- Denlinger, Loren C;
- Phillips, Brenda R;
- Ramratnam, Sima;
- Ross, Kristie;
- Bhakta, Nirav R;
- Cardet, Juan Carlos;
- Castro, Mario;
- Peters, Stephen P;
- Phipatanakul, Wanda;
- Aujla, Shean;
- Bacharier, Leonard B;
- Bleecker, Eugene R;
- Comhair, Suzy AA;
- Coverstone, Andrea;
- DeBoer, Mark;
- Erzurum, Serpil C;
- Fain, Sean B;
- Fajt, Merritt;
- Fitzpatrick, Anne M;
- Gaffin, Jonathan;
- Gaston, Benjamin;
- Hastie, Annette T;
- Hawkins, Gregory A;
- Holguin, Fernando;
- Irani, Anne-Marie;
- Israel, Elliot;
- Levy, Bruce D;
- Ly, Ngoc;
- Meyers, Deborah A;
- Moore, Wendy C;
- Myers, Ross;
- Opina, Maria Theresa D;
- Peters, Michael C;
- Schiebler, Mark L;
- Sorkness, Ronald L;
- Teague, W Gerald;
- Wenzel, Sally E;
- Woodruff, Prescott G;
- Mauger, David T;
- Fahy, John V;
- Jarjour, Nizar N
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-1 + 2 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-1 + 2 multivariable model.Conclusions
EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).