Interstitial Pneumonia

By | 2012-11-11

Interstitial pneumonia is an uncommon cause of acute or chronic disorders of the lower respiratory tract of horses. However, because of the severity of the process, recognition and definitive diagnosis of this entity are important as early as possible in its clinical course.

The term interstitial pneumonia defines a number of diseases that are chronic and progress to pulmonary fibrosis. The course is insidious and morphologically characterized by alveolar structural derangements that lead to loss of functional gas exchange units of the lung and altered mechanical properties of the lung, characterizing the pneumonia as a restrictive lung problem.

Etiology of Interstitial Pneumonia

Pathophysiology of Interstitial Pneumonia

Interstitial pneumonia progresses through four phases. During the first, the initial insult causes parenchymal injury and alveolitis. This is followed by a proliferative phase characterized by cellular and parenchymal alterations in tissues of the lung. Chronic cases progress to the development of interstitial fibrosis, whereas the final stage results in end-stage irreparable fibrosis of the lung.

The structural changes that occur in the lung reduce the number of functional alveoli, adversely affecting ventilatory function of the lung and altering ventilation/per-fusion relationships. Reduced lung compliance is associated with the loss of distensible alveoli and presence of pulmonary edema and fibrosis. Total and vital lung capacities are decreased in association with the loss of functional gas exchange units and reduced lung compliance. The work of breathing is increased, resulting in exercise intolerance and difficulty in breathing. Pulmonary hypertension and cor pulmonale may present as complications of interstitial pneumonia and fibrosis. Although the origin of pulmonary hypertension is unclear, hypoxic vasoconstriction and generation of vasoactive compounds (such as endothelin-1) that alter pulmonary vascular resistance acutely, and vessel anatomy chronically, may play a role.

Interstitial Pneumonia: Clinical Signs

Horses affected with interstitial pneumonia frequently present with fever, cough, weight loss, nasal discharge, exercise intolerance, severe dyspnea, cyanosis, and a restrictive breathing pattern. A “heave line” is frequently present; nostril flare and an anxious expression are usual. The history can be acute or chronic. Although affected foals are frequently depressed and anorectic, adults may be bright and alert with a variable appetite. The disease proceeds toward death in many cases, with progressive respiratory compromise, although some also may improve slowly with time. More than one foal at a farm may be affected.

Diagnosis of Interstitial Pneumonia

In older horses, the primary differential diagnosis of heaves may be excluded by the leukocytosis and hyperfibrinogenemia that commonly occur in horses with interstitial pneumonia and fibrosis but do not occur in horses with heaves. However, these abnormal features are common in horses with infectious bronchopneumonia and thoracic radiography is paramount in the establishment of a definitive diagnosis. Typically, thoracic radiographs reveal extensive interstitial and bronchointerstitial pulmonary patterns (). Nodular infiltrates may be present, either large or miliary, but always diffusely distributed.

Culture of transtracheal or bronchoalveolar lavage (bronchoalveolar lavage) aspirates often yields no significant growth of bacterial or fungal pathogens. This is particularly useful in foals and, in combination with negative results of a Gram-stained tracheal aspirate, reinforces the clinical diagnosis of interstitial pneumonia. Cytologic evaluation of tracheal or bronchoalveolar lavage fluid shows increased numbers of neutrophils and macrophages. If P. carinii is involved, bronchoalveolar lavage fluid may reveal trophozoites or intracystic bodies with special stains, such as toluidine blue or methenamine silver.

Histologic examination of a transthoracic lung biopsy specimen is the definitive diagnostic test for chronic interstitial pneumonia and fibrosis (). Care must be taken to ensure the biopsy is obtained from a representative area and ultrasound guidance has been useful in the hands of the author. Complications from this technique are uncommon but can occur. Biopsy rarely defines the causative agent but confirms the clinical diagnosis.

