JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-M06 (NP)

 

Signalment (JPC #1903018): 20-year-old female Shetland pony

 

HISTORY: The pony was thin and had several episodes of respiratory distress over the last three years; steroids were the only drugs that would relieve the symptoms.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally, bronchi and bronchioles often contain an exudate composed of flocculent amphophilic material (mucus) with entrapped neutrophils and fewer lymphocytes, plasma cells, alveolar macrophages, and karyorrhectic necrotic debris. This exudate occasionally extends into adjacent alveolar lumina. Bronchioles occasionally contain increased numbers of goblet cells (goblet cell metaplasia). There is multifocal mild peribronchiolar fibrosis and smooth muscle hyperplasia. The epithelium of larger bronchioles and bronchi occasionally has loss of cilia and occasionally is replaced by stratified squamous epithelium (squamous metaplasia). Multifocally, alveoli contain mild hemorrhage and are multifocally confluent (hyperinflation).

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchitis and bronchiolitis, mucoid, multifocal, mild, with mild alveolar hyperinflation and hemorrhage, Shetland pony, equine.

 

CONDITION: Equine asthma (formerly recurrent airway obstruction)

 

SYNONYMS: Chronic obstructive pulmonary disease (not an accurate term to describe this condition); “Heaves”; recurrent airway obstruction (RAO)

 

GENERAL DISCUSSION: 

of reversible airway obstruction secondary to bronchospasm due to airway hyper-responsiveness

America and Europe

usually minor

• Slowly progressive 
• Terminology recently changed from “recurrent airway obstruction” to equine asthma (Ferrari, Vet Pathol, 2018) due to shared pathobiology with human asthma
• Equine asthma is associated with indoor stabling; summer pasture-associated recurrent airway obstruction (equine pasture asthma) is associated with grass pasture housing in the southeastern United States

 

PATHOGENESIS:

• Causes and pathogenesis are unknown and probably multifactorial
• Induced or exacerbated by airborne particulates (dusts) that may contain allergens, endotoxins, fungi, or other irritants; toxin and viral factors have also been suggested; these may activate pulmonary macrophages via TLRs (Kang et al., VP, 2022)
• These factors may induce cytokine production and chemoattraction of neutrophils to the bronchoalveolar region; alveolar macrophages may both promote and inhibit inflammation that modulates disease with repeated ‘challenge’ or exposure to a pathogen or irritant leading to permissive anti-inflammatory states or a phenotype shift to a damaging proinflammatory state (Kang et al., VP, 2022)
• Allergic basis supported by elevated IgE and histamine in bronchoalveolar lavage fluid; skin reaction is delayed rather than immediate though

 

TYPICAL CLINICAL FINDINGS:

• Chronic cough, exercise intolerance, wheezing, nasal discharge, and increased expiratory effort
• Signs wax and wane

 

TYPICAL GROSS FINDINGS:

increased expiratory effort

• Alveolar emphysema (alveolar hyperinflation) may be present in severe cases
• Diaphragmatic hypertrophy
• Lesions most severe in the caudodorsal lung lobes

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Small bronchioles are the site of most of the lesions

• Contain mucus, neutrophils, and sloughed epithelial cells
• Increased goblet cells in epithelium (truly metaplasia – they are not typically seen in bronchioles of healthy horses)
• Club cell hyperplasia/sloughing
• Lymphoplasmacytic inflammation in the adventitia
• Smooth muscle hyperplasia
• Peribronchiolar fibrosis

• Alveolar changes can be seen, but are minor

• Mucus overflow into alveoli in severe cases
• Over-inflation of alveoli without septal rupture

 

ADDITIONAL DIAGNOSTIC TESTS:

• Diagnosis usually based on clinical signs and relevant history

• Bronchioalveolar lavage or tracheobronchial aspirates may show increased numbers 

of neutrophils, macrophages and sometimes eosinophils

• Increase in mucus production demonstrating Curschmann’s spirals though this is non-specific
• There may be prominent/hyperplastic goblet cells and ciliated respiratory epithelial cells
• In general, increased eosinophils in TW/BAL indicates a hypersensitivity response

• Brush cytology: Samples a smaller area, but preserves cells well and is less obstructive in severely asthmatic horses. It can detect neutrophilic inflammation in airway accurately and rapidly, but BAL remains the gold standard due better overall test diagnostic sensitivity/specificity
• Endoscopic biopsies are potentially helpful later in the course of disease to assess airway remodeling, but sample of airway exudate may lack from inability to sample widely or deeper in the airway. (Lee et al., VP 2022)

 

DIFFERENTIAL DIAGNOSIS:

• Bacterial, viral and fungal pneumonia
• Verminous pneumonia (Dictyocaulus arnfeldi)
• Exercise Induced Pulmonary Hemorrhage (EIPH)

• Inflammatory airway disease 

• Similar signs to equine asthma, but occurs in young horses (2-4 years) during exercise; no clinical signs at rest
• Histologic features not described

 

COMPARATIVE PATHOLOGY:

• Canine: Chronic bronchitis may be related to infectious or allergic etiologies and is most often seen in older small or toy breeds; there is bronchiectasis, goblet cell metaplasia, and mucopurulent plugs
• Feline asthma and chronic bronchitis: Feline Asthma is reversible air obstruction with concurrent inflammation; major changes/pathogenesis are similar to the equine form and include bronchoconstriction, bronchial inflammation, and smooth muscle hyperplasia. Eosinophils in the wall and lumen are another common feature and the disease is typically acute. Chronic bronchitis is non-reversible obstruction of the airway. Both conditions may reflect allergic components.
• Nonhuman primates: Gross and microscopic findings are similar to the equine disease (reversible air obstruction, mucus plugs, variable eosinophils in the inflammatory infiltrate); recognized in chimpanzees and bonobos; rhesus and cynomolgus macaques have been used as experimental models for allergen-induced asthma and treatment

 

REFERENCES:

1. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, Palmer's Pathology of Domestic Animals. 6th ed. Vol 2, Philadelphia, PA: Elsevier; 2016:501-503;505-506.
2. De Terlizzi R, English K, Cowell RL, Tyler RD, Meinkoth JH. Transtracheal and Bronchoalveolar Washes. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:257. 
3. Ferrari CR, et. al. Horses with pasture asthma have airway remodeling that is characteristic of human asthma. Vet Pathol. 2018;55(1):144-158. 
4. Kang H, Bienzle D, Lee GKC, et. al. Flow cytometric analysis of equine bronchoalveolar lavage fluid cells in horses with and without severe equine asthma. Vet Pathol. 2022;59(1):91-99. 
5. Lee GKC, Beeler-Marfisi J, Viel L, et. al. Bronchial brush cytology, endobronchial biopsy, and SALSA immunohistochemistry in severe equine asthma. Vet Pathol. 2022;59(1):100-111. 
6. Lopez A, Martinson SA. Respiratory system, mediastinum, and pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO:Mosby; 2022:600-601.
7. Lowenstine LJ, Osborn KG. In: Abee CR, ed. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2nd ed. San Diego, CA: Elsevier; 2012:437-438.
8. Zinkl, JG. Lower Respiratory Tract. In: Cowell RL, Tyler RD eds. Diagnostic Cytology and Hematology of the Horse. 2^nd ed. St Louis MO: Mosby; 2002: 82.

 

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