下呼吸道微生态在支气管哮喘中的研究进展

随着二代测序的不断发展,过去人们认为无菌的下呼吸道现已被证实有多种不同的微生物群落定植.同时,越来越多的研究也证明,微生态在宿主免疫系统的发生发展中起着重要的作用.呼吸道微生态紊乱可能与多种呼吸道疾病密切相关,包括肺结核、COPD及支气管哮喘(简称哮喘)等.该研究主要回顾了近年来对哮喘患者及健康人群呼吸道微生态的研究,探讨在哮喘患者中呼吸道菌群定植的改变趋势,以及呼吸道微生态的改变与哮喘发病机制之间的关系,并且对呼吸道微生态在哮喘治疗中的研究进展进行讨论.     

肠道菌群在过敏性支气管哮喘发生和发展中的作用

过敏性支气管哮喘(简称哮喘)是临床上最常见的过敏性疾病之一,主要与免疫紊乱相关.随着“卫生假说”的提出以及微生态学的发展,近年来肠道正常菌群在过敏性哮喘发生、发展中所发挥的作用逐渐为人们所重视.人们在肠道菌群与免疫调节、菌群失调与哮喘发病风险以及利用微生态制剂预防、治疗哮喘等多方面进行了研究,为治疗并预防哮喘开辟了新的空间.     

呼吸道微生物组的变化及其对哮喘发病的影响

呼吸道微生物组由呼吸道菌群与其宿主细胞以及环境中影响两者相互作用的多种因素构成,如呼吸道菌群的种类、气道免疫细胞、物理化学因素等.越来越多的研究表明,呼吸道微生物组的变化与哮喘的免疫学发病存在一定的关系,对其进行深入的研究可为哮喘的诊治提供新的思路.     

支气管哮喘与细胞免疫

支气管哮喘是多种免疫细胞参与的慢性呼吸道炎症,对各种免疫细胞在支气管哮喘发病中的作用及作用机制的深入研究将提高对支气管哮喘发病机制的认识。     

合并呼吸道感染的支气管哮喘诊治

呼吸道感染与支气管哮喘有密切关系.呼吸道感染可使许多支气管哮喘患者诱发喘息,或使支气管哮喘的临床症状加重.支气管哮喘患者支气管的异常和部分平喘药物均易于引起呼吸道和肺部感染.呼吸道合胞病毒、鼻病毒等可引起喘息症状.该文讨论了呼吸道病毒感染诱发支气管哮喘的机制、临床特点和诊治方法.     

呼吸道合胞病毒与支气管哮喘

支气管哮喘是严重危害人类健康的呼吸系统疾病之一,研究表明,呼吸道合胞病毒(RSV)是成人及婴幼儿下呼吸道感染最常见的病原体之一;近年来研究显示,RSV感染是儿童支气管哮喘发生的重要危险因素之一,并可引起成人哮喘喘息症状加重,鉴于RSV感染在支气管哮喘发生、发展中的重要作用,本人将从RSV感染及其由此导致的免疫功能失常、AHR、黏液分泌等方面加以综述。     

下呼吸道微生物菌群对宿主免疫的影响

随着细菌鉴定技术的发展,健康成年人下呼吸道存在常驻微生物菌群的观点逐渐受到认可.这类微生物菌群具有调节天然免疫和获得性免疫反应的作用.在呼吸道疾病如哮喘、COPD的发生发展过程中,宿主下呼吸道微生态环境发生改变,免疫状态也发生了改变,但两者之间的关系尚不明确.我们将围绕下呼吸道微生物菌群对宿主免疫系统的影响进行阐述,以探讨影响呼吸道疾病发生发展的因素.     

气道微生态与哮喘气道免疫反应研究进展

支气管哮喘（简称哮喘）是最常见的慢性气道疾病之一,全球3亿多人患有哮喘。近年来,有研究表明,与健康人相比,哮喘患者的气道微生态结构以及各菌群的相对丰度均发生了改变,且与哮喘气道炎症表型相关。气道微生态可以通过免疫反应影响哮喘的发生发展。气道微生态与哮喘相互作用的机制可以为哮喘精准治疗提供新的思路。本文主要对目前气道微生...     

