Analysis of airway inflammation demonstrates a mechanism for T2-biologic failure in asthma.

Background: Targeted type 2 (T2) biologics have transformed asthma care, but the clinical response to biologic therapy varies between patients.

Objective: We sought to assess airways inflammation in T2-high asthmatic patients treated with anti-IL-5 biologics to investigate whether differential mechanism of airway inflammation explains varied response to biologics.

Methods: Proteomic analysis (Olink, 1463 protein panel) and high-sensitivity cytokine analysis (ELISAs) were performed on induced sputum from T2-high severe asthmatic patients in the UK multicenter Mepolizumab EXacerbation study.

Host-microbial interactions differ with age of asthma onset.

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Deep Learning-based Segmentation of Computed Tomography Scans Predicts Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. To develop automated imaging biomarkers using deep learning-based segmentation of CT scans. We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort.

Associations of Breathing Pattern Disorder and Nijmegen Score With Clinical Outcomes in Difficult-to-Treat Asthma.

Background: Breathing pattern disorder (BPD) reflects altered biomechanical patterns of breathing that drive breathing difficulty and commonly accompanies difficult-to-treat asthma. Diagnosis of BPD has no gold standard, but Nijmegen Questionnaire (NQ) >23 is commonly used.

Objectives: We sought to advance clinical characterization of BPD and better understand the clinical utility of NQ in difficult asthma in patients from the Wessex AsThma CoHort of difficult asthma (WATCH) study.

Comprehensive Characterization of Difficult-to-Treat Asthma Reveals Near Absence of T2-Low Status.

Background: Asthma is conventionally stratified as type 2 inflammation (T2)-high or T2-low disease. Identifying T2 status has therapeutic implications for patient management, but a real-world understanding of this T2 paradigm in difficult-to-treat and severe asthma remains limited.

Objectives: To identify the prevalence of T2-high status in difficult-to-treat asthma patients using a multicomponent definition and compare clinical and pathophysiologic characteristics between patients classified as T2-high and T2-low.

Predicting the risk of chest radiograph abnormality 12-weeks post hospitalisation with SARS CoV-2 PCR confirmed COVID-19.

Background: Routine follow-up of patients hospitalised with COVID-19 is recommended, however due to the ongoing high number of infections this is not without significant health resource and economic burden. In a previous study we investigated the prevalence of, and risk factors for, persistent chest radiograph (CXR) abnormalities post-hospitalisation with COVID-19 and identified a 5-point composite score that strongly predicted risk of persistent CXR abnormality at 12-weeks. Here we sought to validate and refine our findings in an independent cohort of patients.

Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma.

The measurement of exhaled volatile organic compounds (VOCs) in exhaled breath (breathomics) represents an exciting biomarker matrix for airways disease, with early research indicating a sensitivity to airway inflammation. One of the key aspects to analytical validity for any clinical biomarker is an understanding of the short-term repeatability of measures. We collected exhaled breath samples on 5 consecutive days in 14 subjects with severe asthma who had undergone extensive clinical characterisation.

Nontypeable Haemophilus influenzae infection of pulmonary macrophages drives neutrophilic inflammation in severe asthma.

Background: Nontypeable Haemophilus influenzae (NTHi) is a respiratory tract pathobiont that chronically colonizes the airways of asthma patients and is associated with severe, neutrophilic disease phenotypes. The mechanism of NTHi airway persistence is not well understood, but accumulating evidence suggests NTHi can persist within host airway immune cells such as macrophages. We hypothesized that NTHi infection of pulmonary macrophages drives neutrophilic inflammation in severe asthma.

The Clinical Implications of Aspergillus Fumigatus Sensitization in Difficult-To-Treat Asthma Patients.

Background: Fungal sensitivity has been associated with severe asthma outcomes. However, the clinical implication of Aspergillus fumigatus sensitization in difficult-to-treat (or difficult) asthma is unclear.

Objectives: To characterize the clinical implications of A fumigatus sensitization in a large difficult asthma cohort.

Real-world Omalizumab and Mepolizumab treated difficult asthma phenotypes and their clinical outcomes.

Background: Omalizumab and Mepolizumab are biologic drugs with proven efficacy in clinical trials. However, a better understanding of their real-world effectiveness in severe asthma management is needed.

Objectives: To better understand the real-world effectiveness of Omalizumab and Mepolizumab, elucidate the clinical phenotypes of patients treated with these drugs, identify baseline characteristics associated with biologic response and assess the spectrum of responses to these medications.

Clinical evaluation of type 2 disease status in a real-world population of difficult to manage asthma using historic electronic healthcare records of blood eosinophil counts.

Background: Blood eosinophil measurement is essential for the phenotypic characterization of patients with difficult asthma and in determining eligibility for anti-IL-5/IL-5Rα biological therapies. However, assessing such measures over limited time spans may not reveal the true underlying eosinophilic phenotype, as treatment, including daily oral corticosteroid therapy, suppresses eosinophilic inflammation and asthma is intrinsically variable.

Methods: We interrogated the electronic healthcare records of patients in the Wessex AsThma CoHort of difficult asthma (WATCH) study (UK).

Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma.

Background: IL-13 is considered an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL-13 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high-dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways.

New Perspectives on Difficult Asthma; Sex and Age of Asthma-Onset Based Phenotypes.

Background: Asthma is a diverse condition that differs with age and sex. However, it remains unclear how sex, age of asthma onset, and/or their interaction influence clinical expression of more problematic adult "difficult" asthma.

Objectives: To better understand the clinical features of difficult asthma within a real-world clinical setting using novel phenotypic classification, stratifying subjects by sex and age of asthma onset.

Patient perceived barriers to exercise and their clinical associations in difficult asthma.

Background: Exercise is recommended in guidelines for asthma management and has beneficial effects on symptom control, inflammation and lung function in patients with sub-optimally controlled asthma. Despite this, physical activity levels in patients with difficult asthma are often impaired. Understanding the barriers to exercise in people with difficult asthma is crucial for increasing their activity, and in implementing successful, disease modifying, and holistic approaches to improve their health.

Exhaled volatile organic compounds in adult asthma: a systematic review.

The search for biomarkers that can guide precision medicine in asthma, particularly those that can be translated to the clinic, has seen recent interest in exhaled volatile organic compounds (VOCs). Given the number of studies reporting "breathomics" findings and its growing integration in clinical trials, we performed a systematic review of the literature to summarise current evidence and understanding of breathomics technology in asthma.A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-oriented systematic search was performed (CRD42017084145) of MEDLINE, Embase and the Cochrane databases to search for any reports that assessed exhaled VOCs in adult asthma patients, using the following terms (asthma AND (volatile organic compounds AND exhaled) OR breathomics).

Correction: Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala.

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Protocol for the Wessex AsThma CoHort of difficult asthma (WATCH): a pragmatic real-life longitudinal study of difficult asthma in the clinic.

Background: Asthma is now widely recognised to be a heterogeneous disease. The last two decades have seen the identification of a number of biological targets and development of various novel therapies. Despite this, asthma still represents a significant health and economic burden worldwide.