scholarly journals Smoking induces sex-specific changes in the small airway proteome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Spela Kokelj ◽  
Jörgen Östling ◽  
Benjamin Georgi ◽  
Karin Fromell ◽  
Kristina Nilsson Ekdahl ◽  
...  
Keyword(s):  
Drug Targets ◽  
Protein Profile ◽  
Protein Composition ◽  
High Sensitivity ◽  
Small Airway ◽  
Strong Impact ◽  
Small Airways ◽  
Active Smoking ◽  
Former Smokers ◽  
Never Smokers

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.

scholarly journals Tobacco Consumption and High‐Sensitivity Cardiac Troponin I in the General Population: The HUNT Study

2022 ◽  
Author(s):  
Julia Brox Skranes ◽  
Magnus Nakrem Lyngbakken ◽  
Kristian Hveem ◽  
Helge Røsjø ◽  
Torbjørn Omland
Keyword(s):  
Smoking Cessation ◽  
General Population ◽  
Cigarette Smoking ◽  
Cardiac Troponin ◽  
Troponin I ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Former Smokers ◽  
Never Smokers ◽  
Cardiac Troponins

Background Cardiac troponins represent a sensitive index of subclinical myocardial injury and are associated with increased risk of cardiovascular events in the general population. Despite positive associations with cardiovascular risk of both cardiac troponins and cigarette smoking, concentrations of cardiac troponin I measured by high‐sensitivity assays (hs‐cTnI) are paradoxically lower in current smokers than in never‐smokers. The impact of smoking intensity and time from smoking cessation on hs‐cTnI remains unknown. Methods and Results hs‐cTnI concentrations were measured in 32028 subjects free from cardiovascular disease enrolled in the prospective, population‐based HUNT (Trøndelag Health Study). Tobacco habits were self‐reported and classified as never (n=14 559), former (n=14 248), and current (n=3221) smokers. Current smokers exhibited significantly lower concentrations of hs‐cTnI than never‐smokers ( P <0.001). In adjusted models, both current smoking (−17.3%; 95% CI, −20.6 to −13.9%) and former smoking (−6.6%; 95% CI, −8.7 to −4.5%) were associated with significantly lower hs‐cTnI concentrations. Among former smokers, higher smoking burden (>10 pack‐years) were associated with lower concentrations of hs‐cTnI. Time since smoking cessation was associated with increasing concentrations of hs‐cTnI in a dose‐dependent manner ( P for trend<0.001), and subjects who quit smoking >30 years ago had concentrations of hs‐cTnI comparable with those of never‐smokers. Conclusions In the general population, both current and former cigarette smoking is associated with lower concentrations of hs‐cTnI. In former smokers, there was a dose‐response relationship between pack‐years of smoking, and hs‐cTnI. Time since smoking cessation was associated with increasing concentrations of hs‐cTnI, indicating a continuum of hs‐cTnI from current smoker to never‐smokers.

scholarly journals A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways

2021 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlén ◽  
Emilia Viklund ◽  
...  
Keyword(s):  
Extracellular Proteins ◽  
Small Airway ◽  
Small Airways ◽  
Healthy Controls ◽  
Annotation Database ◽  
Epithelial Lining Fluid ◽  
Go Annotation ◽  
Non Invasive ◽  
Invasive Method ◽  
Never Smokers

Abstract BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥2.9 z-score), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc).ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

scholarly journals Current smoking alters phospholipid- and surfactant protein A levels in small airway lining fluid: An explorative study on exhaled breath

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253825
Author(s):  
Emilia Viklund ◽  
Björn Bake ◽  
Laith Hussain-Alkhateeb ◽  
Hatice Koca Akdeva ◽  
Per Larsson ◽  
...  
Keyword(s):  
Lung Function ◽  
Inflammatory Responses ◽  
Protein A ◽  
Surfactant Protein ◽  
Small Airway ◽  
Surfactant Protein A ◽  
Normal Lung ◽  
Small Airways ◽  
Current Smoking ◽  
Never Smokers

