TY - JOUR
T1 - Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma
AU - Rastogi, Deepa
AU - Fraser, Sasha
AU - Oh, Jamie
AU - Huber, Ashley M.
AU - Schulman, Yael
AU - Bhagtani, Renuka H.
AU - Khan, Zeeshan S.
AU - Tesfa, Lydia
AU - Hall, Charles B.
AU - Macian, Fernando
N1 - Publisher Copyright:
Copyright © 2015 by the American Thoracic Society.
PY - 2015/1/15
Y1 - 2015/1/15
N2 - 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+IFNγ+] and Th2 [CD4+IL4+] cells) to stimulation with phytohemagglutinin, leptin, and dust mite, and classical (CD14+CD16-), resident (CD14+CD16+), and patrolling (CD14dimCD16+) 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 (β = 1.09; P = 0.04), while patrolling monocytes correlated with Composite Asthma Severity Index score (β = 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.
AB - 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+IFNγ+] and Th2 [CD4+IL4+] cells) to stimulation with phytohemagglutinin, leptin, and dust mite, and classical (CD14+CD16-), resident (CD14+CD16+), and patrolling (CD14dimCD16+) 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 (β = 1.09; P = 0.04), while patrolling monocytes correlated with Composite Asthma Severity Index score (β = 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.
KW - Asthma
KW - Inflammation
KW - Metabolic dysregulation
KW - Obesity
KW - Pulmonary function
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U2 - 10.1164/rccm.201409-1587OC
DO - 10.1164/rccm.201409-1587OC
M3 - Article
C2 - 25457349
AN - SCOPUS:84921395716
SN - 1073-449X
VL - 191
SP - 149
EP - 160
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 2
ER -
