# Leukocyte telomere length and attrition in association with disease severity in cystic fibrosis patients

## TL;DR

This study explores how lung function and genetic factors affect telomere length in cystic fibrosis patients, suggesting biological aging is accelerated in more severe cases.

## Contribution

The study reveals gender-specific and genotype-specific associations between disease severity and leukocyte telomere length in cystic fibrosis.

## Key findings

- Higher FEV1 is linked to longer leukocyte telomere length, with a stronger effect in men.
- CF asthma is associated with shorter leukocyte telomere length.
- Men homozygous for the ΔF508 genotype show significantly shorter telomere length compared to heterozygotes.

## Abstract

Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a –10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.