Abstract
BackgroundAsthma represents a syndrome for which our understanding of the molecular processes underlying discrete sub-diseases (i.e., endotypes), beyond atopic asthma, is limited. The public health needs to characterize etiology-associated endotype risks is becoming urgent. In particular, the roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes – T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) – warrants clarification.ObjectivesTo explain ambient B[a]P association with non-atopic asthma (i.e., a proxy of non-Th2 endotype) is markedly different from that with atopic asthma (i.e., a proxy for Th2-high endotype).MethodsIn a case-control study, we compare the non-atopic as well as atopic asthmatic boys and girls against their respective controls in terms of the ambient Benzo[a]pyrene concentration nearest to their home, plasma 15-Ft2-isoprostane (15-Ft2-isoP), urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and lung function deficit. We repeated the analysis for i) dichotomous asthma outcome and ii) multinomial asthma—overweight/obese (OV/OB) combined outcomes.ResultsThe non-atopic asthma cases are associated with a significantly higher median B[a]P (11.16 ng/m3) compared to that in the non-atopic controls (3.83 ng/m3; P-value < 0.001). In asthma-OV/OB stratified analysis, the non-atopic girls with lean and OV/OB asthma are associated with a step-wisely elevated B[a]P (median,11.16 and 18.00 ng/m3, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m3, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m3) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m3; P-value > 0.05). Based on the logistic regression model, on ln-unit increate in B[a]P is associated with 4.7-times greater odds (95% CI, 1.9–11.5, P = 0.001) of asthma among the non-atopic boys. The same unit increase in B[a]P is associated with 44.8-times greater odds (95% CI, 4.7–428.2, P = 0.001) among the non-atopic girls after adjusting for urinary Cotinine, lung function deficit, 15-Ft2-isoP, and 8-oxodG.ConclusionsAmbient B[a]P is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among lean children. Furthermore, lung function deficit, 15-Ft2-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.
Highlights
Asthma represents the most common respiratory impairment worldwide, afflicting over 400 million people of all age groups, racial/ethnic backgrounds, and genders [1, 2]
The asthma burden is growing despite the introduction of therapeutic strategies, pharmacologic interventions, and other public health measures [2]
Nearly 50% of the poorly-controlled asthmatic children are expected to emerge as severe adult cases [9]
Summary
Asthma represents the most common respiratory impairment worldwide, afflicting over 400 million people of all age groups, racial/ethnic backgrounds, and genders [1, 2]. In practice, asthma is still diagnosed based on observable clinical characteristics (i.e., phenotypes) [7]. Such ‘once-size-fitsall’ detection and management strategies, focused on symptom easement without considering the etiologic mechanisms, are thought to contribute to the burgeoning economic burden of asthma, by those with poorly controlled subtypes [8]. Mechanism-based definitions of asthma could help identify early effect biomarkers for specific sub-types [7]. The development of such biomarker-based therapies in asthmatic children before the onset of irreversible respiratory injuries represents an urgent public health need [9, 10]. The roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes – T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) – warrants clarification
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