Impact of hypertonic saline nebulisation combined with oscillatory positive expiratory pressure on sputum expectoration and related symptoms in cystic fibrosis: a randomised crossover trial

Objective To evaluate the impact of combining nebulised hyaluronic acid plus hypertonic saline (HA+HS) with oscillatory positive expiratory pressure (oscillatory-PEP) on sputum expectoration and related symptoms in adults with cystic fibrosis (CF). Design Randomised crossover trial. Setting Seven centres. Participants Twenty-two outpatients with CF. Interventions Usual care (HA+HS followed by autogenic drainage) and combined therapy (HA+HS with oscillatory-PEP followed by autogenic drainage]. Each treatment was performed for 5 days. Main outcome measures Sputum expectoration was measured during the nebulisation period (primary outcome), during autogenic drainage and for 24hours post intervention. The Cough and Sputum Assessment Questionnaire (CASA-Q) and its domains (cough symptoms, cough impact, sputum symptoms and sputum impact), the Leicester Cough Questionnaire (LCQ) and lung function tests were used. Tolerance and patient preference were registered. Results Twenty-two participants [mean age 25 (standard deviation 8) years, percentage predicted forced expiratory volume in 1second 67 (22)] were recruited. Combined therapy promoted greater sputum expectoration than usual care during the nebulisation period {median difference 1.8ml [95% confidence interval (CI) 0.2–6.2]}. Both treatments led to similar expectoration during autogenic drainage and for 24hours post intervention. Combined therapy led to a greater improvement in the sputum symptoms domain [6.7 points (95% CI 3.3–13.3] and total CASA-Q score [2.4 points (95% CI 0.1–9.3)] compared with usual care. No differences in LCQ score or lung function were observed. Fewer adverse events were reported using combined therapy, which was selected as the preferred intervention. Conclusions Combined nebulisation increased immediate sputum expectoration, improved sputum symptoms and reduced adverse events compared with usual care in patients with CF. Clinical trial number NCT02303808.