Hilliard Tom N, Regamey Nicolas, Shute Janis K, Nicholson Andrew G, Alton Eric W F W, Bush Andrew, Davies Jane C
Department of Gene Therapy, National Heart and Lung Institute, Imperial College, London, UK.
Thorax. 2007 Dec;62(12):1074-80. doi: 10.1136/thx.2006.074641. Epub 2007 May 25.
The relationship between airway structural changes and inflammation is unclear in early cystic fibrosis (CF) lung disease. A study was undertaken to determine changes in airway remodelling in children with CF compared with appropriate disease and healthy controls.
Bronchoalveolar lavage and endobronchial biopsy were performed in a cross-sectional study of 43 children with CF (aged 0.3-16.8 years), 7 children with primary ciliary dyskinesia (PCD), 26 with chronic respiratory symptoms (CRS) investigated for recurrent infection and/or cough and 7 control children with no lower airway symptoms. Inflammatory cells, cytokines, proteases and matrix constituents were measured in bronchoalveolar lavage fluid (BALF). Reticular basement membrane (RBM) thickness was measured on biopsy specimens using light microscopy.
Increased concentrations of elastin, glycosaminoglycans and collagen were found in BALF from children with CF compared with the CRS group and controls, each correlating positively with age, neutrophil count and proteases (elastase activity and matrix metalloproteinase-9 (MMP-9) concentration). There were significant negative correlations between certain of these and pulmonary function (forced expiratory volume in 1 s) in the CF group (elastin: r = -0.45, p<0.05; MMP-9:TIMP-1 ratio: r = -0.47, p<0.05). Median RBM thickness was greater in the CF group than in the controls (5.9 microm vs 4.0 microm, p<0.01) and correlated positively with levels of transforming growth factor-beta(1) (TGF-beta(1); r = 0.53, p = 0.01), although not with other inflammatory markers or pulmonary function.
This study provides evidence for two forms of airway remodelling in children with CF: (1) matrix breakdown, related to inflammation, proteolysis and impaired pulmonary function, and (2) RBM thickening, related to TGF-beta(1) concentration but independent of other markers of inflammation.
在早期囊性纤维化（CF）肺部疾病中，气道结构变化与炎症之间的关系尚不清楚。开展了一项研究，以确定与适当疾病和健康对照相比，CF患儿气道重塑的变化。
对43例CF患儿（年龄0.3 - 16.8岁）、7例原发性纤毛运动障碍（PCD）患儿、26例因反复感染和/或咳嗽而接受慢性呼吸道症状（CRS）调查的患儿以及7例无下呼吸道症状的对照儿童进行了横断面研究，实施支气管肺泡灌洗和支气管活检。在支气管肺泡灌洗液（BALF）中测量炎性细胞、细胞因子、蛋白酶和基质成分。使用光学显微镜在活检标本上测量网状基底膜（RBM）厚度。
与CRS组和对照组相比，CF患儿BALF中弹性蛋白、糖胺聚糖和胶原蛋白浓度增加，每种物质均与年龄、中性粒细胞计数和蛋白酶（弹性蛋白酶活性和基质金属蛋白酶 - 9（MMP - 9）浓度）呈正相关。在CF组中，其中某些物质与肺功能（1秒用力呼气量）之间存在显著负相关（弹性蛋白：r = -0.45，p<0.05；MMP - 9:TIMP - 1比值：r = -0.47，p<0.05）。CF组的RBM厚度中位数大于对照组（5.9微米对4.0微米，p<0.01），并且与转化生长因子 - β(1)（TGF - β(1)）水平呈正相关（r = 0.53，p = 0.01），尽管与其他炎症标志物或肺功能无关。
本研究为CF患儿气道重塑的两种形式提供了证据：（1）与炎症、蛋白水解和肺功能受损相关的基质分解，以及（2）与TGF - β(1)浓度相关但独立于其他炎症标志物的RBM增厚。
