肠道、肺部菌群直接或通过肠—肺轴对呼吸系统慢性疾病的影响

人体寄生的微生物与人体为共生关系,数量庞大,并形成不同的微生态系统,影响人体免疫、代谢、内分泌等生理过程。菌群失衡导致微生态紊乱,从而导致相关疾病的发生发展。呼吸系统慢性疾病患者常有肠道菌群和肺部菌群的改变,肠道菌群通过肠—肺轴影响呼吸系统免疫及呼吸系统慢性疾病,肺部菌群的改变导致肺部疾病的同时亦会通过血流引起肠道菌群的变化。近年来随着高通量测序及生物信息学技术的发展,相关研究也越发被重视,本文着重对肠道菌群、肺部菌群通过肠—肺轴或直接在肺部免疫及呼吸系统慢性疾病中所起的作用进行综述。     

调控肺部炎症消退的内源性介质

炎症反应是宿主重要防御机制之一。慢性炎症或过度炎症反应可导致严重的肺部疾病,如哮喘、急性呼吸窘迫综合征等。新近研究表明炎症消退是一个主动过程,炎症的及时消退是防止炎症过强及走向慢性化的关键环节。因此,调控炎症消退的内源性介质成为新的研究热点。促进炎症消退内源性介质的发现不仅为肺部疾病研究提供新视野,也为全新的促炎症消退治疗策略防治肺部疾病提供理论依据。     

缺氧诱导肺损伤的病理机制研究进展

大量研究表明,缺氧造成的肺部代谢功能障碍能够诱导肺组织损伤,最终导致慢性阻塞性肺炎、肺动脉高压等呼吸系统疾病。缺氧引起的氧化应激反应及炎症反应是诱导肺损伤的关键环节,而这些反应与缺氧后激活的活性氧自由基、一氧化氮合酶、细胞因子及NF-κB通路等都有密切联系。国内外学者在这方面进行了大量研究并取得了重要进展,本文就近5年的国外文献报道进行综述。     

冬虫夏草在呼吸系统炎性疾病的药理及临床研究进展

通过近30年国内外相关文献分析,系统总结了冬虫夏草在呼吸系统炎性疾病治疗中的药理和临床研究进展。冬虫夏草及其相关产品在肺部疾病治疗的药理和临床研究广泛,药用历史悠久,总结发现其主要通过调节机体免疫、减少肺部渗出、抑制炎症反应而发挥疗效。为加快冬虫夏草抗呼吸系统炎性疾病的中药新药开发及应用提供了参考资料。     

肠道菌群在肺纤维化疾病中的调节作用

肺纤维化是一种以成纤维细胞增殖及大量细胞外基质及胶原聚集,并伴随炎症损伤为特征的呼吸系统疾病终末期改变。该疾病以肺功能障碍和呼吸衰竭为主要病理基础,发病率逐年上升,目前治疗方法有限。在肠肺之间的功能调控研究中,肠道菌群构成变化引起的机体微生态失调能够通过多种方式影响呼吸系统疾病的进程。本文聚焦于肺纤维化等肺部疾病的肠肺调控研究前沿领域,综述了多种肺纤维化疾病的致病机制、肠道菌群的功能、肠肺双向调节和益生菌群干预治疗等方面的最新进展。此外,本文也提出了该领域目前存在的问题,以期为今后的调控机制探索和治疗药物研发提供有力的理论支持及策略支撑。     

肺部微生态与肺癌的关系

近年来肿瘤相关微生物的研究已成为热点,主要涉及细菌、免疫细胞和肿瘤细胞之间的相互作用、细菌致癌途径及其在肿瘤诊断及治疗意义等方面。随着微生物检测手段的飞速发展,人们发现,肺部具有独特的微生态,越来越多的研究在求证肺部微生态与呼吸系统疾病之间的联系。肺癌目前仍然是威胁人类健康的最常见、预后极差的恶性肿瘤。寻求早期筛查、干预、诊治手段是目前攻克肺癌的重点和难点。肺癌患者的肺微生态有其特征性改变,微生物可能通过产生细菌毒素和其他炎性因子而影响肺癌的发生及发展。本文对肺微生态与肺癌相关性进行了综述,并对今后的研究提出了展望。     