Small airways are difficult to access. Exhaled droplets, also referred to as particles, provide a sample of small airway lining fluid and may reflect inflammatory responses. We aimed to explore the effect of smoking on the composition and number of exhaled particles in a smoker-enriched study population. We collected and chemically analyzed exhaled particles from 102 subjects (29 never smokers, 36 former smokers and 37 current smokers) aged 39 to 83 years (median 63). A breathing maneuver maximized the number exhaled particles, which were quantified with a particle counter. The contents of surfactant protein A and albumin in exhaled particles was quantified with immunoassays and the contents of the phospholipids dipalmitoyl- and palmitoyl-oleoyl- phosphatidylcholine with mass spectrometry. Subjects also performed spirometry and nitrogen single breath washout. Associations between smoking status and the distribution of contents in exhaled particles and particle number concentration were tested with quantile regression, after adjusting for potential confounders. Current smokers, compared to never smokers, had higher number exhaled particles and more surfactant protein A in the particles. The magnitude of the effects of current smoking varied along the distribution of each PEx-variable. Among subjects with normal lung function, phospholipid levels were elevated in current smokers, in comparison to no effect of smoking on these lipids at abnormal lung function. Smoking increased exhaled number of particles and the contents of lipids and surfactant protein A in the particles. These findings might reflect early inflammatory responses to smoking in small airway lining fluid, also when lung function is within normal limits.

scholarly journals A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

2020 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlén ◽  
Emilia Viklund ◽  
...  
Keyword(s):  
Extracellular Proteins ◽  
Small Airway ◽  
Small Airways ◽  
Healthy Controls ◽  
Annotation Database ◽  
Epithelial Lining Fluid ◽  
Go Annotation ◽  
Non Invasive ◽  
Invasive Method ◽  
Never Smokers

Abstract BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway dysfunction (SAD), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc). ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with SAD as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with small airway dysfunction. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

scholarly journals A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

2021 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlen ◽  
Emilia Viklund ◽  
...  
Keyword(s):  
Research Question ◽  
Extracellular Proteins ◽  
Small Airway ◽  
Small Airways ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Annotation Database ◽  
Go Annotation ◽  
Cross Sectional Design ◽  
Never Smokers

Abstract BackgroundThere is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways.Research questionOur aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways.Methods and analysis10 healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc). ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement.

Cancer of the Lung, Larynx, and Pleura

2018 ◽  
Author(s):  
Jyoti Malhotra ◽  
Paolo Boffetta ◽  
Lorelei Mucci
Keyword(s):  
Lung Cancer ◽  
Secondhand Smoke ◽  
Lung Cancer Risk ◽  
Occupational Exposures ◽  
Men And Women ◽  
Established Risk Factor ◽  
Former Smokers ◽  
Never Smokers ◽  
Exposure To Secondhand Smoke ◽  
Cancer Of The Lung

Lung cancer is the most commonly diagnosed cancer among men in most countries, and is the primary cause of cancer death in men and women. Its epidemic increase in incidence began in the first half of the twentieth century, paralleling the uptake of cigarette smoking that occurred 20 years before. A series of landmark studies beginning in 1950 established tobacco as the primary cause of lung cancer. Current smokers have a 10- to 20-fold higher lung cancer risk compared to never smokers. Important for prevention, former smokers substantially reduce this excess risk 5 years after smoking cessation. Exposure to secondhand smoke, a well-established risk factor for lung cancer, has a 20%–25% higher risk for those exposed. There are several occupational exposures associated with lung cancer, including asbestos. Despite the success in defining lung cancer’s etiology, this highly preventable disease remains among the most common and most lethal cancers globally.

scholarly journals Comprehensive Metabolomic Analysis Reveals Dynamic Metabolic Reprogramming in Hep3B Cells with Aflatoxin B1 Exposure

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 384
Author(s):  
Shufeng Wang ◽  
Xin Yang ◽  
Feng Liu ◽  
Xinzheng Wang ◽  
Xuemin Zhang ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
Drug Targets ◽  
High Sensitivity ◽  
Tca Cycle ◽  
Acid Synthesis ◽  
Metabolic Reprogramming ◽  
Pyrimidine Metabolism ◽  
Rapid Separation ◽  
Hexosamine Pathway ◽  
Hep3b Cells

