Wang M, Wisniewski A, Pavord I, Knox A, Tattersfield A
Respiratory Medicine Unit, City Hospital, Nottingham, UK.
Thorax. 1996 Aug;51(8):799-804. doi: 10.1136/thx.51.8.799.
Non-steroidal anti-inflammatory drugs (NSAIDs) are used to assess the role of prostaglandins in asthma but their effects on bronchoconstrictor challenges have been inconsistent. The effects of three nebulised nonsteroidal anti-inflammatory drugs on the airway response to inhaled sodium metabisulphite (MBS) and adenosine 5'-monophosphate (AMP) were compared in the same asthmatic subjects to see whether contractile prostaglandins were involved in MBS or AMP induced bronchoconstriction. A possible protective effect of the osmolarity or pH of the inhaled solutions was also assessed.
Two double blind placebo controlled studies were carried out. In study 1, 15 non-aspirin sensitive patients with mild asthma attended on four occasions and inhaled 5 ml of lysine aspirin (L-aspirin) 900 mg, indomethacin 50 mg, sodium salicylate 800 mg, or saline 20 minutes before an inhaled MBS challenge. On four further occasions 14 of the patients inhaled the same solutions followed by an inhaled AMP challenge. In study 2, 10 of the patients attended on four additional occasions and inhaled 5 ml of 0.9%, 3%, 10%, or 9.5% saline with indomethacin 50 mg 20 minutes before an inhaled MBS challenge.
In study 1 inhaled lysine aspirin had a similar effect on MBS and AMP induced bronchoconstriction, increasing the provocative dose causing a 20% fall in FEV1 (PD20) by 1.29 (95% CI 0.54 to 2.03) and 1.23 (95% CI 0.53 to 1.93) doubling doses, respectively. Indomethacin increased the MBS PD20 and AMP PD20 by 0.64 (95% CI -0.1 to 1.38) and 0.99 (95% CI 0.29 to 1.69) doubling doses, respectively. Sodium salicylate had no significant effect on either challenge. The two solutions causing most inhibition were the most acidic and the most alkaline. In study 2 inhaled 9.5% saline with indomethacin (osmolarity 3005 mOsm/kg) increased the MBS PD20 by 1.1 doubling doses (95% CI 0.2 to 2.0) compared with only 0.09 (95% CI -0.83 to 1.0) and 0.04 (95% CI -0.88 to 0.95) doubling doses with 3% saline (918 mOsm/kg) and 10% saline (2994 mOsm/ kg), respectively.
Inhaled L-aspirin and indomethacin have broadly similar protective effects against MBS and AMP induced bronchoconstriction in the doses given, although the effect of indomethacin on MBS was not quite statistically significant. The osmolarity and pH of the solutions did not appear to be important determinants of the response. The effect of L-aspirin and indomethacin is likely to be the result of cyclooxygenase inhibition reducing the production of contractile prostaglandins during MBS and AMP challenge.
非甾体抗炎药（NSAIDs）用于评估前列腺素在哮喘中的作用，但其对支气管收缩激发试验的影响并不一致。在同一组哮喘患者中比较了三种雾化吸入的非甾体抗炎药对吸入偏亚硫酸氢钠（MBS）和5'-单磷酸腺苷（AMP）引起的气道反应的影响，以观察收缩性前列腺素是否参与MBS或AMP诱导的支气管收缩。还评估了吸入溶液的渗透压或pH值可能的保护作用。
进行了两项双盲安慰剂对照研究。在研究1中，15名对阿司匹林不敏感的轻度哮喘患者分四次就诊，在吸入MBS激发试验前20分钟吸入5毫升900毫克赖氨酸阿司匹林（L-阿司匹林）、50毫克吲哚美辛、800毫克水杨酸钠或生理盐水。在另外四次就诊时，14名患者吸入相同溶液，随后进行吸入AMP激发试验。在研究2中，10名患者再分四次就诊，在吸入MBS激发试验前20分钟吸入5毫升含50毫克吲哚美辛的0.9%、3%、10%或9.5%生理盐水。
在研究1中，吸入赖氨酸阿司匹林对MBS和AMP诱导的支气管收缩有相似的作用，使引起第一秒用力呼气容积（FEV1）下降20%的激发剂量（PD20）分别增加1.29（95%可信区间0.54至2.03）和1.23（95%可信区间0.53至1.93）倍剂量。吲哚美辛使MBS的PD20和AMP的PD20分别增加0.64（95%可信区间-0.1至1.38）和0.99（95%可信区间0.29至1.69）倍剂量。水杨酸钠对两种激发试验均无显著影响。引起最大抑制作用的两种溶液分别是酸性最强和碱性最强的。在研究2中，与含50毫克吲哚美辛的3%生理盐水（渗透压918毫摩尔/千克）和10%生理盐水（渗透压2994毫摩尔/千克）相比，吸入含吲哚美辛的9.5%生理盐水（渗透压3005毫摩尔/千克）使MBS的PD20增加1.1倍剂量（95%可信区间0.2至2.0），而含3%生理盐水和10%生理盐水时分别仅增加0.09（95%可信区间-0.83至1.0）和0.04（95%可信区间-0.88至0.95）倍剂量。
吸入L-阿司匹林和吲哚美辛在给定剂量下对MBS和AMP诱导的支气管收缩具有大致相似的保护作用，尽管吲哚美辛对MBS的作用在统计学上不太显著。溶液的渗透压和pH值似乎不是反应的重要决定因素。L-阿司匹林和吲哚美辛的作用可能是由于环氧化酶抑制减少了MBS和AMP激发试验期间收缩性前列腺素的产生。
