Altered microRNA Signatures in Sputum of Patients with Active Pulmonary Tuberculosis

Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differentially expressed between tuberculosis group and controls. More miRNAs (52 out of 95 miRNAs) were underexpressed than overexpressed during tuberculosis infection. Overexpression of miR-3179, miR-147 and underexpression of miR-19b-2* in TB group compared with controls were confirmed in the validation cohort. TNF-α and IL-6 levels were not significantly altered between TB group and controls. For the first time, differential expression of miRNAs in sputum was found in active pulmonary tuberculosis. The study provides rationale for identifying the role of miRNAs in the pathogenesis of pulmonary tuberculosis and indicates potential for miRNA-based therapeutic strategies.     

Blood Neutrophil Counts in HIV-Infected Patients with Pulmonary Tuberculosis: Association with Sputum Mycobacterial Load

Background

Increasing evidence suggests that neutrophils play a role in the host response to Mycobacterium tuberculosis. We determined whether neutrophil counts in peripheral blood are associated with tuberculosis (TB) and with mycobacterial load in sputum in HIV-infected patients.

Methodology/Principal Findings

Adults enrolling in an antiretroviral treatment (ART) clinic in a Cape Town township were screened for TB regardless of symptoms. Paired sputum samples were examined using liquid culture, fluorescence microscopy, and the Xpert MTB/RIF assay. Absolute neutrophil counts (ANC) were measured in blood samples. Of 602 HIV-infected patients screened, 523 produced one or more sputum samples and had complete results available for analysis. Among these 523 patients, the median CD4 count was 169×10⁹/L (IQR, 96–232) and median ANC was 2.6×10⁹/L (IQR, 1.9–3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients. Patients with TB had a median ANC of 3.4×10⁹/L (IQR, 2.4–5.1) compared to 2.5×10⁹/L (IQR, 1.8–3.4) among those who were culture negative (p<0.0001). In multivariable analyses, having pulmonary TB was associated with an adjusted risk ratio (aRR) of 2.6 (95%CI, 1.5–4.5) for having an ANC level that exceeded the median value (ANC ≥2.6×10⁹/L; p = 0.0006) and an aRR of 6.8 (95%CI, 2.3–20.4) for having neutrophilia defined by a neutrophil count exceeding the upper limit of the normal range (ANC >7.5×10⁹/L; p = 0.0005). Patients were then classified into four mutually exclusive groups with increasing sputum mycobacterial load as defined by the results of culture, Xpert MTB/RIF and sputum smear microscopy. Multivariable analyses demonstrated that increasing sputum mycobacterial load was positively associated with blood ANC ≥2.6×10⁹/L and with neutrophilia.

Conclusions/Significance

Increased blood neutrophil counts were independently associated with pulmonary TB and sputum mycobacterial burden in this HIV-infected patient group. This observation supports the growing body of literature regarding the potential role for neutrophils in the host response to TB.     

肺结核患者血细胞结果特点分析

目的:为肺结核的诊断及观察预后提出新的思路。方法:对新住院肺结核患者的血常规标本400份及以上患者出院前血常规标本400份,使用MEK-6318K血细胞分析仪检测分析。结果:新住院400例肺结核患者中血小板计数>300×109/L的92例,占23%。92例血小板计数升高的患者中,除9例贫血患者外,83例患者中红细胞计数和血红蛋白量都不低于参考值,但红细胞计数和血红蛋白量呈现不一致性,即针对血红蛋白量而红细胞计数偏高,体现出小红细胞少量增多,这种情况在83例中所占比例为86%。出院前400例肺结核患者血小板计数>300×109/L的5例,占1.2%。结论:由于肺结核患者大多数伴有营养不良,导致造血系统功能障碍,导致小红细胞少量增多,增多的小红细胞被血细胞分析仪计数到血小板计数里,导致血小板计数偏高。这个指标在肺结核诊断中意义很大,为肺结核的诊断探索出新的思路。     

Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology

Invasive pulmonary aspergillosis (IPA) is a leading cause of morbidity and mortality in haematological malignancy patients and hematopoietic stem cell transplant recipients¹. Detection of IPA represents a formidable diagnostic challenge and, in the absence of a ''gold standard'', relies on a combination of clinical data and microbiology and histopathology where feasible. Diagnosis of IPA must conform to the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycology Study Group (EORTC/MSG) consensus defining "proven", "probable", and "possible" invasive fungal diseases². Currently, no nucleic acid-based tests have been externally validated for IPA detection and so polymerase chain reaction (PCR) is not included in current EORTC/MSG diagnostic criteria.Identification of Aspergillus in histological sections is problematic because of similarities in hyphal morphologies with other invasive fungal pathogens³, and proven identification requires isolation of the etiologic agent in pure culture. Culture-based approaches rely on the availability of biopsy samples, but these are not always accessible in sick patients, and do not always yield viable propagules for culture when obtained.An important feature in the pathogenesis of Aspergillus is angio-invasion, a trait that provides opportunities to track the fungus immunologically using tests that detect characteristic antigenic signatures molecules in serum and bronchoalveolar lavage (BAL) fluids. This has led to the development of the Platelia enzyme immunoassay (GM-EIA) that detects Aspergillus galactomannan and a ''pan-fungal'' assay (Fungitell test) that detects the conserved fungal cell wall component (1 →3)-β-D-glucan, but not in the mucorales that lack this component in their cell walls^1,4. Issues surrounding the accuracy of these tests^1,4-6 has led to the recent development of next-generation monoclonal antibody (MAb)-based assays that detect surrogate markers of infection^1,5.Thornton⁵ recently described the generation of an Aspergillus-specific MAb (JF5) using hybridoma technology and its use to develop an immuno-chromatographic lateral-flow device (LFD) for the point-of-care (POC) diagnosis of IPA. A major advantage of the LFD is its ability to detect activity since MAb JF5 binds to an extracellular glycoprotein antigen that is secreted during active growth of the fungus only⁵. This is an important consideration when using fluids such as lung BAL for diagnosing IPA since Aspergillus spores are a common component of inhaled air. The utility of the device in diagnosing IPA has been demonstrated using an animal model of infection, where the LFD displayed improved sensitivity and specificity compared to the Platelia GM and Fungitell (1 → 3)-β-D-glucan assays⁷.Here, we present a simple LFD procedure to detect Aspergillus antigen in human serum and BAL fluids. Its speed and accuracy provides a novel adjunct point-of-care test for diagnosis of IPA in haematological malignancy patients.     

Early and Efficient Detection of Mycobacterium tuberculosis in Sputum by Microscopic Observation of Broth Cultures

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein–Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7–13), versus 21 days (IQR 14–28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US $11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings.     

Sputum IgE and Cytokines in Asthma: Relationship with Sputum Cellular Profile

Background

Local IgE production may play a role in asthma pathogenesis. The aim of the study was to assess sputum total IgE and cytokines in asthmatics according to sputum cellular phenotype.

Methods

We studied 122 subjects including 22 non atopic healthy subjects, 41 eosinophilic (sputum eosinophils ≥3%), 16 neutrophilic (sputum neutrophils >76%) and 43 pauci-granulocytic asthmatics (sputum eosinophils <3% and sputum neutrophils ≤76%) recruited from the asthma clinic at CHU Liege.Sputum supernatant total IgE (tIgE) was measured by ImmunoCAP and sputum supernatant cytokines (IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ and TNF-α) were measured with the Luminex xMAP Technology by using commercially available Fluorokine MAP kits.

