scholarly journals Smoking-associated increase in mucins 1 and 4 in human airways

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Heta Merikallio ◽  
Riitta Kaarteenaho ◽  
Sara Lindén ◽  
Médea Padra ◽  
Reza Karimi ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Chronic Bronchitis ◽  
Airway Epithelial Cells ◽  
Smoking History ◽  
Normal Lung ◽  
Cell Phenotype ◽  
Muc1 Expression ◽  
Bronchial Wash ◽  
Human Airways ◽  
Never Smokers

Abstract Rationale Smoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD. Methods Mucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sex-matched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot. Results The levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers. Conclusions Smoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease.

scholarly journals Intratumoural heterogeneity and immune modulation in lung adenocarcinoma of female smokers and never smokers

2021 ◽  
Author(s):  
Timo Benedikt Trefzer ◽  
Marc A. Schneider ◽  
Katharina Jechow ◽  
Lorenz Robert Chua ◽  
Thomas Muley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Significant Proportion ◽  
Cellular Heterogeneity ◽  
Tobacco Smoke Exposure ◽  
Smoking History ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Never Smokers

Lung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.

scholarly journals Airborne occupational exposures and the risk of developing respiratory symptoms and airway obstruction in the Lifelines Cohort Study

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216721
Author(s):  
Md Omar Faruque ◽  
H Marike Boezen ◽  
Hans Kromhout ◽  
Roel Vermeulen ◽  
Ute Bültmann ◽  
...  
Keyword(s):  
Cohort Study ◽  
Airway Obstruction ◽  
Chronic Bronchitis ◽  
Chronic Cough ◽  
Respiratory Symptoms ◽  
Occupational Exposures ◽  
Control Measures ◽  
High Exposure ◽  
Pesticides Exposure

ObjectivesTo date, only a few studies have investigated the associations between occupational exposures and respiratory outcomes longitudinally in the general population. We investigated the associations between occupational exposures and the development of respiratory symptoms and airway obstruction in the Lifelines Cohort Study.MethodsWe included 35 739 occupationally active subjects with data on chronic cough, chronic phlegm, chronic bronchitis or airway obstruction at baseline and approximately 4.5 years follow-up. Exposures to biological dust, mineral dust, gases/fumes, pesticides, solvents and metals in the current job at baseline were estimated with the ALOHA+job-exposure matrix (JEM). Airway obstruction was defined as FEV1/FVC below the lower limit of normal. Logistic regression analysis adjusted for baseline covariates was used to investigate the associations.ResultsAt follow-up, 1888 (6.0%), 1495 (4.7%), 710 (2.5%) and 508 (4.5%) subjects had developed chronic cough, chronic phlegm, chronic bronchitis and airway obstruction, respectively. High exposure to biological dust was associated with a higher odds to develop chronic cough and chronic bronchitis. High exposure to pesticides was associated with a higher odds for the development of all respiratory symptoms and airway obstruction. In the multiple exposures analyses, only the association between pesticides exposure and respiratory symptoms remained.ConclusionsSubjects exposed to high pesticides had a higher odds to develop respiratory symptoms on average 4.5 years later. Control measures should be taken to reduce pesticides exposure among the working population to prevent respiratory symptoms and airway obstruction.

Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes

Respiration ◽  
2020 ◽  
pp. 1-11
Author(s):  
Louis-Philippe Boulet ◽  
Marie-Eve Boulay ◽  
Harvey O. Coxson ◽  
Cameron J. Hague ◽  
Joanne Milot ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Obstruction ◽  
Airway Inflammation ◽  
Wall Thickness ◽  
Structural Changes ◽  
Smoking History ◽  
Airway Wall ◽  
Tobacco Exposure ◽  
Airway Wall Thickness ◽  
Irreversible Airway Obstruction

<b><i>Background:</i></b> The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. <b><i>Objective:</i></b> To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. <b><i>Methods:</i></b> We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with &#x3c;5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. <b><i>Results:</i></b> Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (<i>p</i> = 0.0242). Visual analysis showed a higher prevalence of emphysema (<i>p</i> = 0.0001) and higher emphysema score (<i>p</i> &#x3c; 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. <b><i>Conclusions:</i></b> Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.

