COPD

Systemic glucocorticoids play an important role in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. They are recommended to shorten recovery time and increase forced expiratory volume in 1 second (FEV1) during exacerbations.¹ However, the role of the chronic use of inhaled corticosteroids (ICSs) in the treatment of COPD is less clear.

When added to inhaled β-2 agonists and muscarinic antagonists, ICSs can decrease the risk of exacerbations.¹ However, not all patients with COPD benefit from ICS therapy. The degree of benefit an ICS can provide has been shown to correlate with eosinophil count—a marker of inflammation. The expected benefit of using an ICS increases as the eosinophil count increases.¹ Maximum benefit can be observed with eosinophil counts ≥ 300 cells/µL, and minimal benefit is observed with eosinophil counts < 100 cells/µL. Adverse effects (AEs) of ICSs include a hoarse voice, oral candidiasis, and an increased risk of pneumonia.¹ Given the risk of AEs, it is important to limit ICS use in patients who are unlikely to reap any benefits.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines suggest the use of ICSs in patients who experience exacerbations while using long-acting β agonist (LABA) plus long-acting muscarinic antagonist (LAMA) therapy and have an eosinophil count ≥ 100 cells/µL. Switching from LABA or LAMA monotherapy to triple therapy with LAMA/LABA/ICS may be considered if patients have continued exacerbations and an eosinophil count ≥ 300 cells/µL. De-escalation of ICS therapy should be considered if patients do not meet these criteria or if patients experience ICS AEs, such as pneumonia. The patients most likely to have increased exacerbations or decreased FEV1 with ICS withdrawal are those with eosinophil counts ≥ 300 cells/µL.^1,2Several studies have explored the effects of ICS de-escalation in real-world clinical settings. A systematic review of 11 studies indicated that de-escalation of ICS in COPD does not result in increased exacerbations.³ A prospective study by Rossi et al found that in a 6-month period, 141 of 482 patients on ICS therapy (29%) had an exacerbation. In the opposing arm of the study, 88 of 334 patients (26%) with deprescribed ICS experienced an exacerbation. The difference between these 2 groups was not statistically significant.⁴ The researchers concluded that in real-world practice, ICS withdrawal can be safe in patients at low risk of exacerbation.

About 25% of veterans (1.25 million) have been diagnosed with COPD.⁵ To address this, the US Department of Veterans Affairs (VA) and US Department of Defense published updated COPD guidelines in 2021 that specify criteria for de-escalation of ICS.⁶ Guidelines, however, may not be reflected in common clinical practice for several years following publication. The VA Academic Detailing Service (ADS) provides tools to help clinicians identify patients who may benefit from changes in treatment plans. A recent ADS focus was the implementation of a COPD dashboard, which identifies patients with COPD who are candidates for ICS de-escalation based on comorbid diagnoses, exacerbation history, and eosinophil count. VA pharmacists have an expanded role in the management of primary care disease states and are therefore well-positioned to increase adherence to guideline-directed therapy. The objective of this quality improvement project was to determine the impact of pharmacist-driven de-escalation on ICS usage in veterans with COPD.

Methods

This project was conducted in an outpatient clinic at the Robley Rex VA Medical Center beginning September 21, 2023, with a progress note in the Computerized Patient Record System (CPRS). Eligible patients were selected using the COPD Dashboard provided by ADS. The COPD Dashboard defined patients with COPD as those with ≥ 2 outpatient COPD diagnoses in the past 2 years, 1 inpatient discharge COPD diagnosis in the past year, or COPD listed as an active problem. COPD diagnoses were identified using International Statistical Classification of Disease, Tenth Revision (ICD-10) codes (Appendix).

Candidates identified for ICS de-escalation by the dashboard were excluded if they had a history of COPD exacerbation in the previous 2 years. The dashboard identified COPD exacerbations via ICD-10 codes for COPD or acute respiratory failure for inpatient discharges, emergency department (ED) visits, urgent care visits, and community care consults with 1 of the following terms: emergency, inpatient, hospital, urgent, ED (self). The COPD dashboard excluded patients with a diagnosis of asthma.

After patients were selected, they were screened for additional exclusion criteria. Patients were excluded if a pulmonary care practitioner managed their COPD; if identified via an active pulmonary consult in CPRS; if a non-VA clinician prescribed their ICS; or if they were being treated with roflumilast, theophylline, or chronic azithromycin. Individuals taking these 3 drugs were excluded due to potential severe and/or refractory COPD. Patients also were excluded if they: (1) had prior ICS de-escalation failure (defined as a COPD exacerbation following ICS de-escalation that resulted in ICS resumption); (2) had a COPD exacerbation requiring systemic corticosteroids or antibiotics in the previous year; (3) had active lung cancer; (4) did not have any eosinophil levels in CPRS within the previous 2 years; or (5) had any eosinophil levels ≥ 300 cells/µL in the previous year.

Each patient who met the inclusion criteria and was not excluded received a focused medication review by a pharmacist who created a templated progress note, with patient-specific recommendations, that was entered in the CPRS (eAppendix). The recommendations were also attached as an addendum to the patient’s last primary care visit note, and the primary care practitioner (PCP) was alerted via CPRS to consider ICS de-escalation and non-ICS alternatives. Tapering of ICS therapy was offered as an option to de-escalate if abrupt discontinuation was deemed inappropriate. PCPs were also prompted to consider referral to a primary care clinical pharmacy specialist for management and follow-up of ICS de-escalation.

The primary outcome was the number of patients with de-escalated ICS at 3 and 6 months following the recommendation. Secondary outcomes included the number of: patients who were no longer prescribed an ICS or who had a non-ICS alternative initiated at a pharmacist’s recommendation; patients who were referred to a primary care clinical pharmacy specialist for ICS de-escalation; COPD exacerbations requiring systemic steroids or antibiotics, or requiring an ED visit, inpatient admission, or urgent-care clinic visit; and cases of pneumonia or oral candidiasis. Primary and secondary outcomes were evaluated via chart review in CPRS. For secondary outcomes of pneumonia and COPD exacerbation, identification was made by documented diagnosis in CPRS. For continuous data such as age, the mean was calculated.

Results

Pharmacist ICS de-escalation recommendations were made between September 21, 2023, and November 19, 2023, for 106 patients. The mean age was 72 years and 99 (93%) patients were male (Table 1). Forty-one (39%) of the patients used tobacco at the time of the study. FEV1 was available for 69 patients with a mean of 63% (GOLD grade 2).¹ Based on FEV1 values, 16 patients had mild COPD (GOLD grade 1), 37 patients had moderate COPD (GOLD grade 2), 14 patients had severe COPD (GOLD grade 3), and 2 patients had very severe COPD (GOLD grade 4).¹ Thirty-four patients received LABA + LAMA + ICS, 65 received LABA + ICS, 2 received LAMA + ICS, and 5 received ICS monotherapy. The most common dose of ICS was a moderate dose (Table 2). Only 2 patients had an ICS AE in the previous year.

ICS de-escalation recommendations resulted in ICS de-escalation in 50 (47.2%) and 62 (58.5%) patients at 3 and 6 months, respectively. The 6-month ICS de-escalation rate by ICS dose at baseline was 72.2% (high dose), 60.0% (moderate), and 30.8% (low). De-escalation at 6 months by GOLD grade at baseline was 56.3% (9 of 16 patients, GOLD 1), 64.9% (24 of 37 patients, GOLD 2), 50% (7 of 14 patients, GOLD 3), and 50% (1 of 2 patients, GOLD 4). Six months after the ICS de-escalation recommendation appeared in the CPRS, the percentage of patients on LABA + ICS therapy dropped from 65 patients (61.3%) at baseline to 25 patients (23.6%).

Secondary outcomes were assessed at 3 and 6 months following the recommendation. Most patients with de-escalated ICS had their ICS discontinued and a non-ICS alternative initiated per pharmacist recommendations. At 6 months, 39 patients (36.8%) patients were referred to a patient aligned care team (PACT) pharmacist for de-escalation. Of the 39 patients referred to pharmacists, 69.2% (27 patients) were de-escalated; this compared to 52.2% (35 patients) who were not referred to pharmacists (Table 3).

ICS use increases the risk of pneumonia.¹ At 6 months, 11 patients were diagnosed with pneumonia; 3 patients were diagnosed with pneumonia twice, resulting in a total of 14 cases. Ten cases occurred while patients were on ICS and 4 cases occurred following ICS de-escalation. One patient had a documented case of oral candidiasis that occurred while on ICS therapy; no patients with discontinued ICS were diagnosed with oral candidiasis. In addition, 10 patients had COPD exacerbations; however no patients had exacerbations both before and after de-escalation. Six patients were on ICS therapy when they experienced an exacerbation, and 4 patients had an exacerbation after ICS de-escalation.

Discussion

More than half of patients receiving the pharmacist intervention achieved the primary outcome of ICS de-escalation at 6 months. Furthermore, a larger percentage of patients referred to pharmacists for the management of ICS de-escalation successfully achieved de-escalation compared to those who were not referred. These outcomes reflect the important role pharmacists can play in identifying appropriate candidates for ICS de-escalation and assisting in the management of ICS de-escalation. Patients referred to pharmacists also received other services such as smoking cessation pharmacotherapy and counseling on inhaler technique and adherence. These interventions can support improved COPD clinical outcomes.

The purpose of de-escalating ICS therapy is to reduce the risk of AEs such as pneumonia and oral candidiasis.¹ The secondary outcomes of this study support previous evidence that patients who have de-escalated ICS therapy may have reduced risk of AEs compared to those who remain on ICS therapy.³ Specifically, of the 14 cases of pneumonia that occurred during the study, 10 cases occurred while patients were on ICS and 4 cases occurred following ICS de-escalation.

ICS de-escalation may increase risk of increased COPD exacerbations.¹ However, the secondary outcomes of this study do not indicate that those with de-escalated ICS had more COPD exacerbations compared to those who continued on ICS. Pharmacists’ recommendations were more effective for patients with less severe COPD based on baseline FEV1.

The previous GOLD Guidelines for COPD suggested LABA + ICS therapy as an option for patients with a high symptom and exacerbation burden (previously known as GOLD Group D). Guidelines no longer recommend LABA + ICS therapy due to the superiority of triple inhaled therapy for exacerbations and the superiority of LAMA + LABA therapy for dyspnea.⁷ A majority of identified patients in this project were on LABA + ICS therapy alone at baseline. The ICS de-escalation recommendation resulted in a 61.5% reduction in patients on LABA + ICS therapy at 6 months. By decreasing the number of patients on LABA + ICS without LAMA, recommendations increased the number of patients on guideline-directed therapy.