Results

After concentrating sputum samples, total IgE was detectable in the majority of subjects. Sputum IgE was raised in asthmatics when compared to healthy subjects. Overall, asthmatics did not significantly differ from healthy subjects with respect to cytokine levels. The eosinophilic asthma phenotype, however, was characterised by raised sputum tIgE, IL-5 and IL-13 compared to healthy subjects (p<0.001, p<0.001 and p<0.05 respectively) and pauci-granulocytic asthma (p<0.01, p<0.001 and p<0.05 respectively) and raised IL-5 compared to neutrophilic asthma (p<0.01). When patients were classified according to sputum IgE levels, it appeared that IL-5, IL-6, IL-17 and TNF-α sputum supernatant levels were raised in the “IgE high” asthmatics (IgE ≥0.1 kU/l) when compared to “IgE low” asthmatics (IgE<0.1 kU/l).

Conclusion

The eosinophilic asthma phenotype was associated with raised sputum IgE and a Th2 cytokine profile. Raised sputum IgE was associated with a heterogeneous cytokine overproduction.     

Factors Affecting Time to Sputum Culture Conversion in Adults with Pulmonary Tuberculosis: A Historical Cohort Study without Censored Cases

Background

In patients with pulmonary tuberculosis (TB), shortening the time to sputum culture conversion is desirable to reduce the likelihood of mycobacterial transmission. A persistent positive sputum culture after 2 months of treatment is reported to be associated with the presence of cavitation and the extent of disease on chest X-ray, high colony count, diabetes mellitus, and smoking. However, little is known about factors affecting the time to sputum culture conversion. This study was conducted to evaluate factors affecting the time to sputum culture conversion throughout the course of treatment in adults with pulmonary TB.

Methods

This study was performed using a database of the medical records of patients with active pulmonary TB who were treated at Hirakata Kohsai Hospital in Hirakata City, Osaka, Japan, from October 2000 to October 2002. Cox proportional-hazards analysis was used to evaluate factors affecting the time to sputum culture conversion after adjusting for potential confounders.

Results

The data of 86 patients with pulmonary TB were analyzed. The median time to sputum culture conversion was 39 days, and the maximum time was 116 days. The Cox proportional-hazards analysis showed that a higher smear grading (HR, 0.40; 95%CI, 0.23–0.71) and a history of ever smoking (HR, 0.48; 95%CI, 0.25–0.94) were associated with delayed sputum culture conversion.

Conclusion

High smear grading and smoking prolonged the time to sputum culture conversion in adults with pulmonary TB. To effectively control TB, measures to decrease the cigarette smoking rate should be implemented, in addition to early detection and timely anti-TB treatment.     

Mycobactericidal Activity of Sutezolid (PNU-100480) in Sputum (EBA) and Blood (WBA) of Patients with Pulmonary Tuberculosis

Rationale

Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients.

Methods

Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv.

Results

All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy''s criteria for serious liver injury.

Conclusions

The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01225640","term_id":"NCT01225640"}}NCT01225640     

Conflicting Role of Sarcopenia and Obesity in Male Patients with Chronic Obstructive Pulmonary Disease: Korean National Health and Nutrition Examination Survey

Objective

To determine the impact of sarcopenia and obesity on pulmonary function and quality of life (QOL) in chronic obstructive pulmonary disease (COPD) patients.

Research Design and Methods

Data were obtained from the Korea National Health and Nutrition Examination Survey, including data from health interviews, health examinations, nutritional questionnaires, and laboratory findings. Laboratory data included pulmonary function assessment and dual energy X-ray absorptiometry results. Sarcopenia was measured by dual energy X-ray absorptiometry, and obesity was defined by body mass index. Male COPD patients were then classified into 4 groups according to the presence of sarcopenia and obesity.

Results

In male patients with COPD, the prevalence of sarcopenia was found to be 29.3%, and that of sarcopenic obesity was 14.2%. Furthermore, 22.5% of the patients observed in this study had impaired QOL. Following multivariable statistical analysis, both sarcopenia and obesity were independent risk factors for worsening lung function. Adjusted values of forced vital capacity and forced expiratory volume in 1 second were the lowest in the sarcopenic obesity group. Sarcopenia was also associated with more subjective activity limitation and poorer QOL; however obesity was related to less subjective limitation and better QOL after multivariable analysis. Adjusted value of QOL was the lowest in sarcopenic subjects without obesity, and the highest in obese subject without sarcopenia.

