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Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.

Evaluation of different methods for an initial treatment decision in individuals with suspected pulmonary tuberculosis.

BACKGROUND: Recently, important advances regarding the diagnosis of pulmonary tuberculosis have been introduced, which influence the decision to initiate anti-tuberculosis treatment.

METHODS: To evaluate the impact of different methods for the presumed diagnosis of tuberculosis, individuals with suspected tuberculosis were prospectively enrolled following a specific algorithm including initial smear microscopy and Mycobacterium tuberculosis-specific nucleic acid amplification (NAAT) from sputum. In cases of negative initial test results, tuberculin skin testing, bronchoscopy with transbronchial biopsies and interferon-γ release assays (IGRAs) in peripheral blood and bronchoalveolar lavage (BAL) fluid were performed.

RESULTS: Amongst 135 individuals with suspected tuberculosis, 42 had tuberculosis, 10 had nontuberculous mycobacteria pulmonary infection/colonization (one had both tuberculosis and nontuberculous mycobacteria pulmonary infection/colonization) and 84 had an alternative final diagnosis. The sensitivity and specificity were 41% and 99% [positive likelihood ratio (LR+) = 40] for sputum microscopy and 31% and 98% (LR+) = 16) for BAL nucleic acid amplification, respectively. In patients with acid-fast bacilli smear-negative tuberculosis (25/42, 59.5%), M. tuberculosis-specific BAL fluid IGRA was 92% sensitive and 87% specific (LR+) = 7) for the diagnosis of tuberculosis.

CONCLUSION: None of the microbiological or immunological methods that aim to provide a rapid diagnosis of tuberculosis whilst waiting the confirmation of the M. tuberculosis culture results is on its own accurate enough to diagnose or exclude pulmonary tuberculosis. Negative sputum microscopy and M. tuberculosis-specific NAAT results should prompt bronchoscopy including BAL for M. tuberculosis-specific IGRA in individuals with suspected pulmonary tuberculosis.

 

Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011.

This document provides updated guidance for the use of influenza vaccines in the United States for the 2011-12 influenza season. In 2010, the Advisory Committee on Immunization Practices (ACIP) first recommended annual influenza vaccination for all persons aged ≥6 months in the United States.

Vaccination of all persons aged ≥6 months continues to be recommended. Information is presented in this report regarding vaccine strains for the 2011-12 influenza season, the vaccination schedule for children aged 6 months through 8 years, and considerations regarding vaccination of persons with egg allergy. Availability of a new Food and Drug Administration (FDA)-approved intradermally administered influenza vaccine formulation for adults aged 18 through 64 years is reported.

For issues related to influenza vaccination that are not addressed in this update, refer to the 2010 ACIP statement on prevention and control of influenza with vaccines and associated updates.

Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study.

Abstract

More than 50,000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities.

METHODS: In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27,449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud).

FINDINGS: 9-year cumulative incidence of asthma was 27·6% (number at risk: 7027), sinusitis 42·3% (5870), and gastro-oesophageal reflux disease 39·3% (5650). In police officers, cumulative incidence of depression was 7·0% (number at risk: 3648), PTSD 9·3% (3761), and panic disorder 8·4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27·5% (number at risk: 4200), PTSD 31·9% (4342), and panic disorder 21·2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41·8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders.

INTERPRETATION: 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population.

New insights into the immunology of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome associated with abnormal inflammatory immune responses of the lung to noxious particles and gases.

Cigarette smoke activates innate immune cells such as epithelial cells and macrophages by triggering pattern recognition receptors, either directly or indirectly via the release of damage-associated molecular patterns from stressed or dying cells. Activated dendritic cells induce adaptive immune responses encompassing T helper (Th1 and Th17) CD4+ T cells, CD8+ cytotoxicity, and B-cell responses, which lead to the development of lymphoid follicles on chronic inflammation. Viral and bacterial infections not only cause acute exacerbations of COPD, but also amplify and perpetuate chronic inflammation in stable COPD via pathogen-associated molecular patterns.

We discuss the role of autoimmunity (autoantibodies), remodelling, extracellular matrix-derived fragments, impaired innate lung defences, oxidative stress, hypoxia, and dysregulation of microRNAs in the persistence of the pulmonary inflammation despite smoking cessation.

Asthma and obesity – a known association but unknown mechanism

AbstractThe obese asthma phenotype is an increasingly common encounter in our clinical practice. Epidemiologic data indicate that obesity increases the prevalence and incidence of asthma, and evidence that obesity precedes the development of asthma raises the possibility of a causal association. Obese patients with asthma experience more symptoms and increased morbidity compared to non‐obese asthma patients. Despite more than a decade of research into this association, the exact mechanisms that underlie the interaction of obesity with asthma remain unclear. It is unlikely that the asthma‐obesity association is simply due to co‐morbidities such as obstructive sleep apnea or gastro‐esophageal reflux disease. Although inflammatory pathways are purported to play a role, there is scant ...

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