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Airway remodeling in equine asthma.
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Severe equine asthma remains an incurable disease although we have effective therapy to control its clinical signs. We postulate that inflammation-induced airway structural changes (remodeling) are responsible for the progression of equine asthma. Recent findings have revealed that remodeling occurs in airways of all sizes in severe equine asthma, but is most marked in the smaller peripheral airways. The airway smooth muscle (ASM) mass, which contributes to the severity of bronchospasm, is 2 to 3 times greater than in age-matched controls. Furthermore, the ASM composition is altered with an increased expression of fast contracting (+) insert smooth muscle myosin isoform (SMMHC) that may increase bronchoconstriction severity (1, 2). We also found that neutrophil-derived exosomes may participate to the progression of asthma by promoting in situ proliferation of smooth muscle and hyperplasia (3). The changes are not limited to the smooth muscle layer, as a thickening of the airway lamina propria also arises due to increased collagen (type 1 and type 3) and elastic fiber deposition (4). These changes correlate with the lung function confirming that airway remodeling contributes to asthma severity.
The airway subepithelial collagen deposition was fully reversed by 12-month treatment with either antigen avoidance or inhaled corticosteroid (ICS) administration. Therapy also reduced ASM mass (30% on average), but it remained greater (2 fold) than in healthy horses (5). Combined ICS and long-acting ß2-agonist drugs (ICS/LABA) or ICS monotherapy alone equally induced a 30% decrease of the ASM mass at 3 months (but not after 1 month) (6). However, only ICS/LABA or antigen avoidance alone decreased airway luminal neutrophilia.
These findings reveal that, once established, remodeling of the asthmatic airways is only partially reversible with current therapy. Therefore, efforts should be aimed at the early identification of susceptible horses and the implementation of preventative measures. Studies of the molecular pathways contributing to remodeling are needed for the development of novel therapy in asthma.
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