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

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 ≤ .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 FEV₁, 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 ≥ 12 years) was associated with lower lung function and sinopulmonary infections (P ≤ .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.