Liu Andrew H
Division of Pediatric Allergy & Immunology, National Jewish Medical & Research Center, Denver, CO 80206, USA.
Paediatr Respir Rev. 2004;5 Suppl A:S65-71. doi: 10.1016/s1526-0542(04)90013-9.
Endotoxin and allergen exposure have been explored in the context of asthma for more than a century. Building upon a pyramid of knowledge are recent observations that provide new insights to the effect of these exposures on the development of asthma. Some of these studies challenge some previously held concepts of the role of these exposures in asthma inception. Indoor allergens are well established as the basis of inflammation in sensitised asthmatics, contributing to disease severity. Then does greater exposure to indoor allergens cause allergen sensitisation and asthma as well? While risk of sensitisation to house dust mites generally increases with higher levels of exposure, this does not seem to hold for cats, where higher levels of cat allergen exposure are associated with less sensitisation. Indeed, several recent studies suggest that early childhood exposure to animals, as indoor pets or in farming stables, are associated with a lower prevalence of asthma, hay fever, and inhalant allergen sensitisation. Endotoxin in asthma provides a similar paradox. Endotoxin is a potent immune-stimulatory component of the bacterial cell wall of all gram-negative bacteria. As such, endotoxin is ubiquitous in our environment. Endotoxin exposure has been well demonstrated to underlie "Monday Asthma" or byssinosis in cotton workers, and has since emerged as a frequent cause of asthma-like symptoms in a wide range of occupational settings. Asthmatics are particularly sensitive to inhaled endotoxin, and inhalation induces both immediate and sustained airflow obstruction. The paradox of endotoxin exposure is that higher levels of exposure in early life might mitigate the development of allergy and persistent asthma. With endotoxin exposure being significantly higher in homes with animals and in farming households, where allergy and asthma are less likely to develop, endotoxin and other microbial exposures in early life may keep allergen sensitisation and asthma from developing by promoting Th1-type immune development. These observations, consistent with the "Hygiene Hypothesis" of allergy and asthma, are an encouraging glimpse of the potential for early immune modulatory approaches to asthma therapy and prevention.
内毒素和过敏原暴露在哮喘背景下的研究已逾一个多世纪。基于知识积累所产生的最新观察结果，为这些暴露因素对哮喘发展的影响提供了新的见解。其中一些研究对先前关于这些暴露因素在哮喘发病中作用的概念提出了挑战。室内过敏原已被确认为致敏哮喘患者炎症的基础，会加重疾病严重程度。那么，更多地接触室内过敏原是否也会导致过敏原致敏和哮喘呢？虽然对屋尘螨致敏的风险通常会随着接触水平的升高而增加，但对于猫过敏原而言似乎并非如此，更高水平的猫过敏原接触与较低的致敏率相关。事实上，最近的几项研究表明，儿童早期接触室内宠物或农场畜舍中的动物，与哮喘、花粉症和吸入性过敏原致敏的较低患病率相关。内毒素在哮喘中的情况也类似。内毒素是所有革兰氏阴性菌细胞壁的一种强效免疫刺激成分。因此，内毒素在我们的环境中无处不在。内毒素暴露已被充分证明是棉纺织工人“周一哮喘”或棉尘病的病因，并且此后已成为广泛职业环境中哮喘样症状的常见原因。哮喘患者对吸入内毒素特别敏感，吸入会引发即刻和持续的气流阻塞。内毒素暴露的矛盾之处在于，早年较高水平的暴露可能会减轻过敏和持续性哮喘的发展。在有动物的家庭和农户中，内毒素暴露水平显著更高，而这些地方过敏和哮喘的发病可能性较小，早年接触内毒素和其他微生物可能通过促进Th1型免疫发育来防止过敏原致敏和哮喘的发生。这些与过敏和哮喘的“卫生假说”一致的观察结果，令人鼓舞地瞥见了早期免疫调节方法在哮喘治疗和预防方面的潜力。
