Botfly Cephenemyia ulrichii larvae in the nasal cavity and nasopharynx of a dog with respiratory signs.

A Finnish Lapphund dog with acute upper respiratory signs and gagging was presented at veterinary clinic. During rhinoscopy, ten 1- to 2-mm long, actively moving larvae were found in the dog's nasal cavity and nasopharynx and identified as Cephenemyia ulrichii (Diptera: Oestridae). This moose (Alces alces) parasite is widespread in Finland but has not been reported before from an accidental canine host. Clinical signs resolved with imidacloprid/moxidectin spot-on formulation.

Evaluation of VEGF-A and CCL2 in dogs with brachycephalic obstructive airway syndrome or canine idiopathic pulmonary fibrosis and in normocephalic dogs.

Brachycephalic obstructive airway syndrome (BOAS) and canine idiopathic pulmonary fibrosis (CIPF) of West Highland White Terriers (WHWTs) often cause intermittent or chronic hypoxemia. Our objective was to evaluate serum and bronchoalveolar lavage fluid (BALF) concentrations of hypoxemia-related proinflammatory mediators vascular endothelial growth factor A (VEGF-A) and chemokine (CC motif) ligand 2 (CCL2) in brachycephalic dogs (BDs) and WHWTs with and without CIPF. Additionally, effects of BOAS severity and ageing on these mediators were assessed. 114 BDs (28 English Bulldogs (EBs), 37 French Bulldogs, 49 Pugs), 16 WHWTs with CIPF, 26 healthy WHWTs, and 39 normocephalic control dogs were included. Fifty-four BDs were re-examined after two to three years. Bead-based immunoassay was used for proinflammatory mediator measurements. Compared with controls, significantly higher serum concentrations of VEGF-A were seen in EBs (P = 0.009) and of CCL2 in CIPF and healthy WHWTs (P < 0.001; P = 0.002). BALF samples were available from controls, EBs, and WHWTs. VEGF-A was significantly lower in EBs (P < 0.001) and in CIPF and healthy WHWTs (P = 0.006; P = 0.007) and CCL2 was higher in CIPF WHWTs (P = 0.01) compared with controls. Between visits, only serum VEGF-A significantly decreased in BDs (P < 0.001), but breed, BOAS severity, or its change had no significant effect. In conclusion, in EBs with BOAS proinflammatory changes in VEGF-A were detected in both serum and BALF. Ageing reduced serum VEGF-A in BDs. In WHWTs, our results confirmed earlier findings of CCL2 as an important biomarker for CIPF.

Upregulation of alveolar levels of activin B, but not activin A, in lungs of west highland white terriers with idiopathic pulmonary fibrosis and diffuse alveolar damage.

Activins, cytokines belonging to the transforming growth factor-ß superfamily, have an important role in inflammation and fibrosis. Activin A has been suggested to participate in the pathophysiology of human idiopathic pulmonary fibrosis (IPF), but studies on the role of activin B are sparse. Canine IPF (CIPF) is an incurable interstitial lung disease occurring particularly in West Highland white terriers (WHWTs). During the disease course there are acute exacerbations (AEs) and the condition has a poor prognosis. Microscopically, AEs of CIPF are characterized by diffuse alveolar damage, which is also a key feature of acute respiratory distress syndrome (ARDS). The aim of this study was to study expression of activin A and B in lung tissue of WHWTs with CIPF and WHWTs with CIPF and concurrent AE, and dogs of various breeds with ARDS and to compare these findings with those of healthy WHWTs. In addition, western blot analysis of activin B from bronchoalveolar lavage fluid (BALF) from WHWTs with CIPF and healthy WHWTs was conducted. Activin B, but not activin A, was strongly expressed in the altered alveolar epithelium in the lungs of WHWTs with CIPF as well as in the lungs of dogs with ARDS. Activin B was detected in the BALF of WHWTs with CIPF, most notably in samples from dogs with AE, but activin B was not detected in BALF from healthy WHWTs. These findings suggest that activin B may be part of the pathophysiology of CIPF and might act as a marker of alveolar epithelial damage.

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.

The West Highland white terrier (WHWT) is particularly prone to canine idiopathic pulmonary fibrosis (CIPF). We hypothesized that higher circulating concentrations of chemokines CXCL8, CCL2, serotonin (5-HT), or vascular endothelial growth factor (VEGF) could serve as predisposing factors for CIPF development in the WHWT breed. Serum samples from 103 healthy dogs of seven different breeds variably predisposed to CIPF were collected. Serum CXCL8 concentrations were higher in healthy WHWT compared with each of the other groups of healthy dogs. Serum CCL2 concentrations were higher in healthy WHWT and Maltese compared with King Charles spaniels and Malinois Belgian shepherds. No relevant inter-breed differences were observed for serum 5-HT concentrations regarding CIPF predisposition. VEGF values from 89.3% of samples tested were below the kit detection limit. In conclusion, high CXCL8 blood concentrations and possibly CCL2 concentrations might be related to the breed predisposition of the WHWT for CIPF and warrants further investigations.

