One of the major goals of asthma therapy is to maintain asthma control and prevent acute exacerbations. Long-acting bronchodilators are regularly used for the treatment of asthma patients and in clinical studies the anti-cholinergic tiotropium has recently been shown to reduce exacerbations in patients with asthma. So far it is unclear how tiotropium exerts this effect. For this purpose, we designed an allergen-driven rechallenge model of allergic airway inflammation in mice, to assess the effectiveness of tiotropium and the long-acting β-2 adrenoceptor agonist olodaterol on allergen-induced exacerbations of airway disease. Female C57BL/6J mice were sensitized intranasally (i.n.) with 1 μg of house dust mite (HDM) extract followed by a challenge regime (5 consecutive days 10 μg HDM extract i.n.) after one week. Mice were exposed to a secondary challenge five weeks after sensitization and were treated i.n. with different concentrations of tiotropium or olodaterol (1, 10 and 100 μg/kg) or a combination thereof (10 μg/kg each) prior to and during the secondary challenge period. Three days after the last challenge, bronchoalveolar lavage (BAL) fluid and lung tissue were collected for flow cytometry and histologic analysis, respectively. Secondary challenge with HDM extract strongly induced allergic airway disease reflected by inflammatory cell infiltration and goblet cell metaplasia. Treatment with tiotropium, but not with olodaterol reduced tissue inflammation and goblet cell metaplasia in a dose-dependent manner. The combination of tiotropium and olodaterol was more effective in significantly reducing tissue inflammation compared to tiotropium treatment alone, and also led to a decrease in BAL cell counts. These data suggest that in a model of relapsing allergic airway disease tiotropium directly prevents exacerbations by reducing inflammation and mucus production in the airways. In addition, the combination of tiotropium and olodaterol exerts synergistic effects.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.pupt.2017.06.010 | DOI Listing |
Allergy
December 2024
Laboratory of Mitochondrial Biology and Metabolism, NHLBI, NIH, Bethesda, Maryland, USA.
Background: The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4 T cells may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity.
View Article and Find Full Text PDFFront Allergy
December 2024
Allergy and Clinical Immunology Unit, Meir Medical Center, Kfar Saba, Israel.
Background: Asthma, allergic rhinitis, atopic dermatitis, and food allergy are type 2 inflammation diseases. Since the 1960s, the prevalence of those diseases has steadily increased, presumably due to the "Hygiene hypothesis" which suggests that early exposure of infants to pathogens, siblings, and environmental dust, has a protective effect against the development of allergic diseases. The COVID-19 pandemic increased environmental hygiene due to lockdowns, masks, and social distancing.
View Article and Find Full Text PDFJ Allergy Clin Immunol Glob
February 2025
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to . Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.
Objective: We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.
Int Immunopharmacol
December 2024
Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Department of Allergy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address:
Background: Environmental pollutants have been found to contribute to the development and acute exacerbation of asthma. Microplastics (MPs) have received widespread attention as an emerging global pollutant. Airborne MPs can cause various adverse health effects.
View Article and Find Full Text PDFJ Inflamm (Lond)
December 2024
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
The chemokine CCL20, a small cytokine that belongs to the C-C chemokine family, interacts with its homologous receptor CCR6, which is expressed on wide range of cell types. According to current research, the CCL20-CCR6 has been established as acritical player in a diverse range of inflammatory, oncogenic, and autoimmune diseases. Within the respiratory system, CCL20-CCR6 demonstrates heightened expression in conditions such as allergic asthma, chronic airway inflammation, non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), and other respiratory diseases, which is conducive to the inflammatory mediators recruitment and tumor microenvironment remodeling.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!