- 作者列表："Cuthbertson L","Walker AW","Oliver AE","Rogers GB","Rivett DW","Hampton TH","Ashare A","Elborn JS","De Soyza A","Carroll MP","Hoffman LR","Lanyon C","Moskowitz SM","O'Toole GA","Parkhill J","Planet PJ","Teneback CC","Tunney MM","Zuckerman JB","Bruce KD","van der Gast CJ
BACKGROUND:Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF. RESULTS:We tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa. CONCLUSIONS:Our findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF. Video Abstract.
背景: 慢性感染和伴随的气道炎症是囊性纤维化 (CF) 患者发病和死亡的主要原因。尽管 CF 的慢性感染不可否认是多微生物感染，涉及肺部微生物群，但感染监测和控制方法仍然以经典的有氧培养为基础的微生物学为基础。如何利用微生物学指导 CF 气道感染的临床管理仍然是一个至关重要的挑战。在 CF 临床护理中利用微生物组方法的一个关键步骤是了解 CF 肺微生物组的生态学，并确定 CF 微生物组在广泛的肺部疾病中的生态模式。评估来自欧洲和美国 13 个 CF 中心的 299 例患者的痰样本,我们确定了菌群多样性减少与肺功能恶化的新兴关系是否可以被认为是 CF 肺菌群的一种普遍模式，并探索了其作为 CF 肺部疾病状态的信息性指标的潜力。 结果: 我们测试并发现菌群多样性减少与肺功能降低是一种显著的生态模式。此外，多样性的丧失伴随着微生物群优势的增加。随后，我们将患者分层到疾病严重程度增加的肺部疾病类别，以进一步研究微生物群特征与肺功能之间的关系，以及导致微生物群变异的因素。核心类群组成在严重疾病类别内变得高度保守，而更罕见的卫星类群支持在微生物多样性中观察到的高变异性。此外，随着肺功能下降，个体患者的肺部微生物群越来越多地被公认的 CF 病原体所支配。相反，其他细菌，尤其是专性厌氧菌，在肺功能较好的人群中越来越占主导地位。排序分析发现肺功能和抗生素是微生物群和核心及卫星类群组成变异的主要解释因子。发现生物地理学影响更罕见的卫星分类群的获取。 结论: 我们的研究结果表明，菌群多样性和优势，以及优势细菌种类的身份，结合肺功能指标,可作为 CF 中疾病状态的信息性指标。视频摘要。
METHODS:OBJECTIVES:To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS:A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS:A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION:RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified. Key words: rheumatoid arthritis, interstitial lung disease, observational study, rituximab and prognosis
METHODS:The safety of anti-programmed cell death 1 (PD-1) antibody for patients with preexisting interstitial lung disease (ILD) remains unknown. The aim of this study was to evaluate the dependence of preexisting ILD on anti-PD-1 antibody-induced pneumonitis in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the association of preexisting ILD with the incidence, radiographic pattern, and outcome of pneumonitis in NSCLC patients receiving anti-PD-1 antibody. A total of 331 patients were included in this study. Of these patients, 17 had preexisting ILD. The incidence of pneumonitis was higher among the patients with preexisting ILD than among those without preexisting ILD (29% vs. 10%, P = 0.027). The distributions of the CT appearances at the onset of anti-PD-1 antibody-induced pneumonitis were as follows: for the patients with preexisting ILD, two patients (40%) had diffuse alveolar damage (DAD), one patient each with organizing pneumonia-like (OP), hypersensitivity pneumonitis (HP), and other patterns (20% each); for the patients without preexisting ILD, 19 patients (61%) had OP, 8 (26%) had HP, 3 (10%) had DAD, and 1 (3.2%) had other patterns. The median onset time from the initiation of anti-PD-1 antibody treatment until the development of pneumonitis was 1.3 months (range 0.3–2.1 months) for the patients with preexisting ILD and 2.3 months (range 0.2–14.6 months) for the patients without preexisting ILD. Careful attention to the development of pneumonitis is needed, especially within the first 3 months after the start of anti-PD-1 antibody treatment, when using anti-PD-1 antibody to treat patients with preexisting ILD.
METHODS::Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous multidrug resistant organisms and opportunistic pathogens capable of causing life threatening lung infections among cystic fibrosis (CF) patients. No effective therapies are currently available to eradicate Bcc bacteria from CF patients, as these organisms are inherently resistant to the majority of clinically available antimicrobials. An immunoproteomics approach was used to identify Bcc proteins that stimulate the humoral immune response of the CF host, using bacterial cells grown under conditions mimicking the CF lung environment and serum samples from CF patients with a clinical record of Bcc infection. 24 proteins of the Bcc strain B. cenocepacia J2315 were identified as immunoreactive, 19 here reported as immunogenic for the first time. Ten proteins were predicted as extracytoplasmic, 9 of them being conserved in Bcc genomes. The immunogenic Bcc extracytoplasmic proteins are potential targets for development of novel therapeutic strategies and diagnostic tools to protect patients against the onset of chronic Bcc lung infections.