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BackgroundPAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma.ObjectiveWe sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level.MethodsWe studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function.ResultsThere was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P

BackgroundYounger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations.ObjectivesWe sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children.MethodsWe included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship.ResultsMaternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23-0.81).Conclusion and clinical relevanceIn contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.

Rationale: Independent replication of genetic associations in complex diseases, particularly in whole-genome association studies, is critical to confirm the association.Objectives: A whole-genome association study identified ORMDL3 as a promising candidate gene for asthma in white populations. Here, we attempted to confirm the role of ORMDL3 genetic variants in asthma in three ethnically diverse populations: Mexican, Puerto Rican, and African American.Methods: We used family-based analyses to test for association between seven candidate single-nucleotide polymorphisms (SNPs) in and around the ORMDL3 gene and asthma and related phenotypes in 701 Puerto Rican and Mexican parent-child trios. We also evaluated these seven SNPs and an additional ORMDL3 SNP in 264 African American subjects with asthma and 176 healthy control subjects.Measurements and Main Results: We found significant associations between two SNPs within ORMDL3 (rs4378650 and rs12603332) and asthma in Mexicans and African Americans (P = 0.028 and 0.001 for rs4378650 and P = 0.021 and 0.001 for rs12603332, respectively), and a trend toward association in Puerto Ricans (P = 0.076 and 0.080 for SNPs rs4378650 and rs12603332, respectively). These associations became stronger among Mexican and Puerto Rican subjects with asthma with IgE levels greater than 100 IU/ml. We did not find any association between ORMDL3 SNPs and baseline lung function or response to the bronchodilator albuterol.Conclusions: Our results confirm that the ORMDL3 locus is a risk factor for asthma in ethnically diverse populations. However, inconsistent SNP-level results suggest that further studies will be needed to determine the mechanism by which ORMDL3 predisposes to asthma. [ABSTRACT FROM AUTHOR]

Background: Puerto Ricans, an admixed population of African, European, and Native American ancestries, have the highest asthma prevalence, morbidity, and mortality rates of any United States' population. Although socioeconomic status (SES) is negatively correlated with asthma incidence in most populations, no such relationship has been identified among Puerto Ricans. We hypothesized that, in this admixed population, the association between SES and asthma may interact with genetic ancestry.Methods: We analyzed 135 Puerto Rican subjects with asthma and 156 control subjects recruited from six different recruitment centers in Puerto Rico. Individual ancestry for each subject was estimated using 44 ancestry informative markers. SES was assigned using the census tracts' median family income. Analyses of SES were based on the SES of the clinic site from which the subjects were recruited and on a subset of individuals on whom home address-based SES was available.Results: In the two (independent) analyses, we found a significant interaction between SES, ancestry, and asthma disease status. At lower SES, European ancestry was associated with increased risk of asthma, whereas African ancestry was associated with decreased risk. The opposite was true for their higher SES counterparts.Conclusions: The observed interaction may help to explain the unique pattern of risk for asthma in Puerto Ricans and the lack of association with SES observed in previous studies when not accounting for varying proportions of ancestry. [ABSTRACT FROM AUTHOR]

Background: A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. Methods: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families. Results: We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs,-810,-159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV[1] using both family-based (p = 0.0009) and cross-sectional cohort (p = 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV[1] (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP-159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity. Conclusions: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma. [ABSTRACT FROM AUTHOR]

Background: In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. Ethnic-specific differences in the response to drug treatment may contribute to differences in disease outcomes. Genetic variants at the ß[2]-adrenergic receptor (ß[2]AR) may modify asthma severity and albuterol responsiveness. We tested the association of ß[2]AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Ricans and Mexicans with asthma. Methods: We used both family-based and cross-sectional tests of association with 8 ß[2]AR single nucleotide polymorphisms in 684 Puerto Rican and Mexican families. Regression analyses were used to determine the interaction between genotype, asthma severity, and bronchodilator drug responsiveness. Results: Among Puerto Ricans with asthma, the arginine (Arg) 16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.00001-0.01). We found a strong interaction of baseline FEV[1] with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma with baseline FEV[1] < 80% of predicted, but not in those with FEV[1] > 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma. Conclusions: Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity, and bronchodilator response in Puerto Ricans and Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness. [ABSTRACT FROM AUTHOR]

