β-Adrenergic Sweat Secretion as a Diagnostic Test for Cystic Fibrosis

Quinton, Paul M.; Molyneux, Laura; Ip, Wan; Dupuis, Annie; Avolio, Julie; Tullis, Elizabeth; Conrad, Douglas; Shamsuddin, A. K. M.; Durie, Peter R.; Gonska, Tanja

doi:10.1164/rccm.201205-0922oc

Cited by 85 publications

(115 citation statements)

References 24 publications

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“…The SC test is less sensitive and less specific in reliably identifying CFTR dysfunction in individuals with nonclassical presentations (Groman et al, 2005) (Stewart et al, 1995;Quinton et al, 2012). In our study, 38% of those ultimately diagnosed with CF had initial SC between 20 and 30 mM.…”

Section: Discussionmentioning

confidence: 54%

Phenotypes of California CF Newborn Screen-Positive Children with CFTR 5T Allele by TG Repeat Length

Salinas

Azen

Young

et al. 2016

Genetic Testing and Molecular Biomarkers

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Background: At the cystic fibrosis transmembrane conductance regulator (CFTR) gene (IVS8)-(TG)m(T)n locus, a lower number of thymidines (legacy names 9T vs. 7T vs. 5T) and a higher number of (TG) repeats (TG-11 vs. 12 vs. 13) are associated with decreasing translation of functional CFTR protein in vitro. Methods: Retrospective cohort study comparing phenotypes of California CF newborn screen-positive children (followed 2-8 years) who had two CF-causing mutations (diagnosed as CF) with those who had one mutation from a panel of 40 CF-causing mutations (CF40 mut ) and one (IVS8)-(TG)11, 12, or 13-5T mutation detected by sequencing (diagnosed as CFTR-related metabolic syndrome [cRMS]). Results: The study included 428 children, of which 234 had two CF-causing mutations, and were used to compare with the other 194 children with one CF-causing mutation and one isolated 5T allele [CF40 mut /(TG)13-5T = 21, CF40 mut /(TG)12-5T = 85, and CF40 mut /(TG)11-5T = 88]. Among children with CF40 mut /(TG)13-5T, 38% were diagnosed with CF by 8 years, based on sweat chloride results and clinical presentation. Six percent of those with CF40 mut /(TG)12-5T, and none with CF40 mut /(TG)11-5T, reached diagnostic criteria. Conclusions: CFTR (IVS8)-(TG)m-5T allele (TG) tract length determination provides valuable information in predicting the risk of developing a CF phenotype. Of the three types of 5T alleles evaluated, screen-positive children with genotype CF40 mut /(TG)13-5T progressed from CRMS to CF at a high rate, while there was little evidence of clinical disease in those with CF40 mut /(TG)11-5T. Additional data from longer follow-up intervals are needed to fully understand the natural history of individuals with a CF40 mut /(TG)m-5T genotype.

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Section: Discussionmentioning

confidence: 54%

Phenotypes of California CF Newborn Screen-Positive Children with CFTR 5T Allele by TG Repeat Length

Salinas

Azen

Young

et al. 2016

Genetic Testing and Molecular Biomarkers

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“…Sweat evaporimetry was used to measure exocrine function of the sweat gland, and sweat chloride was used to determine ductular function of CFTR. Sweat evaporimetry was considered the primary endpoint because of its proposed sensitivity for minimal abnormalities in CFTR function (8,11). Sweat rates were calculated as the maximal stable rate observed after b-adrenergic injection minus the lowest observed rate after the preceding atropine injection, as previously described (8,11).…”

Section: Methodsmentioning

confidence: 99%

Recovery of Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction after Smoking Cessation

Courville

Raju

Liu

et al. 2015

Am J Respir Crit Care Med

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“…Therefore, parallel development of sensitive functional assays for quantitative assessment of CFTR function at baseline and treatment responses will be important to identity individual CF patients with rare CFTR mutations who may benefit from ivacaftor or other CFTR modulators. In this context, recent studies demonstrated that badrenergic sweat secretion, as well as functional measurements in native intestinal tissues and intestinal organoids, are accurate and reliable assays to assess different levels of mutant CFTR function in individual patients with CF carrying a broad spectrum of mutations [76][77][78][79]. Therefore, these techniques may be helpful tools to improve our current understanding of how much CFTR activity is required to translate into a clinical benefit and facilitate implementation of truly personalised medicine for CF.…”

Section: Emerging Novel Therapies To Rescue Mutant Cftr: Breakthroughmentioning

confidence: 99%

CFTR: cystic fibrosis and beyond

2014

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Cystic fibrosis (CF) remains the most common fatal hereditary lung disease. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene 25 years ago set the stage for: 1) unravelling the molecular and cellular basis of CF lung disease; 2) the generation of animal models to study in vivo pathogenesis; and 3) the development of mutation-specific therapies that are now becoming available for a subgroup of patients with CF. This article highlights major advances in our understanding of how CFTR dysfunction causes chronic mucus obstruction, neutrophilic inflammation and bacterial infection in CF airways. Furthermore, we focus on recent breakthroughs and remaining challenges of novel therapies targeting the basic CF defect, and discuss the next steps to be taken to make disease-modifying therapies available to a larger group of patients with CF, including those carrying the most common mutation DF508-CFTR. Finally, we will summarise emerging evidence indicating that acquired CFTR dysfunction may be implicated in the pathogenesis of chronic obstructive pulmonary disease, suggesting that lessons learned from CF may be applicable to common airway diseases associated with mucus plugging. @ERSpublications CFTR dysfunction causes CF and may be implicated in more common chronic obstructive lung diseases, such as COPD

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β-Adrenergic Sweat Secretion as a Diagnostic Test for Cystic Fibrosis

Abstract: β-Adrenergic sweat secretion rate determined by evaporimetry is an accurate and reliable technique to assess different levels of CFTR function and to identify patients with CF.

Cited by 85 publications

References 24 publications

Phenotypes of California CF Newborn Screen-Positive Children with CFTR 5T Allele by TG Repeat Length

Phenotypes of California CF Newborn Screen-Positive Children with CFTR 5T Allele by TG Repeat Length

Recovery of Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction after Smoking Cessation

CFTR: cystic fibrosis and beyond

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