- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Respiratory and Cough-Related Research
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pediatric health and respiratory diseases
- Diabetes Management and Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Pulmonary Hypertension Research and Treatments
- Immune Response and Inflammation
- Mast cells and histamine
- Respiratory Support and Mechanisms
- Obstructive Sleep Apnea Research
- Pancreatic function and diabetes
- Cardiovascular and exercise physiology
- Eosinophilic Esophagitis
- Neuroscience of respiration and sleep
- Food Allergy and Anaphylaxis Research
- Sports Performance and Training
- Connective tissue disorders research
McMaster University
2015-2025
St. Joseph’s Healthcare Hamilton
2010-2025
University of Saskatchewan
1952-2023
Royal University Hospital
2018-2022
Institute for Respiratory Health
2001-2020
St. Joseph's Hospital
1998-2019
The Ohio State University Wexner Medical Center
2019
St Joseph's Health Care
2018
Saskatoon Medical Imaging
2018
University of Toronto
1952-2016
Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is characteristic feature some forms asthma. However, in three previous clinical trials involving patients with asthma, blockade this cytokine did not result significant improvement outcomes. We studied the prednisone-sparing effect mepolizumab, monoclonal antibody against interleukin-5, rare subgroup who have sputum eosinophilia and airway symptoms despite continued treatment prednisone. Secondary objectives were...
It is now fully appreciated that asthma a disease of chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses continuous antigen exposure, mice were exposed either house dust mite extract (HDM) ovalbumin intranasally for five consecutive days, followed by 2 days rest, up seven weeks. Continuous HDM, unlike ovalbumin, elicited severe and persistent eosinophilic Flow cytometric analysis demonstrated an accumulation...
We have previously demonstrated that oral treatment with live Lactobacillus reuteri can attenuate major characteristics of the asthmatic response in a mouse model allergic airway inflammation. However, mechanisms underlying these effects remain to be determined.We tested hypothesis regulatory T cells play role mediating L. reuteri-induced attenuation response.BALB/c mice were treated daily by gavage. Flourescent-activated cell sorter analysis was used determine CD4(+)CD25(+)Foxp3(+)T...
Clinical trials have demonstrated that probiotics may be effective in the treatment and prevention of atopic disease children but there been few reports therapeutic effects oral outside gastrointestinal tract.We investigated effect two probiotic organisms on response to antigen challenge a mouse model allergic airway inflammation.We used an ovalbumin-sensitized asthma BALB/c Toll-like receptor 9-deficient mice. Animals were treated with via gavaging needle before challenge. After challenge,...
Rationale: Recent findings suggesting transforming growth factor (TGF)-β1 activation by mechanical stimuli in vitro raised the question of whether this phenomenon was relevant vivo context pulmonary fibrosis.Objectives: To explore effect stress on TGF-β1 and its signaling pathway rat human fibrotic lung tissue using a novel ex model.Methods: Rat fibrosis induced transient gene expression active TGF-β1. Lungs were harvested at Day 14 or 21 submitted to various bath equipped with force...
Intranasal instillation techniques are used to deliver various substances the upper and lower respiratory tract (URT LRT) in mice. Here, we quantify relative distribution achieved with intranasal delivery of a nonabsorbable tracer, (99m)Tc-labeled sulfide-colloid. Relative was determined by killing mice after quantifying radioactivity dissected tissues using gamma scintigraphy. A significant effect volume on observed when animals were killed 5 min delivered under gas anesthesia. With microl,...
Abstract It is now well established that passive exposure to inhaled OVA leads a state of immunological tolerance. Therefore, elicit allergic sensitization, researchers have been compelled devise alternative strategies, such as the systemic delivery in context powerful adjuvants, which are alien way humans exposed and sensitized allergens. The objectives these studies were investigate immune-inflammatory responses intranasal purified house dust mite (HDM) extract evaluate role GM-CSF this...
Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary hypertension (PH) and ultimately death. Despite this known association, precise mechanism disease remains unknown. Using a rat model IPF, we explored role proangiogenic antiapoptotic growth factor VEGF in vascular remodeling that underlies PH. In model, adenoviral delivery active TGF-beta1 induces arterial remodeling, loss microvasculature fibrotic areas, increased pressure (PAP). Immunohistochemistry mRNA analysis...
Adding inhaled long-acting β2-agonists to a low dose of corticosteroids (ICS), results in better clinical asthma control than increasing the ICS. However, this approach may mask underlying airway inflammation. In double-blind parallel-group study, we evaluated effect adding formoterol budesonide, compared with higher on composition induced sputum. After 4-wk run-in period treatment budesonide (800 μ g, twice daily), 60 patients moderate were randomly assigned 1-yr 400 g plus placebo, daily...
TNF-α has long been regarded as a proimmune cytokine involved in antimicrobial type 1 immunity. However, the precise role of immunity remains poorly understood. We found that TNF-α–deficient (TNF–/–) mice quickly succumbed to respiratory failure following lung infection with replication-competent mycobacteria, because apoptosis and necrosis granuloma structure. Tissue destruction was result an uncontrolled immune syndrome characterized by expansion activated CD4 CD8 T cells, increased...
Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive disease (COPD), asthma, and idiopathic fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM involved in organization, may be the pathogenesis of these diseases. We found that Fbln1 was increased COPD patients cigarette smoke-induced (CS-induced) experimental mice. Genetic or therapeutic inhibition Fbln1c protected...
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated role of GRP78, main UPR regulator, in an experimental model injury fibrosis. Grp78(+/-) , Chop(-/-) wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation lungs examined at days 7 21. We demonstrate here that strongly protected from bleomycin-induced fibrosis, as...
Experimental models are critical for the understanding of lung health and disease indispensable drug development. However, pathogenetic clinical relevance is often unclear. Further, use animals in biomedical research controversial from an ethical perspective. The objective this task force was to issue a statement with recommendations about by facilitating in-depth discussions between respiratory scientists, provide overview literature on available models. Focus put their specific benefits...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Abstract In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas Ag-presenting activity of macrophages has been linked with development Th1 phenotype. As an switch toward can protect against Th2-mediated allergic response, this study investigated capacity lung to stimulate responses during secondary exposure inhaled allergen, thereby suppressing airway inflammation in a murine model asthma. Following macrophage depletion...
The mechanisms underlying airway hyperresponsiveness remain unclear, although inflammation and remodeling likely play important roles. We have observed sustained hyperreactivity occurring in mice after chronic allergen exposure persisting beyond resolution of allergen-induced inflammation. aim this study was to delineate involved examine evidence for a causal association between hyperreactivity. Wild-type (WT) interleukin (IL)-4-, IL-5-, IL-13-deficient (-/-) were sensitized studied 4 weeks...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Increases in inflammatory cell progenitors, particularly eosinophil/basophil colony-forming cells (Eo/ B-CFU), occur peripheral blood after allergen provocation. The role of bone marrow (BM) these reactions is unclear. We examined the effect challenge on human progenitor growth. Fifteen asthmatic subjects, eight dual responders (DR) and seven isolated early (IER), were challenged with inhaled allergen. BM aspirates taken before 24 h progenitors enumerated by a assay. Eo/B-CFU numbers...
IL-5 is induced locally in the lung and systemically circulation during allergic airways eosinophilic inflammation both humans experimental animals. However, precise role of local systemic development eosinophilia remains to be elucidated. In our current study, we demonstrate that compared with their IL-5(+/+) counterparts, IL-5(-/-) mice lacked an response peripheral blood, yet they released similar amounts IL-4, eotaxin, MIP-1alpha after ovalbumin (OVA) sensitization challenge. At cellular...