Dipartimento di Fisiopatologia e dei Trapianti, Università degli Studi di Milano, Milan, Italy; and.
Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Division of Respiratory Diseases, "L. Sacco" Hospital, Azienda Socio-Sanitaria Territoriale Fatebenefratelli Sacco, Milan, Italy.
J Appl Physiol (1985). 2017 Nov 1;123(5):1266-1275. doi: 10.1152/japplphysiol.00493.2017. Epub 2017 Aug 3.
Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (aged 70 ± 7 yr, mean ± SD; 82% men) with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single-breath N test and transpulmonary pressure-volume curve (P-V), before and 1 h after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) scale and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (-5 ± 4 and -2.5 ± 2.1%, respectively, both < 0.001), with an increase in both slope and height of phase IV and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3 ± 3 mmHg and 2 ± 2%, respectively, both < 0.001); their changes negatively correlated with those of phase III slope ( = -0.659 and = -0.454, respectively, both < 0.01). The vital capacity (VC) increased substantially, but the P-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small-airway damage and positively affect gas exchange. This is the first study investigating in stable chronic obstructive pulmonary disease patients the acute effects of two long-acting bronchodilators, a β-agonist and a muscarinic antagonist, on peripheral airways using simultaneous lung pressure-volume curve and single-breath N test. By lessening airway mechanical property heterogeneity, both drugs similarly reduced ventilation inhomogeneity and extent of small-airway closure, as indicated by the decrease of phase III slope, increased oxygen saturation, and fall of closing volume, often below expiratory reserve volume.
小气道是慢性阻塞性肺疾病（COPD）病理生理学的关键因素。不同类别的支气管扩张剂对小气道的作用仍了解甚少，也难以评估。因此，研究了噻托溴铵（18μg）和茚达特罗（150μg）对 51 例稳定期 COPD 患者（年龄 70±7 岁，均为男性，82%）闭合容积（CV）和通气不均一性的急性影响，并进行了比较。患者在用药前和用药后 1 小时接受了体描法、动脉血气分析、潮气呼气流量限制（EFL）、呼吸困难评估以及同步记录单次呼吸氮测试和跨肺压力-容积曲线（P-V）。根据全球慢性阻塞性肺疾病倡议（GOLD）量表和 EFL 的存在，评估疾病严重程度后发现，茚达特罗对每种变量的作用与噻托溴铵相同。支气管扩张剂显著降低了 III 相斜率和 CV（分别为-5±4%和-2.5±2.1%，均<0.001），同时增加了 IV 相斜率和高度以及解剖死腔。动脉血氧分压和饱和度显著改善（分别增加 3±3mmHg 和 2±2%，均<0.001）；其变化与 III 相斜率的变化呈负相关（分别为-0.659 和-0.454，均<0.01）。肺活量（VC）显著增加，但 CV 以上的 P-V/VC 曲线不受影响。总之，支气管扩张剂降低了周围气道机械特性的异质性和它们的关闭程度，对临界关闭压力的影响较小。这应该降低小气道损伤的风险，并对气体交换产生积极影响。这是第一项研究，使用同步肺压力-容积曲线和单次呼吸氮测试，在稳定的慢性阻塞性肺疾病患者中研究了两种长效支气管扩张剂，一种β激动剂和一种抗毒蕈碱拮抗剂，对周围气道的急性作用。通过减轻气道机械特性的异质性，两种药物均相似地降低了通气不均一性和小气道关闭程度，如 III 相斜率降低、氧饱和度增加和闭合容积下降（通常低于呼气储备容积）所示。
