Rod Franklin

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – Daily sublingual immunotherapy for allergic rhinoconjunctivitis from grass pollens is well tolerated in North American adults, lending support for an alternative treatment modality in a patient population that has conventionally received subcutaneous medication, reported Dr. Harold S. Nelson and his coinvestigators.

Recently published results of a 439-patient randomized, phase III trial showed improved daily symptom and medication scores, compared with placebo, in adult patients using Merck’s Timothy grass (Phleum pratense) allergy immunotherapy tablet (AIT) during the 2009 pollen season, the researchers reported in a poster presentation at a meeting on allergy and respiratory diseases.

Photo credit: CDC

Improvements in total combined score (TCS) in patients aged 5-17 years who used the investigational AIT, compared with those who took placebo, were previously reported.

In all, 213 adults were randomized to the AIT (15 mcg of Phl p 5, a formulation of the Timothy grass allergen); the AIT group had a mean TCS score that was a significant 20% higher than the mean score in the placebo group (P = .005). The TCS score was the primary end point of the study and is a sum of the daily symptom score (DSS) and daily medication score (DMS) during the study period, said Dr. Nelson of National Jewish Health, Denver.

Secondary end points were the average DSS and average DMS during the study period, as well as the average weekly score for the Rhinoconjunctivitis Quality of Life Questionnaire. Similar higher scores for the AIT patients were seen in the secondary end points (J. Allergy Clin. Immunol. 2011;127:72-80).

Increases in specific IgE and IgE-blocking factors also were recorded in the AIT group. Levels of specific and blocking IgE were similar in both the AIT and placebo groups at baseline, but they increased in the AIT group over the 16-week treatment period. Levels were significantly increased during the peak and end phases of the season, Dr. Nelson reported at the meeting, which was sponsored by National Jewish Health.

Eleven patients in the AIT group and eight in the placebo group discontinued treatment as a result of adverse events. Adverse reactions were reported as transient in 73% of the AIT group and in 28% of the placebo group. No patients experienced anaphylactic shock.

The multicenter study was designed with a 2008 observational period preceding a dosing period prior to and during the 2009 grass pollen season. The patients had a mean age of 36 years, and most were white. Approximately 85% reported sensitivity to more than one grass pollen. Timothy grass crossreacts with a number of other grasses, including rye, sweet vernal, meadow fescue, bluegrass/june, orchard/cocksfoot, and redtop/bent/velvet.

Oral therapies for grass pollen allergy have been widely studied and used in Europe, but have been used more sporadically in North America. One long-term Danish study of grass AIT therapy in 257 patients supported evidence of a disease-modifying impact (J. Allergy Clin. Immunol. 2010;125:131-8).

In the United States and elsewhere, support for tablet-based medications has risen because of the safety concerns and inconveniences associated with injected immunotherapies.

Dr. Nelson and his coauthors reported current consultation and employment relationships, as well as prior advisory board or research support relationships, with study sponsor Merck.

KEYSTONE, COLO. – It doesn’t take a long stretch of the imagination to surmise that chronic airway remodeling has an impact on airway obstruction in persistent asthma. But to what degree? And should steroid dosing be adjusted to mediate its progression at younger ages?

Biopsies alone don’t adequately address these questions. The impact of airway narrowing is more of a "reasonable correlation" that physicians must formulate by evaluating asthma-related damage and epithelial tissue thickening over time, then comparing it to airway constriction in the patient, said Dr. Anthony N. Gerber of the University of California, San Francisco.

"What [physicians] are forced to do is perform biopsies and correlate the amount of airway smooth muscle thickening or the quantity of basement membrane thickening with the severity of airway obstruction," he said at a meeting on allergy and respiratory diseases, which was sponsored by National Jewish Health. "I don’t know if it’s really possible to deconvolute the precise amount that airway remodeling is contributing to airway obstruction."

Correlating CT scans with bronchial biopsies and histologic analysis sets the stage for a comparison of findings with forced expiratory volume in 1 second (FEV1 ) readings. The physician can then evaluate remodeling in a more relative sense by analyzing how actively it conspires with three additional airway obstruction components – acute asthmatic inflammation, airway hyperreactivity, and mucus formation.

The central hallmarks of chronic remodeling are increased airway smooth muscle mass and subepithelial fibrosis, or thickening in the lamina reticularis from dense fibrotic responses as a result of accumulated collagens. Inflamed airway smooth muscle mass has been associated with a decline in FEV1 (Am. J. Respir. Crit. Care Med. 2010;182:317-24) and is characterized by abnormal cell turnover and proliferation, presumably in response to the chronic inflammatory stimuli that trigger the patient’s asthma. The proliferating cell nuclear antigen (PCNA) is an acknowledged marker for this part of the process, with patients more likely to demonstrate higher levels of PCNA-positive cells as their asthma severity scores increase, Dr. Gerber said.

In addition, subepithelial fibrosis progression may be chronic, with increased smooth muscle narrowing seen in older patients (Am. J. Respir. Crit. Care Med. 2000;162:663-9).

"The real question I think that comes up is, should we treat people with airway remodeling differently than you would treat a typical asthmatic, where you’re just trying to manage their symptoms? I think that the unfortunate answer to this is that we really don’t know enough about the natural history of airway remodeling. Nor do we know enough about the effects of giving high doses of inhaled corticosteroids to potentially reverse airway remodeling," the pathologist said. "But I do think that there’s evidence to maybe give pause to the idea that we should try and find the lowest corticosteroid dose that effectively controls symptoms."

Dr. Gerber’s presentation didn’t explicitly address the chicken-or-egg quandary: Does persistent asthma bring on airway remodeling, or does remodeling worsen an existing case of asthma?

