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Am J Respir Crit Care Med. 2017 Feb 1;195(3):302-313. doi: 10.1164/rccm.201602-0419OC.

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations.

Author information

1
1 University of Wisconsin, Madison, Wisconsin.
2
2 The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
3
3 Case Western Reserve University, Cleveland, Ohio.
4
4 University of California San Francisco, San Francisco, California.
5
5 Harvard Medical School, Boston, Massachusetts.
6
6 Washington University, St. Louis, Missouri.
7
7 Wake Forest University, Winston-Salem, North Carolina.
8
8 University of Pittsburgh, Pittsburgh, Pennsylvania.
9
9 The Cleveland Clinic, Cleveland, Ohio.
10
10 University of Virginia, Charlottesville, Virginia.
11
11 Emory University, Atlanta, Georgia; and.
12
12 Virginia Commonwealth University, Richmond, Virginia.

Abstract

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).

KEYWORDS:

bronchodilator reversibility; eosinophils; exacerbation-prone asthma; gastroesophageal reflux; sinusitis

Comment in

PMID:
27556234
PMCID:
PMC5328178
DOI:
10.1164/rccm.201602-0419OC
[Indexed for MEDLINE]
Free PMC Article

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