Eosinophilic Pulmonary Diseases

Definition and Causes

Eosinophilic bronchopneumopathy (EBP) is a disease characterized by eosinophilic infiltration of the lung and bronchial mucosa. Several terms, including pulmonary infiltration with eosinophils, pulmonary eosinophilia, and eosinophilic pneumonia have been used in the literature to describe the same disease (Clercx et al, 2000). Possible causes include occult heartworm disease due to Dirofilaria immitis, migration of larvae of Angiostrongylus vasorum through pulmonary parenchyma, and infection with a parasite such as Oslerus osleri, Filaroides hirthi, Crenosoma vulpis, or Paragonimus kellicotti. Suspected but unconfirmed causes in dogs include allergic bronchopulmonary aspergillosis, chronic pulmonary infections caused by mycobacteria or fungi, drug reactions, and tumors (lymphoma and mast cell tumor). However, a specific cause is rarely identified even with extensive diagnostic workup, and most cases of EBP are considered to be idiopathic, although a hypersensitivity to aeroallergens is suspected.

Pathogenesis

In idiopathic EBP, a dominant helper T cell type 2 (T_H2) immune response is suspected, based on a selective increase in CD4⁺ T cells in bronchoalveolar lavage fluid (BALF) (Clercx et al, 2002) and increased levels of messenger RNA encoding for eotaxins, the strongest chemoattractants for eosinophils, in bronchial biopsy specimens from dogs with EBP (Peeters et al, 2006). The cause of these changes is unknown. A limited number of positive intradermal skin test reactions have been described in affected dogs; however, the relationship between positive intradermal skin test results and detection of aeroallergens responsible for EBP is still unclear. Lower airway and pulmonary destruction and remodeling observed in canine EBP may be connected to up-regulation of collagenolysis, related perhaps to increased activity of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 (Rajamaki et al, 2002).

Signalment and Clinical Signs

Dogs affected with EBP are usually young adult dogs, although age at onset of disease varies greatly (up to 13 years). Females are more frequently affected than males. Siberian huskies and Alaskan malamutes appear to be predisposed, and although the disease also is frequently diagnosed in small breeds as well as in dogs of other large breeds, it is rarely encountered in miniature or giant breeds.

Harsh cough, followed by gagging and retching, is the most common clinical sign. Other frequent clinical signs are labored respirations, some degree of exercise intolerance, and nasal discharge. Auscultation findings may be normal, but increased bronchial sounds can be noted as well as wheezes or crackles.

Diagnosis

Diagnosis of EBP is usually suspected based on signalment, history, previous positive response to corticosteroids (and absence of or moderate response to other treatments), and clinical signs. Diagnosis must be confirmed before treatment is initiated and relies on identifying a combination of the frequently observed signs of peripheral eosinophilia, characteristic radiographic and bronchoscopic findings, and airway or tissue eosinophilic infiltration as demonstrated by cytologic analysis of BALF or histopathologic examination of bronchial biopsy specimens. Importantly, known causes of eosinophilic infiltration of the lower airways must be excluded and clinical response to corticosteroid therapy demonstrated.

Thoracic radiographs always show diffuse pulmonary lesions of variable intensity with a moderate to severe bronchointerstitial pattern. Peribronchial cuffing, marked thickening of the bronchial walls, alveolar infiltration, and bronchiectasis are other reported findings. Hematologic abnormalities include leukocytosis in up to half of cases, eosinophilia in up to 60%, neutrophilia in about 25%, and basophilia in up to 50% (Clercx et al, 2000). It is important to note that an absence of peripheral eosinophilia does not exclude a diagnosis of EBP. Serum biochemistry values are unremarkable.

Bronchoscopy allows observation of macroscopic findings typical of EBP, such as the presence of a moderate to large amount of yellow-green secretions (Figure 163-1), moderate to severe thickening of the bronchial mucosa with an irregular to polypoid aspect, bronchiectasis, and possibly bronchomalacia in chronic cases. Eosinophils constitute the predominant inflammatory cell type seen on BALF smear cytology or brush cytology. Secondary bacterial infection is uncommon but should be recognized and treated promptly before treatment with glucocorticoids is initiated. Histopathologic examination of perendoscopic mucosal bronchial biopsy specimens also can reveal eosinophilic infiltrates.