The Role of Active and Passive Smoking in Chronic Obstructive Pulmonary Disease and Systemic Inflammation: A 12-year Prospective Study in China

Abstract

Background: There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions.

Methods: The China Kadoorie Biobank cohort was followed up from the 2004-08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively.

Results: Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P_trend < 0.001) even two years before COPD onset. Among former smokers, COPD risk declined with longer smoking cessation (P_trend < 0.001) and those quitting smoking for over ten years presented no difference in COPD risk and hs-CRP level from non-smokers [HR (95% CI) = 1.05 (0.89, 1.25), β (95% CI) = 0.17 (- 0.09, 0.43)]. Among non-smokers, weekly SHS exposure was associated with a slightly higher COPD risk [HR (95% CI) = 1.06 (1.01, 1.12)].

Conclusions: Incremental exposure to tobacco smoke was related to elevated SCI level before COPD onset, then an increase in COPD susceptibility. Quitting smoking as early as possible is suggested as a practical approach to reducing COPD risk in smokers. Given the high prevalence of both COPD and SHS exposure, the risk associated with SHS exposure deserves attention.

Keywords: Active smoking; Chronic obstructive pulmonary disease; Passive smoking; Prospective cohort study; Systemic inflammation.

Fig. 1

Association of smoking and second-hand smoke exposure characteristics with risk of chronic obstructive pulmonary disease. HR hazard ratio, CI confidence interval. Values of point estimates for HRs were presented and 95% CI were presented as whiskers. The x-coordinate of each dot was set at the midpoint of the corresponding group in Fig. 1a–b, d–e, where appropriate. Cox models were stratified by age, sex, and study regions, with adjustment for marital status, education, household income, occupation, dietary habit (consumption frequency of fresh fruit, fresh vegetable, grains, and red meat), physical activity, drinking status, passive smoking (except for taking passive smoking as exposure), solid fuel use for cooking, solid fuel use for heating, stoves with chimney/extractor, body mass index, and waist circumference. Never or occasional smokers were the reference group in Fig. 1a–d. Those exposed to second-hand smoke less than once a week among never or occasional smokers were the reference group in Fig. 1e. P_trend was calculated by including the midpoint of each category and treating the variable as continuous in each separate regression model. All the P_trend values were < 0.001 except for the duration of second-hand smoke exposure (P_trend = 0.183)

Fig. 2

Correlations between smoking and second-hand smoke exposure status and log-transformed inflammatory markers. ^aThose who quit smoking due to illness were classified as current regular smoker. SHS second-hand smoke, CI confidence interval. Point estimates for HRs were presented as dots and 95% CI were presented as whiskers. Linear models were adjusted for age, sex, study regions, marital status, education, household income, occupation, dietary habit (consumption frequency of fresh fruit, fresh vegetable, grains, and red meat), physical activity, drinking status, passive smoking (except for taking passive smoking as exposure), solid fuel use for cooking, solid fuel use for heating, stoves with chimney/extractor, body mass index, and waist circumference. βs (95% CIs) for the correlations between the age to start smoking (≤ 18, 19–25, > 25 years), the daily cigarette consumption (≤ 10, 11–20, > 20 cigarettes/d), and the depth of inhalation while smoking (down to the mouth, throat, lung) and inflammatory marker levels were estimated with never or occasional smokers as the reference group. βs (95% CIs) for the correlations between average daily second-hand smoke exposure duration (< 2, 2–4, ≥ 4 h/d) and inflammatory marker levels among never or occasional smokers were estimated with those exposed to second-hand smoke exposure less than once a week as the reference group. P_trend was calculated by including the midpoint of each category and treating the variable as continuous in each separate regression model