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Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma).

Abstract: Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. Objective: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Methods: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. Heaves-susceptible horses also received inhalation challenge with HDS particulates with and without the addition of LPS and were housed in two separate dusty environments during which mould and endotoxin exposure was measured. The airway inflammatory and functional response to each challenge was measured. Results: Depletion of endotoxin from HDS attenuated the airway neutrophilia and abrogated the airway dysfunction induced in heaves horses by inhaled HDS. The airway response was re-established by adding back LPS to the depleted HDS, confirming that the attenuation in airway response was due specifically to endotoxin depletion. Interestingly, the magnitude of alteration in airway response following endotoxin depletion and add-back was greater than that which could be attributed solely to endotoxin per se, indicating that the LPS activity was enhanced by the other dust components. Consistent with this possibility, washed particulates harvested from HDS enhanced the airway response to inhaled LPS in heaves horses. Heaves horses given two different hay/straw challenges had a significantly different severity of airway inflammation and dysfunction, despite airborne dust and endotoxin concentrations in the horses' breathing zones being similar. Conclusions: Although inhaled endotoxin appears not to be the only determinant of disease severity in heaves, it does contribute significantly to the induction of airway inflammation and dysfunction. This contribution is largely via the synergistic action of inhaled endotoxin and organic dust particulates, although other soluble dust components also contribute to a lesser degree.
Publication Date: 2003-05-20 PubMed ID: 12752598DOI: 10.1046/j.1365-2222.2003.01640.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study investigates the role of inhaled endotoxin and organic dust particulates, mainly mold spores, in causing a type of asthma in horses known as ‘heaves.’ The researchers found that while inhaled endotoxin contributes significantly to airway inflammation and dysfunction, it is not the only determinant of the disease severity.

Research Objective and Methods

  • The experiment aimed to understand the role that different components found in dust, specifically endotoxin and organic dust particulates, play in the severity of equine heaves, a type of asthma in horses characterized by airway inflammation, excess mucus, and impaired lung function.
  • The study involved control and heaves-susceptible horses receiving inhalation challenges with a hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. LPS is a type of endotoxin found in dust.
  • Heaves-susceptible horses were also exposed to HDS particulates with and without LPS addition, and were kept in two separate dusty environments, allowing the researchers to monitor mold and endotoxin exposure.
  • The airway response of the horses was measured after each challenge.

Research Findings

  • The study found that depletion of endotoxin from HDS reduced the severity of airway inflammation in affected horses, both in terms of inflammation and overall lung function. When LPS was reintroduced to the depleted HDS, the detrimental airway response was reinstated, pointing to the specific role of endotoxin in eliciting the symptoms of heaves.
  • Interestingly, the alteration in the airway response following the depletion and addition of LPS was more pronounced than what could be attributed solely to the endotoxin, suggesting that the chemical reaction of LPS is enhanced by other dust components.
  • This theory was further validated by the fact that washed particulates from HDS intensified the airway response to inhaled endotoxin in heaves horses.
  • Horses exposed to two different types of hay/straw treatments showed variations in the severity of airway inflammation and dysfunction, despite similar concentrations of airborne dust and endotoxin in their breathing environments.

Conclusions

  • These findings verify that while inhaled endotoxin contributes substantially to the induction of airway inflammation and dysfunction in horses suffering from heaves, it is not the sole contributor to disease severity. Other components of organic dust also play an influential role.
  • The study revealed a synergistic effect between inhaled endotoxin and organic dust particulates, suggesting that these components enhance either’s activity, leading to an exacerbation of the condition. Still, other soluble dust components may contribute to a lesser extent as well.

Cite This Article

APA
Pirie RS, Collie DD, Dixon PM, McGorum BC. (2003). Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust-induced asthma). Clin Exp Allergy, 33(5), 676-683. https://doi.org/10.1046/j.1365-2222.2003.01640.x

Publication

ISSN: 0954-7894
NlmUniqueID: 8906443
Country: England
Language: English
Volume: 33
Issue: 5
Pages: 676-683

Researcher Affiliations

Pirie, R S
  • Wellcome Trust Centre for Research in Comparative Respiratory Medicine, Easter Bush Veterinary Centre, Roslin, Midlothian, UK. scottp@staffmail.ed.ac.uk
Collie, D D S
    Dixon, P M
      McGorum, B C

