Eosinophilic bronchitis in a Golden Retriever

Signalment

A 26kg 7 year old neutered female Golden Retriever.

History

This bitch presented with a 3 month history of chronic coughing. The cough had partially responded to symptomatic treatment with chlorpheniramine(Piriton, Stafford-Miller) at a dose of 12mg/day split three times daily. Two weeks previously, a mast cell tumour had been surgically removed from the distal hind leg. The owners noted that the cough had got worse 3 days after the surgery. The character of the cough was dry, harsh and apparently non-productive, and was most frequently noted on excitement.

            Due to a wide excision, the surgical wound was slow to heal. Enrofloxacin (Baytril, Bayer) at 150mg SID was prescribed for post operative wound infection. Coughing continued and further enrofloxacin was given, together with carprofen (Rimadyl, Pfizer, 50mg twice daily) and fenbendazole (Panacur, Intervet 1250mg/day for 7 days). An acute allergic-type reaction was seen two days after the introduction of carprofen, with pruritis, heat, erythema and swelling of the face. Carprofen was discontinued and a two week course of prednisolone was given, initially at 5mg twice daily for five days and reducing the dose thereafter. This resolved the acute symptoms, and the cough also got somewhat better. The prednisolone was stopped however, due to poor healing at the surgical site. The owners then reported the dog was exhibiting orthopnoea.

Physical examination

T 38.8C                        P 120 bpm                    R 40 breaths/minute

The dog was in good physical condition and was bright, alert and responsive. Mucous membrane colour was normal, and CRT < 2 seconds. Tracheal palpation elicited a harsh, non-productive cough. Submandibular lymph nodes were moderately enlarged. Examination of the oral cavity and pharynx was unremarkable.

            On auscultation, the heart exhibited a sinus arrhythmia. No murmur was detected, and there were no pulse deficits. Pulse quality was good. Auscultation of the lungs revealed crackles and wheezes, particularly of the dorsal lung fields. Abdominal palpation was unremarkable. No neoplasms were detected by palpation or visual inspection.

            A moist, erythematous lesion was present on the left hind foot where a surgical wound had not yet healed.

Problem list

Cough

Orthopnoea

Inflammatory response

Differential diagnosis

Cough and orthopnoea

*=more probable based on history, clinical signs and disease incidence

            Inflammatory

                        Bronchiectasis*

                        Chronic bronchitis*

                        Tracheobronchitis*

                        Pneumonia – bacterial, viral, fungal*

                        Abscess*

                        Chronic pulmonary fibrosis*

                        Hilar lymph node enlargement*

                        Inhalation

            Neoplastic

                        Primary lung*

                        Mediastinal*

                        Metastatic*

                        Tracheal

                        Lymphoma*

            Cardiovascular

                        Enlarged heart*

                        Pulmonary oedema (e.g. heart failure)*

                        Pulmonary emboli*

            Allergic

                        Eosinophilic bronchitis*

                        Eosinophilic pneumonitis*

                        Eosinophilic pulmonary granulomatosis*

                        Pulmonary Infiltrate with Eosinophilia (PIE)*

                        Other immune states

            Physical

                        Foreign body*

                        Irritating gases

                        Trauma

            Parasitic

                        Visceral larva migrans*

                        Filaroides osleri*

                        Pneumocystis

                        Dirofilaria immitis

                        Crenosoma vulpis

                        Angiostrongylus vasorum

            The sinus arrhythmia of the heart implied that the heart was not failing, and was more consistent with respiratory disease. Respiratory signs were predominantly confined to the lower respiratory tract (cough, orthopnoea), hence upper respiratory diseases were considered unlikely. There was no regurgitation consistent with oesophageal dysfunction.

Diagnostic Plan

Haematology was performed to find out if there were any abnormalities in leucocyte numbers consistent with infection or allergy. Biochemistry was performed to rule out concurrent metabolic diseases. Thoracic radiography and endoscopy with cytology of airway lavage fluid was performed to make a definitive diagnosis.

