Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses.

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown.

Studies of molecular pathways associated with blood neutrophil corticosteroid insensitivity in equine asthma.

Severe equine asthma is characterized by airway hyperresponsiveness, neutrophilic inflammation and structural alterations of the lower airways. In asthmatic horses with neutrophilic inflammation, there is insensitivity to corticosteroids characterized by the persistence of neutrophils within the airways with therapy. We hypothesized that hypoxia or oxidative stress in the microenvironment of the lung contributes to this insensitivity of neutrophils to corticosteroids in asthmatic horses.

Recellularization of Bronchial Extracellular Matrix With Primary Bronchial Smooth Muscle Cells.

Severe asthma is associated with an increased airway smooth muscle (ASM) mass and altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment.

Tracheal microbial populations in horses with moderate asthma.

Background: There are limited data on potential dysbiosis of the airway microbiota in horses with asthma.

Hypothesis/objectives: We hypothesized that the respiratory microbiota of horses with moderate asthma is altered. Our objectives were (a) to quantify tracheal bacterial populations using culture and qPCR, (2) to compare aerobic culture and qPCR, and (c) to correlate bacterial populations with bronchoalveolar lavage fluid (BALF) cytology.

pneumonia in an adult horse which had travelled in an endemic area.

A gelding from eastern Canada was presented for cough and exercise intolerance 14 months after it had travelled on Vancouver Island. pneumonia was diagnosed based on cytology, antigen titers, and polymerase chain reaction (PCR). The horse was treated with fluconazole for 10 months.

MicroRNA-221 is overexpressed in the equine asthmatic airway smooth muscle and modulates smooth muscle cell proliferation.

Airway wall remodeling, including hyperplasia and hypertrophy of smooth muscle (ASM) cells leading to an increased smooth muscle mass, is considered central to asthma. However, molecular pathways responsible for ASM remodeling remain poorly understood. MicroRNAs (miRNAs) have emerged as key regulators of inflammatory and repair processes affecting the lungs and can downregulate protein expression by inhibiting target mRNA translation.

Adherence to treatment recommendations and short-term outcome of pleasure and sport horses with equine asthma.

Treatments for mild forms of equine asthma are extrapolated from those recommended for severe equine asthma (heaves), but little is known about owner's adherence to recommendations and treatment efficacy. The objective was to determine which recommendations are implemented by owners and their perception of the clinical response to treatment. Medical records of 43 horses diagnosed with moderate asthma between 2010 and 2012 were retrieved from the Université de Montréal database.

SRSF6 is upregulated in asthmatic horses and involved in the MYH11 SMB expression.

Smooth muscle has a central role in bronchospasm-induced airway obstruction in asthma. Alternative mRNA splicing of the smooth muscle myosin heavy chain (myh11) gene produces four different isoforms, one of which (SMB) is characterized by the inclusion of the exon5b, which doubles the smooth muscle cells contraction velocity. Deciphering the regulation of the expression levels of the SMB isoform would represent a major step for the understanding of the triggers and pathways leading to airway smooth muscle contraction in asthma.

Lung Microbiome Is Influenced by the Environment and Asthmatic Status in an Equine Model of Asthma.

There is evidence that the lung microbiome differs between patients with asthma and healthy humans, but the effect of environmental conditions and medication is unknown and difficult to study. Equine asthma is a naturally occurring chronic airway disease characterized by reversible airway inflammation and bronchoconstriction upon exposure to inhaled antigens. In the present study, we evaluated the effect that environmental conditions and disease status have on pulmonary, nasal, and oral microbiomes.

Glucocorticosteroids administration is associated with increased regulatory T cells in equine asthmatic lungs.

Recurrent inflammation in severe equine asthma causes a remodeling of the airways leading to incompletely reversible airway obstruction. Despite the improvement of clinical signs and lung function with glucocorticoids (GC), inflammation, translated by an increased percentage of neutrophils, persists in the airways. Regulatory T cells (Treg) have been shown to have anti-inflammatory properties and play an important role in balancing the immune response by suppressing effector lymphocyte activity.

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma.

Background: Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.

Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways.

Rationale: Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown.

Objectives: To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status.