        MeSH Terms

        • Animals
        • Asthma / etiology
        • Asthma / pathology
        • Asthma / veterinary
        • Bronchoalveolar Lavage Fluid / cytology
        • Cell Count
        • Dust / immunology
        • Edible Grain / immunology
        • Endotoxins / toxicity
        • Female
        • Horse Diseases / etiology
        • Horse Diseases / pathology
        • Horses
        • Inhalation Exposure
        • Lipopolysaccharides / toxicity
        • Spores, Fungal / immunology

        Citations

        This article has been cited 29 times.
        1. Höglund N, Nieminen P, Mustonen AM, Käkelä R, Tollis S, Koho N, Holopainen M, Ruhanen H, Mykkänen A. Fatty acid fingerprints in bronchoalveolar lavage fluid and its extracellular vesicles reflect equine asthma severity.. Sci Rep 2023 Jun 17;13(1):9821.
          doi: 10.1038/s41598-023-36697-xpubmed: 37330591google scholar: lookup
        2. Mainguy-Seers S, Beaudry F, Fernandez-Prada C, Martin JG, Lavoie JP. Neutrophil Extracellular Vesicles and Airway Smooth Muscle Proliferation in the Natural Model of Severe Asthma in Horses.. Cells 2022 Oct 24;11(21).
          doi: 10.3390/cells11213347pubmed: 36359743google scholar: lookup
        3. Intemann S, Reckels B, Schubert D, Wolf P, Kamphues J, Visscher C. The Hygienic Status of Different Forage Types for Horses-A Retrospective Study on Influencing Factors and Associations with Anamnestic Reports.. Vet Sci 2022 May 6;9(5).
          doi: 10.3390/vetsci9050226pubmed: 35622753google scholar: lookup
        4. Basano I, Romolo A, Iamone G, Memoli G, Riccio B, Lavoie JP, Miniscalco B, Bullone M. Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma.. Animals (Basel) 2022 Apr 20;12(9).
          doi: 10.3390/ani12091070pubmed: 35565497google scholar: lookup
        5. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
          doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
        6. Lo Feudo CM, Stucchi L, Alberti E, Conturba B, Zucca E, Ferrucci F. Intradermal Testing Results in Horses Affected by Mild-Moderate and Severe Equine Asthma.. Animals (Basel) 2021 Jul 13;11(7).
          doi: 10.3390/ani11072086pubmed: 34359214google scholar: lookup
        7. Payette F, Charlebois A, Fairbrother JH, Beauchamp G, Leclere M. Nicoletella semolina in the airways of healthy horses and horses with severe asthma.. J Vet Intern Med 2021 May;35(3):1612-1619.
          doi: 10.1111/jvim.16140pubmed: 33942932google scholar: lookup
        8. Pirie RS, Mueller HW, Engel O, Albrecht B, von Salis-Soglio M. Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial.. Equine Vet J 2021 Nov;53(6):1094-1104.
          doi: 10.1111/evj.13419pubmed: 33403727google scholar: lookup
        9. Davis KU, Sheats MK. The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses.. Inflammation 2021 Apr;44(2):450-465.
          doi: 10.1007/s10753-020-01362-2pubmed: 33150539google scholar: lookup
        10. Ceriotti S, Bullone M, Leclere M, Ferrucci F, Lavoie JP. Severe asthma is associated with a remodeling of the pulmonary arteries in horses.. PLoS One 2020;15(10):e0239561.
          doi: 10.1371/journal.pone.0239561pubmed: 33091038google scholar: lookup
        11. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions.. Front Vet Sci 2020;7:450.
          doi: 10.3389/fvets.2020.00450pubmed: 32903600google scholar: lookup
        12. Joubert IA, Geppert M, Johnson L, Mills-Goodlet R, Michelini S, Korotchenko E, Duschl A, Weiss R, Horejs-Höck J, Himly M. Mechanisms of Particles in Sensitization, Effector Function and Therapy of Allergic Disease.. Front Immunol 2020;11:1334.
          doi: 10.3389/fimmu.2020.01334pubmed: 32714326google scholar: lookup
        13. Zhang A, Lacy-Hulbert A, Anderton S, Haslett C, Savill J. Apoptotic Cell-Directed Resolution of Lung Inflammation Requires Myeloid αv Integrin-Mediated Induction of Regulatory T Lymphocytes.. Am J Pathol 2020 Jun;190(6):1224-1235.
          doi: 10.1016/j.ajpath.2020.02.010pubmed: 32201264google scholar: lookup
