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Chloride Conductance, Nasal Potential Difference and Cystic Fibrosis Pathophysiology

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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.

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Acknowledgements

We thank Dr. Teresinha Leal from Louvain Centre for Toxicology and Applied Pharmacology, Universite Catholique de Louvain, Brussels, Belgium, for her assistance on training of nasal potential difference protocol measurement.

Funding

This work was supported by the Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA).

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Authors and Affiliations

  1. Pediatric Pulmonology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Elenara da Fonseca Andrade Procianoy, Fernando Antônio de Abreu e Silva & Paulo José Cauduro Maróstica

  2. Post-Graduation Program in Pneumologic Sciences, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil

    Elenara da Fonseca Andrade Procianoy & Fernando Antônio de Abreu e Silva

  3. Post-Graduation Program in Child and Adolescent Health, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil

    Paulo José Cauduro Maróstica

  4. Department of Pediatrics, UC San Diego School of Medicine, University of California, San Diego, San Diego, CA, USA

    Paul M. Quinton

Authors
  1. Elenara da Fonseca Andrade Procianoy
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  2. Fernando Antônio de Abreu e Silva
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  3. Paulo José Cauduro Maróstica
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  4. Paul M. Quinton
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Contributions

EFAP and FAAS design the study. FAAS, PJCM and PMQ provided critical evaluation of methods, results and conclusions. EFAP wrote the manuscript with critique by PJCM and PMQ.

Corresponding author

Correspondence to Elenara da Fonseca Andrade Procianoy.

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Conflict of interest

The authors declare no conflicts of interest related to this work.

Informed Consent

All subjects or their parents gave and signed a written informed consent. The study was reviewed and approved by the Ethical Review Board of HCPA and registered at HCPA Post-Graduation Research Group as number 05-125.

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Procianoy, E.F.A., de Abreu e Silva, F.A., Maróstica, P.J.C. et al. Chloride Conductance, Nasal Potential Difference and Cystic Fibrosis Pathophysiology. Lung 198, 151–156 (2020). https://doi.org/10.1007/s00408-019-00293-6

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  • DOI: https://doi.org/10.1007/s00408-019-00293-6

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