辣椒素咳嗽激发试验方法的建立及其安全性评价

目的探讨辣椒素咳嗽激发试验的方法并评价其安全性。方法采用吸气触发的定量吸入装置,对60名健康志愿者(A组)、11例上呼吸道感染患者(B组)、10例胃-食管反流性咳嗽患者(C组)以及10例支气管哮喘(简称哮喘)患者(D组)行辣椒素咳嗽激发试验。所有受试者逐步吸入雾化浓度倍增(1.95、3.90、7.80、15.6、31.2、62.5、125、250、500、1 000μm ol/L)的辣椒素溶液,测试期间记录咳嗽次数。将诱发产生≥5次咳嗽的最低浓度(C5)作为咳嗽阈值,以对数值lg C5判断咳嗽反射的敏感性。在咳嗽激发前、后进行常规肺通气功能以及多频脉冲振荡呼吸阻力测定。结果全部受试者中仅6例出现轻微不适,其中1例有烧灼感、2例恶心和3例声嘶。咳嗽激发前A、B、C、D组患者第一秒用力呼气容积(FEV1)、呼吸总阻抗(Zrs)分别为(3.6±0.5)L、(2.6±0.8)mm Hg.L-1.s-1、(3.7±0.7)L、(2.5±0.5)mm Hg.L-1.s-1、(2.7±0.8)L、(2.7±0.8)mm Hg.L-1.s-1、(2.1±0.8)L,(3.3±1.5)mm Hg.L-1.s-1,经激发后分别为(3.6±0.5)L、(2.7±0.7)mm Hg.L-1.s-1、(3.7±0.8)L、(2.6±0.3)mm Hg.L-1.s-1、(2.6±0.7)L、(2.7±0.7)mm Hg.L-1.s-1、(2.1±0.8)L、(3.7±2.0)mm Hg.L-1.s-1,各组激发前、后FEV1、Zrs比较差异均无统计学意义(P均>0.05)。A、B、C、D组的咳嗽敏感性lg C5分别为2.45±0.46、2.51±0.20、1.52±0.70、2.34±0.56,其中C组与A、B、D组比较差异有统计学意义(P均<0.01);而A、B、D组间比较差异无统计学意义(P均>0.05)。结论定量吸入辣椒素咳嗽激发试验安全、可行,可在临床上用于咳嗽敏感性的测定。

The development and safety of cough provocation test by capsaicin inhalation

OBJECTIVE: To assess the application and the safety of capsaicin cough provocation test by dosimeter method. METHODS: Capsaicin inhalation cough challenge test by dosimeter method was performed on 60 healthy volunteers (group A), 11 subjects with upper respiratory infection (group B), 10 patients with gastroesophageal reflux cough (group C) and 10 patients with asthma (group D). Each subject inhaled doubling concentrations of capsaicin (1.95, 3.90, 7.80, 15.6, 31.2, 62.5, 125, 250, 500, 1,000 micromol/L) by a breath-activated dosimeter until the concentration inducing five or more coughs (C(5)) was reached. The lg C(5) was calculated as the cough reflex sensitivity. General lung ventilation and impedance with impulse oscillometry were measured before and after the cough provocation test. RESULTS: There was no serious side effect of the test in all subjects; two subjects complained of slight nausea; one of heartburn, and three of hoarseness. Before the provocation the values of FEV(1) in group A, B, C and D were (3.6 +/- 0.5) L, (3.7 +/- 0.7) L, (2.7 +/- 0.8) L and (2.1 +/- 0.8) L, compared with (3.6 +/- 0.5) L, (3.7 +/- 0.8) L, (2.6 +/- 0.7) L and (2.1 +/- 0.8) L after the test, the differences being not significant (all P > 0.05). Compared with the measurements after provocation, Zrs was (2.6 +/- 0.8) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.8) mm Hg.L(-1).s(-1) in group A, (2.5 +/- 0.5) mm Hg.L(-1).s(-1) vs (2.6 +/- 0.3) mm Hg.L(-1).s(-1) in group B, (2.7 +/- 0.7) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.7) mm Hg.L(-1).s(-1) in group C, (3.3 +/- 1.5) mm Hg.L(-1).s(-1) vs (3.7 +/- 2.0) mm Hg.L(-1).s(-1) in group D, the differences showed no significance (all P > 0.05 respectively). The lg C(5) value was 2.45 +/- 0.46 in group A, 2.51 +/- 0.20 in group B, 1.52 +/- 0.70 in group C, 2.34 +/- 0.56 in group D. Compared with group A, B and D, the lg C(5) value in group C was significantly different (all P < 0.01 respectively). The lg C(5) value showed no significant difference among group A, group B and group D (all P > 0.05). CONCLUSION: Capsaicin inhalation cough provocation test by dosimeter method is a safe and specific tool for measuring cough reflex sensitivity.