ABSTRACT
BACKGROUND: Obesity is well recognized as a state of increased insulin resistance and has been implicated as a significant risk factor for both asthma prevalence and asthma severity in children and adolescents. However, little is known about the specific factors that relate asthma and obesity. Recently, the pro-inflammatory state in obesity and its association with insulin resistance have been recognized. We hypothesize that the effect of morbid obesity on asthma is related to insulin resistance. METHODS: The patient cohort in the obesity management program at the Children's Hospital of Wisconsin was retrospectively reviewed. Variables were collected from the program data base and chart review was done for missing variables. Patients were considered to have asthma if the evaluating physician confirmed the diagnosis through history and/or the patient had been on inhaled corticosteroids. Insulin resistance (IR) was calculated using a homeostasis model assessment (HOMA). Multivariate logistic regression was performed to identify variables that were significantly related to the odds of having asthma. RESULTS: Of the 415 patients included in the study, 146 (35%) were asthmatic and 269 (65%) were non-asthmatic. The asthma (AG) and non-asthma (NAG) groups were similar with respect to mean age (11.3 vs. 11.5 years), gender (45% vs. 43% males), mean body mass index (BMI) (36.4 vs. 34.9), and exposure to smoking (43% vs. 42%). Fhx of asthma was significantly higher in AG (71%) compared to NAG (40%). IR level+/-SD was 8.5+/-9.7 in AG compared to 5.3+/-6.7 in NAG (p<0.0001). Multivariate regression analysis found the following variables to be associated with having asthma: younger age (p<0.05), smoking exposure (p<0.05), positive Fhx of asthma (p<0.0001, odds ratio of 3.1), and IR (p<0.0001, odds ratio of 4.1). CONCLUSION: Morbidly obese asthma patients have a higher degree of insulin resistance compared to morbidly obese non-asthma patients. We speculate that the pro-inflammatory state of insulin resistance may contribute to the pathogenesis of asthma in obese patients. Future prospective studies should address insulin resistance as a possible risk factor for asthma in obese children and adolescents.
Subject(s)
Asthma/etiology , Insulin Resistance , Obesity, Morbid/complications , Adolescent , Asthma/blood , Asthma/diagnosis , Blood Glucose/analysis , Body Mass Index , Child , Family Health , Female , Humans , Insulin/blood , Male , Medical History Taking , Multivariate Analysis , Obesity, Morbid/blood , Odds Ratio , Regression Analysis , Retrospective Studies , Risk Factors , Tobacco Smoke Pollution , WisconsinABSTRACT
Changes in the reticulocyte subtype distribution (high, medium and low reticulocytes count (HR, MR, LR)) measured by flow cytometry following phlebotomy-induced stress erythropoiesis (abruptly dropping hemoglobin to 3-4 g/dl over 4-5 hr) and the pharmacodynamic (PD) relationship to the stimulated erythropoietin (EPO) was investigated in sheep. A PD model was developed that describes the relationship between EPO and the reticulocyte maturity distribution fractions (r=0.95+/-0.02, mean +/- SD). The lag-time between EPO activation of erythroid progenitor cells and the subsequent increase in the least mature HR fraction in the peripheral circulation was 0.72 +/- 0.08 days. The mean transition times (in days) for all three reticulocyte fractions changed at baseline from, T(HR) : 0.09 +/- 0.06, T(MR) : 0.06 +/- 0.04, and T(LR) : 0.46 +/- 0.24 to T(HR) : 0.13 +/- 0.08, T(MR) : 0.29 +/- 0.15, and T(LR) : 2.3 +/- 0.24 under stress erythropoiesis. The total mean residence time for a reticulocyte in the peripheral circulation, T(total) (T(HR) + T(MR) + T(LR)), increased from 0.60 +/- 0.33 days under basal to 2.8 +/- 0.09 days during stress erythropoiesis. The statistically significant increase observed for T(LR) and T(total) supports the hypothesis that stress erythropoiesis perturbs the mean reticulocyte transition times. A correlation analysis between various new, proposed metrics involving the HR, MR and LR fractions and the total reticulocyte count, with the latter indicative of stress erythropoiesis at higher total counts, revealed a highly significant correlation indicating these new metrics may be a valuable adjunct to the reticulocyte maturation index (RMI) and the immature reticulocyte fractions index (IRF) previously used in assessing erythropoietic activity in response to anemia.
