RSV Vaccination to Reduce Recurrent AECOPD

Objectives: To determine whether respiratory syncytial virus (RSV) vaccination reduces the rate of all-cause moderate-to-severe acute exacerbations of COPD (AECOPD) in high-risk patients, and to characterise RSV-specific infection and immune responses in this population.

Hypothesis: RSV vaccination in COPD frequent exacerbators receiving dual long-acting bronchodilators will reduce all-cause moderate-to-severe AECOPD by at least 20-25% over 12 months.

Design and subjects: This multicentre, two-arm, open-label, prospective study will recruit 320 COPD patients with 2 moderate or severe AECOPD in the prior year despite dual long-acting bronchodilator therapy. Eligible subjects will be allocated 1:1 to receive RSV vaccination plus standard care or standard care alone and followed for 12 months.

Interventions: Participants in the vaccine arm will receive a single dose of a licensed RSV vaccine in addition to usual COPD management. Controls will receive usual care without RSV vaccination during the study period.

Main outcome measures: The primary outcome is the rate of all-cause moderate-to-severe AECOPD per patient-year. Secondary outcomes include RSV-positive AECOPD, RSV infection incidence confirmed by virological testing, severe AECOPD requiring hospitalisation, time to first moderate-to-severe AECOPD, and changes in plasma RSV-specific antibody titres over 12 months.

Data analysis and expected results: Exacerbation rates will be compared between groups using negative binomial regression with adjustment for key covariates on an intention-to-treat basis. The investigators expect RSV vaccination to achieve a clinically meaningful (20%) reduction in all-cause moderate-to-severe AECOPD and to provide mechanistic insights linking RSV immunity, RSV infection, and exacerbation risk in COPD frequent exacerbators.