Prescott Susan L
School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital, Perth.
Paediatr Respir Rev. 2006 Jun;7(2):89-96. doi: 10.1016/j.prrv.2006.03.001. Epub 2006 May 30.
With the rising world burden of asthma, it is crucial to define the early events that lead to chronic inflammation and airway remodelling. Chronic airway inflammation appears to be the culmination of both local epithelial dysfunction and a more generalised immune dysregulation that results in allergic predisposition. A number of antenatal and early postnatal events may contribute to this. However, although a systemic propensity for allergic responses (typically food allergy) frequently pre-exists in children who go on to develop asthma, there is still uncertainty over whether epithelial changes occur as a primary event or whether these are consequent to this evolving systemic propensity for type 2 T-helper cell allergic responses. Many children with asthma already show many of the features of chronic airway inflammation, with epithelial desquamation, inflammatory cell infiltrates, subepithelial basement membrane thickening and fibrosis, goblet cell hyperplasia and smooth muscle hypertrophy. These changes can be evident before asthma is diagnosed, and there is also evidence that airway inflammation and early remodelling can progress in a subclinical state. New studies suggest that early airway damage is irreversible and that subsequent lung function is 'set' in the first years of life. These observations highlight the need to identify affected or at-risk children early and to develop interventions that can abort or prevent ongoing airway inflammation and remodelling.
随着全球哮喘负担的不断增加，明确导致慢性炎症和气道重塑的早期事件至关重要。慢性气道炎症似乎是局部上皮功能障碍和更广泛的免疫失调的最终结果，而这种失调会导致过敏易感性。许多产前和产后早期事件可能导致这种情况。然而，尽管在后来发展为哮喘的儿童中，全身性过敏反应倾向（通常是食物过敏）常常预先存在，但上皮变化是作为原发性事件发生，还是继发于这种不断演变的2型辅助性T细胞过敏反应的全身性倾向，仍存在不确定性。许多哮喘儿童已经表现出慢性气道炎症的许多特征，包括上皮剥脱、炎症细胞浸润、上皮下基底膜增厚和纤维化、杯状细胞增生和平滑肌肥大。这些变化在哮喘被诊断之前就可能很明显，并且也有证据表明气道炎症和早期重塑可以在亚临床状态下进展。新的研究表明，早期气道损伤是不可逆的，并且随后的肺功能在生命的最初几年就已“设定”。这些观察结果凸显了尽早识别受影响或有风险的儿童，以及制定能够中止或预防持续气道炎症和重塑的干预措施的必要性。