Haematology and biochemistry (tables 1 and 2)

Blood samples for haematology and biochemistry were run on an Idexx Vettest 8008. There was a mild granulocytosis and hyperglycaemia, both of which were low enough to be caused by stress alone. PCV was also elevated. This may be explained by a mild dehydration, although the dog was not clinically dehydrated and the total proteins were at the lower end of the reference range. There was a marked eosinophilia.

Radiography (figs 1 and 2)

Thoracic radiography revealed a coarse bronchial lung pattern, with numerous “tram-lines” and “doughnuts” indicating thickened bronchial walls viewed laterally or end-on. In the periphery there were small areas of an alveolar pattern, especially on the right in the dorsoventral view. There was a triangular shadow on the right of the heart which may have been indicative of mediastinal fluid accumulation.

            The heart shape, size and position were within normal limits (vertebral heart score 10.0 (normal 9.5 +-0.5 [Buchanan 2000]),) and the bony structures of the thorax were unremarkable.

Endoscopy

Bronchoscopic examination revealed a large amount of green mucoid material in the mainstem and smaller bronchi. No sign of a foreign body was noted. The bronchial walls appeared moderately inflamed. Fluid was collected from a broncho-alveolar lavage for cytology and bacterial culture and sensitivity.

Cytology (fig 3)

No parasites or bacteria were noted on microscopic examination of material collected on broncho-alveolar lavage. The cells were mainly granulocytic, with both neutrophils and a significant number of eosinophils present.

Bacterial culture and sensitivity

No growth of bacteria was found after 48 hours on samples of broncho-alveolar lavage fluid.

Diagnosis

The diagnosis was of eosinophilic bronchitis.

Treatment

Treatment was started with prednisolone initially at 10mg BID and reducing incrementally every 7 days. A dose of 5mg every other day was continued for one month, after which chlorpheniramine at 12 mg/day split into three doses was used for long term maintenance.

Outcome

Within 48 hours of beginning prednisolone treatment, the cough, which had been progressively worsening, completely resolved. At no time since has the cough been reported to have returned. The surgical wound has healed well with no sign of recurrence of a mast cell tumour 6 months later.

Discussion

Chronic bronchitis is a serious disease in dogs and can be fatal due to secondary complications or owner intolerance (Prueter and Sherding 1985). In one retrospective study of 109 cases of canine lower respiratory tract disease, the disease process was classified as eosinophilic bronchitis in 25 cases (Brownlie, 1990) and in another study two out of eighteen dogs with chronic bronchitis were diagnosed with eosinophilic bronchitis on the basis of airway lavage cytology and endobronchial biopsy (Padrid, 1990).

            Seven years of age is not unusual for onset of eosinophilic bronchitis, one study reporting an age range of nine months to eleven years at examination. None of the 25 cases reported were Golden Retrievers (Brownlie, 1990).

            Diagnosis of eosinophilic bronchitis is made on the basis of clinical signs (chronic cough, dyspnoea, exercise intolerance), radiography, endoscopy and cytological examination of fluid from airway lavage or histological examination of endoscopic airway biopsy. Radiographic changes include thickened and increased numbers of visible bronchial walls. Radiography was found to be a specific but insensitive means of diagnosing chronic bronchitis (specificity 91%, sensitivity 52-65%, Mantis et al 1998). Diagnosis should therefore not depend on radiography alone. However, radiography is essential to rule out heart disease and diseases of the pulmonary parenchyma such as neoplasia as causes for a chronic cough.

            Endoscopy is important in obtaining a definitive diagnosis, for ruling out bronchial foreign bodies and nodules caused by parasites, and for collection of samples for bacteriology and cytology or histology. Cytology in this case showed a marked eosinophilia and a blood eosinophilia was also noted.

            Eosinophilia, either in airway lavage fluid or in blood is usually considered to be allergic or parasitic (Shaw et al, 1996). In this case, parasitic causes may be considered unlikely given the lack of response to fenbendazole, the lack of larvae in the airway washes and the excellent response to treatment with prednisolone without relapse. Faecal examination may have helped to confirm the absence of parasites.