"In general, asthma comes first and leads to remodeling over time," he said in an interview. "However, some people appear more prone to develop remodeling than others. And for some, they may eventually have more symptoms from the remodeling than they ever had from acute asthma attacks."

Only after quantifying the impact of airway remodeling can the physician make an informed decision on adjustments to steroid therapy. Glucocorticoid use remains something of a gamble in consideration of the fact that many of the genes that glucocorticoids act on to control catabolism are not inflammatory regulators. But some early findings have identified KLF15 as a possible glucocorticoid target and regulator of airway remodeling, he said.

Dr. Gerber sits on the advisory board and consults for Breathe Technologies.

KEYSTONE, COLO. – It doesn’t take a long stretch of the imagination to surmise that chronic airway remodeling has an impact on airway obstruction in persistent asthma. But to what degree? And should steroid dosing be adjusted to mediate its progression at younger ages?

Biopsies alone don’t adequately address these questions. The impact of airway narrowing is more of a "reasonable correlation" that physicians must formulate by evaluating asthma-related damage and epithelial tissue thickening over time, then comparing it to airway constriction in the patient, said Dr. Anthony N. Gerber of the University of California, San Francisco.

"What [physicians] are forced to do is perform biopsies and correlate the amount of airway smooth muscle thickening or the quantity of basement membrane thickening with the severity of airway obstruction," he said at a meeting on allergy and respiratory diseases, which was sponsored by National Jewish Health. "I don’t know if it’s really possible to deconvolute the precise amount that airway remodeling is contributing to airway obstruction."

Correlating CT scans with bronchial biopsies and histologic analysis sets the stage for a comparison of findings with forced expiratory volume in 1 second (FEV1 ) readings. The physician can then evaluate remodeling in a more relative sense by analyzing how actively it conspires with three additional airway obstruction components – acute asthmatic inflammation, airway hyperreactivity, and mucus formation.

The central hallmarks of chronic remodeling are increased airway smooth muscle mass and subepithelial fibrosis, or thickening in the lamina reticularis from dense fibrotic responses as a result of accumulated collagens. Inflamed airway smooth muscle mass has been associated with a decline in FEV1 (Am. J. Respir. Crit. Care Med. 2010;182:317-24) and is characterized by abnormal cell turnover and proliferation, presumably in response to the chronic inflammatory stimuli that trigger the patient’s asthma. The proliferating cell nuclear antigen (PCNA) is an acknowledged marker for this part of the process, with patients more likely to demonstrate higher levels of PCNA-positive cells as their asthma severity scores increase, Dr. Gerber said.

In addition, subepithelial fibrosis progression may be chronic, with increased smooth muscle narrowing seen in older patients (Am. J. Respir. Crit. Care Med. 2000;162:663-9).

"The real question I think that comes up is, should we treat people with airway remodeling differently than you would treat a typical asthmatic, where you’re just trying to manage their symptoms? I think that the unfortunate answer to this is that we really don’t know enough about the natural history of airway remodeling. Nor do we know enough about the effects of giving high doses of inhaled corticosteroids to potentially reverse airway remodeling," the pathologist said. "But I do think that there’s evidence to maybe give pause to the idea that we should try and find the lowest corticosteroid dose that effectively controls symptoms."

Dr. Gerber’s presentation didn’t explicitly address the chicken-or-egg quandary: Does persistent asthma bring on airway remodeling, or does remodeling worsen an existing case of asthma?

"In general, asthma comes first and leads to remodeling over time," he said in an interview. "However, some people appear more prone to develop remodeling than others. And for some, they may eventually have more symptoms from the remodeling than they ever had from acute asthma attacks."

Only after quantifying the impact of airway remodeling can the physician make an informed decision on adjustments to steroid therapy. Glucocorticoid use remains something of a gamble in consideration of the fact that many of the genes that glucocorticoids act on to control catabolism are not inflammatory regulators. But some early findings have identified KLF15 as a possible glucocorticoid target and regulator of airway remodeling, he said.

Dr. Gerber sits on the advisory board and consults for Breathe Technologies.

KEYSTONE, COLO. – It doesn’t take a long stretch of the imagination to surmise that chronic airway remodeling has an impact on airway obstruction in persistent asthma. But to what degree? And should steroid dosing be adjusted to mediate its progression at younger ages?

Biopsies alone don’t adequately address these questions. The impact of airway narrowing is more of a "reasonable correlation" that physicians must formulate by evaluating asthma-related damage and epithelial tissue thickening over time, then comparing it to airway constriction in the patient, said Dr. Anthony N. Gerber of the University of California, San Francisco.

"What [physicians] are forced to do is perform biopsies and correlate the amount of airway smooth muscle thickening or the quantity of basement membrane thickening with the severity of airway obstruction," he said at a meeting on allergy and respiratory diseases, which was sponsored by National Jewish Health. "I don’t know if it’s really possible to deconvolute the precise amount that airway remodeling is contributing to airway obstruction."

Correlating CT scans with bronchial biopsies and histologic analysis sets the stage for a comparison of findings with forced expiratory volume in 1 second (FEV1 ) readings. The physician can then evaluate remodeling in a more relative sense by analyzing how actively it conspires with three additional airway obstruction components – acute asthmatic inflammation, airway hyperreactivity, and mucus formation.

