Impact of Hypertonic Saline Solutions on Sputum Expectoration and Their Safety Profile in Patients with Bronchiectasis: A Randomized Crossover Trial

摘要

Background: The role of hyaluronic acid plus hypertonic saline (HA+HS) as a mucoactive treatment in patients with bronchiectasis is still unknown. This study evaluated whether HA+HS solution enhances similar sputum quantity with better safety profile than HS alone in patients with bronchiectasis. Methods: In this double-blind randomized crossover trial, three solutions (7% HS; 0.1% HA +7%HS; and 0.9% isotonic saline, IS) were compared in outpatients with bronchiectasis and chronic sputum expectoration. Participants inhaled each solution across four consecutive sessions. All sessions, except on session 3, also included 30 minutes of airway clearance technique. A 7-day washout period was applied. Sputum weight was collected during the sessions (primary outcome) as well as during a 24-hour follow-up. The Leicester Cough Questionnaire (LCQ) and lung function were measured before/after each treatment arm. Safety was assessed by the monitoring of adverse events (AEs). Results: Twenty-eight patients with bronchiectasis (mean age of 64.0 (17.9) and FEV1% 60.9 (24.6) of predicted) were recruited. HS and HA+HS promoted similar expectoration during sessions, both being greater than IS [median difference HS vs. IS 3.7g (95% CI 0.5-6.9); HA+HS vs. IS 3.2g (95%CI 0.5-5.9)]. Sputum expectorated exclusively during the ACT period was similar across all treatment arms [HS vs. IS -0.3g (95% CI -1.7 to 0.9); HA+HS vs. IS 0.0g (95% CI -1.3 to 1.4); HS vs. HA+HS 0.0g (95% CI -1.2 to 0.4)]. Sputum collected over the 24-hour follow-up tended to be lower for HS and HA+HS compared with IS [HS vs. IS -1.7g (95% CI -4.2 to 0.0); HA+HS vs. IS -1.1g (95%CI -3.6 to 0.7)]. No differences in LCQ or lung function were observed. Most severe AEs were reported using HS. Conclusion: HS and HA+HS were more effective on sputum expectoration than IS in patients with bronchiectasis, reporting HA+HS better safety profile than HS.