Joad Jesse P, Kott Kayleen S, Bric John M, Schelegle Edward S, Gershwin Laurel J, Plopper Charles G, Peake Janice L, Pinkerton Kent E
Department of Pediatrics, School of Medicine, University of California at Davis, Davis, CA 95616, USA.
Toxicol Appl Pharmacol. 2008 Jan 15;226(2):153-60. doi: 10.1016/j.taap.2007.09.005. Epub 2007 Sep 16.
Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA)+ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA+ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms.
吸入性糖皮质激素(ICS)被推荐用于治疗哮喘婴儿,包括一些患有间歇性哮喘的婴儿。我们之前发现,将幼年猴子暴露于过敏原/臭氧环境会导致其气道出现类似哮喘的特征。我们评估了ICS对暴露于过敏原/臭氧环境和正常幼年灵长类动物气道的组织学和内在反应性的影响。幼年猴子通过吸入暴露于(1)过滤空气和生理盐水,(2)屋尘螨过敏原(HDMA)+臭氧和生理盐水,(3)过滤空气和ICS(布地奈德)或(4)HDMA+臭氧和ICS。过敏原/臭氧暴露从1月龄开始,ICS从3月龄开始。在6月龄时,使用视频显微镜测定乙酰甲胆碱诱导的近端和远端肺切片气道管腔面积的变化,随后对相同切片进行组织学检查。过敏原/臭氧和ICS均可增加近端气道反应性。过敏原/臭氧使近端和远端气道的嗜酸性粒细胞数量增加,而ICS可降低远端气道的这种作用。在暴露于过敏原/臭氧和空气的猴子中,ICS均可增加远端气道的肺泡附着数量,减少近端气道的黏液分泌,并减少两个气道的上皮体积。ICS可增加暴露于空气的动物气道平滑肌数量,同时减少暴露于过敏原/臭氧的动物气道平滑肌数量。在近端气道中,平滑肌与气道反应性之间以及肺泡附着与反应性之间存在小但显著的正相关。ICS可改变正常气道以及暴露于过敏原/臭氧环境气道的形态和功能,这表明ICS应仅用于有活动症状的婴儿。