Additional diagnostics could include arterial blood gas analysis, abdominocentesis, and thoracocentesis to rule out metastatic neoplastic disease, pulmonary function testing, viral isolation, serologic testing for antibody to fungi and chicken serum if hypersensitivity pneumonitis is suspected, and immunohistochemical evaluation of lung tissue for suspected infectious agents. A complete cardiac evaluation also should be conducted to screen for pulmonary hypertension and cor pulmonale.

Treatment of Interstitial Pneumonia

Treatment of these cases is often unrewarding. Therapeutic goals are treatment of any underlying or secondary infection; suppression of inflammation; maintenance of tissue oxygen delivery within appropriate limits; relief of any associated bronchoconstriction; and prevention or treatment of complications. Environmental control, with appropriate temperature and humidity control and good ventilation, is beneficial.

Parenteral corticosteroid therapy is the mainstay of treatment, with early and aggressive therapy providing the best long-term outcome, particularly in foals. In one report of 23 foals affected with acute bronchointerstitial pneumonia, 9 of 10 treated with corticosteroids survived, whereas none of those not receiving steroid treatment lived. Dexamethasone (0.1 mg/kg q24h) is suggested initially. Inhaled beclomethasone (8 μg/kg q12h) may be considered. Additional antiinflammatory therapy includes, but is not limited to, dimethyl sulfoxide (DMSO; 1 g/kg as a 10% solution IV q24h), flunixin meglumine (Banamine; 1 mg/kg IV q12h) and methyl sulfonyl methane (15-20 mg/kg PO q24h).

Broad-spectrum antimicrobial treatment should be instituted initially, particularly in foals, as described for the treatment of infectious bronchopneumonia (see “Pleuropneumonia”). The choice of antimicrobial and duration of therapy should be dictated finally by the culture and sensitivity results from the transtracheal aspirate and by the patient’s clinical course.

Foals, in particular, and adults with severe respiratory distress may benefit from nasal insufflation of humidified oxygen, with flow rates of 10 L/min for foals and 15 L/min in adults. If necessary, as determined by persistent hypoxemia in the face of intranasal insufflation at the rates given, a second nasal canula can be placed in the opposite nostril to increase the Fio2. Care must be taken to avoid obstruction of the nasal passages. Alternatively, intratracheal or transtracheal insufflation can be considered to further increase Fio2 and improve oxygenation.

Systemic bronchodilator therapy may or may not be indicated in these cases. If utilized, bronchodilators may worsen ventilation-perfusion inequalities. Thus bronchodilator therapy should be accompanied by supplemental oxygen and the effects should be monitored with serial blood gas measurements and discontinued if hypoxemia worsens. Nebulized or aerosolized bronchodilator therapy may be more judicious, and beneficial effects are evident in some foals with respiratory distress. Examples include albuterol (180-360 μg) or ipratropium bromide (40-80 p.g) or two to four puffs of either, or in combination. Aminophylline and theophylline should not be used because of their narrow therapeutic range. Furosemide (0.5 mg/kg q12h) may be appropriate for its bronchodilator effect and its effect on reducing pulmonary artery pressure, particularly if cor pulmonale develops. It is particularly useful in the management of pulmonary edema. Potential useful therapies in the future may include compounds such as endothelin-1 (ETA) receptor antagonists and inhibitors of fibrosis, such as colchicine.

Prognosis of Interstitial Pneumonia

The prognosis of interstitial pneumonia in horses is uniformly poor to guarded. Affected foals, treated early and aggressively with corticosteroid and antimicrobial therapy, have the best outlook for life. The disease is usually progressive in adults and eventually results in the demise of the horse, although the occasional horse recovers sufficiently to return to previous performance levels. A fair number of adult horses, with continuous intense management, live for a period of time but will be severely compromised, limiting their usefulness.

Exceptions to the poor prognosis may be seen in cases of P. carinii pneumonia in foals if they are treated early and aggressively and in cases of idiopathic interstitial pneumonia in adult horses that are treated early with corticosteroids. A trial of treatment for peracute interstitial disease for 48 hours is warranted and chronic interstitial pneumonia should be treated for a minimum of 2 to 4 weeks before discarding the possibility of recovery.