Pavord I, Lazarowicz H, Inchley D, Baldwin D, Knox A, Tattersfield A
Respiratory Medicine Unit, City Hospital, Nottingham, UK.
Thorax. 1994 Mar;49(3):245-9. doi: 10.1136/thx.49.3.245.
Exercise and inhaled sodium metabisulphite are thought to cause bronchoconstriction in asthma through different mechanisms. The response to both stimuli becomes refractory with repeat challenge. The mechanism of refractoriness is unclear, although depletion of mast cell derived mediators or neurotransmitters has been suggested. Recent studies suggest a common mechanism involving release of inhibitory prostaglandins. If this is true, exercise and sodium metabisulphite induced bronchoconstriction should show cross refractoriness.
Thirteen subjects with mild asthma and previously established exercise and sodium metabisulphite induced bronchoconstriction performed two sodium metabisulphite challenges (giving a single dose previously shown to cause a 20% fall in FEV1) on one study day, and two exercise tests on another. The second challenge proceeded after recovery (FEV1 > 95% baseline) from the first. Subjects then attended on two further occasions when an exercise test was performed after sodium metabisulphite and a sodium metabisulphite challenge after exercise.
When expressed as the percentage reduction in the area under the change in percentage FEV1 curve over 20 minutes (AUC) the response to exercise was reduced by a mean 62.3% (95% CI 46.5% to 78.1%) following a first exercise challenge, and by 50.7% (95% CI 27.8% to 73.6%) following a sodium metabisulphite challenge. The response to a sodium metabisulphite challenge was reduced by a mean of 80.2% (95% CI 68.9% to 91.5%) when it followed a sodium metabisulphite challenge, and by 37.3% (95% CI 15.1% to 59.5%) following an exercise challenge.
This study shows some cross refractoriness between exercise and sodium metabisulphite induced bronchoconstriction, in keeping with a partially shared mechanism of refractoriness.
运动和吸入焦亚硫酸钠被认为通过不同机制在哮喘中引起支气管收缩。对这两种刺激的反应在重复激发时会变得不应答。尽管有人提出肥大细胞衍生介质或神经递质的耗竭,但不应答的机制尚不清楚。最近的研究提示了一种涉及抑制性前列腺素释放的共同机制。如果这是真的,那么运动和焦亚硫酸钠诱导的支气管收缩应该表现出交叉不应答。
13名患有轻度哮喘且先前已证实存在运动和焦亚硫酸钠诱导支气管收缩的受试者,在一个研究日进行两次焦亚硫酸钠激发试验(给予先前已证实可使第一秒用力呼气容积(FEV1)下降20%的单次剂量),并在另一天进行两次运动试验。第二次激发试验在第一次激发试验恢复后(FEV1>95%基线)进行。然后,受试者再参加另外两次试验,一次是在焦亚硫酸钠激发试验后进行运动试验,另一次是在运动试验后进行焦亚硫酸钠激发试验。
当以20分钟内FEV1变化百分比曲线下面积(AUC)的减少百分比表示时,在第一次运动激发试验后,运动反应平均降低62.3%(95%可信区间46.5%至78.1%),在焦亚硫酸钠激发试验后降低50.7%(95%可信区间27.8%至73.6%)。当焦亚硫酸钠激发试验在另一次焦亚硫酸钠激发试验之后进行时,其反应平均降低80.2%(95%可信区间68.9%至91.5%),在运动激发试验之后进行时降低37.3%(95%可信区间15.1%至59.5%)。
本研究显示运动和焦亚硫酸钠诱导的支气管收缩之间存在一定的交叉不应答,这与部分共享的不应答机制相符。