Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Department of Paediatrics and Child Health and South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Am J Respir Crit Care Med. 2024 Sep 15;210(6):737-754. doi: 10.1164/rccm.202312-2249SO.
Asthma is a descriptive label for an obstructive inflammatory disease in the lower airways manifesting with symptoms including breathlessness, cough, difficulty in breathing, and wheezing. From a clinician's point of view, asthma symptoms can commence at any age, although most patients with asthma-regardless of their age of onset-seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research. Herein, we present state-of-the-art updates on the role of genetics and epigenetics, early viral and bacterial infections, immune response, and pathophysiology, as well as lifestyle and environmental exposures, in asthma across the life course. We conclude that early environmental insults in genetically vulnerable individuals inducing abnormal, pre-asthmatic airway responses are key events in asthma inception, and we highlight disease heterogeneity across ages and the potential shortsightedness of treating all patients with asthma using the same treatments. Although there are no interventions that, at present, can modify long-term outcomes, a precision-medicine approach should be implemented to optimize treatment and tailor follow-up for all patients with asthma.
哮喘是一种描述性标签，用于下呼吸道的阻塞性炎症性疾病，其症状包括呼吸困难、咳嗽、呼吸困难和喘息。从临床医生的角度来看，哮喘症状可以在任何年龄开始，但大多数哮喘患者——无论其发病年龄如何——在儿童时期似乎都有某种形式的气道问题。因此，哮喘的发病和相关病理生理过程很可能很早就发生了，最近的肺生理和机制研究进一步证明了这一点。在此，我们介绍了遗传学和表观遗传学、早期病毒和细菌感染、免疫反应和病理生理学以及生活方式和环境暴露在整个生命过程中对哮喘的作用的最新进展。我们的结论是，遗传易感性个体中早期环境损伤诱导异常的、哮喘前气道反应是哮喘发病的关键事件，我们强调了不同年龄段疾病异质性以及使用相同治疗方法治疗所有哮喘患者的潜在短视性。虽然目前没有干预措施可以改变长期结果，但应该实施精准医学方法，以优化所有哮喘患者的治疗和随访。