肺泡Ⅱ型上皮细胞与支气管哮喘

支气管哮喘是多种细胞参与的一种小儿常见的慢性呼吸道炎症性疾病。最近研究表明 ,肺泡Ⅱ型上皮细胞 (AT Ⅱ )不仅是支气管哮喘发病过程中的受累细胞 ,也是重要的参与细胞之一。其可合成和分泌肺泡表面活性物质 (PS)、细胞因子、黏附分子和炎症介质而参与哮喘气道慢性炎症过程的发生和气道反应性增高的改变。本文就AT Ⅱ与哮喘关系作一综述 ,以提高对哮喘气道炎症状态的认识 ,促进对哮喘发病机制的研究。     

围手术期支气管哮喘的处理

支气管哮喘是一种对多种刺激发生反应的慢性呼吸道炎症性疾病.目前,全世界有约2亿支气管哮喘患者,而且发病率在逐年上升,所以,支气管哮喘患者恰当的围手术期的治疗显得尤为重要.支气管哮喘患者围手术期肺部并发症的发病风险高,这些并发症导致严重的病死率.因此,在围手术期控制好支气管哮喘、防治肺部并发症对提高手术成功率十分重要.     

Asthma Microbiome Studies and the Potential for New Therapeutic Strategies

Recent applications of culture-independent tools for microbiome profiling have revealed significant relationships between asthma and microbiota associated with the environment, gut, or airways. Studies of the airway microbiome in particular represent a new frontier in pulmonary research. Although these studies are relatively new, current evidence suggests the possibility of new therapeutic strategies for the treatment or prevention of asthma. In this article, recent literature on microbiota and asthma are critically reviewed, with a particular focus on studies of the airway microbiome. Perspectives are presented on how growing knowledge of relationships between the microbiome and asthma is likely to translate into improved understanding of asthma pathogenesis, its heterogeneity, and opportunities for novel treatment approaches.     

Microbiome in the primary prevention of allergic diseases and bronchial asthma

Tremendous progress in the ability to identify and test the function of microorganisms in recent years has led to a much better understanding of the role of environmental and host microbiome in the development of immune function, allergic sensitization and asthma. In this review, the most recent findings on the relationships between environmental microbiota, respiratory, intestinal microbiome, the consequences of early-life microbial exposure type and gut–lung microbial axis and the development of asthma and atopy are summarized. The current perspective on gut and airway microbiome manipulation for the primary prevention of allergic diseases and asthma is also discussed.     

Lactobacillus rhamnosus probiotic prevents airway function deterioration and promotes gut microbiome resilience in a murine asthma model

ABSTRACT

Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity and deterioration of airway function. Immunomodulatory probiotic bacteria are increasingly being explored to prevent asthma development, alone or in combination with other treatments.

In this study, wild-type and recombinant probiotic Lactobacillus rhamnosus GR-1 were tested as preventive treatment of experimental allergic asthma in mice. Recombinant L. rhamnosus GR-1 was designed to produce the major birch pollen allergen Bet v 1, to promote allergen-specific immunomodulation. Administration of wild-type and recombinant L. rhamnosus GR-1 prevented the development of airway hyperreactivity. Recombinant L. rhamnosus GR-1 also prevented elevation of airway total cell counts, lymphocyte counts and lung IL-1β levels, while wild-type L. rhamnosus GR-1 inhibited airway eosinophilia. Of note, a shift in gut microbiome composition was observed after asthma development, which correlated with the severity of airway inflammation and airway hyperreactivity. In the groups that received L. rhamnosus GR-1, this asthma-associated shift in gut microbiome composition was not observed, indicating microbiome-modulating effects of this probiotic.

These data demonstrate that L. rhamnosus GR-1 can prevent airway function deterioration in allergic asthma. Bet v 1 expression by L. rhamnosus GR-1 further contributed to lower airway inflammation, although not solely through the expected reduction in T helper 2-associated responses, suggesting involvement of additional mechanisms. The beneficial effects of L. rhamnosus GR-1 correlate with increased gut microbiome resilience, which in turn is linked to protection of airway function, and thus further adds support to the existence of a gut-lung axis.     

The contribution of respiratory microbiome analysis to a treatable traits model of care

The composition of the airway microbiome in patients with chronic airway diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cystic fibrosis (CF), has the potential to inform a precision model of clinical care. Patients with these conditions share overlapping disease characteristics, including airway inflammation and airflow limitation. The clinical management of chronic respiratory conditions is increasingly moving away from a one‐size‐fits‐all model based on primary diagnosis, towards care targeting individual disease traits, and is particularly useful for subgroups of patients who respond poorly to conventional therapies. Respiratory microbiome analysis is an important potential contributor to such a ‘treatable traits’ approach, providing insight into both microbial drivers of airways disease, and the selective characteristics of the changing lower airway environment. We explore the potential to integrate respiratory microbiome analysis into a treatable traits model of clinical care and provide a practical guide to the application and clinical interpretation of respiratory microbiome analysis.     

