Hunting for a key to the enigma of heaves in the black box of the white cells.

This research article focuses on investigating the characteristics, similarities and differences between equine recurrent airway obstruction (heaves) and allergic conditions like asthma and insect bite hypersensitivity, challenging the common perception of heaves as a simple allergy and suggesting a need to reassess and further understand its complex cellular and molecular mechanisms.

Comparisons between Heaves and Asthma

• Some clinical similarities exist between heaves and human asthma including recurring reversible airway obstruction, worsening conditions with the inhalation of particulate matter and significant improvement with corticoids and bronchodilators.
• Nevertheless, differences are also present. Asthma is typically identified in childhood, often with concurrent food allergies or allergic skin diseases, while heaves does not usually affect young horses and is not associated with these other allergy types.

Functional Alterations and Cellular Differences

• Both heaves and asthma share functional alterations such as bronchospasm, bronchial hyperreactivity and hypersecretion, gas exchange impairment and coughing, primarily involving the bronchi and bronchioles.
• However, the onset of bronchospasm in asthma is almost immediate while in heaves it occurs several hours after exposure to environmental triggers.
• Significant cellular differences exist – atopic asthma is characterised by eosinophilic pulmonary inflammation but heaves shows a predominance of neutrophils. The allergic reaction patterns also differ significantly.

The Role of Cytokines

• A distinguishing feature of asthma is an acute two-phase reaction with both immediate and delayed hypersensitivity responses. In contrast, the inflammatory response in heaves occurs earlier after challenge and is neutrophilic in nature, aligning more closely with farmer’s lung disease, a type III hypersensitivity.
• Analysis of the cytokine pattern or the Th1/Th2 balance shows inconsistency and confusion in its comparison between heaves and human asthmatic pattern, leading to uncertainty in categorising heaves simply as an allergic reaction.
• Some evidence like elevated serum and bronchoalveolar lavage fluid (BALF) IgE concentrations suggest a Th2 polarisation, pointing towards an allergic reaction while several other aspects suggest a Th1 response and involvement of innate immunity, indicating immune response diversity.
• The Th1/Th2 concept is under increasing scrutiny as many diseases previously classified as Th1 or Th2 dominant no longer meet the set criteria due to overlapping cytokine activities.

Need for Further Research

• The existing knowledge implies a need to reconsider Th1/Th2 balance theory in the context of heaves and explore the differentiation of naïve T-cells after a respiratory challenge.
• Future studies should explore the role of Th17, another type of T helper cell, to provide a more accurate and detailed understanding of the complex mechanisms underlying heaves.