The central hallmarks of chronic remodeling are increased airway smooth muscle mass and subepithelial fibrosis, or thickening in the lamina reticularis from dense fibrotic responses as a result of accumulated collagens. Inflamed airway smooth muscle mass has been associated with a decline in FEV1 (Am. J. Respir. Crit. Care Med. 2010;182:317-24) and is characterized by abnormal cell turnover and proliferation, presumably in response to the chronic inflammatory stimuli that trigger the patient’s asthma. The proliferating cell nuclear antigen (PCNA) is an acknowledged marker for this part of the process, with patients more likely to demonstrate higher levels of PCNA-positive cells as their asthma severity scores increase, Dr. Gerber said.

In addition, subepithelial fibrosis progression may be chronic, with increased smooth muscle narrowing seen in older patients (Am. J. Respir. Crit. Care Med. 2000;162:663-9).

"The real question I think that comes up is, should we treat people with airway remodeling differently than you would treat a typical asthmatic, where you’re just trying to manage their symptoms? I think that the unfortunate answer to this is that we really don’t know enough about the natural history of airway remodeling. Nor do we know enough about the effects of giving high doses of inhaled corticosteroids to potentially reverse airway remodeling," the pathologist said. "But I do think that there’s evidence to maybe give pause to the idea that we should try and find the lowest corticosteroid dose that effectively controls symptoms."

Dr. Gerber’s presentation didn’t explicitly address the chicken-or-egg quandary: Does persistent asthma bring on airway remodeling, or does remodeling worsen an existing case of asthma?

"In general, asthma comes first and leads to remodeling over time," he said in an interview. "However, some people appear more prone to develop remodeling than others. And for some, they may eventually have more symptoms from the remodeling than they ever had from acute asthma attacks."

Only after quantifying the impact of airway remodeling can the physician make an informed decision on adjustments to steroid therapy. Glucocorticoid use remains something of a gamble in consideration of the fact that many of the genes that glucocorticoids act on to control catabolism are not inflammatory regulators. But some early findings have identified KLF15 as a possible glucocorticoid target and regulator of airway remodeling, he said.

Dr. Gerber sits on the advisory board and consults for Breathe Technologies.

KEYSTONE, Colo. – Physicians would do well to add habituation, neuropathic triggers, and laryngopharyngeal reflux to the list of factors they assess when tracing the origins of a cough that has persisted for longer than 8 weeks, advised a Colorado pulmonary specialist.

The usually recognized initiators of chronic refractory cough include asthma, upper airway cough syndrome (postnasal drip), and gastroesophageal reflux disease. But looking beyond these common culprits and analyzing combined etiologic factors on a case-by-case basis may be necessary, emphasized Dr. Ronald C. Balkissoon of the division of pulmonary and critical care medicine at National Jewish Health in Denver.

"Most people who have chronic cough have at least two or more underlying problems that are contributing to it," Dr. Balkissoon said at a meeting on allergy and respiratory diseases, sponsored by National Jewish Health. "Often [physicians] will just try to treat one issue like acid reflux and it doesn’t work, so they presume that’s not part of the problem. But you really have to have a multidisciplinary approach and consider all the relative contributing factors."

An especially underappreciated complication is laryngopharyngeal reflux (LPR), he said. Physicians using both classic pH probes or impedance probes often shortchange their diagnoses by missing clues, in large part because LPR is not specific in its presentation. The role LPR plays can be obfuscated by the presence of supraglottic edema or erythema, glottic abnormalities, epiglottic malformations, and lingual tonsillar hypertrophy, among other factors.

Moreover, the cobblestoning of epithelial tissue, an obvious sign of LPR, is not exclusive to that disease. It is also seen in cases where chronic cough derives mostly from a postnasal drip. Bronchoscopy will often reveal a transformation of tissue from normal columnar epithelium into squamous epithelium, even when the reflux is nonacidic, but beyond that, finding the proper context for tissue changes such as cobblestoning and ruling out non-LPR origins can be a challenge.

Chronic cough has a detrimental effect on the lives of many, with almost 30 million clinical visits reported annually in the United States. Females demonstrate a higher cough reflex sensitivity than do males, and the condition is driven by several additional originating factors that range from ACE inhibitor use to chronic bronchitis and bronchiectasis.

The learned and neuropathic origins of persistent cough stand as additional elements that may be more important in the big picture than many clinicians realize.

"Habituation, I think, is a very, very big part of what happens to people who have chronic cough," Dr. Balkissoon said. "They may have postnasal drainage issues. They may have gastroesophageal reflux disease issues and even ongoing asthma, but by the time they develop this cough that’s been going on for 15 or 25 years, there’s clearly habituation."

At another level, neuropathic manifestations of chronic cough are due to the irritant receptors that thrive in the lungs and throat. These include nociceptive C fibers, G protein, transient receptor potential vanilloid 1, and transient receptor potential A1.

The jury is still out on newer receptor antagonists, as well as surgical procedures such as fundoplication and other nonpharmacologic management approaches. But a diagnosis that acknowledges the likelihood of a more complex group of reasons for chronic cough may be the most logical way to seek better-tailored therapies.

"Most of the people who have chronic cough really have the common etiologies, but understanding that they’re often in combination and they have one or more reasons for it being refractory is the most important point," Dr. Balkissoon said.

Dr. Balkissoon disclosed speaking on behalf of AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, and Novartis.

KEYSTONE, Colo. – Physicians would do well to add habituation, neuropathic triggers, and laryngopharyngeal reflux to the list of factors they assess when tracing the origins of a cough that has persisted for longer than 8 weeks, advised a Colorado pulmonary specialist.

The usually recognized initiators of chronic refractory cough include asthma, upper airway cough syndrome (postnasal drip), and gastroesophageal reflux disease. But looking beyond these common culprits and analyzing combined etiologic factors on a case-by-case basis may be necessary, emphasized Dr. Ronald C. Balkissoon of the division of pulmonary and critical care medicine at National Jewish Health in Denver.

"Most people who have chronic cough have at least two or more underlying problems that are contributing to it," Dr. Balkissoon said at a meeting on allergy and respiratory diseases, sponsored by National Jewish Health. "Often [physicians] will just try to treat one issue like acid reflux and it doesn’t work, so they presume that’s not part of the problem. But you really have to have a multidisciplinary approach and consider all the relative contributing factors."

An especially underappreciated complication is laryngopharyngeal reflux (LPR), he said. Physicians using both classic pH probes or impedance probes often shortchange their diagnoses by missing clues, in large part because LPR is not specific in its presentation. The role LPR plays can be obfuscated by the presence of supraglottic edema or erythema, glottic abnormalities, epiglottic malformations, and lingual tonsillar hypertrophy, among other factors.

Moreover, the cobblestoning of epithelial tissue, an obvious sign of LPR, is not exclusive to that disease. It is also seen in cases where chronic cough derives mostly from a postnasal drip. Bronchoscopy will often reveal a transformation of tissue from normal columnar epithelium into squamous epithelium, even when the reflux is nonacidic, but beyond that, finding the proper context for tissue changes such as cobblestoning and ruling out non-LPR origins can be a challenge.

Chronic cough has a detrimental effect on the lives of many, with almost 30 million clinical visits reported annually in the United States. Females demonstrate a higher cough reflex sensitivity than do males, and the condition is driven by several additional originating factors that range from ACE inhibitor use to chronic bronchitis and bronchiectasis.

The learned and neuropathic origins of persistent cough stand as additional elements that may be more important in the big picture than many clinicians realize.

"Habituation, I think, is a very, very big part of what happens to people who have chronic cough," Dr. Balkissoon said. "They may have postnasal drainage issues. They may have gastroesophageal reflux disease issues and even ongoing asthma, but by the time they develop this cough that’s been going on for 15 or 25 years, there’s clearly habituation."

At another level, neuropathic manifestations of chronic cough are due to the irritant receptors that thrive in the lungs and throat. These include nociceptive C fibers, G protein, transient receptor potential vanilloid 1, and transient receptor potential A1.

The jury is still out on newer receptor antagonists, as well as surgical procedures such as fundoplication and other nonpharmacologic management approaches. But a diagnosis that acknowledges the likelihood of a more complex group of reasons for chronic cough may be the most logical way to seek better-tailored therapies.

"Most of the people who have chronic cough really have the common etiologies, but understanding that they’re often in combination and they have one or more reasons for it being refractory is the most important point," Dr. Balkissoon said.

Dr. Balkissoon disclosed speaking on behalf of AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, and Novartis.

KEYSTONE, Colo. – Physicians would do well to add habituation, neuropathic triggers, and laryngopharyngeal reflux to the list of factors they assess when tracing the origins of a cough that has persisted for longer than 8 weeks, advised a Colorado pulmonary specialist.

The usually recognized initiators of chronic refractory cough include asthma, upper airway cough syndrome (postnasal drip), and gastroesophageal reflux disease. But looking beyond these common culprits and analyzing combined etiologic factors on a case-by-case basis may be necessary, emphasized Dr. Ronald C. Balkissoon of the division of pulmonary and critical care medicine at National Jewish Health in Denver.

"Most people who have chronic cough have at least two or more underlying problems that are contributing to it," Dr. Balkissoon said at a meeting on allergy and respiratory diseases, sponsored by National Jewish Health. "Often [physicians] will just try to treat one issue like acid reflux and it doesn’t work, so they presume that’s not part of the problem. But you really have to have a multidisciplinary approach and consider all the relative contributing factors."

An especially underappreciated complication is laryngopharyngeal reflux (LPR), he said. Physicians using both classic pH probes or impedance probes often shortchange their diagnoses by missing clues, in large part because LPR is not specific in its presentation. The role LPR plays can be obfuscated by the presence of supraglottic edema or erythema, glottic abnormalities, epiglottic malformations, and lingual tonsillar hypertrophy, among other factors.

Moreover, the cobblestoning of epithelial tissue, an obvious sign of LPR, is not exclusive to that disease. It is also seen in cases where chronic cough derives mostly from a postnasal drip. Bronchoscopy will often reveal a transformation of tissue from normal columnar epithelium into squamous epithelium, even when the reflux is nonacidic, but beyond that, finding the proper context for tissue changes such as cobblestoning and ruling out non-LPR origins can be a challenge.

Chronic cough has a detrimental effect on the lives of many, with almost 30 million clinical visits reported annually in the United States. Females demonstrate a higher cough reflex sensitivity than do males, and the condition is driven by several additional originating factors that range from ACE inhibitor use to chronic bronchitis and bronchiectasis.

The learned and neuropathic origins of persistent cough stand as additional elements that may be more important in the big picture than many clinicians realize.

"Habituation, I think, is a very, very big part of what happens to people who have chronic cough," Dr. Balkissoon said. "They may have postnasal drainage issues. They may have gastroesophageal reflux disease issues and even ongoing asthma, but by the time they develop this cough that’s been going on for 15 or 25 years, there’s clearly habituation."

At another level, neuropathic manifestations of chronic cough are due to the irritant receptors that thrive in the lungs and throat. These include nociceptive C fibers, G protein, transient receptor potential vanilloid 1, and transient receptor potential A1.

The jury is still out on newer receptor antagonists, as well as surgical procedures such as fundoplication and other nonpharmacologic management approaches. But a diagnosis that acknowledges the likelihood of a more complex group of reasons for chronic cough may be the most logical way to seek better-tailored therapies.

