Smoking induces sex-specific changes in the small airway proteome

• Published in: Respiratory research Vol. 22; no. 1; p. 234
• Main Authors: Kokelj, Spela, Östling, Jörgen, Georgi, Benjamin, Fromell, Karin, Ekdahl, Kristina Nilsson, Olsson, Henric K, Olin, Anna-Carin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24-08-2021; BioMed Central; BMC
• Subjects: Advanced glycosylation end products; Airway (Medicine); Biomedical Sciences; Biomedicinsk vetenskap; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette Smoking - genetics; Cigarette Smoking - metabolism; Cigarette Smoking - pathology; Cigarettes; Cohort Studies; Complement system; COPD; Demographic aspects; Exhaled particles; Female; Females; Gender aspects; Gene expression; Health aspects; Humans; Inflammation; Lavage; Lung - metabolism; Lung - pathology; Lung diseases; Lungmedicin och allergi; Lungs; Male; Men; Middle Aged; Oxidative stress; Pathogenesis; Physiological aspects; Protein composition; Protein S; Proteins; Proteomes; Proteomics; Proteomics - methods; Respiratory Medicine and Allergy; Respiratory tract; Respiratory tract lining fluid; Risk factors; Sex Characteristics; Sex differences; Sex factors in disease; Small airways; Smokers; Smoking; Smoking cessation; Spirometry; Spirometry - methods; Statistical analysis; Statistical methods; Therapeutic targets; Tobacco Smoking - genetics; Tobacco Smoking - metabolism; Tobacco Smoking - pathology; Women; Womens health; Sweden; Proteomics; Small airways; Inflammation; Respiratory tract lining fluid; Exhaled particles; COPD; Smoking
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-021-01825-6

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.
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.
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.
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.