Risk Factor Evaluation for Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa in Community-Acquired Pneumonia.
- 作者列表："Lewis PO
:Background: The 2019 community-acquired pneumonia guidelines recommend using recent respiratory cultures and locally validated epidemiology plus risk factor assessment to determine empirical coverage of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Objective: To develop a methodology for evaluating local epidemiology and validating local risk factors for P aeruginosa and MRSA. Methods: This multicenter, retrospective cohort evaluated adult patients admitted for pneumonia. Risk factors for MRSA and P aeruginosa were evaluated using multivariable logistic regression and reported as adjusted odds ratios (aORs). Results: There were 10 723 cases evaluated. Lung abscess/empyema had the highest odds associated with MRSA (aOR = 4.24; P < 0.0001), followed by influenza (aOR = 2.34; P = 0.01), end-stage renal disease (ESRD; aOR = 2.09; P = 0.006), illicit substance use (aOR = 1.7; P = 0.007), and chronic obstructive pulmonary disease (COPD; aOR = 1.26; P = 0.04). For P aeruginosa, the highest odds were in bronchiectasis (aOR = 6.13; P < 0.0001), lung abscess/empyema (aOR = 3.36; P = 0.005), and COPD (aOR = 1.84; P < 0.0001). Isolated COPD without other risk factors did not pose an increased risk of either organism. Conclusion and Relevance: Influenza, ESRD, lung abscess/empyema, and illicit substance use were local risk factors for MRSA. Bronchiectasis and lung abscess/empyema were risk factors for Pseudomonas. COPD was associated with MRSA and Pseudomonas. However, isolated COPD had similar rates of MRSA and Pseudomonas pneumonia compared with the total population. This study established a feasible methodology for evaluating local risk factors.
背景: 2019 社区获得性肺炎指南推荐使用最近的呼吸道培养和当地验证流行病学学加危险因素评估来确定耐甲氧西林金黄色葡萄球菌 (MRSA) 和铜绿假单胞菌的经验覆盖率。目的: 建立评价当地铜绿假单胞菌和 MRSA 流行病学学和验证当地危险因素的方法。方法: 本多中心、回顾性队列研究评估了因肺炎入院的成人患者。使用多变量 logistic 回归评估 MRSA 和铜绿假单胞菌的危险因素，并报告为调整优势比 (aORs)。结果: 共评价 10 723 例。肺脓肿/脓胸与 MRSA 相关的几率最高 (aOR = 4.24; P <0.0001)，其次是流感 (aOR = 2.34; P = 0.01),终末期肾病 (ESRD; aOR = 2.09; P = 0.006) 、违禁药物使用 (aOR = 1.7; P = 0.007) 、和慢性阻塞性肺疾病 (COPD; aOR = 1.26; P = 0.04)。铜绿假单胞菌中支气管扩张 (aOR = 6.13; P < 0.0001) 、肺脓肿/脓胸 (aOR = 3.36; P = 0.005) 、和 COPD (aOR = 1.84; P <0.0001)。无其他危险因素的孤立性 COPD 不会增加任何一种微生物的风险。结论和相关性: 流感、 ESRD 、肺脓肿/脓胸和非法药物使用是 MRSA 的局部危险因素。支气管扩张和肺脓肿/脓胸是假单胞菌属的危险因素。COPD 与 MRSA 和假单胞菌相关。然而，与总人口相比，孤立性 COPD 的 MRSA 和假单胞菌肺炎发生率相似。本研究建立了一种可行的评价局部危险因素的方法学。
METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.
METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.