Glaab Thomas, Ziegert Michaela, Baelder Ralf, Korolewitz Regina, Braun Armin, Hohlfeld Jens M, Mitzner Wayne, Krug Norbert, Hoymann Heinz G
Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs Str. 1, 30625 Hannover, Germany.
Respir Res. 2005 Nov 25;6(1):139. doi: 10.1186/1465-9921-6-139.
This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice.
Using noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50), we determined early AR (EAR) to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL), dynamic compliance (Cdyn) and EF50 in another group of anesthetized, orotracheally intubated mice.
With both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p < 0.05 versus controls). Dose-response studies to aerosolized methacholine (MCh) were performed in the same animals 48 h later, showing that allergic mice relative to controls were distinctly more responsive (p < 0.05) and revealed acute airway inflammation as evidenced from increased eosinophils and lymphocytes in bronchoalveolar lavage.
We conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF50 method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice.
本研究旨在比较可重复的有创和无创肺功能方法评估完整、自主呼吸的BALB/c小鼠中过敏原特异性和胆碱能气道反应性(AR)的能力。
我们使用无创头出式体容积描记法和呼气中期潮气量下降(EF50),测定清醒小鼠对吸入烟曲霉菌抗原的早期AR(EAR)。在另一组麻醉、经口气管插管的小鼠中,通过有创测定肺电导(GL)、动态顺应性(Cdyn)和EF50来进行平行测量。
两种方法均显示,用烟曲霉菌致敏和激发的过敏性小鼠对烟曲霉菌产生了过敏原特异性EAR(与对照组相比,p < 0.05)。48小时后在同一批动物中进行了雾化乙酰甲胆碱(MCh)的剂量反应研究,结果表明过敏性小鼠相对于对照组反应明显更强(p < 0.05),支气管肺泡灌洗中嗜酸性粒细胞和淋巴细胞增加证明出现了急性气道炎症。
我们得出结论,有创和无创肺功能测试能够检测完整的过敏性小鼠中的过敏原特异性和胆碱能AR。GL和Cdyn的有创测定在灵敏度上更优,而无创EF50方法特别适合对大量清醒小鼠的呼吸功能进行快速且可重复的筛查。