PURPOSE OF THE STUDY.
The purpose of this study was to investigate the role of systemic inflammation and metabolic dysregulation in pulmonary deficits observed in obese urban adolescents with asthma.
This study consisted of 168 Hispanic and African American adolescents, including 42 obese subjects with asthma, 42 normal-weight subjects with asthma, 40 obese subjects without asthma, and 44 healthy control subjects. Obesity was defined as BMI greater than 95th percentile.
During the study visit, all subjects underwent anthropometric measurements, a fasting laboratory draw, and pulmonary function testing. Researchers quantified Th-cell responses to stimulation with various agents, chemokine receptor expression, cytokines, adipokines, and metabolic measures. The primary outcomes of interest were between-group differences in monocyte activation, and Th-cell responses, and their association with metabolic measures, and pulmonary function.
Adolescents with asthma had lower forced expiratory volume in 1 second (FEV1), lower FEV1/forced vital capacity ratio, lower forced expiratory flow midexpiratory phase, and lower high-density lipoprotein cholesterol than adolescents without asthma. Obese adolescents had lower residual volume (RV), RV/total lung capacity ratio, expiratory RV, functional residual capacity, and higher inspiratory capacity. Obese adolescents also had lower high-density lipoprotein levels, higher levels of insulin and leptin, and lower levels of adiponectin. There were no significant interactions observed between obesity and asthma for any of the metabolic or pulmonary function measures. Only 25% of obese and normal-weight subjects with asthma were using inhaled corticosteroids (ICS). Metabolic measures and spirometric indices did not differ by ICS use. The Th1/Th2 ratio in response to PHA, leptin, and Dermatophagoides farina was higher among obese subjects with asthma than normal-weight subjects with asthma. There were no significant differences in metabolic measures, monocyte activation, Th-cell responses, and serum cytokines between obese subjects with asthma and obese subjects without asthma. The proportion of classic and patrolling monocytes did not differ between obese and normal-weight subjects with asthma, there were fewer classic and more patrolling monocytes among obese subjects with asthma on ICS than those not on ICS; a similar difference was not observed among normal-weight subjects with asthma.
Together, these results indicate that systemic immune responses are nonatopic among obese subjects with asthma, differ from atopic inflammation among normal-weight subjects with asthma, and may be exaggerated compared with obese subjects without asthma. These results also suggest that systemic nonatopic inflammation among obese urban adolescents with asthma may be associated with metabolic abnormalities and may underlie pulmonary function deficits found in childhood obesity-related asthma.
Obese children have a higher incidence and severity of asthma, which is typically less responsive to inhaled steroids compared with normal-weight asthmatics. This study highlights an important relationship between metabolic health and lung health, providing us with the potential of using interventions aimed at improving insulin sensitivity or cholesterol profiles as a way to improve asthma control in the obese population. Further investigation of these “outside the box” treatment options for asthma is needed. There is a need for longitudinal studies to address the relationship between onset of obesity and associated metabolic dysregulation, systemic immune responses, and pulmonary morbidity to better define the role of these mechanisms in the pathogenesis of pediatric obesity-related asthma.
- Copyright © 2015 by the American Academy of Pediatrics