Serum and Bronchoalveolar Lavage Fluid Endothelin‐1 Concentrations as Diagnostic Biomarkers of Canine Idiopathic Pulmonary Fibrosis

Abstract

Background: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin-1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown.Objective: To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP).Animals: Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs.Methods: Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF.Results: No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05-3.38) than healthy Beagle dogs (1.28, 1.07-1.53; P o .001), healthy WHWT (1.56, 1.25-1.85; P o .001), dogs with EBP (0.94 0.68-1.01; P 5 .001), and dogs with CB (1.54 0.74-1.82; P 5 .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut-off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818.Conclusions and Clinical Importance: Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF.

Long‐Term Outcome and Use of 6‐Minute Walk Test in West Highland White Terriers with Idiopathic Pulmonary Fibrosis

“…Only variables that were available for at least 10 diseased animals and that had previously been shown to be altered in WHWTs with IPF1, 17 were chosen. The variables analyzed included partial pressures of oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) in arterial blood, alveolar‐arterial oxygen gradient (P(A‐a)O 2 ), serum endothelin‐1 concentration, severity of changes in thoracic radiographs, and HRCT Hounsfield unit values.…”

“…The variables analyzed included partial pressures of oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) in arterial blood, alveolar‐arterial oxygen gradient (P(A‐a)O 2 ), serum endothelin‐1 concentration, severity of changes in thoracic radiographs, and HRCT Hounsfield unit values. These variables were analyzed as previously described 1, 17. The radiographs and HRCT images were viewed by one of the authors (A.K.L).…”

Evaluation of chemokines CXCL8 and CCL2, serotonin, and vascular endothelial growth factor serum concentrations in healthy dogs from seven breeds with variable predisposition for canine idiopathic pulmonary fibrosis

“…Those breeds were considered as highly (WHWT), possibly (ST, JRT), or not (M, KCS, LR, MBS) -CIPF predisposed breeds. ST and JRT were chosen as terrier breeds potentially predisposed to CIPF; given that one CIPF case has already been confirmed by histopathology in a dog from the ST breed (Krafft et al, 2011) and that CIPF has been clinically suspected in five JRT, but not histopathologically confirmed (personal observations). M breed was chosen as a non-terrier breed sharing similarities in weight and size with the WHWT breed.…”

“…Rare cases have also been described in other terrier breeds such as the Staffordshire terrier (Lobetti et al, 2001) and the Scottish terrier (Krafft et al, 2011). Pathogenesis of CIPF is currently unknown, although a genetic basis is strongly suspected due to the breed predisposition (Heikkilä-Laurila and Rajamäki, 2014).…”

TGF-β1 serum concentrations and receptor expressions in the lens capsular of dogs with diabetes mellitus

“…Data from human medicine show variable blood concentrations, compared to healthy controls, in patients with cancer, immunological, fibrotic or sclerotic diseases (Colitz et al, 2000;Prud'homme, 2007;Hills and Squires, 2009;Lopez-Novoa and Nieto, 2009;Shariat et al, 2011). In veterinary medicine, elevated TGF-β1 concentrations were found in dogs with liver fibrosis and lung fibrosis (Neumann et al, 2008;Krafft et al, 2011). Aim of the underlying prospective study was measurement of TGF-β1 in serum of diabetic dogs and its comparison with healthy controls and dogs with different fibrotic diseases.…”