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Simple Summary: Cancer of the upper digestive system is associated with poor survival due to difficulties in diagnosing the disease early, before it has spread around the body. Previous research has shown that the healthy bacteria within the body changes in response to medications, diet and infection. Some of these changes are associated with a greater risk of developing cancers of the oesophagus (gullet) and stomach. This occurs, at least in part, through inflammation. This process is the body's natural response to infection, injury and exposure to potentially harmful substances, which, if uncontrolled can lead to diseases including cancer. This review article aims to explain the ways in which this happens. By developing a deeper understanding of these processes, advances in early diagnosis of this disease can be made, which may lead to better survival. Introduction: The upper gastrointestinal microbiome is a dynamic entity that is involved in numerous processes including digestion, production of vitamins and protection against pathogens. Many external and intrinsic factors may cause changes in the proportions of bacteria within the microbial community, termed 'dysbiosis'. A number of these have been identified as risk factors for a range of diseases, including oesophago-gastric carcinoma. Materials and Methods: A narrative review was conducted to elucidate the current evidence on the role of the microbiome in promoting oesophago-gastric tumourigenesis. Significant causes of dysbiosis including age, medications and GORD were examined and key pro-inflammatory pathways implicated in tumourigenesis and their interaction with the microbiome were described. Results and Discussion: An association between microbial dysbiosis and development of oesophago-gastric cancer may be mediated via activation of pro-inflammatory pathways, the inflammasome and the innate immune system. Advances in sequencing technology allow microbial communities to be fingerprinted by sequencing the 16S rRNA gene, enabling a deeper understanding of the genera that may be implicated in driving tumourigenesis. Conclusions: Developing a greater understanding of the influence of the microbiota on oesophago-gastric tumourigenesis may enable advances to be made in the early detection of malignancy and in the development of novel systemic therapies, leading to improved rates of survival. [ABSTRACT FROM AUTHOR]

The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway mucin 5AC (MUC5AC) and MUC5B concentrations during spontaneous and experimentally induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with viral load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation, as Muc5ac-deficient (Muc5ac-/) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations., Introduction Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disorder punctuated by acute exacerbations that are frequently precipitated by rhinoviruses (RVs) (1, 2). Exacerbations are the major cause of [...]

Electronic nicotine delivery systems (ENDS) are rapidly increasing in popularity due to the perception that they may represent a safe alternative to conventional cigarettes. However, a growing body of evidence indicates that ENDS exposure can disrupt maintenance of pulmonary immune homeostasis and antimicrobial immunity. In this issue of the JCI, Madison et al. demonstrate that in mice, chronic ENDS exposure induces profound alterations in lipid homeostasis. ENDS-exposed mice showed irregularities in the surfactant-secreting lamellar bodies within type 2 alveolar cells and increased intracellular phospholipid accumulation within alveolar macrophages. Moreover, ENDS-exposed mice displayed greater inflammation and tissue damage in response to influenza A, which may be due to downregulated expression of a viral pattern-recognition receptor in alveolar macrophages. Collectively, the results of this study identify previously unrecognized adverse effects of ENDS exposure on pulmonary lipid metabolism, although the implication of these effects on long-term respiratory health requires future exploration., Electronic nicotine delivery systems-what's the harm? The adverse health consequences of long-term cigarette smoking are well established, and it remains the leading cause of preventable death worldwide (1). Although tobacco [...]

Since being identified in 2002, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) lineage, associated with livestock, has been a global public health concern (1). We know less about human [...]

Background and Aims: The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.Methods: Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.Results: Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals.Conclusion: Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma. [ABSTRACT FROM AUTHOR]