Equis ISSN 2398-2977

Lung: recurrent airway obstruction (RAO)

Synonym(s): RAO, Chronic obstructive pulmonary disease, COPD, Heaves, Broken wind, Chronic hypersensitivity bronchitis, Chronic hypersensitivity bronchiolitis, CB, Chronic alveolar emphysema, Small airway disease, SAD, Allergic airway disease

Contributor(s): Christopher Brown, Cody Coyne, Timothy Mair, Vetstream Ltd

Introduction

  • Common, chronic, progressive lower respiratory disease syndrome of horses and ponies.
  • The term RAO is often applied to both young and older horses with lower airway disease characterized by inflammation and accumulation of mucus, however, in younger horses there is not measurable evidence of airway obstruction.
  • Cause: chronic exposure to inhaled dust particles containing allergens, eg moldy hay, thermo-actinomycetes.
  • Signs: poor performance, chronic coughing and increased expiratory effort, poor stable/barn environment.
  • Diagnosis: clinical signs and history; bronchoalveolar lavage or inhalation challenge.
  • Treatment: palliative only; change environment - remove allergens and improve management; control inflammation - corticosteroids; increase airway diameter - bronchodilators.
  • Prognosis: clinical signs usually reversible on removal of allergens; susceptible horses may develop hyper-reactivity.
Print off the Owner factsheets on Emergencies - when to call the vetRecurrent airway obstruction (RAO) and Respiratory problems in your horse to give to your clients.

Pathogenesis

Etiology

  • Exposure of susceptible horses to hay and dusts rich in organic material containing spores of fungi and thermophilic bacteria.
  • Over 50 species of moulds have been identified in stable air.
  • Combination of genetic predisposition, environment and disease history.
  • May be a final common pathway for structural damage to the bronchopulmonary system.
  • An earlier bronchopulmonary infection may be an initiating factor (often history of febrile respiratory episode).
  • Most allergenic bacteria includeAspergillus fumigatus,Faenia rectivirgolaandThermoactinomycetes vulgaris.

Environmental factors

  • Poorly cured hay (high levels of thermo-actinomycetes - see below).
  • Dusty feeds.
  • Poor ventilation.
  • Prolonged stabling.
  • Bacteria.
  • Endotoxins.
  • Animal debris - dander, hair, urine, feces.
  • Plant material.
  • Insect debris, eg forage mitesLepidoglyphus destructor.
  • Fungal debris, eg spores, hyphae, mycotoxins, sporangia.

Fungi

  • Pathogenic mechanism based upon hypersensitivity.
  • Micropolyspora faeni/Faeni rectivirgula: thermophilic actinomycete.
  • Aspergillus fumigatus  Aspergillus spp  - fungal spores.
  • Wet hay and straw   Hay: moldy  (>20% moisture) overheat   →   contamination with thermotolerant fungi and actinomycetes.
  • Water content at baling is main determinant of heating and microbial development in hay.

Stable ventilation is less important than removing the source of dust.

Predisposing factors

General
  • Genetic susceptibility to inhaled allergens.
  • Poor stable management:
    • Inadequate clearance of wet bedding (humid environment).
    • Poor ventilation.
    • Poor quality bedding and hay.
  • Changes in bedding or hay.

Specific

Pathophysiology

  • Precise immunological mechanisms not yet determined.
  • Types 1 (immediate), 3 (arthus) and 4 (delayed) reactions implicated.
  • Repeated/chronic exposure to inhaled spores   →   deposit on mucosa   →   primary irritation; inhaled endotoxin may also have a primary irritant effect or potentiate the effects of allergen inhalation.

