Supinda Bunyavanich

The Impact of Climate Change on Child Health

Human activity has contributed to climate change. The relationship between climate and child health has not been well investigated. This review discusses the role of climate change on child health and suggests 3 ways in which this relationship may manifest. First, environmental changes associated with anthropogenic greenhouse gases can lead to respiratory diseases, sunburn, melanoma, and immunosuppression. Second, climate change may directly cause heat stroke, drowning, gastrointestinal diseases, and psychosocial maldevelopment. Third, ecologic alterations triggered by climate change can increase rates of malnutrition, allergies and exposure to mycotoxins, vector-borne diseases (malaria, dengue, encephalitides, Lyme disease), and emerging infectious diseases. Further climate change is likely, given global industrial and political realities. Proactive and preventive physician action, research focused on the differential effects of climate change on subpopulations including children, and policy advocacy on the individual and federal levels could contain climate change and inform appropriate prevention and response.

Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children.

BACKGROUND Maternal diet during pregnancy may affect childhood allergy and asthma. OBJECTIVE We sought to examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma. METHODS We studied 1277 mother-child pairs from a US prebirth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age, 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum-specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood. RESULTS Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least 1 food allergen (28.0%). Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs, 3.6 to 8.1). CONCLUSION Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma.

Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma

BackgroundAllergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.ObjectiveTo test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.MethodsWe genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.ResultsAcross the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fishers combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.ConclusionsTSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.

Parental psychosocial stress and asthma morbidity in Puerto Rican twins

BACKGROUND Little is known about paternal psychosocial factors and childhood asthma. OBJECTIVE We sought to examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children. METHODS Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 year and again about their childs asthma at age 3 years. Fathers were asked about symptoms of posttraumatic stress disorder (PTSD), depression, and antisocial behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood. RESULTS After multivariable adjustment, paternal PTSD symptoms, depression, and antisocial behavior were each associated with increased asthma symptoms at age 1 year (eg, odds ratio, 1.08 for each 1-point increase in PTSD score; 95% CI, 1.03-1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (odds ratio for each 1-point increase in symptoms, 1.16; 95% CI, 1.00-1.36). In an analysis combining 1- and 3-year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma. CONCLUSIONS Both paternal and maternal psychosocial factors can influence asthma morbidity in young Puerto Rican children.

Peanut allergy prevalence among school-age children in a US cohort not selected for any disease

