Department of Surgery, Duke University Medical Center, DUMC Box 2605, Durham, NC 27710, USA.
Surg Endosc. 2010 May;24(5):1066-74. doi: 10.1007/s00464-009-0727-5. Epub 2009 Nov 14.
A large number of studies point toward chronic aspiration associated with gastroesophageal reflux disease (GERD) as an important factor involved in the development of asthma, the incidence of which has increased dramatically in industrially developed countries. Recent work suggests that medical intervention aimed at acid blockade is not sufficient to relieve the effects of chronic aspiration on asthma pathology, leaving surgical treatment of the disease as one of the few remaining options. This study examined the effect of chronic aspiration on the airway-associated immune response to allergens using a model of experimentally induced airway hypersensitivity in Balb/c mice.
The mice received aspiration of gastric fluid on days 1, 8, 15, 22, 29, 36, 43, and 50 and were sensitized to ovalbumin by intraperitoneal (IP) injection on days 33 and 47, challenged with aerosolized ovalbumin on day 54, and killed on day 56. Control mice received sham gastric fluid aspirations, sham induction of airway hypersensitivity, or both.
Chronic aspiration of 50 microl murine gastric fluid once per week for 8 weeks had a profound effect on the immune system in the lung, with upregulation of the macrophage/monocyte-associated cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12) and profound downregulation of a broad array of T-cell-associated cytokines including interleukins 2, 4, 5, 6, 10, 13, and 23, as well as interferon-gamma. The aspiration-induced depression of IL-5 production in particular was found only in mice with airway hypersensitivity and not in control mice without airway hypersensitivity.
The results indicate that chronic aspiration of gastric fluid has a profound effect on the nature of the allergic response to aerosolized allergens, suggesting that the aspiration may be an important factor affecting the pathogenesis of asthma.
大量研究表明，胃食管反流病（GERD）相关的慢性误吸是导致哮喘的一个重要因素，在工业化发达国家，哮喘的发病率显著增加。最近的研究表明，旨在抑制胃酸的医学干预并不能充分缓解慢性误吸对哮喘病理的影响，这使得针对这种疾病的手术治疗成为为数不多的选择之一。本研究通过 Balb/c 小鼠实验性气道高敏反应模型，研究了慢性误吸对气道相关免疫应答的影响。
小鼠每天接受胃液体吸入，共 8 周 50 次，并于第 33 天和第 47 天通过腹腔内（IP）注射致敏于卵白蛋白，第 54 天接受雾化卵白蛋白激发，第 56 天处死。对照小鼠接受假胃液体吸入、假气道高敏反应诱导或两者均接受。
每周一次吸入 50 微升鼠胃液体 8 周，对肺部免疫系统产生了深远影响，巨噬细胞/单核细胞相关细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-12（IL-12）上调，广泛的 T 细胞相关细胞因子如白细胞介素 2、4、5、6、10、13 和 23，以及干扰素-γ下调。特别是在气道高敏反应的小鼠中发现，吸入诱导的 IL-5 产生抑制仅见于有气道高敏反应的小鼠，而在无气道高敏反应的对照小鼠中未见。
结果表明，胃液体的慢性误吸对雾化过敏原的过敏反应性质有深远影响，提示误吸可能是影响哮喘发病机制的一个重要因素。