PBA increases CFTR expression but at high doses inhibits Cl−secretion in Calu-3 airway epithelial cells

1999 ◽  
Vol 277 (4) ◽  
pp. L700-L708 ◽  
Author(s):  
Johannes Loffing ◽  
Bryan D. Moyer ◽  
Donna Reynolds ◽  
Bruce A. Stanton
Keyword(s):  
Protein Expression ◽  
Apical Membrane ◽  
Basolateral Membrane ◽  
Airway Epithelial Cells ◽  
Cell Phenotype ◽  
Apical Plasma Membrane ◽  
Airway Epithelial ◽  
High Concentration ◽  
Cycle Enzyme ◽  
Cf Transmembrane Conductance Regulator

Sodium 4-phenylbutyrate (PBA), a short-chain fatty acid, has been approved to treat patients with urea cycle enzyme deficiencies and is being evaluated in the management of sickle cell disease, thalassemia, cancer, and cystic fibrosis (CF). Because relatively little is known about the effects of PBA on the expression and function of the wild-type CF transmembrane conductance regulator (wt CFTR), the goal of this study was to examine the effects of PBA and related compounds on wt CFTR-mediated Cl−secretion. To this end, we studied Calu-3 cells, a human airway cell line that expresses endogenous wt CFTR and has a serous cell phenotype. We report that chronic treatment of Calu-3 cells with a high concentration (5 mM) of PBA, sodium butyrate, or sodium valproate but not of sodium acetate reduced basal and 8-(4-chlorophenylthio)-cAMP-stimulated Cl−secretion. Paradoxically, PBA enhanced CFTR protein expression 6- to 10-fold and increased the intensity of CFTR staining in the apical plasma membrane. PBA also increased protein expression of Na+-K+-ATPase. PBA reduced CFTR Cl−currents across the apical membrane but had no effect on Na+-K+-ATPase activity in the basolateral membrane. Thus a high concentration of PBA (5 mM) reduces Cl−secretion by inhibiting CFTR Cl−currents across the apical membrane. In contrast, lower therapeutic concentrations of PBA (0.05–2 mM) had no effect on cAMP-stimulated Cl−secretion across Calu-3 cells. We conclude that PBA concentrations in the therapeutic range are unlikely to have a negative effect on Cl−secretion. However, concentrations >5 mM might reduce transepithelial Cl−secretion by serous cells in submucosal glands in individuals expressing wt CFTR.

scholarly journals Prevalence and burden of chronic bronchitis symptoms: results from the BOLD study

2017 ◽  
Vol 50 (5) ◽  
pp. 1700621 ◽  
Author(s):  
Filip Mejza ◽  
Louisa Gnatiuc ◽  
A. Sonia Buist ◽  
William M. Vollmer ◽  
Bernd Lamprecht ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Disease ◽  
Chronic Bronchitis ◽  
Airflow Obstruction ◽  
Population Based ◽  
Normal Lung ◽  
Increased Risk ◽  
Potential Risk Factors ◽  
Definition Of ◽  
Disease Study

We studied the prevalence, burden and potential risk factors for chronic bronchitis symptoms in the Burden of Obstructive Lung Disease study.Representative population-based samples of adults aged ≥40 years were selected in participating sites. Participants completed questionnaires and spirometry. Chronic bronchitis symptoms were defined as chronic cough and phlegm on most days for ≥3 months each year for ≥2 years.Data from 24 855 subjects from 33 sites in 29 countries were analysed. There were significant differences in the prevalence of self-reported symptoms meeting our definition of chronic bronchitis across sites, from 10.8% in Lexington (KY, USA), to 0% in Ile-Ife (Nigeria) and Blantyre (Malawi). Older age, less education, current smoking, occupational exposure to fumes, self-reported diagnosis of asthma or lung cancer and family history of chronic lung disease were all associated with increased risk of chronic bronchitis. Chronic bronchitis symptoms were associated with worse lung function, more dyspnoea, increased risk of respiratory exacerbations and reduced quality of life, independent of the presence of other lung diseases.The prevalence of chronic bronchitis symptoms varied widely across the studied sites. Chronic bronchitis symptoms were associated with significant burden both in individuals with chronic airflow obstruction and those with normal lung function.