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 μM and 32 μM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.

scholarly journals Tobacco use in the Myeloproliferative neoplasms: symptom burden, patient opinions, and care

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah F. Christensen ◽  
Robyn M. Scherber ◽  
Gina L. Mazza ◽  
Amylou C. Dueck ◽  
Nana Brochmann ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Tobacco Use ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Symptom Burden ◽  
Symptom Assessment ◽  
Cross Sectional ◽  
Former Smokers ◽  
Never Smokers

Abstract Background Patients with Philadelphia-negative Myeloproliferative Neoplasms (MPN) suffer from numerous symptoms and decreased quality of life. Smoking is associated with an increased symptom burden in several malignancies. The aim of this study was to analyze the association between smoking and MPN-related symptom burden and explore MPN patients’ opinions on smoking. Methods A total of 435 patients with MPN participated in a cross-sectional internet-based survey developed by the Mayo Clinic and the Myeloproliferative Neoplasm Quality of Life Group. Patients reported their demographics, disease characteristics, tobacco use, and opinions on tobacco use. In addition, MPN-related symptoms were reported via the validated 10-item version of the Myeloproliferative Neoplasms Symptom Assessment Form. Results Current/former smokers reported worse fatigue (mean severity 5.6 vs. 5.0, p = 0.02) and inactivity (mean severity 4.0 vs. 3.4, p = 0.03) than never smokers. Moreover, current/former smokers more frequently experienced early satiety (68.5% vs. 58.3%, p = 0.03), inactivity (79.9% vs. 71.1%, p = 0.04), and concentration difficulties (82.1% vs. 73.1%, p = 0.04). Although not significant, a higher total symptom burden was observed for current/former smokers (mean 30.4 vs. 27.0, p = 0.07). Accordingly, overall quality of life was significantly better among never smokers than current/former smokers (mean 3.5 vs. 3.9, p = 0.03). Only 43.2% of the current/former smokers reported having discussed tobacco use with their physician, and 17.5% did not believe smoking increased the risk of thrombosis. Conclusion The current study suggests that smoking may be associated with increased prevalence and severity of MPN symptoms and underscores the need to enhance patient education and address tobacco use in the care of MPN patients.

scholarly journals Comparative Analysis of Electrophoretic Profile of Major Proteins of Milk from Alpine and Carpathian Goats

2017 ◽  
Vol 74 (1) ◽  
pp. 20 ◽  
Author(s):  
Alina NASALEAN ◽  
Laurentiu OGNEAN ◽  
Sergiu MUNTEAN ◽  
Stefana BALICI ◽  
Horea MATEI
Keyword(s):  
Protein Profile ◽  
Milk Proteins ◽  
Goat Milk ◽  
Protein Composition ◽  
Raw Milk ◽  
Biologically Active ◽  
Protein Fractions ◽  
Animal Nutrition ◽  
Sds Page ◽  
Percentage Data

The milk’s proteins provide nutritional and biologically active values, essential in human and animal nutrition. In the case of goat milk, the proteins’ concentration and quality represent basic indices for the evaluation of the nutritional and biologically active values. The proposal is to comparatively analyse the protein profile of milk. The milk was collected from two different breeds: French Alpine and Romanian Carpathian. During March and April 2016 there were collected samples of raw milk in hygienic and sanitation conditions. There were two lots: first lot has 10 Carpathian goats and the second lot has 10 Alpine goats. The protein composition of goat milk was established with SDS-PAGE, after the evaluation of the total proteins’ concentration with the Bradford method. The quantitative and percentage data obtained with electrophoresis revealed few differences between those 8 identified protein fractions. Between those two lots, regarding the levels of β-CN, k-CN and β-lactoglobulines there were significant differences. The other protein fractions have values almost identical. Statistical analysis of obtained data shaped the differences in the protein profile at those two breeds. Based on those differences it is to note the superior potential of the Alpine breed regarding the content in biologically active milk proteins. Regarding the obtained data, this study brings new contributions for the evaluation and analysis of protein profile as a nutritive and biologically active component of goat milk, confirming its character as a functional aliment.

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