Hoonhorst Susan J M, Timens Wim, Koenderman Leo, Lo Tam Loi Adèle T, Lammers Jan-Willem J, Boezen H Marike, van Oosterhout Antoon J M, Postma Dirkje S, Ten Hacken Nick H T
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
GRIAC research institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Respir Res. 2014 Oct 10;15(1):121. doi: 10.1186/s12931-014-0121-2.
Cigarette 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.
All 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.
Young 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.
We 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.
Clinicaltrials.gov: NCT00807469.
吸烟是慢性阻塞性肺疾病（COPD）最重要的危险因素。只有一部分吸烟者会患上COPD，目前尚不清楚为何这些个体更容易受到吸烟有害影响。已知COPD家族聚集性个体患COPD的风险更高。本研究旨在调查对香烟烟雾的急性全身和局部免疫反应是否能区分年轻（18 - 40岁）和年老（40 - 75岁）的COPD易感个体与非易感个体。
所有参与者在一小时内吸三支香烟。研究外周血（0小时和3小时）及支气管活检组织（0小时和24小时）中炎症标志物的变化。在易感和非易感个体内部及之间分析吸烟的急性效应，并进行多元回归分析。
年轻易感个体吸烟后中性粒细胞上活性形式（A17和A27）的FcγRII（CD32）表达显著升高（分别为p = 0.016和0.028），与年龄、吸烟状态及基线时各标志物的表达无关。吸烟对血液中的介质或支气管活检组织中的炎症细胞计数无显著影响。在老年组中，健康对照者和COPD患者吸烟的急性效应相当。
我们首次表明，年轻时的COPD易感性与对吸烟的全身固有免疫反应增强有关。这表明全身炎症在COPD早期诱导阶段起作用。
Clinicaltrials.gov：NCT00807469。
