ArticlePloS one2013
In vivo readout of CFTR function: ratiometric measurement of CFTR-dependent secretion by individual, identifiable human sweat glands.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Sweat rate analysis of ivacaftor potentiation of CFTR in non-CF adults.Scientific reports · 2018Trial
- Non pathological sweat test, pancreatic insufficiency and Cystic Fibrosis: an unusual case in a child with F508del-duplication of exons 1-3 CFTR genotype.BMC pediatrics · 2024Article
- CFTR Modulators Rescue the Activity of CFTR in Colonoids Expressing the Complex Allele p.[R74W;V201M;D1270N]/dele22_24.International journal of molecular sciences · 2023Article
- β-adrenergic sweat test in children with inconclusive cystic fibrosis diagnosis: Do we need new reference ranges?Pediatric pulmonology · 2023Article
- Assays of CFTR Function In Vitro, Ex Vivo and In Vivo.International journal of molecular sciences · 2022Review
- Article
- Image-based β-adrenergic sweat rate assay captures minimal cystic fibrosis transmembrane conductance regulator function.Pediatric research · 2020Article
- Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/- IVS8Tn:T7/9 patient with acute recurrent pancreatitis.World journal of clinical cases · 2019Article
- Brushed nasal epithelial cells are a surrogate for bronchial epithelial CFTR studies.JCI insight · 2018Article
- When and how ruling out cystic fibrosis in adult patients with bronchiectasis.Multidisciplinary respiratory medicine · 2018Review
- Nasospheroids permit measurements of CFTR-dependent fluid transport.JCI insight · 2017Article
- Toward inclusive therapy with CFTR modulators: Progress and challenges.Pediatric pulmonology · 2017Review
- Low Beta-Adrenergic Sweat Responses in Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator-Related Metabolic Syndrome Children.Pediatric allergy, immunology, and pulmonology · 2017Article
- The magnitude of ivacaftor effects on fluid secretion via R117H-CFTR channels: Human in vivo measurements.PloS one · 2017Article
- Article
- Novel outcome measures for clinical trials in cystic fibrosis.Pediatric pulmonology · 2015Review
- A little CFTR goes a long way: CFTR-dependent sweat secretion from G551D and R117H-5T cystic fibrosis subjects taking ivacaftor.PloS one · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a β-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.
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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.