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.

Anti-IL-5 therapies for asthma.

Background: This is the second update of previously published reviews in the Cochrane Library (2015, first update 2017). Interleukin-5 (IL-5) is the main cytokine involved in the proliferation, maturation, activation and survival of eosinophils, which cause airway inflammation and are a classic feature of asthma. Studies of monoclonal antibodies targeting IL-5 or its receptor (IL-5R) suggest they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function in appropriately selected patients, justifying their inclusion in the latest guidelines.

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.

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.