Altered Microbiome Promotes Pro-Inflammatory Pathways in Oesophago-Gastric Tumourigenesis.

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.

The airway mycobiome and interactions with immunity in health and chronic lung disease.

The existence of commensal fungi that reside within the respiratory tract, termed the airway mycobiome, has only recently been discovered. Studies are beginning to characterize the spectrum of fungi that inhabit the human upper and lower respiratory tract but heterogeneous sampling and analysis techniques have limited the generalizability of findings to date. In this review, we discuss existing studies that have examined the respiratory mycobiota in healthy individuals and in those with inflammatory lung conditions such as asthma, chronic obstructive pulmonary disease and cystic fibrosis.

Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations.

Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity.

Inflammation as the nexus: exploring the link between acute myocardial infarction and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), particularly following acute exacerbations (AE-COPD), significantly heightens the risks and mortality associated with acute myocardial infarction (AMI). The intersection of COPD and AMI is characterised by a considerable overlap in inflammatory mechanisms, which play a crucial role in the development of both conditions. Although extensive research has been conducted on individual inflammatory pathways in AMI and COPD, the understanding of thrombo-inflammatory crosstalk in comorbid settings remains limited.

The Role of Mucin Expression in the Diagnosis of Oesophago-Gastric Cancer: A Systematic Literature Review.

Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner.

Obesity dysregulates the pulmonary antiviral immune response.

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses.

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae.

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood.

Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection.

Background: Microbiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated.

In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection.

Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-β given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes 4 days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms.

Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium.

Ultrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Here, we examined human airway epithelium infected with three different isolates of SARS-CoV-2 including the B.1.

Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.

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.

Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomised controlled trial.

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.

Our evolving view of neutrophils in defining the pathology of chronic lung disease.

Neutrophils are critical components of the body's immune response to infection, being loaded with a potent arsenal of toxic mediators and displaying immense destructive capacity. Given the potential of neutrophils to impart extensive tissue damage, it is perhaps not surprising that when augmented these cells are also implicated in the pathology of inflammatory diseases. Prominent neutrophilic inflammation is a hallmark feature of patients with chronic lung diseases such as chronic obstructive pulmonary disease, severe asthma, bronchiectasis and cystic fibrosis, with their numbers frequently associating with worse prognosis.

Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression.

Objective: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.

Methods: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases.

Results: Following first-dose vaccine, 28.

Virus-induced Volatile Organic Compounds Are Detectable in Exhaled Breath during Pulmonary Infection.

Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation triggers is important to guide appropriate therapy, but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection etiology.

Gateway to the lungs: Viral entry receptors and susceptibility to COVID-19.

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Rhinovirus-induced CCL17 and CCL22 in Asthma Exacerbations and Differential Regulation by STAT6.

The interplay of type-2 inflammation and antiviral immunity underpins asthma exacerbation pathogenesis. Virus infection induces type-2 inflammation-promoting chemokines CCL17 and CCL22 in asthma; however, mechanisms regulating induction are poorly understood. By using a human rhinovirus (RV) challenge model in human airway epithelial cells and mice we assessed mechanisms regulating CCL17 and CCL22 expression.