Limitations

This study lacked a control group, and the rate of ICS de-escalation in patients who did not receive a pharmacist recommendation was not assessed. Therefore, it could not be determined whether the pharmacist recommendation is more effective than no recommendation. Another limitation was our inability to access records from non-VA health care facilities. This may have resulted in missed COPD exacerbations, pneumonia, and oral candidiasis prior to or following the pharmacist recommendation.

In addition, the method used to notify PCPs of the pharmacist recommendation was a CPRS alert. Clinicians often receive multiple daily alerts and may not always pay close attention to them due to alert fatigue. Early in the study, some PCPs were unknowingly omitted from the alert of the pharmacist recommendation for 10 patients due to human error. For 8 of these 10 patients, the PCP was notified of the recommendations during the 3-month follow-up period. However, 2 patients had COPD exacerbations during the 3-month follow-up period. In these cases, the PCP was not alerted to de-escalate ICS. The data for these patients were collected at 3 and 6 months in the same manner as all other patients. Also, 7 of 35 patients who were referred to a pharmacist for ICS de-escalation did not have a scheduled appointment. These patients were considered to be lost to follow-up and this may have resulted in an underestimation of the ability of pharmacists to successfully de-escalate ICS in patients with COPD.

Other studies have evaluated the efficacy of a pharmacy-driven ICS de-escalation.^8,9 Hegland et al reported ICS de-escalation for 22% of 141 eligible ambulatory patients with COPD on triple inhaled therapy following pharmacist appointments.⁸ A study by Hahn et al resulted in 63.8% of 58 patients with COPD being maintained off ICS following a pharmacist de-escalation initiative.⁹ However, these studies relied upon more time-consuming de-escalation interventions, including at least 1 phone, video, or in-person patient visit.^8,9

This project used a single chart review and templated progress note to recommend ICS de-escalation and achieved similar or improved de-escalation rates compared to previous studies.^8,9 Previous studies were conducted prior to the updated 2023 GOLD guidelines for COPD which no longer recommend LABA + ICS therapy. This project addressed ICS de-escalation in patients on LABA + ICS therapy in addition to those on triple inhaled therapy. Additionally, previous studies did not address rates of moderate to severe COPD exacerbation and adverse events to ICS following the pharmacist intervention.^8,9

This study included COPD exacerbations and cases of pneumonia or oral candidiasis as secondary outcomes to assess the safety and efficacy of the ICS de-escalation. It appeared there were similar or lower rates of COPD exacerbations, pneumonia, and oral candidiasis in those with de-escalated ICS therapy in this study. However, these secondary outcomes are exploratory and would need to be confirmed by larger studies powered to address these outcomes.

CONCLUSIONS

Pharmacist-driven ICS de-escalation may be an effective method for reducing ICS usage in veterans as seen in this study. Additional controlled studies are required to evaluate the efficacy and safety of pharmacist-driven ICS de-escalation.

Systemic glucocorticoids play an important role in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. They are recommended to shorten recovery time and increase forced expiratory volume in 1 second (FEV1) during exacerbations.¹ However, the role of the chronic use of inhaled corticosteroids (ICSs) in the treatment of COPD is less clear.

When added to inhaled β-2 agonists and muscarinic antagonists, ICSs can decrease the risk of exacerbations.¹ However, not all patients with COPD benefit from ICS therapy. The degree of benefit an ICS can provide has been shown to correlate with eosinophil count—a marker of inflammation. The expected benefit of using an ICS increases as the eosinophil count increases.¹ Maximum benefit can be observed with eosinophil counts ≥ 300 cells/µL, and minimal benefit is observed with eosinophil counts < 100 cells/µL. Adverse effects (AEs) of ICSs include a hoarse voice, oral candidiasis, and an increased risk of pneumonia.¹ Given the risk of AEs, it is important to limit ICS use in patients who are unlikely to reap any benefits.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines suggest the use of ICSs in patients who experience exacerbations while using long-acting β agonist (LABA) plus long-acting muscarinic antagonist (LAMA) therapy and have an eosinophil count ≥ 100 cells/µL. Switching from LABA or LAMA monotherapy to triple therapy with LAMA/LABA/ICS may be considered if patients have continued exacerbations and an eosinophil count ≥ 300 cells/µL. De-escalation of ICS therapy should be considered if patients do not meet these criteria or if patients experience ICS AEs, such as pneumonia. The patients most likely to have increased exacerbations or decreased FEV1 with ICS withdrawal are those with eosinophil counts ≥ 300 cells/µL.^1,2Several studies have explored the effects of ICS de-escalation in real-world clinical settings. A systematic review of 11 studies indicated that de-escalation of ICS in COPD does not result in increased exacerbations.³ A prospective study by Rossi et al found that in a 6-month period, 141 of 482 patients on ICS therapy (29%) had an exacerbation. In the opposing arm of the study, 88 of 334 patients (26%) with deprescribed ICS experienced an exacerbation. The difference between these 2 groups was not statistically significant.⁴ The researchers concluded that in real-world practice, ICS withdrawal can be safe in patients at low risk of exacerbation.

About 25% of veterans (1.25 million) have been diagnosed with COPD.⁵ To address this, the US Department of Veterans Affairs (VA) and US Department of Defense published updated COPD guidelines in 2021 that specify criteria for de-escalation of ICS.⁶ Guidelines, however, may not be reflected in common clinical practice for several years following publication. The VA Academic Detailing Service (ADS) provides tools to help clinicians identify patients who may benefit from changes in treatment plans. A recent ADS focus was the implementation of a COPD dashboard, which identifies patients with COPD who are candidates for ICS de-escalation based on comorbid diagnoses, exacerbation history, and eosinophil count. VA pharmacists have an expanded role in the management of primary care disease states and are therefore well-positioned to increase adherence to guideline-directed therapy. The objective of this quality improvement project was to determine the impact of pharmacist-driven de-escalation on ICS usage in veterans with COPD.

Methods

This project was conducted in an outpatient clinic at the Robley Rex VA Medical Center beginning September 21, 2023, with a progress note in the Computerized Patient Record System (CPRS). Eligible patients were selected using the COPD Dashboard provided by ADS. The COPD Dashboard defined patients with COPD as those with ≥ 2 outpatient COPD diagnoses in the past 2 years, 1 inpatient discharge COPD diagnosis in the past year, or COPD listed as an active problem. COPD diagnoses were identified using International Statistical Classification of Disease, Tenth Revision (ICD-10) codes (Appendix).

Candidates identified for ICS de-escalation by the dashboard were excluded if they had a history of COPD exacerbation in the previous 2 years. The dashboard identified COPD exacerbations via ICD-10 codes for COPD or acute respiratory failure for inpatient discharges, emergency department (ED) visits, urgent care visits, and community care consults with 1 of the following terms: emergency, inpatient, hospital, urgent, ED (self). The COPD dashboard excluded patients with a diagnosis of asthma.

After patients were selected, they were screened for additional exclusion criteria. Patients were excluded if a pulmonary care practitioner managed their COPD; if identified via an active pulmonary consult in CPRS; if a non-VA clinician prescribed their ICS; or if they were being treated with roflumilast, theophylline, or chronic azithromycin. Individuals taking these 3 drugs were excluded due to potential severe and/or refractory COPD. Patients also were excluded if they: (1) had prior ICS de-escalation failure (defined as a COPD exacerbation following ICS de-escalation that resulted in ICS resumption); (2) had a COPD exacerbation requiring systemic corticosteroids or antibiotics in the previous year; (3) had active lung cancer; (4) did not have any eosinophil levels in CPRS within the previous 2 years; or (5) had any eosinophil levels ≥ 300 cells/µL in the previous year.

Each patient who met the inclusion criteria and was not excluded received a focused medication review by a pharmacist who created a templated progress note, with patient-specific recommendations, that was entered in the CPRS (eAppendix). The recommendations were also attached as an addendum to the patient’s last primary care visit note, and the primary care practitioner (PCP) was alerted via CPRS to consider ICS de-escalation and non-ICS alternatives. Tapering of ICS therapy was offered as an option to de-escalate if abrupt discontinuation was deemed inappropriate. PCPs were also prompted to consider referral to a primary care clinical pharmacy specialist for management and follow-up of ICS de-escalation.

The primary outcome was the number of patients with de-escalated ICS at 3 and 6 months following the recommendation. Secondary outcomes included the number of: patients who were no longer prescribed an ICS or who had a non-ICS alternative initiated at a pharmacist’s recommendation; patients who were referred to a primary care clinical pharmacy specialist for ICS de-escalation; COPD exacerbations requiring systemic steroids or antibiotics, or requiring an ED visit, inpatient admission, or urgent-care clinic visit; and cases of pneumonia or oral candidiasis. Primary and secondary outcomes were evaluated via chart review in CPRS. For secondary outcomes of pneumonia and COPD exacerbation, identification was made by documented diagnosis in CPRS. For continuous data such as age, the mean was calculated.

Results

Pharmacist ICS de-escalation recommendations were made between September 21, 2023, and November 19, 2023, for 106 patients. The mean age was 72 years and 99 (93%) patients were male (Table 1). Forty-one (39%) of the patients used tobacco at the time of the study. FEV1 was available for 69 patients with a mean of 63% (GOLD grade 2).¹ Based on FEV1 values, 16 patients had mild COPD (GOLD grade 1), 37 patients had moderate COPD (GOLD grade 2), 14 patients had severe COPD (GOLD grade 3), and 2 patients had very severe COPD (GOLD grade 4).¹ Thirty-four patients received LABA + LAMA + ICS, 65 received LABA + ICS, 2 received LAMA + ICS, and 5 received ICS monotherapy. The most common dose of ICS was a moderate dose (Table 2). Only 2 patients had an ICS AE in the previous year.

ICS de-escalation recommendations resulted in ICS de-escalation in 50 (47.2%) and 62 (58.5%) patients at 3 and 6 months, respectively. The 6-month ICS de-escalation rate by ICS dose at baseline was 72.2% (high dose), 60.0% (moderate), and 30.8% (low). De-escalation at 6 months by GOLD grade at baseline was 56.3% (9 of 16 patients, GOLD 1), 64.9% (24 of 37 patients, GOLD 2), 50% (7 of 14 patients, GOLD 3), and 50% (1 of 2 patients, GOLD 4). Six months after the ICS de-escalation recommendation appeared in the CPRS, the percentage of patients on LABA + ICS therapy dropped from 65 patients (61.3%) at baseline to 25 patients (23.6%).

Secondary outcomes were assessed at 3 and 6 months following the recommendation. Most patients with de-escalated ICS had their ICS discontinued and a non-ICS alternative initiated per pharmacist recommendations. At 6 months, 39 patients (36.8%) patients were referred to a patient aligned care team (PACT) pharmacist for de-escalation. Of the 39 patients referred to pharmacists, 69.2% (27 patients) were de-escalated; this compared to 52.2% (35 patients) who were not referred to pharmacists (Table 3).

