Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

Abstract

Background: Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important.

Objective: The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma.

Methods: We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma.

Results: A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P < .0001), more daily symptoms, intense urgent health care utilization, sinusitis, and pneumonia (P < or = .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility (P < .001). The severe group had less atopy by skin tests (P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV(1), history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age < 12 years) in severe asthma was associated with longer disease duration (P < .0001) and more urgent health care, especially intensive care (P = .002). Later disease onset (age > or = 12 years) was associated with lower lung function and sinopulmonary infections (P < or = .02).

Conclusion: Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization.

Clinical implications: Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.

Conflict of interest statement

Disclosure of potential conflict of interest: S. C. Erzurum has received grant support from Alair. L. Bacharier is on the speakers’ bureau for AstraZeneca, GlaxoSmithKline, Genentech, and Merck. W. J. Calhoun has consulting arrangements with Critical Therapeutics and Genentech. B. D. Levy has consulting arrangements with Critical Therapeutics. W. G. Teague is on the speakers’ bureau for Merck. W. W. Busse has consulting arrangements with Genentech/Novartis, Isis, GlaxoSmithKline, Altana, Wyeth, Pfizer, Dynavax, and Centocor, has received grant support from Novartis, Wyeth, Dynavax, Centocor, and GlaxoSmithKline, and is on the speakers’ bureau for GlaxoSmithKline, Novartis, Merck, and Astra-Zeneca. The rest of the authors have declared that they have no conflict of interest.

Figures

FIG 1

Urgent HCU increased with disease severity. Data are shown as lifetime (ever) events and visits in the past year. Hosp, Inpatient hospitalizations; Vent, need for mechanical ventilation. White bars, mild (n = 164); hatched bars, moderate; black bars, severe asthma. *P < .0001, all groups are different from each other; †P < .0001, mild and moderate groups are similar, but different from severe group.