虫草对肺部疾病治疗的研究进展

肺纤维化、慢性阻塞性肺病和哮喘是人类主要的呼吸系统疾病,它们均以肺部或呼吸道的慢性炎症为特征,当前的治疗方法尚不理想并伴随着很多的副作用,人们迫切需要一种更安全的替代疗法。冬虫夏草是我国传统的名贵药用真菌,被广泛用来治疗多种肺部疾病。近年来,冬虫夏草对肺部疾病治疗作用的研究取得了较大进展,本文综述了冬虫夏草、其无性型中国被毛孢(Hirsutella sinensis或Ophicordyceps sinensis)和其他相关虫草及其提取物对肺纤维化、慢性阻塞性肺病、哮喘等肺部疾病治疗作用的研究进展,并介绍了其作用机制的研究成果。     

间充质干细胞外泌体治疗肺部疾病的研究进展

肺部疾病作为一种呼吸系统常见病,与重工业快速发展、环境污染等密切相关,死亡率极高。近来研究发现间充质干细胞(mesenchymal stem cells,MSCs)能够自主归巢至疾病损伤部位、修复受损组织并参与调节全身炎症和免疫反应,在临床上有较好的应用前景。外泌体是一种细胞外膜囊泡,可能通过调节细胞间通讯参与生物系统中的各种活动,分泌至细胞外环境的外泌体也会影响宿主免疫系统。而MSCs外泌体作为MSCs旁分泌过程中的一种介质,携带有蛋白质、脂质、m RNA和microRNA等生物活性物质,比基于细胞的治疗有更高的安全性,其潜在的医学价值受到了研究者的广泛关注。本文综述了近年来研究中MSCs外泌体在常见肺部疾病治疗中的作用机制,将为其在未来的临床应用方面提供依据。     

肺衰老在慢性呼吸系统疾病中的研究进展

细胞衰老是一个极其复杂的过程,其特征表现为线粒体结构功能障碍、端粒缩短、炎症微环境、蛋白稳态失衡、表观遗传改变、DNA损伤修复异常等,进而导致组织和器官的结构、功能损伤并诱发衰老相关疾病的发生和发展。衰老既包括增龄引起的生理性衰老,还包括多种因素所诱发的病理性衰老。值得注意的是,肺作为与外界空气直接接触的靶器官更易于遭受多种刺激而出现病理性早衰,即肺衰老。研究发现在大多数慢性呼吸系统疾病的肺内都存在一定比例的衰老细胞,但是这些衰老细胞诱导肺衰老及其在慢性呼吸系统疾病中作用的内在机制仍很不清楚。本文重点描述了肺衰老的诱因和分类、肺衰老参与慢性呼吸系统疾病的内在机制及抗衰老治疗在慢性呼吸系统疾病中的应用,有望为临床上慢性呼吸系统疾病的防治提供新的研究思路和理论依据。     

动脉钙化发生机制研究进展

动脉钙化是指钙盐沉积在动脉壁组织的一种病理改变,会减少主动脉和支动脉的弹性,改变心血管系统的血液流动力学,导致高血压、主动脉瓣狭窄、心脏肥厚、心肌和下肢缺血、充血性心力衰竭等严重心脑血管疾病发生。动脉钙化在老年人群中是一种常见的疾病。早期研究发现尿毒症患者体内磷酸钙沉积的抑制剂——焦磷酸盐水平升高,故有学者认为钙磷被动地沉积于血管壁是引起血管钙化的主要原因。近年来的研究发现,血管钙化并非简单地由于磷酸钙晶体被动地沉积于血管壁,而是一个与骨发育相似的主动的、可预防和可逆转的高度可调控的生物学过程。动脉钙化的发生受多因素共同调控,但其确切机制尚不清楚,最近发现炎症小体也以某种未知的机制参与钙化调控过程。     

Biomarkers of some pulmonary diseases in exhaled breath

Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to children, including neonates, and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (β₂-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analysers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.     

Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease

BackgroundWhile much is known about the effect of chronic kidney disease (CKD) on composition of body fluids little is known regarding its impact on the gases found in exhaled breath or produced by intestinal microbiome. We have recently shown significant changes in the composition of intestinal microbiome in humans and animals with CKD. This study tested the hypothesis that uremia-induced changes in cellular metabolism and intestinal microbiome may modify the volatile organic metabolites found in the exhaled breath or generated by intestinal flora.MethodsSD rats were randomized to CKD (5/6 nephrectomy) or control (sham operation) groups. Exhaled breath was collected by enclosing each animal in a glass chamber flushed with clean air, then sealed for 45 min and the trapped air collected. Feces were collected, dissolved in pure water, incubated at 37 °C in glass reactors for 24 h and the trapped air collected. Collected gases were analyzed by gas chromatography.ResultsOver 50 gases were detected in the exhaled breath and 36 in cultured feces. Four gases in exhaled breath and 4 generated by cultured feces were significantly different in the two groups. The exhaled breath in CKD rats showed an early rise in isoprene and a late fall in linear aldehydes. The CKD animals' cultured feces released larger amounts of dimethyldisulfide, dimethyltrisulfide, and two thioesters.ConclusionsCKD significantly changes the composition of exhaled breath and gaseous products of intestinal flora.General significanceAnalysis of breath and bowel gases may provide useful biomarkers for detection and progression of CKD and its complications.     

Desaturation of exhaled air in camels

We have found that camels can reduce the water loss due to evaporation from the respiratory tract in two ways: (1) by decreasing the temperature of the exhaled air and (2) by removal of water vapour from this air, resulting in the exhalation of air at less than 100% relative humidity (r.h.). Camels were kept under desert conditions and deprived of drinking water. In the daytime the exhaled air was at or near body core temperature, while in the cooler night exhaled air wat at or near ambient air temperature. In the daytime the exhaled air was fully saturated, but at night its humidity might fall to approximately 75% r.h. The combination of cooling and desaturation can provide a saving of water of 60% relative to exhalation of saturated air at body temperature. The mechanism responsible for cooling of the exhaled air is a simple heat exchange between the respiratory air and the surfaces of the nasal passageways. On inhalation these surfaces are cooled by the air passing over them, and on exhalation heat from the exhaled air is given off to these cooler surfaces. The mechanism responsible for desaturation of the air appears to depend on the hygroscopic properties of the nasal surfaces when the camel is dehydrated. The surfaces give off water vapour during inhalation and take up water from the respiratory air during exhalation. We have used a simple mechanical model to demonstrate the effectiveness of this mechanism.     

呼吸中的疾病诊断标志物及检测技术

人类呼出气体中的各种化合物能提供各种疾病和健康状况的重要信息.近年来,由于红外、电化学、化学发光等新技术的重大突破和质谱仪的使用,使得在极低浓度下精确测量呼出的挥发性有机化合物(VOCs)和气溶胶颗粒成为可能,呼吸检测领域因而取得了重大进展.呼吸检测因其可以作为一种实时、快速和无创的方法来评估和监测各种疾病与健康状况信...     

Exogenous proteins in exhaled human breath condensate

In the course of analysis of protein composition of exhaled breath to diagnose diseases of the respiratory system the problem is raised to distinguish between proteins, expressed in lung tissues and in respiratory tract (endogenous) and those that got into the respiratory system from the ambient air in the process of respiration (exogenous). In this work, an attempt is made to estimate the constitution of exogenous proteins in exhaled air with mass spectrometry and nanoflow high performance liquid chromatography (nano-HPLC). Six months’ indoors isolation of healthy donors with air being cleaned of dust leads to the removal from the spectrum of exhaled proteins of some keratins that are therefore considered to be exogenous. Nonkeratin proteins may also circulate between ambient air and human airways, but their concentration appears to be significantly lower than keratin concentrations (especially than the epidermis keratin). Among nonkeratins, dermicidin seems to be the most significant exogenous protein of the exhaled air. Conclusions concerning the diagnostic value of exhaled proteins can be made only after careful comparison of results of quantitative and qualitative analyses of their normal and pathological composition for a statistically significant sample of donors.     

Exogenic proteins in the human exhaled breath condensate

The analysis of the protein composition of exhaled breath to diagnose diseases of the respiratory system raises a problem of differentiation proteins of expressed in the tissues of the lungs and respiratory tract (endogenous) and got in the respiratory system from the ambient air in the process of respiration (exogenous). In this work an attempt was made to estimate a set of exhaled exogenic proteins by mass spectrometry coupled with nanoflow HPLC. Six-month isolation of healthy donors indoors with air cleaned of dust leads to removal from the spectrum of exhaled proteins of some keratins that are considered therefore to be exogenic. Non-keratin proteins may also circulate between the ambient air and human respiratory ways, but their concentration appears to be significantly lower the keratin concentrations (especially epidermis keratin). Among non-keratins dermcidin seems to be the most significant exogenic protein of exhaled air. The conclusion of the diagnostic value of exhaled proteins can be done only after careful comparison of the results of quantitative and qualitative analysis of their composition in norm and pathology for a statistically significant sample of donors.     