ICS use increases the risk of pneumonia.¹ At 6 months, 11 patients were diagnosed with pneumonia; 3 patients were diagnosed with pneumonia twice, resulting in a total of 14 cases. Ten cases occurred while patients were on ICS and 4 cases occurred following ICS de-escalation. One patient had a documented case of oral candidiasis that occurred while on ICS therapy; no patients with discontinued ICS were diagnosed with oral candidiasis. In addition, 10 patients had COPD exacerbations; however no patients had exacerbations both before and after de-escalation. Six patients were on ICS therapy when they experienced an exacerbation, and 4 patients had an exacerbation after ICS de-escalation.

Discussion

More than half of patients receiving the pharmacist intervention achieved the primary outcome of ICS de-escalation at 6 months. Furthermore, a larger percentage of patients referred to pharmacists for the management of ICS de-escalation successfully achieved de-escalation compared to those who were not referred. These outcomes reflect the important role pharmacists can play in identifying appropriate candidates for ICS de-escalation and assisting in the management of ICS de-escalation. Patients referred to pharmacists also received other services such as smoking cessation pharmacotherapy and counseling on inhaler technique and adherence. These interventions can support improved COPD clinical outcomes.

The purpose of de-escalating ICS therapy is to reduce the risk of AEs such as pneumonia and oral candidiasis.¹ The secondary outcomes of this study support previous evidence that patients who have de-escalated ICS therapy may have reduced risk of AEs compared to those who remain on ICS therapy.³ Specifically, of the 14 cases of pneumonia that occurred during the study, 10 cases occurred while patients were on ICS and 4 cases occurred following ICS de-escalation.

ICS de-escalation may increase risk of increased COPD exacerbations.¹ However, the secondary outcomes of this study do not indicate that those with de-escalated ICS had more COPD exacerbations compared to those who continued on ICS. Pharmacists’ recommendations were more effective for patients with less severe COPD based on baseline FEV1.

The previous GOLD Guidelines for COPD suggested LABA + ICS therapy as an option for patients with a high symptom and exacerbation burden (previously known as GOLD Group D). Guidelines no longer recommend LABA + ICS therapy due to the superiority of triple inhaled therapy for exacerbations and the superiority of LAMA + LABA therapy for dyspnea.⁷ A majority of identified patients in this project were on LABA + ICS therapy alone at baseline. The ICS de-escalation recommendation resulted in a 61.5% reduction in patients on LABA + ICS therapy at 6 months. By decreasing the number of patients on LABA + ICS without LAMA, recommendations increased the number of patients on guideline-directed therapy.

Limitations

This study lacked a control group, and the rate of ICS de-escalation in patients who did not receive a pharmacist recommendation was not assessed. Therefore, it could not be determined whether the pharmacist recommendation is more effective than no recommendation. Another limitation was our inability to access records from non-VA health care facilities. This may have resulted in missed COPD exacerbations, pneumonia, and oral candidiasis prior to or following the pharmacist recommendation.

In addition, the method used to notify PCPs of the pharmacist recommendation was a CPRS alert. Clinicians often receive multiple daily alerts and may not always pay close attention to them due to alert fatigue. Early in the study, some PCPs were unknowingly omitted from the alert of the pharmacist recommendation for 10 patients due to human error. For 8 of these 10 patients, the PCP was notified of the recommendations during the 3-month follow-up period. However, 2 patients had COPD exacerbations during the 3-month follow-up period. In these cases, the PCP was not alerted to de-escalate ICS. The data for these patients were collected at 3 and 6 months in the same manner as all other patients. Also, 7 of 35 patients who were referred to a pharmacist for ICS de-escalation did not have a scheduled appointment. These patients were considered to be lost to follow-up and this may have resulted in an underestimation of the ability of pharmacists to successfully de-escalate ICS in patients with COPD.

Other studies have evaluated the efficacy of a pharmacy-driven ICS de-escalation.^8,9 Hegland et al reported ICS de-escalation for 22% of 141 eligible ambulatory patients with COPD on triple inhaled therapy following pharmacist appointments.⁸ A study by Hahn et al resulted in 63.8% of 58 patients with COPD being maintained off ICS following a pharmacist de-escalation initiative.⁹ However, these studies relied upon more time-consuming de-escalation interventions, including at least 1 phone, video, or in-person patient visit.^8,9

This project used a single chart review and templated progress note to recommend ICS de-escalation and achieved similar or improved de-escalation rates compared to previous studies.^8,9 Previous studies were conducted prior to the updated 2023 GOLD guidelines for COPD which no longer recommend LABA + ICS therapy. This project addressed ICS de-escalation in patients on LABA + ICS therapy in addition to those on triple inhaled therapy. Additionally, previous studies did not address rates of moderate to severe COPD exacerbation and adverse events to ICS following the pharmacist intervention.^8,9

This study included COPD exacerbations and cases of pneumonia or oral candidiasis as secondary outcomes to assess the safety and efficacy of the ICS de-escalation. It appeared there were similar or lower rates of COPD exacerbations, pneumonia, and oral candidiasis in those with de-escalated ICS therapy in this study. However, these secondary outcomes are exploratory and would need to be confirmed by larger studies powered to address these outcomes.

CONCLUSIONS

Pharmacist-driven ICS de-escalation may be an effective method for reducing ICS usage in veterans as seen in this study. Additional controlled studies are required to evaluate the efficacy and safety of pharmacist-driven ICS de-escalation.

Systemic glucocorticoids play an important role in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. They are recommended to shorten recovery time and increase forced expiratory volume in 1 second (FEV1) during exacerbations.¹ However, the role of the chronic use of inhaled corticosteroids (ICSs) in the treatment of COPD is less clear.

When added to inhaled β-2 agonists and muscarinic antagonists, ICSs can decrease the risk of exacerbations.¹ However, not all patients with COPD benefit from ICS therapy. The degree of benefit an ICS can provide has been shown to correlate with eosinophil count—a marker of inflammation. The expected benefit of using an ICS increases as the eosinophil count increases.¹ Maximum benefit can be observed with eosinophil counts ≥ 300 cells/µL, and minimal benefit is observed with eosinophil counts < 100 cells/µL. Adverse effects (AEs) of ICSs include a hoarse voice, oral candidiasis, and an increased risk of pneumonia.¹ Given the risk of AEs, it is important to limit ICS use in patients who are unlikely to reap any benefits.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines suggest the use of ICSs in patients who experience exacerbations while using long-acting β agonist (LABA) plus long-acting muscarinic antagonist (LAMA) therapy and have an eosinophil count ≥ 100 cells/µL. Switching from LABA or LAMA monotherapy to triple therapy with LAMA/LABA/ICS may be considered if patients have continued exacerbations and an eosinophil count ≥ 300 cells/µL. De-escalation of ICS therapy should be considered if patients do not meet these criteria or if patients experience ICS AEs, such as pneumonia. The patients most likely to have increased exacerbations or decreased FEV1 with ICS withdrawal are those with eosinophil counts ≥ 300 cells/µL.^1,2Several studies have explored the effects of ICS de-escalation in real-world clinical settings. A systematic review of 11 studies indicated that de-escalation of ICS in COPD does not result in increased exacerbations.³ A prospective study by Rossi et al found that in a 6-month period, 141 of 482 patients on ICS therapy (29%) had an exacerbation. In the opposing arm of the study, 88 of 334 patients (26%) with deprescribed ICS experienced an exacerbation. The difference between these 2 groups was not statistically significant.⁴ The researchers concluded that in real-world practice, ICS withdrawal can be safe in patients at low risk of exacerbation.

About 25% of veterans (1.25 million) have been diagnosed with COPD.⁵ To address this, the US Department of Veterans Affairs (VA) and US Department of Defense published updated COPD guidelines in 2021 that specify criteria for de-escalation of ICS.⁶ Guidelines, however, may not be reflected in common clinical practice for several years following publication. The VA Academic Detailing Service (ADS) provides tools to help clinicians identify patients who may benefit from changes in treatment plans. A recent ADS focus was the implementation of a COPD dashboard, which identifies patients with COPD who are candidates for ICS de-escalation based on comorbid diagnoses, exacerbation history, and eosinophil count. VA pharmacists have an expanded role in the management of primary care disease states and are therefore well-positioned to increase adherence to guideline-directed therapy. The objective of this quality improvement project was to determine the impact of pharmacist-driven de-escalation on ICS usage in veterans with COPD.

Methods

This project was conducted in an outpatient clinic at the Robley Rex VA Medical Center beginning September 21, 2023, with a progress note in the Computerized Patient Record System (CPRS). Eligible patients were selected using the COPD Dashboard provided by ADS. The COPD Dashboard defined patients with COPD as those with ≥ 2 outpatient COPD diagnoses in the past 2 years, 1 inpatient discharge COPD diagnosis in the past year, or COPD listed as an active problem. COPD diagnoses were identified using International Statistical Classification of Disease, Tenth Revision (ICD-10) codes (Appendix).

Candidates identified for ICS de-escalation by the dashboard were excluded if they had a history of COPD exacerbation in the previous 2 years. The dashboard identified COPD exacerbations via ICD-10 codes for COPD or acute respiratory failure for inpatient discharges, emergency department (ED) visits, urgent care visits, and community care consults with 1 of the following terms: emergency, inpatient, hospital, urgent, ED (self). The COPD dashboard excluded patients with a diagnosis of asthma.

After patients were selected, they were screened for additional exclusion criteria. Patients were excluded if a pulmonary care practitioner managed their COPD; if identified via an active pulmonary consult in CPRS; if a non-VA clinician prescribed their ICS; or if they were being treated with roflumilast, theophylline, or chronic azithromycin. Individuals taking these 3 drugs were excluded due to potential severe and/or refractory COPD. Patients also were excluded if they: (1) had prior ICS de-escalation failure (defined as a COPD exacerbation following ICS de-escalation that resulted in ICS resumption); (2) had a COPD exacerbation requiring systemic corticosteroids or antibiotics in the previous year; (3) had active lung cancer; (4) did not have any eosinophil levels in CPRS within the previous 2 years; or (5) had any eosinophil levels ≥ 300 cells/µL in the previous year.

Each patient who met the inclusion criteria and was not excluded received a focused medication review by a pharmacist who created a templated progress note, with patient-specific recommendations, that was entered in the CPRS (eAppendix). The recommendations were also attached as an addendum to the patient’s last primary care visit note, and the primary care practitioner (PCP) was alerted via CPRS to consider ICS de-escalation and non-ICS alternatives. Tapering of ICS therapy was offered as an option to de-escalate if abrupt discontinuation was deemed inappropriate. PCPs were also prompted to consider referral to a primary care clinical pharmacy specialist for management and follow-up of ICS de-escalation.

