Viral asthma challenge model

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 in vitro and mice in vivo, we assessed mechanisms regulating CCL17 and CCL22 expression. Subjects with mild to moderate asthma and healthy volunteers were experimentally infected with RV and airway CCL17 and CCL22 protein quantified...

Allergic airway inflammation (AAI) involves T helper cell type 2 (Th2) and pro-inflammatory responses to aeroallergens and many predisposing factors remain elusive. Influenza A virus (IAV) is a major human pathogen that causes acute respiratory infections and induces specific immune responses essential for viral clearance and resolution of the infection. Beyond acute infection, IAV has been shown to persistently affect lung homeostasis and respiratory immunity. Here we asked how resolved IAV infection affects subsequently induced AAI...

OBJECTIVE: To identify factors that influence providers' decisions to prescribe antibiotics in patients presenting to the hospital with an asthma exacerbation. METHODS: We performed semi-structured interviews with a purposive sample of providers including sixteen hospitalists, emergency room providers, or pulmonologists, and one focus group with internal medicine residents recruited from one large, urban, teaching hospital and one small, rural, community hospital...

NEW FINDINGS: What is the central question of this study? What is the impact of airway cholinergic history on the properties of airway mucus secretion in a cystic fibrosis-like environment? What is the main finding and its importance? Prior cholinergic challenge slightly modifies the characteristics of mucus secretion in response to a second cholinergic challenge in a diminished bicarbonate and chloride transport environment. Such modifications might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease...

BACKGROUND: The interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbations are frequently caused by viral infections. Polyinosinic:polycytidylic acid (pIC) mimics viral infections through binding to pattern recognition receptors (e.g. TLR-3). We and others have shown that pIC induces the expression of IL-17C in airway epithelial cells. Using different mouse models, we aimed to investigate the function of IL-17RE in the development of experimental allergic asthma and acute exacerbation thereof...

BACKGROUND: Respiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown. OBJECTIVE: To investigate the role of uric acid (UA) and IL-1β in RSV immunopathology and asthma predisposition. METHODS: Tracheal aspirates from human infants with and without RSV were collected and analyzed for pro-IL-1β mRNA and protein to establish a correlation in human disease...

Chronic obstructive pulmonary disease (COPD) and asthma remain prevalent human lung diseases. Variability in epithelial and inflammatory components that results in pathologic heterogeneity complicates the development of treatments for these diseases. Early childhood infection with parainfluenza virus or respiratory syncytial virus is strongly associated with the development of asthma and COPD later in life, and exacerbations of these diseases correlate with the presence of viral RNA in the lung. Well-characterized animal models of postviral chronic lung diseases are necessary to study the underlying mechanisms of viral-related COPD and asthma and to develop appropriate therapies...

OBJECTIVE: Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. METHODS: Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues...

BACKGROUND: Respiratory viral infections are the leading cause of asthma exacerbations. Eosinophil activation results in the formation of eosinophil extracellular traps (EETs), which release web-like structures of DNA and proteins that bind, disarm and extracellularly kill pathogens. OBJECTIVE: We investigated whether the respiratory syncytial virus (RSV) in vitro could induce EETs in bronchoalveolar lavage fluid eosinophils in a murine model of asthma. METHODS: BALB/cJ mice (6-8 weeks old) were sensitized with 2 subcutaneous injections of ovalbumin (20 μg) on days 0 and 7, followed by three intranasal challenges with ovalbumin (100 μg) on days 14, 15, and 16 of the protocol...

Fatal outcomes following influenza infection are often associated with secondary bacterial infections. Allergic airway disease (AAD) is known to influence severe complications from respiratory infections, and yet the mechanistic effect of AAD on influenza virus- Streptococcus pneumoniae coinfection has not been investigated previously. We examined the impact of AAD on host susceptibility to viral-bacterial coinfections. We report that AAD improved survival during coinfection when viral-bacterial challenge occurred 1 week after AAD...

RATIONALE: Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. OBJECTIVES: To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations...

BACKGROUND: House dust mite (HDM)-challenged Apoe-/- mice display enhanced airway hyperreactivity and mucous cell metaplasia. OBJECTIVE: To characterize the pathways that induce APOE expression by asthmatic macrophages and identify how APOE regulates IL-1β secretion. METHODS: Macrophages were isolated from asthmatic bronchoalveolar lavage fluid (BALF) and derived from THP-1 cells and human monocytes. RESULTS: HDM-derived cysteine and serine proteases induced APOE secretion from asthmatic BALF macrophages via protease-activated receptor 2...

We examine the seasonality of asthma-related hospital admissions in Melbourne, Australia, in particular the contribution and predictability of episodic thunderstorm asthma. Using a time-series ecological approach based on asthma admissions to Melbourne metropolitan hospitals, we identified seasonal peaks in asthma admissions that were centred in late February, June and mid-November. These peaks were most likely due to the return to school, winter viral infections and seasonal allergies, respectively. We performed non-linear statistical regression to predict daily admission rates as functions of the seasonal cycle, weather conditions, reported thunderstorms, pollen counts and air quality...

Defective production of antiviral interferon (IFN)-β is thought to contribute to rhinovirus-induced asthma exacerbations. These exacerbations are associated with elevated lung levels of lactate dehydrogenase (LDH), indicating occurrence of cell necrosis. We thus hypothesized that reduced lung IFN-β could contribute to necrotic cell death in a model of asthma exacerbations. Wild-type and IFN-β-/- mice were given saline or house dust mite (HDM) intranasally for 3 weeks to induce inflammation. Double-stranded RNA (dsRNA) was then given for additional 3 days to induce exacerbation...

Eosinophils have been postulated to play a protective role against infection with respiratory syncytial virus (RSV), increase the severity of allergic asthma during respiratory viral infection, and drive vaccine-enhanced disease. To address these questions in the cotton rat model of RSV infection, we characterized cotton rat eosinophils by electron microscopy as well as by bronchoalveolar lavage and histology of lung sections. Using these methods, we demonstrated that eosinophils comprise approximately half of all cells in the bronchoalveolar lavage fluids from cotton rats...

BACKGROUND: Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses. OBJECTIVE: Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling. METHODS: Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice using sequential challenges with HDM and a viral infection mimic, Poly(I:C)...

Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted. Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection...

AIMS: PATCH is a pilot acute community children's nurse led service delivering assessment and treatment for children at home who are moderately unwell and might otherwise be admitted to hospital or attend Paediatric Emergency Department (PED). Children are referred by PED or GP and followed up via telephone support and home visits depending on clinical need for duration of acute illness. METHODS: Pilot year funded by Imperial Charity. Using evaluation to build business case for sustained commissioned service...

BACKGROUND: Rhinovirus infection triggers acute asthma exacerbations. IL-33 is an instructive cytokine of type 2 inflammation whose expression is associated with viral load during experimental rhinovirus infection of asthmatic patients. OBJECTIVE: We sought to determine whether anti-IL-33 therapy is effective during disease progression, established disease, or viral exacerbation using a preclinical model of chronic asthma and in vitro human primary airway epithelial cells (AECs)...

Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes...