Inhaler Devices as Potential Bacterial Reservoirs: A 30-Day Microbiota Analysis in Non-Cystic Fibrosis Bronchiectasis.

Background/Objectives: Handheld inhalers are essential for the management of bronchiectasis, yet their role as potential microbial reservoirs remains poorly understood. We aimed to characterize and compare the bacterial communities in pressurized metered-dose inhalers (pMDIs) and Respimat® devices after 30 days of clinical use. Methods: In this 30-day prospective study of eight adults with non-cystic fibrosis bronchiectasis, inhaler devices (six pMDIs and four Respimat® devices) were analyzed using 16S rRNA gene sequencing of the V4 region. Total bacterial loads (quantitative PCR), α- and β-diversity, differential taxon abundance (ANCOM-BC), and microbial source tracking (SourceTracker2) were compared between device types. Results: After 30 days, pMDIs showed significantly higher bacterial loads than negative controls (adjusted p < 0.05), whereas Respimat® loads were indistinguishable from those of controls. Compared to Respimat® devices, pMDIs showed a trend toward microbial simplification (α-diversity: Shannon index, p = 0.08). However, overall community structures did not differ significantly (β-diversity: PERMANOVA, adjusted p = 0.18). ANCOM-BC identified 12 amplicon sequence variants (ASVs) significantly enriched in pMDIs, including one belonging to the genus Pseudomonas, compared to only one ASV in Respimat® devices. Paired device analyses between two participants who used both devices also revealed differences in the relative abundance of specific potentially pathogenic genera. For instance, in one participant, the pMDI was dominated by Staphylococcus (70.9% vs. 2.5% in the paired Respimat®). Conclusions: After 30 days of use by patients with bronchiectasis, bacterial DNA was detected in the liquid contents of both inhaler types. Only pMDIs showed a significant increase in total bacterial load relative to negative controls, and pMDIs harboured more differentially abundant ASVs than Respimat® devices, suggesting that pMDIs may be more susceptible to microbial contamination in patients with non-cystic fibrosis bronchiectasis.