Update on Canine Idiopathic Pulmonary Fibrosis in West Highland White Terriers

Canine idiopathic pulmonary fibrosis (CIPF) is a chronic, progressive, interstitial lung disease (ILD) affecting older West Highland white terriers (WHWTs). According to one classification, CIPF is a familial fibrotic ILD in the group of idiopathic interstitial pneumonias. Etiology is unknown but likely arises from interplay between genetic and environmental factors. CIPF shares features with human idiopathic pulmonary fibrosis and human nonspecific interstitial pneumonia. This article describes clinical signs, findings in physical examination, arterial oxygenation, diagnostic imaging, bronchoscopy, bronchoalveolar lavage, histopathology, disease course, and outcome of WHWTs with CIPF; compares canine and human diseases; summarizes biomarker research; and gives an overview of potential treatment.Peer reviewe

Assessment of welfare and brachycephalic obstructive airway syndrome signs in young, breeding age French Bulldogs and Pugs, using owner questionnaire, physical examination and walk tests

Brachycephalic obstructive airway syndrome (BOAS) is a major welfare problem in short-nosed breeds, such as the French Bulldog and Pug. In addition to respiratory difficulties, exercise intolerance and impaired recovery are major signs of BOAS. To select healthier breeding animals, exercise tolerance tests, such as the 1,000-m walk test, are already used in several countries for brachycephalic dogs, although evidence supporting their use is still scarce. The aims of this study were to assess the daily welfare of young, breeding-age French Bulldogs (n = 44) and Pugs (n = 51) using an owner questionnaire, and to evaluate 6-min walk test (6MWT) and 1,000-m walk test usability for differentiation between non-or mildly BOAS-affected dogs and more severely affected dogs. Only four out of 95 French Bulldog and Pug owners reported that the BOAS signs limited the daily activities of their dogs. However, according to the physical, examination-based veterinary BOAS grading, 31/95 of the dogs had moderate to severe BOAS signs. In both breeds, the more severely affected dogs performed both exercise tests more poorly than those with no or mild BOAS signs. The longer exercise, namely the 1,000-m test, seemed slightly better able at differentiating between affected dogs and less affected ones. The results of this study further support the use of exercise tests as an important part of the breeding selection in French Bulldogs and Pugs. By influencing the breed standards set by Kennel Clubs and by using breeding selection tools, the harmful impacts of brachycephaly can be diminished.Peer reviewe

A follow-up study of exercise test results and severity of brachycephalic obstructive airway syndrome signs in brachycephalic dogs

To promote successful breeding against brachycephalic obstructive airway syndrome (BOAS), it is important to assess how BOAS signs progress during young adulthood and how evaluation age and ageing affect the results of chosen breeding selection tools. The aims of this study were to assess how veterinary-assessed and owner-reported BOAS signs and exercise test results change when dogs age. Eight English Bulldogs, 25 French Bulldogs, and 31 Pugs that had undergone previous evaluation were re-examined 2- 3 years later. An owner questionnaire regarding BOAS signs, a veterinary assessment of BOAS severity, and exercise, ie walk tests were re-performed. In Pugs, both 6-min walking distance and 1,000-m time worsened and the initial evaluation age had a significant effect on the 1,000-m time. No significant changes were seen in the results of the French Bulldogs but a negative effect on the 1,000-m time was seen with weight gain. Exercise test statistics were not performed with regard to English Bulldogs due to low sample size. The veterinary-assessed BOAS severity class remained the same in the majority of dogs and the BOAS grade worsened mostly in those dogs that were initially evaluated at less than two years of age. Most owners reported no major changes in BOAS severity. BOAS grading and walk tests were easy to repeat and results remained relatively constant in dogs initially evaluated at over two years of age, supporting the use of these breeding selection tools. However, further, large-scale offspring studies are still needed.Peer reviewe

Cell cycle regulators p27 and pRb in lymphomas – correlation with histology and proliferative activity

The cell cycle is a complex event in which multiple regulator-proteins participate. The G 1/S checkpoint of the cell cycle is controlled by pRb protein, which functions in its hypophosphorylated form as a negative regulator of growth. p27 (Kip1), a member of CIP/KIP family of cyclin inhibitory proteins, participates in inhibition of forming complexes that allow pRb to phosphorylate and lead the cell into mitosis. The expression of these important cell cycle regulator proteins was studied in a total of 96 non-Hodgkin’s lymphoma (NHL) samples, which were classified according to the REAL classification. The expression of p27, pRb and the cell proliferation marker Ki-67 (MIB-1) was evaluated in lymphomas using immunohistochemistry. This study showed that there were coordinate changes in the expression of p27 and pRb in NHL. When compared to low-grade lymphomas, high-grade lymphomas showed significantly reduced expression of p27 and inversely pRb expression was increased (P < 0.001). Increase in expression of Ki-67 was parallel with pRb expression, and was mainly seen in cells that lacked p27 expression (P < 0.0001). This study suggests that changes in the control of the cell cycle closely relate to the pathobiology of NHL. © 2000 Cancer Research Campaig

Quantitative proteomic analysis of bronchoalveolar lavage fluid in West Highland white terriers with canine idiopathic pulmonary fibrosis

