{
  "abstract": "Increasing evidence suggests that acquired dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel occurs as a result of cigarette smoke exposure in chronic obstructive pulmonary disease (COPD). CFTR-targeted therapies were developed to treat genetic CFTR defects in cystic fibrosis, but they have not demonstrated consistent clinical efficacy in small trials of patients with COPD. Here, we aimed to characterize CFTR and other ion channel activity and ciliation in primary bronchial epithelial cells (pBECs) from COPD donors compared with healthy controls, and to determine the extent to which CFTR dysfunction can be rescued by clinically relevant CFTR modulators. Air–liquid interface (ALI) cultures generated from conditionally reprogrammed (CR) primary bronchial epithelial cells (pBECs) obtained from healthy controls (n = 7) and COPD donors (n = 7) were assessed for transepithelial electrical resistance, immunofluorescence, cilia activity, ion channel function and expression of cell-type-associated markers at the transcript level. COPD cultures exhibited reduced ciliated area, accompanied by significantly decreased forskolin/IBMX-stimulated CFTR-mediated anion transport and ATP-induced calcium-activated chloride currents compared with healthy-control cultures, despite comparable CFTR mRNA expression. Treatment with CFTR potentiators (VX-770, GLPG1837 and icenticaftor) resulted in modest and highly variable functional responses, with no statistically significant improvement compared with vehicle-treated controls. CFTR function was not significantly associated with cumulative smoking exposure (pack-years) in this cohort, suggesting that smoking burden alone may not account for the observed inter-individual variability in acquired CFTR dysfunction. Collectively, these findings demonstrate abnormalities in ion transport and ciliation in the COPD airway epithelium consistent with an acquired CFTR dysfunction phenotype, but indicate that these abnormalities are not readily reversed by the tested CFTR potentiators. These results highlight differences between genetic and acquired CFTR dysfunction and underscore the need for alternative or combinatorial therapeutic strategies targeting epithelial dysfunction in COPD.",
  "abstract_shown": true,
  "affiliations": [
    "Immune Health Program, Hunter Medical Research Institute, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW 2308, Australia",
    "School of Medicine and Public Health, University of Newcastle, Newcastle, NSW 2308, Australia",
    "Impact and Evaluation, Hunter Medical Research Institute, Locked Bag 1000, New Lambton Heights, Newcastle, NSW 2305, Australia",
    "School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia",
    "Infection Research Program, Hunter Medical Research Institute, School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW 2308, Australia",
    "Breathing and Lung Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Newcastle, NSW 2305, Australia",
    "Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW 2305, Australia",
    "School of Translational Medicine, Monash University, Melbourne, VIC 3800, Australia",
    "Respiratory Medicine, Alfred Hospital, Melbourne, VIC 3004, Australia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Nikhil T. Awatade"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Kurtis F. Budden",
      "orcid": "0000-0002-7435-275X"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Prabuddha S. Pathinayake",
      "orcid": "0000-0002-4947-5918"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Andrew T. Reid"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Kristy S. Nichol"
    },
    {
      "affs": [
        0,
        3,
        6,
        7,
        8
      ],
      "name": "Peter A. B. Wark"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e7zg5h2eww3zx.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198803",
  "fulltext_url": "https://europepmc.org/articles/PMC13664796",
  "id": "e7zg5h2eww3zx",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/19/8803",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Cystic Fibrosis Research Advances"
    ]
  ],
  "openalex": "W7165754452",
  "pdf_url": "https://europepmc.org/articles/PMC13664796?pdf=render",
  "pmcid": "PMC13664796",
  "pmid": "42884046",
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/e7zg5h2eww3zx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198803",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8803"
    },
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42884046",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42884046"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Cystic Fibrosis Research Advances",
      "subfield": "general"
    }
  ],
  "title": "Assessment of CFTR Dysfunction and Responsiveness to CFTR Modulators in COPD Bronchial Air–Liquid Interface Cultures",
  "title_text": "Assessment of CFTR Dysfunction and Responsiveness to CFTR Modulators in COPD Bronchial Air–Liquid Interface Cultures",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/e7zg5h2eww3zx",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}