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J Allergy Clin Immunol. 2016 Dec;138(6):1571-1579.e10. doi: 10.1016/j.jaci.2016.04.022. Epub 2016 May 24.

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

Author information

1
UBC James Hogg Research Center & the Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada; Faculty of Medicine, Department of Respiratory Medicine and Tuberculosis, P.J. Safarik University, Kosice, Slovakia.
2
UBC James Hogg Research Center & the Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada; PROOF Center of Excellence, St Paul's Hospital, Vancouver, British Columbia, Canada.
3
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
4
UBC James Hogg Research Center & the Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada; Department of Medicine (Pulmonary Division), University of British Columbia, Vancouver, British Columbia, Canada.
5
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
6
University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands; Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
7
David Geffen School of Medicine at UCLA, Los Angeles, Calif.
8
Johns Hopkins University School of Medicine, Baltimore, Md.
9
University of Minnesota School of Public Health, Minneapolis, Minn.
10
UBC James Hogg Research Center & the Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada; PROOF Center of Excellence, St Paul's Hospital, Vancouver, British Columbia, Canada; Department of Computer Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
11
UBC James Hogg Research Center & the Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada; PROOF Center of Excellence, St Paul's Hospital, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
12
UBC James Hogg Research Center & the Institute for Heart and Lung Health, St Paul's Hospital, Vancouver, British Columbia, Canada; Department of Medicine (Pulmonary Division), University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: don.sin@hli.ubc.ca.

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.

KEYWORDS:

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

PMID:
27345171
DOI:
10.1016/j.jaci.2016.04.022
[Indexed for MEDLINE]

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