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Author Notes:

Correspondence and requests for reprints should be addressed to Loren C. Denlinger, M.D., Ph.D., Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, CSC Box 9988, Madison, WI 53792. E-mail: loren.denlinger@wisc.edu

Design, L.C.D., B.R.P., S.R., K.R., N.R.B., J.C.C., M.C., S.P.P., W.P., D.T.M., J.V.F., and N.N.J. Acquisition, analysis, and interpretation of data, L.C.D., B.R.P., S.R., K.R., N.R.B., J.C.C., M.C., S.P.P., W.P., S.A., L.B.B., E.R.B., S.A.A.C., A.C., M.DeB., S.C.E., S.B.F., M.F., A.M.F., J.G., B.G., A.T.H., G.A.H., F.H., A.-M.I., E.I., B.D.L., N.L., D.A.M., W.C.M., R.M., M.T.D.O., M.C.P., M.L.S., R.L.S., W.G.T., S.E.W., P.G.W., D.T.M., J.V.F., and N.N.J. Manuscript drafting and critique, L.C.D., B.R.P., N.R.B., J.C.C., M.C., S.P.P., W.P., R.L.S., W.G.T., S.E.W., D.T.M., J.V.F., and N.N.J.

The authors thank the study participants, the SARP-3 clinical research coordinators, and the data coordinating center.

This study was conducted with the support of grants that were awarded by the NHLBI. Spirometers were provided for SARP by nSpire Health, Inc., Longmont, Colorado.


Research Funding:

Supported by NHLBI to the Severe Asthma Research Program (SARP) Principal Investigators, Clinical Centers, and Data Coordinating Center as follows: U10 HL109164 (E.R.B.), U10 HL109257 (M.C.), U10 HL109250 (S.C.E.), U10 HL109146 (J.V.F.), U10 HL109250 (B.G.), U10 HL109172 (E.I. and B.D.L.), U10 HL109168 (N.N.J.), U10 HL109250 (W.G.T.), U10 HL109152 (S.E.W.), and U10 HL109086–04 (D.T.M.).

As an ancillary study to SARP, RO1 HL115118 (L.C.D.) focused on the mechanisms of recovery from virus-induced asthma exacerbations.

In addition, this program is supported through the following National Institutes of Health National Center for Advancing Translational Sciences awards: UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), UL1 TR001102 (Harvard University), and UL1 TR000454 (Emory University).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Critical Care Medicine
  • Respiratory System
  • General & Internal Medicine
  • exacerbation-prone asthma
  • bronchodilator reversibility
  • eosinophils
  • sinusitis
  • gastroesophageal reflux
  • RISK
  • LUNG

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

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Journal Title:

American Journal of Respiratory and Critical Care Medicine


Volume 195, Number 3


, Pages 302-313

Type of Work:

Article | Final Publisher PDF


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 www.clinicaltrials.gov (NCT 01760915).

Copyright information:

© 2017 by the American Thoracic Society

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