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

Wendy C. Moore, Eugene R. Bleecker, Douglas Curran-Everett, Serpil C. Erzurum, Bill Ameredes, Leonard Bacharier, William Calhoun, Mario Castro, Kian Fan Chung, Melissa P. Clark, Raed A. Dweik, Anne M. Fitzpatrick, Benjamin Gaston, Mark Hew, Iftikhar Hussain, Nizar N. Jarjour, Elliot Israel, Bruce D. Levy, James R. Murphy, Stephen P. PetersW. Gerald Teague, Deborah A. Meyers, William W. Busse, Sally E. Wenzel

Research output: Contribution to journalArticle

603 Citations (Scopus)

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 ≤ .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.

Original languageEnglish (US)
Pages (from-to)405-413
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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National Heart, Lung, and Blood Institute (U.S.)
Asthma
Phenotype
Research
Lung
Patient Acceptance of Health Care
Pneumonia
Bronchodilator Agents
Ambulatory Care
Skin Tests
Nitric Oxide
Phlebotomy
Sinusitis
Critical Care
Infection
Age of Onset
Eosinophils
Immunoglobulin E

Keywords

  • bronchodilator response
  • definition
  • pathophysiology
  • phenotype
  • pneumonia
  • Severe asthma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. / Moore, Wendy C.; Bleecker, Eugene R.; Curran-Everett, Douglas; Erzurum, Serpil C.; Ameredes, Bill; Bacharier, Leonard; Calhoun, William; Castro, Mario; Chung, Kian Fan; Clark, Melissa P.; Dweik, Raed A.; Fitzpatrick, Anne M.; Gaston, Benjamin; Hew, Mark; Hussain, Iftikhar; Jarjour, Nizar N.; Israel, Elliot; Levy, Bruce D.; Murphy, James R.; Peters, Stephen P.; Teague, W. Gerald; Meyers, Deborah A.; Busse, William W.; Wenzel, Sally E.

In: Journal of Allergy and Clinical Immunology, Vol. 119, No. 2, 02.2007, p. 405-413.

Research output: Contribution to journalArticle

Moore, WC, Bleecker, ER, Curran-Everett, D, Erzurum, SC, Ameredes, B, Bacharier, L, Calhoun, W, Castro, M, Chung, KF, Clark, MP, Dweik, RA, Fitzpatrick, AM, Gaston, B, Hew, M, Hussain, I, Jarjour, NN, Israel, E, Levy, BD, Murphy, JR, Peters, SP, Teague, WG, Meyers, DA, Busse, WW & Wenzel, SE 2007, 'Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program', Journal of Allergy and Clinical Immunology, vol. 119, no. 2, pp. 405-413. https://doi.org/10.1016/j.jaci.2006.11.639
Moore, Wendy C. ; Bleecker, Eugene R. ; Curran-Everett, Douglas ; Erzurum, Serpil C. ; Ameredes, Bill ; Bacharier, Leonard ; Calhoun, William ; Castro, Mario ; Chung, Kian Fan ; Clark, Melissa P. ; Dweik, Raed A. ; Fitzpatrick, Anne M. ; Gaston, Benjamin ; Hew, Mark ; Hussain, Iftikhar ; Jarjour, Nizar N. ; Israel, Elliot ; Levy, Bruce D. ; Murphy, James R. ; Peters, Stephen P. ; Teague, W. Gerald ; Meyers, Deborah A. ; Busse, William W. ; Wenzel, Sally E. / Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. In: Journal of Allergy and Clinical Immunology. 2007 ; Vol. 119, No. 2. pp. 405-413.
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AU - Moore, Wendy C.

AU - Bleecker, Eugene R.

AU - Curran-Everett, Douglas

AU - Erzurum, Serpil C.

AU - Ameredes, Bill

AU - Bacharier, Leonard

AU - Calhoun, William

AU - Castro, Mario

AU - Chung, Kian Fan

AU - Clark, Melissa P.

AU - Dweik, Raed A.

AU - Fitzpatrick, Anne M.

AU - Gaston, Benjamin

AU - Hew, Mark

AU - Hussain, Iftikhar

AU - Jarjour, Nizar N.

AU - Israel, Elliot

AU - Levy, Bruce D.

AU - Murphy, James R.

AU - Peters, Stephen P.

AU - Teague, W. Gerald

AU - Meyers, Deborah A.

AU - Busse, William W.

AU - Wenzel, Sally E.

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N2 - 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.

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