"Most of the people who have chronic cough really have the common etiologies, but understanding that they’re often in combination and they have one or more reasons for it being refractory is the most important point," Dr. Balkissoon said.

Dr. Balkissoon disclosed speaking on behalf of AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, and Novartis.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. - Lack of the keratin-binding protein filaggrin in the skin's epidermis contributes to immune dysregulations that serve to retard defenses against allergens and microbes such as Staphylococcus aureus, helping pave the way for atopic dermatitis and, possibly, a lifetime of allergies.

Learning how those allergens work in concert with an inflammatory cytokine called thymic stromal lymphopoietin (TSLP) may illuminate a key link between filaggrin deficiency and a "Th2-type milieu," thus helping researchers develop an agent that could prevent atopy, Dr. Donald Y. M. Leung reported at a meeting on allergy and respiratory diseases.

Such an agent would be a welcome addition to current options for the management or prevention of atopic dermatitis (AD), which has a higher prevalence in young children than do food allergies, asthma, and allergic rhinitis.

"Atopic dermatitis is one of the few diseases where we can actually see what's going on, using biopsy or noninvasive techniques, to actually sample which of the proteins are changing and then intervene, I think, in a very scientific way," said Dr. Leung, head of the division of pediatric allergy and clinical immunology at National Jewish Health in Denver and editor-in-chief of the Journal of Allergy and Clinical Immunology.

Because AD is strongly associated with food allergies, some of which progress to asthma, preventing the disease could serve a much larger purpose. Research has shown that breakdown of skin barrier defenses opens the door not only to S. aureus, but also to the herpes simplex virus. The role of filaggrin and lipid deficiency in the negation of barrier mechanisms at the skin's mechanical, chemical, and cellular layers – which in turn may spur the advance of AD to a more persistent level of eczema or to asthma – also has been well studied. And filaggrin-deficient mice have demonstrated high levels of systemic atopic sensitization (J. Allergy Clin. Immunol. 2009;124:485-93).

But even though a lack of filaggrin has been associated with increased microbial invasion, the fact that some patients with filaggrin mutations do not develop AD and others outgrow their AD suggests that other factors are at play in progression of the disease, Dr. Leung said at the meeting, sponsored by National Jewish Health.

Less well understood is TSLP's relative contribution to inflammation and the processes that lead to the atopic march. The responsibility TSLP shares with other causal factors, such as infection, allergen exposure, and the barrier-damaging effects of the AD itch-scratch cycle, have not been well quantified. What researchers do know is that TSLP is commonly found in atopic skin, the gut of food allergy patients, and the lungs of asthmatics.

Dr. Leung calls it the "cytokine of the moment."

"T cells are educated in the milieu of the skin," he explained. "The skin is probably the most highly IgE-inducing organ in the body. There are multiple cytokines, like TSLP and IL-4, which can be released from mast cells, that augment the Th2 response. If one made a systemic anti-TSLP, in theory, and if we knew when to use it, it could reverse atopy."

Researchers are still working to characterize the timing of TSLP production by keratinocytes. Another riddle is just when during the course of a progressing atopic disease any anti-TSLP product should be introduced.

"Because people who come to us often have established disease, we may need to be intervening so early in the disease that we will not get there until we have the right biomarkers," Dr. Leung said.

Dr. Leung reported having no significant disclosures.

KEYSTONE, COLO. - Lack of the keratin-binding protein filaggrin in the skin's epidermis contributes to immune dysregulations that serve to retard defenses against allergens and microbes such as Staphylococcus aureus, helping pave the way for atopic dermatitis and, possibly, a lifetime of allergies.

Learning how those allergens work in concert with an inflammatory cytokine called thymic stromal lymphopoietin (TSLP) may illuminate a key link between filaggrin deficiency and a "Th2-type milieu," thus helping researchers develop an agent that could prevent atopy, Dr. Donald Y. M. Leung reported at a meeting on allergy and respiratory diseases.

Such an agent would be a welcome addition to current options for the management or prevention of atopic dermatitis (AD), which has a higher prevalence in young children than do food allergies, asthma, and allergic rhinitis.

"Atopic dermatitis is one of the few diseases where we can actually see what's going on, using biopsy or noninvasive techniques, to actually sample which of the proteins are changing and then intervene, I think, in a very scientific way," said Dr. Leung, head of the division of pediatric allergy and clinical immunology at National Jewish Health in Denver and editor-in-chief of the Journal of Allergy and Clinical Immunology.

Because AD is strongly associated with food allergies, some of which progress to asthma, preventing the disease could serve a much larger purpose. Research has shown that breakdown of skin barrier defenses opens the door not only to S. aureus, but also to the herpes simplex virus. The role of filaggrin and lipid deficiency in the negation of barrier mechanisms at the skin's mechanical, chemical, and cellular layers – which in turn may spur the advance of AD to a more persistent level of eczema or to asthma – also has been well studied. And filaggrin-deficient mice have demonstrated high levels of systemic atopic sensitization (J. Allergy Clin. Immunol. 2009;124:485-93).

But even though a lack of filaggrin has been associated with increased microbial invasion, the fact that some patients with filaggrin mutations do not develop AD and others outgrow their AD suggests that other factors are at play in progression of the disease, Dr. Leung said at the meeting, sponsored by National Jewish Health.

Less well understood is TSLP's relative contribution to inflammation and the processes that lead to the atopic march. The responsibility TSLP shares with other causal factors, such as infection, allergen exposure, and the barrier-damaging effects of the AD itch-scratch cycle, have not been well quantified. What researchers do know is that TSLP is commonly found in atopic skin, the gut of food allergy patients, and the lungs of asthmatics.

