MORPHOLOGICAL CHANGES OF AIRWAY REMODELING AND AIRWAY INFLAMMATION IN BRONCHIAL ASTHMA

本研究的目的是通过高分辨率计算机断层扫描(HRCT)评估无症状哮喘患者的气道壁厚度和空气滞留情况。对24例缓解期哮喘患者行HRCT扫描，以呼气相和吸气相CT数之比(E/I)为指标，评价右B1期支气管壁厚度和空气滞留。在HRCT检查前，所有患者均吸入糖皮质激素和口服糖皮质激素至少6个月，然后在CT扫描前15min吸入盐酸丙卡特罗20mcg。14例吸入β_2激动剂15分钟后出现固定气流阻塞(FEV_1和/和FEV_1和FEV_1%和F…后肺活量正常的10例患者的B1值和E/I值明显高于正常组更多的吸气。吸入支气管扩张剂后15分钟测得的FEV_1%与室壁厚度、室壁面积百分比、E/I比值呈显著负相关。E/I比值与室壁厚度、室壁面积百分比呈显著正相关。这些发现提示，在有固定气流阻塞的哮喘患者中，不可逆的气道壁结构变化不仅可能发生在大的，也可能发生在小的气道。这意味着在RT时评估气道壁厚度。哮喘患者的B-I型支气管镜和HRCT空气阻滞术为评估呼吸道结构改变提供了一种有用的、非侵入性的手段。钙激活的氯通道(CLCA)家族被认为与气道高反应性和粘膜过度产生有关，已被证明在致敏小鼠的呼吸道上皮细胞中表达。为了探讨CLCA家族中的CLCA1是否参与了哮喘患者的黏液过度产生或气道高反应性，我们检测了21例哮喘患者和13例健康非吸烟者诱导痰细胞CLCA1的mRNA表达。吸入高渗盐水诱导痰。将获得的痰与0.1 mM DTT孵育，纯化痰细胞。将纯化的痰细胞与ISOGEN混合，提取纯化后的痰细胞RNA，用TaqMan Gold RT-PCR试剂盒逆转录得到Loong RNA。使用序列检测仪对对应于10 ng总RNA的CDNA样本进行实时定量聚合酶链式反应。计算经GAPDH基因拷贝校正后的CLCA1基因拷贝数。经GAPDH校正后的哮喘患者和健康非吸烟者痰细胞CLCA1的表达分别为256.2±89.2和73.3±2 5.6(CLCA1X10^4拷贝/GAPDH拷贝)。CLCA1基因的表达与健康非吸烟者相比有升高的趋势，但差异无统计学意义。CLCA1基因的表达与病情严重程度、病程、肺功能和痰嗜酸粒细胞增多之间没有明显的相关性。提示CLCA1基因在哮喘发病机制中的作用可能不大，有待进一步研究。较少

The aim of this study was to evaluate airway wall thickness and air trapping by means of High-Resolution Computed Tomography ( HRCT ) in asymptomatic asthmatics showing fixed airflow obstruction. The bronchial wall thickness of the right B1 bronchus and air trapping which were assessed in terms of the ratio of CT numbers in the lung fields at full expiration and inspiration ( E/I ratio ), were evaluated by means of HRCT of 24 stable and asymptomatic asthmatics. Prior to the HRCT examination, all patients were treated with inhaled corticosteroids /and oral corticosteroids for at least 6 months, and then were given 20mcg procaterol hydrocloride to inhale 15min before CT scanning. In 14 patients who showed fixed airflow obstruction ( % FEV_1 <80 % or/and FEV_<1%> <70 % ) 15 min after the inhalation of β_2 agonists, the wall thickness and % wall area of vertical section of rt. B1 and E/I ratio were significantly greater than those in 10 patients who showed normal spirometric results after … More the inhalation. The wall thickness, % wall area, and E/I ratios showed significantly negative correlation with % FEV_1 measured 15 min after the inhalation ofa bronchodilator. The E/I ratio was also showed significantly positive correlation with the wall thickness and % wall area. These findings suggest that irreversible structural changes of the airway wall may occur not only in large but also in small airways in asthmatics with fixed airflow obstruction. This means that evaluation of airway wall thickness at rt. B I bronchus and air trapping by HRCT in asthmatics may provide a useful and non-invasive means of assessing structural changes in airways.Ca^<2+> activated chloride channel ( CLCA ) family, which is considered to be associated with airway hyperreactivity and mucous overproduction, has been demonstrated to express in airway epithelia in sensitized mouse. In order to examine whether the CLCA1, one of the CLCA families, participates as one factor contributing to mucous overproduction or airway hyperreactivity in patients with bronchial asthma, we measured mRNA expression of CLCA1 on the induced-sputum cells obtained from 21 patients with asthma and 13 healthy non-smokers. Sputum was induced by the inhalation of hypertonic saline. The obtained sputum was incubated with 0.1 mM DTT, and sputum cells were purified. The purified sputum cells were mixed with ISOGEN.RNA from sputum cells was extracted and purified, and lOOng RNA was reverse transcribed using TaqMan Gold RT-PCR Kit. _CDNA samples corresponding 10 ng of total RNA were measured by real-time quantitative PCR using a sequence detection instrument. The copies of CLCA1 gene corrected by the copies of GAPDH gene were calculated. The expressions of CLCA1 corrected by GAPDH of sputum cells from asthma and healthy non-smokers were 256.2±89.2 and 73.3±25.6 ( CLCA1X 10^4 copies/GAPDH copies ). The expression of CLCA1 gene had a tendency to be higher compared with those in healthy non-smokers, but there was no significant difference. There were no significant associations between the CLCA1 gene expression and severity, ill length, pulmonary functions, and sputum eosinophilia. These findings suggest that CLCA1 gene may be not so importantly contribute to the pathogenesis of asthma, and further examination was needed. Less