Airway Hyperresponsiveness in COPD: A Marker of Asthma-COPD Overlap Syndrome?

Publication date: Available online 24 May 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): 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
RationaleThe impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with COPD is largely unknown. We used data from two large studies to determine the relationship between AHR with forced expiratory volume in 1 second (FEV1) decline, respiratory mortality and systemic inflammation.ObjectivesTo 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 GLUCOLD Study.MethodsLHS enrolled current smokers with mild-to-moderate COPD (n=5,887) and GLUCOLD 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, which led to a 20% reduction in FEV1 (PC20).Measurements and ResultsThe primary outcomes were FEV1 decline, respiratory mortality and biomarkers of systemic inflammation. Approximately 24% of LHS participants had AHR. Compared with patients without AHR, AHR increased the risk of respiratory mortality by two-fold (hazard ratio 2.38; 95% confidence interval 1.38-4.11, p=0.002) and accelerated FEV1 decline by 13.2 mL/yr in LHS (p=0.007) and by 12.4 mL/year in the much smaller GLUCOLD Study (p=0.079). Patients with AHR had generally reduced burden of systemic inflammatory biomarkers than those without AHR.ConclusionsAHR is common in mild to moderate COPD, affecting 1 in 4 patients and identifies a distinct sub-set 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.

Teaser

Airway hyperresponsiveness is common in mild to moderate COPD, affecting 1 in 4 patients and identifies a distinct sub-set of patients, who have increased risk of disease progression and respiratory mortality.


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