Introduction

In dogs, idiopathic pulmonary fibrosis (CIPF) has been described with a clear breed predisposition; indeed, canine IPF affects mainly the West Highland white terriers (WHWT). It has been described, much more rarely, in other terrier breeds, such as the bull terrier or the Staffordshire bull terrier,^1,2 although it is not known if pulmonary fibrosis is exactly the same as in the WHWT breed. Since its first description in 1999,³ several studies have been conducted to improve the clinical characterisation of the disease, expand our understanding about the pathophysiology and identify biomarkers of the disease. At the present time, however, several aspects of CIPF remain unknown. A similar condition exists in humans.⁴ In man, idiopathic pulmonary fibrosis (IPF) is an emerging progressive fibrotic lung disease with an unknown aetiology, poorly understood pathophysiology, and a poor prognosis.

Etiology and Pathophysiology

As in humans, the etiopathogenesis of IPF in dogs is not known. There is emerging evidence for the role of genetic factors in the development of the disease. Most cases appear to be caused by an interaction between a specific environmental exposure and a genetic predisposition. In dogs, confinement to related terrier breeds combined with very low incidence within non-terrier breeds also strongly suggests an underlying genetic cause. Current prevailing hypotheses for the condition focus on dysregulated epithelial-mesenchymal interactions promoting a cycle of continued epithelial cell injury and fibroblast activation leading to fibrosis. Multiple abnormalities in a myriad of biological pathways affecting inflammation and wound repair, including matrix regulation, epithelial reconstitution, the coagulation cascade, neovascularization, and antioxidants, modulate this defective process and promote fibrogenesis.

Clinical Presentation

The disease is clinically characterized by progressive dyspnea, exercise intolerance.^1,5 As it occurs gradually in old animals, owners may first think that symptoms are only related to ageing. Most dogs also present chronic cough. In severe cases, exercise intolerance is obvious and the tongue can get a bluish appearance. Pronounced crackles are a hallmark of the disease; they can be heard on auscultation, and can sometimes be heard by the owners without stethoscope. The general body condition is good and dogs do not lose weight and remain happy living pets for a prolonged period.

Diagnosis and Differential Diagnosis

The disease is not easily distinguished from chronic bronchitis, which may co-exist. In IPF, cough can be attributed with tracheal collapse, which is found in a proportion of affected dogs, probably due to the increased work of breathing. Crackles might suggest cardiogenic edema; however, such a diagnosis is not compatible with other clinical findings. In some dogs, crackles can even be heard without stethoscope when the dog is breathing with an open mouth.¹ Radiographic, bronchoscopic, hematologic, or biochemical findings are not specific, but help to eliminate other possible disorders. Echocardiography may reveal signs of secondary pulmonary arterial hypertension. Arterial blood gas analysis shows low levels of Pa02 and a high alveolar-arterial oxygen gradient.¹ The 6 minutes walking test, a totally non-invasive exercise testing, increasingly used in clinical human practice for exercise capacity evaluation, may be used in dogs with IPF.⁶ Other non-invasive pulmonary function tests are rarely used in veterinary practice. Lung imaging using high-resolution CT is currently often used to evaluate IPF in humans, and is the test of choice in dogs as well⁷ and, it can be performed under sedation in most dogs.⁸ A recent study reported that ultimate confirmation of the diagnosis requires lung biopsy and histopathology.⁹ With the goal to better understand this fatal disease and to offer novel therapeutic approaches for the future, as well as to improve its diagnosis, a collaborative research project has jointly initiated a few years ago by our team at the University of Liège and Professor Rajamäki from the University of Helsinki. A dedicated website has been built (www.caninepulmonaryfibrosis.ulg.ac.be/), which aims to share objectives, progress, and information relating to this research project and to improve communications between veterinarians, dogs owners, and breeders around the disease.

