Abstract
BackgroundCigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age.MethodsAll participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis.ResultsYoung susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients.ConclusionsWe show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD.Trial registrationClinicaltrials.gov: NCT00807469Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0121-2) contains supplementary material, which is available to authorized users.
Highlights
Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD)
In COPD, the structural changes in the lung may lead to a different response to smoking
The focus of this study was on the comparison of the acute response to cigarette smoking in young individuals, older subjects were investigated to assess if responses change after many years of smoking
Summary
Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a proportion of all smokers, about 15-20%, will develop COPD, the so-called ‘susceptible’ smokers It is still unclear which factors determine why these individuals are more sensitive to the detrimental. Several studies investigated the acute inflammatory and oxidative stress responses to cigarette smoking in animal and in vitro models, yet only a few studies investigated these responses in humans [2] These studies focused generally on COPD patients and ‘healthy smokers’ without airway obstruction. In COPD, the structural changes in the lung may lead to a different response to smoking For this reason, it might be hypothesized that the very first responses to cigarette smoking in healthy young individuals with a low number of pack-years is an ideal model to investigate the induction and early progression towards COPD
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