Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes
Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes
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DOI：
10.1111/j.1365-2222.2009.03258.x
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发表时间：
2009-06-01
影响因子：
6.1
通讯作者：
Sly, P. D.
中科院分区：
文献类型：
--
作者：
Holt, P. G.;Sly, P. D.
我们提出了一个方案，其中最常见形式的呼吸道炎症性疾病，特别是特应性和非特应性哮喘和慢性阻塞性肺病，被描述为常见“危险”途径的独立分支，该途径以与控制宿主防御和组织修复机制的畸变相关的基因型为基础。我们认为进入这一途径最初是由婴儿期和幼儿期的环境经历编程的，特别是严重的下呼吸道感染，并且特定疾病表型表达的进一步发展取决于随后遇到的额外环境侵害的性质、时间和频率。在一种极端情况下，在对过敏原/病原体的炎症反应的双重攻击下，高危受试者对气源性过敏原的早期敏感可能会导致特应性哮喘表型的快速进展。另一方面，接触烟草烟雾和/或相关化学污染物引起的炎症在较长时间内会放大偶尔感染对呼吸功能的滴灌效应。非特应性哮喘被认为介于这两个极端之间，主要由高危受试者呼吸道感染的下游影响驱动。所有三种疾病表型的一个重要共同因素是，急性加重通常是由感染引起的，宿主对其的反应显示出特征性的T辅助细胞2型足迹，我们认为这表明潜在的基因型导致宿主对呼吸道病原体的反应不平衡。
We present a scheme below in which the most common forms of inflammatory diseases of the respiratory tract, notably atopic and non-atopic asthma and COPD, are depicted as separate offshoots from a common 'at-risk' pathway underpinned by genotypes related to aberrations in control of host defence and tissue repair mechanisms. We propose that entrance into this pathway is initially programmed by environmental experience during infancy and early childhood, in particular by severe lower respiratory tract infection, and that further progression towards expression of specific disease phenotype(s) is determined by the nature, timing and frequency of additional environmental insults subsequently encountered. At the one extreme, early sensitization of at-risk subjects to aeroallergens can potentially drive rapid progression towards expression of the atopic asthmatic phenotype under the dual onslaught of inflammatory responses to allergens/pathogens. At the opposite end of the spectrum the drip-feed effects of occasional infections on respiratory function(s) are amplified over a longer time frame by inflammation resulting from exposure to tobacco smoke and/or related chemical pollutants. Non-atopic asthma is envisaged to fit between these two extremes, being driven essentially by the downstream effects of respiratory infections alone in at-risk subjects. An important common factor in all three disease phenotypes is that acute exacerbations are typically driven by infections, the host responses to which display a characteristic T-helper type 2-like footprint, which in our view points to underlying genotype(s) which result in unbalanced host responses to respiratory pathogens.