Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Cardiopulmonary Exercise Laboratory, Faculty of Motorskill Science, Université Libre de Bruxelles, Brussels, Belgium.
J Appl Physiol (1985). 2024 Jul 1;137(1):154-165. doi: 10.1152/japplphysiol.00467.2023. Epub 2024 May 9.
The effect of bronchodilators is mainly assessed with forced expiratory volume in 1 s (FEV) 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 β-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. FEV, Helium slope (S) from a single-breath washout test (S 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/DL), and transcutaneous oxygenation (TcO) were measured before and 2 h post-LABA () and LAMA () in 30 patients with COPD (FEV 54 ± 18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. We found that TcO increased more ( = 0.03) after LAMA (11 ± 12% from baseline, < 001) compared with LABA (4 ± 11%, = 0.06) despite a lower FEV increase ( = 0.03) and similar S ( = 0.98), AX ( = 0.63), and R5-R19 decreases ( = 0.37). TcO and S changes were negatively correlated ( = -0.47, = 0.01) after LABA, not after LAMA ( = 0.10, = 0.65). DL/DL decreased and Vc increased after LAMA ( = 0.04; = 0.01, respectively) but not after LABA ( = 0.53; = 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. Long-acting muscarinic antagonists (LAMAs) significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with β-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.
长效β-激动剂（LABA-奥达特罗）和毒蕈碱拮抗剂（LAMA-噻托溴铵）对慢性阻塞性肺疾病（COPD）患者组织氧合的作用不同，考虑到它们对近端和外周通气以及肺灌注的影响。在 5-7 天洗脱期后，分别在 30 例 COPD 患者（FEV 54 ± 18%预计值；GOLD A 31%/B 48%/E 21%）中测量了支气管扩张剂后 2 小时的用力呼气量（FEV）、单次呼吸洗脱试验的氦斜率（S 降低反映外周通气改善）、频率依赖性阻力（R5-R19）、电抗面积（AX）、双扩散（DL/DL）的肺毛细血管血容量（Vc）和经皮氧饱和度（TcO）。我们发现，与 LABA（增加 4 ± 11%， = 0.06）相比，LAMA（增加 11 ± 12%， < 001）后 TcO 增加更多（ = 0.03），尽管 FEV 增加较低（ = 0.03），S（ = 0.98）、AX（ = 0.63）和 R5-R19 降低相似（ = 0.37）。在 LABA 后，TcO 和 S 的变化呈负相关（ = -0.47， = 0.01），而 LAMA 后则无相关性（ = 0.10， = 0.65）。与 LABA 后相比，LAMA 后 DL/DL 降低，Vc 增加（ = 0.04； = 0.01），但 LABA 后无变化（ = 0.53； = 0.24）。总之，LAMA 显著改善了 COPD 患者的组织氧合，而 LABA 仅显示出改善趋势。两种药物之间的作用机制可能不同：LABA 增加了外周通气，而 LAMA 增加了肺毛细血管血容量。如果氧合差异持续存在，LAMA 可能会成为 COPD 的首选治疗药物。长效毒蕈碱拮抗剂（LAMAs）显著改善了 COPD 患者的组织氧合，而β-激动剂（LABAs）仅显示出改善趋势。涉及的机制可能因药物而异：LABA 增加了外周通气，而 LAMA 可能增加了肺毛细血管血容量。这可能支持 LAMA 作为 COPD 的首选治疗药物。