In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. To determine whether ethnicity-specific differences in therapeutic response, clinical response, and/or genetic factors contribute to differences in asthma outcomes, we compared asthma-related clinical characteristics among 684 Mexican and Puerto Rican individuals with asthma recruited from San Francisco, New York City, Puerto Rico, and Mexico City. Puerto Ricans with asthma had reduced lung function, greater morbidity, and longer asthma duration than did Mexicans with asthma. Bronchodilator responsiveness, measured as percentage change from baseline FEV1, was significantly lower among Puerto Ricans with asthma than among Mexicans with asthma. Puerto Ricans with asthma had on average 7.3% (95% confidence interval [CI], 4.6 to 9.9; p < 0.001) lower bronchodilator reversibility in FEV1, higher risk of an emergency department visit in the previous year (odds ratio, 2.63; 95% CI, 1.6 to 4.3; p < 0.001), and of previous hospitalization for asthma (odds ratio, 1.94; 95% CI, 1.2 to 3.2; p = 0.009) than Mexicans. Subgroup analysis corroborated that Puerto Ricans with asthma had more severe disease than did Mexicans on the basis of lung function measurements, responsiveness to beta2-adrenergic agonists, and health care use. We conclude that Puerto Ricans with asthma respond less to albuterol than do Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and response to therapy. [ABSTRACT FROM AUTHOR]

Although integrated management and control programs implement intense control measures for adult, pupal, larval, and breeding sites during outbreaks, there is a lack of studies to understand the role of the vector egg stage in disease dynamics. This study aimed to assess the dry season quiescent Aedes aegypti and Aedes albopictus egg populations in houses and backyards in Tapachula, southern Mexico. Two hundred and fifty ovitraps were placed in 125 homes in the Las Americas neighborhood. A total of 7290 eggs were collected from 211 (84.4%) ovitraps. Only 5667 (77.7%) hatched under insectary water immersion and food supply conditions, with 4031 (71.1%) identified as Ae. aegypti , and 1636 (28.8%) as Ae . albopictus , respectively. The remaining 1623 (22.3%) did not hatch due to Delayed Hatching and/or quiescence tropical stage. Eighty-three larval containers were sampled with desiccated eggs during the dry season; most of them were described as trash waste because larvicides are only used for larger containers of 5-10 L. Evolutionary characteristics for the two species including partial egg hatching, ambient-regulated quiescence, the ability of the embryo to survive for a more extended period intra-seasonally, the egg sticking to inner container walls, demands urgent operational research to achieve successful egg-proof larval container methods.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers., Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans., Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts., Results: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics., Conclusions: Serotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Walker, Bloodworth, Kountz, McCarty, Green, Ferrie, Campbell, Averill, Beckman, Grammer, Eng, Avila, Farber, Rodriguez-Cintron, Rodriguez-Santana, Serebrisky, Thyne, Seibold, Burchard, Kumar and Cook-Mills.)

