ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
170 citing papers in PubMed, 1 synthesis or guideline pooled it, 251 citations in OpenAlex.
- Pooled it
- Efficacy and Safety of the CFTR Potentiator Icenticaftor (QBW251) in COPD: Results from a Phase 2 Randomized Trial.International journal of chronic obstructive pulmonary disease · 2020Trial
- Mucociliary Clearance in Former Tobacco Smokers with Both Chronic Obstructive Pulmonary Disease and Chronic Bronchitis and the Effect of Roflumilast.Journal of aerosol medicine and pulmonary drug delivery · 2019Trial
- CFTR in alveolar type 1 cells contributes to lung liquid secretion and host defense.JCI insight · 2026Article
- Chest CT imaging toward personalized management of chronic obstructive pulmonary disease, asthma, and bronchiectasis: pulmonologist perspectives.Japanese journal of radiology · 2026Review
- Review
- Air pollution-induced airway epithelial barrier dysfunction in COPD: a narrative review of mechanisms and therapeutic implications.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Review
- Mucoactive Agents in Muco-Obstructive Lung Diseases: A Critical Reappraisal of Pharmacological Effects and Clinical Outcomes.Pharmaceuticals (Basel, Switzerland) · 2026Review
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- Altered functional interactions between CFTR disease mutants ΔF508 and G551D and the protein kinase A catalytic subunit.The Journal of physiology · 2026Article
- Research Progress on the Mechanisms of High Mucus Secretion in the Airway: A Scoping Review.International journal of chronic obstructive pulmonary disease · 2026Article
- A novel drug series optimized to address cystic fibrosis and other CFTR deficiency diseases of human airways.npj drug discovery · 2025Article
- Therapeutic strategies to reverse cigarette smoke-induced ion channel and mucociliary dysfunction in COPD airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Secondhand vape exposure regulation of CFTR and immune function in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Inflammation-induced loss of CFTR-expressing airway ionocytes in non-eosinophilic asthma.Respirology (Carlton, Vic.) · 2025Article
- Multimorbidities in COPD are Associated With Increased Exacerbations and Health Care Resource Utilization in Real-World Patients from a U.S. Database.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2024Article
- Quantifying abnormal alveolar microstructure in cystic fibrosis lung disease via hyperpolarizedJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2024Article
- Association between biomarkers of tobacco smoke exposure and clinical efficacy of ivacaftor in the G551D observational trial (GOAL).Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2024Observational
- Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2024Observational
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.