Inflammation, Metabolic Dysregulation, and Pulmonary Function among Obese Urban Adolescents with Asthma

Abstract

Rationale: Insulin resistance and low high-density lipoprotein (HDL) are associated with pulmonary morbidity, including asthma, but the underlying mechanisms are not well elucidated.Objectives: To investigate whether systemic inflammation underlies the association of metabolic abnormalities with pulmonary function among urban adolescents.Methods: Th-cell responses and monocyte subsets, and their association with serum homeostatic model assessment of insulin resistance (HOMA-IR) and HDL, and pulmonary function were quantified in 168 adolescents, including 42 obese subjects with asthma, 42 normal-weight subjects with asthma, 40 obese subjects without asthma, and 44 healthy control subjects. Th-cell responses (Th1 [CD4 ) monocytes, and their C-C chemokine receptor type-2 (CCR2) expression were quantified by flow cytometry.Measurements and Main Results: Th1/Th2 ratio to all three stimuli was higher in obese subjects with asthma than normal-weight subjects with asthma and directly correlated with HOMA-IR. Classical monocytes inversely associated with Th1/Th2 ratio to phytohemagglutinin (r = 20.43; P = 0.01) and directly with Asthma Control Test score (b = 1.09; P = 0.04), while patrolling monocytes correlated with Composite Asthma Severity Index score (b = 1.11; P = 0.04) only among obese subjects with asthma. HDL was inversely associated with patrolling monocytes and directly associated with CCR2 expression on resident monocytes. CCR2 expression on patrolling monocytes predicted residual volume (RV), RV/TLC ratio, and FRC, after adjusting for HDL, but not after adjusting for body mass index. Association of Th1/Th2 ratio with RV, FRC, and inspiratory capacity was attenuated after adjusting for HOMA-IR.Conclusions: Th1 polarization and monocyte activation among obese subjects with asthma correlates with metabolic abnormalities. Association of monocyte activation with pulmonary function is mediated by body mass index, whereas that of Th1 polarization is mediated by insulin resistance.

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

“…128 Recent studies have found that insulin resistance mediates the association of systemic Th1 polarization with obesity-mediated pulmonary function deficits among ethnic minority children. 103 Given these initial investigations into the association among insulin resistance, inflammation, and pulmonary function impairment, further study of the underlying immunometabolic pathways is needed to determine the mechanism through which insulin resistance contributes to the obese asthma phenotype.…”

“…34 There is preliminary evidence to suggest that this effect may be mediated in part by the protective effect of HDL on monocyte activation. 103 There is also increasing evidence to suggest that the origins of the association of diet-induced metabolic dysregulation and pulmonary morbidity may start as early as in utero. For instance, altered fat intake, with low intake of poly-unsaturated fatty acids in the mother, has been associated with an increased predisposition to asthma among the offspring.…”

Asthma and Obesity - the Recent Advancements

“…This clearly suggests that obesity has a direct impact on lung function, and is associated with pathophysiology of asthma. Nonetheless, it also appears that insulin resistance may induce structural changes in the lungs besides driving the inflammatory invasion in lungs 12,13 . Such changes are also known to be associated with metabolic syndrome 14 .…”

Asthma and Obesity - the Recent Advancements

“…This clearly suggests that obesity has a direct impact on lung function, and is associated with pathophysiology of asthma. Nonetheless, it also appears that insulin resistance may induce structural changes in the lungs besides driving the inflammatory invasion in lungs 12,13 . Such changes are also known to be associated with metabolic syndrome 14 .…”