Abstract
BackgroundThe effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear.MethodsWe performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs).ResultsFour RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI − 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI − 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001).ConclusionsIn patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.
Highlights
The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pul‐ monary fibrosis (IPF) is unclear
Shulgina et al reported a Randomized control trial (RCT) of 181 IPF patients, and concluded that co-trimoxazole therapy could improve the quality of life and reduce mortality in those adhering to treatment [18]
Study selection The search results yielded a total of 1374 studies from the online databases including PubMed (n = 27), Web of Science Core Collection (n = 24), Embase (n = 806), Cochrane Library (n = 507), clinicaltrials.gov (n = 4), and WHO International Clinical Trials Registry Platform (n = 6) (e-Table 1)
Summary
The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pul‐ monary fibrosis (IPF) is unclear. Chen et al Respir Res (2021) 22:243 and nintedanib, can reduce the progression of IPF in lung function, exercise tolerance, and mortality These two agents have obtained approval from the United States (US) Food and Drug Administration for the treatment of IPF and are widely used in the European Union (EU) and other countries worldwide. In vitro studies have demonstrated that doxycycline and minocycline can improve pulmonary fibrosis by inhibiting growth factor and matrix metalloproteinase (MMP) production [12, 13] Based on these promising findings, the effect of the additional use of antimicrobial agents such as doxycycline, co-trimoxazole, and macrolides on the outcomes of IPF patients have been assessed in further clinical studies [15,16,17].
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