慢性气道疾病气道细菌及真菌群落微生态研究

发布时间：2018-01-01 06:26

本文关键词：慢性气道疾病气道细菌及真菌群落微生态研究　出处：《南方医科大学》2017年博士论文　论文类型：学位论文

【摘要】：背景:慢性气道疾病,主要包括慢性阻塞性肺病(COPD)和哮喘,以气流受限、呼吸困难、气促为主要特征。此类人群气道微生态结构组成与健康人相比较有其独特的特征。早期研究表明了气道微生物与慢性气道疾病急性加重、发展与预后相关联。然早期的研究病例数较少,较少有研究联合分析细菌和真菌生态群落与慢性气道疾病的临床指标的关联。目的:阐述COPD与哮喘人群气道微生态结构组成,探索气道微生态在COPD和哮喘的不同临床事件中发挥作用的机理。方法:我们开展了一个为期2年的横断面研究,并于南方医科大学南方医院、广州呼吸疾病研究所2个地方招募合格的研究志愿者。共纳入COPD 263例,哮喘154例,健康志愿者33例。通过对痰液总DNA的16S rRNA V4片段以及ITS1片段进行扩增,我们详细阐述了 COPD、哮喘以及健康人群的气道微生态群落的主要特征。通过随机森林法将微生态群落运用于疾病的诊断和鉴别诊断,并使用随机森林法挖掘临床事件与气道微生态的关联。此外,我们通过大数据分析和多种统计手段共同挖掘了哮喘同COPD的临床事件与微生态结构组成以及重点种属的关系。结果:不同人群的气道微生态群落的组成结构有其各自的特征。随机森林模型对哮喘和健康人区分的细菌群落和真菌群落的AUC分别为97.70和98.13;COPD与健康人区分的细菌群落和真菌群落的AUC分别为96.91和99.23;哮喘和COPD的鉴别诊断细菌群落和真菌群落的AUC分别为90.33和90.86。COPD急性加重(AECOPD)人群的微生态群落结构与COPD稳定期人群有显著差异,随机森林模型鉴别诊断细菌群落和真菌群落的AUC分别为89.31和86.97。部分临床指标和用药与COPD的微生态群落结构有密切关联,包括血液淋巴细胞、吸入性糖皮质激素+长效β2受体激动剂(ICS+LABA)、长效抗胆碱能药物(LAMA)、氨茶碱、吸烟。另外,假单胞菌属、莫拉氏菌属、肠球菌属、念珠菌属、曲霉菌属在COPD发作和部分临床指标发挥临床作用中起到了较为关键的作用。哮喘的微生态群落结构与其急性加重期关联不大。但是其他临床指标与哮喘患者的微生态群落结构密切相关,包括痰液嗜酸性粒细胞、哮喘控制测试(ACT)评分、吸烟。其中,卟啉单胞菌属、纤毛菌属、念珠菌属在哮喘发作和在部分临床指标发挥临床作用中起到了较为关键的作用。结论:COPD、哮喘、健康人的气道微生态结构各有特征。我们的研究为哮喘的嗜酸性粒细胞型分型、哮喘控制程度、COPD吸入药物导致的肺部感染、COPD的部分炎症因子导致的临床事件以及哮喘/COPD吸烟的病理生理机制的研究提供了微生态学数据的支持。
[Abstract]:Background: chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma, airflow limitation, dyspnea, shortness of breath as the main characteristics of this population. Airway structure and micro ecological health compared to people who have their unique characteristics. The early studies show that airway microorganisms and chronic airway disease associated with acute exacerbation the development and prognosis. Although the number of cases is less, associated with clinical indicators combined with analysis of bacteria and fungi in ecological communities and the chronic airway disease less. Objective: to discuss the airway COPD and asthma micro ecological structure, mechanism of action of play to explore airway Microecology in COPD and asthma in different clinical events. We conducted a cross-sectional study for a period of 2 years, and in the South Hospital of Southern Medical University, the research of Guangzhou Institute of respiratory disease in 2 places to recruit qualified volunteers were satisfied. In 263 cases of COPD, 154 cases of asthma and 33 healthy volunteers. The total DNA was amplified by 16S rRNA sputum V4 fragment and ITS1 fragments, we elaborate on the COPD, the main features of asthma and the healthy airway micro ecological communities. By random forest method of micro ecological community for the diagnosis and differential diagnosis the disease, and the mining association of clinical events and airway micro ecology using random forest method. In addition, through the analysis and several statistical means of big data mining common clinical event of asthma with COPD and micro ecological structure and key species. Results: the structure of different groups of airway micro ecological community has its the features of their own. Random forest model for asthma and healthy people to distinguish between bacterial community and fungal communities in AUC were 97.70 and 98.13; COPD and healthy people distinguish between bacterial community and fungal community A UC were 96.91 and 99.23; asthma and COPD differential diagnosis of bacterial and fungal communities in AUC were 90.33 and 90.86.COPD in acute exacerbation (AECOPD) in micro ecological community structure and stable COPD groups have significant differences, random forest model and differential diagnosis of bacterial community of AUC fungal communities respectively are closely related to micro ecology the community structure of 89.31 and 86.97. and COPD and clinical indicators of medication, including blood lymphocytes, inhaled corticosteroids plus long-acting beta 2 agonists (ICS+LABA), long-acting anticholinergic drugs (LAMA), ammonia tea alkali, smoking. In addition, Pseudomonas, Moraxella, Enterococcus, Candida genus of Aspergillus play a clinical role plays a more key role in the onset of COPD and some clinical indicators of asthma. Micro ecological community structure and its acute exacerbation. But is not associated with other clinical indicators Closely related to the micro ecological community structure of patients with asthma, including sputum eosinophils, asthma control test (ACT) score, smoking. Among them, gingivalis genus Leptotrichia, Candida in asthma and in some clinical parameters play a clinical role played a key role. Conclusion: COPD healthy people, asthma, airway micro ecological structures have different characteristics. Our study divided asthma eosinophil type, the degree of asthma control, COPD inhalation drug induced pulmonary infection, provide support for micro ecology research data lead to some inflammatory factors of COPD clinical events and asthma /COPD smoking pathology the physiological mechanism.

【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R56

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