Dr. Leung calls it the "cytokine of the moment."

"T cells are educated in the milieu of the skin," he explained. "The skin is probably the most highly IgE-inducing organ in the body. There are multiple cytokines, like TSLP and IL-4, which can be released from mast cells, that augment the Th2 response. If one made a systemic anti-TSLP, in theory, and if we knew when to use it, it could reverse atopy."

Researchers are still working to characterize the timing of TSLP production by keratinocytes. Another riddle is just when during the course of a progressing atopic disease any anti-TSLP product should be introduced.

"Because people who come to us often have established disease, we may need to be intervening so early in the disease that we will not get there until we have the right biomarkers," Dr. Leung said.

Dr. Leung reported having no significant disclosures.

KEYSTONE, COLO. - Lack of the keratin-binding protein filaggrin in the skin's epidermis contributes to immune dysregulations that serve to retard defenses against allergens and microbes such as Staphylococcus aureus, helping pave the way for atopic dermatitis and, possibly, a lifetime of allergies.

Learning how those allergens work in concert with an inflammatory cytokine called thymic stromal lymphopoietin (TSLP) may illuminate a key link between filaggrin deficiency and a "Th2-type milieu," thus helping researchers develop an agent that could prevent atopy, Dr. Donald Y. M. Leung reported at a meeting on allergy and respiratory diseases.

Such an agent would be a welcome addition to current options for the management or prevention of atopic dermatitis (AD), which has a higher prevalence in young children than do food allergies, asthma, and allergic rhinitis.

"Atopic dermatitis is one of the few diseases where we can actually see what's going on, using biopsy or noninvasive techniques, to actually sample which of the proteins are changing and then intervene, I think, in a very scientific way," said Dr. Leung, head of the division of pediatric allergy and clinical immunology at National Jewish Health in Denver and editor-in-chief of the Journal of Allergy and Clinical Immunology.

Because AD is strongly associated with food allergies, some of which progress to asthma, preventing the disease could serve a much larger purpose. Research has shown that breakdown of skin barrier defenses opens the door not only to S. aureus, but also to the herpes simplex virus. The role of filaggrin and lipid deficiency in the negation of barrier mechanisms at the skin's mechanical, chemical, and cellular layers – which in turn may spur the advance of AD to a more persistent level of eczema or to asthma – also has been well studied. And filaggrin-deficient mice have demonstrated high levels of systemic atopic sensitization (J. Allergy Clin. Immunol. 2009;124:485-93).

But even though a lack of filaggrin has been associated with increased microbial invasion, the fact that some patients with filaggrin mutations do not develop AD and others outgrow their AD suggests that other factors are at play in progression of the disease, Dr. Leung said at the meeting, sponsored by National Jewish Health.

Less well understood is TSLP's relative contribution to inflammation and the processes that lead to the atopic march. The responsibility TSLP shares with other causal factors, such as infection, allergen exposure, and the barrier-damaging effects of the AD itch-scratch cycle, have not been well quantified. What researchers do know is that TSLP is commonly found in atopic skin, the gut of food allergy patients, and the lungs of asthmatics.

Dr. Leung calls it the "cytokine of the moment."

"T cells are educated in the milieu of the skin," he explained. "The skin is probably the most highly IgE-inducing organ in the body. There are multiple cytokines, like TSLP and IL-4, which can be released from mast cells, that augment the Th2 response. If one made a systemic anti-TSLP, in theory, and if we knew when to use it, it could reverse atopy."

Researchers are still working to characterize the timing of TSLP production by keratinocytes. Another riddle is just when during the course of a progressing atopic disease any anti-TSLP product should be introduced.

"Because people who come to us often have established disease, we may need to be intervening so early in the disease that we will not get there until we have the right biomarkers," Dr. Leung said.

Dr. Leung reported having no significant disclosures.

KEYSTONE, COLO. – Lack of the keratin-binding protein filaggrin in the skin’s epidermis contributes to immune dysregulations that serve to retard defenses against allergens and microbes such as Staphylococcus aureus, helping pave the way for atopic dermatitis and, possibly, a lifetime of allergies.

Learning how those allergens work in concert with an inflammatory cytokine called thymic stromal lymphopoietin (TSLP) may illuminate a key link between filaggrin deficiency and a "Th2-type milieu," thus helping researchers develop an agent that could prevent atopy, Dr. Donald Y. M. Leung reported at a meeting on allergy and respiratory diseases.

Such an agent would be a welcome addition to current options for the management or prevention of atopic dermatitis (AD), which has a higher prevalence in young children than do food allergies, asthma, and allergic rhinitis.

"Atopic dermatitis is one of the few diseases where we can actually see what’s going on, using biopsy or noninvasive techniques, to actually sample which of the proteins are changing and then intervene, I think, in a very scientific way," said Dr. Leung, head of the division of pediatric allergy and clinical immunology at National Jewish Health in Denver and editor-in-chief of the Journal of Allergy and Clinical Immunology.

Because AD is strongly associated with food allergies, some of which progress to asthma, preventing the disease could serve a much larger purpose. Research has shown that breakdown of skin barrier defenses opens the door not only to S. aureus, but also to the herpes simplex virus. The role of filaggrin and lipid deficiency in the negation of barrier mechanisms at the skin’s mechanical, chemical, and cellular layers – which in turn may spur the advance of AD to a more persistent level of eczema or to asthma – also has been well studied. And filaggrin-deficient mice have demonstrated high levels of systemic atopic sensitization (J. Allergy Clin. Immunol. 2009;124:485-93).

