Abstract: Inflammatory airway disease (IAD) is very common in stabled horses. Short-acting beta agonist (SABA) drugs are often used to relieve clinical signs, although long-term exposure to these drugs may result in rebound bronchoconstriction. The purpose of this study was twofold: i) to describe the deposition of radiolabeled drugs using a novel one-nostril design mask-spacer combination with a breath-activated inhaler (BAI), and ii) to determine whether treatment for 10 d with inhaled albuterol using this device would impair the ability of albuterol to prevent bronchospasm during a histamine challenge test. The percentage of radio-aerosol deposited in the total lung was 12.39% ± 5.05%. All study horses demonstrated airway hyperresponsiveness (AHR) before enrollment in the study [mean provocative concentration eliciting 35% increase in delta flow (PC35) < 6 mg/mL histamine]. There was no significant difference in airway hyperresponsiveness to post-albuterol histamine challenge before or after treatment with albuterol. A 10-d treatment with placebo, however, caused a significant increase in airway hyperresponsiveness in all horses (P < 0.001). The results of this study show that the novel mask-spacer device was effective in delivering radiolabeled aerosolized drug to the lung and that delivery of a SABA for 10 d using this device did not result in increased airway hyperresponsiveness. La maladie inflammatoire des voies respiratoires (IAD) est très courante chez les chevaux gardés en écurie. Les médicaments agonistes bêta à courte action (SABA) sont souvent utilisés pour soulager les signes cliniques, bien qu’une exposition prolongée à ces médicaments puisse résulter en une bronchoconstriction rebond. Le but de la présente étude était double : i) décrire le dépôt de médicaments radio-marqués en utilisant un nouveau design de chambre d’inhalation pour une seule narine avec un inhalateur activé par l’haleine (BAI), et ii) déterminer si un traitement pendant 10 j avec de l’albuterol inhalé avec cet appareil compromettrait la capacité de l’albuterol à prévenir un bronchospasme durant un test défi à l’histamine. Le pourcentage d’aérosol radio-marqué déposé dans le poumon total était de 12,39 % ± 5,05 %. Tous les chevaux dans l’étude ont montré une hyperréactivité des voies respiratoires (AHR) avant l’incorporation dans l’étude [concentration moyenne induisant une augmentation de 35 % du delta flot (PC35) < 6 mg/mL d’histamine]. Il n’y avait pas de différence significative d’hyperréactivité des voies respiratoires au challenge à l’histamine post-albuterol avant ou après traitement avec de l’albuterol. Toutefois, un traitement pendant 10 j avec un placebo a causé une augmentation significative d’hyperréactivité des voies respiratoires chez tous les chevaux ( < 0,001). Les résultats de la présente étude ont montré que le nouveau design d’inhalateur était efficace pour la distribution par aérosol de médicament radio-marqué dans les poumons et que l’administration de SABA pendant 10 j à l’aide de cet appareil n’a pas causé d’augmentation de l’hyperréactivité des voies respiratoires.(Traduit par Docteur Serge Messier).
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research paper presents a study of a novel one-nostril mask-spacer device employed to evaluate airway hyperresponsiveness in horses after chronic administration of the drug, albuterol. The study showed that the new mask-spacer device was effective for delivering aerosolized drug to the lungs, and 10-day usage did not cause increased airway hyperresponsiveness.
Objective of the Study
The study was conducted with two major goals: Firstly, to describe the deposition of radiolabeled drugs using a new one-nostril design mask-spacer combination with a breath-activated inhaler (BAI). It aimed to assess how effectively the device can deliver the medication directly to the lungs. Secondly, to investigate if a 10-day treatment using inhaled albuterol with this device would affect albuterol’s ability to prevent bronchospasm during a histamine challenge test.
Methods Used
The research team used radiolabeled aerosolized drugs to precisely detail their deposition in the respiratory system when applied via the one-nostril mask-spacer device. This methodology helped them quantify the level of drug delivered to the lungs.
They ran a histamine challenge test before and after the treatment with albuterol to probe if there is any change in airway hyperresponsiveness. This test helped to determine whether the bronchial tubes of the horses would respond differently to histamine – a neurotransmitter that can cause narrowing of the airways – after the medication was administered.
Results of the Study
The study found that the one-nostril mask-spacer device successfully delivered 12.39% ± 5.05% of the radiolabeled aerosol to the lungs. This indicated a reasonably effective delivery of the medication directly into the lungs.
All the horses included in the study exhibited airway hyperresponsiveness before the start of the treatment. However, there was no significant increase in airway hyperresponsiveness to post-albuterol histamine challenge before or after the treatment with albuterol. This implies that chronic administration of the drug didn’t alter the airway reaction to histamine.
A notable outcome was that a 10-day placebo treatment resulted in a significant increase in airway hyperresponsiveness across all horses. This suggests implicitly that horses could be prone to increased airway reaction in absence of the drug.
Conclusion of the Study
The findings led to the conclusion that the novel mask-spacer device is effective in delivering aerosolized drugs to the lungs of horses. Moreover, a 10-day administration of a short-acting beta agonist drug like albuterol, utilizing this device, didn’t lead to increased airway hyperresponsiveness.
The results reinforce the need for well-designed inhalation devices for horses, specifically those suffering from inflammatory airway disease, to facilitate better aerosol drug delivery and potentially improve treatment outcomes.
Cite This Article
APA
Mazan MR, Lascola K, Bruns SJ, Hoffman AM.
(2014).
Use of a novel one-nostril mask-spacer device to evaluate airway hyperresponsiveness (AHR) in horses after chronic administration of albuterol.
Can J Vet Res, 78(3), 214-220.
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Mazan, Hoffman); Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61801, USA (Lascola); Equine Health Studies Program, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA (Bruns).
Lascola, Kara
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Mazan, Hoffman); Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61801, USA (Lascola); Equine Health Studies Program, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA (Bruns).
Bruns, Susan J
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Mazan, Hoffman); Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61801, USA (Lascola); Equine Health Studies Program, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA (Bruns).
Hoffman, Andrew M
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Mazan, Hoffman); Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61801, USA (Lascola); Equine Health Studies Program, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA (Bruns).
Lundblad LK, Rinaldi LM, Poynter ME, Riesenfeld EP, Wu M, Aimi S, Barone LM, Bates JH, Irvin CG. Detrimental effects of albuterol on airway responsiveness requires airway inflammation and is independent of β-receptor affinity in murine models of asthma.. Respir Res 2011 Mar 7;12(1):27.
Funch-Nielsen H, Roberts C, Weekes JS, Deaton CM, Marlin DJ. Evaluation of a new spacer device for delivery of drugs into the equine respiratory tract.. Proceedings of the WEAS-CRS Symposium 2001;p. 56.
Viel LC, Celly C, Staempfli H, Tesarowski DB. Therapeutic efficacy of inhaled fluticasone propionate in horses with chronic obstructive pulmonary disease.. Proceedings of the 45th Ann Conv Am Assoc Equine Pract 1999;45:306–307.
Harrison LI. Local versus total systemic bioavailability of beclomethasone dipropionate CFC and HFA metered dose inhaler formulations.. J Aerosol Med 2002 Winter;15(4):401-6.
Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone : a cross-over study in healthy volunteers.. Chest 2002 Aug;122(2):510-6.
Lipworth BJ, Clark DJ. Lung delivery of non-CFC salbutamol via small volume metal spacer and large volume plastic spacer devices compared with an open vent jet nebulizer.. Br J Clin Pharmacol 1998 Feb;45(2):160-3.
Hoffman AM, Foley M, Spendlove PJ. Respiratory medicine: Advances in inter-species aerosol delivery.. Proc Austr Equine Sci Symp 2008;2:47.
Lee Z, Berridge MS, Nelson AD, Heald DL. The effect of scatter and attenuation on aerosol deposition as determined by gamma scintigraphy.. J Aerosol Med 2001 Summer;14(2):167-83.
Bondesson E, Bengtsson T, Borgström L, Nilsson LE, Norrgren K, Trofast E, Wollmer P. Planar gamma scintigraphy--points to consider when quantifying pulmonary dry powder aerosol deposition.. Int J Pharm 2003 Jun 4;258(1-2):227-40.
Marlin DJ, Kingston DA, Weekes J, Deaton CM, Schroter RC. Attenuation of 99m-Technetium in the equine thorax.. Oral presentation; 21st Veterinary and Comparative Respiratory Symposium 2003.
Morrison D, Skwarski K, Millar AM, Adams W, MacNee W. A comparison of three methods of measuring 99mTc-DTPA lung clearance and their repeatability.. Eur Respir J 1998 May;11(5):1141-6.
Pansegrouw DF. Acute resistant asthma caused by excessive beta-2-adrenoceptor agonist inhalation and reversed by inhalation of beclomethasone.. S Afr Med J 1992 Sep;82(3):179-82.
Keir S, Page C, Spina D. Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role of sensory nerves.. J Allergy Clin Immunol 2002 Sep;110(3):388-94.
Reinero CR, Delgado C, Spinka C, DeClue AE, Dhand R. Enantiomer-specific effects of albuterol on airway inflammation in healthy and asthmatic cats.. Int Arch Allergy Immunol 2009;150(1):43-50.
Cooper PR, Panettieri RA Jr. Steroids completely reverse albuterol-induced beta(2)-adrenergic receptor tolerance in human small airways.. J Allergy Clin Immunol 2008 Oct;122(4):734-740.
Adner M, Larsson B, Säfholm J, Naya I, Miller-Larsson A. Budesonide prevents cytokine-induced decrease of the relaxant responses to formoterol and terbutaline, but not to salmeterol, in mouse trachea.. J Pharmacol Exp Ther 2010 Apr;333(1):273-80.
Dennis SM, Sharp SJ, Vickers MR, Frost CD, Crompton GK, Barnes PJ, Lee TH. Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy Working Group of the National Asthma Task Force and the MRC General Practice Research Framework.. Lancet 2000 May 13;355(9216):1675-9.
Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ, Deykin A, Fagan JK, Fahy JV, Fish J, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF Jr, Liggett SB, Martin RJ, Mitra N, Peters SP, Silverman E, Sorkness CA, Szefler SJ, Wechsler ME, Weiss ST, Drazen JM. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.. Lancet 2004 Oct 23-29;364(9444):1505-12.
Klotz LR, Klotz SD, Moeller RK. The use of beclomethasone diproprionate inhaler complicated by the development of an eosinophilic pneumonia reaction.. Ann Allergy 1977 Aug;39(2):133-6.
Vanden Burgt JA, Busse WW, Martin RJ, Szefler SJ, Donnell D. Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma.. J Allergy Clin Immunol 2000 Dec;106(6):1209-26.