Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Lavoie, Jean‐Pierre; Léguillette, Renaud; Pasloske, Kirby; Charette, L.; Sawyer, Nicole; Guay, Daniel; Murphy, Terry; Hickey, Gerard J.

doi:10.2460/ajvr.2002.63.579

Cited by 49 publications

(44 citation statements)

References 22 publications

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“…9,34,35 Furthermore, an LTD 4 -receptor antagonist failed to improve airway function in RAO-affected horses. 36 Overall, these results do not support a role for the cysteinyl-LTs in RAO.…”

Section: Discussionmentioning

confidence: 86%

Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction

Lindberg

Robinson²,

Näsman-Glaser³

et al. 2004

ajvr

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“…9,34,35 Furthermore, an LTD 4 -receptor antagonist failed to improve airway function in RAO-affected horses. 36 Overall, these results do not support a role for the cysteinyl-LTs in RAO.…”

Section: Discussionmentioning

confidence: 86%

Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction

Lindberg

Robinson²,

Näsman-Glaser³

et al. 2004

ajvr

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“…Previous studies have revealed that daily administration of 0.04 mg/kg of dexamethasone to RAO-affected horses maintained in moldy hay environments results in significant improvement in lung function starting on the 3rd day of administration with a maximum benefit by the end of 2 weeks of therapy. 20,21 If horses are maintained in the moldy hay environment, pulmonary function may return to pretreatment levels as early as 6 days after discontinuation of treatment. 20 This could explain the lack of effect of dexamethasone 21-isonicotinate on pulmonary function 10 days after a single injection under these experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

“…20,21 If horses are maintained in the moldy hay environment, pulmonary function may return to pretreatment levels as early as 6 days after discontinuation of treatment. 20 This could explain the lack of effect of dexamethasone 21-isonicotinate on pulmonary function 10 days after a single injection under these experimental conditions. In this study, horses received a microcrystalline insoluble form of dexamethasone 21-isonicotinate (VorenH Depot TM ) that results in peak dexamethasone concentration 24 hours after administration and sustained serum concentrations as long as 14 days.…”

Section: Discussionmentioning

confidence: 99%

Effect of Beclomethasone Dipropionate and Dexamethasone Isonicotinate on Lung Function, Bronchoalveolar Lavage Fluid Cytology, and Transcription Factor Expression in Airways of Horses with Recurrent Airway Obstruction

Couëtil

Art

Moffarts

et al. 2006

Veterinary Internal Medicne

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Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kB (NF-kB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kB and AP-1 in bronchial cells of RAO-affected horses. Seven horses with RAO were exposed to moldy hay until they developed airway obstruction on 3 separate occasions. In a crossover design, they were then treated with a placebo (injection on day 1), inhaled beclomethasone (500 mg q12h for 10 days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days. Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kB and AP-1 activity in bronchial brushing cells were measured before (day 1) and after treatment (day 10). Treatment with beclomethasone resulted in significantly improved pulmonary function of RAOaffected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kB and AP-1 activity. These findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled beclomethasone on pulmonary function are not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kB and AP-1 DNA-binding activity.

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“…Lavoie et al could not demonstrate improved lung function in horses with RAO after administration of a leukotriene D 4 antagonist [14]. A more recent study suggested that there is increased leukotriene B 4 and C 4 production in airways of horses affected with RAO which may contribute to infiltration of neutrophils into the lungs and the sustained inflammation associated with RAO [15].…”

Section: Introductionmentioning

confidence: 99%

Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

et al. 2012

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BackgroundGlucocorticoids have been proven to be effective in the therapy of recurrent airway obstruction (RAO) in horses via systemic as well as local (inhalative) administration. Elective analysis of the effects of this drug on bronchoconstriction in viable lung tissue offers an insight into the mechanism of action of the inflammatory cascade occurring during RAO which is still unclear. The mechanism of action of steroids in treatment of RAO is thought to be induced through classical genomic pathways. We aimed at electively studying the effects of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung slices (PCLS).PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices.ResultsAfter 30 minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP) differed significantly from each other (p = 0.002). The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period.ConclusionsIn human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.

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Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

Cited by 49 publications

References 22 publications

Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction

Assessment of leukotriene B4 production in leukocytes from horses with recurrent airway obstruction

Effect of Beclomethasone Dipropionate and Dexamethasone Isonicotinate on Lung Function, Bronchoalveolar Lavage Fluid Cytology, and Transcription Factor Expression in Airways of Horses with Recurrent Airway Obstruction

Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

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