An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study
An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study
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DOI：
10.1186/1465-9921-7-116
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发表时间：
2006-09-06
影响因子：
5.8
通讯作者：
Johnston, Sebastian L.
中科院分区：
文献类型：
--
作者：
Mallia, Patrick;Message, Simon D.;Johnston, Sebastian L.
背景：COPD急性加重是发病、死亡和住院的主要原因。呼吸道病毒与大多数急性加重相关，但尚未证实因果关系，并且对病毒诱导的急性加重机制了解甚少。人类实验模型的发展将提供证据的因果关系，并将大大促进了解机制，但没有这样的模型existing.Methods：我们的目的是评估的可行性，发展鼻病毒引起的COPD急性加重的实验模型，并评估鼻病毒感染的COPD患者的安全性。我们进行了一项试验性病毒剂量递增研究，以评估在COPD受试者（GOLD II期）中诱导实验性鼻病毒感染所需的鼻病毒16的最小剂量。结果进行了评估，通过监测的上，下呼吸道症状，肺功能，病毒复制和炎症反应，在鼻腔lavage.Results：所有4名受试者开发症状性感冒与最低剂量的病毒测试，与证据的病毒复制和增加促炎细胞因子在鼻腔灌洗。这些伴随着下呼吸道症状的显著增加以及PEF和FEV1的降低。有没有严重的急性加重或其他不良事件。结论：低剂量实验性鼻病毒感染COPD患者诱导的症状和肺功能的变化典型的COPD急性加重，似乎是安全的，并提供了初步证据的因果关系。
Background: Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.Methods: We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD ( GOLD stage II). Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.Results: All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events.Conclusion: Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.