Acute

  • Airway reactivity:
    • Susceptible horses develop severe airway obstruction in response to apparently minor stimuli   →   hyper-reactive airways.
    • Airway hyper-reactivity is non-specific - occurs in response to exposure to anything, including inflammatory mediators, that might cause bronchospasm.
    • Reactivity lessens when exposure to agents is avoided.
    • Exposure for 7 h to a dusty environment   →   hyper-reactivity persists for <72 h.
  • Inflammation   →   :
    • Neutrophils invade airways.
    • Release of proinflammatory mediators, eg histamine   →   smooth muscle contraction, increased airway sensitivity.
    • Leukotrienes   →   bronchospasm.
    • Reduced availability of inhibitory mediators, eg prostaglandin E2.
    • Inactivation of nitric oxide, a neurotransmittor in the iNANC nervous system.
    • Increased mucous production and secretion + increased bronchial blood flow and vascular permeability   →   edema and plugging of airways with mucous.
  • Lung function   →   :
    • Airway obstruction   →   increased pulmonary resistance + decreased compliance   →   increased respiratory effort to achieve necessary tidal volume.
    • Ventilation-perfusion mismatching and hypoxemia.

    Although the horse must increase its respiratory effort there is no evidence of hypoventilation expressed as an increase in PaCO2.

    • Increased respiratory drive + airway obstruction   →   'heaves' (double expiratory effort).
    • Despite airway narrowing   →   increased peak tidal flow rates.

Structural changes

  • Clara cells (non-ciliated bronchiolar epithelial cells) undergo ultrastructural alteration even in mild disease leading to degeneration and loss of differentiation.
  • Metaplasia of goblet cells.
  • Focal changes in peribronchiolar alveoli including necrosis of Type I cells, fibrosis, transformation of Type II cells, emphysema and increased numbers of Kohn's pores.
  • Conducting airways show secondary non-specific changes including focal loss of ciliated cells.
  • Viral respiratory infection   →   mucosal ulceration and decreased mucociliary clearance   →   enhanced penetration of antigens across damaged epithelial surfaces in respiratory tract; damaged mucociliary clearance means enhanced antigen/allergen retention.
  • Chronic inflammation   →   mucosal and smooth muscle proliferate enhancing the ability of the airways to contract.
  • Although an immune-mediated basis for RAO has been supported by many studies, positive skin tests and serum precipitins to fungal and thermophilic actinomycete antigens probably reflect a history of exposure in normal and susceptible horses, rather than a specific susceptibility to RAO.

