Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses

Beeler-Marfisi, Janet; Clark, Mary E.; Wen, Xin; Sears, William; Huber, Leslie; Ackerley, Cameron; Viel, Laurent; Bienzle, Dorothee

doi:10.2460/ajvr.71.6.682

Cited by 39 publications

(42 citation statements)

References 29 publications

(37 reference statements)

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“…The results of this test varied greatly which corresponds to the results of other studies 21, 22, 23, 24, 25, 26, 27, 28. Numerous horses reacted to pollen antigens, which should be associated with seasonal deterioration in the spring and summer months.…”

Section: Discussionsupporting

confidence: 81%

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A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Klier

Geis

Steuer

et al. 2017

Immunity Inflam & Disease

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IntroductionNew therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T‐regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T‐helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle‐CpG formulation (CpG‐GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a model for human asthma.MethodsTwenty equine asthma‐affected horses were treated either with CpG‐GNP alone or CpG‐GNP with allergens. Two specific allergens were selected for each horse based on history and an in‐vitro test. Each horse received seven administrations of the respective nebulized composition and was examined before treatment, immediately after and 6 weeks after the treatment course.ResultsClinical parameters such as breathing rate, indirect interpleural measurement, arterial blood gases, amount of tracheal mucus and percentage of neutrophils and cytokines in tracheal washes and serum samples were evaluated. Treatment with CpG‐GNP alone as well as in combinations with relevant allergens resulted in clinical improvement of nasal discharge, breathing rate, amount of secretion and viscosity, neutrophil percentage and partial oxygen pressure directly after and 6 weeks after treatment. There were no significant differences between the two treatments in clinical parameters or local cytokine profiles in the tracheal wash fluid (IL‐10, IFN‐g, and IL‐17). IL‐4 concentrations decreased significantly in both groups.ConclusionNonspecific CpG‐GNP‐based immunotherapy shows potential as a treatment for equine and possibly also human allergic asthma.

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Section: Discussionsupporting

confidence: 81%

“…In particular, mold spores were shown to play an important role in the allergic reactions of equine asthma horses 22, 23, 24, 25, 28, 29, 30. Three horses showed no reactions in the FIT.…”

Section: Discussionmentioning

confidence: 99%

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Klier

Geis

Steuer

et al. 2017

Immunity Inflam & Disease

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“…The in vivo stimuli or significance of NETs are incompletely defined, but a wide range of microbial components and inflammatory mediators such as GM-CSF, ROS, IL-8 and MIP-2 may induce NETosis [25]. Since agents that incite asthmatic responses in horses include LPS and fungal spores [48], and the bronchial epithelium responds with abundant IL-8 production [49], it is not surprising that neutrophils are activated in vivo and form NETs. From data presented here it appears that NETs are present in the most severe the inflammatory states, but the precise role of NETs in RAO remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation

et al. 2014

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Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma. RAO is characterized by reversible airway obstruction, bronchoconstriction and neutrophilic inflammation. Direct effects of SCGB 1A1 on neutrophil functions are unknown. We have recently identified that the SCGB1A1 gene is triplicated in equids and gives rise to two distinct proteins. In this study we produced the endogenously expressed forms of SCGBs (SCGB 1A1 and 1A1A) as recombinant proteins, and analyzed their effects on reactive oxygen species production, phagocytosis, chemotaxis and neutrophil extracellular trap (NET) formation ex vivo. We further evaluated whether NETs are present in vivo in control and inflamed lungs. Our data show that SCGB 1A1A but not SCGB 1A1 increase neutrophil oxidative burst and phagocytosis; and that both proteins markedly reduce neutrophil chemotaxis. SCGB 1A1A reduced chemotaxis significantly more than SCGB 1A1. NET formation was significantly reduced in a time- and concentration-dependent manner by SCGB 1A1 and 1A1A. SCGB mRNA in bronchial biopsies, and protein concentration in bronchoalveolar lavage fluid, was lower in horses with RAO. NETs were present in bronchoalveolar lavage fluid from horses with exacerbated RAO, but not in fluid from horses with RAO in remission or in challenged healthy horses. These findings indicate that SCGB 1A1 and 1A1A have overlapping and diverging functions. Considering disparities in the relative abundance of SCGB 1A1 and 1A1A in airway secretions of animals with RAO suggests that these functional differences may contribute to the pathogenesis of RAO and other neutrophilic inflammatory lung diseases.

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“…The most important of all environmental effects in the development of RAO, hay feeding10, 11, 12, 13, 27 was deliberately eliminated by defining continuous hay feeding throughout the study period as an inclusion criterion for all horses. It was somewhat surprising, however, that age group had no effect, because age has previously been shown to be an independent risk factor for the development of RAO 11, 26.…”

Section: Discussionmentioning

confidence: 99%

“…RAO, in contrast, affects middle‐aged to older horses and provokes more severe respiratory signs. A strong genetic basis was shown for RAO7, 8, 9 and hay feeding is the most important environmental factor for its development4, 10, 11 and exacerbation 12, 13…”

mentioning

confidence: 99%

Evaluation of Coughing and Nasal Discharge as Early Indicators for An Increased Risk to Develop Equine Recurrent Airway Obstruction (RAO)

Bosshard

Gerber

2014

Veterinary Internal Medicne

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BackgroundIt is often assumed that horses with mild respiratory clinical signs, such as mucous nasal discharge and occasional coughing, have an increased risk of developing recurrent airway obstruction (RAO).HypothesisCompared to horses without any clinical signs of respiratory disease, those with occasional coughing, mucous nasal discharge, or both have an increased risk of developing signs of RAO (frequent coughing, increased breathing effort, exercise intolerance, or a combination of these) as characterized by the Horse Owner Assessed Respiratory Signs Index (HOARSI 1–4).AnimalsTwo half‐sibling families descending from 2 RAO‐affected stallions (n = 65 and n = 47) and an independent replication population of unrelated horses (n = 88).MethodsIn a retrospective cohort study, standardized information on occurrence and frequency of coughing, mucous nasal discharge, poor performance, and abnormal breathing effort—and these factors combined in the HOARSI—as well as management factors were collected at intervals of 1.3–5 years.ResultsCompared to horses without clinical signs of respiratory disease (half‐siblings 7%; unrelated horses 3%), those with mild respiratory signs developed clinical signs of RAO more frequently: half‐siblings with mucous nasal discharge 35% (P < .001, OR: 7.0, sensitivity: 62%, specificity: 81%), with mucous nasal discharge and occasional coughing 43% (P < .001, OR: 9.9, sensitivity: 55%, specificity: 89%); unrelated horses with occasional coughing: 25% (P = .006, OR = 9.7, sensitivity: 75%, specificity: 76%).Conclusions and Clinical importanceOccasional coughing and mucous nasal discharge might represent an increased risk of developing RAO.

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Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses

Abstract: Results indicated that inhalation of fungal spores in combination with lipopolysaccharide and silica microspheres can induce disease exacerbation in susceptible horses and may thus be a useful model for future standardized studies of RAO in horses.

Cited by 39 publications

References 29 publications

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Secretoglobin 1A1 and 1A1A Differentially Regulate Neutrophil Reactive Oxygen Species Production, Phagocytosis and Extracellular Trap Formation

Evaluation of Coughing and Nasal Discharge as Early Indicators for An Increased Risk to Develop Equine Recurrent Airway Obstruction (RAO)

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