Interstitial Pneumonia – If It’s Not Asthma What Can We Do?

Interstitial lung disease or interstitial pneumonia are umbrella terms for various inflammatory pulmonary disorders that progress to lung fibrosis. They are reported to be uncommon in adult horses, but multiple infectious, toxic, and irritant causes, as well as immune-mediated diseases and hypersensitivity have been described. Determining the causative agent can be difficult at the time of diagnosis of the disease because the pulmonary response to different insults is similar. After injury to the lung parenchyma and alveolitis, cellular changes occur and lead to structural derangements finally resulting in fibrosis.

Because interstitial lung diseases are rare in adult horses they are easily missed. Equine asthma is the most common lower airway disease affecting horses. Therefore, it is the main differential diagnosis in horses showing clinical signs of lower airway disease. But there are differences in history, clinical signs, and findings of further diagnostic tests, which can raise the suspicion that the horse is not suffering from asthma but from an interstitial lung disease. Due to severity of interstitial lung diseases an early diagnosis is desirable.

History

Horses with severe equine asthma usually have a very typical history (HOARSI score), whereas horses with interstitial lung disease may have additional abnormalities, like weight loss, pyrexia, or an abnormal breathing pattern. Many horses with interstitial lung disease have already been treated for another pulmonary disease, like asthma, without sufficient improvement of clinical signs despite appropriate management changes and medical therapy.

Clinical examination

Horses with moderate asthma might not show any clinical signs of lower airway disease at rest, while horses with severe asthma usually have dyspnoea at rest with increased respiratory rate but also increased abdominal effort. One of the main clinical differences in breathing pattern is the restrictive rather than obstructive breathing pattern in horses with interstitial lung disease, compared with horses with asthma. Sometimes tachypnoea, a rapid shallow breathing pattern, is obvious. They might also have tachycardia, a variable increase in temperature, and exercise intolerance. Depending on the severity of disease, cyanosis and respiratory dyspnoea with nostril flare and an anxious facial expression might be apparent. Lung auscultation can be quite unrewarding; diffuse crackles and wheezes may be heard but sometimes absence of lung sounds might be striking in the face of increased respiratory effort.

Diagnostic methods

Haematology and blood biochemistry are usually unremarkable in horses with asthma. Depending on the type of interstitial pneumonia, abnormalities consistent with chronic inflammation can be found, like neutrophilic leucocytosis and hyperfibrinogenaemia in equine multinodular pulmonary fibrosis (EMPF), or peripheral eosinophilia in idiopathic eosinophilic pneumonia or hypersensitivity pneumonitis.

Arterial blood gas analysis will usually show the results of altered ventilation–perfusion relationship, reduced number of functional alveoli and increased diffusion barrier thickness: hypoxaemia, but also hypercapnia if the disease is already advanced.

Although thoracic radiographs are not a specific or sensitive method, in some interstitial lung diseases fairly typical lesions can be found, like a nodular pattern in EMPF or pulmonary infiltrates with fungal pneumonia or a granular pattern with eosinophilic pneumonia. In others an extensive interstitial or bronchointerstitial pattern might be seen.

Ultrasonographic findings may demonstrate changes suggestive of severe fibrosis or nodular infiltrates. Echocardiography can show signs of pulmonary hypertension or even cor pulmonale.

Tracheal wash (TW) and bronchoalveolar lavage fluid (BALF) cytology usually reveal unspecific changes, like an increased number of neutrophils. Suspicion for interstitial lung disease sometimes arises if cytology does not match the severity of clinical signs. But in some cases, discrete evidence of interstitial lung disease can be found, like eosinophilic intranuclear inclusion bodies in macrophages in EMPF or eosinophilic crystals in silicosis. In humans, the lymphocyte/macrophage ratio and an increased number of lymphocytes point towards an interstitial disease. If this is also true for horses still needs to be evaluated but could be the case in hypersensitivity pneumonitis. Granulomatous disease might be accompanied by an increase in multinucleated giant cells. In cases of interstitial pneumonia involving pneumocystis those might be found on cytology. But it needs to be considered that the role of pneumocystis in equine lung disease is still unclear and pneumocystis is sometimes also found in horses without further evidence of interstitial pulmonary disorders.

PCR testing of TW and BALF can also be used, for example for pneumocystis. An EHV-5 PCR positive BALF strongly suggests EMPF in suspicious cases. Microbiological culture is usually negative or only yields nonspecific growth, but can be positive if a secondary bacterial infection is present.

Histopathological examination of a lung tissue sample taken by transthoracic biopsy can provide a definitive antemortem diagnosis in cases of interstitial pneumonia and fibrosis, either in diffuse disease or taken from a representative area in cases of localised disease identified by ultrasound. Immunohistochemistry and PCR evaluation of the biopsy sample may even help to identify the causative agent.

Further diagnostic tests might be necessary in cases where neoplastic disease needs to be ruled out or if further information is needed, for example in cases with hypersensitivity pneumonitis. Changes in compliance can be shown by sensitive lung mechanics/lung function testing.

Treatment and prognosis

An early diagnosis and identification of a causative agent are desirable to initiate treatment. Unfortunately, treatment in most cases will be nonspecific and supportive only, for example with bronchodilators or oxygen. In case of a superimposed bacterial infection, antimicrobials might be necessary. Specific treatment, for example valacyclovir used to treat herpes viral infections, is rarely initiated because in many cases the causative agent cannot be identified. The aims of the treatment of chronic interstitial lung disease are to suppress inflammation, immunomodulation or suppression, prevention of further fibrosis, and decreasing pulmonary hypertension. Various drugs, like corticosteroids, azathioprine, methotrexate, pentoxifylline, doxycycline, macrolides and sildenafil have been used with very variable success. Due to the rare nature of the diseases, evaluating the efficacy of treatment is challenging. Prognosis is reported to be guarded to poor for most interstitial lung diseases.

References

Available on request from the author.

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