Air Pollution and Childhood Respiratory Allergies in the United States

BackgroundChildhood respiratory allergies, which contribute to missed school days and other activity limitations, have increased in recent years, possibly due to environmental factors.ObjectiveIn this study we examined whether air pollutants are associated with childhood respiratory allergies in the United States.MethodsFor the approximately 70,000 children from the 1999-2005 National Health Interview Survey eligible for this study, we assigned between 40,000 and 60,000 ambient pollution monitoring data from the U.S. Environmental Protection Agency, depending on the pollutant. We used monitors within 20 miles of the child's residential block group. We used logistic regression models, fit with methods for complex surveys, to examine the associations between the reporting of respiratory allergy or hay fever and annual average exposure to particulate matter < or = 2.5 microm in diameter (PM2.5), PM < or = 10 microm in diameter, sulfur dioxide, and nitrogen dioxide and summer exposure to ozone, controlling for demographic and geographic factors.ResultsIncreased respiratory allergy/hay fever was associated with increased summer O3 levels [adjusted odds ratio (AOR) per 10 ppb = 1.20; 95% confidence interval (CI), 1.15-1.26] and increased PM2.5 (AOR per 10 microg/m3 = 1.23; 95% CI, 1.10-1.38). These associations persisted after stratification by urban-rural status, inclusion of multiple pollutants, and definition of exposures by differing exposure radii. No associations between the other pollutants and the reporting respiratory allergy/hay fever were apparent.ConclusionsThese results provide evidence of adverse health for children living in areas with chronic exposure to higher levels of O3 and PM2.5 compared with children with lower exposures

Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma

Identification of KIF3A as a Novel Candidate Gene for Childhood Asthma Using RNA Expression and Population Allelic Frequencies Differences

Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach.Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes

Linkage of the US National Health Interview Survey to air monitoring data: An evaluation of different strategies

The goal of this study is to describe linkages between the National Health Interview Survey (NHIS) and Environmental Protection Agency (EPA) air monitoring data, specifically how the linkage method affects characteristics and exposure estimates of study samples and estimated associations between exposure and health. In the USA, nationally representative health data are collected in the NHIS and annual air quality data are collected by the EPA. The linkage of these data for research is not straightforward and the choices made may introduce bias into results. The 2000–2003 NHIS and air quality data for six air pollutants were linked by residential block group and monitor location, which differ by pollutants. For each pollutant, three annual exposure variables were assigned to respondents: (1) average of all monitors in the county, (2) of monitors within a 5-mile radius of the distance between block group and monitor, and (3) within a 20-mile radius. Exposure estimates, study sample characteristics, and association between fine particle exposure and respondent-reported health status were compared for different geographic linkage methods. The results showed that study sample characteristics varied by geographic linkage method and pollutant linked. Generally, the fewer the NHIS respondents linked, the higher is the pollution exposure and lower is the percentage of non-Hispanic whites. After adjustment for sociodemographic and geographic factors, associations between fine particles and health status were generally comparable across study samples. Because exposure information is not available for all potential participants in an epidemiological study, selection effects should be considered when drawing inferences about air quality–health associations. With the current monitoring data system, the study sample is substantially reduced when linkage to multiple pollutants is performed

Influenza Vaccination Among US Children With Asthma, 2005–2013

BACKGROUND: Children with asthma face higher risk of complications from influenza. Trends in influenza vaccination among children with asthma are unknown. METHODS: We used 2005-2013 National Health Interview Survey data for children 2 to 17 years of age. We assessed, separately for children with and without asthma, any vaccination (received August through May) during each of the 2005-2006 through 2012-2013 influenza seasons and, for the 2010-2011 through 2012-2013 seasons only, early vaccination (received August through October). We used April-July interviews each year (n = 31,668) to assess vaccination during the previous influenza season. Predictive margins from logistic regression with time as the independent and vaccination status as the dependent variable were used to assess time trends. We also estimated the association between several sociodemographic variables and the likelihood of influenza vaccination. RESULTS: From 2005 to 2013, among children with asthma, influenza vaccination receipt increased about 3 percentage points per year (P \u3c .001), reaching 55% in 2012-2013. The percentage of all children with asthma vaccinated by October (early vaccination) was slightly above 30% in 2012-2013. In 2010-2013, adolescents, the uninsured, children of parents with some college education, and those living in the Midwest, South, and West were less likely to be vaccinated. CONCLUSIONS: The percentage of children 2 to 17 years of age with asthma receiving influenza vaccination has increased since 2004-2005, reaching approximately 55% in 2012-2013