The Burden of COPD with Type 2 Inflammation in North-West Continental Europe.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that places a huge burden on patients, health systems and societies. Yet despite this, COPD is often neglected: it is frequently underdiagnosed or misdiagnosed, and since tobacco exposure is a primary risk factor for its development, patients are often stigmatized and marginalized because they are perceived as having a "self-inflicted" disease. COPD is primarily understood to be a functional disorder with chronic airway obstruction, yet there are several underlying inflammatory pathways.

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.

Impact of the metabolic syndrome on cardiopulmonary morbidity and mortality in individuals with lung function impairment: a prospective cohort study of the Danish general population.

Background: Whether the metabolic syndrome plays a role for the prognosis of individuals with lung function impairment (preserved ratio impaired spirometry (PRISm) or airflow limitation) is unclear. We hypothesised that the metabolic syndrome in individuals with lung function impairment is associated with increased cardiopulmonary morbidity and mortality.

Methods: The Copenhagen General Population Study was initiated in 2003 based on a random sample of white men and women aged 20-100 years drawn from the Danish general population.

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.

Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease.

Background: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features.

Objective: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRS) and spirometry (FEV and FEV/forced vital capacity; PRS) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO).

Methods: We developed and tested 2 asthma PRSs and applied the higher performing PRS and a previously published PRS to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record-based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies.

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.

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.

Repeated bronchoscopy in health and obstructive lung disease: is the airway microbiome stable?

Objective: Little is known concerning the stability of the lower airway microbiome. We have compared the microbiota identified by repeated bronchoscopy in healthy subjects and patients with ostructive lung diseaseases (OLD).

Methods: 21 healthy controls and 41 patients with OLD completed two bronchoscopies.

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.

Coagulation markers as predictors for clinical events in COPD.

Background And Objective: Activation of the blood coagulation system is a common observation in inflammatory diseases. The role of coagulation in COPD is underexplored.

Methods: The study included 413 COPD patients and 49 controls from the 3-year Bergen COPD Cohort Study (BCCS).

The airway microbiota and exacerbations of COPD.

Aim: The aim of this study was to investigate whether the compositionality of the lower airway microbiota predicts later exacerbation risk in persons with COPD in a cohort study.

Materials And Methods: We collected lower airways microbiota samples by bronchoalveolar lavage and protected specimen brushes, and oral wash samples from 122 participants with COPD. Bacterial DNA was extracted from all samples, before we sequenced the V3-V4 region of the 16S RNA gene.

Respiratory symptoms and mortality in four general population cohorts over 45 years.

Objective: This study assessed the association between respiratory symptoms and mortality in four cohorts of the general population in Norway aged 15-75 years and in selected subgroups in the pooled sample.

Methods: The study comprised 158,702 persons, who were drawn randomly from the Norwegian population register. All subjects received a standardized, self-administered questionnaire on 11 respiratory symptoms between 1972 and 1998, with follow-up of death until December 31, 2017.

Urinary Leukotriene E and Prostaglandin D Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study.

New approaches are needed to guide personalized treatment of asthma. To test if urinary eicosanoid metabolites can direct asthma phenotyping. Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants.

Complications and discomfort after research bronchoscopy in the MicroCOPD study.

Background: Data on discomfort and complications from research bronchoscopy in chronic obstructive pulmonary disease (COPD) and asthma is limited. We present complications and discomfort occurring within a week after bronchoscopy, and investigate personal and procedural risk factors.

Methods: 239 subjects with COPD, asthma or without lung disease underwent research bronchoscopies as part of a microbiome study of the lower airways (the MicroCOPD study).

Sputum microbiota and inflammation at stable state and during exacerbations in a cohort of chronic obstructive pulmonary disease (COPD) patients.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are debilitating events and spur disease progression. Infectious causes are frequent; however, it is unknown to what extent exacerbations are caused by larger shifts in the airways' microbiota. The aim of the current study was to analyse the changes in microbial composition between stable state and during exacerbations, and the corresponding immune response.

Risk factors for lung cancer in COPD - results from the Bergen COPD cohort study.

Background: COPD patients have an increased risk of developing lung cancer, but the underlying mechanisms are poorly understood. We aimed to identify risk factors for lung cancer in patients from the Bergen COPD Cohort Study.

Methods: We compared 433 COPD patients with 279 healthy controls, all former or current smokers.

Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Motivation and response rates in bronchoscopy studies.

Background: Bronchoscopy is frequently used to sample the lower airways in lung microbiome studies. Despite being a safe procedure, it is associated with discomfort that may result in reservations regarding participation in research bronchoscopy studies. Information on participation in research bronchoscopy studies is limited.