Study Case – Pulmonary Infiltrates with Eosinophils (PIE)

Justin Boggs, DVM, Heather L. Tarpley, DVM; Perry J. Bain, DVM, PhD; Kenneth S. Latimer, DVM, PhD; Bruce E. LeRoy, DVM, PhD

Class of 2004 (Boggs) and Department of Pathology (Tarpley, Bain, Latimer, LeRoy), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388

Signalment - Canine, Shetland Sheepdog, M/N, 2.5-year-old

Presenting problems - Coughing unresponsive to therapy (antimicrobials and bronchodilators) that progressively worsened prior to presentation, expiratory dyspnea

Physical examination – Patient was bright, alert, and responsive but had obvious dyspnea characterized by increased abdominal effort with each breath. Lung auscultation revealed increased bronchovesicular sounds and wheezing. Murmurs and arrhythmias were not auscultated.

Laboratory Data -

Sputum Cytology - Eosinophilic inflammation and mucus (Fig. 1)

Figure 1. Mucus, eosinophils, and neutrophils in the sputum of a dog with dyspnea.

1. Leukocytosis, neutrophilia with a very mild left shift, eosinophilia, and monocytosis.

Day 1: Leukocytosis with eosinophilia and monocytosis.
Eosinophilia is most likely due to respiratory inflammation since the history, clinical signs, and thoracic radiographs suggest respiratory pathology. Though evidence of intestinal parasites was not observed with fecal floatation, intestinal parasitism cannot be entirely excluded. Heartworm status was unknown. Chronic antigenic stimulation (including allergies) may also be a contributing factor. Other causes for eosinophilia, such as adrenocortical insufficiency and neoplasia, are not likely since values on the biochemistry panel were within reference intervals, and abdominal and thoracic radiographs were not suggestive of a mass. Monocytosis may occur with acute and chronic inflammatory disease; this finding is nonspecific.

Day 2: Leukocytosis, mature neutrophilia, lymphocytosis, eosinophilia, and monocytosis.
The mature neutrophilia and decrease in eosinophils (though mild eosinophilia persists) is most likely secondary to steroid therapy. Corticosteroid administration decreases neutrophil emigration, decreases neutrophil adhesion to blood vessel walls, and increases release of neutrophils from the bone marrow. The circulating neutrophil pool:marginal neutrophil pool in untreated dogs is approximately 1:1. The resolution of the left shift also suggests that glucocorticoids have also likely reduced much of the inflammatory component of the disease. Corticosteroids increase margination and sequestration of eosinophils in tissue and decrease their release from the bone marrow. The mechanism of the lymphocytosis in this case is unclear. Sequestration of lymphocytes would be the expected immediate effect of corticosteroid therapy. Other potential causes of a lymphocytosis would include a physiologic response (e.g. excitement prior to blood sampling).

Day 3: Leukocytosis, mature neutrophilia, eosinophilia, and monocytosis.
The mature neutrophilia and a lymphocyte count at the lower end of the reference interval are most likely secondary to previous use of corticosteroids. The exact length of treatment is unknown. Neutrophil counts typically return to the reference interval within 2-3 days of cessation of therapy. Lymphocyte counts may remain decreased after cessation of therapy if therapy caused lymphocytic lysis. The return of moderate eosinophilia most likely reflects decreased margination after cessation of corticosteroid administration rather than increased production.

2. Hypoxemia with decreased oxygen saturation and mild metabolic alkalosis. Hypoxemia with decreased oxygen saturation, PCO₂ within the reference interval, and a high alveolar-arterial oxygen gradient in this patient suggest venous admixture due to alveolar ventilation/perfusion (V_A/Q) mismatch and diffusion impairment. The alveolar-arterial oxygen gradient is 39.3 mmHg (based on the equation A-a=150-PaCO₂(0.8)-PaO₂ where (A-a) is the alveolar-arterial oxygen gradient). Values >15-20 mmHg indicate parenchymal disease; patients with pure mechanical hypoventilation have a normal gradient which is <15 mmHg. Diffusion of oxygen across alveolar-capillary membranes thickened by inflammation is compromised. The PCO₂ level is at the high end of the reference interval. CO₂ easily diffuses out of blood due to its high solubility, so membrane thickness will have little effect on its movement from the capillary to the alveolus. The slight elevation of the HCO₃^- concentration and a base excess >0 indicate the presence of a very mild metabolic alkalosis in this patient. HCO₃^- concentration in blood gas analyses is a calculated (not measured) value determined by the Henderson-Hasselbalch equation using pH and PCO₂ measurements. BE is also derived from a calculation using standard HCO₃^-, measured hemoglobin, PCO₂, and body temperature. The reason for a very mild metabolic alkalosis in this patient is unclear since there is no known history of vomiting.

Summary -

Pulmonary infiltrates with eosinophils (PIE), also known as eosinophilic bronchopneumopathy, is characterized by marked eosinophilic infiltration of pulmonary parenchyma. This disease represents a marked hypersensitivity reaction. Potential causes of hypersensitivity include pulmonary parasites, heartworms, drugs, inhaled allergens, and occasionally bacteria, fungi, or neoplasia.

Definitive diagnosis requires observation of eosinophilic inflammation in cytologic or histologic preparations of bronchoalveolar fluid, lung aspiration, or lung biopsies. Marked peripheral eosinophilia may or may not be present. Thoracic radiographs frequently show a moderate to severe bronchointerstitial pattern.

Patients respond well to corticosteroid therapy though relapse is common. Potential antigens should be identified and eliminated, if possible.

In this case of PIE, presenting signs included coughing and dyspnea. Peripheral eosinophilia and hypoxemia were also present. Hypoxemia is attributable mostly to impaired diffusion and alveolar ventilation/perfusion mismatch. With treatment, this dog clinically improved.

Follow-up radiographs and a transtracheal wash also showed diminished inflammation. Because clinical signs worsened as the dosage of corticosteroids was tapered, the initial dose was reinstituted, and the dog was treated with fenbendazole to eliminate potential lung parasites.

References

1. Clercx C: Is canine eosinophilic bronchopneumopathy an asthmatic disease? 12th ECVIM-CA Conference, VIN, 2002.

2. Clercx C, Peeters D, German AJ, Khelil Y, McEntee K, Vanderplasschen A, Schynts F, Hansen P, Detilleux J, Day MJ: Eosinophilic bronchopneumopathy in dogs. J Vet Intern Med 14:282-291, 2000.

3. Latimer KS, Mahaffey EA, Prasse KW (eds): Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Ames, Iowa State Press, 2003, pp. 65-69, 72-74, 270-278.

4. Hawkins EC: Pulmonary parenchymal disease. In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, 5th ed. Philadelphia, WB Saunders Co, 2000, pp. 1071-1072.

5. Corcoran B: Clinical evaluation of the patient with respiratory disease. In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, 5th ed. Philadelphia, WB Saunders Co, 2000, pp. 1038-1039

Acknowledgement

Sheltie Quilt is from Picture Quilts by Sharon Malec and is used with permission.

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