光梳光谱技术对PM2.5诱发的呼吸道疾病肺泡炎症检测的研究

PM2.5 (particulate matter) is the major air pollutants in cities. Studies on human anatomy show 96% of the particles deposited in the alveoli are PM2.5 which could lead to alveolar airway inflammation and increase respiratory disease morbidity and mortality. Alveolar inflammation monitoring can provide more direct scientific basis for the early diagnosis of respiratory disease condition assessment and guidance for drug use. Fractional exhaled nitric oxide (FeNO) is recognized as a monitoring index of airway inflammation.Untill now, there is no effective method on clinical direct detection of the alveolar airway inflammation without trauma and invasion. A simple and reliable tool to measure alveolar NO concentration (CalvNO) in daily clinical practice is called for. Frequency-comb spectroscopy is a newly developed technique on spectral detection and analysis with high sensitivity. We develop non-traumatic frequency-comb spectroscopy FeNO method which can be applied to clinic diagnosis and treatment.Laser absorption spectroscopy is an important method used for research in atomic and molecular physics and frequency metrology. It has been successfully applied to the issues of fundamental scientific reasearch and serves as the backbone for numerous applications in physics, chemistry, and biology. Molecular fingerprinting based on the absorption spectroscopy is a powerful analytical method for bio-science and medical science. Light is sent through the sample and record its fingerprinting information by chromatic absorption. Fundamental and applied domains benefit from absorption spectroscopy essentially based on laser and Fourier transform spectroscopies. Time-resolved spectroscopy with wide spectral ranges are achieved with excellent sensitivities. Based on the in linear regression method, the frequency-comb spectroscopy can measure and calculate the patient's FeNO at different flow rate, and obtain the level of bronchogenic NO and alveolar NO which can be used to assess the alveolar airway inflammation. Laser absorption spectroscopy on alveolar inflammation detection has wide prospect of clinical application and will have enormous social and economic benefits.

PM2.5是主要的大气污染物。研究显示，沉积在肺泡内的粒子96%为PM2.5，可导致肺泡炎症，增加呼吸疾病发病率和死亡率。肺泡炎症的监测可为呼吸疾病早期诊断、病情评估及指导用药提供更直接的科学依据。呼出气一氧化氮(FeNO)是反映气道炎症的指标。然而，临床中尚无非创伤性、直接检测肺泡炎症的有效方法。光梳光谱技术是最新的灵敏光谱检测技术。本项目基于"两腔室模型"，采用探测光梳和参考光梳相互拍频，将光学检测信号的频率降低到微波频段，通过微波检测技术即可测量并计算出患者的FeNO，进一步精确测定不同呼气流速下的FeNO，经线性回归得到支气管NO和肺泡NO的含量。开发无创伤性光梳光谱FeNO检测方法并用于临床，对呼吸疾病患者呼出的气体成分和含量进行精确测定，建立人体呼出气中肺泡NO的特征峰和吸收谱的标准光谱数据库和成分分析模型。光梳光谱技术对肺泡炎症检测具广泛临床应用前景，可产生巨大社会经济效益。

第一部分：拟研究呼吸疾病患者呼出气生物分子的痕量分析，直接检测呼出气中肺泡内的一氧化氮（NO）水平的光梳光谱新方法。.本课题通过光梳光谱气体痕量分析的新方法，精确地测定人体呼出气体中的一氧化氮（FeNO）等多种生物分子的痕量。光梳光谱检测气体分析系统先对气体样品进行近红外吸收光谱的探测，获取样品的光谱信息，扫描完成后对信息进行智能识别，读取吸收峰的光谱位置，强度等信息，然后与标准数据库比对，得出样品的组成成分和相应含量，最后经过神经网络算法，结合已完成的数据库就能对患者呼出气体的成分进行识别。光梳光谱新方法的应用依赖于高精度光纤飞秒光梳产生和放大技术，高稳定度的光梳光源和痕量分析单元可提高对机械震动和温度变化的抵抗能力。全光纤型光梳激光的产生、放大和精密控制的单元技术可应用于呼出气NO检测，并可为其在呼吸系统疾病的诊断、治疗评估上提供技术保障。.第二部分：将新研发的光梳光谱新技术应用到临床医学，用于慢性气道炎症患者FeNO检测以评估呼吸疾病的气道炎症。.本研究首先完成了光梳光谱新技术的对照仪器，即传统应用化学电流方法呼出气一氧化氮分析仪检测临床慢性气道疾病患者FeNO；其次，应用研制的“光梳光谱新技术”完成了慢性呼吸疾病患者呼出气体吸收光谱检测。首先临床中收集及测试了460例慢性气道炎症患者FeNO，确定具有临床意义的截断值。同时对上述患者外周血嗜酸细胞、诱导痰、肺功能、哮喘控制测试评分等数据与FeNO相关性、哮喘治疗前后FeNO水平及与FeNO相关致病基因进行了分析。此外，采用光梳光谱新技术完成了4例慢性呼吸疾病患者的呼出气体NO吸收光谱检测并对NO含量进行了定量分析。光梳光谱新技术具有无创、定量、安全、简单、快速，具有可重复性的优点，其将为慢性气道炎症疾病的早期诊断、早期预防、病情监测、疗效判断、指导用药等提供科学依据，是未来呼吸疾病诊治的重要手段。