Steroid-resistant inflammation in a mouse model of severe asthma is not inhibited by the combination of theophylline and budesonide

2018 ◽  
Author(s):  
Vince Russell ◽  
Mariapia Brana ◽  
Daniela Pompilio ◽  
Giulia Ambrosi ◽  
Filippo Andreetta ◽  
...  
Keyword(s):  
Mouse Model ◽  
Severe Asthma ◽  
Steroid Resistant

scholarly journals Steroid-Resistant Neutrophilic Inflammation in a Mouse Model of an Acute Exacerbation of Asthma

2008 ◽  
Vol 39 (5) ◽  
pp. 543-550 ◽  
Author(s):  
Kazuhiro Ito ◽  
Cristan Herbert ◽  
Jessica S. Siegle ◽  
Chaitanya Vuppusetty ◽  
Nicole Hansbro ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acute Exacerbation ◽  
Steroid Resistant ◽  
Neutrophilic Inflammation

scholarly journals Novel mouse model of steroid-resistant allergic rhinitis by repeated intranasal administration of OVA

2015 ◽  
Vol 8 ◽  
pp. A30
Author(s):  
Kazunari Izumi ◽  
Hideki Kawasome ◽  
Atsushi Azuma ◽  
Kenjiro Sasaki ◽  
Masayuki Kamada ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Mouse Model ◽  
Intranasal Administration ◽  
Steroid Resistant

scholarly journals Serum Prednisolone Levels as a Marker of Oral Corticosteroid Adherence in Severe Asthma

2020 ◽  
Author(s):  
James Michael Ramsahai ◽  
Emily King ◽  
Robert Niven ◽  
Gael Tavernier ◽  
Peter Wark ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Prospective Observational Study ◽  
Oral Prednisolone ◽  
Sputum Eosinophil ◽  
Steroid Resistant ◽  
Sputum Eosinophilia ◽  
Advanced Therapies ◽  
Objective Marker ◽  
Eosinophil Counts

Abstract Background Severe asthma is a complex heterogeneous disease typically requiring advanced therapies. Underlying the treatment of all asthma, however, is the consistent recommendation across international guidelines to ensure that adherence to therapy is adequate. Currently, there is no consensus on an objective marker of adherence.Methods We performed a prospective observational study of 17 participants taking oral prednisolone using serum prednisolone levels as a marker of adherence, and sputum eosinophilia as a marker of control of type 2 airway inflammation. Based on these biomarkers, we classified participants into a non-adherent and an adherent cohort, and further stratified by the presence of ongoing sputum eosinophilia.Results We identified 3 non-adherent participants and 14 who were adherent, based on their serum prednisolone levels. Stratification using sputum eosinophil counts identified one participant as having ongoing sputum eosinophilia in the setting of non-adherence, while six were identified as steroid resistant with ongoing sputum eosinophilia despite adherence to oral prednisolone therapy.Conclusion Serum prednisolone can be used an objective marker of adherence in those patients with severe asthma taking daily oral prednisolone. In combination with sputum eosinophil counts, a steroid resistant cohort can be distinguished from one with ongoing inflammation in the setting of non-adherence. This information can then be used by clinicians to differentiate the optimal next steps for treatment in these specific populations.

Mapping a mouse model of severe asthma to human asthma using gene set variation analysis

2015 ◽  
Author(s):  
Kirsty Russell ◽  
Stelios Pavlidis ◽  
Coen Wiegman ◽  
Jeannette Bigler ◽  
Navin Rao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Severe Asthma ◽  
Variation Analysis ◽  
Gene Set

No exacerbation but impaired anti-viral mechanisms in a rhinovirus-chronic allergic asthma mouse model

2013 ◽  
Vol 126 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Sabine Rochlitzer ◽  
Heinz-Gerd Hoymann ◽  
Meike Müller ◽  
Armin Braun
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Severe Asthma ◽  
Allergic Airway Inflammation ◽  
Interleukin 12 ◽  
Cell Counts ◽  
Asthma Exacerbations ◽  
Eosinophil Cell

Severe asthma and viral-induced asthma exacerbations represent a high unmet medical need as no therapy is currently available for these patients. HRV (human rhinovirus) is prominently associated with asthma exacerbations in humans. The aim of the present study was to establish a mouse model of severe asthma with additional rhinovirus infection to investigate the interplay between chronic allergic airway inflammation and acute respiratory viral infection. Balb/c mice were sensitized with HDM (house dust mite) extract (25 μg in 50 μl of saline) by i.n. (intranasal) delivery to the lung over 7 weeks. HRV1B (HRV serotype 1B) inoculation was performed i.n. on the last 3 days. Therapeutic treatment with FP (fluticasone propionate) was performed to assess steroid efficacy. Lung resistance was measured invasively to assess AHR (airway hyper-responsiveness). BAL (bronchoalveolar lavage) differential cell count, cytokines, lung histology and the proliferative and cytokine response of MLN (mediastinal lymph node) cells upon in vitro restimulation were analysed. Chronic HDM application induced a strong Th2-skewed eosinophilic airway inflammation and AHR, which was not exacerbated by superimposed HRV1B infection. Therapeutic steroid intervention in the chronic HDM model reduced BAL eosinophil cell counts, cytokine levels and AHR, while neutrophil numbers were unaffected. Steroid efficacy against inflammatory readouts was maintained during additional HRV1B infection. Animals with chronic allergic airway inflammation exhibited a diminished immune response towards superimposed HRV1B infection compared with HRV1B alone, as induction of the anti-viral and pro-inflammatory cytokines IFN (interferon)-α, IFN-γ and IL (interleukin)-12 were suppressed. Although superimposed HRV1B infection did not provoke asthma exacerbation in this severe model, a deficient anti-viral immune response to HRV1B was present under chronic allergic airway inflammatory conditions. Thus, this model is able to reflect some aspects of the complex interplay of respiratory virus infection in chronic allergic asthma.

scholarly journals Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias

JCI Insight ◽  
2017 ◽  
Vol 2 (13) ◽  
Author(s):  
Marc Gauthier ◽  
Krishnendu Chakraborty ◽  
Timothy B. Oriss ◽  
Mahesh Raundhal ◽  
Sudipta Das ◽  
...  
Keyword(s):  
Mouse Model ◽  
Severe Asthma

scholarly journals Development of highly potent glucocorticoids for steroid-resistant severe asthma

2019 ◽  
Vol 116 (14) ◽  
pp. 6932-6937 ◽  
Author(s):  
Yuanzheng He ◽  
Jingjing Shi ◽  
Quang Tam Nguyen ◽  
Erli You ◽  
Hongbo Liu ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Unique Property ◽  
Asthma Treatment ◽  
Delivery Method ◽  
Fluticasone Furoate ◽  
Steroid Resistant ◽  
Inhalation Delivery ◽  
Pharmacokinetic Properties ◽  
Inhaled Glucocorticoids ◽  
Insight Into

Clinical application of inhaled glucocorticoids (GCs) has been hampered in the case of steroid-resistant severe asthma. To overcome this limitation, we have developed a series of highly potent GCs, including VSGC12, VSG158, and VSG159 based on the structural insight into the glucocorticoid receptor (GR). Particularly, VSG158 exhibits a maximal repression of lung inflammation and is 10 times more potent than the currently most potent clinical GC, Fluticasone Furoate (FF), in a murine model of asthma. More importantly, VSG158 displays a unique property to reduce neutrophilic inflammation in a steroid-resistant airway inflammation model, which is refractory to clinically available GCs, including dexamethasone and FF. VSG158 and VSG159 are able to deliver effective treatments with reduced off-target and side effects. In addition, these GCs also display pharmacokinetic properties that are suitable for the inhalation delivery method for asthma treatment. Taken together, the excellent therapeutic and side-effect profile of these highly potent GCs holds promise for treating steroid-resistant severe asthma.

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