Morice A H, Higgins K S, Yeo W W
University Dept of Medicine & Pharmacology, Royal Hallamshire Hospital, Sheffield, UK.
Eur Respir J. 1992 Jul;5(7):841-7.
Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
吸入性咳嗽激发试验已成为研究镇咳药的一种公认方法。因此，研究重复咳嗽激发试验中速发耐受的程度很重要。此外，不同类型的激发试验可能揭示咳嗽反射所涉及的神经通路的重要差异。在健康受试者的急性和长期吸入研究中，对柠檬酸、蒸馏水和辣椒素进行了检测，以确定咳嗽反应的适应性。为研究急性速发耐受，进行了两次单独的1分钟持续吸入激发试验（n = 13）。使用柠檬酸和辣椒素以10分钟间隔吸入40分钟，并在4小时和6小时时检测长期速发耐受（n = 10）。在另一项单独的随机交叉研究（n = 10）中检测了对柠檬酸和辣椒素的交叉速发耐受。在1分钟柠檬酸激发试验的第一个和最后10秒之间出现了高度显著的适应性（90 - 100%），蒸馏水激发试验中也有显著适应性（74 - 84%），但辣椒素激发试验中适应性较弱（2微摩尔时为37 - 49%）。柠檬酸激发试验中，第二次试验全程的咳嗽显著减少（50%）。在长期激发试验中，柠檬酸（100毫摩尔，p < 0.05；300毫摩尔，p < 0.001；1摩尔，p < 0.001）和辣椒素（3微摩尔，p < 0.01；10、30、100微摩尔，各p < 0.001）在40分钟内咳嗽均减弱。使用更高剂量时，柠檬酸（300毫摩尔，p < 0.05）和辣椒素（100微摩尔，p < 0.008）在180分钟时仍存在速发耐受。（摘要截选至250字）