Conclusions

Both sarcopenia and obesity were found to be associated with worsening lung function in male COPD patients. However, obesity was positively correlated with improved QOL while sarcopenia was negatively correlated with QQL.     

Randomized Clinical Trial of Thrice-Weekly 4-Month Moxifloxacin or Gatifloxacin Containing Regimens in the Treatment of New Sputum Positive Pulmonary Tuberculosis Patients

Background

Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.

Methods

Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.

Results

Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.

Conclusions

4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.

Trial Registration

Clinical Trials Registry of India CTRI/2012/10/003060     

Magnetotactic Bacteria in Microcosms Originating from the French Mediterranean Coast Subjected to Oil Industry Activities

Magnetotactic bacteria (MTB) mineralize nanosized magnetite or greigite crystals within cells and thus play an important role in the biogeochemical process. Despite decades of research, knowledge of MTB distribution and ecology, notably in areas subjected to oil industry activities, is still limited. In the present study, we investigated the presence of MTB in the Gulf of Fos, French Mediterranean coast, which is subjected to intensive oil industry activities. Microcosms containing sediments/water (1:2, v/v) from several sampling sites were monitored over several weeks. The presence of MTB was revealed in five of eight sites. Diverse and numerous MTB were revealed particularly from one site (named CAR), whilst temporal variations of a homogenous magnetotactic cocci population was shown within the LAV site microcosm over a 4-month period. Phylogenetic analysis revealed that they belonged to Alphaproteobacteria, and a novel genus from the LAV site was evidenced. Among the physicochemical parameters measured, a correlation was shown between the variation of MTB abundance in microcosms and the redox state of sulphur compounds.     

Prophylaxis and Treatment of Pneumocystis jiroveci Pneumonia in Lymphoma Patients Subjected to Rituximab-Contained Therapy: A Systemic Review and Meta-Analysis

Pneumocystis jiroveci pneumonia (PCP) is frequently reported in lymphoma patients treated with rituximab-contained regimens. There is a trend toward a difference in PCP risk between bi- and tri-weekly regimens. The aims of this systemic review and meta-analysis were to estimate the risk for PCP in these patients, compare the impact of different regimens on the risk, and evaluate the efficacy of prophylaxis. The cohort studies with incept up to January 2014 were retrieved from the Cochrane Library, Medline, Embase, and Web of Science databases. Studies that compared the incidence of PCP in patients with and without rituximab treatment were conducted. Studies that reported the results of prophylaxis were concentrated to evaluate the efficacy of prophylaxis. Fixed effect Mantel-Haenszel model was chosen as the main analysis method. Funnel plots were examined to estimate the potential selection bias. Egger’s test and Begg’s test were used for the determination of possible small study bias. Eleven cohort studies that met the inclusion criteria were finally included. Results indicated that rituximab was associated with a significantly increased risk for PCP (28/942 vs 5/977; risk ratio: 3.65; 95% confidence interval 1.65 to 8.07; P=0.001), and no heterogeneity existed between different studies (I²=0%). Little significant difference in PCP risk was found between bi-weekly and tri-weekly regimens (risk ratio: 3.11; 95% confidence interval 0.92 to 10.52, P=0.068). PCP risk was inversely associated with prophylaxis in patients treated with rituximab (0/222 vs 26/986; risk ratio: 0.28; 95% confidence interval 0.09 to 0.94; P=0.039). In conclusion, PCP risk was increased significantly in lymphoma patients subjected to rituximab-contained chemotherapies. Difference in PCP risk between bi-weekly and tri-weekly regimens was not significant. Additionally, prophylaxis was dramatically effective in preventing PCP in rituximab-received lymphoma patients, suggesting that rituximab should be recommended for these patients.     