To the Editor: What is the prevalence of peanut allergy among US children? Given that 90% of US households consume peanut butter,1 this is an important question. The answer is not straightforward, however, as estimates of peanut allergy prevalence among US children differ by allergy definition, study population, and methodology.2 Previous estimates for US children have been based on self-report3–6 or specific IgE (sIgE) criteria,7 which are thought to be inaccurate.2 Estimates have varied according to whether they were based on telephone surveys,3 electronic surveys,4 or nationally representative surveys such as the National Health and Nutrition Examination Survey (NHANES) (Table 1).5–7 One must consider that self-report is hindered by reporting bias, surveys of food allergy are more likely to enlist those with the condition, and nationally representative surveys are limited in the extent of phenotyping possible given their wide scope. It can therefore be difficult to discern how differences in definition, study population, and methodology affect prevalence estimates across studies. Here we report and compare prevalence estimates of childhood peanut allergy according to varying criteria among 7–10 year-old children participating in a US birth cohort not selected for any disease. Table 1 Previously reported prevalence estimates of childhood peanut allergy in the US We determined prevalence of childhood peanut allergy based on reported symptoms, sIgE levels, clinical information, and combinations of these variables among participants of Project Viva. Project Viva is a large, observational cohort study based in eastern Massachusetts with enrollment from Harvard Vanguard Medical Associates, a multi-site group medical practice. Participants were not selected for any disease. The study was designed to examine maternal dietary and other factors that could influence child health outcomes, with health broadly defined.8 Enrollment occurred between 1999 and 2002 in early pregnancy and resulted in delivery of 2128 singleton children. Interviews and questionnaires on child health were administered when the children were age 6 months, 1 year, and annually thereafter. We collected outcome data for this study at the mid-childhood in-person visit (mean age 7.9 years). Among the 1277 children who presented for an in-person interview at mid-childhood, 699 (55%) had blood drawn, and 616 (87.7% of those with blood samples) had sIgE measured by Phadia ImmunoCAP. Compared to those who did not follow up, participants who did follow up showed higher proportions of maternal white race (69% vs. 62%), college or graduate education (69% vs. 58%), and annual household income (63% vs. 58%), but there were no significant differences in parental atopy (P value 0.13). Compared with the general US population, there was a higher proportion of blacks and lower proportion of Hispanics among participants. Further details regarding the comparability of the 616 children to the larger cohort have been previously described.8 We considered a child to have self-reported peanut allergy if his/her mother answered yes to, “Has your child ever had an allergic reaction to peanuts,” and yes to at least one of the following categories of allergic reaction symptoms with peanut ingestion: “Skin related (e.g. hives, swelling),” “Respiratory (e.g., shortness of breath, wheezing, cough),” “Cardiovascular (e.g. low blood pressure, dizziness or fainting,” “Gastrointestinal (e.g. vomiting, diarrhea),” or “Anaphylaxis (severe, multi-system allergic reaction).” These questions, which assess convincing symptoms of IgE-mediated reaction, are comparable to those used in previous studies of self-reported peanut allergy by Sicherer et al.3 We assessed prescription of an epinephrine auto-injector with the question, “Has a health care professional, such as a doctor, physician assistant or nurse practitioner, ever prescribed an EpiPen for your child?” The prevalence of self-reported peanut allergy in this cohort of US children not selected for any disease was 4.6% (Table 2), higher than previously reported estimates of self-reported peanut allergy among US children of comparable age (Table 1). Similarly, we observed a 5.0% prevalence of “clinical peanut allergy” according to sIgE-based criteria that previously resulted in a 2.7% prevalence among comparably aged children in the 2005–2006 NHANES study.7 Within Project Viva, the 4.9% prevalence of peanut allergy defined by both sensitization and prescribed epinephrine auto-injector was similar in magnitude to the estimates defined by self-reported allergy and sIgE-based “clinical allergy” criteria. Table 2 Prevalence of peanut allergy among school-age children in a US observational birth cohort not selected for any disease (N = 616) The relatively high prevalence rates we observed may reflect continued rise of peanut allergy prevalence in the US, consistent with the rising trend in self-reported peanut allergy that Sicherer et al. observed between 1997, 2002, and 2008.3 Additionally, our cohort was based in the Northeast, where rates of peanut sensitization may be higher relative to western US regions.9 Application of a more stringent definition for peanut allergy than self-reported allergy or “clinical allergy,” such as the peanut sIgE ≥ 14 kU/L decision point for 90% specificity reported by Sampson,10 yielded a prevalence of 2.9% (Table 2), which is still higher than previously reported estimates by any criteria (Table 1). Our strictest definition of peanut allergy, requiring peanut sIgE greater than the 90% specificity decision point and prescribed epinephrine auto-injector, yielded a prevalence of 2.0%. While it could be argued that despite Project Viva’s general health goals, the relatively high prevalence rates we observed could be due to food allergic families preferentially returning for mid-childhood visits, the rates of parental atopy (assessed prenatally) among those who did and did not present at mid-childhood were not significantly different, supporting that selection bias was not at play. As we assessed peanut allergy using different criteria within this cohort, we also assessed for agreement between the definitions. Agreement was the highest between self-reported peanut allergy and peanut allergy defined by both peanut sensitization and prescribed epinephrine auto-injector (Κ = 0.75, 95%CI 0.62–0.88). There was moderate agreement between self-reported peanut allergy and peanut allergy defined by both the 90% specificity decision point and prescribed epinephrine auto-injector (Κ = 0.57, 95%CI 0.38–0.76), and less agreement between self-reported peanut allergy and peanut allergy defined by the 90% specificity decision point only (Κ = 0.49, 95%CI 0.31–0.68). Each epidemiologic method for assessing peanut allergy prevalence has strengths and limitations. Double-blind, placebo-controlled food challenges are the gold standard for clinical peanut allergy diagnosis, but these are challenging to implement in large, unselected cohorts and have not been done in unselected US cohorts.2 As diagnostic adjuncts, component resolved diagnostics may also be increasingly implemented in epidemiologic cohorts going forward. In this letter, we have provided prevalence estimates according to several criteria that can be compared to one another and to previous estimates. Our results come from a US cohort of children not selected for allergy or any disease, and they support that peanut allergy is an increasingly prevalent condition.

Prenatal and Infant Exposure to Acetaminophen and Ibuprofen and the Risk for Wheeze and Asthma in Children

BACKGROUND Several studies have reported an association between use of over-the-counter antipyretics during pregnancy or infancy and increased asthma risk. An important potential limitation of these observational studies is confounding by indication. OBJECTIVES We investigated the association of antipyretic intake during pregnancy and during the first year of life (infancy) with asthma-related outcomes before and after controlling for early-life respiratory tract infections. METHODS We included 1490 mother-child pairs in Project Viva, a longitudinal prebirth cohort study. We categorized prenatal acetaminophen exposure as the maximum intake (never, 1-9 times, or ≥10 times) in early pregnancy or midpregnancy and ibuprofen intake as presence or absence in early pregnancy. We expressed intake of antipyretics in infancy as never, 1 to 5 times, 6 to 10 times, or more than 10 times. We examined the associations of acetaminophen and ibuprofen (per unit increase in exposure category) during pregnancy and infancy with wheeze, asthma, and allergen sensitization in early childhood (3-5 years of age, n = 1419) and midchildhood (7-10 years of age, n = 1220). RESULTS Unadjusted models showed an increased asthma risk in early childhood for higher infant acetaminophen (odds ratio [OR], 1.21; 95% CI 1.04-1.41) and ibuprofen (OR, 1.35; 95% CI, 1.19-1.52) intake. Controlling for respiratory tract infections attenuated estimates for acetaminophen (OR, 1.03; 95% CI, 0.88-1.22) and ibuprofen (OR, 1.19; 95% CI, 1.05-1.36). Prenatal acetaminophen was associated with increased asthma (OR, 1.26; 95% CI, 1.02-1.58) in early childhood but not midchildhood. CONCLUSIONS Adjustment for respiratory tract infections in early life substantially diminished associations between infant antipyretic use and early childhood asthma. Respiratory tract infections should be accounted for in studies of antipyretics and asthma to mitigate bias caused by confounding by indication.

