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Allergic Asthma Is Associated with Altered Sphingolipid Composition in Children
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A1167 - Allergic Asthma Is Associated with Altered Sphingolipid Composition in Children
Author Block: J. G. Ono1, T. Worgall2, B. I. Kim2, S. Worgall1; 1Weill Cornell Medicine, New York, NY, United States, 2Columbia University Medical Center, New York, NY, United States.
Rationale: The genetic asthma susceptibility locus 17q21 includes ORMDL3 which affects sphingolipid metabolism. Increased airway-hyper reactivity has been associated with altered sphingolipids in mouse models, but the role of sphingolipids in asthma remains unclear. We have recently shown that C18 Dihydroceramide is positively associated with exercise-induced wheezing, a phenotype of asthma in children which may be variably associated with allergy. This association predicted asthma persistence overtime in a large cohort of children with asthma. Alterations of sphingolipids, in particular sphingosine-1-phosphate (S1P) and ceramides, have been associated with inflammatory and allergic asthma in mouse models, but little is known about how sphingolipids are affected in childhood asthma. To address this, we examined plasma and whole blood sphingolipid profiles in a cohort of children with and without allergic asthma.
Methods: Sphingolipid compositions were analyzed in a cohort of pediatric subjects (ages 5-17 years) with asthma (n=28), and in non-asthmatic controls (n=21). The cohort includes males and females with no prior history of asthma or wheezing, and those who have been previously diagnosed with asthma by a pediatric pulmonologist and have been symptomatic within the last year. Asthma and non-asthma phenotypes were determined through clinical history, standardized asthma symptom checklists, medical record review and spirometry. Masses of sphingolipids were quantified by mass spectrometry (HPLC-MS/MS) in plasma and whole blood samples. Allergy status was determined through clinical questionnaire, blood IgE (> 150 IU/ml) and blood eosinophils (> 0.3 x 103/mcl).
Results: In children with allergic asthma associated with a total IgE >150 IU/ml (n=18), C18:1 Dihydroceramide (DHC18:1) is elevated in both plasma (p=.03) and whole blood samples (p=0.01) compared to children without asthma. No differences in DHC18:1 concentration was identified between non-asthmatic controls with or without allergies. In addition, DHC18:1 concentration is higher in allergic asthma (n=18) compared to non-allergic asthma (n=10) in both plasma (p=0.02) and whole blood samples (p=0.006).
Conclusions: These data suggest that sphingolipids are altered in children with allergic asthma compared to children without asthma. These data also confirm a role of sphingolipids (particularly dihydroceramides) in two cohorts of children with asthma. This suggests that altered sphingolipids may contribute towards the underlying pathophysiology of allergic asthma and may lead to improved characterization of pediatric asthma phenotypes.
Author Block: J. G. Ono1, T. Worgall2, B. I. Kim2, S. Worgall1; 1Weill Cornell Medicine, New York, NY, United States, 2Columbia University Medical Center, New York, NY, United States.
Rationale: The genetic asthma susceptibility locus 17q21 includes ORMDL3 which affects sphingolipid metabolism. Increased airway-hyper reactivity has been associated with altered sphingolipids in mouse models, but the role of sphingolipids in asthma remains unclear. We have recently shown that C18 Dihydroceramide is positively associated with exercise-induced wheezing, a phenotype of asthma in children which may be variably associated with allergy. This association predicted asthma persistence overtime in a large cohort of children with asthma. Alterations of sphingolipids, in particular sphingosine-1-phosphate (S1P) and ceramides, have been associated with inflammatory and allergic asthma in mouse models, but little is known about how sphingolipids are affected in childhood asthma. To address this, we examined plasma and whole blood sphingolipid profiles in a cohort of children with and without allergic asthma.
Methods: Sphingolipid compositions were analyzed in a cohort of pediatric subjects (ages 5-17 years) with asthma (n=28), and in non-asthmatic controls (n=21). The cohort includes males and females with no prior history of asthma or wheezing, and those who have been previously diagnosed with asthma by a pediatric pulmonologist and have been symptomatic within the last year. Asthma and non-asthma phenotypes were determined through clinical history, standardized asthma symptom checklists, medical record review and spirometry. Masses of sphingolipids were quantified by mass spectrometry (HPLC-MS/MS) in plasma and whole blood samples. Allergy status was determined through clinical questionnaire, blood IgE (> 150 IU/ml) and blood eosinophils (> 0.3 x 103/mcl).
Results: In children with allergic asthma associated with a total IgE >150 IU/ml (n=18), C18:1 Dihydroceramide (DHC18:1) is elevated in both plasma (p=.03) and whole blood samples (p=0.01) compared to children without asthma. No differences in DHC18:1 concentration was identified between non-asthmatic controls with or without allergies. In addition, DHC18:1 concentration is higher in allergic asthma (n=18) compared to non-allergic asthma (n=10) in both plasma (p=0.02) and whole blood samples (p=0.006).
Conclusions: These data suggest that sphingolipids are altered in children with allergic asthma compared to children without asthma. These data also confirm a role of sphingolipids (particularly dihydroceramides) in two cohorts of children with asthma. This suggests that altered sphingolipids may contribute towards the underlying pathophysiology of allergic asthma and may lead to improved characterization of pediatric asthma phenotypes.
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