Dry NaCl Inhalation Fails to Improve Mucociliary Clearance in COPD

BACKGROUND: Inhaled saline may improve mucus transport in respiratory diseases, for example, cystic fibrosis. This randomised, placebo-controlled, crossover study examined the effect of inhaled dry NaCl on mucociliary clearance in patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty-five patients with GOLD stage I-III COPD (72% with excess mucus) were tested on two separate days after inhalation from a dry powder inhaler containing either 40 mg dry NaCl or placebo (empty). Pulmonary mucociliary clearance was assessed using inhalation of a radioactive Tc-labelled nanocolloid tracer and gamma camera imaging. Clearance was measured for 2 h post-intervention. Co-primary outcomes were clearance after 1 and 2 h. RESULTS: The study was terminated early due to COVID-19 after enrolling 25 of 35 planned patients. No significant differences were observed in mucociliary clearance between NaCl and placebo after 1 h (11.3% ± 9.0% vs. 11.4% ± 7.0%, p = 0.97) or 2 h (15.3% ± 9.8% vs.16.1% ± 8.7%, p = 0.55). Normalised clearance based on initial radioaerosol deposition also showed no difference. CONCLUSIONS: Inhalation of 40 mg dry NaCl was well tolerated without acute adverse effects in COPD patients. However, early termination left the study underpowered, increasing the risk of type II error. Non-significant findings should not be interpreted as evidence of no effect. Larger, adequately powered trials are needed to clarify the impact of dry NaCl inhalation on mucociliary clearance in COPD.