Timecourse

  • Chronic.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Pirie R S (2014)Recurrent airway obstruction: A review.Equine Vet J46(3), 276-288PubMed.
  • Venugopal Cet al(2013)Effect of potential therapeutic agents in reducing oxidative stress in pulmonary tissues of recurrent airway obstruction-affected and clinically healthy horses.Equine Vet J45(1), 80-84PubMed.
  • Bertin F R, Ivester K M & Couetil L L (2011)Comparative efficacy of inhaled albuterol between two and-held delivery devices in horses with recurrent airway obstruction.Equine Vet J43(4), 393-398PubMed.
  • Leclere M, Lefebvre-Lavoie J, Beauchamp G & Lavoie J P (2010)Efficacy of oral prednisolone and dexamethasone in horses with recurrent airway obstruction in the presence of continuous antigen exposure.Equine Vet J42(4), 316-321PubMed.
  • Laumen E, Doherr M G & Gerber V (2010)Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families.Equine Vet J42(2), 142-148PubMed.
  • Berndt A, Derksen F J, Venta P J, Karmaus W, Ewart S, Yuzbasiyan-Gurkan V & Robinson N E (2009)Expression of toll-like receptor 2 mRNA in bronchial epithelial cells is not induced in RAO-affected horses.Equine Vet J41(1), 76-81PubMed.
  • Lavoie J-P, Thompson D, Hamilton E, Debrue M, David F & Hickey G (2008)Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction.Equine Vet J40(6), 577-583PubMed.
  • Bakos Z (2008)Digital luminescence thoracic radiography in horses with recurrent airway obstruction.Vet Rec162(4), 122-124PubMed.
  • Barrelet A (2007)Laboratory investigation of poor performance in horses: Part 2 - Investigation of respiratory disease.UK Vet12(1), 15-21VetMedResource.
  • Camargo F Cet al(2007)Trimetoquinol: bronchodilator effects in horses with heaves following aerolised and oral administration.Equine Vet J39(3), 215-220PubMed.
  • Jost Uet al(2007)A region on equine chromosome 13 is linked to recurrent airway obstruction in horses.Equine Vet J39(3), 236-241PubMed.
  • Camargo F Cet al(2006)Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with 'heaves'.Equine Vet J38(6), 563-569PubMed.
  • Cesarini C, Hamilton E, Picandet V & Lavoie J P (2006)Theophylline does not potentiate the effects of a low dose of dexamethasone in horses with recurrent airway obstruction.Equine Vet J38(6), 570-573PubMed.
  • Deaton C Met al(2006)Comparison of the antioxidant status in tracheal and bronchoalveolar epithelial lining fluids in recurrent airway obstruction.Equine Vet J38(5), 417-422PubMed.
  • Ghio A J, Mazan M R, Hoffman A M & Robinson N E (2006)Correlates between human lung injury after particle exposure and recurrent airway obstruction in the horse.Equine Vet J38(4), 362-367PubMed.
  • Lavoie J-Pet al(2006)Lack of clinical efficacy of a phosphodiesterase-4 inhibitor for treatment of heaves in horses.J Vet Intern Med20(1), 175-181PubMed.
  • Laan T T J M, Bull S, Pirie S R, Fink-Gremmels J (2006)The role of alveolar macrophages in the pathogenesis of recurrent airway obstruction in horses.J Vet Intern Med20(1), 167-174PubMed.
  • Simonen-Jokinen Tet al(2005)Effect of composition and different fractions of hay dust suspension on inflammation in lungs of heaves-affected horses: MMP-9 and MMP-2 as indicators of tissue destruction.Equine Vet J37(5), 412-417PubMed.
  • Deaton C Met al(2005)Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone.Equine Vet J37(3), 243-249PubMed.
  • Gerber V, Lindberg A, Berney C & Robinson N E (2004)Airway mucus in recurrent airway obstruction - short-term response to environmental challenge.J Vet Intern Med18(1), 92-97PubMed.
  • Rossdale P Det al(2004)Pulmonary leiomyosarcoma in a 13-year-old Thoroughbred stallion presenting as a differential diagnosis to recurrent airway obstruction.Equine Vet Educ16(1), 21-28VetMedResource.
  • Herholz C, Straub R, Braendlin C, Imhof A, Luthi S & Busato A (2003)Measurement of tidal breathing flow-volume loop indices in horses used for different sporting purposes with and without recurrent airway obstruction.  Vet Rec152(10), 288-292PubMed.
  • Kolm G, Zappe H, Schmid R, Riedelberger K & van Den Hoven R (2003)Efficacy of Montelukast in the treatment of chronic obstructive disease in five horses.Vet Rec152(26), 804-806PubMed.
  • van Den Hoven R, Zappe H, Zitterl-Eglseer K, Jugl M & Franz C (2003)Study of the effect of Bronchipret on the lung function of five Austrian saddle horses suffering recurrent airway obstruction (heaves).Vet Rec152(18), 555-557PubMed.
  • Picandet V, Leguillette R & Lavoie J P (2003)Comparison of efficacy and tolerability of isoflupredone and dexamethasone in the treatment of horses affected with recurrent airway obstruction ('heaves').Equine Vet J35(4), 419-424PubMed.
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  • Robinson N Eet al(2001)Management of heaves.Equine Vet Educ13(5), 247VetMedResource.
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  • Raulo S M et al (2001)MMP-9 as a marker of inflammation in tracheal epithelial lining fluid (TELF) and in bronchoalveolar fluid (BALF) of COPD horses.Equine Vet J33(2), 128-136PubMed.
  • Pirie R Set al(2001)Pulmonary and systemic effects of inhaled endotoxin in control of heaves horses.Equine Vet J33(3), 311-318PubMed.
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Other sources of information

  • McGorum B (1998)Inflammation and COPD in Horses.In:Proc World Equine Airway Symposium(detailed pathophysiology of inflammatory process in COPD).
  • Robinson N E (1998)COPD - Past, Present and Future.In:Proc World Equine Airway Symposium.
  • Robinson N E (1997)Pharmacology of the Equine Tracheobronchial Tree.In:Proc 43rd Annual AAEP Conv. pp 95-105.
  • Robinson N E (1997)Pathogenesis and Management of Airway Disease.In:Proc 43rd Annial AAEP Conv. pp 106-115.


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