The primary outcome was the number of patients with de-escalated ICS at 3 and 6 months following the recommendation. Secondary outcomes included the number of: patients who were no longer prescribed an ICS or who had a non-ICS alternative initiated at a pharmacist’s recommendation; patients who were referred to a primary care clinical pharmacy specialist for ICS de-escalation; COPD exacerbations requiring systemic steroids or antibiotics, or requiring an ED visit, inpatient admission, or urgent-care clinic visit; and cases of pneumonia or oral candidiasis. Primary and secondary outcomes were evaluated via chart review in CPRS. For secondary outcomes of pneumonia and COPD exacerbation, identification was made by documented diagnosis in CPRS. For continuous data such as age, the mean was calculated.

Results

Pharmacist ICS de-escalation recommendations were made between September 21, 2023, and November 19, 2023, for 106 patients. The mean age was 72 years and 99 (93%) patients were male (Table 1). Forty-one (39%) of the patients used tobacco at the time of the study. FEV1 was available for 69 patients with a mean of 63% (GOLD grade 2).¹ Based on FEV1 values, 16 patients had mild COPD (GOLD grade 1), 37 patients had moderate COPD (GOLD grade 2), 14 patients had severe COPD (GOLD grade 3), and 2 patients had very severe COPD (GOLD grade 4).¹ Thirty-four patients received LABA + LAMA + ICS, 65 received LABA + ICS, 2 received LAMA + ICS, and 5 received ICS monotherapy. The most common dose of ICS was a moderate dose (Table 2). Only 2 patients had an ICS AE in the previous year.

ICS de-escalation recommendations resulted in ICS de-escalation in 50 (47.2%) and 62 (58.5%) patients at 3 and 6 months, respectively. The 6-month ICS de-escalation rate by ICS dose at baseline was 72.2% (high dose), 60.0% (moderate), and 30.8% (low). De-escalation at 6 months by GOLD grade at baseline was 56.3% (9 of 16 patients, GOLD 1), 64.9% (24 of 37 patients, GOLD 2), 50% (7 of 14 patients, GOLD 3), and 50% (1 of 2 patients, GOLD 4). Six months after the ICS de-escalation recommendation appeared in the CPRS, the percentage of patients on LABA + ICS therapy dropped from 65 patients (61.3%) at baseline to 25 patients (23.6%).

Secondary outcomes were assessed at 3 and 6 months following the recommendation. Most patients with de-escalated ICS had their ICS discontinued and a non-ICS alternative initiated per pharmacist recommendations. At 6 months, 39 patients (36.8%) patients were referred to a patient aligned care team (PACT) pharmacist for de-escalation. Of the 39 patients referred to pharmacists, 69.2% (27 patients) were de-escalated; this compared to 52.2% (35 patients) who were not referred to pharmacists (Table 3).

ICS use increases the risk of pneumonia.¹ At 6 months, 11 patients were diagnosed with pneumonia; 3 patients were diagnosed with pneumonia twice, resulting in a total of 14 cases. Ten cases occurred while patients were on ICS and 4 cases occurred following ICS de-escalation. One patient had a documented case of oral candidiasis that occurred while on ICS therapy; no patients with discontinued ICS were diagnosed with oral candidiasis. In addition, 10 patients had COPD exacerbations; however no patients had exacerbations both before and after de-escalation. Six patients were on ICS therapy when they experienced an exacerbation, and 4 patients had an exacerbation after ICS de-escalation.

Discussion

More than half of patients receiving the pharmacist intervention achieved the primary outcome of ICS de-escalation at 6 months. Furthermore, a larger percentage of patients referred to pharmacists for the management of ICS de-escalation successfully achieved de-escalation compared to those who were not referred. These outcomes reflect the important role pharmacists can play in identifying appropriate candidates for ICS de-escalation and assisting in the management of ICS de-escalation. Patients referred to pharmacists also received other services such as smoking cessation pharmacotherapy and counseling on inhaler technique and adherence. These interventions can support improved COPD clinical outcomes.

The purpose of de-escalating ICS therapy is to reduce the risk of AEs such as pneumonia and oral candidiasis.¹ The secondary outcomes of this study support previous evidence that patients who have de-escalated ICS therapy may have reduced risk of AEs compared to those who remain on ICS therapy.³ Specifically, of the 14 cases of pneumonia that occurred during the study, 10 cases occurred while patients were on ICS and 4 cases occurred following ICS de-escalation.

ICS de-escalation may increase risk of increased COPD exacerbations.¹ However, the secondary outcomes of this study do not indicate that those with de-escalated ICS had more COPD exacerbations compared to those who continued on ICS. Pharmacists’ recommendations were more effective for patients with less severe COPD based on baseline FEV1.

The previous GOLD Guidelines for COPD suggested LABA + ICS therapy as an option for patients with a high symptom and exacerbation burden (previously known as GOLD Group D). Guidelines no longer recommend LABA + ICS therapy due to the superiority of triple inhaled therapy for exacerbations and the superiority of LAMA + LABA therapy for dyspnea.⁷ A majority of identified patients in this project were on LABA + ICS therapy alone at baseline. The ICS de-escalation recommendation resulted in a 61.5% reduction in patients on LABA + ICS therapy at 6 months. By decreasing the number of patients on LABA + ICS without LAMA, recommendations increased the number of patients on guideline-directed therapy.

Limitations

This study lacked a control group, and the rate of ICS de-escalation in patients who did not receive a pharmacist recommendation was not assessed. Therefore, it could not be determined whether the pharmacist recommendation is more effective than no recommendation. Another limitation was our inability to access records from non-VA health care facilities. This may have resulted in missed COPD exacerbations, pneumonia, and oral candidiasis prior to or following the pharmacist recommendation.

In addition, the method used to notify PCPs of the pharmacist recommendation was a CPRS alert. Clinicians often receive multiple daily alerts and may not always pay close attention to them due to alert fatigue. Early in the study, some PCPs were unknowingly omitted from the alert of the pharmacist recommendation for 10 patients due to human error. For 8 of these 10 patients, the PCP was notified of the recommendations during the 3-month follow-up period. However, 2 patients had COPD exacerbations during the 3-month follow-up period. In these cases, the PCP was not alerted to de-escalate ICS. The data for these patients were collected at 3 and 6 months in the same manner as all other patients. Also, 7 of 35 patients who were referred to a pharmacist for ICS de-escalation did not have a scheduled appointment. These patients were considered to be lost to follow-up and this may have resulted in an underestimation of the ability of pharmacists to successfully de-escalate ICS in patients with COPD.

Other studies have evaluated the efficacy of a pharmacy-driven ICS de-escalation.^8,9 Hegland et al reported ICS de-escalation for 22% of 141 eligible ambulatory patients with COPD on triple inhaled therapy following pharmacist appointments.⁸ A study by Hahn et al resulted in 63.8% of 58 patients with COPD being maintained off ICS following a pharmacist de-escalation initiative.⁹ However, these studies relied upon more time-consuming de-escalation interventions, including at least 1 phone, video, or in-person patient visit.^8,9

This project used a single chart review and templated progress note to recommend ICS de-escalation and achieved similar or improved de-escalation rates compared to previous studies.^8,9 Previous studies were conducted prior to the updated 2023 GOLD guidelines for COPD which no longer recommend LABA + ICS therapy. This project addressed ICS de-escalation in patients on LABA + ICS therapy in addition to those on triple inhaled therapy. Additionally, previous studies did not address rates of moderate to severe COPD exacerbation and adverse events to ICS following the pharmacist intervention.^8,9

This study included COPD exacerbations and cases of pneumonia or oral candidiasis as secondary outcomes to assess the safety and efficacy of the ICS de-escalation. It appeared there were similar or lower rates of COPD exacerbations, pneumonia, and oral candidiasis in those with de-escalated ICS therapy in this study. However, these secondary outcomes are exploratory and would need to be confirmed by larger studies powered to address these outcomes.

CONCLUSIONS

Pharmacist-driven ICS de-escalation may be an effective method for reducing ICS usage in veterans as seen in this study. Additional controlled studies are required to evaluate the efficacy and safety of pharmacist-driven ICS de-escalation.

Quality improvement (QI) initiatives within the US Department of Veterans Affairs (VA) play an important role in enhancing health care for veterans.^1,2 While effective QI programs are often developed, veterans benefit only if they receive care at sites where the program is offered.³ It is estimated only 1% to 5% of patients receive benefit from evidence-based programs, limiting the opportunity for widespread impact.^4,5

The Chronic Obstructive Pulmonary Disease (COPD) Coordinated Access to Reduce Exacerbations (CARE) Academy is a national training program designed to promote the adoption of a COPD primary care service.⁶ The Academy was created and iteratively refined by VA staff to include both clinical training emphasizing COPD management and program implementation strategies. Training programs such as COPD CARE are commonly described as a method to support adoption of health care services, but there is no consensus on a universal approach to training design.

This article describes COPD CARE training and implementation strategies (Table). The Academy began as a training program at 1 VA medical center (VAMC) and has expanded to 49 diverse VAMCs. The Academy illustrates how implementation strategies can be leveraged to develop pragmatic and impactful training. Highlights from the Academy's 9-year history are outlined in this article.

COPD CARE

One in 4 veterans have a COPD diagnosis, and the 5-year mortality rate following a COPD flare is ≥ 50%.^7,8 In 2015, a pharmacy resident designed and piloted COPD CARE, a program that used evidence-based practice to optimize management of the disease.^9,10

The COPD CARE program is delivered by interprofessional team members. It includes a postacute care call completed 48 hours postdischarge, a wellness visit (face-to-face or virtual) 1 month postdischarge, and a follow-up visit scheduled 2 months postdischarge. Clinical pharmacist practitioners (CPPs) prescribe and collaborate with the COPD CARE health care team. Evidence-based practices embedded within COPD CARE include treatment optimization, symptom evaluation, severity staging, vaccination promotion, referrals, tobacco treatment, and comorbidity management.^11-16 The initial COPD CARE pilot demonstrated promising results; patients received timely care and high rates of COPD best practices.¹¹

Academy Design and Implementation

Initial COPD CARE training was tailored to the culture, context, and workflow of the William S. Middleton Memorial Veteran’s Hospital in Madison, Wisconsin. Further service expansion required integration of implementation strategies that enable learners to apply and adapt content to fit different processes, staffing, and patient needs.

Formal Implementation Blueprint

A key aspect of the Academy is the integration of a formal implementation blueprint that includes training goals, scope, and key milestones to guide implementation. The Academy blueprint includes 4 phased training workbooks: (1) preimplementation support from local stakeholders; (2) integration of COPD CARE operational infrastructure into workflows; (3) preparing clinical champions; and (4) leading clinical training (Figure 1). Five weekly 1-hour synchronous virtual discussions are used for learning the workbook content that include learning objectives and opportunities to strategize how to overcome implementation barriers.

Promoting and Facilitating Implementation

As clinicians apply content from the Academy to install informatics tools, coordinate clinical training, and build relationships across service lines, implementation barriers may occur. A learning collaborative allows peer-mentorship and shared problem solving. The Academy learning collaborative includes attendees across multiple VAMCs, allowing for diverse perspectives and cross-site learning. Within the field of dissemination and implementation science, this process of shared problem-solving to support individuals is referred to as implementation facilitation.¹⁷ Academy facilitators with prior experience provide a unique perspective and external facilitation from outside local VAMCs. Academy learners form local teams to engage in shared decision-making when applying Academy content. Following Academy completion, learning collaboratives continue to meet monthly to share clinical insights and operational updates.

Local Champions Promote Adaptability

One or more local champions were identified at each VAMC who were focused on the implementation of clinical training content and operational implementation of Academy content.¹⁸ Champions have helped develop adaptations of Academy content, such as integrating telehealth nursing within the COPD CARE referral process, which have become new best practices. Champions attend Academy sessions, which provide an opportunity to share adaptations to meet local needs.¹⁹

Using a Train-The-Trainer Model

Clinical training was designed to be dynamic and included video modeling, such as recorded examples of CPPs conducting COPD CARE visits and video clips highlighting clinical content. Each learner received a clinical workbook summarizing the content. The champion shares discussion questions to relate training content to the local clinical practice setting. The combination of live training, with videos of clinic visits and case-based discussion was intended to address differing learning styles. Clinical training was delivered using a train-the-trainer model led by the local champion, which allows clinicians with expertise to tailor their training. The use of a train-the-trainer model was intended to promote local buy-in and was often completed by frontline clinicians.

Informatics note templates provide clinicians with information needed to deliver training content during clinic visits. Direct hyperlinks to symptomatic scoring tools, resources to promote evidence-based medication optimization, and patient education resources were embedded within the electronic health record note templates. Direct links to consults for COPD referrals services discussed during clinical training were also included to promote ease of care coordination and awareness of referral opportunities. The integration of clinical training with informatics note template support was intentional to directly relate clinical training to clinical care delivery.

Audit and Feedback

To inform COPD CARE practice, the Academy included informatics infrastructure that allowed for timely local quality monitoring. Electronic health record note templates with embedded data fields track COPD CARE service implementation, including timely completion of patient visits, completion of patient medication reviews, appropriate testing, symptom assessment, and interventions made. Champions can organize template installation and integrate templates into COPD CARE clinical training. Data are included on a COPD CARE implementation dashboard.

An audit and feedback process is allows for the review of performance metrics and development of action plans.^20,21 Data reports from note templates are described during the Academy, along with resources to help teams enhance delivery of their program based on performance metrics.

Building a Coalition

Within VA primary care, clinical care delivery is optimized through a team-based coalition of clinicians using the patient aligned care team (PACT) framework. The VA patient-centered team-based care delivery model, patient facilitates coordination of patient referrals, including patient review, scheduling, and completion of patient visits.²²

Partnerships with VA Pharmacy Benefits Manager, VA Diffusion of Excellence, VA Quality Enhancement Research Initiative, VA Office of Pulmonary Medicine, and the VA Office of Rural Health have facilitated COPD CARE successes. Collaborations with VA Centers of Innovation helped benchmark the Academy’s impact. An academic partnership with the University of Wisconsin-Madison was established in 2017 and has provided evaluation expertise and leadership as the Academy has been iteratively developed, and revised.

Preliminary Metrics

COPD CARE has delivered > 2000 visits. CPPs have delivered COPD care, with a mean 9.4 of 10 best practices per patient visit. Improvements in veteran COPD symptoms have also been observed following COPD CARE patient visits.

DISCUSSION

The COPD CARE Academy was developed to promote rapid scale-up of a complex, team-based COPD service delivered during veteran care transitions. The implementation blueprint for the Academy is multifaceted and integrates both clinical-focused and implementation-focused infrastructure to apply training content.²³ A randomized control trial evaluating the efficacy of training modalities found a need to expand implementation blueprints beyond clinical training alone, as training by itself may not be sufficient to change behavior.²⁴ VA staff designed the Academy using clinical- and implementation-focused content within its implementation blueprint. Key components included leveraging clinical champions, using a train-the-trainer approach, and incorporating facilitation strategies to overcome adoption barriers.

Lewis et al emphasize matching implementation strategies to barriers within VA staff who identify care coordination as a key challenge.²³ The informatics infrastructure developed for Academy learners, including standardized note templates, video modeling examples of clinic visits, and data capture for audit and feedback, was designed to complement clinical training and standardize service workflows (Figure 2). There are opportunities to explore how to optimize technology in the Academy.

While Academy clinical training specifically focuses on COPD management, many implementation strategies can be considered to promote care delivery services for other chronic conditions. The Academy blueprint and implementation infrastructure, are strategies that may be considered within and outside the federal health care system. The opportunity for adaptations to Academy training enables clinical champions to promote tailored content to the needs of each unique VAMC. The translation of Academy implementation strategies for new chronic conditions will similarly require adaptations at each VAMC to promote adoption of content.

CONCLUSIONS

COPD CARE Academy is an example of the collaborative spirit within VA, and the opportunity for further advancement of health care programs. The VA is a national leader in Learning Health Systems implementation, in which “science, informatics, incentives and culture are aligned for continuous improvement and innovation.”^25,26 There are many opportunities for VA staff to learn from one another to form partnerships between leaders, clinicians, and scientists to optimize health care delivery and further the VA’s work as a learning health system.

Quality improvement (QI) initiatives within the US Department of Veterans Affairs (VA) play an important role in enhancing health care for veterans.^1,2 While effective QI programs are often developed, veterans benefit only if they receive care at sites where the program is offered.³ It is estimated only 1% to 5% of patients receive benefit from evidence-based programs, limiting the opportunity for widespread impact.^4,5

The Chronic Obstructive Pulmonary Disease (COPD) Coordinated Access to Reduce Exacerbations (CARE) Academy is a national training program designed to promote the adoption of a COPD primary care service.⁶ The Academy was created and iteratively refined by VA staff to include both clinical training emphasizing COPD management and program implementation strategies. Training programs such as COPD CARE are commonly described as a method to support adoption of health care services, but there is no consensus on a universal approach to training design.

This article describes COPD CARE training and implementation strategies (Table). The Academy began as a training program at 1 VA medical center (VAMC) and has expanded to 49 diverse VAMCs. The Academy illustrates how implementation strategies can be leveraged to develop pragmatic and impactful training. Highlights from the Academy's 9-year history are outlined in this article.

COPD CARE

One in 4 veterans have a COPD diagnosis, and the 5-year mortality rate following a COPD flare is ≥ 50%.^7,8 In 2015, a pharmacy resident designed and piloted COPD CARE, a program that used evidence-based practice to optimize management of the disease.^9,10

The COPD CARE program is delivered by interprofessional team members. It includes a postacute care call completed 48 hours postdischarge, a wellness visit (face-to-face or virtual) 1 month postdischarge, and a follow-up visit scheduled 2 months postdischarge. Clinical pharmacist practitioners (CPPs) prescribe and collaborate with the COPD CARE health care team. Evidence-based practices embedded within COPD CARE include treatment optimization, symptom evaluation, severity staging, vaccination promotion, referrals, tobacco treatment, and comorbidity management.^11-16 The initial COPD CARE pilot demonstrated promising results; patients received timely care and high rates of COPD best practices.¹¹

Academy Design and Implementation

Initial COPD CARE training was tailored to the culture, context, and workflow of the William S. Middleton Memorial Veteran’s Hospital in Madison, Wisconsin. Further service expansion required integration of implementation strategies that enable learners to apply and adapt content to fit different processes, staffing, and patient needs.

Formal Implementation Blueprint

A key aspect of the Academy is the integration of a formal implementation blueprint that includes training goals, scope, and key milestones to guide implementation. The Academy blueprint includes 4 phased training workbooks: (1) preimplementation support from local stakeholders; (2) integration of COPD CARE operational infrastructure into workflows; (3) preparing clinical champions; and (4) leading clinical training (Figure 1). Five weekly 1-hour synchronous virtual discussions are used for learning the workbook content that include learning objectives and opportunities to strategize how to overcome implementation barriers.

Promoting and Facilitating Implementation

As clinicians apply content from the Academy to install informatics tools, coordinate clinical training, and build relationships across service lines, implementation barriers may occur. A learning collaborative allows peer-mentorship and shared problem solving. The Academy learning collaborative includes attendees across multiple VAMCs, allowing for diverse perspectives and cross-site learning. Within the field of dissemination and implementation science, this process of shared problem-solving to support individuals is referred to as implementation facilitation.¹⁷ Academy facilitators with prior experience provide a unique perspective and external facilitation from outside local VAMCs. Academy learners form local teams to engage in shared decision-making when applying Academy content. Following Academy completion, learning collaboratives continue to meet monthly to share clinical insights and operational updates.

Local Champions Promote Adaptability

One or more local champions were identified at each VAMC who were focused on the implementation of clinical training content and operational implementation of Academy content.¹⁸ Champions have helped develop adaptations of Academy content, such as integrating telehealth nursing within the COPD CARE referral process, which have become new best practices. Champions attend Academy sessions, which provide an opportunity to share adaptations to meet local needs.¹⁹

Using a Train-The-Trainer Model

Clinical training was designed to be dynamic and included video modeling, such as recorded examples of CPPs conducting COPD CARE visits and video clips highlighting clinical content. Each learner received a clinical workbook summarizing the content. The champion shares discussion questions to relate training content to the local clinical practice setting. The combination of live training, with videos of clinic visits and case-based discussion was intended to address differing learning styles. Clinical training was delivered using a train-the-trainer model led by the local champion, which allows clinicians with expertise to tailor their training. The use of a train-the-trainer model was intended to promote local buy-in and was often completed by frontline clinicians.

Informatics note templates provide clinicians with information needed to deliver training content during clinic visits. Direct hyperlinks to symptomatic scoring tools, resources to promote evidence-based medication optimization, and patient education resources were embedded within the electronic health record note templates. Direct links to consults for COPD referrals services discussed during clinical training were also included to promote ease of care coordination and awareness of referral opportunities. The integration of clinical training with informatics note template support was intentional to directly relate clinical training to clinical care delivery.

Audit and Feedback

To inform COPD CARE practice, the Academy included informatics infrastructure that allowed for timely local quality monitoring. Electronic health record note templates with embedded data fields track COPD CARE service implementation, including timely completion of patient visits, completion of patient medication reviews, appropriate testing, symptom assessment, and interventions made. Champions can organize template installation and integrate templates into COPD CARE clinical training. Data are included on a COPD CARE implementation dashboard.

An audit and feedback process is allows for the review of performance metrics and development of action plans.^20,21 Data reports from note templates are described during the Academy, along with resources to help teams enhance delivery of their program based on performance metrics.

Building a Coalition

Within VA primary care, clinical care delivery is optimized through a team-based coalition of clinicians using the patient aligned care team (PACT) framework. The VA patient-centered team-based care delivery model, patient facilitates coordination of patient referrals, including patient review, scheduling, and completion of patient visits.²²

Partnerships with VA Pharmacy Benefits Manager, VA Diffusion of Excellence, VA Quality Enhancement Research Initiative, VA Office of Pulmonary Medicine, and the VA Office of Rural Health have facilitated COPD CARE successes. Collaborations with VA Centers of Innovation helped benchmark the Academy’s impact. An academic partnership with the University of Wisconsin-Madison was established in 2017 and has provided evaluation expertise and leadership as the Academy has been iteratively developed, and revised.

Preliminary Metrics

COPD CARE has delivered > 2000 visits. CPPs have delivered COPD care, with a mean 9.4 of 10 best practices per patient visit. Improvements in veteran COPD symptoms have also been observed following COPD CARE patient visits.

DISCUSSION

The COPD CARE Academy was developed to promote rapid scale-up of a complex, team-based COPD service delivered during veteran care transitions. The implementation blueprint for the Academy is multifaceted and integrates both clinical-focused and implementation-focused infrastructure to apply training content.²³ A randomized control trial evaluating the efficacy of training modalities found a need to expand implementation blueprints beyond clinical training alone, as training by itself may not be sufficient to change behavior.²⁴ VA staff designed the Academy using clinical- and implementation-focused content within its implementation blueprint. Key components included leveraging clinical champions, using a train-the-trainer approach, and incorporating facilitation strategies to overcome adoption barriers.

Lewis et al emphasize matching implementation strategies to barriers within VA staff who identify care coordination as a key challenge.²³ The informatics infrastructure developed for Academy learners, including standardized note templates, video modeling examples of clinic visits, and data capture for audit and feedback, was designed to complement clinical training and standardize service workflows (Figure 2). There are opportunities to explore how to optimize technology in the Academy.

While Academy clinical training specifically focuses on COPD management, many implementation strategies can be considered to promote care delivery services for other chronic conditions. The Academy blueprint and implementation infrastructure, are strategies that may be considered within and outside the federal health care system. The opportunity for adaptations to Academy training enables clinical champions to promote tailored content to the needs of each unique VAMC. The translation of Academy implementation strategies for new chronic conditions will similarly require adaptations at each VAMC to promote adoption of content.

CONCLUSIONS

COPD CARE Academy is an example of the collaborative spirit within VA, and the opportunity for further advancement of health care programs. The VA is a national leader in Learning Health Systems implementation, in which “science, informatics, incentives and culture are aligned for continuous improvement and innovation.”^25,26 There are many opportunities for VA staff to learn from one another to form partnerships between leaders, clinicians, and scientists to optimize health care delivery and further the VA’s work as a learning health system.

Quality improvement (QI) initiatives within the US Department of Veterans Affairs (VA) play an important role in enhancing health care for veterans.^1,2 While effective QI programs are often developed, veterans benefit only if they receive care at sites where the program is offered.³ It is estimated only 1% to 5% of patients receive benefit from evidence-based programs, limiting the opportunity for widespread impact.^4,5

The Chronic Obstructive Pulmonary Disease (COPD) Coordinated Access to Reduce Exacerbations (CARE) Academy is a national training program designed to promote the adoption of a COPD primary care service.⁶ The Academy was created and iteratively refined by VA staff to include both clinical training emphasizing COPD management and program implementation strategies. Training programs such as COPD CARE are commonly described as a method to support adoption of health care services, but there is no consensus on a universal approach to training design.

This article describes COPD CARE training and implementation strategies (Table). The Academy began as a training program at 1 VA medical center (VAMC) and has expanded to 49 diverse VAMCs. The Academy illustrates how implementation strategies can be leveraged to develop pragmatic and impactful training. Highlights from the Academy's 9-year history are outlined in this article.

COPD CARE

One in 4 veterans have a COPD diagnosis, and the 5-year mortality rate following a COPD flare is ≥ 50%.^7,8 In 2015, a pharmacy resident designed and piloted COPD CARE, a program that used evidence-based practice to optimize management of the disease.^9,10

The COPD CARE program is delivered by interprofessional team members. It includes a postacute care call completed 48 hours postdischarge, a wellness visit (face-to-face or virtual) 1 month postdischarge, and a follow-up visit scheduled 2 months postdischarge. Clinical pharmacist practitioners (CPPs) prescribe and collaborate with the COPD CARE health care team. Evidence-based practices embedded within COPD CARE include treatment optimization, symptom evaluation, severity staging, vaccination promotion, referrals, tobacco treatment, and comorbidity management.^11-16 The initial COPD CARE pilot demonstrated promising results; patients received timely care and high rates of COPD best practices.¹¹

Academy Design and Implementation

Initial COPD CARE training was tailored to the culture, context, and workflow of the William S. Middleton Memorial Veteran’s Hospital in Madison, Wisconsin. Further service expansion required integration of implementation strategies that enable learners to apply and adapt content to fit different processes, staffing, and patient needs.

Formal Implementation Blueprint

A key aspect of the Academy is the integration of a formal implementation blueprint that includes training goals, scope, and key milestones to guide implementation. The Academy blueprint includes 4 phased training workbooks: (1) preimplementation support from local stakeholders; (2) integration of COPD CARE operational infrastructure into workflows; (3) preparing clinical champions; and (4) leading clinical training (Figure 1). Five weekly 1-hour synchronous virtual discussions are used for learning the workbook content that include learning objectives and opportunities to strategize how to overcome implementation barriers.

Promoting and Facilitating Implementation

As clinicians apply content from the Academy to install informatics tools, coordinate clinical training, and build relationships across service lines, implementation barriers may occur. A learning collaborative allows peer-mentorship and shared problem solving. The Academy learning collaborative includes attendees across multiple VAMCs, allowing for diverse perspectives and cross-site learning. Within the field of dissemination and implementation science, this process of shared problem-solving to support individuals is referred to as implementation facilitation.¹⁷ Academy facilitators with prior experience provide a unique perspective and external facilitation from outside local VAMCs. Academy learners form local teams to engage in shared decision-making when applying Academy content. Following Academy completion, learning collaboratives continue to meet monthly to share clinical insights and operational updates.

Local Champions Promote Adaptability

One or more local champions were identified at each VAMC who were focused on the implementation of clinical training content and operational implementation of Academy content.¹⁸ Champions have helped develop adaptations of Academy content, such as integrating telehealth nursing within the COPD CARE referral process, which have become new best practices. Champions attend Academy sessions, which provide an opportunity to share adaptations to meet local needs.¹⁹

Using a Train-The-Trainer Model

Clinical training was designed to be dynamic and included video modeling, such as recorded examples of CPPs conducting COPD CARE visits and video clips highlighting clinical content. Each learner received a clinical workbook summarizing the content. The champion shares discussion questions to relate training content to the local clinical practice setting. The combination of live training, with videos of clinic visits and case-based discussion was intended to address differing learning styles. Clinical training was delivered using a train-the-trainer model led by the local champion, which allows clinicians with expertise to tailor their training. The use of a train-the-trainer model was intended to promote local buy-in and was often completed by frontline clinicians.

Informatics note templates provide clinicians with information needed to deliver training content during clinic visits. Direct hyperlinks to symptomatic scoring tools, resources to promote evidence-based medication optimization, and patient education resources were embedded within the electronic health record note templates. Direct links to consults for COPD referrals services discussed during clinical training were also included to promote ease of care coordination and awareness of referral opportunities. The integration of clinical training with informatics note template support was intentional to directly relate clinical training to clinical care delivery.

Audit and Feedback

To inform COPD CARE practice, the Academy included informatics infrastructure that allowed for timely local quality monitoring. Electronic health record note templates with embedded data fields track COPD CARE service implementation, including timely completion of patient visits, completion of patient medication reviews, appropriate testing, symptom assessment, and interventions made. Champions can organize template installation and integrate templates into COPD CARE clinical training. Data are included on a COPD CARE implementation dashboard.

An audit and feedback process is allows for the review of performance metrics and development of action plans.^20,21 Data reports from note templates are described during the Academy, along with resources to help teams enhance delivery of their program based on performance metrics.

Building a Coalition

Within VA primary care, clinical care delivery is optimized through a team-based coalition of clinicians using the patient aligned care team (PACT) framework. The VA patient-centered team-based care delivery model, patient facilitates coordination of patient referrals, including patient review, scheduling, and completion of patient visits.²²

Partnerships with VA Pharmacy Benefits Manager, VA Diffusion of Excellence, VA Quality Enhancement Research Initiative, VA Office of Pulmonary Medicine, and the VA Office of Rural Health have facilitated COPD CARE successes. Collaborations with VA Centers of Innovation helped benchmark the Academy’s impact. An academic partnership with the University of Wisconsin-Madison was established in 2017 and has provided evaluation expertise and leadership as the Academy has been iteratively developed, and revised.

Preliminary Metrics

COPD CARE has delivered > 2000 visits. CPPs have delivered COPD care, with a mean 9.4 of 10 best practices per patient visit. Improvements in veteran COPD symptoms have also been observed following COPD CARE patient visits.

DISCUSSION

The COPD CARE Academy was developed to promote rapid scale-up of a complex, team-based COPD service delivered during veteran care transitions. The implementation blueprint for the Academy is multifaceted and integrates both clinical-focused and implementation-focused infrastructure to apply training content.²³ A randomized control trial evaluating the efficacy of training modalities found a need to expand implementation blueprints beyond clinical training alone, as training by itself may not be sufficient to change behavior.²⁴ VA staff designed the Academy using clinical- and implementation-focused content within its implementation blueprint. Key components included leveraging clinical champions, using a train-the-trainer approach, and incorporating facilitation strategies to overcome adoption barriers.

Lewis et al emphasize matching implementation strategies to barriers within VA staff who identify care coordination as a key challenge.²³ The informatics infrastructure developed for Academy learners, including standardized note templates, video modeling examples of clinic visits, and data capture for audit and feedback, was designed to complement clinical training and standardize service workflows (Figure 2). There are opportunities to explore how to optimize technology in the Academy.

While Academy clinical training specifically focuses on COPD management, many implementation strategies can be considered to promote care delivery services for other chronic conditions. The Academy blueprint and implementation infrastructure, are strategies that may be considered within and outside the federal health care system. The opportunity for adaptations to Academy training enables clinical champions to promote tailored content to the needs of each unique VAMC. The translation of Academy implementation strategies for new chronic conditions will similarly require adaptations at each VAMC to promote adoption of content.

CONCLUSIONS

COPD CARE Academy is an example of the collaborative spirit within VA, and the opportunity for further advancement of health care programs. The VA is a national leader in Learning Health Systems implementation, in which “science, informatics, incentives and culture are aligned for continuous improvement and innovation.”^25,26 There are many opportunities for VA staff to learn from one another to form partnerships between leaders, clinicians, and scientists to optimize health care delivery and further the VA’s work as a learning health system.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

New biologic drugs for chronic obstructive pulmonary disease (COPD) are finally here, said Stephen Rennard, MD, in a presentation in a session on new drugs at the 2024 GOLD International COPD Conference.

The inflammatory pathways associated with COPD are diverse and offer a range of potential targets for biologics, said Rennard, a professor of pulmonary, critical care, and sleep medicine at the University of Nebraska Medical Center, Omaha. 

The therapeutic goals of biologics remain the same as with other treatments for COPD, namely restoration of normal inflammatory response and alteration of disease progression, as well as restoration of lost structure and function and improvement of systemic effects, Rennard said in his presentation. Most studies of new and up-and-coming drugs have improvement in acute exacerbation of COPD as the primary outcome.

 

The Biology Behind the Biologics

T2 inflammation is “an inflammatory cascade led by IL [interleukin]-4, IL-13, and IL-5,” Mona Bafadhel, MD, chair of Respiratory Medicine at King’s College London in England, said in her presentation during the session.

Bafadhel, who served as one of the investigators on the BOREAS and NOTUS studies, explained some of the science behind the development of the new biologics.

Eosinophils are powerful regulators of immune response and inflammation by stimulating T-cell production and affecting other immune cell types, she noted.

In the context of COPD and drug development, high blood eosinophil counts have been associated with increased COPD-related exacerbations, Bafadhel said. She cited data from a Dutch study of more than 7000 patients with COPD (with and without clinical diagnoses), in which absolute eosinophil counts ≥ 3.3% were associated with increased risk for severe exacerbations of 32% and 84% across all patients with COPD and clinical COPD, respectively.

Understanding the mechanisms of the eosinophil in COPD is important for research and development, Bafadhel said. Along with standardizing measurement of T2 inflammatory markers (IL-4, IL-13, and IL-5), more research is needed to fully understand the role of eosinophils in immunoregulation and repair.

 

Fitting the Biologic to the Patient

Several recent studies of up-and-coming biologics have focused on subsets of COPD patients, said Dave Singh, MD, professor of clinical pharmacology and respiratory medicine at The University of Manchester in England, in his presentation at the meeting. In September 2024, the Food and Drug Administration approved dupilumab as the first biologic treatment for patients with uncontrolled COPD and type 2 inflammation on the basis of eosinophil counts. Singh cited data from the BOREAS and NOTUS studies in which dupilumab significantly reduced exacerbations and improved lung function in these patients, compared with a placebo.

Mepolizumab, a biologic approved for asthma, is not currently approved for COPD, but data from a 2017 study showed a trend toward reduced exacerbations, compared with placebo, in a subset of patients with high blood eosinophil counts, Singh said.

In addition, a recent unpublished phase 3 study (MATINEE) showed a reduction in the annualized rate of exacerbations, compared with placebo, on the basis of up to 2 years’ follow-up.

Singh also highlighted data from a phase 2a study of astegolimab, a biologic drug that focuses on the IL-33 receptor, in which COPD exacerbation rates were not significantly different between treatment and placebo groups. However, astegolimab has shown safety and efficacy in adults with severe asthma and is under development in phase 3 trials for COPD.

Tezepelumab, which was approved by the FDA in 2021 as an add-on therapy for severe asthma in patients aged 12 years or older, is also in development as a therapy for COPD exacerbations, Singh said.

In a study presented at the 2024 American Thoracic Society annual meeting, Singh and colleagues found that tezepelumab at a subcutaneous dose of 420 mg every 4 weeks reduced the annualized rate of moderate or severe COPD exacerbations compared with placebo based on data from approximately 300 patients, although the difference was not statistically significant.

Itepekimab, another biologic, showed promise in a phase 2a genetic association study involving current and former smokers with moderate to severe COPD, Singh said.

In that study, published in 2022 in The Lancet Respiratory Medicine, itepekimab failed to meet the primary endpoint in the overall study population of reduced annualized rate of moderate to severe exacerbations; however, a subgroup analysis of former smokers showed a significant (42%) reduction in exacerbations, Singh said in his presentation. Two phase 3 clinical studies (AERIFY-1/2) are ongoing to confirm the safety and efficacy of itepekimab in former smokers with COPD.

 

Takeaways and Next Steps

“These therapies provide the first new classes of medications approved for COPD in nearly 20 years,” said David M. Mannino, MD, of the University of Kentucky, Lexington, in an interview. “Dupilumab will be available to a subset of patients who are poorly controlled and have evidence of high eosinophils in their blood and is only used once every 2 weeks,” added Mannino, who has served as a consultant to companies developing COPD drugs.

Both dupilumab and ensifentrine, a phosphodiesterase (PDE) 3 and PDE4 inhibitor also recently approved for maintenance treatment of COPD, have been shown in clinical trials to reduce exacerbations and improve symptoms, said Mannino. Both offer additional options for patients who continue to have symptoms and exacerbations in spite of their current therapy.

Some barriers to the use of biologics in practice include the high cost. “Access and overcoming insurance-related issues such as preauthorization and high copays will be a challenge,” he said. Also, because dupilumab is an injectable drug, some patient training will be required.

Newer biologic therapies in development are also injectables, but some studies are examining longer time intervals as long as every 6 months, which could be a major advancement for some patients. The newer therapies in development are similar to dupilumab in that they will be injected therapies. Some in development are looking at longer time intervals as long as every 6 months, which may be a major advancement for some patients. “All of these therapies, however, are currently targeting more advanced or serious disease,” he said.

Looking ahead, more therapies are needed for the treatment of early COPD, as well as therapies that can be administered to a large number of patients at a reasonable cost, Mannino added.

Rennard disclosed serving as a consultant for Verona Pharma, Sanofi, Beyond Air, RS BioTherapeutics, RespirAI, and Roche, as well as speaker fees from Sanofi and temporary ownership interest while employed by AstraZeneca. Rennard is also the founder of Great Plains Biometrix. Bafadhel disclosed funding from the National Institute for Health Research (NIHR), grants from Asthma + Lung UK, Horizon Europe, NIHR, and AstraZeneca to her institution, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer. Singh disclosed relationships including speaking sponsorships, honoraria, and advisory board memberships for Adovate, Aerogen, Almirall, Apogee, Arrowhead, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, Connect Biopharm, Covis, CSL Behring, DevPro Biopharm, Elpen, Empirico, EpiEndo, Genentech, Generate Biomedicines, GlaxoSmithKline, Glenmark, Kamada, Kinaset Therapeutics, Kymera, Menarini, MicroA, OM Pharma, Orion, Pieris Pharmaceuticals, Pulmatrix, Revolo, Roivant Sciences, Sanofi, Synairgen, Tetherex, Teva, Theravance Biopharma, Upstream, and Verona Pharma. Mannino disclosed serving as a consultant to multiple companies currently developing COPD therapies (AstraZeneca, GlaxoSmithKline, Roche, Regeneron, Sanofi, Genentech, Amgen, and Chiesi).

A version of this article appeared on Medscape.com.

Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggested.

“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute in Ontario, Canada, said in an interview.

“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.

“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”

The study was published online in The Canadian Medical Association Journal.

 

Potential Risk Reduction 

In March 2017, Ontario Health launched a pilot low-dose CT lung cancer screening program for high-risk individuals between the ages of 55 and 74 years, Small explained. As CAC, a marker of coronary artery disease, is seen easily during such a scan, the researchers analyzed the lung CTs to determine the prevalence of coronary artery disease and whether CAC was associated with increased risk.

The team quantified CAC using an estimated Agatston score and identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from Ottawa Hospital up to December 2023. Among the 1486 people who underwent screening (mean age, 66 years; 52% men; 68% current smokers), CAC was detected in 1232 (82.9%). CAC was mild to moderate in 793 participants (53.4%) and extensive in 439 (29.5%). No CAC was detected in 254 (17.1%) participants.

At follow-up, 78 participants (5.2%) experienced the primary composite outcome, including 39 (8.9%) with extensive CAC, 32 (4.0%) with mild to moderate CAC, and 7 (2.8%) with no CAC.

A total of 49 deaths occurred, including 16 cardiovascular deaths and 19 cancer deaths, of which 10 were from lung cancer. Cardiovascular events included sudden cardiac death (eight participants), fatal stroke (six participants), and one each from heart failure and peripheral vascular disease.

On multivariable analysis, extensive CAC was associated with the composite primary outcome (adjusted hazard ratio [aHR], 2.13), all-cause mortality (aHR, 2.39), and cardiovascular events (aHR, 2.06).

Extensive CAC remained predictive of cardiovascular events even after adjustment for noncardiovascular death as a competing risk (HR, 2.05).

“Our data highlight to lung cancer screening professionals the prevalence of this silent risk factor and re-emphasize the importance of this finding [ie, CAC] as an opportunity for risk reduction,” Small said.

“In terms of next steps, the journey toward cardiovascular risk reduction begins with a clear report of CAC on the lung cancer screening record,” he noted. “Following this step, professionals involved in the lung cancer screening program might consider a local management pathway to ensure that this opportunity for health improvement is not lost or ignored. Preventive medicine of this type would typically involve primary care.”

 

Managing Other Findings

Commenting on the study, Anna Bader, MD, assistant professor of radiology and biomedical imaging at the Yale School of Medicine in New Haven, Connecticut, said that “low-dose CT for lung cancer screening offers valuable insights beyond nodule detection, with CAC being among the most significant incidental findings.”

However, she added, a “robust mechanism” to effectively manage other findings — such as thoracic aortic disease, low bone density, and abnormalities in the thyroid or upper abdominal organs — without overdiagnosis, is needed. A mechanism also is needed to notify cardiologists or primary care providers about severe CAC findings.

Challenges that need to be overcome before such mechanisms can be put in place, she said, “include ensuring standardized CAC reporting, avoiding overburdening healthcare providers, mitigating the risk of excessive downstream testing, and ensuring equitable access to follow-up care for underserved and rural communities.”

