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

doi:10.1016/j.jaci.2006.11.639

Journal of Allergy and Clinical Immunology

Volume 119, Issue 2, February 2007, Pages 405-413

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https://doi.org/10.1016/j.jaci.2006.11.639 Get rights and content

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.

Section snippets

Methods

After establishing standard operating procedures, including a review by an independent Data Safety Monitoring Board and approval by the Institutional Review Boards at each site, subjects underwent a comprehensive phenotypic characterization.

Classification of disease severity

From August 2003 to May 16, 2005, the network enrolled 204 subjects with severe asthma, 70 subjects with moderate asthma receiving ICS, and 164 subjects with mild asthma (94 of whom were on ICS). Despite treatment with high doses of corticosteroids, the subjects with severe asthma had an average of 4 to 5 total minor criteria. Nearly all subjects with severe asthma were using a second controller medication, 78% had persistent airflow obstruction, and more than half were having frequent

Discussion

The overall goal of SARP is to investigate prospectively subjects with severe asthma to understand better the pathophysiologic and biologic mechanisms that result in this level of disease severity. This article describes the clinical and physiologic characteristics of the SARP cohort that consists of more than 400 subjects and includes the largest group of comprehensively characterized subjects with severe asthma published to date. This study presents a unique opportunity to confirm results of

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Supported by HL69116, HL69130, HL69149, HL69155, HL69167, HL69170, HL69174, HL69349, M01 RR018390, M01 RR007122-14, and M01 RR03186.

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 AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

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

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Methods

Classification of disease severity

Discussion

Costs of asthma according to the degree of severity

Eur Respir J

Asthma severity and medical resource utilization

Eur Respir J

Costs of asthma are correlated with severity

Eur Respir J

Pathophysiology of severe asthma

J Allergy Clin Immunol

Severe asthma in adults

Am J Respir Crit Care Med

Design and baseline characteristics of the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study-a large cohort of patients with severe or difficult-to-treat-asthma

Ann Allergy Asthma Immunol

Severity assessment in asthma: an evolving concept

J Allergy Clin Immunol

Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society

Am J Respir Crit Care Med

A comparison of the clinical characteristics of children and adults with severe asthma

Chest

Distinguishing severe asthma phenotypes: role of age of onset and eosinophilic inflammation

J Allergy Clin Immunol

Parameters associated with persistent airflow obstruction in chronic severe asthma

Eur Respir J

National Asthma Education and Prevention Program. Expert Panel report 2: guidelines for the diagnosis and management of asthma

National Asthma Education and Prevention Program. Expert Panel report: guidelines for the diagnosis and management of asthma: update on selected topics 2002

Global Initiative for Asthma

ATS/ERS Standardisation of spirometry

Eur Respir J

Recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide

Am J Respir Crit Care Med

Multiple comparisons: philosophies and illustrations

Am J Physiol Regul Integr Comp Physiol

Categorizing asthma severity: an overview of national guidelines

Clin Med Res

The ENFUMOSA cross-sectional European multicenter study of the clinical phenotype of chronic severe asthma

Eur Respir J

Relationship of physician estimate of underlying asthma severity to asthma outcomes

Ann Allergy Asthma Immunol

Risk factors for near-fatal asthma

Am J Respir Crit Care Med

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