Cystic Fibrosis Transmembrane Conductance Regulator Function Is Suppressed in Cigarette Smokers

Cantin, André M.; Hanrahan, John W.; Bilodeau, Ginette; Ellis, Lynda; Dupuis, Annie; Liao, Jie; Zielenski, Julian; Durie, Peter R.

doi:10.1164/rccm.200508-1330oc

Cited by 251 publications

(259 citation statements)

References 37 publications

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“…Both in vitro and in vivo studies have shown that cigarette smoke decreases the expression of cystic fibrosis transmembrane regulator (CFTR) gene, protein, and function contributing to the pathophysiology of existing CFTR deficiencies [84]. …”

Section: Resultsmentioning

confidence: 99%

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

Vanker

Gie

Zar

2017

Expert Review of Respiratory Medicine

151

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Introduction: Childhood respiratory illness is a major cause of morbidity and mortality particularly in low and middle-income countries. Environmental tobacco smoke (ETS) exposure is a recognised risk factor for both acute and chronic respiratory illness.Areas covered: The aim of this paper was to review the epidemiology of ETS exposure and impact on respiratory health in children. We conducted a search of 3 electronic databases of publications on ETS and childhood respiratory illness from 1990–2015. Key findings were that up to 70% of children are exposed to ETS globally, but under-reporting may mask the true prevalence. Maternal smoking and ETS exposure influence infant lung development and are associated with childhood upper and lower respiratory tract infection, wheezing or asthma. Further, exposure to ETS is associated with more severe respiratory disease. ETS exposure reduces lung function early in life, establishing an increased lifelong risk of poor lung health.Expert commentary: Urgent and effective strategies are needed to decrease ETS exposure in young children to improve child and long-term lung health in adults especially in low and middle income countries where ETS exposure is increasing.

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Section: Resultsmentioning

confidence: 99%

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

Vanker

Gie

Zar

2017

Expert Review of Respiratory Medicine

151

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“…The recent demonstration that active smoking decreases CFTR expression at the gene and protein levels in participants without CF supports this hypothesis. 40 The observed effect of the CFTR genotype may explain why the best-powered study to date on lung function in patients with CF and secondhand smoke exposure did not detect the effect of secondhand smoke exposure on lung function in their subgroup of ΔF508 homozygotes. 4 Our findings suggest that future studies of gene-environment interactions in CF lung disease should not be solely confined to ΔF508 homozygotes because non-ΔF508 homozygotes may be better suited to detect the negative effects of modifiers of lung function.…”

Section: Commentmentioning

confidence: 99%

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

Collaco¹,

Vanscoy²,

Bremer³

et al. 2008

JAMA

133

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Context Disease variation can be substantial even in conditions with a single gene etiology such as cystic fibrosis (CF). Simultaneously studying the effects of genes and environment may provide insight into the causes of variation.Objective To determine whether secondhand smoke exposure is associated with lung function and other outcomes in individuals with CF, whether socioeconomic status affects the relationship between secondhand smoke exposure and lung disease severity, and whether specific gene-environment interactions influence the effect of secondhand smoke exposure on lung function. Design, Setting, and ParticipantsRetrospective assessment of lung function, stratified by environmental and genetic factors. Data were collected by the US Cystic Fibrosis Twin and Sibling Study with missing data supplemented by the Cystic Fibrosis Foundation Data Registry. All participants were diagnosed with CF, were recruited between October 2000 and October 2006, and were primarily from the United States.Main Outcome Measures Disease-specific cross-sectional and longitudinal measures of lung function. ResultsOf 812 participants with data on secondhand smoke in the home, 188 (23.2%) were exposed. Of 780 participants with data on active maternal smoking during gestation, 129 (16.5%) were exposed. Secondhand smoke exposure in the home was associated with significantly lower cross-sectional (9.8 percentile point decrease; PϽ.001) and longitudinal lung function (6.1 percentile point decrease; P=.007) compared with those not exposed. Regression analysis demonstrated that socioeconomic status did not confound the adverse effect of secondhand smoke exposure on lung function. Interaction between gene variants and secondhand smoke exposure resulted in significant percentile point decreases in lung function, namely in CFTR non-⌬F508 homozygotes (12.8 percentile point decrease; P=.001), TGF␤1−509 TT homozygotes (22.7 percentile point decrease; P=.006), and TGF␤1 codon 10 CC homozygotes (20.3 percentile point decrease; P=.005).Conclusions Any exposure to secondhand smoke adversely affects both crosssectional and longitudinal measures of lung function in individuals with CF. Variations in the gene that causes CF (CFTR) and a CF-modifier gene (TGF␤1) amplify the negative effects of secondhand smoke exposure.

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“…The great majority of this is in the reduced state: 96% of the GSH in ELF of nonsmokers and 98% of that in smokers are reduced. In human epithelial cells, the GSH increase induced by oxidants and cigarette smoke is associated with a simultaneous decrease in CFTR function [26,52]. CFTR function is also decreased in healthy smokers as determined by nasal potential difference measurements [52], a response that may represent an antioxidant defense aimed at transiently increasing mucus viscosity and decreasing GSH loss from epithelial cells.…”

Section: Antioxidants In the Airway Lumen Mucinmentioning

confidence: 99%

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

Cantin

White

Cross

et al. 2007

Free Radical Biology and Medicine

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Although great strides are being made in the care of individuals with cystic fibrosis (CF), this condition remains the most common fatal hereditary disease in North America. Numerous links exist between progression of CF lung disease and oxidative stress. The defect in CF is the loss of function of the transmembrane conductance regulator (CFTR) protein; recent evidence that CFTR expression and function are modulated by oxidative stress suggests that the loss may result in a poor adaptive response to oxidants. Pancreatic insufficiency in CF also increases susceptibility to deficiencies in lipophilic antioxidants. Finally the airway infection and inflammatory processes in the CF lung are potential sources of oxidants that can affect normal airway physiology and contribute to the mechanisms causing characteristic changes associated with bronchiectasis and loss of lung function. These multiple abnormalities in the oxidant/antioxidant balance raise several possibilities for therapeutic interventions that must be carefully assessed. IntroductionCystic fibrosis (CF) is the most common fatal disease caused by a single gene defect in Europe and North America [1,2]. The defective gene was identified in 1989 [3][4][5] and shown to encode the cystic fibrosis trans-membrane conductance regulator protein (CFTR). CFTR is a cyclic AMP-regulated anion channel with greatest selectivity for chloride, and bicarbonate [6][7][8]. Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10]. The expression of CFTR is located in the apical membrane of epithelial cells that line mucous membranes and submucosal glands ☆ A list of participants may be found in the Acknowledgments.

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Cystic Fibrosis Transmembrane Conductance Regulator Function Is Suppressed in Cigarette Smokers

Cited by 251 publications

References 37 publications

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

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