Robinson P J, Hegele R G, Schellenberg R R
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Pediatr Pulmonol. 1996 Oct;22(4):248-54. doi: 10.1002/(SICI)1099-0496(199610)22:4<248::AID-PPUL4>3.0.CO;2-I.
Bronchiolitis due to the respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in the first year of life. It has been suggested that RSV infection may cause subsequent asthma, but a mechanism for this relationship has not been demonstrated. Studies examining the presence of airway reactivity in infants with RSV bronchiolitis are limited by our inability to administer provocative agents such as histamine to such ill infants. This makes a small animal model of this condition a useful tool in which to investigate the pathophysiology of RSV bronchiolitis. We, therefore, evaluated airway responsiveness in vivo and airway morphometric changes in 20 guinea pigs infected by instilling 4,000 plaque-forming units of human RSV virus onto the nasal mucosa under halothane anaesthesia, while 20 control animals received an equivalent volume of sterile cell culture medium. Six days following instillation, 10 infected animals and 10 controls underwent measurements of pulmonary resistance (RL) following increasing doses of inhaled acetylcholine (Ach). These guinea pigs were then sacrificed and the lung and heart removed en bloc for morphometric studies. There were no differences in baseline RL between infected and control groups. At Ach concentrations of 15 and 50 mg/mL, RSV-infected animals had higher RL values than controls (P < 0.05). Fourteen days following RSV instillation no differences in Ach responses were detected in the 10 infected and 10 control animals studied. To determine whether the increase in airway reactivity 6 days after RSV instillation was associated with changes in airway wall morphometry, 125 airways (69 infected, 56 control) were studied. Analysis of wall area, wall area internal to the smooth muscle, or smooth muscle area standardized by the internal perimeter of the airway showed no significant differences between the infected and control airways. These results demonstrated that airway hyperresponsiveness correlated with previously reported histologic changes of acute bronchiolitis 6 days after guinea pigs were infected with human RSV, but neither hyperresponsiveness nor histological changes persisted following resolution of the primary infection. The increased airway reactivity and the previously observed histological changes seen at day 6 following infection was not due to increased airway wall thickness.
呼吸道合胞病毒（RSV）引起的细支气管炎是一岁以内儿童下呼吸道感染最常见的病因。有人提出，RSV感染可能会导致后续哮喘，但这种关系的机制尚未得到证实。由于无法给患病婴儿施用组胺等激发剂，关于RSV细支气管炎婴儿气道反应性的研究受到限制。这使得这种疾病的小动物模型成为研究RSV细支气管炎病理生理学的有用工具。因此，我们评估了20只豚鼠在体内的气道反应性以及气道形态计量学变化，这些豚鼠在氟烷麻醉下通过向鼻粘膜滴注4000个空斑形成单位的人RSV病毒进行感染，而20只对照动物接受等量的无菌细胞培养基。滴注后6天，10只感染动物和10只对照动物在吸入递增剂量的乙酰胆碱（Ach）后测量肺阻力（RL）。然后处死这些豚鼠，将肺和心脏整块取出进行形态计量学研究。感染组和对照组的基线RL没有差异。在Ach浓度为15和50mg/mL时，RSV感染动物的RL值高于对照组（P<0.05）。RSV滴注后14天，在研究的10只感染动物和10只对照动物中未检测到Ach反应的差异。为了确定RSV滴注后6天气道反应性增加是否与气道壁形态计量学变化有关，研究了125条气道（69条感染，56条对照）。对气道壁面积、平滑肌内部的壁面积或通过气道内周长标准化的平滑肌面积的分析显示，感染气道与对照气道之间没有显著差异。这些结果表明，豚鼠感染人RSV后6天，气道高反应性与先前报道的急性细支气管炎组织学变化相关，但在原发性感染消退后，高反应性和组织学变化均未持续存在。感染后第6天观察到的气道反应性增加和先前观察到的组织学变化并非由于气道壁厚度增加。
