Changes in peripheral blood leukocyte profiles during elexacaftor/tezacaftor/ivacaftor therapy in cystic fibrosis according to baseline lung function.

BACKGROUND

Cystic fibrosis (CF) is a chronic genetic disease characterised by impaired ion transport, persistent airway inflammation and recurrent respiratory infections. The introduction of CFTR modulators, including elexacaftor/tezacaftor/ivacaftor (ETI), has markedly improved clinical outcomes. However, the impact of ETI on peripheral blood leukocyte profiles remains insufficiently characterised.

OBJECTIVE

To evaluate changes in peripheral blood leukocyte differential counts, Pseudomonas aeruginosa isolation frequency and pulmonary exacerbation frequency during 12 months of ETI therapy in patients with CF aged ≥12 years, stratified by baseline FEV1/FVC ratio.

METHODS

A retrospective analysis was conducted in 28 patients treated with ETI for ≥12 months. Neutrophils, monocytes, basophils, lymphocytes and eosinophils were assessed at baseline and after 6 and 12 months. P. aeruginosa isolation and exacerbations requiring intravenous antibiotics were recorded. Patients were compared according to baseline FEV1/FVC above or below the 5th percentile.

RESULTS

ETI therapy was associated with reductions in neutrophil and monocyte counts, with more pronounced changes in patients with preserved lung function. P. aeruginosa isolation frequency decreased from 32.1% to 17.9%. Patients with reduced FEV1/FVC exhibited higher basophil counts at baseline and after 12 months. The mean number of pulmonary exacerbations decreased from 1.32 to 0.21 episodes per year.

CONCLUSIONS

Twelve-month ETI therapy was associated with reduced neutrophil and monocyte counts, lower P. aeruginosa isolation frequency and fewer pulmonary exacerbations. The observed changes were more pronounced in patients with preserved lung function. These findings should be interpreted cautiously given the retrospective design and limited sample size.