三、哮喘发作的预防和治疗中呼吸道病毒感染的重要性
1.急性病毒感染遗留的慢性改变：急性呼吸道病毒感染对人体可产生较多影响,但大多数患者气道功能可完全恢复,而对哮喘患者呼吸功能可产生明显的、较长时间的恶化。部分患者呼吸道病毒感染控制后存在持续性气流受限,如儿童急性病毒性支气管炎后出现反复发作的喘息［18］。流行病学研究表明，呼吸道病毒感染尤其是RSV、RV、IV、PIV和腺病毒参与哮喘发病。儿童急性RSV支气管炎,其特异性RSV-IgE滴度是预测BHR的指标,RSV-IgE滴度升高伴随着咽喉部冲洗物中LTC4的增加,这些结果证明RSV本身可作为可溶性抗原诱发易感者Ⅰ型高反应性。呼吸道病毒感染可促使易感者发展成BHR,Frick等［19］对13例双亲有变应性 疾病史的儿童进行随访研究,发现其中11例儿童患RSV、RV呼吸道感染后2个月内发展成对非病毒性抗原的BHR。
2.持续／潜在的病毒感染：随着急性呼吸道病毒感染的延续,宿主丧失了完全排出病原微生物的能力,病毒以较低的速率连续不断地繁殖,导致持续／潜在的病毒感染,参与哮喘发病。采用RT-PCR和免疫组化方法,证明豚鼠病毒感染后至少4个月,肺内持续存在RSV基因组及蛋白,尽管最初RSV感染的位点是气道上皮,4个月后病毒蛋白仅能在肺泡巨噬细胞中检出,可能肺泡巨噬细胞是病毒感染持续的来源,造成病毒感染复发。巨噬细胞内RSV能改变宿主对吸入物质的防御机能,触发易感者哮喘发作。与持续病毒感染不同,潜在性病毒感染病毒不复制,但其基因组物质仍存留于宿主,或分离或整合于宿主的基因组,许多引起呼吸道感染的常见病毒都产生潜在感染,增加气道炎症反应,导致BHR及气道狭窄［14］。
3.呼吸道病毒感染的预防展望：呼吸道病毒感染是诱发哮喘发作、使哮喘恶化的重要原因之一,目前尚无确切有效的特异性抗病毒药物,寻找预防呼吸道病毒感染的方法就显得尤为迫切。研究人员正在进行病毒特异性免疫球蛋白(IG)如RSV-IG和病毒疫苗如RSV疫苗以及DNA颗粒多价疫苗等的研制,但由于呼吸道病毒感染的普遍性和病毒自然感染后不能产生持久的免疫保护等因素,临床预防作用和疗效尚不能肯定,亟待深入研究。
1 Teichtahl H, Buckmaster N, Pertnikovs e. The incidence of respiratory tract infection in adults requiring hospitalization for asthma. Chest,1997,112:591-596.
2 Gern JE, Busse WW. The effects of rhinovirus infections on allergic airway reponses. Am J Respir Crit Care Med, 1995,152:40-45.
3 Busse WW, Gern JE. Viruses in asthma. J Allergy Clin Immunol,1997,100:147-150.
4 Busse WW. Viral infections in humans. Am J Respir Crit Care Med,1995,151:1675-1677.
5 Johnston SL, Pattemore PK, Sanderson G,et al. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ, 1995，310:1225-1229.
6 Calhoun WJ, Dick EC, Schwartz LB, et al. A common cold virus, rhinovirus16, potenti ates airway inflammation after segmental antigen bronchoprovocation in allergic subjects. J Clin Invest, 1994,94:2200-2208.
7 Folkerts G, Nijkamp FP. Virus-induced airway hyperresponsiveness. role of inflammatory cells and mediators. Am J Respir Crit Care Med, 1995,151:1666-1674.
8 Welliver RC, Kaul TN, Ogra PL. The appearance of cell-bound IgE in respiratory-tract&127;epithelium after respiratory-syncytial-virus infections. N Engl J Med,1986,303:1198-1202.
9 Gbadero DA, Johnson AW, Aderele WI, et al. Microbial inciters of acute asthma in urban Nigerian children. Thorax, 1995,50:739-745.
10 Hennet T, Ziltener HJ, Frei K, et al. A kinetic of immune mediators in the lungs of mice&127;infected with influenza A virus. J Immunol,1992,149:932-939.
11 Barnett K, Jacoby DB, Nadel JA, et al.&127;The effects of epithelial cell supernatant on contractions of isolated canine tracheal smooth muscle. Am rev Respir Dis, 1988,138:780-783.
12 Hook GER, Brody AR, Cameron GS, et al. Repopulation of denuded tracheas by clara cells isolated from the lungs of rabbits. Exp Lung Res, 1987,12:311-329.
13 Kharitonov& nbsp;SA, Yates D, Barnes PJ. Increased nitric oxide&127;in exhaled air of normal human subjects with upper respiratory tract infections. eur Respir J, 1995,8:295-297.
14 Hegele RG, Hayashi S, Hogg JC, et al. Mechanisms of airway narrowing and hyperresponsiveness in viral respiratory tract infections. Am J Respir Crit Care med, 1995,151:1659-1664.
15 Phelps DS, Floros J. Localization of surfactant protein synthesis in human lung by in situ hybridization. Am Rev Respir Dis, 1988,137:939-942.
16 Barnes PJ. Neuropeptides in the lung: localization, function and pathophysiologic implications. J Allergy Clin Immunol, 1987,79:285-295.
17 Busse WW, Swenson CA, Borden EC, et al. Effect of influenza a virus on leukocyte histamine release. J Allergy Clin Immunol, 1983,71:382-388.
18 Strannegard O, Cello J, Bjarnason R, et al. Association between pronounced igA response in RSV bronchiolitis and development of allergic sensitization. pediatr Allergy Immunol, 1997,8:1-6.
19 Frick OL, German DF, Mills J. Development of allergy in children, i:&127;association with virus infections. J Allergy Clin Immunol,1979,63:228- 241.