scholarly journals Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

2015 ◽  
Vol 24 (137) ◽  
pp. 451-461 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Clive Page ◽  
Josè Jardim ◽  
Alexander G. Chuchalin ◽  
...  
Keyword(s):  
Relative Risk ◽  
Airway Obstruction ◽  
Chronic Bronchitis ◽  
Meta Analysis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Regular Treatment ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
High Doses

In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a meta-analysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (≤600 mg per day) and high (>600 mg per day) doses of NAC.The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n=1933; placebo or controls n=2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66–0.84; p<0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68–0.82; p=0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89–0.97; p=0.40; high doses relative risk 1.11, 95% CI 0.89–1.39; p=0.58).The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ≥1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient.

scholarly journals Substance use, trait measures, and subjective response to nicotine in never-smokers stratified on parental smoking history and sex

2009 ◽  
Vol 11 (9) ◽  
pp. 1055-1066 ◽  
Author(s):  
Ovide F. Pomerleau ◽  
Cynthia S. Pomerleau ◽  
Sandy M. Snedecor ◽  
Raphaela Finkenauer ◽  
Ann M. Mehringer ◽  
...  
Keyword(s):  
Substance Use ◽  
Parental Smoking ◽  
Smoking History ◽  
Subjective Response ◽  
Never Smokers

Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas

2006 ◽  
Vol 24 (11) ◽  
pp. 1700-1704 ◽  
Author(s):  
DuyKhanh Pham ◽  
Mark G. Kris ◽  
Gregory J. Riely ◽  
Inderpal S. Sarkaria ◽  
Tiffani McDonough ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
Epidermal Growth ◽  
Former Smokers ◽  
Never Smokers ◽  
Lung Adenocarcinomas ◽  
Exon 19

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

scholarly journals Cross-sectional study of smoking exposure: no differential effect on OCT metrics in a cohort of MS patients

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731982840 ◽  
Author(s):  
Mattia Rosso ◽  
Dorlan J Kimbrough ◽  
Cindy T Gonzalez ◽  
Bonnie I Glanz ◽  
Brian C Healy ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Cross Sectional Study ◽  
Smoking History ◽  
Retinal Layer ◽  
Fiber Layer ◽  
Cross Sectional ◽  
Macular Volume ◽  
Smoking Exposure ◽  
Significant Difference ◽  
Never Smokers

Background Optical coherence tomography (OCT) provides quantitative measures of retinal layer thickness. Cigarette smoking is a risk factor for multiple sclerosis (MS) onset and disease severity: its effects on OCT metrics have not been assessed. Objective The objective of this study was to assess the effect of smoking history on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform (GCIP) of MS patients by OCT. Methods 112 MS patients were recruited from the Brigham and Women’s Hospital. Spectralis OCT scans were acquired to measure GCIP, peripapillary RNFL, and total macular volume. Multivariable linear mixed effects regression model assessed RNFL and GCIP change with fixed effects for smoking history while adjusting for optic neuritis eye status, age, disease duration, sex, baseline EDSS, and disease modifying therapies (DMTs). Results Smoking histories were available for 102 patients: 46 (45.10%) had a history of smoking cigarettes and 56 (54.90%) never smoked. No statistically significant differences were found between ever-smokers and never-smokers with respect to GCIP, RNFL, and macular volume. Conclusion Our study shows no significant difference in retinal thickness between ever-smokers and never-smokers. If confirmed, this result suggests mechanistic differences between the retina and other central nervous system (CNS) compartments in response to smoking and should be noted when considering OCT as a surrogate measure of CNS activity.

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