Experimental Rhinovirus Infection as a Human Model of Chronic Obstructive Pulmonary Disease Exacerbation
Experimental Rhinovirus Infection as a Human Model of Chronic Obstructive Pulmonary Disease Exacerbation
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DOI：
10.1164/rccm.201006-0833oc
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发表时间：
2011-03-15
影响因子：
24.7
通讯作者：
Johnston, Sebastian L.
中科院分区：
文献类型：
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作者：
Mallia, Patrick;Message, Simon D.;Johnston, Sebastian L.
理由：呼吸道病毒感染与慢性阻塞性肺病 (COPD) 恶化有关，但因果关系尚未得到证实。对自然发生的病情加重的研究很困难，并且对病毒感染与病情加重之间的联系机制知之甚少。我们假设 COPD 受试者的实验性鼻病毒感染将再现自然发生的 COPD 恶化的特征，并且是 COPD 恶化的有效模型。 目的：评估实验性鼻病毒感染作为 COPD 恶化的模型，并研究病毒诱导的恶化的机制。 方法：我们在 13 名 COPD 受试者和 13 名无阻塞对照受试者中使用实验性鼻病毒感染，以调查临床、生理、病理和抗病毒反应以及病毒载量与这些结果之间的关系。测量和主要结果：临床数据；血液、痰液和支气管肺泡灌洗液中的炎症介质；在基线时和感染鼻病毒 16 后测量鼻灌洗液、痰液和支气管肺泡灌洗液中的病毒载量。鼻病毒感染后，慢性阻塞性肺病患者出现下呼吸道症状、气流阻塞以及全身和气道炎症，与对照组相比，这些症状更严重、持续时间更长。痰中的中性粒细胞标记物与临床结果相关，病毒载量与炎症标记物相关。 COPD 受试者的病毒载量较高，支气管肺泡灌洗细胞产生的 IFN 受损。结论：我们开发了一种新的 COPD 恶化模型，有力地支持了鼻病毒感染与 COPD 恶化之间的因果关系。干扰素产生受损和中性粒细胞炎症可能是病毒诱导的慢性阻塞性肺病恶化的重要机制。
Rationale: Respiratory virus infections are associated with chronic obstructive pulmonary disease (COPD) exacerbations, but a causative relationship has not been proven. Studies of naturally occurring exacerbations are difficult and the mechanisms linking virus infection to exacerbations are poorly understood. We hypothesized that experimental rhinovirus infection in subjects with COPD would reproduce the features of naturally occurring COPD exacerbations and is a valid model of COPD exacerbations.Objectives: To evaluate experimental rhinovirus infection as a model of COPD exacerbation and to investigate the mechanisms of virus-induced exacerbations.Methods: We used experimental rhinovirus infection in 13 subjects with COPD and 13 nonobstructed control subjects to investigate clinical, physiologic, pathologic, and antiviral responses and relationships between virus load and these outcomes.Measurements and Main Results: Clinical data; inflammatory mediators in blood, sputum, and bronchoalveolar lavage; and viral load in nasal lavage, sputum, and bronchoalveolar lavage were measured at baseline and after infection with rhinovirus 16. After rhinovirus infection subjects with COPD developed lower respiratory symptoms, airflow obstruction, and systemic and airway inflammation that were greater and more prolonged compared with the control group. Neutrophil markers in sputum related to clinical outcomes and virus load correlated with inflammatory markers. Virus load was higher and IFN production by bronchoalveolar lavage cells was impaired in the subjects with COPD.Conclusions: We have developed a new model of COPD exacerbation that strongly supports a causal relationship between rhinovirus infection and COPD exacerbations. Impaired IFN production and neutrophilic inflammation may be important mechanisms in virus-induced COPD exacerbations.