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Tuberculosis.

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Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (~9 million cases and ~1·5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis.

Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity.

Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes.

Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial.

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Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.

We conducted a randomised, double-blind, placebo-controlled, proof-of-concept study in house dust mite (HDM) allergic asthma patients. Patients were randomised to receive intravenous rhAPC (24 µg·kg(-1)·h(-1); n=12) or placebo (n=12) for 11 h. 4 h after the start of infusion, a first bronchoscopy was performed to challenge one lung segment with saline (control) and a contralateral segment with a combination of HDM extract and lipopolysaccharide (HDM+LPS), thereby mimicking environmental house dust exposure. A second bronchoscopy was conducted 8 h after intrabronchial challenge to obtain bronchoalveolar lavage fluid (BALF).rhAPC did not influence HDM+LPS induced procoagulant changes in the lung. In contrast, rhAPC reduced BALF leukocyte counts by 43% relative to placebo, caused by an inhibitory effect on neutrophil influx (64% reduction), while leaving eosinophil influx unaltered. rhAPC also reduced neutrophil degranulation products in the airways.

Intravenous rhAPC attenuates HDM+LPS-induced neutrophil migration and protein release in allergic asthma patients by an effect that does not rely on coagulation inhibition.

Risk factors for asthma: is prevention possible?

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Asthma is one of the most common diseases in the world, resulting in a substantial burden of disease. Although rates of deaths due to asthma worldwide have reduced greatly over the past 25 years, no available therapeutic regimens can cure asthma, and the burden of asthma will continue to be driven by increasing prevalence.

The reasons for the increase in asthma prevalence have not been defined, which limits the opportunities to develop targeted primary prevention measures. Although associations are reported between a wide range of risk factors and childhood asthma, substantiation of causality is inherently difficult from observational studies, and few risk factors have been assessed in primary prevention studies. Furthermore, none of the primary prevention intervention strategies that have undergone scrutiny in randomised controlled trials has provided sufficient evidence to lead to widespread implementation in clinical practice. A better understanding of the factors that cause asthma is urgently needed, and this knowledge could be used to develop public health and pharmacological primary prevention measures that are effective in reducing the prevalence of asthma worldwide.

To achieve this it will be necessary to think outside the box, not only in terms of risk factors for the causation of asthma, but also the types of novel primary prevention strategies that are developed, and the research methods used to provide the evidence base for their implementation. In the interim, public health efforts should remain focused on measures with the potential to improve lung and general health, such as: reducing tobacco smoking and environmental tobacco smoke exposure; reducing indoor and outdoor air pollution and occupational exposures; reducing childhood obesity and encouraging a diet high in vegetables and fruit; improving feto-maternal health; encouraging breastfeeding; promoting childhood vaccinations; and reducing social inequalities.

Socioeconomic inequalities in non-communicable diseases and their risk factors: an overview of systematic reviews.

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Non-communicable diseases (NCDs) are the largest cause of premature death worldwide. Socioeconomic inequalities contribute to a disparity in the burden of NCDs among disadvantaged and advantaged populations in low (LIC), middle (MIC), and high income countries (HIC). We conducted an overview of systematic reviews to systematically and objectively assess the available evidence on socioeconomic inequalities in relation to morbidity and mortality of NCDs and their risk factors.

METHODS: We searched PubMed, The Cochrane Library, EMBASE, SCOPUS, Global Health, and Business Source Complete for relevant systematic reviews published between 2003 and December 2013. Two authors independently screened abstracts and full-text publications and determined the risk of bias of the included systematic reviews.

RESULTS: We screened 3302 abstracts, 173 full-text publications and ultimately included 22 systematic reviews. Most reviews had major methodological shortcomings; however, our synthesis showed that having low socioeconomic status (SES) and/or living in low and middle income countries (LMIC) increased the risk of developing cardiovascular diseases (CVD), lung and gastric cancer, type 2 diabetes, and chronic obstructive pulmonary disease (COPD). Furthermore, low SES increased the risk of mortality from lung cancer, COPD, and reduced breast cancer survival in HIC. Reviews included here indicated that lower SES is a risk factor for obesity in HIC, but this association varied by SES measure. Early case fatalities of stroke were lower and survival of retinoblastoma was higher in MIC compared to LIC.

CONCLUSIONS: The current evidence supports an association between socioeconomic inequalities and NCDs and risk factors for NCDs. However, this evidence is incomplete and limited by the fairly low methodological quality of the systematic reviews, including shortcomings in the study selection and quality assessment process.

TB meets COPD: An emerging global co-morbidity in human lung disease.

Chronic obstructive pulmonary disease (COPD) is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. There is growing evidence of a co-morbidity between COPD and tuberculosis (TB), the leading cause of death globally due to respiratory infection. Thus, the increase in the burden of COPD over the coming decades, as predicted by the World Health Organisation, is of concern with respect to the control of TB. A better understanding of the interactions between these two diseases is essential for the design of complementary preventive and control strategies.

In this review, some of the known risk factors that are common to both diseases are discussed. Furthermore, we examine how impairment of the innate immune system, and corticosteroid therapy, in COPD patients may increase the risk of TB manifestation. Conversely, we review how TB lung pathology may heighten susceptibility to subsequent development of COPD, even after completion of effective TB treatment.

Growing evidence appears to point towards a bi-directional relationship between these two lung diseases where each may act as an independent risk factor for the other. This has important implications for the respective long-term management of TB and COPD.

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