LAMA improves tissue oxygenation more than LABA in patients with COPD

The effect of bronchodilators is mainly assessed with forced expiratory volume in 1 s (FEV₁) in chronic obstructive pulmonary disease (COPD). Their impact on oxygenation and lung periphery is less known. Our objective was to compare the action of long-acting β₂-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD, considering their impact on proximal and peripheral ventilation as well as lung perfusion. FEV₁, Helium slope (S_He) from a single-breath washout test (S_He decreases reflecting a peripheral ventilation improvement), frequency dependence of resistance (R5-R19), area under reactance (AX), lung capillary blood volume (Vc) from double diffusion (DL_NO/DL_CO), and transcutaneous oxygenation (TcO₂) were measured before and 2 h post-LABA (day 1) and LAMA (day 3) in 30 patients with COPD (FEV₁ 54 ± 18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. We found that TcO₂ increased more (P = 0.03) after LAMA (11 ± 12% from baseline, P < 001) compared with LABA (4 ± 11%, P = 0.06) despite a lower FEV₁ increase (P = 0.03) and similar S_He (P = 0.98), AX (P = 0.63), and R5-R19 decreases (P = 0.37). TcO₂ and S_He changes were negatively correlated (r = -0.47, P = 0.01) after LABA, not after LAMA (r = 0.10, P = 0.65). DL_NO/DL_CO decreased and Vc increased after LAMA (P = 0.04; P = 0.01, respectively) but not after LABA (P = 0.53; P = 0.24). In conclusion, LAMA significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation, whereas LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.NEW & NOTEWORTHY Long-acting muscarinic antagonists (LAMAs) significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with β₂-agonists (LABAs). The mechanisms involved may differ between drugs: increased peripheral ventilation for LABA and likely lung capillary blood volume for LAMA. This could argue for LAMA as the first therapeutic choice in COPD.