Incidence and characterization of aerophagia in dogs using videofluoroscopic swallow studies.

BACKGROUND: Aerophagia (ingestion of air), is a functional aerodigestive disorder in people. Criteria for diagnosis of aerophagia in dogs are >1/3 of bolus volume containing air or ingested air resulting in gastric distention (>1/3 of end gastric volume). Aerophagia is highlighted during eating and drinking. Videofluoroscopic swallow studies (VFSS) document aerophagia in dogs, but the incidence, clinical signs (CS), and associated disorders are unknown. OBJECTIVES: Identify the incidence of aerophagia, compare CS between dogs with and without aerophagia, and identify associated and predisposing disorders using VFSS. ANIMALS: A total of 120 client-owned dogs. METHODS: Sequential VFSS and associated medical records from dogs presenting to veterinary teaching hospitals at Auburn University and the University of Missouri were retrospectively reviewed. Statistical comparisons were made using Mann-Whitney and chi-squared tests, odds ratios (OR), and multiple logistic regression (P < .05). RESULTS: The incidence (95% confidence interval [CI]) of aerophagia was 40% (31.7-48.9). Dogs with mixed CS (gastrointestinal [GI] and respiratory; P < .001, 58.3%) were more likely to have aerophagia than dogs with exclusively respiratory CS (25%). Aerophagia was significantly more common in brachycephalic dogs (P = .01; 45.8% vs 13.8%), dogs with nonbrachycephalic upper airway obstruction (P < .001; 33.3% vs 4.1%), pathologic penetration and aspiration (P-A) scores (P = .04; 41.6% vs 23.6%), and gagging (P < .001; 25% vs 11.7%). Mixed CS (P = .01), brachycephaly (P < .001), and upper airway obstruction (P < .001) were independent predictors of aerophagia. CONCLUSIONS AND CLINICAL IMPORTANCE: Aerophagia was common, particularly in dogs with mixed CS. Brachycephalic dogs and dogs with upper airway obstruction are predisposed. Aspiration risk was high, emphasizing overlapping upper aerodigestive pathways.

The impact of single-dose trazodone administration on plasma endogenous adrenocorticotropic hormone and serum cortisol concentrations in healthy dogs.

BACKGROUND: Conditions affecting the hypothalamic-pituitary-adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha-1 adrenergic activity. OBJECTIVES: Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. ANIMALS: Fourteen healthy, adult, companion dogs. METHODS: Prospective, randomized placebo-controlled study. Trazodone (8-10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7-day wash-out period, dogs received the opposite treatment. Differences in eACTH, pre- and post-ACTH stimulation cortisol concentrations, and delta (difference between pre- and post-ACTH) cortisol concentrations were analyzed using a paired t or signed-rank test with a P < .05 significance level. RESULTS: The eACTH concentrations were not significantly different (P = .23) between treatments. Similarly, no significant differences were found in the pre-ACTH cortisol concentrations between treatments (P = .40). Post-ACTH cortisol concentrations (P = .05) and delta cortisol concentrations (P = .04) were significantly lower when the dogs were treated with trazodone. CONCLUSIONS: Preliminary data suggest trazodone administration dampens the adrenocortical response to stimulation in healthy dogs. If similar effects are found in dogs with adrenal disease, the use of trazodone may affect diagnosis and clinical decision making in these populations.

A One Health review of aerodigestive disease in dogs.

This review article seeks to define and describe aerodigestive disease in dogs, and review current and emerging methods of diagnostic evaluation. Aspiration of gastric contents into the respiratory tract is associated with the development and progression of numerous respiratory diseases in humans. In veterinary medicine the term "aspiration" is considered synonymous with "aspiration pneumonia" which, while frequently encountered, does not accurately reflect the breadth of aspiration associated respiratory syndromes (AARS). In the clinical veterinary literature, the effect of alimentary dysfunction on respiratory disease and vice versa (aerodigestive disease) is rarely investigated despite evidence in the human literature, animal models, and some studies and case reports linking alimentary and respiratory disease in small animals. Current methods of investigating aerodigestive diseases in veterinary patients are limited by inadeqate  sensitivity or specificity, potential for bias, cost, and availability. This necessitates investigations into advanced diagnostics to identify potentially underrecognized animals with AARS. Additionally, similarities in anatomy, physiology, and several disorders between dogs and humans, make experimental and naturally occurring canine models of AARS integral to translational research. Thus, evaluating dogs with aerodigestive disease might represent an area of substantial clinical relevance in human as well as veterinary medicine.

Evaluation of infrared thermography and 6-minute walk tests to assess airflow limitation, impaired thermoregulation, and exercise intolerance in dogs with brachycephalic obstructive airway syndrome.

Brachycephalic obstructive airway syndrome (BOAS) is associated with significant morbidity and mortality. Routine clinical evaluation fails to detect physiologic consequences of BOAS including airflow limitation, exercise intolerance, and impaired thermoregulation. A six-minute walk test (6MWT) with infrared thermography (IRT) may aid detection and clinical management by assessing the physiologic consequences of BOAS. IRT has been used in dogs to assess thermoregulation and in people with obstructive sleep apnea. Our objectives were to compare 6MWT and IRT parameters between healthy mesaticephalic (Mesa) and brachycephalic (Brachy) dogs, and dogs with BOAS. 6MWT parameters include normalized distance walked (ND), rectal temperature, pulse, respiratory rate, and pulse oximetry (SPO2). Mean (Tmean) and maximum (Tmax) IRT temperatures at 3 regions of interest (ROI) were evaluated. Evaluation timepoints were pre-6MWT, immediately post-6MWT (T0) and 5 (T5) and 15min post-6MWT (T15). No significant difference in ND, SPO2, or temperature were found between groups (p>.05). BOAS dogs had higher dorsal and rostral Tmax and Tmean temperatures compared to Mesa dogs at all timepoints (p < .05). BOAS dogs had higher Tmean temperatures compared to Brachy dogs at baseline and T15 and T5 and T15 for dorsal and rostral ROIs respectively (p < .001). ROC analysis showed significant discrimination between BOAS and non-BOAS (Brachy and Mesa) dogs with areas under the curve between 0.79-0.96. Significant moderate correlations were found between IRT temperatures, ND and rectal temperature. This pilot study demonstrates the potential in pairing the 6MWT and IRT with evaluation of clinical signs as screening tool to identify dogs with BOAS.

Videofluoroscopic swallow study abnormalities identify aerodigestive disorders in dogs with respiratory disease versus healthy controls.

BACKGROUND: Aerodigestive diseases (AeroD) pathologically link respiratory and alimentary tracts. Dogs with respiratory signs lacking dysphagia, vomiting, or regurgitation typically do not undergo diagnostic testing that identifies comorbid alimentary disease. A videofluoroscopic swallow study (VFSS) identifies defects in swallowing, reflux, and aspiration. OBJECTIVES/HYPOTHESIS: We hypothesized that dogs with respiratory and no alimentary disease (RESP) would have significantly more abnormal VFSS metrics versus controls (CON). We hypothesized RESP dogs with pulmonary parenchymal disease would have more reflux and higher penetration-aspiration score (PAS) than those with airway disease. ANIMALS: Client-owned dogs: RESP (n = 45) and CON (n = 15) groups. METHODS: Prospectively, all dogs underwent VFSS. The RESP dogs had advanced respiratory diagnostic testing. Eight subjective and 3 objective VFSS metrics (pharyngeal constriction ratio [PCR], PAS, and esophageal transit time [ETT]) were assessed. Fisher's exact test compared differences between groups (presence or absence of VFSS abnormalities). The Mann-Whitney rank sum test was used to compare PCR and PAS. RESULTS: Subjective VFSS abnormalities were present in 34/45 (75%) RESP and 2/15 (13%) CON dogs, with RESP dogs significantly more likely to have VFSS abnormalities (P = .01). No difference in PCR was found between groups. Pathologic PAS was more common in RESP than CON dogs (P = .03). The RESP dogs with airway disease had higher PAS than CON dogs (P = .01) but not RESP dogs with parenchymal disease (P = .25). CONCLUSIONS: Most (75%) RESP dogs had VFSS abnormalities, emphasizing that AeroD are common. The VFSS has value in diagnostic evaluation of respiratory disease.

Incidence, clinical signs, and videofluoroscopic swallow study abnormalities associated with airway penetration and aspiration in 100 dogs.

BACKGROUND: Videofluoroscopic swallow studies (VFSS) utilizing penetration-aspiration (P-A) scoring assesses airway protection in people. On VFSS, penetration (ingesta or secretions immediately cranial to the vocal folds) and aspiration (material caudal to the vocal folds) are associated with increased risk of lung injury in people. Penetration-aspiration (P-A) scoring has been validated in animal models, but the incidence of P-A, clinical signs (CS), and dysphagic disorders associated with P-A in dogs are unknown. OBJECTIVES: Using VFSS, identify the incidence of P-A, compare CS between dogs with and without P-A, and identify predisposing dysphagic abnormalities for P-A. ANIMALS: One hundred client-owned dogs. METHODS: Sequential VFSS and associated medical records from dogs presenting to the veterinary teaching hospitals at Auburn University (n = 53) and the University of Missouri (n = 47) were retrospectively reviewed. Statistical comparisons were made using Mann-Whitney tests, one-way analysis of variance (ANOVA) on ranks, multiple linear regression, and Spearman rank order correlation (P < .05). RESULTS: On VFSS, the incidence of pathologic P-A was 39%. No significant differences in CS were found between dogs with or without P-A (P > .05), with 14/39 dogs with P-A presenting without respiratory CS. Pharyngeal (P < .001) and esophageal (P = .009), but not oral-preparatory (P = .2) dysphagia was more common with P-A. Pharyngeal weakness (P < .001) and esophago-oropharyngeal reflux (EOR; P = .05) were independent predictors of P-A and were moderately and weakly positively correlated with P-A score respectively (P < .001, r = 0.489; P = .04, r = 0.201). CONCLUSIONS: Penetration-aspiration occurs in dogs in the absence of respiratory CS (i.e., occult P-A). Dogs with pharyngeal weakness and EOR should be considered at risk for P-A.

Evaluation of aerodigestive disease and diagnosis of sliding hiatal hernia in brachycephalic and nonbrachycephalic dogs.

BACKGROUND: Aerodigestive diseases (AeroD), hybrid disorders between the respiratory and gastrointestinal (GI) tracts, may present without GI signs. Sliding hiatal hernia (sHH) is an important AeroD in brachycephalic dogs linked to respiratory pathology. The spectrum of other AeroD and respiratory clinical signs (CS) in brachycephalic and nonbrachycephalic dogs with sHH is unknown. OBJECTIVES: Characterize CS of AeroD in dogs with sHH, compare CS between brachycephalic and nonbrachycephalic dogs, and compare thoracic radiographs and videofluoroscopic swallow study (VFSS) for diagnosing sHH. ANIMALS: Sixty-seven client-owned dogs with sHH. METHODS: Medical records of dogs with sHH presented to the veterinary teaching hospitals at Auburn University and the University of Missouri between 1 January 2009 and 31 December 2020 were retrospectively reviewed. Between group, comparisons were made using Mann-Whitney test, Chi-square analysis, and Spearman correlation (P < .05). RESULTS: Dogs with sHH presented with exclusively GI signs (28/67), mixed respiratory and GI signs (22/67), or with exclusively respiratory signs (17/67). Wheras brachycephalic dogs were not significantly more likely to present with respiratory CS (P = .145), they were younger (P < .001), and more likely to present in respiratory distress (P = .02), and with radiographic evidence of aspiration pneumonia (P < .001) compared to nonbrachycephalic dogs. Six of 12 dogs with normal thoracic radiographs having sHH presented with respiratory CS. For detection of sHH, VFSS was superior to radiographs (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with sHH may present with exclusively respiratory signs. Respiratory signs may be more severe in brachycephalic compared to nonbrachycephalic dogs. Videofluoroscopic swallow study was superior to thoracic radiographs for detection of sHH in dogs.

Etiology and outcome of extreme neutrophilic leukocytosis: A multi-institutional retrospective study of 269 dogs.

BACKGROUND: The magnitude of diagnostic abnormalities can influence the perception of clinical outcome. Extreme neutrophilic leukocytosis (ENL) is an uncommon finding caused by markedly increased granulopoiesis. A lack of recent, large-scale studies limits our understanding of the importance, causation, and prognosis associated with ENL in dogs. HYPOTHESIS/OBJECTIVES: Describe disease categories (DC) identified in dogs with ENL and identify variables associated with survival. We hypothesized that factors including fever, segmented and band neutrophil counts, and DC would be negatively associated with survival. ANIMALS: Two-hundred sixty-nine dogs with ENL (segmented neutrophils ≥50 × 103  cells/µL) presented to the veterinary teaching hospitals at Auburn University (n = 164), the University of Missouri (n = 81), and Oklahoma State University (n = 24) between January 1, 2009 and December 31, 2019. METHODS: Retrospective study. Demographic data and outcome variables including temperature, CBC findings, DC, duration of hospitalization (DOH) and outcome were acquired from the medical record. Statistical analyses included chi-squared and Kruskal-Wallis tests, and Pearson product moment correlations with a P < .05 significance level. RESULTS: Mortality was 41%. Survival differed with DC (P = .002). Mortality was higher (P < .05) in dogs with neoplasia (56.2%) vs immune-mediated disease (20.5%) or tissue damage/necrosis (19%). Weight (P = .001, r = -0.14) and total neutrophil count (P = .04, r = -0.02) were weakly negatively associated with survival whereas DOH was weakly positively associated with survival (P = .03, r = 0.14). CONCLUSIONS AND CLINICAL IMPORTANCE: Mortality in dogs with ENL is high but differed according to DC. Only weak correlations between clinical or clinicopathologic variables and mortality were identified. Extreme neutrophilic leukocytosis should be interpreted in conjunction with the underlying disease process, and not broadly used to predict clinical outcome.

