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Human infection with a novel avian-origin influenza A (H7N9) virus.

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Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus.

METHODS: We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses.

RESULTS: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died.

CONCLUSIONS: Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Global strategies for reducing the burden from asthma.

Asthma is one of the most important chronic diseases in childhood. For several decades, a steady increase in prevalence has been observed worldwide. In the structural collaboration between the Centre for Population Health Services in Edinburgh and the Research Institute CAPHRI of Maastricht we investigated the possibilities for primary prevention of asthma in childhood.

We found that a multifaceted approach might be effective in delaying or preventing asthma, whereas a mono-intervention does not seem to have such a protective effect. The most likely explanation is that the development of a multifactorial disease, such as asthma, is extremely difficult, if not impossible, to prevent by eliminating only one risk factor. Underdiagnosis of asthma is still a big problem in primary care. Most patients do not present bronchial symptoms to the general practitioner, even though they have decreased lung function, so they remain unknown and undiagnosed. However, patients who do present with respiratory problems and who have reduced lung function are not always recognised as such. We found that the perception of dyspnoea seems to determine, at least in part, the presentation to the general practitioner with symptoms.

These observations show that both the prevention of the development of asthma in early childhood, as well as case finding of asthma in adulthood, do not seem to be very effective in primary care. More research is needed to clarify what steps can be taken to reduce the global burden from asthma.

Autophagy: a potential therapeutic target in lung diseases.

Macroautophagy (hereafter referred to as autophagy) is an evolutionally-conserved intracellular process to maintain cellular homeostasis by facilitating the turnover of protein aggregates, cellular debris and damaged organelles. During autophagy, cytosolic constituents are engulfed into double-membrane-bound vesicles called "autophagosome", which are subsequently delivered to the lysosome for degradation.

Accumulated evidence suggests that autophagy is critically involved in not only the basal physiological states but also in the pathogenesis of various human diseases. Interestingly, a diverse variety of clinically approved drugs modulate autophagy to varying extents, although they are not currently utilized for the therapeutic purpose of manipulating autophagy.

In this review, we highlight the functional roles of autophagy in lung diseases with focus on the recent progress of the potential therapeutic use of autophagy modifying drugs in clinical medicine. The purpose of this review is to discuss the merits- and the pitfalls- of modulating autophagy as a therapeutic strategy in lung diseases.

Asbestos and the lung in the 21st century: an update.

The asbestos-related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries but asbestos is still used in many developing countries and the number of cases of asbestos-related disorders worldwide is rising.

Many countries are now experiencing an epidemic of asbestos-related diseases which is the legacy of occupational exposure in the 1960s-80s, due to the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos-related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening and asbestosis (pulmonary fibrosis due to asbestos). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy.

This review provides an update on the respiratory manifestations of asbestos exposure, and also considers advances in screening methods which may affect future management in the workplace.

Diagnosis of chronic obstructive pulmonary disease in lung cancer screening Computed Tomography scans: independent contribution of emphysema, air trapping and bronchial wall thickening.

Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD). Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation. Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans.

METHODS: Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants. Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans. Logistic regression analysis was performed to derivate a model to diagnose COPD. The model was internally validated using bootstrapping techniques.

RESULTS: Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status. The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively. The positive and negative predictive value were 80.2% and 84.2%, respectively. Of all participants, 82.8% was assigned the correct status. The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any CT biomarkers was 44.4%. However, the added value of the expiratory CT data was limited, with an increase in Net Reclassification Index of 4.5% compared to a model with only inspiratory CT data.

CONCLUSION: Quantitatively assessed CT emphysema, air trapping and bronchial wall thickness each contain independent diagnostic information for COPD, and these imaging biomarkers might prove useful in the absence of lung function testing and may influence lung cancer screening strategy. Inspiratory CT biomarkers alone may be sufficient to identify patients with COPD in lung cancer screening setting.

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