due to its poor specificity. A prospective study conducted on 168 consecutive patients who presented with cough showed that a CRP level > 40 mg/L had a sensitivity and specificity of 70% and 90%, respectively.³⁸

Summary

CAP remains a leading cause of hospitalization and death in the 21st century. Traditionally, pneumococcus has been considered the major pathogen causing CAP; however, the 2015 EPIC study found that S. pneumoniae was detected in only 5% of patients diagnosed with CAP. Despite the new findings, it is still recommended that empiric treatment for CAP target common typical bacteria (pneumococcus, H. influenzae, Moraxella catarrhalis) and atypical bacteria (M. pneumonia, C. pneumoniae, L. pneumophila).

Because diagnosing pneumonia through history and clinical examination is less than 50% sensitive, a chest imaging study (a plain chest radiograph or a chest CT scan) is usually required to make the diagnosis. Laboratory tests, such as sputum Gram stain/culture, blood culture, urinary antigen tests, PCR test, procalcitonin, and CRP are important adjunctive diagnostic modalities to assist in the diagnosis and management of CAP. However, because no single test is sensitive and specific enough to be a stand-alone test, they should be used in conjunction with history, physical examination, and imaging studies.

Despite advances in medical science, pneumonia remains a major cause of morbidity and mortality. In 2017, 49,157 patients in the United States died from the disease.¹ Pneumonia can be classified as community-acquired, hospital-acquired, or ventilator-associated. Another category, healthcare-associated pneumonia, was included in an earlier Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) guideline but was removed from the 2016 guideline because there was no clear evidence that patients diagnosed with healthcare-associated pneumonia were at higher risk for harboring multidrug-resistant pathogens.² This review is the first of 2 articles focusing on the management of community-acquired pneumonia (CAP). Here, we review CAP epidemiology, microbiology, predisposing factors, and diagnosis; current treatment and prevention of CAP are reviewed in a separate article.

Definition and Epidemiology

CAP is defined as an acute infection of the lungs that develops in patients who have not been hospitalized recently and have not had regular exposure to the health care system.³ A previously ambulatory patient who is diagnosed with pneumonia within 48 hours after admission also meets the criteria for CAP. Approximately 4 to 5 million cases of CAP are diagnosed in the United States annually.⁴ About 25% of CAP patients require hospitalization, and about 5% to 10% of these patients are admitted to the intensive care unit (ICU).⁵ In-hospital mortality is considerable (~10% in population-based studies),⁶ and 30-day mortality was found to be as high as 23% in a review by File and Marrie.⁷ CAP also confers a high risk of long-term morbidity and mortality compared with the general population who have never had CAP, irrespective of age.⁸

Causative Organisms

Numerous microorganisms can cause CAP. Common causes and less common causes are delineated in Table 1. Until recently, many studies had demonstrated that pneumococcus was the most common cause of CAP. However, in the CDC Etiology of Pneumonia in the Community (EPIC) study team’s 2015 prospective, multicenter, population-based study, no pathogen was detected in the majority of patients diagnosed with CAP requiring hospitalization. The most common pathogens they detected were rhinovirus (9%), followed by influenza virus (6%) and pneumococcus (5%).⁹ Factors considered to be contributing to the decrease in the percentage of pneumococcus in patients diagnosed with CAP are the widespread use of pneumococcal vaccine and reduced rates of smoking.^10,11

Predisposing Factors

Most people diagnosed with CAP have 1 or more predisposing factors (Table 2).^12,13 Patients who develop CAP typically have a combination of these predisposing factors rather than a single factor. Aging, in combination with other risk factors, increases the susceptibility of a person to pneumonia.