(1) Background : Localized cutaneous leishmaniasis is a neglected vector-borne disease that has become a serious public health problem in the Yucatan Peninsula. Although more than 60% of cases originate from the state of Quintana Roo, it is one of the least explored areas in terms of incriminating vectors of the Leishmania parasite. Additionally, cases of leishmaniasis have increased substantially in that region in recent years. For this reason, we explored and provided primary evidence of Leishmania DNA in sand fly species from four localities during outbreaks of leishmaniasis in Quintana Roo. We also contributed information on the regional genetic diversity of Leishmania parasites. (2) Methods : Sand flies were collected during several periods from November 2022 to April 2023 using Mosquito Light Circle and Shannon traps, as well as an active entomological search in refuges. For Leishmania detection, we amplified a fragment of 300-350 bp of the internal transcribed spacer subunit 1 (ITS-1). (3) Results: Of the 242 females collected, we detected Leishmania DNA in 25 specimens represented by Bichromomyia olmeca (1), Psathyromyia shannoni (17), Lutzomyia cruciata (4), Psathyromyia undulata (2), and Dampfomyia deleoni (1). The detection of Leishmania in these last two species represents new records for the Yucatan Peninsula and for Mexico. Leishmania ( Leishmania ) mexicana was the only species detected in the Phlebotominae species, with prevalence values that ranked between 7.41% and 33.33% from specimens collected in the sylvatic areas of Cozumel Island and Petcacab. (4) Conclusions: This study provides the first evidence of infection of Da . deleoni and Pa . undulata by L. ( L .) Mexicana . In addition, the presence of three dominant haplotypes in all the evaluated localities was evidenced using the analysis of genetic diversity, and the locality of Petcacab was the one with the circulation of two new haplotypes not previously described in Mexico or neighboring countries. These results highlight the importance of intensive epidemiological surveillance due to the dynamics of transmission of Leishmania between different species.

Background: Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses., Objective: We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis., Methods: We conducted a double-blind parallel design trial in patients with cat allergy. A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation. Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study., Results: At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUC 0-1h ] and as peak score [Peak 0-1h ] during the first hour after NAC) were significantly reduced in patients receiving tezepelumab/SCIT compared to SCIT alone. At week 104, one year after stopping treatment, the primary end point TNSS AUC 0-1h was not significantly different in the tezepelumab/SCIT group compared to SCIT alone, while TNSS Peak 0-1h was significantly lower in those receiving combination treatment versus SCIT. Transcriptomic analysis of nasal epithelial samples demonstrated that treatment with the combination of SCIT/tezepelumab, but neither monotherapy, caused persistent downregulation of a gene network related to type 2 inflammation that was associated with improvement in NAC responses., Conclusions: Inhibition of TSLP augments the efficacy of SCIT during therapy and may promote tolerance after a 1-year course of treatment. (ClinicalTrials.gov NCT02237196)., (Copyright © 2022. Published by Elsevier Inc.)

Aedes albopictus is an important vector of several arboviruses that affect human health worldwide; thus, knowledge of its distribution is a key factor for the implementation of disease control strategies. In Mexico, Ae. albopictus was recorded for the first time in 1988 in Tamaulipas State (northeast), but currently it has been recorded in 14 of the 32 states in the country. In 2012, it was recorded for the first time in a single locality in Quintana Roo (Cancún). In this study, we provide new distribution information for Ae. albopictus in the center and south of Quintana Roo State and comment on its medical importance., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

Short-acting β 2 -adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10 -9 ). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10 -8 ). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

Background: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response., Objective: We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings., Methods: A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10 -6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations., Results: A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10 -6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10 -3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10 -3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified., Conclusions and Clinical Relevance: This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment., (© 2019 John Wiley & Sons Ltd.)

Background: Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures., Objective: We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups., Methods: We included 1849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1136 Mexican Americans, and 218 other Latino children) aged 8 to 21 years from 4 urban regions in the United States. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the United States. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study), adjusting for demographic, socioenvironmental, and clinical variables., Results: For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the United States), greater levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (P = .009 and .02, respectively). Similarly, high language acculturation was associated with increased FEV 1 compared with low language acculturation (P = .02). There was insufficient evidence of heterogeneity for associations across Latino subgroups., Conclusions: Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is an important factor to consider in the management of Latino youth with asthma., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Culicidae mosquitoes are potential vectors of pathogens that affect human health. The correct species identification, as well as the discovery and description of cryptic species, is important in public health for the control and management of specific vectors. In the present study, the diversity of anthropophagous mosquitoes in Quintana Roo, at the border between Mexico and Belize, was evaluated using morphological and molecular data (COI-DNA Barcoding). A total of 1,413 adult female specimens were collected, belonging to eight genera and 31 morphospecies. Most species formed well-supported clades. Intraspecific Kimura 2 parameters (K2P) distance average was 0.75%, and a maximum distance of 4.40% was observed for Anopheles crucians s.l. ABGD method identified 28 entities, while 32 entities were identified with the BIN system. In Culex interrogator and Culex nigripalpus a low interspecific genetic distance of 0.1% was observed. One undescribed species belonging to the genus Aedes ( Aedes n. sp.) was discovered, but no clear genetic divergence was found between this species and the closely related species Aedes angustivittatus . An intraspecific K2P distance greater than 2.7% was observed in Aedes serratus (3.9%), Anopheles crucians s.l. (4.4%), Culex taeniopus (3.7%), Haemagogus equinus (3.9%), Culex erraticus (5.0%), Psorophora ferox (4.5%), and in Anopheles apicimacula (8.10%); therefore, evidences of cryptic diversity are shown in these species. This study showed that DNA barcodes offer a reliable framework for mosquito species identification in Quintana Roo, except for some closely related species for which it is recommended to use additional nuclear genetic markers such as ITS2, in order to resolve these small discrepancies., Competing Interests: None declared.

