Department of Pulmonology, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, The Netherlands.
Am J Respir Crit Care Med. 2011 Jun 15;183(12):1588-94. doi: 10.1164/rccm.201011-1796PP. Epub 2011 Feb 4.
Asthma and chronic obstructive pulmonary disease (COPD) show similarities and substantial differences. The Dutch hypothesis stipulated that asthma and COPD have common genetic and environmental risk factors (allergens, infections, smoking), which ultimately lead to clinical disease depending on the timing and type of environmental exposures (Postma and Boezen, Chest 2004;126:96S-104S). Thus, a particular group of shared genetic factors may lead to asthma when combined with specific environmental factors that are met at a certain stage in life, whereas combination with other environmental factors, or similar environmental factors at a different stage in life, will lead toward COPD. Multiple genes have been found for asthma and COPD. In addition to genes unique to these diseases, some shared genetic risk factors exist. Moreover, there are both common host risk factors and environmental risk factors for asthma and COPD. Here we put forward, based on the data available, that genes that affect lung development in utero and lung growth in early childhood in interaction with environmental detrimental stimuli, such as smoking and air pollution, are contributing to asthma in childhood and the ultimate development of COPD. Additional genes and environmental factors then drive specific immunological mechanisms underlying asthma, and others may contribute to the ultimate development of specific subtypes of COPD (i.e., airway disease with mucous hypersecretion, small airway disease, and emphysema). The genetic predisposition to the derailment of certain pathways may further help to define subgroups of asthma and COPD. In the end this may lead to stratification of patients by their genetic make-up and open new therapeutic prospects.
哮喘和慢性阻塞性肺疾病（COPD）既有相似之处，也有显著差异。荷兰假说规定，哮喘和 COPD 具有共同的遗传和环境危险因素（过敏原、感染、吸烟），这些因素最终会导致临床疾病，具体取决于环境暴露的时间和类型（Postma 和 Boezen，Chest 2004；126：96S-104S）。因此，当特定的一组共同遗传因素与在生命的某个特定阶段遇到的特定环境因素结合时，可能会导致哮喘，而与其他环境因素或生命中不同阶段的类似环境因素结合则可能导致 COPD。已经发现了多个与哮喘和 COPD 相关的基因。除了这些疾病特有的基因外，还存在一些共同的遗传危险因素。此外，哮喘和 COPD 既有共同的宿主危险因素，也有共同的环境危险因素。在这里，我们根据现有数据提出，那些在子宫内影响肺发育和婴幼儿期肺生长的基因，与吸烟和空气污染等有害环境刺激相互作用，导致儿童期哮喘和最终 COPD 的发展。然后，其他基因和环境因素驱动哮喘背后的特定免疫机制，而其他因素可能导致特定类型的 COPD（即气道疾病伴黏液分泌过度、小气道疾病和肺气肿）的最终发展。特定通路脱轨的遗传倾向可能进一步有助于定义哮喘和 COPD 的亚组。最终，这可能导致根据患者的遗传构成对患者进行分层，并开辟新的治疗前景。
