抗原激发后的哮喘气道高反应性与气道重塑相关而非持续气道炎症

2007/06/27

    抗原激发后的哮喘气道高反应性可持续至两周,炎症细胞浸润和气道重塑可在激发试验24小时后观察到。本研究目的在明确持续气道反应性与气道重塑和炎症浸润的关系。气道活检在激发试验后24小时和七周进行。分析了气道内细胞外基织蛋白、胶元蛋白、热休克蛋白和actin等气道重塑相关蛋白。结果显示,抗原激发的气道高反应性可持续一周,与气道重塑相关的胶元表达等亦可持续到一周,而炎症细(嗜酸性粒细胞、巨噬细胞、中型粒细胞和CD3+T细胞)胞浸润则仅维持24小时,与一周后消失。研究结果表明,在双向反应哮喘过程中,但气道反应性与气道重塑相关,而非炎症浸润细胞。
 
(刘颖格  西安第四军医大学西京医院呼吸内科 710032 摘译)
(Critical Care Medicine 2007;175:896-904)
 
Remodeling and Airway Hyperresponsiveness but Not Cellular Inflammation Persist after Allergen Challenge in Asthma
Harsha H. Kariyawasam, Maxine Aizen, Julia Barkans, Douglas S. Robinson and A. Barry Kay
 
ABSTRACT
 
Rationale: Airway hyperresponsiveness (AHR) increases up to 2 weeks after allergen inhalational challenge of subjects with asthma who show a late-phase asthmatic reaction (dual responders). Cellular inflammation and airway remodeling are increased 24 hours after allergen challenge.
 
Objectives: To determine whether persistence of increased AHR is associated with persistent activation of remodeling and enhanced inflammation.
 
Methods: Fiberoptic bronchoscopy was performed at baseline and at 24 hours and 7 days after allergen inhalational challenge of dual responders with mild–moderate asthma. At each time point, AHR, spirometry, and expression of tenascin (extracellular matrix protein), procollagen I, procollagen III, and heat shock protein (HSP)-47 (markers of collagen synthesis), and {alpha}-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of airway remodeling, together with numbers of mucosal major basic protein–positive eosinophils, CD68+ macrophages, CD3+, CD4+, CD8+ T cells, elastase-positive neutrophils, and tryptase-positive mast cells.
 
Measurements and Main Results: AHR was increased from baseline at 24 hours and 7 days after allergen challenge. Reticular basement membrane tenascin expression was elevated at 24 hours and returned to baseline levels at 7 days. Reticular basement membrane procollagen III expression was significantly elevated at 7 days. Expression of procollagen I, HSP-47, and {alpha}-smooth muscle actin were all higher at 7 days compared with 24 hours. At 24 hours, eosinophil, macrophage, neutrophil, and CD3+ T cells were increased but had returned to baseline by 7 days.
 
Conclusions: In dual responders with asthma, the 24-hour increase in airway wall cellular inflammation after allergen challenge resolves by 7 days, whereas the increases in AHR and markers of remodeling persist.


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