Thickening of arterial walls in the lungs of badly asthmatic horses seen in study – Horsetalk

Muscular pulmonary artery and annexed bronchus: GLA (red outline) = great longitudinal axis; ED (green outline) = external diameter; EP (yellow outline) = external perimeter; IP* (blue outline) = internal perimeter; LP (pink outline) = lumen perimeter; TA (within yellow outline) = total area; IA* (within blue outline) = internal area; LA (within pink outline) = lumen area. https://doi.org/10.1371/journal.pone.0239561.g001

Severe asthma in horses can trigger thickening of the walls of lung arteries, researchers have found.

This kind of remodeling is also seen in the pulmonary arteries of humans with chronic obstructive pulmonary disease, which contributes to the development of pulmonary hypertension.

Similar changes to the pulmonary arteries have also been seen in rodent experiments as a result of allergic airway inflammation.

Severe equine asthma, also known as heaves and recurrent airway obstruction, is a chronic, non-infectious inflammatory lower airway disease. It is characterized by recurrent episodes of airway obstruction caused by exposure to environmental antigens, such as fungi, hay mites and endotoxins.

Serena Ceriotti and her colleagues, reporting in the open-access journal PLOS ONE, note that pulmonary hypertension and changes to the function of the right ventricle of the heart are complications of severe equine asthma, arising from pulmonary hypoxic vasoconstriction.

However, as pulmonary hypertension is only partially reversible by giving oxygen, other factors are likely involved.

The study team set out to investigate the presence of changes to the pulmonary arteries in cases of severe equine asthma and their distribution throughout the lungs. They also examined the potential reversibility of this remodeling either through long-term avoidance of the allergens that trigger the condition, or inhaled corticosteroids.

The researchers measured the total wall area of pulmonary arteries from different regions of the lungs of asthmatic horses and compared the results with those from healthy control horses. The smooth muscle mass of pulmonary arteries was also estimated.

Reversibility of changes to the blood vessels in asthmatic horses was assessed after a year of avoiding the allergens alone, or treatment with inhaled fluticasone for a similar time.

The scientists found that the pulmonary arteries showed increased wall area in the apical (upper reaches) and in the caudodorsal (closest to the spine, toward the tail) lung regions of asthmatic horses in both exacerbation and remission.

The pulmonary artery smooth muscle mass was similarly increased.

Both treatments reversed the increase in wall area, they reported. However, a trend for normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone.

In conclusion, severe equine asthma is associated with remodeling (thickening) of the pulmonary arteries consisting of an increased smooth muscle mass.

The resulting narrowing of the artery could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension, they said.

In our study population, the antigen avoidance strategy appeared more promising than inhaled corticosteroids in controlling vascular remodeling.

However, further studies are needed to support the reversibility of vascular smooth muscle mass remodeling after asthma treatment.

Discussing their findings, the researchers said their work revealed significant pulmonary artery wall thickening in asthmatic horses compared to controls.

The average wall area of muscular pulmonary arteries in asthmatic horses was 7% to 12% greater than that of controls increases similar to those seen in humans with chronic obstructive pulmonary disease.

This remodeling affected only the caudodorsal lung fields and the lung apex, they said.

An increase in airway smooth muscle mass was also present in severely asthmatic horses, they said.

Short-term antigen avoidance significantly improved lung function and airway inflammation in asthmatic horses, while smooth muscle mass was not reduced in muscular pulmonary arteries in the present study, nor in small peripheral airways in a previous work.

While pulmonary artery wall thickening was reversed by long-term antigen avoidance (12 months), this was not the case for horses treated that inhaled corticosteroids for the same period, despite six months of associated antigen avoidance.

While inhaled corticosteroids were mainly effective on airway obstruction, long-term antigen avoidance better controlled neutrophilic airway inflammation.

This, they said, supports a possible role of inflammation in the development of pulmonary artery remodeling, facilitated by the strict anatomic relationship between pulmonary circulation and the airways, as already investigated in acute allergic human asthma.

The researchers say further studies should focus on the role of hypoxemia and inflammation in inducing remodeling of pulmonary arteries smooth muscle, as well as its impact on pulmonary artery pressure and cardiovascular complications in severe equine asthma.

The full study team comprised Ceriotti, who is Auburn University in Alabama; Michela Bullone, Mathilde Leclere and Jean-Pierre Lavoie, who are with the University of Montreal in Quebec; and Francesco Ferrucci, who is with the University of Milan in Italy.

Ceriotti S, Bullone M, Leclere M, Ferrucci F, Lavoie J-P (2020) Severe asthma is associated with a remodeling of the pulmonary arteries in horses. PLoS ONE 15(10): e0239561. https://doi.org/10.1371/journal.pone.0239561

The study, published under a Creative Commons License, can be read here.

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Thickening of arterial walls in the lungs of badly asthmatic horses seen in study - Horsetalk