Bacterial infection in dogs with aspiration pneumonia at 2 tertiary referral practices.

BACKGROUND: In dogs, antimicrobial drugs are widely prescribed for aspiration pneumonia (AP) despite poor documentation of bacterial infection in AP (b-AP) using bronchoalveolar lavage fluid (BALF) analysis. Interpretating discordant cytology and culture results is challenging, contributing to lack of a criterion standard, and highlighting differences between veterinary and human medical criteria for b-AP. OBJECTIVES: Determine how many dogs with AP had BALF collection and differences in diagnosis of b-AP using veterinary vs human medical criteria. Report findings of noninvasive markers (e.g. fever, band neutrophilia, radiographic severity score) in dogs with and without b-AP. ANIMALS: Retrospective cohort study of client-owned dogs (n = 429) with AP at 2 university veterinary hospitals. Twenty-four dogs met enrollment criteria. METHODS: Inclusion criteria were radiographic diagnosis of AP, ≥1 risk factor, CBC findings, and BALF cytology and culture results. Veterinary medical b-AP criteria were cytology findings compatible with sepsis with or without positive culture, or cytology findings not consistent with sepsis and positive culture (≥1.7 × 103  cfu/mL). Human medical b-AP criteria required culture with ≥104  cfu/mL or > 7% cells with intracellular bacteria on cytology. RESULTS: Only 24/429 dogs met all enrollment criteria; 379/429 dogs lacked BALF collection. Diagnosis of b-AP differed using veterinary (79%) vs human (29%) medical criteria. Fever, band neutrophils and high radiographic scores were noted in dogs with and without b-AP. CONCLUSIONS AND CLINICAL IMPORTANCE: Lack of routine BALF collection hampers definitive recognition of bacterial infection in AP. Differences in dogs meeting veterinary vs human medical definitions for b-AP and usefulness of noninvasive markers warrant further study to improve understanding of the role of bacteria in AP.

Proteomic Characterization of Canine Gastric Fluid by Liquid Chromatography-Mass Spectrometry for Development of Protein Biomarkers in Regurgitation, Vomiting, and Cough.

Reflux and aspiration in people cause and exacerbate respiratory diseases in the absence of gastrointestinal signs. Protein biomarkers in humans detect extraesophageal reflux (EER) from oropharyngeal (OP) and bronchoalveloar lavage samples. Reflux likely contributes to respiratory disease in dogs. The objectives of this study were to analyze the canine gastric fluid (GF) proteome and compare this to the OP proteome in normal, vomiting/regurgitating, and coughing dogs to identify biomarkers for EER/aspiration. Twenty-three client-owned dogs were enrolled. Canine GF samples (n = 5) and OP swabs in normal (n = 6), vomiting/regurgitating (n = 7), and coughing (n = 5) dogs were within 2 weeks of sample collection. Protein digests were analyzed by liquid chromatography-mass spectrometry. Differential abundance (DA) of proteins between groups was evaluated by Fisher's exact test with p < 0.0004 significance level after correction for multiple comparisons. DA was found between all groups (p < 0.0001): GF vs. normal (n = 130 proteins), coughing vs. normal (n = 22 proteins), and vomiting/regurgitating vs. normal (n = 20 proteins). Protein abundance was highly variable between dogs. Gastrointestinal-specific proteins were found in OP swabs from vomiting/regurgitating and coughing dogs but not from healthy dogs. In conclusion, the proteomic composition of the OP varies between health and disease. The presence of gastrointestinal-specific proteins in OP of coughing dogs may suggest reflux and/or aspiration as contributing factors. The variable protein abundance warrants investigation into biomarker panels.

Aerodigestive Disease in Dogs.

Aerodigestive disorders (AeroDs) in people encompass a wide range of clinical syndromes, reflecting the complex relationship between the respiratory and digestive tracts. In veterinary medicine, aspiration is used interchangeably with aspiration pneumonia. Although aspiration pneumonia is a common disorder in dogs, it does not reflect the breadth of AeroDs. Unfortunately, AeroDs rarely are investigated in veterinary medicine because of lack of clinical recognition, limitations in available diagnostics, and the fact that AeroDs may be caused by occult digestive disease. Recognizing patients with AerodD represents an area of significant clinical importance that may provide additional areas of clinical intervention.

Detection of silent reflux events by nuclear scintigraphy in healthy dogs.

BACKGROUND: Reflux and aspiration in people are associated with respiratory disease, whereas approximately 50% of healthy adults microaspirate without apparent consequence. In dogs, analogous information is lacking. HYPOTHESIS: Healthy dogs commonly have gastroesophageal reflux and a proportion of these dogs will have laryngopharyngeal reflux with silent aspiration. ANIMALS: Twelve healthy, client-owned dogs. METHODS: Prospective study: Dogs were free-fed a meal containing (111 MBq) colloidal 99 m-technetium phytate. Dynamic-scans were performed 5 and 30 minutes postingestion. Time-activity curves, reflux margination, volume, frequency, and duration were evaluated over 7 regions of interest in dorsal ± left-lateral recumbency. Static scans (dorsal recumbency) were performed 2 and 18 hours postfeeding to detect aspiration. Reflux and aspiration were defined as counts ≥200% background activity ± decreased gastric counts. Between-group comparisons were performed by Wilcoxon rank-sum test or one-way ANOVA on ranks with significance of P < .05. RESULTS: In this study, reflux of variable magnitude was detected in 12/12 dogs. No significant differences in outcome parameters were detected with recumbency (P > .05). Margination to the pharynx and proximal, middle, and distal esophagus was identified in 5/12, 2/12, 3/12, and 2/12 dogs, respectively. Median (IQR) reflux frequency and duration were 2 events/5 minutes (1-3.3 events/5 minutes) and 6 seconds (4-9 seconds) respectively. No dog had detectable aspiration. CONCLUSIONS AND CLINICAL IMPORTANCE: Nuclear scintigraphy can document reflux in dogs. Reflux, but not aspiration, is common in healthy dogs and must be considered when interpreting results in clinically affected dogs.

Respiratory dysbiosis and population-wide temporal dynamics in canine chronic bronchitis and non-inflammatory respiratory disease.

The lungs of people and companion animals are now recognized to harbor diverse, low biomass bacterial communities. While these communities are difficult to characterize using culture-based approaches, targeted molecular methods such as 16S rRNA amplicon sequencing can do so using DNA extracted from samples such as bronchoalveolar lavage fluid (BALF). Previous studies identified a surprisingly uniform composition of the microbiota in the lungs of healthy research dogs living in a controlled environment, however there are no reports of the lung microbiota of client-owned dogs. Moreover, compositional changes in the lung microbiota depending on disease status have been reported in people, suggesting that similar events may occur in dogs, a species subject to several respiratory disease mechanisms analogous to those seen in people. To address these knowledge gaps, BALF samples from client-owned dogs presenting to the University of Missouri Veterinary Health Center for respiratory signs between 2014 and 2017 were processed for and subjected to 16S rRNA sequencing. Based on specific diagnostic criteria, dogs were categorized as Chronic Bronchitis (CB, n = 53) or non-CB (n = 11). Community structure was compared between groups, as well as to historical data from healthy research dogs (n = 16) of a uniform breed and environment. The lung microbiota detected in all client-owned dogs was markedly different in composition from that previously detected in research dogs and contained increased relative abundance of multiple canine fecal and environmental bacteria, likely due to aspiration associated with their clinical signs. While inter-sample diversity differed significantly between samples from CB and non-CB dogs, the variability within both groups made it difficult to discern reproducible bacterial classifiers of disease. During subsequent analyses to identify other sources of variability within the data however, population-wide temporal dynamics in community structure were observed, with substantial changes occurring in late 2015 and again in early 2017. A review of regional climate data indicated that the first change occurred during a historically warm and wet period, suggesting that changes in environmental conditions may be associated with changes in the respiratory microbiota in the context of respiratory disease. As the lung microbiota in humans and other animals is believed to result from repetitive micro-aspirations during health and in certain disease states associated with dyspnea and laryngeal dysfunction, these data support the increased colonization of the lower airways during compromised airway function, and the potential for temporal effects due to putative factors such as climate.

