Kate E. Creevy

Multiple morbidities in companion dogs: a novel model for investigating age-related disease

The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality.

Do Female Dogs Age Differently Than Male Dogs

Humans, as well as their closest ancestors, the higher African primates, exhibit female-biased survival and multiple sex differences in causes of death. However, the effects of sex on aging and longevity in an excellent model of human health, the companion dog, have not been well explored. Using two large independent databases on companion dog longevity and causes of death, we performed the most extensive analysis of sex differences in dog aging to date. Unlike the findings in humans, we observed only a small effect of sex on canine longevity. When broken down by neutering status, we discovered a small male advantage in survival among intact dogs but a clear female survival advantage among neutered dogs. Overall, the effect of neutering on life span was greater than the effect of sex. However, we found few sex differences in causes of death in either intact or neutered dogs. The results of this study suggest limited sex effects on either longevity or causes of death in the companion dog. Our analysis suggests that the majority of apparent sex differences in the wider canine populations may be due to the effects of neutering.

The companion dog as a model for human aging and mortality

Around the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans. Recently, the companion dog has been proposed as a powerful model to better understand the genetic and environmental determinants of morbidity and mortality in humans. However, it is not known to what extent the age‐related dynamics of morbidity, comorbidity, and mortality are shared between humans and dogs. Here, we present the first large‐scale comparison of human and canine patterns of age‐specific morbidity and mortality. We find that many chronic conditions that commonly occur in human populations (obesity, arthritis, hypothyroidism, and diabetes), and which are associated with comorbidities, are also associated with similarly high levels of comorbidity in companion dogs. We also find significant similarities in the effect of age on disease risk in humans and dogs, with neoplastic, congenital, and metabolic causes of death showing similar age trajectories between the two species. Overall, our study suggests that the companion dog may be an ideal translational model to study the many complex facets of human morbidity and mortality.

Evaluation of baseline cortisol concentration to monitor efficacy of twice-daily administration of trilostane to dogs with pituitary-dependent hyperadrenocorticism: 22 cases (2008–2012)

OBJECTIVE To evaluate use of cortisol concentration prior to ACTH stimulation (baseline) to monitor efficacy of twice-daily administration of trilostane to dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN Retrospective case series. ANIMALS 22 dogs with PDH. PROCEDURES The database of a veterinary hospital was searched to identify dogs with PDH that were treated with the FDA-approved veterinary formulation of trilostane twice daily between January 1, 2008, and December 31, 2012. For each dog, signalment and details regarding each hospital visit including comorbidities, electrolyte concentrations, and clinical signs were extracted from the record. For each ACTH stimulation test performed, the respective correlations between baseline cortisol concentration and the cortisol concentration after ACTH stimulation (ACTH-stimulated cortisol concentration) and resultant decision regarding trilostane dose adjustment were determined. Excessive suppression of cortisol production was defined as an ACTH-stimulated cortisol concentration < 2.0 μg/dL. The ability of various baseline cortisol concentrations to predict whether a dog had excessive suppression of cortisol production was determined. RESULTS 109 ACTH stimulation tests were performed for the 22 dogs. A baseline cortisol concentration > 3.2 μg/dL predicted that ACTH-stimulated cortisol concentration would be ≥ 2.0 μg/dL with 100% certainty; however, 14 of 64 tests with a baseline cortisol concentration > 3.2 μg/dL had an ACTH-stimulated cortisol concentration ≤ 3.2 μg/dL, which was suggestive of inadequate adrenocortical cortisol reserves. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that baseline cortisol concentration should not be used as the sole monitoring tool for management of dogs with PDH treated with trilostane twice daily.

Outcomes of and risk factors for presumed canine H3N2 influenza virus infection in a metropolitan outbreak

OBJECTIVE To determine clinical signs, case fatality rate, and factors associated with positive results of PCR testing for canine influenza virus (CIV) in dogs during an H3N2 CIV outbreak in the Atlanta area. DESIGN Cross-sectional study. ANIMALS 220 dogs with a nasal swab specimen submitted to an Atlanta-area diagnostic laboratory between May 1 and July 2, 2015, for PCR assay detection of CIV specifically or CIV and 5 other respiratory pathogens. PROCEDURES Veterinarians of tested dogs were surveyed by various means to collect information regarding clinical signs, survival status at the time of survey completion, vaccination history (≤ 12 months prior to testing), and travel history (≤ 2 months prior to testing). Data were compared between CIV-positive and CIV-negative dogs. RESULTS Surveys for 120 (55%) dogs were completed. Forty (33%) of these dogs had positive results of CIV testing. No significant differences were identified between CIV-positive and CIV-negative dogs regarding breed, sex, reproductive status, duration of clinical signs prior to testing, other dogs in the household, or travel history. When other factors were controlled for, CIV-positive dogs were more likely to be adult (> 1 year of age) than juvenile (≤ 1 year of age) and to be inappetent. Only 1 (3%) CIV-positive dog died during the study period (shortly after it was evaluated because of respiratory signs). CONCLUSIONS AND CLINICAL RELEVANCE From May 1 to July 2, 2015, the reported clinical signs of dogs tested during the Georgia H3N2 CIV outbreak were similar to those reported for dogs with H3N8 CIV infection, and the case fatality rate was low.