Airway hyperresponsiveness in chronic obstructive pulmonary disease: A marker of asthma-chronic obstructive pulmonary disease overlap syndrome?

Ruzena Tkacova, Darlene L Y Dai, Judith M. Vonk, Janice M. Leung, Pieter S. Hiemstra, Maarten van den Berge, Lisette Kunz, Zsuzsanna Hollander, Donald Tashkin, Robert Wise, John Connett, Raymond Ng, Bruce McManus, S. F. Paul Man, Dirkje S. Postma, Don D. Sin

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background The impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with chronic obstructive pulmonary disease (COPD) is largely unknown. We used data from 2 large studies to determine the relationship between AHR and FEV1 decline, respiratory mortality, and systemic inflammation. Objectives We sought to determine the relationship of AHR with FEV1 decline, respiratory mortality, and systemic inflammatory burden in patients with COPD in the Lung Health Study (LHS) and the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study. Methods The LHS enrolled current smokers with mild-to-moderate COPD (n = 5887), and the GLUCOLD study enrolled former and current smokers with moderate-to-severe COPD (n = 51). For the primary analysis, we defined AHR by a methacholine provocation concentration of 4 mg/mL or less, which led to a 20% reduction in FEV1 (PC20). Results The primary outcomes were FEV1 decline, respiratory mortality, and biomarkers of systemic inflammation. Approximately 24% of LHS participants had AHR. Compared with patients without AHR, patients with AHR had a 2-fold increased risk of respiratory mortality (hazard ratio, 2.38; 95% CI, 1.38-4.11; P = .002) and experienced an accelerated FEV1 decline by 13.2 mL/y in the LHS (P = .007) and by 12.4 mL/y in the much smaller GLUCOLD study (P = .079). Patients with AHR had generally reduced burden of systemic inflammatory biomarkers than did those without AHR. Conclusions AHR is common in patients with mild-to-moderate COPD, affecting 1 in 4 patients and identifies a distinct subset of patients who have increased risk of disease progression and mortality. AHR may represent a spectrum of the asthma-COPD overlap phenotype that urgently requires disease modification.

Original languageEnglish (US)
Pages (from-to)1571-1579.e10
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number6
DOIs
StatePublished - Dec 1 2016

Bibliographical note

Funding Information:
The Lung Health Study (LHS) Biomarker Study was funded by the Canadian Institutes of Health Research (CIHR) & Genome Canada (grant no. 144COP) and the Canadian Respiratory Research Network. The original LHS was funded by the US National Heart, Lung, and Blood Institute (NHLBI-1U10-HL59275). The Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease study was originally funded by the Netherlands Organization for Scientific Research , the Netherlands Asthma Foundation , GlaxoSmithKline , University Medical Center Groningen , and Leiden University Medical Center . D.D.S. is supported by a Tier 1 Canada Research Chair in chronic obstructive pulmonary disease.

Publisher Copyright:
© 2016 American Academy of Allergy, Asthma & Immunology

Keywords

  • Respiratory hypersensitivity
  • airway obstruction
  • death rate
  • lung function tests

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