Medicine and Health Sciences Commons^™

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Genetic Overlap Analysis Of Endometriosis And Asthma Identifies Shared Loci Implicating Sex Hormones And Thyroid Signalling Pathways, Emmanuel O. Adewuyi, D. Mehta, D. R. Nyholt, International Endogene Consortium (Iec), 23andme Research Team

Research outputs 2022 to 2026

STUDY QUESTION: Is there a shared genetic or causal association of endometriosis with asthma or what biological mechanisms may underlie their potential relationships? SUMMARY ANSWER: Our results confirm a significant but non-causal association of endometriosis with asthma implicating shared genetic susceptibility and biological pathways in the mechanisms of the disorders, and potentially, their co-occurrence. WHAT IS KNOWN ALREADY: Some observational studies have reported a pattern of co-occurring relationship between endometriosis and asthma; however, there is conflicting evidence and the aetiology, as well as the underlying mechanisms of the relationship, remain unclear. STUDY DESIGN, SIZE, DURATION: We applied multiple statistical genetic …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Student and Faculty Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Derivation Of A Prototype Asthma Attack Risk Scale Centred On Blood Eosinophils And Exhaled Nitric Oxide, Simon Couillard, Annette Laugerud, Maisha Jabeen, Sanjay Ramakrishnan, James Melhorn, Timothy Hinks, Ian Pavord

Research outputs 2014 to 2021

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide. Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment.

Combination Fixed-Dose Β Agonist And Steroid Inhaler As Required For Adults Or Children With Mild Asthma: A Cochrane Systematic Review, Iain Crossingham, Sally Turner, Sanjay Ramakrishnan, Anastasia Fries, Matthew Gowell, Farhat Yasmin, Rebekah Richardson, Philip Webb, Emily O'Boyle, Timothy S. C. Hinks

Research outputs 2014 to 2021

Background:

In people with mild asthma poor adherence to regular therapy is common and increases the risk of exacerbations, morbidity and mortality. The use of fixed-dose combination inhalers containing an inhaled corticosteroid (ICS) and a fast-acting β2-agonist (FABA) is established in moderate asthma, but they may also have potential utility in mild asthma.

Objectives:

To evaluate the efficacy and safety of single combined FABA/ICS inhaler only used as needed in people with mild asthma. Design and setting: Cochrane meta-analysis of available trial data.

Participants:

Children aged 12+ and adults with mild asthma. Search methods: We searched the Cochrane Airways Trials …

Air Pollutant Levels And Asthma Emergency Room Visits In A Highly Populous Us Urban County During 2018-19, Osaremhen Ikhile, Jingjing Yin, Atin Adhikari

Journal of the Georgia Public Health Association

Objective: Air pollutants are linked to asthma exacerbation. The study purpose was to demonstrate an association between air pollutants levels and asthma emergency room (ER) visit trends in a highly populated US urban county in Georgia during 2018-2019.

Methods: Time series analyses were conducted for the variations in daily numbers of children and adult asthma emergency room visits and changes in daily mean PM_2.5, daily mean PM₁₀ concentrations, daily max 1-hour SO₂ concentrations, daily max 1-hour NO₂ concentrations, daily max 8-hour ozone concentrations, and airborne pollen loads for 2018 to 2019 and potential trends were …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Student and Faculty Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Characterisation Of Lung Function Trajectories And Associated Early-Life Predictors In An Australian Birth Cohort Study, Francesca Sanna, Francesca Locatelli, Peter D. Sly, Elisha White, Jane Heyworth, Graham L. Hall, Rachel E. Foong, David Blake

Research outputs 2022 to 2026

Background There is growing evidence that lung function in early-life predicts later lung function. Adverse events over the lifespan might influence an individual’s lung function trajectory, resulting in poor respiratory health. The aim of this study is to identify early-life risk factors and their impact on lung function trajectories to prevent long-term lung impairments. Methods Our study included participants from the Raine Study, a prospective pregnancy cohort, with at least two spirometry measurements. Lung function trajectories from the 6-to 22-year follow-ups were characterised using finite mixture modelling. Multinomial logistic regression analyses were used to evaluate the association between early-life predictors …