Response to biologics along a gradient of T2 involvement in patients with severe asthma: a data-driven biomarker clustering approach.

Background: Asthma with low levels of T2-biomarkers is poorly understood.

Objective: To characterize severe asthma phenotypes and compare pre- to post-biologic change in asthma outcomes along a gradient of T2-involvement.

Methods: This was a registry-based, cohort study including data from 24 countries.

Biomarker profile and disease burden associated with intermittent and long-term oral corticosteroid use in patients with severe asthma prior to biologic initiation in real-life (STAR).

Background: Asthma characterization using blood eosinophil count (BEC) (among other biomarkers and clinical indices) is recommended in severe asthma (SA), but the masking effect of oral corticosteroids (OCS), makes this challenging.

Aim: Our aim was to explore the effect of OCS use (both intermittent [iOCS] and long-term [LTOCS]) prior to biologic initiation on SA phenotype and biomarker profile in real-life and to characterize the burden of SA among patients prescribed LTOCS by biomarker profile.

Methods: This was a registry-based cohort study, including data from 23 countries collected between 2003 and 2023 and shared with the Internatonal Severe Asthma Registry (ISAR).

Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics.

Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom).

Impact of Biologics Initiation on Oral Corticosteroid Use in the International Severe Asthma Registry and the Optimum Patient Care Research Database: A Pooled Analysis of Real-World Data.

Background: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited.

Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings.

Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2).

Serum sphingomyelin levels define oxyhemoglobin desaturation-related metabolic threshold in symptomatic obstructive sleep apnea.

Hypoxia is a contributing factor for the morbidity and mortality in patients with obstructive sleep apnea (OSA). We aimed at identifying the percentage of sleep time with oxyhemoglobin desaturation below 90% (Tc90%) breakpoint from which the most significant changes occur in systemic metabolome of patients with OSA. In a prospective observational study on patients with polysomnography-confirmed symptomatic OSA, profiles of 186 metabolites including amino acids, biogenic amines, acylcarnitines (AC), lysophosphatidylcholines, phosphatidylcholines (PC) and sphingomyelins (SM) were analyzed with liquid chromatography-mass-spectrometry in peripheral blood, obtained at 3 time points that covered patients' night sleep.

Real-World Biologic Use Patterns in Severe Asthma, 2015-2021: The CLEAR Study.

Background: Biologics targeting immunoglobulin E, interleukin (IL)-4/IL-13 or IL-5 signaling are effective at treating severe asthma; however, individual patients' responses may be suboptimal, leading to therapy switching or stopping. The CLEAR study aimed to assess real-world biologic use patterns and associated clinical outcomes in patients receiving care for severe asthma.

Methods: CLEAR was a multicenter, observational study that included adults (≥18 years old) from 23 countries enrolled in the International Severe Asthma Registry between December 2015 and August 2021.

NLRP1 Is a Prominent Inflammasome Sensor Found in Bronchial Epithelial Cells in Asthma and Can Be Activated by Rhinovirus A16.

Background: Asthma exacerbations are frequently triggered by human rhinoviruses (RVs). Among other pro-inflammatory responses, RV infection of airway epithelium promotes the activation of the inflammasome pathway, the role of which in asthma exacerbations and disease progression is still poorly understood.

Methods: Bronchial brushing or biopsy specimens were collected from asthma patients and control subjects.

International Severe Asthma Registry (ISAR): 2017-2024 Status and Progress Update.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research.

Use of High-Dose Inhaled Corticosteroids and Risk of Corticosteroid-Related Adverse Events in Asthma Findings From the NORDSTAR Cohort.

Background: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown.

Objective: To examine the association between ICS exposure and corticosteroid (CS)-related AEs.

Disease Burden and Access to Biologic Therapy in Patients with Severe Asthma, 2017-2022: An Analysis of the International Severe Asthma Registry.

Introduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies.

Methods: This was a historical cohort study of patients with severe asthma (aged ≥18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4.

Pattern of Expression of Genes Involved in Systemic Inflammation and Glutathione Metabolism Reveals Exacerbation of COPD.

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.

Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13).

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.

Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.

Antioxidant Glutathione Analogues UPF1 and UPF17 Modulate the Expression of Enzymes Involved in the Pathophysiology of Chronic Obstructive Pulmonary Disease.

Increased oxidative stress (OS) and systemic inflammation are key players in the pathophysiology of chronic obstructive pulmonary disease (COPD). We aimed to clarify the effects of synthetic glutathione (GSH) analogue peptides UPF1 and UPF17 on the mRNA levels of enzymes involved in systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs) from patients with acute exacerbation of COPD (AE-COPD) and stable COPD along with non-obstructive smokers and non-smokers. UPF1 and UPF17 increased the expression of enzymes involved in the formation of the antioxidant capacity: superoxide dismutase 1 (SOD1) and the catalytic subunit of glutamyl-cysteine ligase (GCLC) in patients with AE-COPD and stable COPD, but also in non-obstructive smokers and non-smokers.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

Background: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma.

Objective: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma.

Methods: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.

Adult Severe Asthma Registries: A Global and Growing Inventory.

Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.

Severe asthma trajectories in adults: findings from the NORDSTAR cohort.

Background: There is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma.

Methods: We conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone.

Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS.

Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry.