Idiopathic pulmonary fibrosis (IPF) in small animals

Please, DO NOT use the contents of this blog post as veterinary advice. The purpose of this blog is to help me revise for my exams. If your animal has any symptoms, consult with a registered veterinary surgeon as to what is the best course of treatment.

IDIOPATHIC PULMONARY FIBROSIS (IPF) IN SMALL ANIMALS

Histology of A - healthy lung and B - lung with IPF source: http://www.caninepulmonaryfibrosis.ulg.ac.be/about-ipf/

Idiopathic pulmonary fibrosis (IPF) is a chronic, non-inflammatory, progressive, fibrotic respiratory condition seen in the lung tissue of affected species. In small animal practice, those species are more commonly dogs and cats.

Anecdotally, there's a predisposition for this condition in West Highland white terriers (this is the reason why, sometimes this condition is referred to as "Westie lung disease"). Other terrier breeds often affected by IPF are Staffordshire Bull terriers, Jack Russell terriers, Carin terriers; in addition to Schipperkes (Webb and Armstrong, 2002; Nelson and Couto, 2013).

Usually, dogs and cats start presenting signs of this condition when they are middle-aged, but younger patients can be affected as well (mean age of onset was 9 years old and life expectancy after onset of clinical signs was around 18 months in a study with West Highland white terriers in the late 1990's- Corcoran et al. 1999). There is no evidence of a sex predilection.

There is no consensus on the aetiology of IPF, "in dogs it has been associated with a primary lesion of collagen deposition in the alveolar septa (Nelson and Couto, 2013)", which could be caused by a number of things such as "infectious processes, drug reactions, exposure to toxins or dust and connective tissue disorders (Webb and Armstrong, 2002)". Nevertheless, Cohn (2006) affirms "IPF is not associated with prior lung injury or inflammation and Nelson and Couto (2013) claim "a defect in wound healing has been hypothesised as the cause". So, the origin of the condition is still very much debated, but the pathogenesis is clearer.

"Although the initiating factor or factors of IPF are not known, the progression of the disease is better understood. Chronic alveolitis develops slowly over a period of months to years, reducing gas exchange across the alveolar wall and the surrounding capillary bed. At some point, injury to the alveolar wall becomes irreversible and fibrosis of the alveolar wall begins. This fibrosis results in an increase in the density of interstitial lung tissue. Secondary mineralization of the pulmonary parenchyma may follow this initial fibrosis." (Webb and Armstrong, 2002)

Concerning the histopathology of IPF, we are able to observe the following features in affected tissues: fibrosis, fibroblast proliferation, metaplasia of alveolar epithelium, and mild to moderate inflammation. Lungs are heterogeneously affected with abnormal areas often in the subpleural region (Nelson and Couto, 2013).

These histological alterations lead to hypoxaemia in later stages of the disease, which cause great distress and can lead to death.

Clinical signs

In cats, duration of signs can be shorter - in a study by Cohn et al. (2004) quoted by Nelson and Couto (2013), 6 of 23 cats showed signs for 2 days to 2 weeks. Later, Cohn (2006) confirms that signs in cats may seem acute because they often don't display exercise intolerance.

In general, signs progress slowly over months. Clinical signs of IPF include dyspnoea, severe exercise intolerance (laboured breathing, cyanosis and even syncope), cough (if this is the predominant sign - consider bronchitis), crackles and wheezes (more often in dogs than cats).

Diagnosis

Differentials -- dogs: valvular heart disease with or without congestive heart failure (CHF), chronic bronchitis, pulmonary neoplasia, pneumonia and others; cats: feline asthma, pulmonary neoplasia, CHF, pleural effusion and others; non-idiopathic causes: infection (e.g. FIV, calicivirus, herpesvirus, distemper virus, Toxoplasma, Histoplasma), toxic or environmental insults (e.g. paraquat, asbestos, silica, diesel exhaust, oxygen toxicity, bleomycin, radiation), immune-mediated connective tissue disease (e.g. systemic lupus erythematosus, Sjogren's syndrome), pulmonary neoplasia  (Cohn, 2006).

Laboratory testing - CBC, biochem profile, urinalysis, faecal - are usually unremarkable, but are useful to rule out possible differentials. Polycythaemia may be present secondary to chronic hypoxaemia. Faecal exams, such as Baermann test to rule out lung worms and a SNAP test for heartworms are appropriate.

