Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements.

Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker-high and -low severe asthma.

Background: The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO-high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood.

Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography-mass spectrometry.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has claimed over two and a half million lives worldwide so far. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is perceived to be seasonally recurrent, and a rapid noninvasive biomarker to accurately diagnose patients early on in their disease course will be necessary to meet the operational demands for COVID-19 control in the coming years.

Objective: The aim of this study was to evaluate the role of exhaled breath volatile biomarkers in identifying patients with suspected or confirmed COVID-19 infection, based on their underlying PCR status and clinical probability.

A Feasibility Study of a Randomized Controlled Trial of Asthma-Tailored Pulmonary Rehabilitation Compared with Usual Care in Adults with Severe Asthma.

Background: Currently, the acceptability and efficacy of pulmonary rehabilitation for adults with severe asthma is unknown.

Objective: To investigate the feasibility of performing a randomized controlled trial of asthma-tailored pulmonary rehabilitation (AT-PR) versus usual care (UC).

Methods: Adults with severe asthma were recruited and randomized 2:1 to AT-PR and UC.

Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum.

Background: Asthma is a heterogeneous disease and understanding this heterogeneity will enable the realisation of precision medicine. We sought to compare the sputum and serum inflammatory profiles in moderate-to-severe asthma during stable disease and exacerbation events.

Methods: We recruited 102 adults and 34 children with asthma.

Lung Computational Models and the Role of the Small Airways in Asthma.

Asthma is characterized by disease within the small airways. Several studies have suggested that forced oscillation technique-derived resistance at 5 Hz (R5) - resistance at 20 Hz (R20) is a measure of small airway disease; however, there has been limited validation of this measurement to date. To validate the use of forced oscillation R5 - R20 as a measure of small airway narrowing in asthma, and to investigate the role that small airway narrowing plays in asthma.

Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study.

Introduction: Patients presenting with acute undifferentiated breathlessness are commonly encountered in admissions units across the UK. Existing blood biomarkers have clinical utility in distinguishing patients with single organ pathologies but have poor discriminatory power in multifactorial presentations. Evaluation of volatile organic compounds (VOCs) in exhaled breath offers the potential to develop biomarkers of disease states that underpin acute cardiorespiratory breathlessness, owing to their proximity to the cardiorespiratory system.

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.

The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.

The use of oral methotrexate for refractory eosinophilic asthma in a tertiary asthma referral centre, Glenfield Hospital, Leicester, was evaluated between January 2006 and December 2014. The patients ( n = 61) were carefully phenotyped at baseline with markers of airway inflammation. In addition, a structured oral methotrexate proforma was utilized to evaluate response to therapy and adverse events.

Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation.

Background: Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear.

A CEACAM6-High Airway Neutrophil Phenotype and CEACAM6-High Epithelial Cells Are Features of Severe Asthma.

Severe asthma represents a major unmet clinical need; understanding the pathophysiology is essential for the development of new therapies. Using microarray analysis, we previously found three immunological clusters in asthma: Th2-high, Th17-high, and Th2/17-low. Although new therapies are emerging for Th2-high disease, identifying molecular pathways in Th2-low disease remains an important goal.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.

TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma.

Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A.

COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils.

Background: Eosinophilic airway inflammation is observed in 10-30% of COPD subjects. Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.

Methods: We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥ 3%/year).

Lung function decline and variable airway inflammatory pattern: longitudinal analysis of severe asthma.

Background: Eosinophilic airway inflammation measured by using induced sputum is an important treatment stratification tool in patients with severe asthma. In addition, sputum eosinophilia has been shown to be associated with severe exacerbations and airflow limitation.

Objectives: We sought to identify whether eosinophilic inflammation in sputum is associated with FEV₁ decrease in patients with severe asthma and whether we could identify subgroups of decrease behavior based on the variation of eosinophilic airway inflammation over time.

Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study).

Background: IgE sensitization to Aspergillus fumigatus and a positive sputum fungal culture result are common in patients with refractory asthma. It is not clear whether these patients would benefit from antifungal treatment.

Objectives: We sought to determine whether a 3-month course of voriconazole improved asthma-related outcomes in patients with asthma who are IgE sensitized to A fumigatus.

Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients.

Background: Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)-assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms.

Objectives: The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes.