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Objective: This work endeavored to examine the correlation between dietary choline intake and the odds of asthma, utilizing data from the National Health and Nutrition Examination Survey (NHANES). Methods: Aggregated data from seven cycles (2005–2018) in the NHANES database were utilized. The independent variable was dietary choline intake, and the dependent variable was asthma. The weighted logistic regression method was used to construct a model reflecting the relationship between these two factors. This work employed stratified analysis without adjusting for confounding factors and subgroup analysis with adjusted confounding factors to mine the association between dietary choline intake and asthma. Additionally, restricted cubic spline analysis examined nonlinear associations of the two in age subgroups. Results: Forty five thousand and seven hundreds ninety seven samples were included here. The model indicating the relationship between dietary choline intake and asthma was constructed (OR: 0.86, 95% CI: 0.79–0.93, p < 0.001). Stratified analysis indicated that the interaction terms of age (p < 0.001) and body mass index (BMI) (p = 0.002) with dietary choline intake significantly influenced the relationship model. In the adjusted models, accounting for demographic characteristics, poverty impact ratio, BMI, exposure to environmental tobacco smoke, and total energy intake, an increase in dietary choline intake significantly reduced the odds of asthma (OR: 0.79, 95% CI: 0.72–0.88, p < 0.001). Subgroup analyses based on age and BMI revealed a significant negative correlation between dietary choline intake and the odds of asthma in the adult population (OR: 0.76, 95% CI: 0.67–0.86, p < 0.001), as well as in individuals with a BMI between 25 and 30 kg/m2 (OR: 0.79, 95% CI: 0.63–0.99, p = 0.042), and those with a BMI >30 kg/m2 (OR: 0.73, 95% CI: 0.60–0.89, p = 0.002). Conclusion: Dietary choline intake was significantly inversely correlated with asthma prevalence, especially in adults and overweight/obese individuals, suggesting that increasing choline intake may reduce asthma risk. Further research is needed to explore this relationship and provide tailored dietary recommendations for different age and BMI groups to enhance asthma prevention and management. [ABSTRACT FROM AUTHOR]

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (p = 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a great risk factor for developing asthma, and its pathogenesis is affected by various factors, such as gene and environment. GSDMB is related to allergic diseases. Our purpose is to explore the correlation of single nucleotide polymorphisms (SNPs) in GSDMB and AR risk in the Chinese population. We performed a case-control study including 1005 cases and 1004 controls. Rs2305479, rs4795400, and rs12450091 in GSDMB were geneotyped using Agena MassARRAY. The relationships between GSDMB SNPs and AR risk were assessed by logistic regression analysis in PLINK1.9. Our study showed that rs4795400 was a protective factor for AR in overall (TT vs. CC: OR = 0.66, p = 0.009; TT vs. CC/TC: OR = 0.67, p = 0.008; additive: OR = 0.87, p = 0.042 males, people with BMI ≤ 24, and living in wind-blown sand area. Rs2305479 was associated with a reduced AR risk in males (TT vs. CC: OR = 0.47, p = 0.014; TT vs. CC/TC: OR = 0.43, p = 0.004). However, rs12450091 was a risk factor for AR in people living in the loess hilly region (CC: OR = 4.75, p = 0.047). The levels of EO and EO_per in the case group were significantly higher than those in the control group (p < 0.05). This study indicated that GSDMB polymorphisms (rs4795400, rs2305479, and rs12450091) were associated with AR susceptibility. Further studies are required to confirm our findings and to clarify the functional relationship. [ABSTRACT FROM AUTHOR]

Aim: This study investigated febrile children with petechial rashes who presented to European emergency departments (EDs) and investigated the role that mechanical causes played in diagnoses. Methods: Consecutive patients with fever presenting to EDs in 11 European emergency departments in 2017–2018 were enrolled. The cause and focus of infection were identified and a detailed analysis was performed on children with petechial rashes. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: We found that 453/34010 (1.3%) febrile children had petechial rashes. The focus of the infection included sepsis (10/453, 2.2%) and meningitis (14/453, 3.1%). Children with a petechial rash were more likely than other febrile children to have sepsis or meningitis (OR 8.5, 95% CI 5.3–13.1) and bacterial infections (OR 1.4, 95% CI 1.0–1.8) as well as need for immediate life‐saving interventions (OR 6.6, 95% CI 4.4–9.5) and intensive care unit admissions (OR 6.5, 95% CI 3.0–12.5). Conclusion: The combination of fever and petechial rash is still an important warning sign for childhood sepsis and meningitis. Ruling out coughing and/or vomiting was insufficient to safely identify low‐risk patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the joint effect of neighborhood disadvantages on asthma prevalence and evaluate whether individual-level variables protect residents against neighborhood disadvantages. Data from the Chicago Multiethnic Prevention and Surveillance Study (from 2013–2020) were analyzed. Eight neighborhood characteristics were measured using the Chicago Health Atlas, including neighborhood unsafety, limited access to healthy food, neighborhood alienation, severe rent burden, vacant housing, single-parent household, neighborhood poverty, and unemployment. A structured questionnaire measured asthma diagnosis (childhood or adulthood) and individual-level variables including sex, age, income, education, and race. Weighted quantile sum (WQS) regression was used to evaluate the impact of neighborhood disadvantages. Stratified analysis was performed by income and education. A total of 6,592 participants (mean age = 53.5 (standard deviation, 11.1) years) were included. Most of the study population were non-Hispanic Black (82.5%) and reported an annual household income less than $15,000 (53%). Asthma prevalence was 23.6%. The WQS index, which represents the overall neighborhood disadvantages, was associated with asthma prevalence (odds ratio = 1.14, 95% confidence interval: 1.07, 1.22) when adjusted for individual-level confounders. Neighborhood poverty contributed 40.8% to the overall impact, followed by vacant housing (23.1%) and neighborhood alienation (22.9%). When stratified by individual-level income or education, no difference was observed for the association between WQS index and asthma prevalence. [ABSTRACT FROM AUTHOR]

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; β = 0.12, 95% CI = 0.06–0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure. Author summary: Lung function is determined by both genetic and environmental factors. Impairment of lung function can result from harmful environmental exposures in early life, which disproportionally affect children living in low-income, urban communities. However, most genetic association studies of lung function have been performed in adults and without regard for socioeconomic status. Therefore, genetic risk factors discovered to date may not reflect those most relevant to high-risk populations. In this study, we sought to identify genetic variants correlated with lung function in a multiethnic cohort of children living in low-income, urban neighborhoods and analyze how tobacco smoke exposure may influence any genetic effects. We discovered a common genetic variant associated with lower lung function in this population, and we found that the association was mediated by nearby epigenetic changes in DNA methylation, which were in turn correlated with smoking exposure. We then identified a nearby gene, PPP1R13B, which is known to aid in the deactivation of damaged cells, whose expression in airway cells aligned with these genetic and epigenetic effects. This study reveals a potential mechanism through which genetic risk and environmental exposures can affect airway development, perhaps leading to interventions that can help reduce the burden of asthma in socioeconomically disadvantaged children. [ABSTRACT FROM AUTHOR]

Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother–child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother–child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76–1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring. [ABSTRACT FROM AUTHOR]

Rationale: Chronic respiratory diseases, the third leading cause of death worldwide, have been associated with significant morbidity, mortality, and increased economic burden that make a profound impact on individuals and communities. However, limited research has delineated complex relationships between specific sociodemographic disparities and chronic respiratory disease outcomes among U.S. counties. Objectives: To assess the association of county-level sociodemographic vulnerabilities with chronic respiratory disease mortality in the United States. Methods: Chronic respiratory disease mortality data among U.S. counties for 2014-2018 was obtained from the CDC WONDER (Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research) database. The social vulnerability index (SVI), including subindices of socioeconomic status, household composition and disability, minority status and language, and housing type and transportation, is a composite, percentilebased measure developed by the CDC to evaluate county-level sociodemographic vulnerabilities to disasters. We examined countylevel sociodemographic characteristics from the SVI and classified the percentile rank into quartiles, with a higher quartile indicating greater vulnerability. The associations between chronic respiratory disease mortality and overall SVI, its four subindices, and each county characteristic were analyzed by negative binomial regression. Results: From 2014 to 2018, the age-adjusted mortality per 1,000,000 population attributed to chronic lower respiratory disease was 406.4 (95% confidence interval [CI], 405.5-407.3); chronic obstructive pulmonary disease (COPD), 393.7 (392.8-394.6); asthma, 10.0 (9.9-10.2); interstitial lung disease (ILD), 50.5 (50.1-50.8); idiopathic pulmonary fibrosis (IPF), 37.0 (36.7-37.3); and sarcoidosis, 5.3 (5.2-5.4). Counties in the higher quartile of overall SVI were significantly associated with greater disease mortality (chronic lower respiratory disease, incidence rate ratios: fourth vs. first quartile, 1.43 [95% CI, 1.39-1.48]; COPD, 1.44 [1.39-1.49]; asthma, 2.06 [1.71-2.48]; ILD, 1.07 [1.02-1.13]; IPF, 1.14 [1.06-1.22]; sarcoidosis, 2.01 [1.44-2.81]). In addition, higher mortality was also found in counties in the higher quartile of each subindex and most sociodemographic characteristics. Conclusions: Chronic respiratory disease mortalities were significantly associated with county-level sociodemographic determinants as measured by the SVI in the United States. These findings suggested sociodemographic determinants may add a considerable barrier to establishing health equity. Multidegree public health strategies and clinical interventions addressing inequitable outcomes of chronic respiratory disease should be developed and targeted in areas with greater social vulnerability and disadvantage. [ABSTRACT FROM AUTHOR]

Few studies have compared the prevalence of asthma in urban and rural settings or explored the issue of whether these two manifestations of the disease may represent different phenotypes. The aim of this study was: (a) to establish whether the prevalence of asthma differs between rural and urban settings, and b) to identify differences in the clinical presentation of asthma in these two environments. Descriptive epidemiological study involving individuals aged 18 or over from a rural (n = 516) and an urban population (n = 522). In the first phase, individuals were contacted by letter in order to organize the administration of a first validated questionnaire (Q1) designed to establish the possible prevalence of bronchial asthma. In the second phase, patients who had presented association patterns in the set of variables related to asthma in Q1 completed a second validated questionnaire (Q2), designed to identify the characteristics of asthma. According to Q1, the prevalence of asthma was 15% (n = 78) and 11% (n = 59) in rural and urban populations respectively. Sixty-five individuals with asthma from the rural population and all 59 individuals from the urban population were contacted and administered the Q2. Thirty-seven per cent of the individuals surveyed had previously been diagnosed with bronchial asthma (35% in the rural population and 40% in the urban setting). In the urban asthmatic population there was a predominance of women, a greater personal history of allergic rhinitis and a family history of allergic rhinitis and/or eczema. Asthma was diagnosed in adulthood in 74.8% of the patients, with no significant differences between the two populations. Regarding symptoms, cough (morning, daytime and night) and expectoration were more frequent in the urban population. The prevalence of asthma does not differ between urban and rural settings. The differences in exposure that characterize each environment may lead to different manifestations of the disease and may also affect its severity. [ABSTRACT FROM AUTHOR]

The effect of air pollution on the lung function of adults with asthma remains unclear to date. This study followed 112 patients with asthma at 3-month intervals for 2 years. The pollutant exposure of the participants was estimated using the inverse distance weight method. The participants were divided into three groups according to their lung function level at every visit. A linear mixed-effect model was applied to predict the change in lung function with each unit change in pollution concentration. Exposure to carbon monoxide (CO) and particles less than 2.5 micrometers in diameter (PM2.5) was negatively associated with large airway function in participants. In the severe group, exposure to chronic sulfur dioxide (SO2) was negatively associated with post-bronchodilator forced expiratory flow at 50%, between 25% and 75% of vital capacity % predicted (change of 95% CI per unit: −0.34 (−0.55, −0.12), −0.24 (−0.44, −0.03), respectively). In the mild group, the effect of SO2 on the small airways was similar to that in the severe group, and it was negatively associated with large airway function. Exposure to CO and PM2.5 was negatively associated with the large airway function of adults with asthma. The negative effects of SO2 were more evident and widely observed in adults with severe and mild asthma than in adults with moderate asthma. Patients with asthma react differently to air pollutants as evidenced by their lung function levels. [ABSTRACT FROM AUTHOR]

Gustatory cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animal's health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFPs) from healthy rats and rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in 7 to 12 Hz LFP power at approximately 12 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness—a result reflecting the collapse of responses toward a simple "good-bad" code visible in the entire sample, but focused on a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness' impact on consumption. Sickness is an internal state that impacts consumption, and so could be expected to influence the neural processing of tastes. This study shows that onset of illness changes basic properties of gustatory cortical network processing and taste responses, such that activity comes more purely to reflect the "goodness" or "badness" of tastes. [ABSTRACT FROM AUTHOR]

Variability in response to short-acting β2-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities. We sought to identify genetic variants associated with bronchodilator response (BDR) to identify potential mechanisms of drug response and risk factors for worse asthma outcomes. Genome-wide association studies of bronchodilator response (BDR) were performed using TOPMed Whole Genome Sequencing data of the Asthma Translational Genomic Collaboration (ATGC), which corresponded to 1136 Puerto Rican, 656 Mexican and 4337 African American patients with asthma. With the population-specific GWAS results, a trans-ethnic meta-analysis was performed to identify BDR-associated variants shared across the three populations. Replication analysis was carried out in three pediatric asthma cohorts, including CAMP (Childhood Asthma Management Program; n = 560), GACRS (Genetics of Asthma in Costa Rica Study; n = 967) and HPR (Hartford-Puerto Rico; n = 417). A genome-wide significant locus (rs35661809; P = 3.61 × 10–8) in LINC02220, a non-coding RNA gene, was identified in Puerto Ricans. While this region was devoid of protein-coding genes, capture Hi-C data showed a distal interaction with the promoter of the DNAH5 gene in lung tissue. In replication analysis, the GACRS cohort yielded a nominal association (1-tailed P < 0.05). No genetic variant was associated with BDR at the genome-wide significant threshold in Mexicans and African Americans. Our findings help inform genetic underpinnings of BDR for understudied minority patients with asthma, but the limited availability of genetic data for racial/ethnic minority children with asthma remains a paramount challenge. [ABSTRACT FROM AUTHOR]

Rationale: Outdoor air pollution causes emergency department visits and hospitalizations for childhood asthma. In the United States, the Air Quality Index (AQI) alerts the public to air quality and provides behavioral recommendations to reduce exposure and harm, yet little is known about the relationship between the AQI and childhood asthma exacerbations. Objectives: To test for association between the AQI and childhood asthma exacerbations resulting in emergency department visits and hospitalizations. Methods: This was a retrospective time-stratified case-crossover study, conducted using medical records data from 2010 through 2018 for children aged 6-17 years with a primary diagnosis of an asthma exacerbation (defined as an emergency department visit or hospitalization for asthma) at UPMC Children's Hospital of Pittsburgh. Daily AQI data was obtained for Allegheny County, Pennsylvania from the Environmental Protection Agency. Conditional logistic regression was used for analyses of the AQI (as both a continuous and categorical variable) and asthma exacerbations. Stratified analyses were conducted to explore modification of the AQI effects on asthma exacerbations by race and other covariates. Results: There were 6,573 events. Particulate matter <2.5 μm (PM2.5) was the primary pollutant responsible for the AQI, followed by ozone (62% and 29% of days with events, respectively). The overall AQI was associated with asthma exacerbations (e.g., as continuous, per 10-unit increase, Lag Day 2: odds ratio [OR], 1.014; 95% confidence interval [CI], 1.003-1.025; Lag Day 3: OR, 1.012; 95% CI, 1.001-1.023). By pollutant-specific AQI, the association was strongest for PM2.5. In stratified analyses, the AQI was associated with exacerbations in Black and younger children (6-11 yr) on Lag Day 4. Conclusions: The AQI is associated with asthma exacerbations among children in Allegheny County. This is driven primarily by PM2.5, with Black and younger children particularly affected. Healthcare providers should discuss the AQI in asthma management. [ABSTRACT FROM AUTHOR]

