Prevention of Acute Exacerbation in Subjects with Moderate-to-very Severe COPD by Modulating Lower Respiratory Microbiome: Protocol of a Prospective, Multicenter, Randomized Controlled Trial.

Background: COPD is a global respiratory disease that has produced a worldwide health care burden. Acute exacerbation of COPD (AECOPD) is the leading cause of death in patients with COPD and accounts for the majority of expenditure of COPD management. The colonization of potential pathogenic bacteria in the lower respiratory tract is an important cause of the acute exacerbation especially in patients with moderate and severe COPD. Some clinical studies have shown the potential of oral probiotics, aerosol-inhaled amikacin and combined vaccination to prevent AECOPD. Methods and Analysis: We hypothesize that patients with stable COPD will benefit from aerosol-inhaled amikacin, oral probiotics or combined vaccination in terms of preventing acute exacerbation of COPD, slowing the progression of the disease and improving their quality of life. The trial aimsto investigate the efficacy and safety of the above interventions to decolonize bacteria in the lower respiratory tract and prevent acute exacerbation of COPD. In the study, 144 patients with stable phase of moderate-to-very severe COPD will be recruited and randomized into aerosol-inhaled amikacin group, oral probiotics group, combined vaccination group and the control group at a 1:1:1:1 ratio. The primary outcome is time to the first COPD exacerbation. Other endpoints include colonization of potential pathogenic bacteria in induced sputum, microbiome in induced sputum, pulmonary function and symptoms of patients, inflammation level and adverse events, serious adverse events, and death.