Long-term outcome and use of 6-minute walk test in West Highland White Terriers with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable interstitial lung disease occurring mainly in West Highland White Terriers (WHWTs). The effects of IPF on survival and on exercise tolerance in WHWTs are unknown. OBJECTIVES: To evaluate survival, prognostic factors, and exercise tolerance in WHWTs with IPF. ANIMALS: Privately owned WHWTs; 15 with IPF and 11 healthy controls. METHODS: Prospective case-control study conducted in 2007-2012. For survival, descriptive statistics and Kaplan-Meier (KM) survival curves with Cox proportional hazard ratios were performed. For the prognostic factor study, KM curves, Cox regression analysis, and logistic regression models were used. The 6-minute walk test (6MWT) was used for measurement of exercise tolerance. RESULTS: The median IPF-specific survival of deceased WHWTs (7/15) with IPF was 32 (range 2-51) months from onset of clinical signs. The risk of death from birth in WHWTs with IPF in age-adjusted Cox model was significantly higher (hazard ratio 4.6; 95% confidence interval 1.05-19.74, P = .04) than in control WHWTs. No significant prognostic factors were identified. In 6MWT, WHWTs with IPF walked a shorter distance, median 398 m (range 273-519 m), than healthy controls, median 492 m (420-568 m), P = .05, and the partial pressure of oxygen in arterial blood in diseased dogs had a moderate positive correlation with walking distance (Kendall's tau-b = 0.69, P = .06). CONCLUSION AND CLINICAL IMPORTANCE: IPF had a negative impact on life expectancy, but individual survival varied considerably. 6MWT proved to be a well-tolerated, noninvasive test to evaluate exercise tolerance.

Transforming growth factor beta 1 activation, storage, and signaling pathways in idiopathic pulmonary fibrosis in dogs.

BACKGROUND: The pathogenesis of idiopathic pulmonary fibrosis (IPF) in dogs is poorly understood. In human, transforming growth factor ß1 (TGF-ß1) is considered central in the pathogenesis. OBJECTIVES: To investigate TGF-ß1 pathway in IPF. ANIMALS: Lung tissues from 12 affected and 11 control dogs. Serum from 16 affected West Highland white Terriers (WHWTs) and healthy dogs from predisposed (13 WHWTs, 12 Scottish Terriers and 13 Bichons Frise) and nonpredisposed breeds (10 Whippets, 10 Belgian shepherds, 8 Labradors). METHODS: In this prospective study, immunohistochemistry was used to evaluate expression and localization of TGF-ß1 protein and proteins involved in TGF-ß1 signaling (TGF-ß receptor type I and phospho-Smad2/3). Pulmonary expression of TGF-ß1 and molecules involved in its storage (latent TGF-ß binding proteins [LTBP] 1, 2, and 4), activation (ανß6 and ανß8 integrins, thrombospondin-1) and signal inhibition (Smad 7) was analyzed by quantitative reverse transcriptase PCR. Circulating TGF-ß1 concentration was measured by ELISA. RESULTS: In IPF, high level of TGF-ß1 protein was found in areas of fibrosis, epithelial cells had strong expression of TGF-ß receptor type 1 and phospho-Smad2/3, gene expression was decreased for LTBP 4 (P = .009) and ß8 integrin (P < .001) and increased for thrombospondin-1 (P = .016); no difference was seen for Smad7, LTBP1 and 2. Serum TGF-ß1 concentration was higher in predisposed compared with nonpredisposed breeds (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: This study identified an enhanced TGF-ß1 signaling activity in IPF. TGF-ß1 storage and activation proteins with altered expression represent potential therapeutic targets. Higher circulating TGF-ß1 concentration in predisposed breeds might partly explain their susceptibility for IPF.

Comparative study of transforming growth factor-ß signalling and regulatory molecules in human and canine idiopathic pulmonary fibrosis.

Activation of transforming growth factor (TGF)-ß is a key event in the progression of fibrosis in human lung tissue. Idiopathic pulmonary fibrosis (IPF) in West Highland white terriers (WHWTs) shares histopathological features of human usual interstitial pneumonia (UIP), the histopathological counterpart of IPF and non-specific interstitial pneumonia (NSIP). The aim of the present immunohistochemical study was to investigate TGF-ß signalling activity and its known extracellular matrix (ECM) regulatory proteins, latent TGF-ß binding protein (LTBP)-1 and fibrillin-2, in lung tissue of WHWTs with IPF and healthy WHWTs and to compare these with findings in human UIP and NSIP. P-Smad2 immunoreactivity, indicating TGF-ß signalling activity, was increased in WHWTs with IPF relative to healthy WHWTs and expression was localized predominantly in the altered alveolar epithelium, as seen in both UIP and NSIP. Increased peribronchial and perivascular LTBP-1 immunoreactivity was seen in WHWTs with IPF compared with controls, possibly indicating the importance of the small airways in the canine disease. Alveolar LTPB-1 immunolabelling in diseased WHWTs was seen mainly in the altered alveolar epithelium, resembling more closely the labelling in UIP than in NSIP. Alveolar interstitial fibrillin-2 immunoreactivity, which is up-regulated in the lungs of people with UIP, was also detected in the lungs of WHWTs with IPF and people with NSIP. However, no significant difference was seen between WHWTs with IPF and control WHWTs. The results suggest that increased TGF-ß signalling and expression of the ECM regulatory proteins LTBP-1 and fibrillin-2 are part of the molecular pathophysiology of canine IPF.

Serum C-reactive protein as a diagnostic biomarker in dogs with bacterial respiratory diseases.

BACKGROUND: C-reactive protein (CRP) is a major acute-phase protein in dogs. Serum concentrations are low in healthy animals, but increase rapidly after inflammatory stimuli. OBJECTIVE: The aim of the study was to investigate CRP concentrations in various respiratory diseases of dogs and to determine if CRP can be used as a biomarker in the diagnosis of bacterial respiratory diseases. ANIMALS: A total of 106 privately owned dogs with respiratory diseases (17 with bacterial tracheobronchitis [BTB], 20 with chronic bronchitis [CB], 20 with eosinophilic bronchopneumopathy [EBP], 12 with canine idiopathic pulmonary fibrosis [CIPF], 15 with cardiogenic pulmonary edema [CPE], and 22 with bacterial pneumonia [BP]) and 72 healthy controls. METHODS: The study was conducted as a prospective cross-sectional observational study. CRP was measured in serum samples. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and selected diagnostic methods such as cytological and microbiological analysis of respiratory samples, echocardiography, and histopathology. RESULTS: Dogs with BP had significantly higher CRP concentrations (median, 121 mg/L; interquartile range, 68-178 mg/L) than dogs with BTB (23, 15-38, P = .0003), CB (13, 8-14, P < .0001), EBP (5, 5-15, P < .0001), CIPF (17, 10-20, P < .0001), or CPE (19, 13-32, P < .0001) and healthy controls (14, 8-20, P < .0001). Dogs with BTB had significantly higher CRP concentrations than dogs with CB (P = .001) or EBP (P < .0001) and healthy controls (P = .029). CONCLUSION AND CLINICAL IMPORTANCE: These results indicate that CRP has potential for use as an additional biomarker, especially in the diagnostics of BP.

Analysis of gene expression in canine idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) in dogs is a rare disease of unknown aetiology, seen in terrier breeds, particularly the West Highland white terrier (WHWT). The aim of this study was to determine pulmonary gene expression in canine IPF in order to gain insights into the pathogenesis of the disease and to identify possible biomarkers. Microarray analyses were conducted to determine gene expression profiles in the lungs of dogs with IPF and control dogs of various breeds. More than 700 genes were identified as having greater than two-fold difference in expression between the two groups. The significant biological functions associated with these genes were related to cellular growth and proliferation, developmental processes, cellular movement, cell to cell signalling and interaction, and antigen presentation. Altered levels of expression were confirmed by quantitative reverse transcriptase PCR for genes encoding chemokine (C-C) ligand (CCL) 2 (+4.9 times), CCL7 (+6.8 times), interleukin 8 (+4.32 times), chemokine (C-X-C) ligand 14 (+3.4 times), fibroblast activation protein (+4.7 times) and the palate, lung and nasal associated protein (PLUNC, -25 times). Serum CCL2 concentrations were significantly higher in WHWTs with IPF (mean 628.1 pg/mL, interquartile range 460.3-652.7 pg/mL) than unaffected WHWTs (mean 344.0 pg/mL, interquartile range 254.5-415.5 pg/mL; P=0.001). The results support CCL2 as a candidate biomarker for IPF in dogs.