Introduction

Canine eosinophilic bronchopneumopathy (EBP) is a disease characterised by eosinophilic infiltration of lung and bronchial mucosa, considered to be manifestations of immunological hypersensitivity. Although the aetiology of EBP is still unknown, the association of eosinophilic infiltration and predominance of CD4+ T-cells is in favour of a dominant Th2 immune response mounted in the lower airways.¹ Suspected and known causes of pulmonary hypersensitivities in humans and animals include fungi, molds, drugs, bacteria, and parasites. However, in many cases, no underlying cause is found. The role of inhaled allergens in EBP is still unclear.

Signalment and Clinical Presentation

Dogs affected with EBP are usually young adults (4 to 6 years), although the disease can be diagnosed in animals younger than 1 year or older than 10.^2-5

A breed predisposition has been shown for Siberian huskies and malamutes, but the disease can be diagnosed in large breeds (mainly Labradors, Rottweilers, German shepherds), less commonly in smaller breeds (such as Jack Russell terriers, dachshunds), but very rarely in miniature, or in giant breeds.

Usually, the general condition is good, unless the disease is associated with concomitant bacterial bronchopneumonia. The main clinical signs include mainly cough, gagging and retching and are present in 100% of the cases. Some dyspnea is a very frequently present. A less commonly encountered sign is nasal discharge.

Diagnostic Tests

Diagnostic elements for the diagnosis of idiopathic EBP include anamnetic factors (breed, young age, previous response to corticosteroids, and clinical signs), radiographic and bronchoscopic findings, blood eosinophilia, tissue eosinophilic infiltration as demonstrated by cytological and histopathological examinations, response to adequate treatment, and also rests on exclusion of other respiratory diseases.⁵ The most common radiographic findings are a mixed moderate to severe bronchointerstitial pattern. Computed tomographic findings associated with eosinophilic bronchopneumopathy are variable and heterogeneous, and include marked to moderate bronchial wall thickening, plugging of the bronchial lumen by mucus/debris, bronchiectasis, presence of pulmonary nodules, and lymphadenopathy.⁶ Bronchoscopy can reveal typical macroscopic features such as the presence of abundant yellow-green mucous or mucopurulent material, severe thickening of the mucosa with irregular or polypoid surface and in some cases partial airway closure during expiration.⁵ Peripheral blood eosinophilia is frequent, but not always observed. BALF or brush cytology demonstrates a marked eosinophilic component; frequently, more than 50% of the inflammatory cells are eosinophils. In most cases, eosinophilic infiltration of the bronchial mucosa can also be observed in biopsies. Concomitant neutrophilic infiltration can be seen.

Differential Diagnosis

In the dog, occult heartworm disease caused by Dirofilaria immitis can cause eosinophilic pneumonitis. Migration of larvae of Angiostrongylus vasorum through pulmonary parenchyma may also result in eosinophilic pneumonia in dogs. Infection by the nematode worm Angiostrongylus vasorum (also called the French heartworm disease) is an emerging disease, with reported increase in both distribution and incidence in United Kingdom, Europe, South Africa, and Canada. The expanding geographic range might be related to the influence of the climate on parasite distribution. The worm infects dogs and foxes and is spread through ingestion of intermediate hosts, including slugs and snails. Other bronchopulmonary parasites, like Capillaria aerophila, Oslerus osleri, Filaroides hirthi, Crenosoma vulpis, or Paragonimus kellicotti, are also implicated in the afflux of eosinophils in the airways (0. osleri) or lungs (other parasites) in dogs, and can mimic EBP. Frequency of bronchial disease due to infection by Crenosoma vulpis is also becoming emerging on the continent.⁷ Therefore, infection by Angiostrongylus vasorum or Crenosoma vulpis should now be considered in the differential diagnosis in dogs with chronic cough. The presence of parasites should be searched, using BALF analysis, faeces examination (Baermann sedimentation procedure) or in clinic antigen detection test in blood. In the meantime, appropriate antihelmintic drugs can be used in order to treat the animal against potential parasites.

