BACKGROUND: Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced @entity55 and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. OBJECTIVE: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the @entity55 and dysfunction. METHODS: We measured the response of six heaves @entity1641 following inhalation of saline (placebo) and three doses of @entity54 extract. We then compared the response of six heaves @entity1641 to A. fumigatus extract inhalation before and after lipopolysaccharide (LPS) depletion. RESULTS: Inhalation challenge with 0.5, 1.6 and 5 mg of A. fumigatus extract resulted in a significant increase in bronchoalveolar lavage fluid (BALF) neutrophil ratio when compared with saline inhalation. Only 1.6 and 5 mg extract inhalation resulted in significant @entity358 compared with saline. There was no significant difference between 1.6 and 5 mg extract inhalation with respect to airway neutrophil numbers or lung function, suggesting a plateau in both measured responses. LPS depletion of 1.6 mg A. fumigatus extract resulted in a significant reduction in airway neutrophil numbers and increase in arterial @entity26 tension. There was no significant difference between saline and the LPS-depleted A. fumigatus extract challenges with respect to neutrophil count and lung function. The reduction in airway neutrophil numbers was greater than would be predicted by extrapolation from previously reported soluble LPS dose-response inhalation experiments. CONCLUSION: This study supports a role for other inhalants, in addition to soluble components of A. fumigatus, in the aetiopathogenesis of heaves. Also the amplification in response to LPS when inhaled with A. fumigatus extract, suggests that the role of inhaled endotoxin in the @entity55 and dysfunction in naturally occurring heaves may currently be underestimated.

Endotoxin contamination contributes to the pulmonary inflammatory and functional response to @entity54 extract inhalation in heaves XXXX .

@entity1641 :: ('9796', 'Species') :: ['horses'] @entity55 :: ('MESH:D011014', 'Disease') :: ['pulmonary neutrophilic inflammation', 'pulmonary inflammation'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity54 :: ('746128', 'Species') :: ['Aspergillus fumigatus'] @entity358 :: ('MESH:D008171', 'Disease') :: ['lung dysfunction']
@entity1641 :: (9796,Species) :: ['horses']