Pharmacodynamic assessment of ex-vivo canine T-lymphocyte proliferation: Responses to dexamethasone, cyclosporine, mycophenolic acid, and the active metabolite of leflunomide.

A lack of understanding of specific immune defects underlying canine immune-mediated diseases hampers optimal therapy. Failure to tailor treatment to an individual's immune abnormality can result in lack of efficacy, secondary complications, added expense, and drug-potentiated adverse effects. We adopted a small-volume whole-blood flow cytometric assay to determine the effect of immunosuppressant drugs on T-lymphocyte proliferation. Using healthy dogs in this proof-of-principle study, we hypothesized that there would be dose-dependent suppression of T-lymphocyte proliferation in response to dexamethasone, cyclosporine, mycophenolic acid, and the active metabolite of leflunomide (A77 1726). Whole blood was collected from 6 healthy pet dogs and incubated for 4 d with or without the mitogens concanavalin A and lipopolysaccharide and with increasing concentrations of immunosuppressant. Samples were subsequently stained with viability dye and with antibodies against the pan-T-lymphocyte marker CD5 and the cell proliferation marker Ki67. Percentages of proliferating T-lymphocytes were determined by flow cytometry, and the 50% inhibitory concentration (IC50) was calculated. Inhibition of T-lymphocyte proliferation by the panel of immunosuppressants was shown to be dose-dependent, with marked variability among the dogs. The mean IC50 was 394.8 ± 871 (standard deviation) µM for dexamethasone, 18.89 ± 36.2 ng/mL for cyclosporine, 106.3 ± 157.7 nM for mycophenolic acid, and 3.746 ± 6.8 µM for A77 1726. These results support the use of this assay for detecting the efficacy of individual immunosuppressants used to diminish T-lymphocyte proliferation. In future, the assay may be applied to pet dogs with spontaneous immune-mediated disease to help tailor individual treatment.

Un manque de compréhension des défauts immunitaires spécifiques sous-jacents aux maladies à médiation immunitaire canines nuit à une thérapie optimale. L'incapacité à concevoir un traitement approprié à l'anomalie immunitaire d'un individu peut résulter en une perte d'efficacité, des complications secondaires, une dépense supplémentaire, et des effets secondaires indésirables induits par les médicaments. Nous avons adopté un essai de cytométrie en flux sur un petit volume de sang entier afin de déterminer l'effet de médicaments immunosuppresseurs sur la prolifération de lymphocytes-T. En utilisant des chiens en santé dans cette étude de preuve de principe, nous avons émis l'hypothèse qu'il y aurait une suppression dose-dépendante de la prolifération des lymphocytes-T en réponse à la dexaméthasone, à la cyclosporine, à l'acide mycophénolique, et au métabolite actif du leflunomide (A77 1726). Du sang entier fut prélevé de six chiens en santé et incubé pendant 4 j avec et sans les agents mitogènes concanavaline A et lipopolysaccharide et avec des concentrations croissantes d'immunosuppresseurs. Les échantillons étaient par la suite colorés avec des colorants de viabilité et des anticorps contre le marqueur pan-lymphocyte-T CD5 et le marqueur de prolifération cellulaire Ki67. Les pourcentages de lymphocytes-T proliférant étaient déterminés par cytométrie en flux, et la concentration inhibitrice 50 % (IC50) fut calculée. L'inhibition de la prolifération de lymphocytes-T par la panoplie d'immunosuppresseurs a été démontrée comme étant dose-dépendante, avec une variabilité marquée parmi les chiens. L'IC50 moyenne était 394,8 ± 871 (écart-type) µM pour la dexaméthasone, 18,89 ± 36,2 ng/mL pour la cyclosporine, 106,3 ± 157,7 nm pour l'acide mycophénolique, et 3,746 ± 6,8 µM pour le A77 1726. Ces résultats appuient l'utilisation de cet essai pour détecter l'efficacité d'immunosuppresseurs individuels utilisés pour diminuer la prolifération de lymphocytes-T. Dans le futur, cet essai pourrait être utilisé chez des chiens de compagnie avec des maladies à médiation immunitaire spontanées afin d'aider à concevoir des traitements individuels.(Traduit par Docteur Serge Messier).

Videofluoroscopic swallow study features of lower esophageal sphincter achalasia-like syndrome in dogs.