Management

The response to oral steroid therapy is generally very good, although achievement of total lack of symptoms is not always obtained. Prednisolone is initiated at a dosage of 0.5 to 1 mg/kg (in severe cases) q12h the first week; the same dose is given on alternate days during the second week, and then the dosage is progressively and gradually reduced on alternated days until maintenance dosage. Since chronic oral steroid therapy may unfortunately lead to well-recognized systemic side effects (i.e., iatrogenic hyperadrenocorticism) and since its use can also be contraindicated in dogs with other concomitant health problems such as diabetes mellitus, obesity, or cardiac diseases, alternative treatment with inhaled steroid therapy (IST) has been increasingly used in the past years in both human and veterinary medicines, with the suggested advantages to provide both high drug concentrations within the airways and a reduced systemic and potentially deleterious absorption. Inhaled corticosteroid therapy is well tolerated, results in improvement in clinical signs and reduction in side effects, and allow a reduction of oral steroid dosage in steroid-dependent animals.^8,9 However, it seems that treatment of EBP with long-term IST alone does not allow a proper management in all affected dogs and that sustained long-term IST may induce inhibition of pituitary-adrenal axis (PAA).⁹ Other drugs with immunomodulatory effect have not been proposed, but no published trial results are available to date.

Prognosis

Relapse frequently occurs within weeks to months after drug discontinuation although, some dogs may remain asymptomatic after discontinuation.

Take Home Message

Eosinophilic bronchopneumopathy (EBP) is a disease characterized by eosinophilic infiltration of the lung and bronchial mucosa, as demonstrated by cytological examination of either bronchoalveolar lavage fluid or bronchial brush fluid cytospin preparations or histologic examination of the bronchial mucosa. In idiopathic EBP, hypersensitivity to aeroallergens is suspected. However, the precise cause is often unknown. The diagnosis relies on typical history and clinical signs, demonstration of bronchopulmonary eosinophilia by cytology or histopathologic examination, and exclusion of known causes of lower airway eosinophilia. Most dogs display an excellent response to oral corticosteroid therapy; however, treatment can rarely be discontinued and side effects can be limiting. In most cases, corticosteroids will be used for long periods of time, if not lifelong.

Nebulized administration of corticosteroids can help reduce the oral dosages or even replace oral therapy.

References

1.  Peeters D, Peters IR, Helps CR, Gabriel A, Day MJ, Clercx C. Distinct tissue cytokine and chemokine mRNA expression in canine sino-nasal aspergillosis and idiopathic lymphoplasmacytic rhinitis. Vet lmmunol lmmunopathol. 2007;117(1–2):95–105.

2.  Clercx C, Peeters D, Snaps F, et al. Eosinophilic bronchopneumopathy in dogs. J Vet Intern Med. 2000;14(3):282–291.

3.  Clercx C, Peeters D, German AJ, et al. An immunologic investigation of canine eosinophilic bronchopneumopathy. J Vet Intern Med. 2002;16(3):229–237.

4.  Rajamäki MM, Järvinen A-K, Sorsa T, Maisi P. Clinical findings, bronchoalveolar lavage fluid cytology and matrix meralloproteinase-2 and -9 in canine pulmonary eosinophilia. Vet J. 2002;163(2):168–181.

5.  Clercx C, Peeters D. Canine eosinophilic bronchopneumopathy. Vet Clin North Am Small Anim Pract. 2007;37(5):917–935.

6.  Mesquita L, Lam R, Lamb CR, McConnell JF. Computed tomographic findings in 15 dogs with eosinophilic bronchopneumopathy. Vet Radiol Ultrasound. 2015;56(1):33–39.

7.  Maksimov P, Hermosilla C, Taubert A, et al. GIS-supported epidemiological analysis on canine Angiostrongylus vasorum and Crenosoma vulpis infections in Germany. Parasit Vectors. 2017;10(1):108.

8.  Bexfield NH, Foale RD, Davison LJ, Watson PJ, Skelly BJ, Herrtage ME. Management of 13 cases of canine respiratory disease using inhaled corticosteroids. J Small Anim Pract. 2006;47(7):377–382.

9.  Canonne A-M, Bolen G, Peeters D, Billen F, Clercx C. Long-term follow up in dogs with idiopathic eosinophilic bronchopneumopathy treated with inhaled steroid therapy. J Small Anim Pract. 2016;57(10):537–542.