Dupilumab reduces acute exacerbations and improves lung function in patients with COPD with type 2 inflammation irrespective of body mass index, airflow obstruction, dyspnea, and exercise capacity index scores.

Background: The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index predicts 5-year mortality risk in chronic obstructive pulmonary disease (COPD); higher scores predict worse outcomes. Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4/13, reduced exacerbations and improved lung function in patients with COPD in phase 3 BOREAS trial (NCT03930732). We assessed dupilumab efficacy in patients with COPD and type 2 inflammation by baseline BODE index.

Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS.

Introduction: Neutrophilic asthma has been suggested to be a clinically distinct phenotype characterised by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results. We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls.

Current Smoker: A Clinical COPD Phenotype Affecting Disease Progression and Response to Therapy.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition of the lungs, characterized by chronic respiratory symptoms, primarily dyspnea, cough, and sputum production, due to airway and/or alveoli abnormalities that cause persistent, and often progressive, airflow obstruction. Although the underlying mechanisms responsible for COPD remain poorly understood, over the last several decades, clinical phenotypes and endotypes have been suggested. These include frequent exacerbator and eosinophilic groups that guide tailored therapies for patients with that clinical expression.

Dupilumab for chronic obstructive pulmonary disease with type 2 inflammation: a pooled analysis of two phase 3, randomised, double-blind, placebo-controlled trials.

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13, which are key drivers of type 2 inflammation. We aimed to characterise the efficacy and safety of dupilumab in patients with COPD and type 2 inflammation.

Methods: For this pooled analysis, we pooled and analysed data from all patients in the intention-to-treat populations of the phase 3, randomised, double-blind, placebo-controlled BOREAS and NOTUS trials, which comprised 206 hospitals and clinics in BOREAS and 217 in NOTUS in 38 countries across Europe, Asia, North America, South America, Africa, and Australia.

Dupilumab Improves Health-Related Quality of Life and Respiratory Symptoms in Patients With COPD and Type 2 Inflammation: BOREAS and NOTUS.

Background: Patient-reported outcomes should be considered alongside clinical assessments to guide therapy for COPD.

Research Question: Does add-on dupilumab treatment improve health-related quality of life and respiratory symptoms in patients with COPD and type 2 inflammation?

Study Design And Methods: In this pooled analysis of two phase 3 trials, patients with COPD and type 2 inflammation receiving triple therapy were randomized 1:1 to receive dupilumab 300 mg (n = 938) or placebo (n = 936) every 2 weeks for 52 weeks. Quality of life and respiratory symptom severity were measured by change from baseline to week 52 in St.

Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression-Quantitative Trait Loci.

Asthma is a genetically complex inflammatory airway disease associated with over 200 Single nucleotide polymorphisms (SNPs). However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples.

The epithelial era of asthma research: knowledge gaps and future direction for patient care.

The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated.

GOLD COPD Exacerbation History Categories and Disease Outcomes.

Importance: Previous exacerbations of chronic obstructive pulmonary disease (ECOPD) are associated with future events. For more than a decade, patients at high risk have been defined as individuals with a history of 2 or more moderate ECOPD, 1 or more severe ECOPD, or both within 12 months, and treatments have been allocated accordingly, but these cutoffs lack validation.

Objectives: To validate ECOPD history categories by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and explore alternative cutoffs to estimate moderate and severe ECOPD and all-cause mortality in COPD.

Unravelling the Information Contained in the Single Items of the COPD Assessment Test for Different Outcomes and Smoking Status in Patients with COPD: Results from COSYCONET.

Background: The COPD Assessment Test (CAT) comprises eight questions. We evaluated the information that each of the questions and the total score contributed to outcomes and characteristics of chronic obstructive lung disease (COPD), including their dependence on smoking status.

Methods: Patients with COPD of the COSYCONET cohort with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 and the former grade 0 were included.

Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial.

Background: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, which has shown increased expression in patients with chronic obstructive pulmonary disease (COPD) compared with healthy individuals. We aimed to assess the efficacy and safety of tezepelumab in patients with moderate to very severe COPD despite receiving triple inhaled therapy.

Methods: COURSE was a double-blind, randomised, placebo-controlled, phase 2a trial across 90 sites in ten countries in Asia, Europe, and North America.

Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections.

Background: Humans are subjected to various environmental stressors (bacteria, viruses, pollution) throughout life. As such, an inherent relationship exists between the effect of these exposures with age. The impact of these environmental stressors can manifest through DNA methylation (DNAm).

Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS).

Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation in the phase 3 BOREAS trial.

Objective: To assess clinical outcomes in patients from BOREAS by emphysema status.

Methods: Patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/μL) on maximal inhaled therapy were randomized to add-on dupilumab 300 mg or placebo every 2 weeks for 52 weeks.

Dupilumab Induces Long-Term On-Treatment Clinical Remission in Patients With Type 2 Asthma.

Background: Remission is proposed as a multicomponent outcome for patients with severe asthma.

Objective: This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroid use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not receiving maintenance oral corticosteroids.

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.

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD.

Background: Accumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.

Methods: The study designs of AERIFY-1 and AERIFY-2 are described in this article.

[TELEMEdical moNiTORing for COPD patients (Telementor COPD): Study protocol of a multicentre, randomised, controlled study].

Background: COPD is one of the most common causes of death in Europe, and is associated with a high exacerbation and hospitalization rate as well as high medical costs. The aim of the study was early detection of exacerbations, preventative intervention through optimized outpatient care, and thereby to decrease rates of rehospitalizations.

Methods And Intervention: Telementor COPD is a prospective, multicentre, unblinded, randomized, controlled study with a study duration of 12 months, implemented at seven clinics and 16 pneumology practices in Hamburg and Schleswig-Holstein.

Association of airway inflammation and smoking status with IL-33 level in sputum of patients with asthma or COPD.

https://bit.ly/3SFspww

Airway specific deregulation of asthma-related serpins impairs tracheal architecture and oxygenation in D. melanogaster.

Serine proteases are important regulators of airway epithelial homeostasis. Altered serum or cellular levels of two serpins, Scca1 and Spink5, have been described for airway diseases but their function beyond antiproteolytic activity is insufficiently understood. To close this gap, we generated fly lines with overexpression or knockdown for each gene in the airways.

Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.

Introduction: Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).

Background: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD.

Sex differences in asthma control, lung function and exacerbations: the ATLANTIS study.

Background: Asthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients.

Question: What are differences between male and female patients with asthma with regard to asthma control, lung function, inflammation and exacerbations?

Methods: We performed a post hoc analysis in the ATLANTIS (Assessment of Small Airways Involvement in Asthma) study, an observational cohort study including patients with asthma from nine countries with a follow-up of 1 year during which patients were characterised with measures of large and small airway function, questionnaires, inflammation and imaging. We compared differences in baseline characteristics and longitudinal outcomes between male and female patients with asthma.

Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma.

Introduction: Eosinophil-derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non-invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma.