Identification of allergens from Aspergillus fumigatus-Potential association with lung damage in asthma.

Background: Component-resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1- or 2-dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained.

Methods: We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus.

Eosinophils in Health and Disease: A State-of-the-Art Review.

Eosinophils play a homeostatic role in the body's immune responses. These cells are involved in combating some parasitic, bacterial, and viral infections and certain cancers and have pathologic roles in diseases including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal disorders, and hypereosinophilic syndromes. Treatment of eosinophilic diseases has traditionally been through nonspecific eosinophil attenuation by use of glucocorticoids.

The causes of a peripheral blood eosinophilia in a secondary care setting.

Background: A peripheral blood eosinophilia of greater than 1.0 × 10 /L is relatively unusual and offers a clue to the underlying diagnosis. In 2003, we established a specialist service to diagnose unexplained eosinophilia.

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease.

Allergy to airway-colonising, thermotolerant, filamentous fungi represents a distinct eosinophilic endotype of often severe lung disease. This endotype, which particularly affects adult asthma, but also complicates other airway diseases and sometimes occurs de novo, has a heterogeneous presentation ranging from severe eosinophilic asthma to lobar collapse. Its hallmark is lung damage, characterised by fixed airflow obstruction (FAO), bronchiectasis and lung fibrosis.

Allergic fungal airways disease (AFAD): an under-recognised asthma endotype.

The term allergic fungal airways disease has a liberal definition based on IgE sensitisation to thermotolerant fungi and evidence of fungal-related lung damage. It arose from a body of work looking into the role of fungi in asthma. Historically fungi were considered a rare complication of asthma, exemplified by allergic bronchopulmonary aspergillosis; however, there is a significant proportion of individuals with Aspergillus fumigatus sensitisation who do not meet these criteria, who are at high risk for the development of lung damage.

Fungal bronchitis is a distinct clinical entity which is responsive to antifungal therapy.

Chronic productive cough in the context of exacerbations of airway disease can be associated with positive sputum cultures for fungi, in particular and spp., suggesting fungal bronchitis, a condition not widely recognised, as a possible cause for the exacerbation. Our objective was to determine the response to antifungal therapy in patients with suspected fungal bronchitis.

Fungal sensitization and positive fungal culture from sputum in children with asthma are associated with reduced lung function and acute asthma attacks respectively.

Background: Sensitization to thermotolerant fungi, including filamentous fungi and Candida albicans, is associated with poor lung function in adults with severe asthma. Data in children are lacking. Environmental exposure to fungi is linked with acute severe asthma attacks, but there are few studies reporting the presence of fungi in the airways during asthma attacks.

The airway fungal microbiome in asthma.

Background: Fungal involvement in asthma is associated with severe disease. The full spectrum of fungal species in asthma is not well described and is derived largely from insensitive culture techniques.

Objectives: To use high-throughput sequencing to describe the airway mycobiota in asthmatics with and without fungal sensitization and healthy controls; to compare samples representing different airway compartments; to determine whether the mycobiota was influenced by the fungal composition of outdoor air; and to compare findings with clinically relevant outcomes.

DP antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment.

Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D type 2 receptor (DP) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP in airway smooth muscle cells.

Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis.

Background: Asthma is a complex chronic disease underpinned by pathological changes within the airway wall. How variations in structural airway pathology and cellular inflammation contribute to the expression and severity of asthma are poorly understood.

Objectives: Therefore we evaluated pathological heterogeneity using topological data analysis (TDA) with the aim of visualizing disease clusters and microclusters.

Associations in asthma between quantitative computed tomography and bronchial biopsy-derived airway remodelling.

Airway remodelling in asthma remains poorly understood. This study aimed to determine the association of airway remodelling measured on bronchial biopsies with 1) lung function impairment and 2) thoracic quantitative computed tomography (QCT)-derived morphometry and densitometry measures of proximal airway remodelling and air trapping.Subjects were recruited from a single centre.

Sputum Inflammatory Mediators Are Increased in Aspergillus fumigatus Culture-Positive Asthmatics.

Aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. We investigated the profile of 24 sputum inflammatory mediators in A. fumigatus culture-positive or-negative moderate-to-severe asthmatics.

Experimental Investigation of Cavitation as a Possible Damage Mechanism in Blast-Induced Traumatic Brain Injury in Post-Mortem Human Subject Heads.

The potential of blast-induced traumatic brain injury from the mechanism of localized cavitation of the cerebrospinal fluid (CSF) is investigated. While the mechanism and criteria for non-impact blast-induced traumatic brain injury is still unknown, this study demonstrates that local cavitation in the CSF layer of the cranial volume could contribute to these injuries. The cranial contents of three post-mortem human subject (PMHS) heads were replaced with both a normal saline solution and a ballistic gel mixture with a simulated CSF layer.

The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro.

Introduction: Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model.

Methods: Immunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells.

Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial.

Background: Eosinophilic airway inflammation is often present in asthma, and reduction of such inflammation results in improved clinical outcomes. We hypothesised that fevipiprant (QAW039), an antagonist of prostaglandin D2 receptor 2, might reduce eosinophilic airway inflammation in patients with moderate-to-severe eosinophilic asthma.

Methods: We performed a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial at Glenfield Hospital (Leicester, UK).