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.

In Mexico, genus Anopheles includes 27 species divided into three subgenera: Anopheles, Kerteszia, and Nyssorhynchus. Some species occur in the Nearctic region (northern Mexico), whereas other species occur in the Neotropical region (south and southeast Mexico) and only a few species occur in both regions. In Quintana Roo State (southeast Mexico) 11 species have been recorded: An. apicimacula, An. atropos, An. bradleyi, An. crucians, An. franciscanus, An. neomaculipalpus, An. pseudopunctipennis, An. punctimacula, An. veruslanei, An. vestitipennis and An. albimanus. However, the occurrence and identity of An. veruslanei has been questioned in recent years, since its description 39 years ago, it has not been reported in recent studies. In October 2015, five females of An. veruslanei were collected and identified. To corroborate their occurrence and identity in Quintana Roo State, we used morphological and molecular evidence that confirms it, and the type material of this species was studied to compare with the specimens of our collections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Secondhand smoke (SHS) exposures have been linked to asthma-related outcomes but quantitative dose-responses using biomarkers of exposure have not been widely reported., Objectives: Assess dose-response relationships between plasma cotinine-determined SHS exposure and asthma outcomes in minority children, a vulnerable population exposed to higher levels of SHS and under-represented in the literature., Methods: We performed analyses in 1172 Latino and African-American children with asthma from the mainland USA and Puerto Rico. We used logistic regression to assess relationships of cotinine levels ≥0.05 ng/mL with asthma exacerbations (defined as asthma-related hospitalisations, emergency room visits or oral steroid prescription) in the previous year and asthma control. The shape of dose-response relationships was assessed using a continuous exposure variable in generalised additive logistic models with penalised splines., Results: The OR for experiencing asthma exacerbations in the previous year for cotinine levels ≥0.05 ng/mL, compared with <0.05 ng/mL, was 1.40 (95% CI 1.03 to 1.89), while the OR for poor asthma control was 1.53 (95% CI 1.12 to 2.13). Analyses for dose-response relationships indicated increasing odds of asthma outcomes related with increasing exposure, even at cotinine levels associated with light SHS exposures., Conclusions: Exposure to SHS was associated with higher odds of asthma exacerbations and having poorly controlled asthma with an increasing dose-response even at low levels of exposure. Our results support the conclusion that there are no safe levels of SHS exposures., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective : Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined. The objective of this study is to externally validate the computable phenotype across diverse Chicago institutions to accurately identify pediatric and adult patients with asthma. Methods : A cohort of 900 asthma and control patients was identified from the electronic health record between January 1, 2012 and November 30, 2014. Two physicians at each site independently reviewed the patient chart to annotate cases. Results : The inter-observer reliability between the physician reviewers had a κ-coefficient of 0.95 (95% CI 0.93-0.97). The accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the computable phenotype were all above 94% in the full cohort. Conclusions : The excellent positive and negative predictive values in this multi-center external validation study establish a useful tool to identify asthma cases in in the electronic health record for research and care. This computable phenotype could be used in large-scale comparative-effectiveness trials.

Rationale: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response., Objectives: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children., Methods: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR., Measurements and Main Results: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 × 10 -7 ) and suggestive (P < 7.06 × 10 -6 ) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings., Conclusions: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.

Background: Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment., Objectives: We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma., Methods: Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment., Results: The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome., Conclusion: Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: We have previously shown that oncostatin M (OSM) levels are increased in nasal polyps (NPs) of patients with chronic rhinosinusitis (CRS), as well as in bronchoalveolar lavage fluid, after segmental allergen challenge in allergic asthmatic patients. We also showed in vitro that physiologic levels of OSM impair barrier function in differentiated airway epithelium., Objective: We sought to determine which hematopoietic or resident cell type or types were the source of the OSM expressed in patients with mucosal airways disease., Methods: Paraffin-embedded NP sections were stained with fluorescence-labeled specific antibodies against OSM, GM-CSF, and hematopoietic cell-specific markers. Live cells were isolated from NPs and matched blood samples for flow cytometric analysis. Neutrophils were isolated from whole blood and cultured with the known OSM inducers GM-CSF and follistatin-like 1, and OSM levels were measured in the supernatants. Bronchial biopsy sections from control subjects, patients with moderate asthma, and patients with severe asthma were stained for OSM and neutrophil elastase., Results: OSM staining was observed in NPs, showed colocalization with neutrophil elastase (n = 10), and did not colocalize with markers for eosinophils, macrophages, T cells, or B cells (n = 3-5). Flow cytometric analysis of NPs (n = 9) showed that 5.1% ± 2% of CD45 + cells were OSM + , and of the OSM + cells, 56% ± 7% were CD16 + Siglec-8 - , indicating neutrophil lineage. Only 0.6 ± 0.4% of CD45 + events from matched blood samples (n = 5) were OSM + , suggesting that increased OSM levels in patients with CRS was locally stimulated and produced. A majority of OSM + neutrophils expressed arginase 1 (72.5% ± 12%), suggesting an N2 phenotype. GM-CSF levels were increased in NPs compared with those in control tissue and were sufficient to induce OSM production (P < .001) in peripheral blood neutrophils in vitro. OSM + neutrophils were also observed at increased levels in biopsy specimens from patients with severe asthma. Additionally, OSM protein levels were increased in induced sputum from asthmatic patients compared with that from control subjects (P < .05)., Conclusions: Neutrophils are a major source of OSM-producing cells in patients with CRS and severe asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma disproportionately affects minority populations and is associated with psychosocial stress such as racial/ethnic discrimination. We aimed to examine the association of perceived discrimination with asthma and poor asthma control in African American and Latino youth., Methods: We included African American (n = 954), Mexican American (n = 1,086), other Latino (n = 522), and Puerto Rican Islander (n = 1,025) youth aged 8 to 21 years from the Genes-Environments and Admixture in Latino Americans study and the Study of African Americans, Asthma, Genes, and Environments. Asthma was defined by physician diagnosis, and asthma control was defined based on the National Heart, Lung, and Blood Institute guidelines. Perceived racial/ethnic discrimination was assessed by the Experiences of Discrimination questionnaire, with a focus on school, medical, and public settings. We examined the associations of perceived discrimination with each outcome and whether socioeconomic status (SES) and global African ancestry modified these associations., Results: African American children reporting any discrimination had a 78% greater odds of experiencing asthma (OR, 1.78; 95% CI, 1.33-2.39) than did those not reporting discrimination. Similarly, African American children faced increased odds of poor asthma control with any experience of discrimination (OR, 1.97; 95% CI, 1.42-2.76) over their counterparts not reporting discrimination. These associations were not observed among Latino children. We observed heterogeneity of the association between reports of discrimination and asthma according to SES, with reports of discrimination increasing the odds of having asthma among low-SES Mexican American youth (interaction P = .01) and among high-SES other Latino youth (interaction P = .04)., Conclusions: Perceived discrimination is associated with increased odds of asthma and poorer control among African American youth. SES exacerbates the effect of perceived discrimination on having asthma among Mexican American and other Latino youth., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Skin pigmentation is a complex trait that varies largely among populations. Most genome-wide association studies of this trait have been performed in Europeans and Asians. We aimed to uncover genes influencing skin colour in African-admixed individuals. We performed a genome-wide association study of melanin levels in 285 Hispanic/Latino individuals from Puerto Rico, analyzing 14 million genetic variants. A total of 82 variants with p-value ≤1 × 10 -5 were followed up in 373 African Americans. Fourteen single nucleotide polymorphisms were replicated, of which nine were associated with skin colour at genome-wide significance in a meta-analysis across the two studies. These results validated the association of two previously known skin pigmentation genes, SLC24A5 (minimum p = 2.62 × 10 -14 , rs1426654) and SLC45A2 (minimum p = 9.71 × 10 -10 , rs16891982), and revealed the intergenic region of BEND7 and PRPF18 as a novel locus associated with this trait (minimum p = 4.58 × 10 -9 , rs6602666). The most significant variant within this region is common among African-descent populations but not among Europeans or Native Americans. Our findings support the advantages of analyzing African-admixed populations to discover new genes influencing skin pigmentation.