Management/Prognosis

As the disease is a progressive condition, the long-term prognosis is poor. A mean survival time of about 18 months has been reported.⁶ However, some dogs survive more than 4 years. Treatment in dogs with IPF is essentially symptomatic and supportive. In animals with concomitant arterial pulmonary hypertension, treatment with sildenafil is indicated. Oral glucocorticoid drugs are often used but have no proven benefit, while subjecting the dog to potentially detrimental side-effects. In dogs with chronic cough associated with tracheal collapse and/or chronic bronchitis, treatment with inhaled steroid therapy is helpful. Antitussives can be used if cough is irritating. Bronchodilators, such as theophylline may be used to promote bronchodilation, enhance mucociliary clearance, and increase the contractility of the diaphragm muscle.

References

1.  Heikkilä HP, Lappalainen AK, Day MJ, Clercx C, Rajamäki MM. Clinical, bronchoscopic, histopathologic, diagnostic imaging, and arterial oxygenation findings in West Highland white terriers with idiopathic pulmonary fibrosis. J Vet Intern Med. 2011;25(3):433–439. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2011.0694.x/full. (VIN editor: Link not accessible).

2.  Heikkilä-Laurila HP, Rajamäki MM. Idiopathic pulmonary fibrosis in West Highland white terriers. Vet Clin North Am Small Anim Pract. 2017;44(1):129–142. Available from: www.sciencedirect.com/science/article/pii/S0195561613001769?via%3Dihub. (VIN editor: Original link was modified on 1-03-2018).

3.  Corcoran BM, Cobb M, Martin MW, Dukes-McEwan J, French A, Fuentes VL, et al. Chronic pulmonary disease in West Highland white terriers. Vet Rec. 1999;144(22):611–616.

4.  Sgalla G, Biffi A, Richeldi L. Idiopathic pulmonary fibrosis: Diagnosis, epidemiology and natural history. Respirology. 2017;21(3):427–473. Available from: http://onlinelibrary.wiley.com/doi/10.1111/resp.12683/abstract. (VIN editor: Original link was modified on 1-03-2018).

5.  Heikkilä-Laurila HP, Rajamäki MM. Idiopathic pulmonary fibrosis in West Highland white terriers. Vet Clin North Am Small Anim Pract. 2014;44(1):129–142. Available from: www.sciencedirect.com/science/article/pii/S0195561613001769?via%3Dihub. (VIN editor: Original link was modified on 1-03-2018).

6.  Lilja-Maula LI, Laurila HP, Syrjä P, Lappalainen AK, Krafft E, Clercx C, et al. Long-term outcome and use of 6-minute walk test in West Highland white terriers with idiopathic pulmonary fibrosis. J Vet Intern Med. 2014;28(2):379–385. Available from: http://onlinelibrary.wiley.com/doi/10.1111/jvim.12281/full. (VIN editor: Original link was modified on 1-03-2018).

7.  Johnson VS, Corcoran BM, Wotton PR, Schwarz T, Sullivan M. Thoracic high-resolution computed tomographic findings in dogs with canine idiopathic pulmonary fibrosis. J Small Anim Pract. 2005;46(8):381–388.

8.  Roels E, Couvreur T, Farnir F, Clercx C, Verschakelen J, Bolen G. Comparison between sedation and general anesthesia for high resolution computed tomographic characterization of canine idiopathic pulmonary fibrosis in West Highland white terriers. Vet Radiol Ultrasound. 2017;58(3):284–294. Available from: www.ncbi.nlm.nih.gov/pubmed/28229501.

9.  Syrjä P, Heikkilä HP, Lilja-Maula LI, Krafft E, Clercx C, Day MJ, et al. The histopathology of idiopathic pulmonary fibrosis in West Highland white terriers shares features of both non-specific interstitial pneumonia and usual interstitial pneumonia in man. J Comp Pathol. 2013;149(2–3):303–313. Available from: www.sciencedirect.com/science/article/pii/S0021997513000571. (VIN editor: Original link was modified on 1-03-2018).