Introduction: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Prevention of exacerbations is fundamental to COPD management. Methods: The RETRIEVE study was a multicenter, 7-year retrospective study (NCT03858348) of patients with spirometry confirmation of COPD, who received LABA/ICS for at least 1 year and either continued or escalated to open triple therapy, according to their physicians’ judgment. In this post hoc analysis, we explored exacerbation rate and lung function pre- and post-pneumococcal vaccination in a real-world setting. Results: Among 466 COPD patients, 48.1% received LABA/ICS for a mean 32 months, while 51.9% received LABA/ICS for a mean 21 months and then escalated to open triple therapy. Patients treated solely with LABA/ICS presented a significant reduction in COPD exacerbations (incidence rate ratio 0.66, 95% confidence interval [0.56, 0.78]) and related hospitalizations (0.43 [0.25, 0.72]) after pneumococcal vaccination compared to pre-vaccination. High-risk patients, who ultimately escalated to triple therapy, presented no reduction in exacerbations post-vaccination compared to pre-vaccination, and their airflow obstruction tended to deteriorate over time post-vaccination while they received LABA/ICS. However, after escalation to open triple therapy, there was significant reduction in exacerbations (0.78 [0.66, 0.94]) and related hospitalizations (0.41 [0.26, 0.66]) post-vaccination compared to pre-vaccination. Pneumococcal vaccination rates increased from 2012 to 2018 in our study, exceeding 90% from 2015 onward. Preserved lung function potentially delayed vaccination. Conclusion: This post hoc analysis of the RETRIEVE real-world study highlights the importance of appropriate, personalized maintenance COPD treatment, along with pneumococcal vaccination, for the prevention of COPD exacerbations.

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