Airway hyperresponsiveness in chronic obstructive pulmonary disease: A marker of asthma-chronic obstructive pulmonary disease overlap syndrome?
Pubmed ID: 27345171
Journal: The Journal of allergy and clinical immunology
Publication Date: 12/01/2016
Affiliation: 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: email@example.com.
MeSH Terms: Humans, Adult, Aged, Middle Aged, Smoking, Survival Analysis, Asthma, Risk, Pulmonary Disease, Chronic Obstructive, Spirometry, Inflammation Mediators, Syndrome, Biomarkers, Netherlands, Respiratory Hypersensitivity
Authors: Tkacova R, Vonk JM, Leung JM, Hiemstra PS, van den Berge M, Kunz L, Hollander Z, Tashkin D, Wise R, Connett J, Ng R, McManus B, Paul Man SF, Postma DS, Sin DD, Dai DLY
Cite As: Tkacova R, Dai DLY, Vonk JM, Leung JM, Hiemstra PS, van den Berge M, Kunz L, Hollander Z, Tashkin D, Wise R, Connett J, Ng R, McManus B, Paul Man SF, Postma DS, Sin DD. Airway hyperresponsiveness in chronic obstructive pulmonary disease: A marker of asthma-chronic obstructive pulmonary disease overlap syndrome? J Allergy Clin Immunol 2016 Dec;138(6):1571-1579.e10. Epub 2016 May 24.
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 FEV<sub>1</sub> decline, respiratory mortality, and systemic inflammation. OBJECTIVES: We sought to determine the relationship of AHR with FEV<sub>1</sub> 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 FEV<sub>1</sub> (PC<sub>20</sub>). RESULTS: The primary outcomes were FEV<sub>1</sub> 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 FEV<sub>1</sub> 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.