BACKGROUND: Megaesophagus (ME) carries a poor long-term prognosis in dogs. In people, lower esophageal sphincter (LES) disorders causing functional obstruction are rare causes of ME that may respond to targeted treatment. Functional LES disorders are reported rarely in dogs because of challenges in diagnostic methodologies. HYPOTHESIS/OBJECTIVES: To identify dogs with videofluoroscopic swallow study (VFSS) features of LES achalasia-like syndrome (LES-AS). We hypothesized that dogs with LES-AS could be distinguished from normal dogs using standardized VFSS criteria. ANIMALS: Dogs with LES-AS by VFSS (n = 19), healthy normal dogs (n = 20). METHODS: Retrospective study. One-hundred thirty dogs presented to the University of Missouri Veterinary Health Center (MU-VHC) between April 2015 and December 2017 for a free-feeding VFSS; 20 healthy dogs were included as controls. Swallow studies were evaluated for failure of the LES to relax during pharyngeal swallow (LES-AS). Affected dogs subsequently were evaluated using standardized criteria to identify metrics important for identifying and characterizing dogs with LES-AS. RESULTS: Nineteen dogs with LES-AS were identified out of 130 VFSS. Megaesophagus was present in 14 of 19 (73.7%) dogs with LES-AS. A baseline esophageal fluid-line and "bird beak" were present in 68.4% (95% confidence interval [CI], 47.5%-89.3%) and 63.2% (95% CI, 41.5%-84.8%) of affected dogs, respectively. The esophagus was graded as acontractile (8/19), hypomotile (8/19), or hypermotile (3/19). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with LES-AS may successfully be identified by VFSS using a free-feeding protocol. These data are of critical clinical importance because a subpopulation of dogs with functional LES obstruction may be candidates for targeted intervention.

Perspectives in veterinary medicine: Description and classification of bronchiolar disorders in cats.

This Perspectives in Veterinary Medicine article seeks to define, describe putative causes, and discuss key diagnostic tests for primary and secondary bronchiolar disorders to propose a classification scheme in cats with support from a literature review and case examples. The small airways (bronchioles with inner diameters <2 mm), located at the transitional zone between larger conducting airways and the pulmonary acinus, have been overlooked as major contributors to clinical syndromes of respiratory disease in cats. Because the trigger for many bronchiolar disorders is environmental and humans live in a shared environment with similar susceptibility, understanding these diseases in pet cats has relevance to One Health. Thoracic radiography, the major imaging modality used in the diagnostic evaluation of respiratory disease in cats, has low utility in detection of bronchiolar disease. Computed tomography (CT) with paired inspiratory and expiratory scans can detect pathology centered on small airways. In humans, treatment of bronchiolar disorders is not well established because of heterogeneous presentations and often late definitive diagnosis. A review of the human and veterinary medical literature will serve as the basis for a proposed classification scheme in cats. A case series of cats with CT or histopathologic evidence of bronchiolar lesions or both, either as a primary disorder or secondary to extension from large airway disease or interstitial lung disease, will be presented. Future multi-institutional and multidisciplinary discussions among clinicians, radiologists, and pathologists will help refine and develop this classification scheme to promote early and specific recognition and optimize treatment.

18 F-FDG-PET/CT as adjunctive diagnostic modalities in canine fever of unknown origin.

Fever of unknown origin (FUO) is a persistent or recurrent fever for which the underlying source has not been identified despite diagnostic investigation. In people, 18 F-fluoro-2-deoxyglucose positron emission tomography (18 F-FDG-PET) alone or in combination with computed tomography (CT) is often beneficial in detecting the source of fever when other diagnostics have failed. Veterinary reports describing use of these modalities in animals with fever of unknown origin are currently lacking. Aims of this retrospective case series were to describe 18 F-FDG-PET or 18 F-FDG-PET/CT findings in a group of dogs with fever of unknown origin. Dogs presenting to a single center between April 2012 and August 2015 were included. A total of four dogs met inclusion criteria and underwent either positron emission tomography (n = 2) or positron emission tomography/CT (n = 2) as a part of their diagnostic investigation. All subjects underwent extensive diagnostic testing prior to 18 F-FDG-PET/CT. Initial diagnostic evaluation failed to identify either a cause of fever or an anatomic location of disease in these four dogs. In each dog, positron emission tomography or positron emission tomography/CT was either able to localize or rule out the presence of focal lesion thereby allowing for directed sampling and/or informed disease treatment. Follow up 18 F-FDG-PET/CT scans performed in two patients showed improvement of observed abnormalities (n = 1) or detected recurrence of disease allowing for repeated treatment before clinical signs recurred (n = 1). Fever resolved after specific treatment in each dog. Findings from the current study supported the use of positron emission tomography or positron emission tomography/CT as adjunctive imaging modalities for diagnosis and gauging response to therapy in dogs with fever of unknown origin.