Clinical Signs and Symptoms

Symptoms of CAP include fever, chills, rigors, fatigue, anorexia, diaphoresis, dyspnea, cough (with or without sputum production), and pleuritic chest pain. There is no individual symptom or cluster of symptoms that can absolutely differentiate pneumonia from other acute respiratory diseases, including upper and lower respiratory infections. However, patients presenting with the constellation of symptoms of fever ≥ 100°F (37.8°C), productive cough, and tachycardia is more suggestive of pneumonia.¹⁴ Abnormal vital signs include fever, hypothermia, tachypnea, tachycardia, and oxygen desaturation. Auscultation of the chest reveals crackles or other adventitious breath sounds. Elderly patients with pneumonia report a significantly lower number of both respiratory and nonrespiratory symptoms compared with younger patients. Clinicians should be aware of this phenomenon to avoid delayed diagnosis and treatment.¹⁵

Imaging Evaluation

The presence of a pulmonary consolidation or an infiltrate on chest radiograph is required to diagnose CAP, and a chest radiograph should be obtained when CAP is suspected.¹⁶ However, there is no pattern of radiographic abnormalities reliable enough to differentiate infectious pneumonia from noninfectious causes.¹⁷

There are case reports and case series demonstrating false-negative plain chest radiographs in dehydrated patients¹⁸ or in patients in a neutropenic state. However, animal studies have shown that dogs challenged with pneumococcus showed abnormal pulmonary shadow, suggestive of pneumonia, regardless of hydration status.¹⁹ There is also no reliable scientific evidence to support the notion that severe neutropenia can cause false-negative radiographs because of the inability to develop an acute inflammatory reaction in the lungs.²⁰

A chest computed tomography (CT) scan is more sensitive than a plain chest radiograph in detecting pneumonia. Therefore, a chest CT should be performed in a patient with negative plain chest radiograph when pneumonia is still highly suspected.²¹ A chest CT scan is also more sensitive in detecting cavitation, adenopathy, interstitial disease, and empyema. It also has the advantage of better defining anatomical changes than plain films.²²

Because improvement of pulmonary opacities in patients with CAP lags behind clinical improvement, repeating chest imaging studies is not recommended in patients who demonstrate clinical improvement. Clearing of pulmonary infiltrate or consolidation sometimes can take 6 weeks or longer.²³

Laboratory Evaluation

Generally, the etiologic agent of CAP cannot be determined solely on the basis of clinical signs and symptoms or imaging studies. Although routine microbiological testing for patients suspicious for CAP is not necessary for empirical treatment, determining the etiologic agent of the pneumonia allows the clinician to narrow the antibiotics from a broad-spectrum empirical regimen to specific pathogen-directed therapy. Determination of certain etiologic agents causing the pneumonia can have important public health implications (eg, Mycobacterium tuberculosis and influenza virus).²⁴

Sputum Gram Stain and Culture

Sputum Gram stain is an inexpensive test that may identify pathogens that cause CAP (eg, Streptococcus pneumoniae and Haemophilus influenzae). A quality specimen is required. A sputum sample must contain more than 25 neutrophils and less than 10 squamous epithelial cells/low power field on Gram stain to be considered suitable for culture. The sensitivity and specificity of sputum Gram stain and culture are highly variable in different clinical settings (eg, outpatient setting, nursing home, ICU). Reed et al’s meta-analysis of patients diagnosed with CAP in the United States showed the sensitivity and specificity of sputum Gram stain (compared with sputum culture) ranged from 15% to 100% and 11% to 100%, respectively.²⁴ In cases of proven bacteremic pneumococcal pneumonia, positive cultures from sputum samples were positive less than 50% of the time.²⁵

For patients who cannot provide sputum samples or are intubated, deep-suction aspirate or bronchoalveolar lavage through a bronchoscopic procedure may be necessary to obtain pulmonary secretion for Gram stain and culture. Besides bacterial culture, sputum samples can also be sent for fungal and mycobacterial cultures and acid-fast stain, if deemed clinically necessary.

