Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma

Deepa Rastogi, Sasha Fraser, Jamie Oh, Ashley M. Huber, Yael Schulman, Renuka H. Bhagtani, Zeeshan S. Khan, Lydia Tesfa, Charles B. Hall, Fernando Macian-Juan

Research output: Contribution to journalArticle

57 Citations (Scopus)

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+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.

Original languageEnglish (US)
Pages (from-to)149-160
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume191
Issue number2
DOIs
StatePublished - Jan 15 2015

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Asthma
Monocytes
Inflammation
Lung
Insulin Resistance
HDL Lipoproteins
Residual Volume
Chemokine Receptors
C Chemokines
Phytohemagglutinins
Body Mass Index
Inspiratory Capacity
Weights and Measures
CC Chemokines
Th1 Cells
Mites
Leptin
Dust
LDL Lipoproteins
Interleukin-4

Keywords

  • Asthma
  • Inflammation
  • Metabolic dysregulation
  • Obesity
  • Pulmonary function

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma. / Rastogi, Deepa; Fraser, Sasha; Oh, Jamie; Huber, Ashley M.; Schulman, Yael; Bhagtani, Renuka H.; Khan, Zeeshan S.; Tesfa, Lydia; Hall, Charles B.; Macian-Juan, Fernando.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 191, No. 2, 15.01.2015, p. 149-160.

Research output: Contribution to journalArticle

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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+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.",
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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-Juan, Fernando

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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.

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KW - Asthma

KW - Inflammation

KW - Metabolic dysregulation

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