Evidence map›Paper›PMID 27556234›Full record

Trial reportAmerican journal of respiratory and critical care medicine2017

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 and 32 more

Erratum issuedAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in American journal of respiratory and critical care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 220 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed, 7 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

220 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Association between air pollution and allergic upper respiratory diseases: a meta-analysis.European respiratory review : an official journal of the European Respiratory Society · 2025
    Pooled it
  2. Pooled it
  3. Differential gene expression in nasal airway epithelium from overweight or obese youth with asthma.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management.American journal of respiratory and critical care medicine · 2020
    Pooled it
  7. Eosinophils and eosinophil-associated diseases: An update.The Journal of allergy and clinical immunology · 2018
    Pooled it
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  10. Treatment by biomarker-informed endotype vs guideline care in children with difficult-to-treat asthma.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2022
    Trial
  11. Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2020
    Trial
  12. Proceedings of the National Academy of Sciences of the United States of America · 2020
    Trial
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  16. Article
  17. Review
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  20. Article

160 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

42 authors.

Loren C Denlinger1 University of Wisconsin, Madison, Wisconsin.
Brenda R Phillips2 The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
Sima Ramratnam1 University of Wisconsin, Madison, Wisconsin.
Kristie Ross3 Case Western Reserve University, Cleveland, Ohio.
Nirav R Bhakta4 University of California San Francisco, San Francisco, California.
Juan Carlos Cardet5 Harvard Medical School, Boston, Massachusetts.
Mario Castro6 Washington University, St. Louis, Missouri.
Stephen P Peters7 Wake Forest University, Winston-Salem, North Carolina.
Wanda Phipatanakul5 Harvard Medical School, Boston, Massachusetts.
Shean Aujla8 University of Pittsburgh, Pittsburgh, Pennsylvania.
Leonard B Bacharier6 Washington University, St. Louis, Missouri.
Eugene R Bleecker7 Wake Forest University, Winston-Salem, North Carolina.
Suzy A A Comhair9 The Cleveland Clinic, Cleveland, Ohio.
Andrea Coverstone6 Washington University, St. Louis, Missouri.
Mark DeBoer10 University of Virginia, Charlottesville, Virginia.
Serpil C Erzurum9 The Cleveland Clinic, Cleveland, Ohio.
Sean B Fain1 University of Wisconsin, Madison, Wisconsin.
Merritt Fajt8 University of Pittsburgh, Pittsburgh, Pennsylvania.
Anne M Fitzpatrick11 Emory University, Atlanta, Georgia; and.
Jonathan Gaffin5 Harvard Medical School, Boston, Massachusetts.
Benjamin Gaston3 Case Western Reserve University, Cleveland, Ohio.
Annette T Hastie7 Wake Forest University, Winston-Salem, North Carolina.
Gregory A Hawkins7 Wake Forest University, Winston-Salem, North Carolina.
Fernando Holguin8 University of Pittsburgh, Pittsburgh, Pennsylvania.
Anne-Marie Irani12 Virginia Commonwealth University, Richmond, Virginia.
Elliot Israel5 Harvard Medical School, Boston, Massachusetts.
Bruce D Levy5 Harvard Medical School, Boston, Massachusetts.
Ngoc Ly4 University of California San Francisco, San Francisco, California.
Deborah A Meyers7 Wake Forest University, Winston-Salem, North Carolina.
Wendy C Moore7 Wake Forest University, Winston-Salem, North Carolina.
Ross Myers3 Case Western Reserve University, Cleveland, Ohio.
Maria Theresa D Opina7 Wake Forest University, Winston-Salem, North Carolina.
Michael C Peters4 University of California San Francisco, San Francisco, California.
Mark L Schiebler1 University of Wisconsin, Madison, Wisconsin.
Ronald L Sorkness1 University of Wisconsin, Madison, Wisconsin.
W Gerald Teague10 University of Virginia, Charlottesville, Virginia.
Sally E Wenzel8 University of Pittsburgh, Pittsburgh, Pennsylvania.
Prescott G Woodruff4 University of California San Francisco, San Francisco, California.
David T Mauger2 The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
John V Fahy4 University of California San Francisco, San Francisco, California.
Nizar N Jarjour1 University of Wisconsin, Madison, Wisconsin.
National Heart, Lung, and Blood Institute’s Severe Asthma Research Program-3 Investigators

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
INSTITUTIONAL CTSA (UW-MADISON): CLINICAL TRIALSUL1RR025011 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2007 to 2011
$29.5M
Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
PEDIATRIC ASTHMA NETWORK DATA COORDINATING CENTERU10HL064313 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI MAUGER, DAVID T. · 1999 to 2008
$18.3M
Clinical Coordinating Center for the Severe Asthma Research Program (SARP)U10HL109086 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI MAUGER, DAVID T. · 2011 to 2017
$8.1M
Wisconsin Allergy Research Training (WISCART) ProgramT32AI007635 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI James E. Gern, DANIEL J JACKSON · 2000 to 2026
$6.5M
Specialized Pro-Resolving Mediators in AsthmaR01HL122531 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LEVY, BRUCE D · 2014 to 2024
$4.7M
AMSA: ALXR/FBR Mediated Signaling in Severe AsthmaU10HL109172 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ISRAEL, ELLIOT, LEVY, BRUCE D · 2011 to 2016
$4.2M
Airway redox biochemistry as a deteriminant of asthma phenotype during adolescen*U10HL109250 · NHLBI · UNIVERSITY OF VIRGINIA · PI ERZURUM, SERPIL C., GASTON, BENJAMIN · 2011 to 2016
$4.2M
Clinical and Molecular Phenotypes of Severe AsthmaU10HL109146 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2011 to 2016
$4.0M
NCATS NIH HHS UL1 TR000427NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1 TR001102NCATS NIH HHS UL1 TR001420NCRR NIH HHS UL1 RR025011NHLBI NIH HHS K12 HL119997NHLBI NIH HHS K23 HL116657NHLBI NIH HHS R01 HL115118NHLBI NIH HHS R01 HL122531NHLBI NIH HHS U10 HL064313NHLBI NIH HHS U10 HL109086NHLBI NIH HHS U10 HL109146NHLBI NIH HHS U10 HL109152NHLBI NIH HHS U10 HL109164NHLBI NIH HHS U10 HL109168NHLBI NIH HHS U10 HL109172NHLBI NIH HHS U10 HL109250NHLBI NIH HHS U10 HL109257NIAID NIH HHS K23 AI106945NIAID NIH HHS T32 AI007635
6 · The paper itself

Abstract

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).

Indexed as

Disease ProgressionAdolescentAdultAlbuterolAsthmaBiomarkersBody Mass IndexBreath TestsBronchodilator AgentsChildChi-Square DistributionComorbidityDisease SusceptibilityDrug ResistanceEosinophilsFemaleAlbuterolBiomarkersBronchodilator AgentsImmunoglobulin ENitric Oxidebronchodilator reversibilityeosinophilsexacerbation-prone asthmagastroesophageal refluxsinusitis

Identifiers

PMID27556234
PMCPMC5328178

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.