Immunoenzymatic Detection of Collagen Production by Pulmonary Fibroblasts in Serum-Free Culture

We have developed an improved assay for the production of collagen by fibroblasts. Early passage adult mouse lung fibroblasts, established and maintained in serum-free culture, were employed as the target cells. An enzyme immunoassay was used for detection of type I collagen deposited on the substratum, permitting adaptation of the technique to cultures in 96-well microplates. Approximately two-fold enhancement of collagen deposition was induced by exposure to a concentration of 3 ng/ml of transforming growth factor-β1 or of 100 ng/ml of insulin-like growth factor-1 for 48 hr.     

Toward the Standardization of Mycological Examination of Sputum Samples in Cystic Fibrosis: Results from a French Multicenter Prospective Study

Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: “MucoFong” program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media. After mucolytic pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37), erythritol-enriched (ERY37), benomyl dichloran–rose bengal (BENO37) and chromogenic (CAN37) media incubated at 37 °C and on Sabouraud–chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20–27 °C. Each plate was checked twice a week during 3 weeks. Fungi were conventionally identified; time for detection of fungal growth was noted for each species. Fungal prevalences and media performances were assessed; an optimal combination of media was determined using the Chi-squared automatic interaction detector method. At least one fungal species was isolated from 81% of sputa. Candida albicans was the most prevalent species (58.8%), followed by Aspergillus fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days provided an optimal combination, detecting C. albicans, A. fumigatus, Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5, 98.8, 100 and 100%. Combination of these four culture media is recommended to ensure the growth of key fungal pathogens in CF respiratory specimens. The use of such consensual protocol is of major interest for merging results from future epidemiological studies.     

Ventilatory Tests and Pulmonary Conductance in Hospitalized Patients

In a series of 49 patients, including individuals with varying lung pathology and some older patients with no lung disease, the usual excellent correlation between first-second forced expiratory volume and maximum breathing capacity was found (coefficient of correlation=0.88). The first-second forced expiratory volume and maximum mid-expiratory flow rate were also seen to be closely related (coefficient of correlation=0.87). The relationship between these ventilatory tests and direct mechanical measurements of pulmonary resistance, however, was not as striking. Reduction in pulmonary compliance not due to loss or removal of pulmonary tissue did not affect the interrelationships between these tests. First-second forced expiratory volume, expressed as a percentage of the predicted vital capacity, was more closely related to the expression “% of predicted maximum breathing capacity” than the first-second forced expiratory volume, expressed as a percentage of the actual vital capacity (p<.05).     

诱导痰黏蛋白5AC对支气管哮喘和慢性阻塞性肺疾病的鉴别价值

摘要 目的：对支气管哮喘（BA）患者和慢性阻塞性肺疾病（COPD）患者诱导痰黏蛋白5AC（MUC5AC）、炎症细胞和炎症因子水平进行比较以及相关性分析,评估MUC5AC鉴别BA和COPD的价值。方法：选取2018年9月至2019年9月来海南医学院第一附属医院就诊的BA稳定期患者（BA组）60例,同期COPD稳定期（COPD组）患者60例。诱导痰法采样并处理痰液,检测诱导痰MUC5AC、炎症细胞中性粒细胞（Neu）、巨噬细胞（Mac）、嗜酸性粒细胞（Eos）、淋巴细胞（Lym）、炎症因子血管内皮生长因子（VEGF）、细胞间黏附分子-1（ICAM-1）、白介素13（IL-13）和白介素17（IL-17）水平,通过Pearson相关分析对MUC5AC水平与Neu、Mac、Eos、Lym、VEGF、ICAM-1、IL-13、IL-17的关系进行分析。此外,采用受试者工作特征(ROC)曲线分析MUC5AC、炎症细胞及炎症因子鉴别诊断BA及COPD的效能。结果：COPD组诱导痰MUC5AC水平高于BA组,差异有统计学意义（P＜0.05）;COPD组诱导痰Mac和Eos水平均低于BA组,COPD组诱导痰Neu水平高于BA组,差异均有统计学意义（P＜0.05）;COPD组诱导痰VEGF、ICAM-1、IL-13和IL-17水平均低于BA组,差异均有统计学意义（P＜0.05）;Pearson相关分析结果显示,诱导痰MUC5AC与炎症细胞Mac、Eos和炎症因子VEGF、ICAM-1、IL-13和IL-17呈负相关（P＜0.05）,与炎症细胞Neu呈正相关（P＜0.05）。经ROC曲线分析可得：诱导痰MUC5AC鉴别BA和COPD的曲线下面积、灵敏度、特异度以及约登指数均高于炎症细胞Neu、Mac、Eos以及炎症因子VEGF、ICAM-1、IL-13、IL-17。结论：COPD患者诱导痰MUC5AC水平高于BA患者,MUC5AC与炎症细胞和炎症因子有关,MUC5AC的检测有助于鉴别BA或COPD,其有望作为临床BA或COPD的监测指标和治疗靶点。     

