ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Combination therapy with cystic fibrosis transmembrane conductance regulator modulators augment the airway functional microanatomy.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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.
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Who cites it
50 citing papers in PubMed, 64 citations in OpenAlex.
- Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.Respiratory research · 2021Trial
- Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies.Science translational medicine · 2019Trial
- Clinical Outcomes in Patients with Cystic Fibrosis-Related Chronic Rhinosinusitis Treated with Functional Endoscopic Sinus Surgery or Triple Highly Effective Modulator Therapy: A Monocentric Retrospective Experience.Journal of clinical medicine · 2025Article
- Ultrahigh-resolution spectral domain optical coherence tomography with a blue-diode-pumped Ti:sapphire laser and an axicon lens.Biomedical optics express · 2025Article
- Toward in vivo bronchoscopic functional CFTR assessment using a short circuit current measurement probe.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Reduced sialylation of airway mucin impairs mucus transport by altering the biophysical properties of mucin.Scientific reports · 2024Article
- Hypoxia-induced cystic fibrosis transmembrane conductance regulator dysfunction is a universal mechanism underlying reduced mucociliary transport in sinusitis.International forum of allergy & rhinology · 2024Article
- Reduced Sialylation of Airway Mucin Impairs Mucus Transport by Altering the Biophysical Properties of Mucin.Research square · 2024Article
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- Mechanisms by which the cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection and COVID-19 disease severity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Understanding and addressing the needs of people with cystic fibrosis in the era of CFTR modulator therapy.The Lancet. Respiratory medicine · 2023Review
- Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Preclinical evaluation of the epithelial sodium channel inhibitor AZD5634 and implications on human translation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Physiology and pathophysiology of human airway mucus.Physiological reviews · 2022Review
- Net benefit of ivacaftor during prolonged tezacaftor/elexacaftor exposure in vitro.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- Effect of lumacaftor-ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis: Results from the PROSPECT MCC sub-study.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- Culture and Imaging of Human Nasal Epithelial Organoids.Journal of visualized experiments : JoVE · 2021Article
- A Review of Trikafta: Triple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy.Cureus · 2021Review
- CFTR function and clinical response to modulators parallel nasal epithelial organoid swelling.American journal of physiology. Lung cellular and molecular physiology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Recently approved therapies that modulate CFTR function have shown significant clinical benefit, but recent investigations regarding their molecular mechanism when used in combination have not been consistent with clinical results. We employed micro-optical coherence tomography as a novel means to assess the mechanism of action of CFTR modulators, focusing on the effects on mucociliary clearance. Primary human airway monolayers from patients with a G551D mutation responded to ivacaftor treatment with increased ion transport, airway surface liquid depth, ciliary beat frequency, and mucociliary transport rate, in addition to decreased effective viscosity of the mucus layer, a unique mechanism established by our findings. These endpoints are consistent with the benefit observed in G551D patients treated with ivacaftor, and identify a novel mechanism involving mucus viscosity. In monolayers derived from F508del patients, the situation is more complicated, compounded by disparate effects on CFTR expression and function. However, by combining ion transport measurements with functional imaging, we establish a crucial link between in vitro data and clinical benefit, a finding not explained by ion transport studies alone. We establish that F508del cells exhibit increased mucociliary transport and decreased mucus effective viscosity, but only when ivacaftor is added to the regimen. We further show that improvement in the functional microanatomy in vitro corresponds with lung function benefit observed in the clinical trials, whereas ion transport in vitro corresponds to changes in sweat chloride. Functional imaging reveals insights into clinical efficacy and CFTR biology that significantly impact our understanding of novel therapies.
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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.