吸入短效支气管舒张剂对慢性阻塞性肺疾病患者等二氧化碳高通气过程中膈肌功能和中枢驱动的影响

目的探讨吸入短效支气管舒张剂对慢性阻塞性肺疾病（COPD）患者在等二氧化碳高通气（MIV）过程中膈肌功能和呼吸
中枢驱动的影响。方法47 例中重度稳定期COPD患者随机分为安慰剂组（n=12）、沙丁胺醇组（n=13）、异丙托溴铵组（n=
10）和联合组（沙丁胺醇+异丙托溴铵，n=12）。所有患者在基础状态下进行3 min MIV，并按组别吸入安慰剂400 μg，或沙丁胺
醇400 μg，或异丙托溴胺80 μg，或沙丁胺醇400 μg和异丙托溴胺80 μg，30 min后再进行3 min MIV。连续监测并计算MIV过
程中膈肌功能和中枢驱动各项指标的变化。结果MIV过程中，在基础状态下的4组患者膈肌肌电均方根（RMS）呈线性增加，
跨膈压（Pdi）、分钟通气量（VE）、通气-中枢偶联（VE/RMS）均呈线性下降（P均<0.05）。吸入药物后，沙丁胺醇组、异丙托溴铵组
和联合组各项测量指标较前均有改善（P均<0.05）；与安慰剂组比较，其余3组在同一时间段的RMS、呼吸困难评分（Borg score）
均降低，Pdi、VE、VE/RMS均增加；与单药吸入比较，联合组同一时间段的VE/RMS显著增高（P均<0.05）。△Borg与△Pdi、△
VE、△RMS、△VE/RMS均有显著相关性（P均<0.05）。结论吸入短效支气管舒张剂可以改善COPD患者MIV过程中膈肌疲
劳状态，增加通气量，降低呼吸中枢驱动，提高通气-中枢偶联，从而缓解呼吸困难症状；联合用药优于单一用药。

Effects of inhaled short-acting bronchodilators on diaphragm function and neuralrespiratory drive during maximal isocapnic ventilation in patients with chronicobstructive pulmonary disease

Objective To investigate the effects of inhaled short-acting bronchodilators on diaphragm function and neural
respiratory drive in patients with chronic obstructive pulmonary disease (COPD) during maximal isocapnic ventilation (MIV).
Methods Forty-seven patient with moderate to severe COPD were randomized into 4 groups: placebo group (n=12),
salbutamol group (n=13), ipratropium group (n=10), and combined group (salbutamol and ipratropium, n=12). Each subject
received an initial MIV for 3 min at baseline and inhaled placebo (400 μg), salbutamol (400 μg), ipratropium (80 μg), or both
salbutamol and ipratropium, followed 30 min later by another 3 min of MIV. The parameters of diaphragm function and
neural respiratory drive were monitored continuously and calculated during MIV. Results During the initial MIV, all the
patients experienced a linear increase in root mean square (RMS) of diaphragm electromyogram with a gradual decrease in
transdiaphragmatic pressure (Pdi), minute ventilation (VE), and VE/RMS, and these parameters all improved significantly
after inhalation of the bronchodilators. Compared with the placebo group at the same time point, the 3 bronchodilator-treated
groups showed significantly decreased RMS and Borg score and increased Pdi, VE and VE/RMS; VE/RMS was the highest in
the combined treatment group (P<0.05). The △Borg was significantly correlated with △Pdi, △VE, △RMS, and △VE/RMS (P<
0.05). Conclusion In COPD patients, inhaled short-acting bronchodilators can alleviate diaphragm fatigue during MIV,
increase lung ventilation, reduce neural respiratory drive, and improve neuro-ventilatory coupling to relieve dyspnoea, and
the combination of β-2 agonists and anti-muscarinic antagonists produces a stronger efficacy.