Abstract Background Bronchiectasis is a chronic progressive lung disease characterized by cough, sputum production and recurrent respiratory infections and gradual airway damage. This is seen millions globally and it causes decreased Quality of Life, Significant morbidity and accelerated mortality. The pathogenesis involves a vicious cycle of neutrophilic inflammation, impaired mucociliary clearance and progressive structural lung damage. The current standard of care involves airway clearance, antibiotics and symptomatic care, but hardly none focuses on underlying inflammatory pathogenesis. Neutrophil serine proteases are activated by dipeptidyl peptidase-1 (DPP-1) during neutrophil maturation and they disrupt protease-antiprotease balance and perpetuates inflammation. DPP-1 inhibitors interfere in this pathway and therefore they break the vicious cycle and potentially improve clinical outcomes in bronchiectasis patients. Methods We searched PubMed, Embase, Google Scholar, and Cochrane databases for studies evaluating Efficacy and safety of DPP-1 inhibitors in bronchiectasis patients. Three randomized controlled trials met inclusion criteria. Data were pooled using inverse variance weighting method. Random-effects model was used and Forest plots were generated to illustrate pooled effect estimates. Analysis was done using R software(version 4.5.0). Results A total of 1502 patients from three studies were included. DPP-1 inhibitors significantly decreased annual pulmonary exacerbation rates (IRR:0.75;95% CI:0.59-0.97;p=0.0267) and prolonged the time to first exacerbation during treatment(HR:0.66;95% CI:0.46-0.96;p=0.0291) compared to placebo. Many patients in the treatment group remained exacerbation-free compared to placebo, but its statistical significance is not established (RR:1.42;95% CI:0.96-2.08;p=0.0756).Quality of life score significantly improved from baseline in the treatment group (MD:2.69;95% CI:0.66-4.72;p=0.0094). Overall adverse events (RR:0.97;95% CI:0.92-1.01;p=0.1417), serious adverse events (RR:0.84;95% CI:0.68-1.04;p=0.1054) and deaths (RR:0.70;95% CI:0.22-2.18;p=0.5348) slightly favoured the treatment group, but they are not statistically significant. DPP-1 inhibitors particularly increased the risk of dermatological adverse events (RR:2.51;95% CI:1.28-4.91;p=0.0075). Conclusion DPP-1 inhibitors significantly reduced exacerbation rates and improved quality of life in bronchiectasis patients. They also showed favorable safety profile, except for few dermatological conditions which should be carefully monitored for. Future research should focus on optimal dosing strategies, long term safety profile and identifying patient subgroup who benefit most from DPP-1 inhibitors. This abstract is funded by: None
Krishnamaneni et al. (Fri,) studied this question.