The 2019 ATS/IDSA guidelines for diagnosis and treatment of adults with CAP recommend sputum culture in patients with severe disease and in all inpatients empirically treated for MRSA or Pseudomonas aeruginosa.²⁶

 

 

Blood Culture

Because the positivity rate of blood culture in patients who are suspected to have pneumonia but not exposed to antimicrobial agents is low (5%–14%), blood cultures are not recommended for all patients with CAP. Another reason for not recommending blood culture is positive culture rarely leads to changes in antibiotic regimen in patients without underlying diseases.²⁷ However, the 2019 ATS/IDSA guidelines recommend blood culture in patients with severe disease and in all inpatients treated empirically for MRSA or P. aeruginosa.²⁶

A multinational study published in 2008 examined 125 patients with pneumococcal bacteremic CAP versus 1847 patients with non-bacteremic CAP.²⁸ Analysis of the data demonstrated no association between pneumococcal bacteremic CAP and time to clinical stability, length of hospital stay, all-cause mortality, or CAP-related mortality. The authors concluded that pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP compared to non-bacteremic patients, and the presence of pneumococcal bacteremia should not deter de-escalation of therapy in clinically stable patients.

Urinary Antigen Tests

Urinary antigen tests may assist clinicians in narrowing antibiotic therapy when test results are positive. There are 2 US Food and Drug Administration–approved tests available to clinicians for detecting pneumococcal and Legionella antigen in urine. The test for Legionella pneumophila detects disease due to serogroup 1 only, which accounts for 80% of community-acquired Legionnaires’ disease. The sensitivity and specificity of the Legionella urine antigen test are 90% and 99%, respectively. The pneumococcal urine antigen test is less sensitive and specific than the Legionella urine antigen test (sensitivity 80% and specificity > 90%).^29,30

Advantages of the urinary antigen tests are that they are easily performed, results are available in less than an hour if done in-house, and results are not affected by prior exposure to antibiotics. However, the tests do not meet Clinical Laboratory Improvements Amendments criteria for waiver and must be performed by a technician in the laboratory. A multicenter, prospective surveillance study of hospitalized patients with CAP showed that the 2007 IDSA/ATS guidelines’ recommended indications for S. pneumoniae and L. pneumophila urinary antigen tests do not have sufficient sensitivity and specificity to identify patients with positive tests.³¹

Polymerase Chain Reaction

There are several FDA-approved polymerase chain reaction (PCR) tests commercially available to assist clinicians in diagnosing pneumonia. PCR testing of nasopharyngeal swabs for diagnosis of influenza has become standard in many US medical facilities. The great advantages of using PCR to diagnose influenza are its high sensitivity and specificity and rapid turnaround time. PCR can also be used to detect Legionella species, S. pneumonia, Mycoplasma pneumoniae, Chlamydophila pneumonia, and mycobacterial species.²⁴

One limitation of using PCR tests on respiratory specimens is that specimens can be contaminated with oral or upper airway flora, so the results must be interpreted with caution, bearing in mind that some of the pathogens isolated may be colonizers of the oral or upper airway flora.³²

Biologic Markers

Two biologic markers—procalcitonin and C-reactive protein (CRP)—can be used in conjunction with history, physical examination, laboratory tests, and imaging studies to assist in the diagnosis and treatment of CAP.²⁴ Procalcitonin is a peptide precursor of the hormone calcitonin that is released by parenchymal cells into the bloodstream, resulting in increased serum level in patients with bacterial infections. In contrast, there is no remarkable procalcitonin level increase with viral or noninfectious inflammation. The reference value of procalcitonin in the blood of an adult individual without infection or inflammation is < 0.15 ng/mL. In the blood, procalcitonin has a half-life of 25 to 30 hours. The quantitative immunoluminometric method (LUMI test, Brahms PCT, Berlin, Germany) is the preferred test to use because of its high sensitivity.³³ A meta-analysis of 12 studies involving more than 2400 patients with CAP demonstrated that serum procalcitonin does not have sufficient sensitivity or specificity to distinguish between bacterial and nonbacterial pneumonia. The authors concluded that procalcitonin level cannot be used to decide whether an antibiotic should be administered.³⁴

