The effect of inhaled therapies on exacerbation risk in patients with chronic hypercapnic COPD receiving long-term non-invasive ventilation

<bold>Introduction:</bold> Prevention of acute exacerbations (AE) is paramount in COPD. Chronic hypercapnia is prevalent in severe COPD and can increase the risk for AE. Reducing hypercapnia with long-term non-invasive ventilation (LT-NIV) may decrease the risk; however, it is unclear how different inhalers affect AE prevention in this cohort. <bold>Methods:</bold> 364 (age: 65±9 yrs, 42% male) patients with chronic hypercapnic COPD receiving LT-NIV were enrolled and followed up until the end of the data collection period or death (median follow-up 19 [IQR=9-43] months). Time from setup until the first AE was recorded, and annualized AE rates were calculated. Patients were categorized by the type of inhaler (MDI vs. DPI) and medication combinations (LAMA/LABA (L/L), ICS/LABA (I/L), triple therapy (T)). <bold>Results:</bold> 186 (51.1%) patients used MDI and 178 (48.9%) used DPI at NIV setup, while 34 (9.5%) used L/L, 37 (10.3%) I/L, and 287 (80.2%) T. Median time to the first AE (MDI: 3.5 [1.2-10] vs. DPI: 3.2 [1.3-10] months, p=0.81) and the follow-up AE rate (2.4 [0.5-5.1] vs. 2.3 [0.5-4.4] AE/y, p=0.52) was similar between the MDI and DPI users. The time to the first AE did not differ between medication combinations (L/L: 7 [2.1-12] vs. I/L: 3.4 [1.5-12] vs. T: 2.8 [1.2-9] months, p=0.10). Notably, the annual number of AEs was the lowest with L/L (0.8 [0-1.7]), higher with T (2.4 [0.6-4.9]), and the highest with I/L combination (4.1 [1.1-6.6] AE/y, p<0.001). <bold>Conclusions:</bold> Our findings suggest that different inhalers may be equally effective in prolonging AE-free time in patients with hypercapnic COPD receiving LT-NIV, while LAMA/LABA is associated with the fewest annual AEs.