Background Canine idiopathic pulmonary fibrosis (CIPF) is a chronic, progressive, interstitial fibrosing lung disease, manifesting as cough, exercise intolerance and ultimately, dyspnea and respiratory failure. It mainly affects West Highland white terriers (WHWTs), lacks curable treatment and has a poor prognosis. Aspiration of gastroesophageal refluxate may play a role in the development of CIPF. In the first part of this study, we completed label-free quantitative proteomic analysis of bronchoalveolar lavage fluid (BALF) from CIPF and healthy WHWTs. In the second part, we evaluated potential protein markers of reflux aspiration from canine gastric juice and vomitus and whether these were present in BALF from the two groups. Results Across all BALF samples, 417 proteins were identified, and of these, 265 proteins were identified by two or more unique tryptic peptides. Using the 265 high confidence assignments, the quantitative proteome profiles were very similar in the two cohorts, but they could be readily resolved by principal component analysis on the basis of differential protein expression. Of the proteins that were differentially abundant in the two groups, several (including inflammatory and fibrotic markers) were elevated in CIPF, and a smaller, more diverse group of proteins were diminished in CIPF. No protein markers indicative of reflux aspiration were identified. Conclusions Label-free proteomics allowed discrimination between CIPF and healthy WHWTs, consistent with fibrotic process but did not provide clear evidence for gastrointestinal aspiration. The measurement of proteins may provide a proteomics signature of CIPF that could be used to evaluate treatment options.Peer reviewe

S100A12 concentrations and myeloperoxidase activity in the intestinal mucosa of healthy dogs

Background: Relatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively. Results: Based on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p <0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p <0.05). Moreover, its concentration was higher in the jejunum than in the duodenum. Conclusions: This study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation.Peer reviewe

S100A12 concentrations and myeloperoxidase activities are increased in the intestinal mucosa of dogs with chronic enteropathies

Background: Intestinal mucosal S100A12 and myeloperoxidase (MPO) are inflammatory biomarkers in humans with inflammatory bowel disease (IBD). However, these biomarkers have not been studied in the intestinal mucosa of dogs with chronic enteropathies (CE), even though dogs with CE have increased S100A12 concentrations in feces and serum. This study investigated mucosal S100A12 concentrations and MPO activities in both dogs with CE and healthy Beagles. ELISA (S100A12 concentrations) and spectrophotometric methods (MPO activity) were used. The associations of both biomarkers with canine IBD activity index (CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations were also investigated. We studied intestinal mucosal samples originating from different intestinal regions of 40 dogs with CE and 18 healthy Beagle dogs (duodenum, ileum, colon, and cecum). Results: Compared with healthy Beagles, mucosal S100A12 concentrations in dogs with CE were significantly higher in the duodenum (p <0.0001) and colon (p = 0.0011), but not in the ileum (p = 0.2725) and cecum (p = 0. 2194). Mucosal MPO activity of dogs with CE was significantly higher in the duodenum (p <0.0001), ileum (p = 0. 0083), colon (p <0.0001), and cecum (p = 0.0474). Mucosal S100A12 concentrations in the duodenum were significantly higher if the inflammatory infiltrate consisted mainly of neutrophils (p = 0.0439) or macrophages (p = 0.037). Mucosal S100A12 concentrations also showed a significant association with the severity of total histopathological injury and epithelial injury in the colon (p <0.05). Mucosal MPO activity showed a significant association (p <0.05) with the severity of total histopathological injury, epithelial injury, and eosinophil infiltration in the duodenum. There was no significant association of both biomarkers with CIBDAI or clinical outcome. Conclusions: This study showed that both mucosal S100A12 concentrations and MPO activities are significantly increased in the duodenum and colon of dogs with CE; mucosal MPO was also increased in the ileum and cecum. Future research should focus on assessing the clinical utility of S100A12 and MPO as diagnostic markers in dogs with CE.Peer reviewe

Description of a novel method for detection of sleep-disordered breathing in brachycephalic dogs

Background: Sleep-disordered breathing (SDB), defined as any difficulty in breathing during sleep, occurs in brachycephalic dogs. Diagnostic methods for SDB in dogs require extensive equipment and laboratory assessment. Objectives: To evaluate the usability of a portable neckband system for detection of SDB in dogs. We hypothesized that the neckband is a feasible method for evaluation of SDB and that brachycephaly predisposes to SDB. Animals: Twenty-four prospectively recruited client-owned dogs: 12 brachycephalic dogs and 12 control dogs of mesocephalic or dolicocephalic breeds. Methods: Prospective observational cross-sectional study with convenience sampling. Recording was done over 1 night at each dog's home. The primary outcome measure was the obstructive Respiratory Event Index (OREI), which summarized the rate of obstructive SDB events per hour. Additionally, usability, duration of recording, and snore percentage were documented. Results: Brachycephalic dogs had a significantly higher OREI value (Hodges-Lehmann estimator for median difference = 3.5, 95% confidence interval [CI] 2.2-6.8; P <.001) and snore percentage (Hodges-Lehmann estimator = 34.2, 95% CI 13.6-60.8; P <.001) than controls. A strong positive correlation between OREI and snore percentage was detected in all dogs (rs =.79, P <.001). The neckband system was easy to use. Conclusions and Clinical Importance: Brachycephaly is associated with SDB. The neckband system is a feasible way of characterizing SDB in dogs.publishedVersionPeer reviewe

Extraesophageal reflux and reflux aspiration in dogs with respiratory diseases and in healthy dogs

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