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10 -64 ) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation., Competing Interests: The authors declare that no competing interests exist.

The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry., Competing Interests: Nadia N. Hansel has a consulting relationship with GSK (Advisory Board). All other authors declare no competing financial interests.

Background: Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk., Methods: We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function., Results: RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted., Conclusions: A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking., Objectives: To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry., Methods: The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry., Measurements and Main Results: A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function., Conclusions: Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

Rationale: Restoration of vitamin D sufficiency may reduce asthma exacerbations, events that are often associated with respiratory tract infections and cold symptoms., Objectives: To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency., Methods: Colds were assessed in the AsthmaNet VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness) trial, in which 408 adult patients were randomized to receive placebo or cholecalciferol (100,000 IU load plus 4,000 IU/d) for 28 weeks as add-on therapy. The primary outcome was cold symptom severity, which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey., Measurements and Main Results: A total of 203 participants experienced at least one cold. Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml (95% confidence interval [CI], 40.1-43.7 ng/ml) by 12 weeks, vitamin D supplementation had no effect on the primary outcome: the average peak WURSS-21 scores (62.0 [95% CI, 55.1-68.9; placebo] and 58.7 [95% CI, 52.4-65.0; vitamin D]; P = 0.39). The rate of colds did not differ between groups (rate ratio [RR], 1.2; 95% CI, 0.9-1.5); however, among African Americans, those receiving vitamin D versus placebo had an increased rate of colds (RR, 1.7; 95% CI, 1.1-2.7; P = 0.02). This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency, regardless of treatment assignment (RR, 1.4; 95% CI, 1.1-1.7; P = 0.009)., Conclusions: Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency.

