Pulmonary exacerbations in cystic fibrosis after fatherhood with and without CFTR modulators

Background: Advances in cystic fibrosis (CF) management, quality of life, and fertility treatments have encouraged more men with CF (mwCF) to pursue parenthood. However, data on the impact of fatherhood on CF disease course, particularly in the era of CFTR modulators (CFTRm), remain limited. Methods: We conducted a multicenter retrospective cohort study in six CF centers (2007-2023). Demographic and clinical parameters, including forced expiratory volume in 1 s (FEV₁), body mass index (BMI), bacterial colonization, and pulmonary exacerbation (PEx) rates were compared for the year before and the year after fatherhood. Data were stratified by CFTRm therapy and analyzed per child for the effect of having multiple children, as well as grouped data. Results: Among 170 mwCF (18-50 years), 32 fathered 52 children (17 had multiple children). Mean paternal age at childbirth was 30.5 ± 5.5, mean FEV₁ declined from 74.6 ± 18.9% to 73.4 ± 19.6% (p = 0.03), while BMI remained stable (23.3 ± 3.2 to 23.4 ± 3.3; p = 1). Mild PEx increased from 0.4 ± 0.6 to 1.0 ± 1 (p = 0.001), and severe PEx (requiring intravenous antibiotic treatment), from 0.4 ± 0.9 to 0.7 ± 1.2 (p = 0.02). In mwCF on CFTRm, no significant changes were observed in FEV1, or PEx. Outcomes were not affected by the number of prior children, their order, or having had twins. Conclusion: Fatherhood may be associated with an increase in PEx, particularly among mwCF not treated with CFTRm. CFTRm therapy, therefore, appears to mitigate this risk, supporting its protective effect. These findings underscore the importance of routine and structured follow-up and counseling for mwCF during fatherhood.