Clinical importance of patient-reported outcome measures in severe asthma: results from U-BIOPRED.

Rationale: Knowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited.

Objectives: To assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care.

Methods: Data of 421 patients with severe asthma (62% female; mean age 51.

Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics.

Background: Lung quantitative computed tomography (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence.

Methods: We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort.

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.

Elevated serum polyclonal immunoglobulin free light chains in patients with severe asthma.

Inflammation plays a pivotal role in the pathophysiology of asthma. Free light chains (FLC) can cause inflammation by mast cell antigen-activation. Serum immunoglobulin (Ig) FLC κ, but not λ, were shown elevated in adult males with asthma.

Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation.

Background: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma.

Methods: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs).

Stratification of asthma by lipidomic profiling of induced sputum supernatant.

Background: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features.

Objective: We performed a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as from healthy controls.

Dupilumab and tezepelumab in severe refractory asthma: new opportunities.

Bronchial asthma is a chronic inflammatory condition with increasing prevalence worldwide that may present as heterogeneous phenotypes defined by the T2-mediated pattern of airway inflammation T2-high and T2-low asthma. Severe refractory asthma includes a subset of asthmatic patients who fail to control their disease despite maximal therapy and represent a group of patients needing marked resource utilization and hence may be eligible to add-on biological therapies. Among the new biologics, we focused our attention on two monoclonal antibodies: dupilumab, exerting a dual blockade of cytokine (interleukin (IL)-4 and IL-13) signaling; and tezepelumab, acting at a higher level preventing the binding of thymic stromal lymphopoietin (TSLP) to its receptor, thus blocking TSLP, IL-25, and IL-33 signaling, hence modulating airway T2 immune responses.

Exploring the performance of a functionalized CNT-based sensor array for breathomics through clustering and classification algorithms: from gas sensing of selective biomarkers to discrimination of chronic obstructive pulmonary disease.

An array of carbon nanotube (CNT)-based sensors was produced for sensing selective biomarkers and evaluating breathomics applications with the aid of clustering and classification algorithms. We assessed the sensor array performance in identifying target volatiles and we explored the combination of various classification algorithms to analyse the results obtained from a limited dataset of exhaled breath samples. The sensor array was exposed to ammonia (NH), nitrogen dioxide (NO), hydrogen sulphide (HS), and benzene (CH).

Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort.

Background: Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.

Objectives: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.

Sleep Deprivation, Immune Suppression and SARS-CoV-2 Infection.

Sleep health and its adaptation to individual and environmental factors are crucial to promote physical and mental well-being across animal species. In recent years, increasing evidence has been reported regarding the relationship between sleep and the immune system and how sleep disturbances may perturb the delicate balance with severe repercussions on health outcomes. For instance, experimental sleep deprivation studies in vivo have reported several major detrimental effects on immune health, including induced failure of host defense in rats and increased risk for metabolic syndrome (MetS) and immune suppression in humans.

Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study.

Introduction: Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms.

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation.

Rationale: Asthma phenotyping requires novel biomarker discovery.

Objectives: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).

Methods: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR.

Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study.

Objective: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis.

Predictive Markers of Bronchial Hyperreactivity in a Large Cohort of Young Adults With Cough Variant Asthma.

Cough variant asthma (CVA), a common asthma phenotype characterized by nonproductive cough and bronchial hyperreactivity (BHR), is usually detected by bronchial provocation tests (BPTs) which are timeconsuming, expensive, and unsafe. The primary study objective was to provide proof of concept for the use of fractional exhaled nitric oxide (FNO), eosinophil count percentage in induced sputum (sEOS%), forced expiratory flow between 25 and 75% of forced vital capacity (FEF) % predicted value, and FEF z-scores as surrogate markers predicting BHR in young adults with suspected CVA; the secondary objective was to compare the diagnostic performance of the various techniques. Three hundred and ten subjects (median age 24 years) were included in a cross-sectional study.

Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma.

Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.

Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti-IL-22 (fezakinumab [FZ]) is enriched in severe asthma.

Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies.

Medication Adherence in Patients With Severe Asthma Prescribed Oral Corticosteroids in the U-BIOPRED Cohort.

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high.

Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity?

Study Design And Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry.