Neuroimmune Mechanisms in Equine Asthma: Primary Inflammatory Triggers, Neuroimmune Modulation and Chronic Airway Remodelling.

Neuroimmune interactions play a significant role in the modulation and progression of equine asthma, a chronic inflammatory lung disease caused by inhaled environmental factors, though they are unlikely to initiate the disease. Understanding these interactions, which have been well-studied in humans and rodents but are less explored in horses, could offer insights into chronic airway dysfunction and potential therapeutic targets.

Background and Context

• Equine asthma is a chronic inflammatory condition affecting the lower respiratory tract of horses.
• The disease is primarily triggered by inhalation of organic dust, microbial particles, and environmental aeroallergens.
• Although the immune inflammatory mechanisms have been extensively studied, the role of neuroimmune pathways in equine asthma remains poorly understood.
• In human and rodent models, asthma is recognized as involving complex interactions between the nervous system and immune responses.

Neuroimmune Mechanisms and Asthma in Humans and Rodents

• Asthma involves bidirectional communication between the nervous and immune systems.
• Activation of sensory nerve fibers can trigger neuropeptide release, which influences inflammation and airway function.
• Key features influenced by neuroimmune interactions include bronchoconstriction, airway hyperresponsiveness, excessive mucus secretion, and chronic airway remodeling.
• Neuronal remodeling and autonomic nervous system dysregulation contribute to the chronicity and severity of asthma symptoms.
• Specific molecules and pathways, such as neuropeptides (e.g., substance P, calcitonin gene-related peptide), transient receptor potential (TRP) channels, and neurogenic inflammation, are implicated in these processes.

Findings Specific to Equine Asthma

• Evidence shows the presence of substance P- and calcitonin gene-related peptide-immunoreactive nerve fibers in equine airways, similar to humans and rodents.
• Severe equine asthma is associated with increased bronchoconstriction mediated by neurokinin receptors.
• Airway innervation appears enhanced in horses affected by asthma, suggesting neuronal involvement in disease progression.
• Despite these findings, compared to the robust literature from human and rodent studies, research specifically targeting neuroimmune mechanisms in horses is limited.

Implications for Disease Development and Management

• Current evidence indicates neuroimmune pathways do not primarily initiate equine asthma but are important modulators influencing chronic airway inflammation and remodeling.
• These pathways may exacerbate disease progression by sustaining airway dysfunction and possibly influencing treatment responsiveness.
• Understanding neuroimmune contributions could identify new therapeutic targets aimed at modulating nerve-immune interactions to alleviate symptoms and slow disease progression.

Research Gaps and Future Directions

• There is a marked scarcity of studies examining neuroimmune signaling in equine asthma compared to human and rodent models.
• Further research is necessary to characterize the molecular and cellular neuroimmune mechanisms in horses.
• Future studies should aim to elucidate how neuronal remodeling and neuropeptide dynamics influence chronic airway remodeling and severity in equine asthma.
• Developing targeted neuroimmune-based therapies could significantly advance equine respiratory medicine and improve outcomes for affected horses.