Mepolizumab improves small airway function in severe eosinophilic asthma.

BACKGROUND AND OBJECTIVE: Treatment with mepolizumab in severe eosinophilic asthma (SEA) significantly reduces exacerbations with modest improvements in symptom control and spirometry. The time course of any changes in small airway function is unknown. OBJECTIVE: To describe changes in ventilation inhomogeneity, a marker of small airway function, after commencing mepolizumab. METHODS: Prospective cohort of 20 adults (12 male) with SEA commencing monthly mepolizumab. Measurements at baseline, Week 4 and Week 26 included the Asthma Control Questionnaire (ACQ-5), spirometry, fraction of exhaled nitric oxide (FeNO) and multiple breath nitrogen washout to measure global (Lung Clearance Index, [LCI]) and regional ventilation inhomogeneity in acinar (Sacin) and conducting (Scond) airways. Other asthma therapy remained unchanged between baseline and Week 4. Treatment related changes were assessed using RM-ANOVA and paired t-tests. Relationships between changes in lung function and symptoms were assessed by Pearson's correlation. RESULTS: At Week 4, ACQ-5, spirometry, LCI and Sacin improved significantly (p < 0.04) and all were sustained at Week 26. The change in ACQ-5 correlated with the change in Sacin (r = 0.48, p = 0.03) and FRC (r = 0.46, p = 0.04), but not spirometry. CONCLUSION: Improved symptom control improved rapidly after commencing mepolizumab in patients with SEA. The early improvement in small airway function was associated with asthma control and may be a significant contributor to the therapeutic response.

Relationship between vitamin D status and leukocytes in hospitalised cats.

Objectives Vitamin D deficiency, as assessed by serum 25-hydroxyvitamin D (25[OH]D) concentrations, has been linked to markers of systemic inflammation in human and canine medicine. However, the relationship between vitamin D status and inflammation has not been previously investigated in cats. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and leukocyte counts in hospitalised sick cats. Methods Serum 25(OH)D concentrations and haematology profiles were measured in 170 consecutive hospitalised sick cats. A binary logistical regression model examined the relationship between serum 25(OH)D concentration, age, sex, breed and neutrophil, monocyte, eosinophil and lymphocyte counts. Results Cats with neutrophilia had lower serum 25(OH)D concentrations than cats with neutrophil concentrations below the upper limit of the reference interval (RI). There were no differences in serum 25(OH)D concentrations in cats with monocyte, lymphocyte or eosinophil counts above their respective RI compared with cats with counts below the upper limit of the RI. Conclusions and relevance Hospitalised cats with a neutrophil count above the RI had lower vitamin D status. There is a need to establish whether lower vitamin D status is a cause or consequence of increased neutrophil counts.

Plasma cytokine concentrations in dogs with a congenital portosystemic shunt.

Congenital portosystemic shunts (cPSS) are a well-recognised vascular anomaly in dogs. Recent studies have shown an association between inflammation and hepatic encephalopathy (HE), which is a common clinical syndrome in dogs with a cPSS. Pro-inflammatory cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α are frequently increased in the plasma of human patients with liver disease and have been implicated in the development of HE. In the current study, plasma concentrations of IL-2, IL-6, IL-8 and TNF-α were measured using a multiplex electrochemiluminescence immunoassay in 36 dogs with a cPSS and compared to 25 healthy dogs. There were no significant differences in plasma IL-2, IL-8 and TNF-α concentrations between the two groups; however, plasma concentrations of IL-6 were significantly higher in dogs with a cPSS compared to healthy dogs (P=0.02).

The ecological significance of tool use in New Caledonian crows.

Tool use is so rare in the animal kingdom that its evolutionary origins cannot be traced with comparative analyses. Valuable insights can be gained from investigating the ecological context and adaptive significance of tool use under contemporary conditions, but obtaining robust observational data is challenging. We assayed individual-level tool-use dependence in wild New Caledonian crows by analyzing stable isotope profiles of the birds' feathers, blood, and putative food sources. Bayesian diet-mixing models revealed that a substantial amount of the crows' protein and lipid intake comes from prey obtained with stick tools--wood-boring beetle larvae. Our calculations provide estimates of larva-intake rates and show that just a few larvae can satisfy a crow's daily energy requirements, highlighting the substantial rewards available to competent tool users.

