Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations

Loren C. Denlinger, Brenda R. Phillips, Sima Ramratnam, Kristie Ross, Nirav R. Bhakta, Juan Carlos Cardet, Mario Castro, Stephen P. Peters, Wanda Phipatanakul, Shean Aujla, Leonard B. Bacharier, Eugene R. Bleecker, Suzy A.A. Comhair, Andrea Coverstone, Mark DeBoer, Serpil C. Erzurum, Sean B. Fain, Merritt Fajt, Anne M. Fitzpatrick, Jonathan GaffinBenjamin Gaston, Annette T. Hastie, Gregory A. Hawkins, Fernando Holguin, Anne Marie Irani, Elliot Israel, Bruce D. Levy, Ngoc Ly, Deborah A. Meyers, Wendy C. Moore, Ross Myers, Maria Theresa D. Opina, Michael C. Peters, Mark L. Schiebler, Ronald L. Sorkness, W. Gerald Teague, Sally E. Wenzel, Prescott G. Woodruff, David T. Mauger, John V. Fahy, Nizar N. Jarjour

Research output: Contribution to journalArticlepeer-review

313 Scopus citations


Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined. Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA. Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (>3). Replication of a multivariable model was performed with data from the SARP-112 cohort. Measurements and Main Results: Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2-2.1] for every log unit of eosinophils, 1.3 [1.1-1.4] for every 10 body mass index units, and 1.2 [1.1-1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4-2.1] and 1.6 [1.3-2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP-112 multivariable model. Conclusions: EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with (NCT 01760915).

Original languageEnglish (US)
Pages (from-to)302-313
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Issue number3
StatePublished - Feb 1 2017

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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