73 Influence of treatment with sildenafil on lung function and exercise tolerance in cystic fibrosis adults

Abstract

Objectives: Phosphodiesterase 5 inhibitors (IPDE5) are able to restore chloride transport in F508del cystic fibrosis (CF) airway epithelium. CF patients with severe lung disease are at risk of pulmonary hypertension and impaired exercise tolerance. Treatment with IPDE5 is a promising strategy in CF. Methods: We conducted a study in 12 stable F508del homozygous CF adults (5 males and 7 females) with median (IQR) age of 25.9 (22.8–27.6) years without Burkholderia cepacia complex airway colonization. We administered sildenafil for 30 days and evaluated pulmonary function, respiratory symptoms and exercise tolerance before and after treatment using spirometry (forced expiratory volume in 1 sec. [FEV1]), 6-minute walking test (6-minute walking distance [6-MWD]) and CFQ-R quality of life questionaire (physical and respiratory domain [PHYS and RESP, respectively]). 8 patients completed the study (2 dropped due to pulmonary exacerbation and further 2 due to headaches). Exercise tolerance changed significantly (median and IQR; Wilcoxon test): 6-MWD 618 (612–692) vs. 577 (562–633) m, p = 0.012, and PHYS 93.8 (68.8–100.0) vs. 89.6 (60.4–97.9), p = 0.043, whereas pulmonary function and respiratory symptoms did not. Transient headaches were common adverse events during the first 1−2 weeks of sildenafil treatment in 7 of the 12 patients. Conclusion: We conclude that short-term sildenafil treatment in CF adults led to an improvement of exercise tolerance without changing pulmonary function and respiratory symptoms. Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic).