TOPLINE:

DPP‑1 inhibitors and long‑term macrolides appeared to effectively reduce the frequency of exacerbations in patients with non-cystic fibrosis bronchiectasis compared with placebo, with macrolides showing a more pronounced effect. 

METHODOLOGY:

• Researchers conducted a network meta-analysis of 31 randomized controlled trials, including 4092 patients with non-cystic fibrosis bronchiectasis (mean age, 60.7 years; 60.4% women) to evaluate the efficacy and safety of anti-inflammatory therapies.
• Systematic literature searches spanning January 1965 to April 2025 found studies in which the intervention arm used an anti-inflammatory agent for at least 4 weeks.
• Intervention arms received multiple anti-inflammatory agents — including inhaled corticosteroids, macrolides, DPP-1 inhibitors, phosphodiesterase-4 inhibitors; comparators were placebo, standard of care, anti-inflammatory agents not used in the intervention group, oral corticosteroids, inhaled bronchodilators, and mucolytic agents.
• The primary outcome was the frequency of overall and severe exacerbations, and additional outcomes included adverse events.

TAKEAWAY:

• In a meta-analysis of 21 trials, long-term macrolide therapy vs placebo reduced the frequency of overall exacerbations by 56% (rate ratio [RR], 0.44; 95% CI, 0.35-0.56); DPP-1 inhibitors also reduced frequency by 27% (RR, 0.73; 95% CI, 0.60-0.88).
• The frequency of severe exacerbations decreased by 30% with DPP-1 inhibitors (RR, 0.70; 95% CI, 0.54-0.89), whereas a nonsignificant trend toward reduction was seen with macrolides in a meta-analysis of eight trials.
• Rates of mortality (31 trials) and serious adverse events (23 trials) were similar with placebo vs macrolides and DPP‑1 inhibitors. The incidence of treatment‑emergent adverse events (24 trials) was similar across most therapies but higher with phosphodiesterase‑4 inhibitors.
• DPP‑1 inhibitors reduced the frequency of overall exacerbations irrespective of whether patients were on long‑term macrolides. Among macrolides, azithromycin was the most effective in lowering the frequency of exacerbations.

IN PRACTICE:

“These findings position DPP-1 inhibitors, alongside long-term macrolides, as a promising new option for managing bronchiectasis with frequent exacerbations and warrant their evaluation in future head-to-head and implementation studies,” the authors wrote.

SOURCE:

The study was led by Shota Yamamoto, MD, PhD, University of Wisconsin-Madison. It was published online on January 11, 2026, in Chest.

LIMITATIONS:

Some trials allowed patients to use macrolides and/or inhaled corticosteroids concomitantly, which may have affected the results. Definitions of severe exacerbations differed across studies, making it harder to interpret the effects of macrolides on severe events. Limited or no data on patterns of inflammation and airway microbiota restricted further analyses.

DISCLOSURES:

The authors reported having no relevant financial or nonfinancial relationships, and the study received no funding support.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.