Retrospective analysis of selected predictors of mortality within a veterinary intensive care unit.

The records of 204 cats entering the intensive care unit (ICU) at the University of Edinburgh Small Animal Hospital between December 2002 and October 2006 were retrospectively analysed. Of these, 37 cats over 12 months of age had a systolic blood pressure recorded on entry into the ICU, and this group comprised our study population. Of these 37 cats, 36 had both heart rate and respiratory rate recorded on entry into the ICU, whilst 24 of these cats also had body temperature recorded. The relationship between (i) survival to discharge and (ii) survival until 21 days after admission to the ICU was analysed using univariate generalised linear models with binomial errors. The robustness of any significant relationship was assessed using multivariate analysis methods. In addition, receiver operator curves (ROC) were generated for any of the significant predictors of mortality and from these curves the threshold values, optimal sensitivity and specificity were calculated. Using these values survival curves were generated for any significant prognostic indexes. A decreased blood pressure at the time of admission to the ICU was found to be a significant negative predictor of survival until discharge from the hospital. Overall, a systolic blood pressure of 124 mmHg or higher at the time of admission to the ICU has a sensitivity of 47.8% and a specificity of 85.7% for predicting that a cat will survive until discharge from the hospital.

Cobalamin, folate and inorganic phosphate abnormalities in ill cats.

Hypocobalaminaemia in cats has previously been identified, but the incidence reported has varied, and the frequency of folate deficiency is unknown. The aims of this study were to evaluate the incidence of low cobalamin and folate levels in a population of cats that were suffering predominantly from diseases of the alimentary tract (including the liver and pancreas) and to ascertain whether severity of disease (as assessed by bodyweight and body condition score (BCS)) related to degree of deficiency. The study population comprised 103 cats, of which 16.5% had low cobalamin levels and 38.8% had low folate levels. A serendipitous finding was inorganic phosphate levels below the reference range in 48% of the cases. Significant associations were found between subnormal cobalamin levels and median BCS (P=0.049); combined low folate and low cobalamin and bodyweight (P=0.002), BCS (P=0.024) and inorganic phosphate levels (P=0.003). The finding of low levels of folate and cobalamin in clinical cases suggests that supplementation may be indicated more frequently than is currently recognised.

Effect of sample type, and timing of assay, on feline blood potassium concentration.

Blood samples were collected from 41 cats presented for pre-anaesthetic assessments, routine geriatric screening, or re-assessment of ongoing chronic medical disorders. Samples were either left to clot or anticoagulated with lithium heparin, then assessed for their potassium concentration within 1h of collection, and again after remaining in contact with their cell pellet for 48 h. There was a significantly higher potassium concentration in the serum samples compared to the plasma samples, both in the basal and 48-h samples (although this difference was most marked in the basal samples). Ageing of both serum and plasma samples also resulted in an increase in the potassium concentration when compared with the basal values for each sample type. The mean difference (basal serum minus basal plasma) in potassium concentration was 0.47 mmol/l. While it is probable that the potassium came from either leukocytes and/or thrombocytes the mean total leukocyte count and the mean thrombocyte count were below the upper limit of the reference intervals for our laboratory and the rise in the potassium level did not appear to be directly related to either of these values.

Unusual histiocytic disease in a Somali cat.

An 8-year-old Somali cat presented with a 9-month history of inappetence, vomiting and weight loss. The disease progressed to involve neurological signs associated with a mass lesion at the level of the first lumbar vertebra. Histopathology identified the condition as malignant histiocytosis affecting the lungs, stomach, mesenteric lymph nodes, liver, spleen, brain and spinal cord. However, the presentation of this case differs from previously reported cases of malignant histiocytosis, and may therefore represent a variant form of histiocytic disease.