title: 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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. wmoore@wfubmc.edu <wmoore@wfubmc.edu>
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: Bill T
authors.initials: BT
authors.lastname: Ameredes
authors.forename: Leonard
authors.initials: L
authors.lastname: Bacharier
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Clark
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Mark
authors.initials: M
authors.lastname: Hew
authors.forename: Iftikhar
authors.initials: I
authors.lastname: Hussain
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.forename: James R
authors.initials: JR
authors.lastname: Murphy
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
mesh_terms: D000328:Adult; D017668:Age of Onset; D001249:Asthma / Q000145:classification / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D003695:Delivery of Health Care / Q000706:statistics & numerical data; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D012720:Severity of Illness Index; D012882:Skin Tests
chemical_list: D009569:Nitric Oxide