Background: Serum cotinine has become the most widely used biomarker of secondhand smoke exposure (SHS) over time in all ages. The aim of this study was to review the serum cotinine cut-points used to classify children under 5 years as exposed to SHS. Methods: A systematic review performed in the Pubmed (MEDLINE) and EMBASE databases up to April 2021 was conducted using as key words "serum cotinine", "tobacco smoke pollution" (MeSH), "secondhand smoke", "environmental tobacco smoke" and "tobacco smoke exposure". Papers which assessed SHS exposure among children younger than 5 years old were included. The PRISMA 2020 guidelines were followed. Analysis was pre-registered in PROSPERO (registration number: CRD42021251263). Results: 247 articles were identified and 51 fulfilled inclusion criteria. The selected studies were published between 1985–2020. Most of them included adolescents and adults. Only three assessed postnatal exposure exclusively among children under 5 years. None of the selected studies proposed age-specific cut-points for children < 5 years old. Cut-point values to assess SHS exposure ranged from 0.015 to 100 ng/ml. The most commonly used cut-point was 0.05 ng/ml, derived from the assay limit of detection used by the National Health and Nutrition Examination Survey (NHANES). Conclusions: No studies have calculated serum cotinine age-specific cut-points to ascertained SHS exposure among children under 5 years old. Children's age-specific cut-points are warranted for health research and public health purposes aimed at accurately estimating the prevalence of SHS exposure and attributable burden of disease to such exposure, and at reinforcing 100% smoke-free policies worldwide, both in homes, private vehicles and public places. [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying the known link between overweight/obesity and childhood asthma are unclear. We aimed to identify differentially expressed genes and pathways associated with obesity‐related asthma through a transcriptomic analysis of nasal airway epithelium. Methods: We compared the whole transcriptome in nasal airway epithelium of youth with overweight or obesity and asthma with that of youth of normal weight and asthma, using RNA sequencing data from a cohort of 235 Puerto Ricans aged 9–20 years (EVA‐PR) and an independent cohort of 66 children aged 6–16 years in Pittsburgh (VDKA). Differential expression analysis adjusting for age, sex, sequencing plate number, and sample sorting protocol, and the first five principal components were performed independently in each cohort. Results from the two cohorts were combined in a transcriptome‐wide meta‐analysis. Gene enrichment and network analyses were performed on top genes. Results: In the meta‐analysis, 29 genes were associated with obesity‐related asthma at an FDR‐adjusted p <.05, including pro‐inflammatory genes known to be differentially expressed in adipose tissue of obese subjects (e.g., CXCL11, CXCL10, and CXCL9) and several novel genes. Functional enrichment analyses showed that pathways for interferon signaling, and innate and adaptive immune responses were down‐regulated in overweight/obese youth with asthma, while pathways related to ciliary structure or function were up‐regulated. Upstream regulatory analysis predicted significant inhibition of the IRF7 pathway. Network analyses identified "hub" genes like GBP5 and SOCS1. Conclusion: Our transcriptome‐wide analysis of nasal airway epithelium identified biologically plausible genes and pathways for obesity‐related asthma in youth. [ABSTRACT FROM AUTHOR]

