Efficacy of Antiinflammatory Therapies for Adults With Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Network Meta-Analysis

Shota Yamamoto; Takayuki Niitsu; Kiyoharu Fukushima; Ayako Shiozawa; Ryosuke Imai; Kazuki Hashimoto; Kenneth N Olivier; Timothy R Aksamit; Kozo Morimoto

doi:10.1016/j.chest.2025.12.035

Efficacy of Antiinflammatory Therapies for Adults With Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Network Meta-Analysis

Chest. 2026 Jan 12:S0012-3692(26)00010-3. doi: 10.1016/j.chest.2025.12.035. Online ahead of print.

Authors

Shota Yamamoto¹, Takayuki Niitsu², Kiyoharu Fukushima², Ayako Shiozawa³, Ryosuke Imai⁴, Kazuki Hashimoto⁵, Kenneth N Olivier³, Timothy R Aksamit⁶, Kozo Morimoto⁷

Affiliations

¹ Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI. Electronic address: yamasho1113x1987@gmail.com.
² Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
³ Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
⁴ Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
⁵ Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison, Madison, WI.
⁶ Pulmonary Disease and Critical Care Medicine, Mayo Clinic, Rochester, MN.
⁷ Division of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan; Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan; Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Kiyose, Tokyo, Japan.

PMID: 41534709
DOI: 10.1016/j.chest.2025.12.035

Abstract

Background: Non-cystic fibrosis bronchiectasis is characterized by chronic respiratory symptoms and radiologic airway dilatation. Sustained neutrophilic inflammation is a key driver, prompting interest in antiinflammatory pharmacotherapy as a new treatment paradigm; however, comparisons among antiinflammatory agents are lacking.

Research question: What is the current profile concerning efficacy and safety of antiinflammatory therapies for bronchiectasis?

Study design and methods: We performed a systematic review and network meta-analysis of randomized controlled trials that evaluated inhaled or oral antiinflammatory agents in adults with CT scan-confirmed bronchiectasis. PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched. Trials enrolling adults and using ≥ 4 weeks of treatment were eligible. The primary outcome was the rate of overall and severe exacerbations; secondary outcomes were quality of life, 6-minute walk distance, FEV₁, and adverse events. The certainty of evidence was rated with Grading of Recommendations Assessment, Development, and Evaluation.

Results: Thirty-one trials (N = 4,092) evaluating 8 antiinflammatory agents were included. Compared with placebo, macrolides (rate ratio [RR], 0.44; 95% CI, 0.35-0.56) and dipeptidyl-peptidase-1 (DPP-1) inhibitors (RR, 0.73; 95% CI, 0.60-0.88) reduced overall exacerbation frequency (both moderate certainty). DPP-1 inhibitors reduced the frequency of severe exacerbations (RR, 0.70; 95% CI, 0.54-0.89; moderate certainty). Macrolides showed a similar downward trend of severe exacerbations with very serious imprecision (RR, 0.54; 95% CI, 0.19-1.54; low certainty). Adverse events and treatment discontinuation rates were trivial or small for all interventions. In subgroup analyses, DPP-1 inhibitors remained effective irrespective of baseline long-term macrolide use (with macrolide: RR, 0.77; 95% CI, 0.60-0.99; without macrolide: RR, 0.77; 95% CI, 0.67-0.89). Among individual macrolides, azithromycin showed the greatest reduction in exacerbation frequency (RR, 0.37; 95% CI, 0.29-0.48).

Interpretation: These findings support the use of DPP-1 inhibitors and macrolide antibiotics as antiinflammatory treatment options for bronchiectasis with frequent exacerbations.

Clinical trial registration: PROSPERO; No.: CRD42024605694; URL: https://www.crd.york.ac.uk/prospero/.

Keywords: adults; antiinflammatory agents; network meta-analysis; non-cystic fibrosis bronchiectasis; systematic review.