From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study. Method: The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002–04 (n = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002–2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2–3 with rapid decline in FEV1 and group B) COPD grade 2–3 without rapid decline in FEV1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A–C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D. Results: From the database groups A–D were identified; group A n = 37, group B n = 29, group C n = 41, and group D n = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A (n = 12) and B (n = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome. Conclusion: The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.

Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking

“…In the current study, data on lymphocyte populations and subpopulations are presented in relative and not absolute cell numbers. The reason for this is that BAL recovery volumes, as in previous studies [ 19 , 27 ], were found to be lower in COPD subjects compared to both non-smokers and ex-smokers with normal lung function [ 14 ]. We therefore believe that relative cell numbers better reflect differences in the inflammatory response when comparing these groups.…”

“…We have previously reported that the participation of COPD subjects in bronchoscopy studies is negatively affected by the large burden of co-morbidities within that group. As a result, the recruitment process might be disabled even if the basis for recruitment is large [ 14 ]. Nevertheless, to allow analyses stratified for sex, future studies should consider study population structure and size.…”

“…All subjects were recruited, according to pre-determined criteria, from the longitudinal OLIN COPD study [ 13 ], providing spirometry data over time. The recruitment process has been described in a previous report on the ‘Respiratory and Cardiovascular Effects in COPD’ (KOLIN) project [ 14 ].…”

“…COPD was defined using the Global Initiative for Obstructive Lung Disease (GOLD) spirometric criterion [ 15 ]; all COPD subjects had GOLD spirometric grades 2–3 at time of inclusion. Rapid decline was defined as a loss of forced expiratory volume in one second (FEV 1 ) ≥ 60 ml/year and non-rapid decline as a loss ≤30 ml/year; both measured over a period of at least five years and calculated using data from the OLIN COPD study as (FEV 1 at recruitment – FEV 1 at follow-up)/number of years of follow-up [ 14 ]. COPD and Ever-smokers groups consisted of both current and ex-smokers, all with a smoking history of at least 10 pack-years.…”

“…Ex-smokers had stopped smoking since at least 12 months. Subjects with medical conditions contradicting bronchoscopy and/or inflammatory conditions or medication expected to affect the outcome of the study were excluded from participation [ 14 ]. Subject demographics and basic characteristics are given in Table 1 .…”