• 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 Gaffin, Benjamin 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, and National Heart, Lung, and Blood Institute’s Severe Asthma Research Program-3 Investigators.
• 1 University of Wisconsin, Madison, Wisconsin.
• Am. J. Respir. Crit. Care Med. 2017 Feb 1; 195 (3): 302-313.

RationaleReducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.ObjectivesTo describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.MethodsBaseline 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-1 + 2 cohort.Measurements And Main ResultsOf 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-1 + 2 multivariable model.ConclusionsEPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).

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