Hendeles L, Harman E
Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville, USA.
Pharmacotherapy. 1997 Jan-Feb;17(1 Pt 2):39S-49S.
In the atopic patient with asthma, allergens are an important cause of chronic airway inflammation and symptoms. Natural exposure to seasonal allergens, such as grass pollen, may result in exacerbation of asthma, increased airway responsiveness (i.e., increased susceptibility of the airways to constrict), and an increased frequency of emergency room visits. Removal of patients from exposure to indoor allergens, such as dust mites, results in a marked reduction in symptoms, less airway responsiveness, and a decrease in drug requirements. In the pulmonary function laboratory, inhalation of increasing doses of allergen, in a safe and controlled manner (allergen bronchoprovocation), produces physiological responses similar to those observed after natural exposure. These include an immediate decrease in the forced expiratory volume in 1 second (FEV1) that is rapid in onset but short in duration (early response), a subsequent gradual decline in FEV1 4-8 hours after allergen inhalation that is sustained (late response), an increase in airway responsiveness, and infiltration of the airway mucosa by inflammatory cells. Drugs that are effective as maintenance therapy for chronic asthma generally attenuate the late response to allergen bronchoprovocation, and those with antiinflammatory effects (e.g., inhaled corticosteroids) also attenuate the allergen-induced increase in airway responsiveness and cellular infiltration of the airways. However, the magnitude of drug effect in this clinical model does not correlate well with the drug's relative efficacy in chronic asthma. In contrast, drugs that have no effect in this clinical model, such as calcium channel blockers, ketotifen, and antihistamines, are ineffective as maintenance therapy for chronic asthma. Thus, it appears that allergen bronchoprovocation is most useful as a screening tool for excluding drugs that are unlikely to be effective for chronic asthma and for determining whether a drug has antiinflammatory and/or immunomodulatory actions on the airway mucosa.
在患有哮喘的特应性患者中，过敏原是慢性气道炎症和症状的重要原因。自然接触季节性过敏原，如草花粉，可能导致哮喘加重、气道反应性增加（即气道收缩的易感性增加）以及急诊室就诊频率增加。让患者避免接触室内过敏原，如尘螨，可使症状明显减轻、气道反应性降低以及药物需求减少。在肺功能实验室中，以安全且可控的方式吸入递增剂量的过敏原（过敏原支气管激发试验）会产生与自然接触后观察到的类似生理反应。这些反应包括1秒用力呼气量（FEV1）立即下降，起病迅速但持续时间短（早期反应），随后在吸入过敏原4 - 8小时后FEV1逐渐持续下降（晚期反应），气道反应性增加以及炎性细胞浸润气道黏膜。作为慢性哮喘维持治疗有效的药物通常会减轻对过敏原支气管激发试验的晚期反应，而具有抗炎作用的药物（如吸入性糖皮质激素）也会减轻过敏原诱导的气道反应性增加和气道细胞浸润。然而，在这个临床模型中药物效果的大小与药物在慢性哮喘中的相对疗效并无很好的相关性。相比之下，在这个临床模型中无效的药物，如钙通道阻滞剂、酮替芬和抗组胺药，作为慢性哮喘的维持治疗是无效的。因此，过敏原支气管激发试验似乎最适合作为一种筛选工具，用于排除不太可能对慢性哮喘有效的药物，并确定一种药物是否对气道黏膜具有抗炎和/或免疫调节作用。