Radiographs - the next step after a good clinical exam and possibly along side laboratory testing is thoracic radiographs. Dogs typically show diffuse interstitial pattern and bronchial pattern concurrently, with evidence of pulmonary hypertension. Cats may have bronchial, interstitial, alveolar or mixed pattern and are often quite severe by the time of the exam. Both species can present bronchiectasis - caused by traction of the airways (Nelson and Couto, 2013). In humans, CT scan would be gold standard, but this technique is not as often used in animals.

CT scan of A - healthy dog thorax and B - thorax of dog with IPF
source: http://www.caninepulmonaryfibrosis.ulg.ac.be/about-ipf/

Echocardiography (ECG) - is indicated to rule out a primary cardiac condition and to give more accurate prognosis by assessing pulmonary hypertension when tricuspid jet is present (Cohn, 2006).

Invasive respiratory diagnostics - bronchoscopy, tracheal lavage, pulmonary lavage, pulmonary fine-needle aspiration need to be fully consented by the person responsible for the animal and can rule out differentials such as infectious causes, chronic bronchitis and neoplasia. However, definitive diagnosis requires lung biopsy and histopathological analysis

Serum endothilin-1 (ET-1) - not yet commercially available, has been used in research and shown promise as a diagnostic marker for IPF in dogs with 100% sensitivity and 81% specificity (Nelson and Couto, 2013).

Treatment

Even in human medicine a curative treatment for IPF does not exist. In small animal practice, all treatment is symptomatic and none has been proved effective yet.

Treatment based mainly in the use of corticosteroids (prednisone 0.5 - 1 mg/kg/day, PO) and bronchodilators (e.g. theophylline derivatives - which theoretically potentiate steroid activity). Cough suppressants (e.g. Hydrocodone - 0.22 mg/kg PO q 6-12 h; butorphanol - 0.05-1 mg/kg PO q 6-12h), N-acetylcysteine (antifibrotic) and oxygen therapy may help with symptoms.

Immune modulators such as azathioprine and cyclophosphamide have been used in human medicine, but the risk of death and hospitalisation was increased in patients having this combination (quoted in Nelson and Couto, 2013).

If pulmonary hypertension is severe (tricuspid regurgitant velocity ≥ 2.8 m/s or pulmonary insufficiency velocity ≥ 2.2 m/s), some drugs such as ACE-inhibitors (enalapril 0.5 mg/kg PO q12-24 h), calcium-channel blockers (amlodipine 0.1 mg/kg titrated up to maximum of 0.4 mg/kg PO q12 h) and sildenafil (0.5-2 mg/kg/day PO) could be used and potentially help. Always monitor systemic blood pressure when administering this treatment. Ideally, pulmonary pressures should also be monitored to assess efficacy of therapy.

Sedatives may be of use if the animal is distressed or severely anxious (acepromazine 0.05 mg/kg SC or IM).

Diuretic therapy is NOT indicated for IPF.

Be careful not to put patient through strenuous activities, allow them to self-limit exercise (only if they are reasonable!)

Additionally, unconventional therapy with proteolytic enzyme serrapeptase has been used occasionally and there are a few accounts of this treatment among pet owners as well as some studies about this protein.

Prognosis

Guarded to grave. Dogs usually survive approximately 18 months after diagnosis, but Corcoran et al. (1999) reports survival of up to 3 years after diagnosis. Unfortunately, cats have worse prognosis - Cohn et al. (2004) reported 14 cats out of 23 died or were euthanised within weeks of onset of signs and only 7 survived longer than 1 year.

Sources: 

Cohn (2006) Idiopathic Pulmonary Fibrosis - https://www.cliniciansbrief.com/article/idiopathic-pulmonary-fibrosis

Cohn et al. (2004) Identification and characterization of an idiopathic pulmonary fibrosis-like condition in cats. Journal of Veterinary Internal Medicine, 2004 Sep-Oct;18(5):632-41. https://www.ncbi.nlm.nih.gov/pubmed/15515577

Corcoran et al. (1999) Chronic pulmonary disease in West Highland white terriers. Veterinary Record, 1999;144:611–616. https://www.ncbi.nlm.nih.gov/pubmed/10390801

Nelson and Couto (2013) Small Animal Internal Medicine, Elsevier, 5th ed.

Webb and Armstrong (2002) Chronic idiopathic pulmonary fibrosis in a West Highland white terrier. Canadian Veterinary Journal, 2002 Sep; 43(9): 703–705. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC339552

http://www.caninepulmonaryfibrosis.ulg.ac.be/about-ipf/

http://www.westielungdisease.co.uk/visitors/

https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1440-1843.2003.00482.x