The ageing of Cystic Fibrosis patients with new modulators: current gaps and challenges

Felipe Montiel, Almudena; Álvarez Fernández, Antonio; Traversi, Letizia; Polverino, Eva

doi:10.1080/17476348.2024.2311109

Expert Review of Respiratory Medicine

2023

DOI: 10.1080/17476348.2024.2311109

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The ageing of Cystic Fibrosis patients with new modulators: current gaps and challenges

Almudena Felipe Montiel,

Antonio Álvarez Fernández,

Letizia Traversi

et al.

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2024

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Cited by 2 publications

References 14 publications

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Effects of hyperglycemia on airway epithelial barrier function in WT and CF 16HBE cells

Vazquez Cegla,

Jones,

Cui

et al. 2024

Sci Rep

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Cystic fibrosis related diabetes (CFRD), the main co-morbidity in cystic fibrosis (CF), is associated with higher rates of lung function decline. We hypothesize that airway epithelial barrier function is impaired in CF and is further exacerbated under hyperglycemia, worsening pulmonary outcomes. Using 16HBE cells, we studied the effects of hyperglycemia in airway epithelial barrier function. Results show increased paracellular dye flux in CF cells in response to insulin under hyperglycemia. Gene expression experiments identified claudin-4 (CLDN4) as a key tight junction protein dysregulated in CF cells. CLDN4 protein localization by confocal microscopy showed that CLDN4 was tightly localized at tight junctions in WT cells, which did not change under hyperglycemia. ln contrast, CLDN4 was less well-localized in CF cells at normal glucose and localization was worsened under hyperglycemia. Treatment with highly effective modulator compounds (ETI) reversed this trend, and CFTR rescue was not affected by insulin or hyperglycemia. Bulk RNA sequencing showed differences in transcriptional responses in CF compared to WT cells under normal or high glucose, highlighting promising targets for future investigation. One of these targets is protein tyrosine phosphatase receptor type G (PTPRG), which has been previously found to play a role in defective Akt signaling and insulin resistance. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-76526-3.

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Effects of hyperglycemia on airway epithelial barrier function in WT and CF 16HBE cells

Vazquez Cegla,

Jones,

Cui

et al. 2024

Sci Rep

View full text Add to dashboard Cite

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The ageing of people living with cystic fibrosis: what to expect now?

Felipe Montiel,

Fernández,

Amigo

et al. 2024

Eur Respir Rev

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The prognosis of people with cystic fibrosis (pwCF) has improved dramatically with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm). The ageing of the cystic fibrosis (CF) population is changing the disease landscape with the emergence of different needs and increasing comorbidities related to both age and long-term exposure to multiple treatments including CFTRm. Although the number of pwCF eligible for this treatment is expected to increase, major disparities in care and outcomes still exist in this population. Moreover, the long-term impact of the use of CFTRm is still partly unknown due to the current short follow-up and experience with their use, thus generating some uncertainties. The future spread and initiation of these drugs at an earlier stage of the disease is expected to reduce the systemic burden of systemic inflammation and its consequences on health. However, the prolonged life expectancy is accompanied by an increasing burden of age-related comorbidities, especially in the context of chronic disease. The clinical manifestations of the comorbidities directly or indirectly associated with CFTR dysfunction are changing, along with the disease dynamics and outcomes. Current protocols used to monitor slow disease progression will need continuous updates, including the composition of the multidisciplinary team for CF care, with a greater focus on the needs of the adult population.

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The ageing of Cystic Fibrosis patients with new modulators: current gaps and challenges

Cited by 2 publications

References 14 publications

Effects of hyperglycemia on airway epithelial barrier function in WT and CF 16HBE cells

Effects of hyperglycemia on airway epithelial barrier function in WT and CF 16HBE cells

The ageing of people living with cystic fibrosis: what to expect now?

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