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Obesity Is Associated with Sustained Symptomatology and Unique Inflammatory Features in Children with Asthma
Anne M Fitzpatrick1, Abby D Mutic2, Ahmad F Mohammad3
1Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga; Children's Healthcare of Atlanta, Atlanta, Ga.
Insights
Obese children with asthma experience worse symptoms and more exacerbations, with limited improvement from corticosteroids. Unique inflammation and oxidative stress markers in these children suggest novel treatment approaches are needed.
Area of Science:
- Pediatric Pulmonology
- Immunology
- Metabolomics
Background:
- Obesity complicates asthma management in children.
- Limited research exists on longitudinal outcomes and systemic inflammation in pediatric obese asthmatics.
Purpose of the Study:
- To investigate if obese children with asthma have poorer clinical outcomes, reduced corticosteroid response, increased systemic inflammation, and unique amino acid metabolites.
- To identify potential biomarkers for asthma control in obese children.
Main Methods:
- A 12-month longitudinal study of 494 children (6-17 years) categorized by BMI (lean, overweight, obese).
- Assessed asthma control, quality of life, lung function, exacerbations, and systemic inflammatory markers (cytokines, C-reactive protein, leptin, adiponectin).
- Evaluated corticosteroid response in a subset and analyzed plasma amino acid metabolites.
Main Results:
- Obesity correlated with increased asthma symptoms, poorer quality of life, and more exacerbations over 1 year, requiring higher medication doses.
- Obese children showed minimal improvement in asthma control and lung function post-corticosteroid treatment.
- Distinct profiles of leptin, C-reactive protein, and amino acid metabolites linked to oxidative stress were observed in obese children. Lower arginine metabolites differentiated uncontrolled asthma.
Conclusions:
- Obesity is linked to worse asthma outcomes and distinct systemic inflammation in children, inadequately addressed by current therapies.
- Unique inflammatory and oxidative stress signatures in obese asthmatic children necessitate novel therapeutic strategies.
Background:
Obesity complicates the clinical manifestations of asthma in children. However, few studies have examined longitudinal outcomes or markers of systemic inflammation in obese asthmatic children.
Objective:
We hypothesized that obese children with asthma would have: (1) poorer clinical outcomes over 12 months, (2) decreased responsiveness to systemic corticosteroid administration, (3) greater markers of systemic inflammation, and (4) unique amino acid metabolites associated with oxidative stress.
Methods:
Children 6 to 17 years of age (lean, N = 257; overweight, N = 99; obese, N = 138) completed a baseline visit and follow-up visit at 12 months. Outcome measures included asthma control, quality of life, lung function, and exacerbations. A subset received intramuscular triamcinolone and were re-evaluated at 7(+7) days. Leptin, adiponectin, C-reactive protein, total cholesterol, interleukin (IL)-1β, IL-6, IL-17, interferon gamma, tumor necrosis factor alpha, monocyte-chemoattractant protein-1, and amino acid metabolites were also quantified in plasma as potential biomarkers of outcomes in obese children.
Results:
Obesity was associated with more symptoms, poorer quality life, and more exacerbations that persisted over 1 year despite greater medication requirements. Obese children also had minimal clinical improvement in asthma control and lung function after intramuscular triamcinolone. Leptin, C-reactive protein, and amino acid metabolites associated with glutathione synthesis and oxidative stress differed in obese children. Within the obese group, lower concentrations of arginine-related metabolites also distinguished uncontrolled from controlled asthma at 12 months.
Conclusion:
Obesity is associated with poorer asthma outcomes and unique systemic inflammatory features that may not be adequately modified with conventional asthma therapies. Novel approaches may be needed given increased symptoms and unique inflammation and oxidative stress in obese children with asthma.
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