A 2012 Cochrane meta-analysis that involved 4221 patients with acute respiratory infections (with half of the patients diagnosed with CAP) from 14 prospective trials found the use of procalcitonin test for antibiotic use significantly decreased median antibiotic exposure from 8 to 4 days without an increase in treatment failure, mortality rates in any clinical setting (eg, outpatient clinic, emergency room), or length of hospitalization.³⁵ An update of the 2012 Cochrane review that examined the safety and efficacy of using procalcitonin for starting or stopping antibiotics again demonstrated procalcitonin use was associated with a reduction of antibiotic use (2.4 days).³⁶ A prospective study conducted in France on 100 ICU patients showed that increased procalcitonin from day 1 to day 3 has a poor prognosis factor for severe CAP, whereas decreasing procalcitonin levels is associated with a favorable outcome.³⁷

Because of conflicting data, the 2019 ATS/IDSA guidelines do not recommend using procalcitonin to determine need for initial antibacterial therapy.²⁶

CRP is an acute phase protein produced by the liver. CRP level in the blood increases in response to acute infection or inflammation. Use of CRP in assisting diagnosis and guiding treatment of CAP is more limited in part due to its poor specificity. A prospective study conducted on 168 consecutive patients who presented with cough showed that a CRP level > 40 mg/L had a sensitivity and specificity of 70% and 90%, respectively.³⁸

Summary

CAP remains a leading cause of hospitalization and death in the 21st century. Traditionally, pneumococcus has been considered the major pathogen causing CAP; however, the 2015 EPIC study found that S. pneumoniae was detected in only 5% of patients diagnosed with CAP. Despite the new findings, it is still recommended that empiric treatment for CAP target common typical bacteria (pneumococcus, H. influenzae, Moraxella catarrhalis) and atypical bacteria (M. pneumonia, C. pneumoniae, L. pneumophila).

Because diagnosing pneumonia through history and clinical examination is less than 50% sensitive, a chest imaging study (a plain chest radiograph or a chest CT scan) is usually required to make the diagnosis. Laboratory tests, such as sputum Gram stain/culture, blood culture, urinary antigen tests, PCR test, procalcitonin, and CRP are important adjunctive diagnostic modalities to assist in the diagnosis and management of CAP. However, because no single test is sensitive and specific enough to be a stand-alone test, they should be used in conjunction with history, physical examination, and imaging studies.

The number of possible cases of vaping-related pulmonary illness has risen to 215, reported from 25 states, as of Aug. 27, 2019, according to the Centers for Disease Control and Prevention, Atlanta. Additional reports of pulmonary illness are under investigation.

The CDC has released a standardized case definition that states are using to complete their own investigations and verifications of cases. It appears that all cases are linked to e-cigarette product use, but the cause of the respiratory illnesses is still unconfirmed.

In many cases, patients reported a gradual start of symptoms, including breathing difficulty, shortness of breath, and/or chest pain before hospitalization. Some cases reported mild to moderate gastrointestinal illness including vomiting and diarrhea, or other symptoms such as fevers or fatigue. In many cases, patients have also acknowledged recent use of tetrahydrocannabinol (THC)-containing e-cigarette products while speaking to health care personnel or in follow-up interviews by health department staff, according to a statement from the CDC and the Food and Drug Administration.

The agencies are working with state health departments to standardize information collection at the state level to help build a more comprehensive picture of these incidents, including the brand and types of e-cigarette products, whether any of them would fall within the FDA’s regulatory authority, where they were obtained, and whether there is a link to specific devices, ingredients, or contaminants in the devices or substances associated with e-cigarette product use.

CDC staff have been deployed to Illinois and Wisconsin to assist their state health departments. The agencies have released a Clinician Outreach and Communication Activity (COCA) Clinical Action Alert describing this investigation and asking providers to report possible cases to their state health departments. In addition to a standardized case definition, the agencies have issued a medical chart abstraction form and case interview questionnaire, are reviewing and providing feedback on data collection and health messaging tools for states, and are facilitating information sharing between states with possible cases.

More information on the cases and reporting are available from the CDC.

mdales@mdedge.com

The number of possible cases of vaping-related pulmonary illness has risen to 215, reported from 25 states, as of Aug. 27, 2019, according to the Centers for Disease Control and Prevention, Atlanta. Additional reports of pulmonary illness are under investigation.

The CDC has released a standardized case definition that states are using to complete their own investigations and verifications of cases. It appears that all cases are linked to e-cigarette product use, but the cause of the respiratory illnesses is still unconfirmed.

In many cases, patients reported a gradual start of symptoms, including breathing difficulty, shortness of breath, and/or chest pain before hospitalization. Some cases reported mild to moderate gastrointestinal illness including vomiting and diarrhea, or other symptoms such as fevers or fatigue. In many cases, patients have also acknowledged recent use of tetrahydrocannabinol (THC)-containing e-cigarette products while speaking to health care personnel or in follow-up interviews by health department staff, according to a statement from the CDC and the Food and Drug Administration.

The agencies are working with state health departments to standardize information collection at the state level to help build a more comprehensive picture of these incidents, including the brand and types of e-cigarette products, whether any of them would fall within the FDA’s regulatory authority, where they were obtained, and whether there is a link to specific devices, ingredients, or contaminants in the devices or substances associated with e-cigarette product use.

CDC staff have been deployed to Illinois and Wisconsin to assist their state health departments. The agencies have released a Clinician Outreach and Communication Activity (COCA) Clinical Action Alert describing this investigation and asking providers to report possible cases to their state health departments. In addition to a standardized case definition, the agencies have issued a medical chart abstraction form and case interview questionnaire, are reviewing and providing feedback on data collection and health messaging tools for states, and are facilitating information sharing between states with possible cases.

More information on the cases and reporting are available from the CDC.

mdales@mdedge.com

The number of possible cases of vaping-related pulmonary illness has risen to 215, reported from 25 states, as of Aug. 27, 2019, according to the Centers for Disease Control and Prevention, Atlanta. Additional reports of pulmonary illness are under investigation.

The CDC has released a standardized case definition that states are using to complete their own investigations and verifications of cases. It appears that all cases are linked to e-cigarette product use, but the cause of the respiratory illnesses is still unconfirmed.

In many cases, patients reported a gradual start of symptoms, including breathing difficulty, shortness of breath, and/or chest pain before hospitalization. Some cases reported mild to moderate gastrointestinal illness including vomiting and diarrhea, or other symptoms such as fevers or fatigue. In many cases, patients have also acknowledged recent use of tetrahydrocannabinol (THC)-containing e-cigarette products while speaking to health care personnel or in follow-up interviews by health department staff, according to a statement from the CDC and the Food and Drug Administration.

The agencies are working with state health departments to standardize information collection at the state level to help build a more comprehensive picture of these incidents, including the brand and types of e-cigarette products, whether any of them would fall within the FDA’s regulatory authority, where they were obtained, and whether there is a link to specific devices, ingredients, or contaminants in the devices or substances associated with e-cigarette product use.

CDC staff have been deployed to Illinois and Wisconsin to assist their state health departments. The agencies have released a Clinician Outreach and Communication Activity (COCA) Clinical Action Alert describing this investigation and asking providers to report possible cases to their state health departments. In addition to a standardized case definition, the agencies have issued a medical chart abstraction form and case interview questionnaire, are reviewing and providing feedback on data collection and health messaging tools for states, and are facilitating information sharing between states with possible cases.

More information on the cases and reporting are available from the CDC.

mdales@mdedge.com