Providers involved in lung cancer screening “must be trained to recognize the importance of CAC findings and act upon them,” she added. “Awareness campaigns or continuing medical education modules could address this.”

Multidisciplinary lung cancer screening programs can help with patient education, she noted. “Clear communication about potential findings, including the significance of incidental CAC, should be prioritized and addressed proactively, ideally before the exam, to enhance patient understanding and engagement.”

Matthew Tomey, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said that, “as a practicing cardiologist, I find it very helpful to look at my patients’ recent or past CT scans to look for vascular calcification. Whether or not a scan is specifically protocoled as a cardiac study, we can often appreciate vascular calcification when it is present. I would encourage every physician involved in helping their patients to prevent heart disease to take advantage of looking at any prior CT scans for evidence of vascular calcification.

“Systems of care to facilitate recognition of patients with incidentally discovered vascular calcification would be welcome and, on a large scale, could help prevent cardiovascular events,” he noted. “Such a system might involve facilitating referral to a prevention specialist. It could involve evidence-based guidance for referring physicians who ordered scans.”

Like Bader, he noted the importance of patient education, adding that it could be quite powerful. “We should be doing more to empower our patients to understand the findings of their imaging and to give them actionable, evidence-based guidance on how they can promote their own cardiovascular health,” he concluded.

No funding for the study was reported. Small reported receiving a research grant for amyloid research from Pfizer and honoraria from Pfizer and Alnylam (all paid to the institution, outside the submitted work). Bader and Tomey declared no relevant conflicts.

A version of this article first appeared on Medscape.com.

Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggested.

“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute in Ontario, Canada, said in an interview.

“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.

“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”

The study was published online in The Canadian Medical Association Journal.

 

Potential Risk Reduction 

In March 2017, Ontario Health launched a pilot low-dose CT lung cancer screening program for high-risk individuals between the ages of 55 and 74 years, Small explained. As CAC, a marker of coronary artery disease, is seen easily during such a scan, the researchers analyzed the lung CTs to determine the prevalence of coronary artery disease and whether CAC was associated with increased risk.

The team quantified CAC using an estimated Agatston score and identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from Ottawa Hospital up to December 2023. Among the 1486 people who underwent screening (mean age, 66 years; 52% men; 68% current smokers), CAC was detected in 1232 (82.9%). CAC was mild to moderate in 793 participants (53.4%) and extensive in 439 (29.5%). No CAC was detected in 254 (17.1%) participants.

At follow-up, 78 participants (5.2%) experienced the primary composite outcome, including 39 (8.9%) with extensive CAC, 32 (4.0%) with mild to moderate CAC, and 7 (2.8%) with no CAC.

A total of 49 deaths occurred, including 16 cardiovascular deaths and 19 cancer deaths, of which 10 were from lung cancer. Cardiovascular events included sudden cardiac death (eight participants), fatal stroke (six participants), and one each from heart failure and peripheral vascular disease.

On multivariable analysis, extensive CAC was associated with the composite primary outcome (adjusted hazard ratio [aHR], 2.13), all-cause mortality (aHR, 2.39), and cardiovascular events (aHR, 2.06).

Extensive CAC remained predictive of cardiovascular events even after adjustment for noncardiovascular death as a competing risk (HR, 2.05).

“Our data highlight to lung cancer screening professionals the prevalence of this silent risk factor and re-emphasize the importance of this finding [ie, CAC] as an opportunity for risk reduction,” Small said.

“In terms of next steps, the journey toward cardiovascular risk reduction begins with a clear report of CAC on the lung cancer screening record,” he noted. “Following this step, professionals involved in the lung cancer screening program might consider a local management pathway to ensure that this opportunity for health improvement is not lost or ignored. Preventive medicine of this type would typically involve primary care.”

 

Managing Other Findings

Commenting on the study, Anna Bader, MD, assistant professor of radiology and biomedical imaging at the Yale School of Medicine in New Haven, Connecticut, said that “low-dose CT for lung cancer screening offers valuable insights beyond nodule detection, with CAC being among the most significant incidental findings.”

However, she added, a “robust mechanism” to effectively manage other findings — such as thoracic aortic disease, low bone density, and abnormalities in the thyroid or upper abdominal organs — without overdiagnosis, is needed. A mechanism also is needed to notify cardiologists or primary care providers about severe CAC findings.

Challenges that need to be overcome before such mechanisms can be put in place, she said, “include ensuring standardized CAC reporting, avoiding overburdening healthcare providers, mitigating the risk of excessive downstream testing, and ensuring equitable access to follow-up care for underserved and rural communities.”

Providers involved in lung cancer screening “must be trained to recognize the importance of CAC findings and act upon them,” she added. “Awareness campaigns or continuing medical education modules could address this.”

Multidisciplinary lung cancer screening programs can help with patient education, she noted. “Clear communication about potential findings, including the significance of incidental CAC, should be prioritized and addressed proactively, ideally before the exam, to enhance patient understanding and engagement.”

Matthew Tomey, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said that, “as a practicing cardiologist, I find it very helpful to look at my patients’ recent or past CT scans to look for vascular calcification. Whether or not a scan is specifically protocoled as a cardiac study, we can often appreciate vascular calcification when it is present. I would encourage every physician involved in helping their patients to prevent heart disease to take advantage of looking at any prior CT scans for evidence of vascular calcification.

“Systems of care to facilitate recognition of patients with incidentally discovered vascular calcification would be welcome and, on a large scale, could help prevent cardiovascular events,” he noted. “Such a system might involve facilitating referral to a prevention specialist. It could involve evidence-based guidance for referring physicians who ordered scans.”

Like Bader, he noted the importance of patient education, adding that it could be quite powerful. “We should be doing more to empower our patients to understand the findings of their imaging and to give them actionable, evidence-based guidance on how they can promote their own cardiovascular health,” he concluded.

No funding for the study was reported. Small reported receiving a research grant for amyloid research from Pfizer and honoraria from Pfizer and Alnylam (all paid to the institution, outside the submitted work). Bader and Tomey declared no relevant conflicts.

A version of this article first appeared on Medscape.com.

Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggested.

“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute in Ontario, Canada, said in an interview.

“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.

“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”

The study was published online in The Canadian Medical Association Journal.

 

Potential Risk Reduction 

In March 2017, Ontario Health launched a pilot low-dose CT lung cancer screening program for high-risk individuals between the ages of 55 and 74 years, Small explained. As CAC, a marker of coronary artery disease, is seen easily during such a scan, the researchers analyzed the lung CTs to determine the prevalence of coronary artery disease and whether CAC was associated with increased risk.

The team quantified CAC using an estimated Agatston score and identified the composite primary outcome of all-cause death and cardiovascular events using linked electronic medical record data from Ottawa Hospital up to December 2023. Among the 1486 people who underwent screening (mean age, 66 years; 52% men; 68% current smokers), CAC was detected in 1232 (82.9%). CAC was mild to moderate in 793 participants (53.4%) and extensive in 439 (29.5%). No CAC was detected in 254 (17.1%) participants.

At follow-up, 78 participants (5.2%) experienced the primary composite outcome, including 39 (8.9%) with extensive CAC, 32 (4.0%) with mild to moderate CAC, and 7 (2.8%) with no CAC.

A total of 49 deaths occurred, including 16 cardiovascular deaths and 19 cancer deaths, of which 10 were from lung cancer. Cardiovascular events included sudden cardiac death (eight participants), fatal stroke (six participants), and one each from heart failure and peripheral vascular disease.

On multivariable analysis, extensive CAC was associated with the composite primary outcome (adjusted hazard ratio [aHR], 2.13), all-cause mortality (aHR, 2.39), and cardiovascular events (aHR, 2.06).

Extensive CAC remained predictive of cardiovascular events even after adjustment for noncardiovascular death as a competing risk (HR, 2.05).

“Our data highlight to lung cancer screening professionals the prevalence of this silent risk factor and re-emphasize the importance of this finding [ie, CAC] as an opportunity for risk reduction,” Small said.

“In terms of next steps, the journey toward cardiovascular risk reduction begins with a clear report of CAC on the lung cancer screening record,” he noted. “Following this step, professionals involved in the lung cancer screening program might consider a local management pathway to ensure that this opportunity for health improvement is not lost or ignored. Preventive medicine of this type would typically involve primary care.”

 

Managing Other Findings

Commenting on the study, Anna Bader, MD, assistant professor of radiology and biomedical imaging at the Yale School of Medicine in New Haven, Connecticut, said that “low-dose CT for lung cancer screening offers valuable insights beyond nodule detection, with CAC being among the most significant incidental findings.”

However, she added, a “robust mechanism” to effectively manage other findings — such as thoracic aortic disease, low bone density, and abnormalities in the thyroid or upper abdominal organs — without overdiagnosis, is needed. A mechanism also is needed to notify cardiologists or primary care providers about severe CAC findings.

Challenges that need to be overcome before such mechanisms can be put in place, she said, “include ensuring standardized CAC reporting, avoiding overburdening healthcare providers, mitigating the risk of excessive downstream testing, and ensuring equitable access to follow-up care for underserved and rural communities.”

Providers involved in lung cancer screening “must be trained to recognize the importance of CAC findings and act upon them,” she added. “Awareness campaigns or continuing medical education modules could address this.”

Multidisciplinary lung cancer screening programs can help with patient education, she noted. “Clear communication about potential findings, including the significance of incidental CAC, should be prioritized and addressed proactively, ideally before the exam, to enhance patient understanding and engagement.”

Matthew Tomey, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said that, “as a practicing cardiologist, I find it very helpful to look at my patients’ recent or past CT scans to look for vascular calcification. Whether or not a scan is specifically protocoled as a cardiac study, we can often appreciate vascular calcification when it is present. I would encourage every physician involved in helping their patients to prevent heart disease to take advantage of looking at any prior CT scans for evidence of vascular calcification.

“Systems of care to facilitate recognition of patients with incidentally discovered vascular calcification would be welcome and, on a large scale, could help prevent cardiovascular events,” he noted. “Such a system might involve facilitating referral to a prevention specialist. It could involve evidence-based guidance for referring physicians who ordered scans.”

Like Bader, he noted the importance of patient education, adding that it could be quite powerful. “We should be doing more to empower our patients to understand the findings of their imaging and to give them actionable, evidence-based guidance on how they can promote their own cardiovascular health,” he concluded.

No funding for the study was reported. Small reported receiving a research grant for amyloid research from Pfizer and honoraria from Pfizer and Alnylam (all paid to the institution, outside the submitted work). Bader and Tomey declared no relevant conflicts.

A version of this article first appeared on Medscape.com.