Dynamic changes of the respiratory microbiota and its relationship to fecal and blood microbiota in healthy young cats.

Advances in the field of metagenomics using culture-independent methods of microbial identification have allowed characterization of rich and diverse communities of bacteria in the lungs of healthy humans, mice, dogs, sheep and pigs. These data challenge the long held belief that the lungs are sterile and microbial colonization is synonymous with pathology. Studies in humans and animals demonstrate differences in the composition of airway microbiota in health versus disease suggesting respiratory dysbiosis occurs. Using 16S rRNA amplicon sequencing of DNA extracted from rectal and oropharyngeal (OP) swabs, bronchoalveolar lavage fluid (BALF), and blood, our objective was to characterize the fecal, OP, blood, and lower airway microbiota over time in healthy cats. This work in healthy cats, a species in which a respiratory microbiota has not yet been characterized, sets the stage for future studies in feline asthma in which cats serve as a comparative and translational model for humans. Fecal, OP and BALF samples were collected from six healthy research cats at day 0, week 2, and week 10; blood was collected at week 10. DNA was extracted, amplified via PCR, and sequenced using the Illumina MiSeq platform. Representative operational taxonomic units (OTUs) were identified and microbial richness and diversity were assessed. Principal component analysis (PCA) was used to visualize relatedness of samples and PERMANOVA was used to test for significant differences in microbial community composition. Fecal and OP swabs provided abundant DNA yielding a mean±SEM of 65,653±6,145 and 20,6323±4,360 sequences per sample, respectively while BALF and blood samples had lower coverage (1,489±430 and 269±18 sequences per sample, respectively). Oropharyngeal and fecal swabs were significantly richer than BALF (mean number OTUs 93, 88 and 36, respectively; p < 0.001) with no significant difference (p = 0.180) in richness between time points. PCA revealed site-specific microbial communities in the feces, and upper and lower airways. In comparison, blood had an apparent compositional similarity with BALF with regard to a few dominant taxa, but shared more OTUs with feces. Samples clustered more by time than by individual, with OP swabs having subjectively greater variation than other samples. In summary, healthy cats have a rich and distinct lower airway microbiome with dynamic bacterial populations. The microbiome is likely to be altered by factors such as age, environmental influences, and disease states. Further data are necessary to determine how the distinct feline microbiomes from the upper and lower airways, feces and blood are established and evolve. These data are relevant for comparisons between healthy cats and cats with respiratory disease.

Composition and Predicted Metabolic Capacity of Upper and Lower Airway Microbiota of Healthy Dogs in Relation to the Fecal Microbiota.

The upper and lower airways of healthy humans are reported to harbor stable and consistent bacterial populations, and the composition of these communities is altered in individuals affected with several respiratory diseases. Data regarding the presence of airway microbiota in other animals are scant and a better understanding of the composition and metabolic function of such bacterial populations is essential for the development of novel therapeutic and diagnostic modalities for use in both veterinary and human medicine. Based on targeted next-generation sequencing of feces and samples collected at multiple levels of the airways from 16 healthy female dogs, we demonstrate that canine airways harbor a topographically continuous microbiota with increasing relative abundance of proteobacterial species from the upper to lower airways. The lung-associated microbiota, as assessed via bronchoalveolar lavage fluid (BALF), was the most consistent between dogs and was dominated by three distinct taxa, two of which were resolved to the species level and one to the level of family. The gene content of the nasal, oropharyngeal, and lung-associated microbiota, predicted using the Phylogenetic Investigations into Communities by Reconstruction of Unobserved States (PICRUSt) software, provided information regarding the glyoxylate and citrate cycle metabolic pathways utilized by these bacterial populations to colonize such nutrient-poor, low-throughput environments. These data generated in healthy subjects provide context for future analysis of diseased canine airways. Moreover, as dogs have similar respiratory anatomy, physiology, and immune systems as humans, are exposed to many of the same environmental stimuli, and spontaneously develop similar respiratory diseases, these data support the use of dogs as a model species for prospective studies of the airway microbiota, with findings translatable to the human condition.