A proportion of severe asthma patients suffers from persistent airflow limitation (PAL), often associated with more symptoms and exacerbations. Little is known about the underlying mechanisms. Here, our aim was to discover unexplored potential mechanisms using Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples.Severe asthma patients from the U-BIOPRED cohort with PAL (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal) were compared with those without PAL. Gene expression was assessed on the total RNA of sputum cells, nasal brushings, and endobronchial brushings and biopsies. GSVA was applied to identify differentially enriched predefined gene signatures based on all available gene expression publications and data on airways disease.Differentially enriched gene signatures were identified in nasal brushings (n=1), sputum (n=9), bronchial brushings (n=1) and bronchial biopsies (n=4) that were associated with response to inhaled steroids, eosinophils, interleukin-13, interferon-α, specific CD4 T-cells and airway remodelling.PAL in severe asthma has distinguishable underlying gene networks that are associated with treatment, inflammatory pathways and airway remodelling. These findings point towards targets for the therapy of PAL in severe asthma.
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http://dx.doi.org/10.1183/13993003.02298-2016 | DOI Listing |
Rhinology
January 2025
Kuopio, Finland.
Chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) frequently coexist, forming a complex multimorbid condition often referred to as "global airway disease." This concept reflects shared pathophysiological mechanisms of eosinophilic inflammation and underscores the need for integrated treatment strategies targeting both upper and lower airway manifestations (1). The burden of severe CRSwNP, asthma, and N-ERD is substantial, particularly in terms of reduced quality of life, recurrent exacerbations, revision endoscopic sinus surgeries (ESS), and healthcare utilization (2).
View Article and Find Full Text PDFFood Sci Nutr
January 2025
Faculty of Chemical and Food Engineering, Bahir Dar Institute of Technology Bahir Dar University Bahir Dar Ethiopia.
Luteolin is widely distributed phytochemical, a flavonoid, in kingdom plantae. Luteolin with potential antioxidant activity prevent ROS-induced damages and reduce oxidative stress which is mainly responsible in pathogenesis of many diseases. Several chemo preventive activities and therapeutic benefits are associated with luteolin.
View Article and Find Full Text PDFJ Asthma Allergy
January 2025
Amgen Inc., Thousand Oaks, CA, USA.
Airway inflammation, a hallmark feature of asthma, drives many canonical features of the disease, including airflow limitation, mucus plugging, airway remodeling, and hyperresponsiveness. The T2 inflammatory paradigm is firmly established as the dominant mechanism of asthma pathogenesis, largely due to the success of inhaled corticosteroids and biologic therapies targeting components of the T2 pathway, including IL-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP). However, up to 30% of patients may lack signatures of meaningful T2 inflammation (ie, T2 low).
View Article and Find Full Text PDFFront Pharmacol
January 2025
Phase I Clinical Trial Site, Nanjing Gaoxin Hospital, Nanjing, Jiangsu, China.
Background: Fluticasone propionate is a synthetic trifluoro-substituted glucocorticoid, a highly selective glucocorticoid receptor agonist. Fluticasone propionate nebuliser suspensions is an inhaled corticosteroid with the low systemic bioavailability which provides a low risk (benefit outcome without the adverse effects that accompany systemically administered corticosteroids), referred as a first-line preventive agent for patients with persistent asthma. China has become one of the countries with the highest asthma mortality rate in the world in the past years.
View Article and Find Full Text PDFWorld Allergy Organ J
January 2025
Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.
Background: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment.
Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria.
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