Smoking induces sex-specific changes in the small airway proteome

Abstract

Introduction Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Methods Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Results Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers. Conclusions The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.

Global, regional and national burden of chronic obstructive pulmonary disease over a 30‐year period: Estimates from the 1990 to 2019 Global Burden of Disease Study

“…Smoking was the main risk factor for COPD in males of all regions, but other risk factors, such as household and ambient air pollution, had a significant impact on females across Asia and Africa. Smoking was the most important reason for the high incidence of COPD in developed countries, such as North America 8,26 . Smoking in higher SDI regions caused a high proportion of deaths and DALYs, and there was no household air pollution among the risk factors in high SDI region.…”

“…Smoking was the most important reason for the high incidence of COPD in developed countries, such as North America. 8,26 Smoking in higher SDI regions caused a high proportion of deaths and DALYs, and there was no household air pollution among the risk factors in high SDI region. However, the proportion of deaths and DALYs caused by household air pollution and ambient particulate matter in the low SDI regions was relatively larger.…”

Activation of the Complement and Coagulation Systems in the Small Airways in Asthma

“…SOMAscan (SomaLogic Inc, Boulder, USA) is an aptamer-based proteomics platform that uses slow off-rate-modified DNA aptamers (SOMAmers) as high-affinity protein capture reagents to quantify proteins. PEx sample preparation and SOMAscan analysis has been previously described in detail [20, 21]. Prior to SOMAscan analysis, the volume of sample buffer was adjusted to reach the same concentration of PEx in all samples in order to normalize the samples for the differences in the collected amount of PEx.…”

Exhaled biomarkers in adults with non-productive cough

“…As current smoking has been found to have a significant effect on the small airway protein profile [ 16 ], current smokers were excluded from further analysis.…”

“…The SOMAscan (SomaLogic Inc, Boulder, USA) proteomics platform that uses slow off-rate modified DNA aptamers can simultaneously quantify more than 1300 human proteins in blood samples. SOMAscan analysis of PEx samples and processing of data has been previously described in detail [ 16 ]. In short, prior to SOMAscan analysis, the volume of sample buffer was adjusted to reach the same concentration of PEx in all samples in order to normalize the samples for the differences in the collected amount of PEx.…”