        14. Leclere M, Costa MC. Fecal microbiota in horses with asthma.. J Vet Intern Med 2020 Mar;34(2):996-1006.
          doi: 10.1111/jvim.15748pubmed: 32128892google scholar: lookup
        15. Bright LA, Dittmar W, Nanduri B, McCarthy FM, Mujahid N, Costa LR, Burgess SC, Swiderski CE. Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation.. Vet Med (Auckl) 2019;10:43-63.
          doi: 10.2147/VMRR.S194427pubmed: 31119093google scholar: lookup
        16. Orard M, Hue E, Couroucé A, Bizon-Mercier C, Toquet MP, Moore-Colyer M, Couëtil L, Pronost S, Paillot R, Demoor M, Richard EA. The influence of hay steaming on clinical signs and airway immune response in severe asthmatic horses.. BMC Vet Res 2018 Nov 15;14(1):345.
          doi: 10.1186/s12917-018-1636-4pubmed: 30442129google scholar: lookup
        17. Ivester KM, Couëtil LL, Moore GE. An observational study of environmental exposures, airway cytology, and performance in racing thoroughbreds.. J Vet Intern Med 2018 Sep;32(5):1754-1762.
          doi: 10.1111/jvim.15226pubmed: 30222207google scholar: lookup
        18. Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H. A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma-affected horses, an animal model.. Immun Inflamm Dis 2018 Mar;6(1):81-96.
          doi: 10.1002/iid3.198pubmed: 29094511google scholar: lookup
        19. Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.. BMC Genomics 2017 Jan 5;18(1):34.
          doi: 10.1186/s12864-016-3390-ypubmed: 28056766google scholar: lookup
        20. Yu G, Wang Y, Wang S, Duan C, Wei L, Gao J, Chai T, Cai Y. Effects of Microbial Aerosol in Poultry House on Meat Ducks' Immune Function.. Front Microbiol 2016;7:1245.
          doi: 10.3389/fmicb.2016.01245pubmed: 27582731google scholar: lookup
        21. Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
          doi: 10.1371/journal.pone.0136103pubmed: 26292153google scholar: lookup
        22. Ivester KM, Couëtil LL, Zimmerman NJ. Investigating the link between particulate exposure and airway inflammation in the horse.. J Vet Intern Med 2014 Nov-Dec;28(6):1653-65.
          doi: 10.1111/jvim.12458pubmed: 25273818google scholar: lookup
        23. Bosshard S, Gerber V. Evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine recurrent airway obstruction (RAO).. J Vet Intern Med 2014 Mar-Apr;28(2):618-23.
          doi: 10.1111/jvim.12279pubmed: 24417562google scholar: lookup
        24. Werners AH, Bryant CE. Pattern recognition receptors in equine endotoxaemia and sepsis.. Equine Vet J 2012 Jul;44(4):490-8.
        25. Wålinder R, Riihimäki M, Bohlin S, Hogstedt C, Nordquist T, Raine A, Pringle J, Elfman L. Installation of mechanical ventilation in a horse stable: effects on air quality and human and equine airways.. Environ Health Prev Med 2011 Jul;16(4):264-72.
          doi: 10.1007/s12199-010-0195-5pubmed: 21431789google scholar: lookup
        26. Adhikari A, Jung J, Reponen T, Lewis JS, DeGrasse EC, Grimsley LF, Chew GL, Grinshpun SA. Aerosolization of fungi, (1-->3)-beta-D glucan, and endotoxin from flood-affected materials collected in New Orleans homes.. Environ Res 2009 Apr;109(3):215-24.
          doi: 10.1016/j.envres.2008.12.010pubmed: 19201399google scholar: lookup
        27. Riihimäki M, Raine A, Elfman L, Pringle J. Markers of respiratory inflammation in horses in relation to seasonal changes in air quality in a conventional racing stable.. Can J Vet Res 2008 Oct;72(5):432-9.
          pubmed: 19086376
        28. Madsen AM, Hansen VM, Nielsen SH, Olsen TT. Exposure to dust and endotoxin of employees in cucumber and tomato nurseries.. Ann Occup Hyg 2009 Mar;53(2):129-38.
          doi: 10.1093/annhyg/men073pubmed: 19033558google scholar: lookup
        29. Theegarten D, Sachse K, Mentrup B, Fey K, Hotzel H, Anhenn O. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease.. Respir Res 2008 Jan 29;9(1):14.
          doi: 10.1186/1465-9921-9-14pubmed: 18230187google scholar: lookup