Publications by authors named "Gail M Gauvreau"

Chronic cough is associated with several respiratory diseases and is a significant burden on physical, social, and psychological health. Non-invasive, real-time, continuous, and quantitative monitoring tools are highly desired to assess cough severity, the effectiveness of treatment, and monitor disease progression in clinical practice and research. There are currently limited tools to quantitatively measure spontaneous coughs in daily living settings in clinical trials and in clinical practice.

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This paper presents a comprehensive review of cardiorespiratory auscultation sensing devices (i.e., stethoscopes), which is useful for understanding the theoretical aspects and practical design notes.

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Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations.

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Background: Atopic dermatitis (AD) is a skin barrier dysfunction characterized by tissue eosinophilia.

Objective: In patients with AD, we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge.

Methods: A total of 20 patients with moderate-to-severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses of benralizumab (30 mg each) administered subcutaneously every 4 weeks (n = 9) with placebo (n = 11).

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Background: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma.

Methods: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses).

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Article Synopsis
  • - The study explores immune response changes in COVID-19 patients, focusing on leukocyte levels, eosinophil activity, and cytokine profiles during hospitalization.
  • - Researchers collected serum samples and medical data within the first 10 days of infection, finding increased levels of certain cytokines but decreased eosinophil levels in COVID-19 patients compared to hospitalized controls.
  • - The findings suggest a complex immune response in COVID-19, with low eosinophil activity and high cytokine levels, indicating the need for more research on immune biomarkers and treatment approaches.
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Disruption of the airway epithelium triggers a defensive immune response that begins with the production and release of alarmin cytokines. These epithelial-derived alarmin cytokines, including thymic stromal lymphopoietin (TSLP), are produced in response to aeroallergens, viruses, and toxic inhalants. An alarmin response disproportionate to the inhaled trigger can exacerbate airway diseases such as asthma.

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This issue highlights and details the program and scientific presentations at the International Eosinophil Society's 12th biennial symposium, which was held in Hamilton, Ontario, Canada, in July 2023. The meeting included sessions on regulation of eosinophil development; cell death, stress, and autophagy in eosinophils; local immunity interactions of eosinophils with multiple cell types; eosinophils in host defense; eosinophils and mast cells in gastrointestinal disorders; reciprocal interactions between eosinophils and the microbiome in homeostasis and dysbiosis; and eosinophils in tissue injury and repair and in tumor biology and cancer therapy. There was a mixture of special invited lectures and cutting-edge abstracts on specific aspects of eosinophil science, as well as enlivened pro-con debates on targeting eosinophils with biologics.

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In asthma, sputum group 2 innate lymphoid cells (ILC2s) are activated within 7 hours after allergen challenge. Neuroimmune interactions mediate rapid host responses at mucosal interfaces. In murine models of asthma, lung ILC2s colocalize to sensory neuronal termini expressing the neuropeptide neuromedin U (NMU), which stimulates type 2 (T2) cytokine secretion by ILC2s, with additive effects to alarmins .

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Background: Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators.

Methods: 20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961).

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Article Synopsis
  • The study investigates the role of alarmin cytokines in COVID-19, especially their effect on immune response and disease severity, while exploring the influence of genetic variations and sex differences.
  • Researchers measured levels of specific cytokines (IL-33 and IL-25) in COVID-19 patients, finding them elevated compared to non-COVID patients, suggesting their potential as treatment targets.
  • Genetic analysis revealed that certain genetic variations are associated with protective effects against severe COVID-19 and highlight the importance of considering individual genetic and sex factors in treatment strategies.
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Background: Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma.

Methods: This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany.

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The alarmin cytokines thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 are epithelial cell-derived mediators that contribute to the pathobiology and pathophysiology of asthma. Released from airway epithelial cells exposed to environmental triggers, the alarmins drive airway inflammation through the release of predominantly T2 cytokines from multiple effector cells. The upstream positioning of the alarmins is an attractive pharmacological target to block multiple T2 pathways important in asthma.

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Poorly controlled asthma can affect neonatal outcomes including congenital anomalies, which can be reduced with appropriate asthma care during pregnancy. Although there is a concern regarding the safety of asthma medication use during pregnancy and congenital anomalies, the risk of uncontrolled asthma outweighs any potential risks of controller and reliever medication use. Patient education before and during pregnancy is critical to ensure good compliance to therapy and reduce the risk of poor asthma control.

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Asthma is a chronic disease of the airways characterized by inflammation, tightened muscles, and thickened airway walls leading to symptoms such as shortness of breath, chest tightness, and cough in patients. The increased risk of asthma in children of asthmatics parents supports the existence of genetic factors involved in the pathogenesis of this disease. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with asthma.

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The airway epithelium is the first line of defense for the lungs, detecting inhaled environmental threats through pattern recognition receptors expressed transmembrane or intracellularly. Activation of pattern recognition receptors triggers the release of alarmin cytokines IL-25, IL-33, and TSLP. These alarmins are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells.

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Article Synopsis
  • The allergen provocation test helps scientists understand how things like pollen and dust can make people with allergies or asthma feel sick in their lungs and nose.
  • It studies early reactions in the upper airways and late reactions in the lower airways, which helps researchers develop new medicines for asthma.
  • Recent advancements in research are helping to create more personalized treatments by looking at different types of asthma and better ways to test lung function.
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BackgroundAdenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity.

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Background: Cough is a common troublesome symptom in asthma which is neuronally mediated. Limosilactobacillus reuteri DSM-17938 (L. reuteri DSM-17938) is a probiotic shown to be effective in pre-clinical models at suppressing neuronal responses to capsaicin, a transient receptor potential vanilloid agonist (TRPV1).

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Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis.

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