In this month’s issue, the Severe Asthma Research Program [SARP] presents their findings from a cross-sectional study of the SARP database, which holds clinical, immunological, and physiological data for over 1300 subjects with asthma (Gamble C, Talbott E, Youk A, Holguin F, Pitt B, Silveira L, et al. Racial differences in biologic predictors of severe asthma: Data from the Severe Asthma Research Program. J Allergy Clin Immunol 126;1149-1156.e1). Gamble et al. partition the severe asthma subjects into two categories, “blacks” and “whites” 40 years of age and older, to evaluate variability in asthma presentation. The authors employ a univariable model and a multivariate model to detect in- and between-group differences.
In univariable analyses, higher BMI, reported GERD, and current employment are associated with severe asthma in blacks. Additionally, the presence of 2 or more family members with asthma is positively associated with severe asthma; however, the presence of atopy and 5 or more positive prick skin tests are negatively associated. Whites are more likely to report additional co-morbidities, such as hypertension and diabetes, as well as GERD, and a positive family history of asthma was not significant in whites. Interestingly, owning a pet decreased the risk of severe asthma in whites. Unlike blacks, current employment is not significant in whites with severe asthma. In both blacks and whites, second-hand smoke exposure and serum IgE are not risk factors.
Multivariate models reveal that, unlike the univariable modeling, IgE was strongly associated with severe asthma and a family history of asthma doubled the risk of severe asthma in blacks. Current employment drops out as a risk factor for blacks in this model. Blacks with GERD, high serum IgE, baseline % predicted FEV1, and 2 or more family members with asthma strongly associate with severe asthma. While whites share GERD and baseline % predicted FEV1 as risk factors with blacks, not having a pet, and no family history of asthma predict risk for severe asthma in whites.
Gamble et al. conclude that biologic/genetic factors and family history are equally or more important than socioeconomic factors as in accounting for risk of severe asthma in blacks. We asked the authors about the implications for their study. According to first author, Christy Gamble, DrPHc, MPH, and senior author, Sally Wenzel, MD, “the different predictors for blacks and whites suggest the mechanisms for severe asthma could be different and thus, approaches to treatment of severe asthma in blacks may very well differ from those in whites.”
Do you have any questions for the authors, or comments about this study? We want to hear from you. Please feel free to post your own questions or comments. All questions and comments will be forwarded to the authors for a response.
Monday, December 6, 2010
Maternal antioxidant SNPs modify link between acetaminophen exposure in utero and childhood asthma
Shaheen and colleagues report their findings from studies on acetaminophen and childhood asthma from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in this month’s issue (Shaheen SO, Newson RB, Rose-Zerilli MJ, Holloway JW, Henderson AJ. Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma. J Allergy Clin Immunol 2010;126:1141-1148.e7). The authors follow up on their previous studies demonstrating association of childhood asthma with acetaminophen use in pregnancy by investigating possible causality between the two.
Shaheen et al. reason that prenatal acetaminophen exposure may increase the risk of childhood asthma by increasing oxidative stress and glutathione depletion and that polymorphisms in antioxidant genes may influence acetaminophen toxicity in the womb. They genotyped transcription factor nuclear erythroid 2 p45-related factor 2 (Nrf2), a primary regulator of antioxidant genes, and the glutathione-S-transferases GSTM1, -P1, and T1, which protect the lung from oxidative stress. Previous research has shown that Nrf2-negative mice readily develop liver toxicity in response to acetaminophen exposure.
The authors find that early [≤20 weeks gestation] and late [≥20 weeks gestation] acetaminophen exposure in utero is associated with increased risk for wheezing and asthma in childhood. Late gestation acetaminophen exposure has a more profound effect on wheezing and, in addition, is associated with increased serum IgE.
They also find that effects of prenatal acetaminophen exposure on asthma risk are modified by Nrf2 and GST variants in the mother, but not in the child, strengthening evidence that the link between acetaminophen use in pregnancy and childhood asthma may be causal.
Shaheen et al. reason that prenatal acetaminophen exposure may increase the risk of childhood asthma by increasing oxidative stress and glutathione depletion and that polymorphisms in antioxidant genes may influence acetaminophen toxicity in the womb. They genotyped transcription factor nuclear erythroid 2 p45-related factor 2 (Nrf2), a primary regulator of antioxidant genes, and the glutathione-S-transferases GSTM1, -P1, and T1, which protect the lung from oxidative stress. Previous research has shown that Nrf2-negative mice readily develop liver toxicity in response to acetaminophen exposure.
The authors find that early [≤20 weeks gestation] and late [≥20 weeks gestation] acetaminophen exposure in utero is associated with increased risk for wheezing and asthma in childhood. Late gestation acetaminophen exposure has a more profound effect on wheezing and, in addition, is associated with increased serum IgE.
They also find that effects of prenatal acetaminophen exposure on asthma risk are modified by Nrf2 and GST variants in the mother, but not in the child, strengthening evidence that the link between acetaminophen use in pregnancy and childhood asthma may be causal.
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