Elenara da Fonseca Andrade Procianoy1,2, Fernando Antônio de Abreu E Silva3,4, Paulo José Cauduro Maróstica3,5, Paul M Quinton6. 1. Pediatric Pulmonology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. efaprocianoy@gmail.com. 2. Post-Graduation Program in Pneumologic Sciences, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil. efaprocianoy@gmail.com. 3. Pediatric Pulmonology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. 4. Post-Graduation Program in Pneumologic Sciences, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil. 5. Post-Graduation Program in Child and Adolescent Health, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil. 6. Department of Pediatrics, UC San Diego School of Medicine, University of California, San Diego, San Diego, CA, USA.
Abstract
PURPOSE: Cystic fibrosis (CF) is a multisystem genetic disease caused by dysfunction of the epithelial anionic channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Decreased mucociliary clearance because of thickened mucus is part of the pulmonary disease pathophysiology. It is controversial if the thickened airway surface liquid (ASL) is caused by the deficient chloride secretion and excessive sodium (through ENaC) and water hyperabsorption from the periciliar fluid or by the lack of bicarbonate secretion with relative acidification of the ASL. Correlations between the magnitude of in vivo chloride conductance with phenotypic characteristics and CF genotype can help to elucidate these mechanisms and direct to new treatments. METHODS: Nasal potential difference was measured in 28 CF patients (age from 0.3 to 28 year) and correlated with pulmonary function, pancreatic phenotype, pulmonary colonization and genotype severity. RESULTS: The CFTR-chloride conductance was better in older patients (r = 0.40; P = 0.03), in patients with better pulmonary function (r = 0.48; P = 0.01), and was associated with genotype severity. Higher chloride diffusion in the presence of a favorable chemical gradient was associated with Pseudomonas aeruginosa negativity (P < 0.05). More negative NPDmax was associated with pancreatic insufficiency (P < 0.01) as well with genotype severity, but not with the pulmonary function. CONCLUSIONS: The anion permeability through CFTR, mainly chloride, but bicarbonate as well, is the most critical factor in CF airway pathophysiology. Treatments primarily directed to correct CFTR function and/or airway acidity are clearly a priority.
PURPOSE:Cystic fibrosis (CF) is a multisystem genetic disease caused by dysfunction of the epithelial anionic channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Decreased mucociliary clearance because of thickened mucus is part of the pulmonary disease pathophysiology. It is controversial if the thickened airway surface liquid (ASL) is caused by the deficient chloride secretion and excessive sodium (through ENaC) and water hyperabsorption from the periciliar fluid or by the lack of bicarbonate secretion with relative acidification of the ASL. Correlations between the magnitude of in vivo chloride conductance with phenotypic characteristics and CF genotype can help to elucidate these mechanisms and direct to new treatments. METHODS: Nasal potential difference was measured in 28 CFpatients (age from 0.3 to 28 year) and correlated with pulmonary function, pancreatic phenotype, pulmonary colonization and genotype severity. RESULTS: The CFTR-chloride conductance was better in older patients (r = 0.40; P = 0.03), in patients with better pulmonary function (r = 0.48; P = 0.01), and was associated with genotype severity. Higher chloride diffusion in the presence of a favorable chemical gradient was associated with Pseudomonas aeruginosa negativity (P < 0.05). More negative NPDmax was associated with pancreatic insufficiency (P < 0.01) as well with genotype severity, but not with the pulmonary function. CONCLUSIONS: The anion permeability through CFTR, mainly chloride, but bicarbonate as well, is the most critical factor in CF airway pathophysiology. Treatments primarily directed to correct CFTR function and/or airway acidity are clearly a priority.
Authors: Teresinha Leal; Isabelle Fajac; Helen L Wallace; Patrick Lebecque; Jean Lebacq; Dominique Hubert; Josette Dall'Ava; Daniel Dusser; Anusha P Ganesan; Christiane Knoop; Jean Cumps; Pierre Wallemacq; Kevin W Southern Journal: Clin Biochem Date: 2008-04-08 Impact factor: 3.281
Authors: Otávio Guilherme Gonçalves de Almeida; Carolina Paulino da Costa Capizzani; Ludmilla Tonani; Patrícia Helena Grizante Barião; Anderson Ferreira da Cunha; Elaine Cristina Pereira De Martinis; Lidia Alice Gomes Monteiro Marin Torres; Marcia Regina von Zeska Kress Journal: Front Cell Infect Microbiol Date: 2020-11-11 Impact factor: 5.293