苏黄止咳胶囊联合舒利迭对咳嗽变异性哮喘患者肺功能、免疫功能及诱导痰炎性介质的影响

目的:探讨苏黄止咳胶囊联合舒利迭对咳嗽变异性哮喘(CVA)患者肺功能、免疫功能及诱导痰炎性介质的影响。方法:选取2017年1月-2019年12月期间我院收治的93例CVA患者,按照随机数字表法分为对照组(n=46)和研究组(n=47),对照组患者给予舒利迭治疗,研究组在对照组的基础上联合苏黄止咳胶囊治疗,比较两组患者疗效、肺功能、免疫功能、诱导痰炎性介质以及不良反应情况。结果:研究组治疗2个疗程后的临床总有效率高于对照组(P0.05)。两组患者治疗2个疗程后第1秒用力呼气容积(FEV1)、用力肺活量(FVC)以及呼气峰值流量(PEF)、CD4+、CD4+/CD8+均较治疗前升高,且研究组高于对照组(P0.05)。两组患者治疗2个疗程后CD8+以及诱导痰白介素-6(IL-6)、白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平均较治疗前降低,且研究组低于对照组(P0.05)。两组不良反应发生率比较无差异(P0.05)。结论:舒利迭联合苏黄止咳胶囊治疗CVA患者,可有效改善患者肺功能、免疫功能,降低诱导痰炎性介质水平,且不增加不良反应发生率,安全可靠,疗效显著。     

2017-2019年某某医院ICU患者痰液病原菌分布及耐药性分析

摘要 目的：探究医院ICU患者痰液病原菌分布,并就其耐药性进行分析,以期为临床经验性选择抗生素治疗提供必要的细菌学依据。方法：选择2017年1月至2019年12月于北京中医医院顺义医院入住ICU的84例患者为研究对象,采集其痰液标本,并实施细菌学培养和药敏学试验。结果：（1）84例患者合计提取菌株91种,其中G^-杆菌45种,占比49.45 %,G⁺菌36种,占比39.56 %,真菌10种,占比10.99 %;（2）分析显示亚胺培南对G^-杆菌的敏感性较好,万古霉素对G⁺菌的敏感性较好,尚未发现耐万古霉素的肠球菌和葡萄球菌出现。结论：ICU患者痰液病原菌类型较多,其中以G^-杆菌为主,病原菌呈现多重耐药性,亚胺培南对G^-杆菌敏感性较好,万古霉素对G⁺菌敏感性较好。     

Evaluation of Giant African Pouched Rats for Detection of Pulmonary Tuberculosis in Patients from a High-Endemic Setting

BackgroundThis study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting.MethodsThe TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania.ResultsOf 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66–0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0–66.3), specificity of 80.5% (95% CI 72.5–86.9), positive and negative predictive value of 71.3% (95% CI 60.6–80.5) and 68.7% (95% CI 60.6–76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status.ConclusionGiant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health Organization.