The microbiome in allergic disease: Current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology

&NA; PRACTALL is a joint initiative of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology to provide shared evidence‐based recommendations on cutting‐edge topics in the field of allergy and immunology. PRACTALL 2017 is focused on what has been established regarding the role of the microbiome in patients with asthma, atopic dermatitis, and food allergy. This is complemented by outlining important knowledge gaps regarding its role in allergic disease and delineating strategies necessary to fill these gaps. In addition, a review of progress in approaches used to manipulate the microbiome will be addressed, identifying what has and has not worked to serve as a baseline for future directions to intervene in allergic disease development, progression, or both.

Safety, Costs, and Efficacy of Rapid Drug Desensitizations to Chemotherapy and Monoclonal Antibodies

BACKGROUND Rapid drug desensitization (RDD) is used to address hypersensitivity reactions to chemotherapeutics and monoclonal antibodies, allowing patients to be treated with optimal pharmacological agents. RDD protocols are tailored to each individual patients reaction and needs, and protect against anaphylaxis, but overall risks, costs, and benefits have not been determined. OBJECTIVE We investigated the safety, efficacy, costs, and life expectancy of patients in a large population undergoing RDD. METHODS We analyzed 2177 RDD procedures performed in 370 patients with cancer, vasculitis, and hematological and connective tissue diseases who presented 402 reactions. A subgroup of carboplatin allergic patients with ovarian cancer treated with RDD was analyzed for costs and life expectancy and compared with a nonallergic control group. RESULTS RDD allowed all patients to receive safely the full dose of the medication to which they were reactive. A gradual increase in the fraction of outpatient desensitizations from 81% to 98% was achieved through risk stratification. Of the 2177 desensitizations, 93% had no or mild reactions whereas 7% had moderate to severe reactions, which did not preclude the completion of the treatment, and there were no deaths. Overall health costs in the carboplatin allergic group were not higher than those in the nonallergic group treated with standard of care. Administration of carboplatin through RDD was as effective as standard administration with a nonsignificant increase in life expectancy in desensitized patients as compared with nonallergic, nondesensitized controls. CONCLUSIONS RDD is cost effective and safe for allergic patients with cancer and chronic disease to remain on first line therapy.

Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis

BackgroundAllergic rhinitis is a common disease whose genetic basis is incompletely explained. We report an integrated genomic analysis of allergic rhinitis.MethodsWe performed genome wide association studies (GWAS) of allergic rhinitis in 5633 ethnically diverse North American subjects. Next, we profiled gene expression in disease-relevant tissue (peripheral blood CD4+ lymphocytes) collected from subjects who had been genotyped. We then integrated the GWAS and gene expression data using expression single nucleotide (eSNP), coexpression network, and pathway approaches to identify the biologic relevance of our GWAS.ResultsGWAS revealed ethnicity-specific findings, with 4 genome-wide significant loci among Latinos and 1 genome-wide significant locus in the GWAS meta-analysis across ethnic groups. To identify biologic context for these results, we constructed a coexpression network to define modules of genes with similar patterns of CD4+ gene expression (coexpression modules) that could serve as constructs of broader gene expression. 6 of the 22 GWAS loci with P-value ≤ 1x10−6 tagged one particular coexpression module (4.0-fold enrichment, P-value 0.0029), and this module also had the greatest enrichment (3.4-fold enrichment, P-value 2.6 × 10−24) for allergic rhinitis-associated eSNPs (genetic variants associated with both gene expression and allergic rhinitis). The integrated GWAS, coexpression network, and eSNP results therefore supported this coexpression module as an allergic rhinitis module. Pathway analysis revealed that the module was enriched for mitochondrial pathways (8.6-fold enrichment, P-value 4.5 × 10−72).ConclusionsOur results highlight mitochondrial pathways as a target for further investigation of allergic rhinitis mechanism and treatment. Our integrated approach can be applied to provide biologic context for GWAS of other diseases.

Gene‐by‐environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma

Distinct receptors likely exist for leukotriene (LT)E4, a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE4‐induced airways inflammation, and P2Y12 antagonism attenuates house dust mite‐induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied.