Benzo[a]pyrene-associated Oxidative Stress is Divergent in Non-atopic Versus Atopic Children, and Suggest They May Represent Asthma Endotypes: A Case-control Study
Abstract Background For nearly 50% of the asthmatic children, effective treatments against exacerbation do not exist, because existing therapies do not target the mechanistic origins of discrete sub-diseases (i.e. endotypes). While non-atopic and atopic asthma represent known phenotypes, it is unknown whether they arise from disparate processes. The objective is to classify two phenotypes (non-atopic vs. atopic asthma) into endotypes using polyaromatic hydrocarbon, namely, benzo[a]pyrene, as putative marker of endotype. Methods In a case-control study, lean controls (i.e. reference) are compared against three outcomes of interest – overweight/obese controls, lean asthmatics (without overweight/obesity), and overweight/obese asthmatics – in terms of benzo[a]pyrene exposure level, plasma 15-Ft2-isoprostane, urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine, as well as their history of co-morbidities until age three, following atopy- and gender-stratification. Results The non-atopic girls are associated with significantly elevated median benzo[a]pyrene for the lean asthmatics (11.2 ng/m3) and the overweight/obese asthmatics (18.0 ng/m3), compared to the non-atopic control girls (4.3 ng/m3; p-value < 0.001). A natural-log (ln) unit increase B[a]P exposure predicts 10-times greater odds of asthma in the lean non-atopic boys, while the same exposure is not associated with asthma among the lean atopic boys. The diagnosis of lung function deficit, which only appear among those with highest median value of B[a]P, appears to be a particularly important predictor of non-atopic asthma only. The non-atopic asthmatic boys with highest exposure to B[a]P (median, 20 ng/m3) were also positively diagnosis with lung function deficit, compared to the non-atopic controls (median, 4.3 ng/m3). An elevated exposure to B[a]P is associated with depressed systemic oxidant levels, and correspondingly elevated odds of non-atopic asthma. On the other hand, low ambient exposure to B[a]P, and weakly pro-inflammatory effect of oxidative stress of such exposure, is not associated with atopic asthma. Conclusions Ambient benzo[a]pyrene is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among the lean children. Our observation, once validated in a prospective cohort design, could aid the development of targeted and personalized therapies in children in whom the respiratory injuries are still reversible..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 28. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Choi, Hyunok [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-41716/v1 |
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| PPN (Katalog-ID): |
XRA033936552 |
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| 520 | |a Abstract Background For nearly 50% of the asthmatic children, effective treatments against exacerbation do not exist, because existing therapies do not target the mechanistic origins of discrete sub-diseases (i.e. endotypes). While non-atopic and atopic asthma represent known phenotypes, it is unknown whether they arise from disparate processes. The objective is to classify two phenotypes (non-atopic vs. atopic asthma) into endotypes using polyaromatic hydrocarbon, namely, benzo[a]pyrene, as putative marker of endotype. Methods In a case-control study, lean controls (i.e. reference) are compared against three outcomes of interest – overweight/obese controls, lean asthmatics (without overweight/obesity), and overweight/obese asthmatics – in terms of benzo[a]pyrene exposure level, plasma 15-Ft2-isoprostane, urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine, as well as their history of co-morbidities until age three, following atopy- and gender-stratification. Results The non-atopic girls are associated with significantly elevated median benzo[a]pyrene for the lean asthmatics (11.2 ng/m3) and the overweight/obese asthmatics (18.0 ng/m3), compared to the non-atopic control girls (4.3 ng/m3; p-value < 0.001). A natural-log (ln) unit increase B[a]P exposure predicts 10-times greater odds of asthma in the lean non-atopic boys, while the same exposure is not associated with asthma among the lean atopic boys. The diagnosis of lung function deficit, which only appear among those with highest median value of B[a]P, appears to be a particularly important predictor of non-atopic asthma only. The non-atopic asthmatic boys with highest exposure to B[a]P (median, 20 ng/m3) were also positively diagnosis with lung function deficit, compared to the non-atopic controls (median, 4.3 ng/m3). An elevated exposure to B[a]P is associated with depressed systemic oxidant levels, and correspondingly elevated odds of non-atopic asthma. On the other hand, low ambient exposure to B[a]P, and weakly pro-inflammatory effect of oxidative stress of such exposure, is not associated with atopic asthma. Conclusions Ambient benzo[a]pyrene is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among the lean children. Our observation, once validated in a prospective cohort design, could aid the development of targeted and personalized therapies in children in whom the respiratory injuries are still reversible. | ||
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