Background: Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown cause characterized by sinonasal inflammation, increased mucus production, and defective mucociliary clearance. Expression of Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance., Objectives: We sought to investigate the expression of pendrin and the mucus-related protein Muc5AC in sinonasal tissues of control subjects and patients with CRS and to evaluate the regulation of pendrin expression in nasal epithelial cells (NECs) in vitro., Methods: The expression and distribution of pendrin in sinonasal tissues was analyzed by using real-time PCR, immunoblot analysis, and immunohistochemistry. Differentiated NECs were used to study the regulation of pendrin expression., Results: Increased pendrin expression was observed in nasal polyp (NP) tissue of patients with CRS. Immunohistochemistry analysis revealed that pendrin was largely restricted to the epithelial layer. Pendrin expression significantly correlated with inflammatory cell markers, suggesting that the factors made by these cells might induce pendrin expression. Furthermore, both pendrin and periostin levels (a biomarker in asthma) correlated with IL-13 levels, suggesting that pendrin can be induced by this cytokine in sinonasal tissues. Expression of the mucus component protein Muc5AC correlated weakly with pendrin expression, indicating that pendrin might modulate mucus production in NPs. In cultured NECs pendrin expression was induced by TH2 cytokines and induced synergistically when TH2 cytokines were combined with IL-17A. Interestingly, human rhinovirus had a potentiating effect on IL-13-induced pendrin expression. Dexamethasone suppressed pendrin expression, suggesting that the therapeutic benefit of dexamethasone in asthmatic patients and those with CRS might involve regulation of pendrin expression., Conclusions: TH2-mediated pendrin expression is increased in NPs of patients with CRS and might lead to increased inflammation, mucus production, and decreased mucociliary clearance., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) is a common condition encountered in primary care medicine and is estimated to affect 12.5% of the United States population. This study aims to compare methods of assessing health utility in CRS., Methods: A cross-sectional sample of CRS patients (n = 137) were interviewed using direct health utility assessment measures: the visual analogue scale (VAS), time trade-off (TTO), and standard gamble (SG). General quality of life (QOL) scores were obtained via the 36-item Short Form Health Survey (SF-36) and converted to SF-6D health utility values using a Bayesian algorithm. Disease-specific QOL was measured with the 22-item Sino-Nasal Outcome Test (SNOT-22). A selected subgroup of patients (n = 51) not initiating surgery or new treatment for CRS were re-interviewed within 3 weeks., Results: The mean ± SD health utilities were VAS 0.69 ± 0.19; TTO 0.80 ± 0.27; SG 0.93 ± 0.11; and SF-6D 0.72 ± 0.12; they differed significantly (p < 0.001). Only VAS scores differed based on disease state classification or the presence of nasal polyposis. Correlations between methods of determining health utility were weak, but significant. VAS, TTO, and SF-6D scores were significantly associated with SNOT-22 (p < 0.001 for all); however, SG and SNOT-22 were poorly correlated (Spearman correlation = -0.33). The test-retest reliability of TTO (Spearman correlation = 0.71) and SG (0.73) was strong., Conclusion: CRS patients show significant impairment in QOL, with health utility values similar to those of patients with acquired immune deficiency syndrome (AIDS) or intermittent claudication using similar methods. The method of ascertainment significantly affects measured health utility, but the degree of impairment warrants improved recognition and appropriate treatment of the condition., (© 2015 ARS-AAOA, LLC.)

Purpose of Review: In this review, we summarize the latest publications on the genetic and environmental determinants of allergic rhinitis., Recent Findings: Recent advances in genetic technology and bioinformatics have enabled simultaneous unbiased analysis of the entire genome regarding DNA sequence variants, epigenetic modifications and gene expression, providing functional correlates for DNA variants and phenotypes. As a result, new genes of mitochondrial and B-lymphocyte metabolism have been associated with allergic rhinitis phenotypes. Epidemiological studies recently showed an increased risk to develop allergic rhinitis in all age groups with reduction in farm exposure and in children with few older siblings. Climate changes seem to have also influenced pollen exposure and pollen-induced allergic disease. Lastly, occupational rhinitis has been increasingly recognized as a large burden to society., Summary: In summary, new high throughput genetics research technologies have pointed to new previously unsuspected pathways that may modulate the risk of developing allergic rhinitis such as mitochondrial metabolism. In addition, recent environmental factors found to influence the risk of developing allergic rhinitis include exposure to farm, pollution, occupational agents, and changes in climate.

Background: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders., Objective: We sought to identify genetic variants associated with IgE levels in Latinos., Methods: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies., Results: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 × 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 × 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 × 10(-6)) and replicated in non-African American samples (P = .011)., Conclusion: We confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Obesity is associated with poor asthma control, increased asthma morbidity, and decreased response to inhaled corticosteroids. We hypothesized that obesity would be associated with decreased bronchodilator responsiveness in children and adolescents with asthma. In addition, we hypothesized that subjects who were obese and unresponsive to bronchodilator would have worse asthma control and would require more asthma controller medications., Methods: In the Study of African Americans, Asthma, Genes, and Environments (SAGE II) and the Genes-environments and Admixture in Latino Americans (GALA II) study, two identical, parallel, case-control studies of asthma, we examined the association between obesity and bronchodilator response in 2,963 black and Latino subjects enrolled from 2008 to 2013 using multivariable logistic regression. Using bronchodilator responsiveness, we compared asthma symptoms, controller medication usage, and asthma exacerbations between nonobese (< 95th% BMI) and obese (≥ 95th% BMI) subjects., Results: The odds of being bronchodilator unresponsive were 24% (OR, 1.24; 95% CI, 1.03-1.49) higher among obese children and adolescents compared with their not obese counterparts after adjustment for age, race/ethnicity, sex, recruitment site, baseline lung function (FEV1/FVC), and controller medication. Bronchodilator-unresponsive obese subjects were more likely to report wheezing (OR, 1.38; 95% CI, 1.13-1.70), being awakened at night (OR, 1.34; 95% CI, 1.09-1.65), using leukotriene receptor inhibitors (OR, 1.33; 95% CI, 1.05-1.70), and using inhaled corticosteroid with long-acting β2-agonist (OR, 1.37; 95% CI, 1.05-1.78) than were their nonobese counterpart. These associations were not seen in the bronchodilator-responsive group., Conclusions: Obesity is associated with bronchodilator unresponsiveness among black and Latino children and adolescents with asthma. The findings on obesity and bronchodilator unresponsiveness represent a unique opportunity to identify factors affecting asthma control in blacks and Latinos.

Background: Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest., Objective: To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children., Methods: We analyzed 5493 Latinos with and without asthma from 3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry., Results: Native American ancestry was associated with lower odds of asthma (OR = 0.72, 95% CI: 0.66-0.78, P = 8.0 × 10(-15)), while African ancestry was associated with higher odds of asthma (OR = 1.40, 95% CI: 1.14-1.72, P = .001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of FEV1 (-77 ± 19 mL; P = 5.8 × 10(-5) and -83 ± 19 mL; P = 1.1 x 10(-5), respectively) and forced vital capacity (-100 ± 21 mL; P = 2.7 × 10(-6) and -107 ± 22 mL; P = 1.0 x 10(-6), respectively)., Conclusion: Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Asthma occurs as complex interactions of the environmental and genetics. Clinical studies and animal models of asthma indicate dietary factors such as vitamin E and vitamin D as protective for asthma risk. In this review, we discuss opposing regulatory functions of tocopherol isoforms of vitamin E and regulatory functions of vitamin D in asthma and how the variation in global prevalence of asthma may be explained, at least in part, by these dietary components., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Children who begin wheezing during early childhood are frequently seen by health care providers in primary care, in hospitals, and in emergency departments, and by allergists and pulmonologists. When a young child, such as the 2 year-old patient presented here, is evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors that influence prognosis are not mutually exclusive, are interrelated (ie, cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent., Objective: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping., Methods: Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci., Results: We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies., Conclusions: Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21., (Published by Mosby, Inc.)

Background: Mechanisms underlying the development of virus-induced asthma exacerbations remain unclear. To investigate if epigenetic mechanisms could be involved in virus-induced asthma exacerbations, we undertook DNA methylation profiling in asthmatic and healthy nasal epithelial cells (NECs) during Human Rhinovirus (HRV) infection in vitro., Methods: Global and loci-specific methylation profiles were determined via Alu element and Infinium Human Methylation 450 K microarray, respectively. Principal components analysis identified the genomic loci influenced the most by disease-status and infection. Real-time PCR and pyrosequencing were used to confirm gene expression and DNA methylation, respectively., Results: HRV infection significantly increased global DNA methylation in cells from asthmatic subjects only (43.6% to 44.1%, p = 0.04). Microarray analysis revealed 389 differentially methylated loci either based on disease status, or caused by virus infection. There were disease-associated DNA methylation patterns that were not affected by HRV infection as well as HRV-induced DNA methylation changes that were unique to each group. A common methylation locus stood out in response to HRV infection in both groups, where the small nucleolar RNA, H/ACA box 12 (SNORA12) is located. Further analysis indicated that a relationship existed between SNORA12 DNA methylation and gene expression in response to HRV infection., Conclusions: We describe for the first time that Human rhinovirus infection causes DNA methylation changes in airway epithelial cells that differ between asthmatic and healthy subjects. These epigenetic differences may possibly explain the mechanism by which respiratory viruses cause asthma exacerbations.