Research project
Idiopathic pulmonary fibrosis is a fatal disease. At present, the mechanisms of initiation and progression of this disease are poorly understood, the diagnosis is difficult to achieve and the prognosis is guarded. It is for these reasons that a research program was jointly initiated a few years ago in the faculties of Veterinary Medicine of Liege and Helsinki under the supervision of Professors Clercx and Rajamäki respectively.
This research protocol was approved by the ethical committees of the University of Liege, Helsinki and Bristol and received grants from the FNRS and the University of Liege, as well as from the European College of Veterinary Internal Medicine (ECVIM-CA).
Through the partnership of some breed clubs, national French vet schools and veterinary partners in several European countries, new cases are recruited and allow us to collect new information about this disease.
Clinical studies
Through ongoing collaboration with breeders, dogs’ owners and veterinary partners, we are actively collecting clinical information in IPF dogs. The purpose of this collection of clinical information is to characterize the disease as much as possible in order to improve the diagnosis, the estimation of prognosis and to correctly select animals for genetic and molecular studies.
Molecular studies
Molecular studies are conducted jointly at the Universities of Liège and Helsinki and aim to identify biomarkers of pulmonary fibrosis. A biomarker is a molecule that can be measured in the blood and/or in the bronchoalveolar lavage fluid and which increases only in diseased animals. In addition to helping in the diagnosis and prognosis, identification of biomarkers of fibrosis also helps to discover potential new therapeutic targets. Different molecules have already been studied (see “Articles”) and have shown encouraging results.
Recently, in human medicine, studies on the pulmonary microbiota in idiopathic pulmonary fibrosis have been carried out and showed a link between bacterial load (the amount of bacterial DNA found in the bronchoalveolar lavage fluid), specific bacterial genera and the progression of the disease. Those studies suggest that the lung microbiota can act as a trigger or a perpetuation factor of the disease. This is why we are looking at the lung microbiota in both diseased and healthy West Highland White Terriers. We also compare the lung microbiota in young and old healthy Westies, and in healthy Westies compared with healthy dogs of other breeds non predisposed to the disease, since only older Westies have the disease. We are also interested by the interactions between the lung microbiota and the innate immune response mounted. More recently macrophages populations in the bronchoalveolar lavage fluid have been studied in diseased and healthy West Highland White Terrier.
Genetic studies
Due to the fact that pulmonary fibrosis appears mainly in purebred West Highland White Terrier dogs, a strong genetic component of the disease is suspected. To identify possible genetic mutations responsible for this disease, a genome wide association study (GWAS) has recently been initiated at the University of Helsinki based on blood samples (EDTA blood) collected so far. Such a genetic study requires a high number of well-phenotyped diseased individuals and control individuals. The number of dogs collected so far is not yet high enough and identification of control dogs is challenging. Indeed, pulmonary fibrosis affects old dogs. It is therefore possible that some of the dogs included in the “control group” would develop the disease later on. This greatly complicates the interpretation of the results and increases the requirement for strict selection criteria such as performing a thoracic CT-scan to ensure the absence of lesions in the group of controls.
At the University of Liege, other studies are performed. Based on lung tissue samples collected after death, we try to identify differences in gene expression in the lung affected or not by IPF. By this approach, we hope to better understand the mechanisms of the disease and identify possible therapeutic targets. So far, several molecules of interest have been identified and are currently being studied in more details.
Who supports us
Our project is supported by
The FNRS (Fonds de la Recherche Scientifique) by funding of two research fellows on this project and granting research credits.
The University of Liège through Special Funds and research sectorial credits.
FARAH, the faculty of veterinary medicine research center (comparative veterinary medicine section).
SAMsoc (Small Animal Médicine Society) who offers support to promote collaboration in clinical research.