The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review

Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early‐life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early‐life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies.

     

Obesity and severe asthma

Obesity is an important global health issue for both children and adults. Obesity increases the prevalence and incidence of asthma and also increases the risk for severe asthma. Here we describe the features of severe asthma phenotypes for which obesity is a defining characteristic, including steroid resistance, airway inflammation, and co-morbidities. We also review current concepts regarding the mechanistic basis for the impact of obesity in severe asthma, including possible roles for vitamin D deficiency, systemic inflammation, and the microbiome. Finally, we describe data indicating a role for diet, weight loss, and exercise in the treatment of severe asthma with obesity. Better understanding of the mechanistic basis for the role of obesity in severe asthma could lead to new therapeutic options for this population.     

A multidimensional approach to the management of severe asthma: Inflammometry,molecular microbiology and bronchial thermoplasty

The authors illustrate the merits of identifying the components of diseases (eg, bronchitis and airway hyper-responsiveness) that contribute to exacerbations in the management of a patient with severe asthma. Quantitative cell counts in sputum identified a neutrophilic – as opposed to eosinophilic – bronchitis that enabled a stepwise weaning of prednisone. Molecular microbiology and extended culture methods identified anaerobes and other airway microbiome that helped to guide the use of antibiotics. Further control of asthma was achieved by performing bronchial thermoplasty.     

Role of airway epithelial cells in development of asthma and allergic rhinitis

Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.     

Airway hyperresponsiveness: the usefulness of airway hyperresponsiveness testing in epidemiology,in diagnosing asthma and in the assessment of asthma severity

The present PhD thesis was conducted at the Respiratory Research Unit at the Pulmonary Department L in Bispebjerg Hospital, Copenhagen, Denmark and describes airway hyperresponsiveness in asthma patients in four studies. The first study concerned risk factors for the development of asthma in young adults in a 12‐year prospective follow‐up study of a random population sample of 291 children and adolescents from Copenhagen, who were followed up from the age of 7–17 years (1986) until the age of 19–29 years (1998). During follow‐up, 16.1% developed asthma, and in these subjects, the most important predictor of asthma development was airway hyperresponsiveness to histamine at baseline. Airway hyperresponsiveness is associated with more severe asthma and a poorer prognosis in terms of more exacerbations and less chance of remission of the disease. The second study described the relation between airway hyper‐responsiveness to methacholine and the quality of life in 691 asthma patients: In asthma patients with airway hyperresponsiveness to methacholine, the quality of life measured with a validated questionnaire (Junipers Asthma Quality of Life Questionnaire) was significantly reduced compared to asthma patients who did not respond to bronchial provocation with methacholine. Airway hyperresponsiveness is not uncommonly observed in non‐asthmatics, and the response to bronchial provocation with methacholine is therefore relatively non‐specific. The mannitol test is a relatively new bronchial provocation test that acts indirectly on the smooth airway muscle cells through the release of mediators from inflammatory cells in the airways; the mannitol could consequently be a more specific test compared with methacholine. The third study showed that out of 16 non‐asthmatics with airway hyperresponsiveness to methacholine, 15 did not respond to bronchial provocation with mannitol Because of the mechanism of action of mannitol, it seems plausible that the response to mannitol is more closely correlated to airway inflammation in asthma compared with the response to methacholine. The fourth study showed that in 53 adult asthma patients, who did not receive treatment with inhaled steroids, there was a positive correlation between the degree of airway inflammation and the degree of airway responsiveness to mannitol as well as to methacholine. The mannitol does, however, have the advantage of being a faster and simpler test to perform, requiring no additional equipment apart from a spirometer. Conclusions: Airway hyperresponsiveness in children and in adolescents without asthma predicts asthma development in adulthood. Asthma patients with airway hyperresponsiveness to methacholine have a poorer quality of life as well as more severe disease and a poorer prognosis compared with asthma patients without airway hyperresponsiveness. Bronchial provocation with mannitol as well as with methacholine were useful for evaluating the severity of asthma and the degree of airway inflammation, and accordingly for determining the need for steroid statement. The mannitol test does, however, have practical advantages over the methacholine test that make it preferable for clinical use.