The microbial effect of inhaled steroids in severe COPD patients with associated bronchiectasis (TEMPESTAS): an exploratory pilot randomised controlled trial

Introduction Bronchiectasis overlap in high-risk COPD predicts mortality, yet the impact of inhaled corticosteroids (ICS) in this group remains unclear. The object of the present study was to compare clinical and microbiological outcomes in a cohort of COPD–bronchiectasis overlap patients receiving ICS-containing triple therapy versus dual bronchodilator therapy. Methods In this multicentre, open-label, randomised trial, participants underwent a 4-week dual-therapy washout before receiving 1 year of dual or triple inhaled therapy. The primary outcome was change in sputum bacterial load (CFU·mL −1 ) at 1 year; secondary outcomes included clinical measures and microbiota composition analysis. Results Of the planned 80 participants, 23 were enrolled (11 dual therapy, 12 triple therapy). Recruitment challenges lead to a reduced sample size (n=16 with evaluable data: 6 dual, 10 triple), limiting statistical power and rendering the findings exploratory. At 1 year, there was no significant difference in microbial load between groups (mean difference −0.32 log CFU·mL −1 (95% CI −1.12–0.49; p=0.42). Secondary outcomes were also largely unchanged, although time to first exacerbation was numerically longer (169.4 versus 109.5 days; p=0.83) and an improvement was observed in the St. George's Respiratory Questionnaire (SGRQ-C) activity domain in the triple therapy group (p=0.02). Given the small sample size and lack of adjustment for multiple comparisons, these findings should be considered hypothesis-generating. Two hospitalisations for pneumonia occurred in the triple therapy group; both patients had a high baseline sputum abundance of Streptococcus spp. and Rothia spp. Conclusion This exploratory study, despite being underpowered, yields important feasibility and methodological insights that will inform future trials examining the microbial effects of ICS in this high-risk population.