围术期体温监测及保温的现状分析

体温是人体重要的生命体征,其过低或过高都会对患者的预后造成不利影响,在临床中最常见也最容易被忽视的是围术期低体温。围术期长时间的体温过低会引起麻醉苏醒延迟、心律失常、影响切口愈合等多种并发症,增加死亡率,延迟出院时间。体温监测及相应的保温措施对于防治低体温至关重要,围术期及时有效地体温监测能反映病人术中病情的变化,但目前临床中对于体温的监控却普遍重视不足。本文对近年来临床常用的体温监测方法及保温手段做一综述。     

Seasonal Changes in Endotoxin Exposure and Its Relationship to Exhaled Nitric Oxide and Exhaled Breath Condensate pH Levels in Atopic and Healthy Children

Endotoxin, a component of the cell walls of gram-negative bacteria, is a contaminant in organic dusts (house dust) and aerosols. In humans, small amounts of endotoxin may cause a local inflammatory response. Exhaled nitric oxide (eNO) levels, an inflammation indicator, are associated with the pH values of exhaled breath condensate (EBC). This study evaluated seasonal changes on indoor endotoxin concentrations in homes and the relationships between endotoxin exposure and eNO/EBC pH levels for healthy children and children with allergy-related respiratory diseases. In total, 34 children with allergy-related respiratory diseases and 24 healthy children were enrolled. Indoor air quality measurements and dust sample analysis for endotoxin were conducted once each season inside 58 surveyed homes. The eNO, EBC pH levels, and pulmonary function of the children were also determined. The highest endotoxin concentrations were on kitchen floors of homes of children with allergy-related respiratory diseases and healthy children, and on bedroom floors of homes of asthmatic children and healthy children. Seasonal changes existed in endotoxin concentrations in dust samples from homes of children with allergic rhinitis, with or without asthma, and in EBC pH values among healthy children and those with allergy-related respiratory diseases. Strong relationships existed between endotoxin exposure and EBC pH values in children with allergic rhinitis.     

Thermal equilibrium of goats

The effects of air temperature and relative humidity on thermal equilibrium of goats in a tropical region was evaluated. Nine non-pregnant Anglo Nubian nanny goats were used in the study. An indirect calorimeter was designed and developed to measure oxygen consumption, carbon dioxide production, methane production and water vapour pressure of the air exhaled from goats. Physiological parameters: rectal temperature, skin temperature, hair-coat temperature, expired air temperature and respiratory rate and volume as well as environmental parameters: air temperature, relative humidity and mean radiant temperature were measured. The results show that respiratory and volume rates and latent heat loss did not change significantly for air temperature between 22 and 26 °C. In this temperature range, metabolic heat was lost mainly by convection and long-wave radiation. For temperature greater than 30 °C, the goats maintained thermal equilibrium mainly by evaporative heat loss. At the higher air temperature, the respiratory and ventilation rates as well as body temperatures were significantly elevated. It can be concluded that for Anglo Nubian goats, the upper limit of air temperature for comfort is around 26 °C when the goats are protected from direct solar radiation.     

Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide.

Nitric oxide (NO) is released into nasal air, but its function is unknown. We hypothesized that nasal vascular tone and/or flow influences temperature conditioning of nasal air and that NO participates in this process. We measured nasal air temperature (via a thermocouple) and exhaled nasal NO release (by chemiluminescence) in five humans and examined the effects of an aerosolized vasoconstrictor (oxymetazoline), a vasodilator (papaverine), N(G)-nitro-L-arginine methyl ester, an inhibitor of NO synthase, or saline (control). Compared with saline (which caused no changes in nasal air temperature or exhaled NO release), oxymetazoline (0.05%) reduced nasal air temperature and NO release (130.8 +/- 15.1 to 81.3 +/- 12.8 nl. min(-1). m(-2); P < 0.01). Papaverine (0.01 M) increased nasal air temperature and NO release (131.8 +/- 13.1 to 157.2 +/- 17.4 nl. min(-1). m(-2); P < 0.03). N(G)-nitro-L-arginine methyl ester reduced nasal air temperature and NO release (123.7 +/- 14.2 to 44.2 +/- 23.7 nl. min(-1). m(-2); P < 0.01). The results suggest that vascular tone and/or flow modulates temperature conditioning and that NO may participate in that function.