Exosomes and Exosomal miRNA in Respiratory Diseases

Exosomes are nanosized vesicles released from every cell in the body including those in the respiratory tract and lungs. They are found in most body fluids and contain a number of different biomolecules including proteins, lipids, and both mRNA and noncoding RNAs. Since they can release their contents, particularly miRNAs, to both neighboring and distal cells, they are considered important in cell-cell communication. Recent evidence has shown their possible importance in the pathogenesis of several pulmonary diseases. The differential expression of exosomes and of exosomal miRNAs in disease has driven their promise as biomarkers of disease enabling noninvasive clinical diagnosis in addition to their use as therapeutic tools. In this review, we summarize recent advances in this area as applicable to pulmonary diseases

What Immunological Defects Predispose to Non-tuberculosis Mycobacterial Infections?

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors.  Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections

Centralised busbar differential and wavelet-based line protection system for multi- terminal direct current grids, with practical IEC-61869-compliant measurements

This paper presents a method for discriminative detection of DC faults on VSC-powered multi-terminal HVDC transmission systems using two fundamental guiding principles, namely instantaneous current-differential and travelling waves. The proposed algorithm utilises local voltage and current measurements from all transmission lines connected to a DC busbar, and current measurement from the DC side of the converter. The scheme operates at a sampling frequency of 96 kHz which conforms with IEC 61869-9. No long distance communication is involved while measurements and signal exchange within DC substations are enabled by the utilisation of IEC 61850. Performance is assessed firstly through detailed transient simulation, using verified models of modular multi-level converters, hybrid DC circuit breakers and inductive DC-line terminations. Furthermore, practical performance and feasibility of the scheme is evaluated through laboratory testing, using the real time Opal-RT hardware prototyping platform. Simulation and experimental results demonstrate that the proposed protection algorithm can effectively, and within a very short period of time (i.e. less than 1 ms), discriminate between busbar and line faults (internal faults), while remaining stable during external faults. Additionally, it has been demonstrated that IEC 61869-9 is suitable for enabling fast DC protection schemes incorporating travelling waves

Increased activation and expansion of a CD57+ subset within peripheral CD8+ T lymphocytes in mycobacterium tuberculosis-infected patients

Background: Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M. tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M. tuberculosis replication. Methods: In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated γδ and αβ receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant patients) and 20 control subjects, using flowcytometry. Results: We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects (P < 0.003). Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings (P < 0.002). This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ (P < 0.003). No significant changes were observed in the percentages of CDB+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects (P < 0.002), but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases (P < 0.0001). No significant changes were observed in percentages of γδ receptor-bearing T cells between different groups. Conclusion: We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype

Primary multi-drug resistant tuberculosis presented as lymphadenitis in a patient without HIV infection

Primary multi-drug resistant extrapulmonary tuberculosis is an uncommon form of the disease, but it seems that by increasing the number drug resistant tuberculosis around the world, the number of cases of primary multidrug resistant tuberculosis with extrapulmonary presentation also is going to rise. In this report, we describe a 19- year old, HIV negative man with primary multi-drug resistant TB lymphadenitis, presented with cervical lymphadenopathy and sinus discharge at the site of involved lymph nodes. The Acid Fast Bacilli (AFB) smear of sputum was negative but the AFB smear of discharged fluid as well as the excisional biopsy of the lymph nodes confirmed the M. tuberculosis infection. The patient underwent the treatment with a combination of isoniazide, clofazimine, pyrazinamide, ofloxacin and amikacin with promising results. By increasing the number of drug resistant tuberculosis patients around the world, appropriate diagnosis and treatment of different presentations of the disease need a special attention

Pulmonary Mycobacterium Simiae infection and HTLV1 infection: an incidental co-infection or a predisposing factor?

There is little information on atypical mycobacterium and human T lymphothropic virus Type I (HTLV-I) co-infection. We present the first case of pulmonary M. simiae infection in co-infection with HTLV-1, confirmed by ELISA antibody test and Western Blot. We discuss the clinical characteristics and laboratory tests of the patient and presumptive immunological relation. We propose that in patients with the HTLV infection and pulmonary symptoms and signs compatible with tuberculosis, evaluation for atypical mycobacteriosis may be recommendable

Tuberculosis suspicion and knowledge among private and public general practitioners: Questionnaire Based Study in Oman

<p>Abstract</p> <p>Background</p> <p>Early detection of smear positive TB cases by smear microscopy requires high level of suspicion of TB among primary care physicians. The objective of this study is to measure TB suspicion and knowledge among private and public sector general practitioners using clinical vignette-based survey and structured questionnaire.</p> <p>Methods</p> <p>Two questionnaires were distributed to both private and public GPs in Muscat Governorate. One questionnaire assessed demographic information of the respondent and had 10 short clinical vignettes of TB and non-TB cases. The second questionnaire had questions on knowledge of TB, its diagnosis, treatment, follow up and contact screening based on Ministry of Health policy. TB suspicion score and TB Knowledge score were computed and analyzed.</p> <p>Results</p> <p>A total of 257 GPs participated in the study of which 154 were private GPs. There was a significant difference between private and public GPs in terms of age, sex, duration of practice and nationality. Among all GPs, 37.7% considered TB as one of the three most likely diagnoses in all 5 TB clinical vignettes. Private GPs had statistically significantly lower TB suspicion and TB knowledge scores than public GPs.</p> <p>Conclusion</p> <p>In Oman, GPs appear to have low suspicion and poor knowledge of TB, particularly private GPs. To strengthen TB control program, there is a need to train GPs on TB identification and adopt a Private Public Mix (PPM) strategy for TB control.</p

The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE:The study protocol

Background: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients' demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease's awareness

Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis

Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio