MORPHOLOGICAL CHANGES OF AIRWAY REMODELING AND AIRWAY INFLAMMATION IN BRONCHIAL ASTHMA

支气管哮喘气道重塑和气道炎症的形态变化

• 批准号: 12670554
• 负责人: FUJIMOTO Keisaku
• 金额: $ 2.18万
• 依托单位: SHINSHU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670554/
• 关键词: Bronchial asthma; Airway remodeling; High-resolution computed tomography ( HRCT ); Airwav wall thickness; Air trapping; Epithelial cell; Sputum; Goblet cell metaplasia; 気道過敏性; HRCT; 不可逆性; 気流閉塞; 気管支壁肥厚; Air Trap; MMP

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

本研究的目的是通过高分辨率计算机断层扫描（HRCT）评估显示固定气流阻塞的无症状哮喘患者的气道壁厚度和空气潴留。对24例稳定期和无症状的哮喘患者行HRCT检查，以呼气末和吸气末肺野CT值比值（E/I比值）评价右B1支气管壁厚度和空气潴留。所有患者在HRCT检查前均给予吸入或口服糖皮质激素治疗至少6个月，然后在CT扫描前15 min给予盐酸丙卡特罗20 mcg吸入。吸入β_2受体激动剂15 min后出现固定气流阻塞（% FEV_1 &lt;80%或/和FEV_1 &lt;70%）的14例患者<1%>，其右室壁厚度、B_1垂直切面面积%和E/I比值均显著大于吸入β_2受体激动剂后肺功能正常的10例患者。 ...更多信息 吸入。吸入支气管扩张剂15分钟后测得的% FEV_1与室壁厚度、%室壁面积和E/I比值呈显著负相关。E/I比值与管壁厚度、管壁面积%呈显著正相关。这些发现表明，不可逆的结构变化的气道壁不仅可能发生在大，而且在小气道哮喘患者固定气流阻塞。这意味着HRCT检测支气管壁厚度和空气潴留可为评估哮喘患者气道结构变化提供一种有用的、无创的方法。钙激活氯离子通道（CLCA）家族被认为与气道高反应性和粘液过度分泌有关，已被证实在致敏小鼠气道上皮中表达。为了检测CLCA家族中的CLCA 1是否参与支气管哮喘患者的粘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中CLCA 1的mRNA表达。通过吸入高渗盐水诱导痰。将所得痰液与0.1mM DTT一起孵育，并纯化痰液细胞。将纯化的痰液细胞与ISOGEN混合，提取并纯化痰液细胞的RNA，并使用TaqMan Gold RT-PCR试剂盒逆转录IOOng RNA。使用序列检测仪器通过实时定量PCR测量对应于10 ng总RNA的cDNA样品。计算经GAPDH基因拷贝数校正的CLCA 1基因拷贝数。经GAPDH校正的哮喘患者和健康非吸烟者痰细胞CLCA 1的表达量分别为256.2±89.2和73.3±25.6（CLCA 1X 10^4拷贝/GAPDH拷贝）。CLCA 1基因的表达与健康非吸烟者相比有增高的趋势，但差异无统计学意义。CLCA 1基因表达与病情严重程度、病程长短、肺功能和痰嗜酸性粒细胞增多之间无显著相关性。提示CLCA 1基因在哮喘发病中的作用可能不是很重要，有待进一步研究。少

项目成果

Imamura H: "Two cases of bronchial asthma after treatment with amiodarone"Pqcing Clin Electrophysiol. 24. 1563-1565 (2001)

Imamura H：“胺碘酮治疗后支气管哮喘的两例”Pqcing Clin Electrophysiol。

Imamura H: "Two cases of brunchial asthma after treatment with amiodarone"Pacing Clin Electrophysiol. 24. 1563-1565 (2001)

Imamura H：“胺碘酮治疗后支气管哮喘的两例”起搏临床电生理学。

Honda T.: "Type II pneumocytes are preferentially located along thick elastic fibers forming the framework of human alveoli."Anatomical Record. 258. 34-38 (2000)

Honda T.：“II 型肺细胞优先位于形成人类肺泡框架的厚弹性纤维上。”解剖记录。

Okubo Y: "Cnemotaxis of human CD4^+ eosinophils"Int Arch Allergy Immunol. 125. S19-S21 (2001)

Okubo Y：“人类 CD4^ 嗜酸性粒细胞的趋向性”Int Arch Allergy Immunol。

Honda,T.: "Type II pneumocytes are proferentially located along thick fibers forming the framework of human alveoli"Anatomical Record. 258. 34-38 (2000)

Honda,T.：“II 型肺细胞主要沿着形成人类肺泡框架的粗纤维分布”解剖记录。