                        It has been reported in humans that acute exacerbation of chronic bronchitis may be associated with a marked airway eosinophilia (Saetta et al 1994). In this case, the cough was noted to worsen shortly after surgery to remove a mast cell tumour. The possibility of the mast cell tumour contributing to inflammation by exerting a paraneoplastic effect was considered unlikely as the cough persisted after the mast cell tumour was removed. Possibly, the stress of surgery or endotracheal intubation exacerbated the condition, causing the eosinophilia. However, given the long term control provided by anti-histamines, allergic eosinophilic bronchitis was the most likely diagnosis, although a specific allergen was not identified.

            Corticosteroids are reported to be efficacious and are indicated for eosinophilic bronchitis. Benefits include decreased migration of inflammatory cells and protection of cells from damage and consequent release of inflammatory mediators. Risks include inhibition of macrophages and lymphocytes causing vulnerability to infection. Broad spectrum antibiotics are therefore indicated during acute exacerbations to prevent potentially life-threatening secondary complications (Prueter and Sherding 1985). In this case, steroids were also contra-indicated because of a delay in wound healing following surgery, and their long term use was consequently delayed until the wound was healed.

            Theophylline may be useful as a bronchodilator in chronic bronchitis (Prueter and Sherding 1985) but its metabolism is inhibited when used concurrently with enrofloxacin, potentially leading to toxic plasma levels  (Intorre et al 1995). Mucolytic agents may be given, but these can induce bronchospasm and the efficacy of expectorants such as guaifenesin has been questioned (Prueter and Sherding 1985). Therefore these treatments were not used in the management of this case.

            Bronchitis is a chronic disease which cannot be cured and treatment aims are to control inflammation and prevent worsening of airway disease (Johnson 1999). This case responded excellently to steroid treatment and symptoms are well-controlled by anti-histamines alone.

References

BROWNLIE, S. E., (1990) A retrospective study of diagnosis in 109 cases of canine lower respiratory

                           disease. Journal of Small Animal Practice 31: 371-376

BUCHANAN, J. W., (2000) Vertebral scale system to measure heart size in radiographs. Veterinary        

         Clinics of North America Small Animal Practice 30, 379-93

ETTINGER, S. J., (1999) Couging.   In: Textbook of Veterinary Internal Medicine, 5th edn.              

                    Eds S. J. Ettinger & E. C. Feldman. W. B. Saunders, Philadelphia, pp 158-165

INTORRE, L., MENGOZZI, G., MACCHERONI, M., et al (1995) Enrofloxacin-theophylline            

                      interaction: Influence of enrofloxacin on theophylline steady-state pharmacokinetics in the             

                      Beagle dog. Journal of Veterinary Pharmacology and Therapeutics 19: 352

JOHNSON, L. (1999) Diseases of the bronchus. In: Textbook of Veterinary Internal Medicine, 5th edn.              

              Eds S. J. Ettinger & E. C. Feldman. W. B. Saunders, Philadelphia, pp 1055-1061

PRUETER, J. C., & SHERDING, R. G., (1985) Canine chronic bronchitis. Veterinary clinics of North

                 America Small Animal Practice 15: 1085-1097

SAETTA, M., DI STEFANO, A., MAETRELLI, P., TURATA, G., RUGGIERI, M. P., ROGGERI,

                          A., CALGANI, P., MAPP, C. E., CIACCIA, A., FABBRI, L. M., (1994) Airway eosinophilia   

                      in chronic bronchitis during exacerbations. American Journal of Respiratory Critical Care

                                Medicine 160: 1646-1652

SHAW, H. D., CONBOY, G. A., HOGAN., P. M., HORNEY, B. S., (1996) Eosinophilic bronchitis   

                     caused by Crenosoma vulpis infection in dogs. Canadian Veterinary Journal 37: 361-363

Figs 1 and 2 Lateral and DV thoracic radiographs

Fig 3 Tracheal wash cytology

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