Frequent exacerbators--a distinct phenotype of severe asthma

Clin Exp Allergy. 2014 Feb;44(2):212-21. doi: 10.1111/cea.12179.


Background: Exacerbations represent a major source of morbidity and mortality in asthma and are a prominent feature of poorly controlled, difficult-to-treat disease.

Objective: The goal of our study was to provide a detailed characterization of the frequent exacerbator phenotype and to identify risk factors associated with frequent and seasonal exacerbations.

Methods: Ninety-three severe asthmatics (SA) and 76 mild-to-moderate patients (MA) were screened and prospectively followed up for 1 year (NCT00555607). Medical history, baseline clinical data and biomarkers were used to assess risk factors for frequent exacerbations.

Results: During the study, 104 exacerbations were recorded in the SA group and 18 in the MA. Frequent exacerbators were characterized by use of higher doses of inhaled (1700 vs. 800 μg) and oral (6.7 vs. 1.7 mg) glucocorticosteroids, worse asthma control (ACQ score 2.3 vs. 1.4), lower quality of life (SGRQ score 48.5 vs. 33.3), higher sputum eosinophils (25.7% vs. 8.2%) and a more rapid decline in FEV1 /FVC ratio (-0.07 vs. -0.01 ΔFEV1 /FVC, frequent vs. non-frequent, respectively, P < 0.05). Exhaled NO > 45 p.p.b. and a history of smoking were associated with an increased risk of frequent exacerbations (odds ratios: 4.32 and 2.90 respectively).

Conclusion and clinical relevance: We were able to distinguish and characterize a subphenotype of asthma subjects--frequent exacerbators--who are significantly more prone to exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at increased risk of frequent exacerbations and require careful monitoring in clinical practice.

Keywords: asthma exacerbation; risk factors for exacerbations; severe asthma.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Asthma* / drug therapy
  • Asthma* / metabolism
  • Asthma* / pathology
  • Asthma* / physiopathology
  • Eosinophils* / metabolism
  • Eosinophils* / pathology
  • Female
  • Follow-Up Studies
  • Glucocorticoids / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Severity of Illness Index*
  • Sputum / metabolism*


  • Glucocorticoids