But even though a lack of filaggrin has been associated with increased microbial invasion, the fact that some patients with filaggrin mutations do not develop AD and others outgrow their AD suggests that other factors are at play in progression of the disease, Dr. Leung said at the meeting, sponsored by National Jewish Health.

Less well understood is TSLP’s relative contribution to inflammation and the processes that lead to the atopic march. The responsibility TSLP shares with other causal factors, such as infection, allergen exposure, and the barrier-damaging effects of the AD itch-scratch cycle, have not been well quantified. What researchers do know is that TSLP is commonly found in atopic skin, the gut of food allergy patients, and the lungs of asthmatics.

Dr. Leung calls it the "cytokine of the moment."

"T cells are educated in the milieu of the skin," he explained. "The skin is probably the most highly IgE-inducing organ in the body. There are multiple cytokines, like TSLP and IL-4, which can be released from mast cells, that augment the Th2 response. If one made a systemic anti-TSLP, in theory, and if we knew when to use it, it could reverse atopy."

Researchers are still working to characterize the timing of TSLP production by keratinocytes. Another riddle is just when during the course of a progressing atopic disease any anti-TSLP product should be introduced.

"Because people who come to us often have established disease, we may need to be intervening so early in the disease that we will not get there until we have the right biomarkers," Dr. Leung said.

Dr. Leung reported having no significant disclosures.

KEYSTONE, COLO. – Lack of the keratin-binding protein filaggrin in the skin’s epidermis contributes to immune dysregulations that serve to retard defenses against allergens and microbes such as Staphylococcus aureus, helping pave the way for atopic dermatitis and, possibly, a lifetime of allergies.

Learning how those allergens work in concert with an inflammatory cytokine called thymic stromal lymphopoietin (TSLP) may illuminate a key link between filaggrin deficiency and a "Th2-type milieu," thus helping researchers develop an agent that could prevent atopy, Dr. Donald Y. M. Leung reported at a meeting on allergy and respiratory diseases.

Such an agent would be a welcome addition to current options for the management or prevention of atopic dermatitis (AD), which has a higher prevalence in young children than do food allergies, asthma, and allergic rhinitis.

"Atopic dermatitis is one of the few diseases where we can actually see what’s going on, using biopsy or noninvasive techniques, to actually sample which of the proteins are changing and then intervene, I think, in a very scientific way," said Dr. Leung, head of the division of pediatric allergy and clinical immunology at National Jewish Health in Denver and editor-in-chief of the Journal of Allergy and Clinical Immunology.

Because AD is strongly associated with food allergies, some of which progress to asthma, preventing the disease could serve a much larger purpose. Research has shown that breakdown of skin barrier defenses opens the door not only to S. aureus, but also to the herpes simplex virus. The role of filaggrin and lipid deficiency in the negation of barrier mechanisms at the skin’s mechanical, chemical, and cellular layers – which in turn may spur the advance of AD to a more persistent level of eczema or to asthma – also has been well studied. And filaggrin-deficient mice have demonstrated high levels of systemic atopic sensitization (J. Allergy Clin. Immunol. 2009;124:485-93).

But even though a lack of filaggrin has been associated with increased microbial invasion, the fact that some patients with filaggrin mutations do not develop AD and others outgrow their AD suggests that other factors are at play in progression of the disease, Dr. Leung said at the meeting, sponsored by National Jewish Health.

Less well understood is TSLP’s relative contribution to inflammation and the processes that lead to the atopic march. The responsibility TSLP shares with other causal factors, such as infection, allergen exposure, and the barrier-damaging effects of the AD itch-scratch cycle, have not been well quantified. What researchers do know is that TSLP is commonly found in atopic skin, the gut of food allergy patients, and the lungs of asthmatics.

Dr. Leung calls it the "cytokine of the moment."

"T cells are educated in the milieu of the skin," he explained. "The skin is probably the most highly IgE-inducing organ in the body. There are multiple cytokines, like TSLP and IL-4, which can be released from mast cells, that augment the Th2 response. If one made a systemic anti-TSLP, in theory, and if we knew when to use it, it could reverse atopy."

Researchers are still working to characterize the timing of TSLP production by keratinocytes. Another riddle is just when during the course of a progressing atopic disease any anti-TSLP product should be introduced.

"Because people who come to us often have established disease, we may need to be intervening so early in the disease that we will not get there until we have the right biomarkers," Dr. Leung said.

Dr. Leung reported having no significant disclosures.

KEYSTONE, COLO. – Lack of the keratin-binding protein filaggrin in the skin’s epidermis contributes to immune dysregulations that serve to retard defenses against allergens and microbes such as Staphylococcus aureus, helping pave the way for atopic dermatitis and, possibly, a lifetime of allergies.

Learning how those allergens work in concert with an inflammatory cytokine called thymic stromal lymphopoietin (TSLP) may illuminate a key link between filaggrin deficiency and a "Th2-type milieu," thus helping researchers develop an agent that could prevent atopy, Dr. Donald Y. M. Leung reported at a meeting on allergy and respiratory diseases.

Such an agent would be a welcome addition to current options for the management or prevention of atopic dermatitis (AD), which has a higher prevalence in young children than do food allergies, asthma, and allergic rhinitis.

"Atopic dermatitis is one of the few diseases where we can actually see what’s going on, using biopsy or noninvasive techniques, to actually sample which of the proteins are changing and then intervene, I think, in a very scientific way," said Dr. Leung, head of the division of pediatric allergy and clinical immunology at National Jewish Health in Denver and editor-in-chief of the Journal of Allergy and Clinical Immunology.

Because AD is strongly associated with food allergies, some of which progress to asthma, preventing the disease could serve a much larger purpose. Research has shown that breakdown of skin barrier defenses opens the door not only to S. aureus, but also to the herpes simplex virus. The role of filaggrin and lipid deficiency in the negation of barrier mechanisms at the skin’s mechanical, chemical, and cellular layers – which in turn may spur the advance of AD to a more persistent level of eczema or to asthma – also has been well studied. And filaggrin-deficient mice have demonstrated high levels of systemic atopic sensitization (J. Allergy Clin. Immunol. 2009;124:485-93).

But even though a lack of filaggrin has been associated with increased microbial invasion, the fact that some patients with filaggrin mutations do not develop AD and others outgrow their AD suggests that other factors are at play in progression of the disease, Dr. Leung said at the meeting, sponsored by National Jewish Health.

Less well understood is TSLP’s relative contribution to inflammation and the processes that lead to the atopic march. The responsibility TSLP shares with other causal factors, such as infection, allergen exposure, and the barrier-damaging effects of the AD itch-scratch cycle, have not been well quantified. What researchers do know is that TSLP is commonly found in atopic skin, the gut of food allergy patients, and the lungs of asthmatics.

Dr. Leung calls it the "cytokine of the moment."

"T cells are educated in the milieu of the skin," he explained. "The skin is probably the most highly IgE-inducing organ in the body. There are multiple cytokines, like TSLP and IL-4, which can be released from mast cells, that augment the Th2 response. If one made a systemic anti-TSLP, in theory, and if we knew when to use it, it could reverse atopy."

Researchers are still working to characterize the timing of TSLP production by keratinocytes. Another riddle is just when during the course of a progressing atopic disease any anti-TSLP product should be introduced.

"Because people who come to us often have established disease, we may need to be intervening so early in the disease that we will not get there until we have the right biomarkers," Dr. Leung said.

Dr. Leung reported having no significant disclosures.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.

KEYSTONE, COLO. – Parents often fail to acknowledge the earliest signs of a child’s eosinophilic esophagitis, such as vomiting, coughing, choking, or refusing certain foods, because the brevity of such manifestations make them seem relatively unimportant.

Due to the pathologic similarities it shares with gastroesophageal reflux disease (GERD), a more common malady, physicians may be just as likely to miss early signals of eosinophilic esophagitis – often waiting until the child begins to lose weight before making the proper call, warned Dr. F. Dan Atkins, medical director of the pediatric day program at National Jewish Health in Denver.

"Oftentimes we have to get to the point where the child is failing to thrive before we say that there is something really wrong here," he said at a meeting on allergy and respiratory diseases. "We tend to ascribe the majority of their symptoms to the more common GERD that we see."

Eosinophilic esophagitis and GERD are both characterized by abnormal eosinophil counts, and can manifest at the same time. In one scenario, peptic erosion in the esophagus may lead to increased allergen sensitivity and promote the onset of eosinophilic esophagitis. In other cases, stiffening of the esophagus can damage the lower esophageal sphincter and stimulate the onset of GERD in tandem with eosinophilic esophagitis.

"I kind of think about this just like that group we see in asthma," Dr. Atkins said at the meeting, which was sponsored by National Jewish Health. "There are some people who have vocal cord dysfunction and some people who have asthma, and then some who have a combination of both."

The study of eosinophilic esophagitis has accelerated in recent years. It is a T cell–mediated sickness in which eosinophils invade the esophagus, creating rigidity, along with ring structures, ridges, or furrows in the wall of the organ. Symptoms include eating-related pain in children and adults and dysphagia in adults. Due to its frequent misdiagnosis, the condition has often been treated improperly with proton-pump inhibitor (PPI) therapy. Signs of normal pH in the digestive tract and lack of response to PPI therapy are usually sufficient to rule out GERD (Gastroenterology 2007;133:1342-63). The physician can then biopsy multiple sites at the upper and lower esophagus for confirmation of 15 eosinophils per high-power field, indicating the presence of eosinophilic esophagitis, said Dr. Atkins, also of the department of pediatrics at the University of Colorado, Denver.

In a review that included 500 children over the past 4 years, Dr. Atkins and his associates identified 33 eosinophilic esophagitis patients in an attempt to quantify feeding dysfunctions. Over the course of a year’s observation, 88% of this group demonstrated sensitivity to food allergens and 94% exhibited a variety of maladaptive eating behaviors. Failure to thrive was evident in 21%. About 70% of the children ultimately required feeding therapy.

"When we looked at the learned maladaptive behaviors they had, a large number of them had selected out their diet. Usually what they’re doing is avoiding all foods that have significant texture. So they don’t eat meats, they don’t like breads, and they don’t like foods that distend their esophagus," he said.

Children can have signs of eosinophilic esophagitis at any age, including their first year. Evidence of the cytokine eotaxin-3 is especially notable because it is the protein particularly implicated in the recruitment of eosinophils to the esophagus. Physicians and parents should be alert to early vomiting and choking, as well as complaints of epigastric or chest pain, he advised.

The psychology associated with eating disorder therapy doesn’t make the management of eosinophilic esophagitis any easier. Continual shunning of a three-meal-per-day eating pattern changes the child’s attitude toward food in general. Those kids who do not manifest symptoms until several days after eating a favorite food to which they are sensitized will typically protest when told to stay away from it, and psychological feeding dysfunctions often continue even after inflammation has subsided.

Just as in asthma patients, eosinophilic esophagitis carries with it a risk of progression to esophageal fibrosis. "That’s what we’re trying to prevent, particularly in children," Dr. Atkins added. "We’d like to prevent the occurrence of these esophageal strictures over time."

Dr. Atkins is a consultant to Sunovion Pharmaceuticals and an investigator for AstraZeneca.