Asthma affects a large number of people living in the Americas, a vast and diverse geographic region comprising 35 nations in the Caribbean and North, Central, and South America. The marked variability in the prevalence, morbidity, and mortality from asthma across and within nations in the Americas offers a unique opportunity to improve our understanding of the risk factors and management of asthma phenotypes and endotypes in children and adults. Moreover, a better assessment of the causes and treatment of asthma in less economically developed regions in the Americas would help diagnose and treat individuals migrating from those areas to Canada and the United States. In this focused review, we first assess the epidemiology of asthma, review known and potential risk factors, and examine commonalities and differences in asthma management across the Americas. We then discuss future directions in research and health policies to improve the prevention, diagnosis, and management of pediatric and adult asthma in the Americas, including standardized and periodic assessment of asthma burden across the region; large-scale longitudinal studies including omics and comprehensive environmental data on racially and ethnically diverse populations; and dissemination and implementation of guidelines for asthma management across the spectrum of disease severity. New initiatives should recognize differences in socioeconomic development and health care systems across the region while paying particular attention to novel or more impactful risk factors for asthma in the Americas, including indoor pollutants such as biomass fuel, tobacco use, infectious agents and the microbiome, and psychosocial stressor and chronic stress. [ABSTRACT FROM AUTHOR]

Objective: Asthma is a major contributor to childhood morbidity. Several environmental and socioeconomic status (SES) factors have been implicated in its etiopathogeneses such as indoor moisture and parental education level. Our study examined the association between exposure to indoor dampness and/or mould (IDM) with adolescent asthma and how parental education could modify or mediate this relationship.Method: A total of 1934 adolescents (boys: 47.5%, mean age (standard variation): 12.7(0.6) years) and their parents were voluntarily enrolled and completed a validated questionnaire on adolescents' asthma status, parental educational level, and adolescents' indoor exposure to IDM during three different lifetime periods, i.e., pregnancy, the first year of life and the current time.Results: There was a significant modification effect of parental education only for the current exposure; higher parental education lowered almost 50% the odds of IDM and asthma (adjusted odds ratio (aOR): 1.96, 95% Confidence Intervals (CI): (1.05-3.68) and aOR:1.55, 95% CI (1.04-2.32), for primary/secondary and tertiary parental education, respectively).Conclusion: Adolescents whose parents had a higher education level had lesser odds to have asthma, even if they were exposed to a moisture home environment. This could be attributed to the increased knowledge about asthma risk factors and the improved measures for the amelioration of moisture-home environment that highly educated parents are more likely to take. Further research is needed in order to elucidate the interweaved role of family SES in the aforementioned relation. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has disproportionately affected the socially and environmentally vulnerable, including through indirect effects on other health conditions. Asthma is one such condition, which may be exacerbated by both prolonged adverse in-home exposures if quarantining in unhealthy homes and prolonged outdoor exposures if the ambient air quality is unhealthy or hazardous. As both are often the case in Environmental Justice (EJ) communities, here we have analyzed data at the census tract (CT) level for Louisiana to assess any correlation between social and environmental vulnerability, and health issues like COVID-19 and asthma. Higher Social Vulnerability Index (SVI), Particulate Matter less than 2.5 μm in diameter (PM2.5) and Ozone levels were associated with higher rates of cumulative COVID-19 incidence at various time points during the pandemic, as well as higher average annual asthma hospitalization rates and estimated asthma prevalence. Further, cumulative COVID-19 incidence during the first three months of the pandemic was moderately correlated with both asthma hospitalizations and estimated prevalence, suggesting similar underlying factors may be affecting both conditions. Additionally, 137 CTs were identified where social and environmental vulnerabilities co-existed, of which 75 (55%) had high estimated prevalence of asthma. These areas are likely to benefit from asthma outreach that considers both social and environmental risk factors. Fifteen out of the 137 CTs (11%) not only had higher estimated prevalence of asthma but also a high burden of COVID-19. Further research in these areas may help to elucidate any common social determinants of health that underlie both asthma and COVID-19 burdens, as well as better clarify the possible role of the environment as related to the COVID-19 burden in Louisiana. [ABSTRACT FROM AUTHOR]

Introduction: DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population. Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos. Results: We conducted an EWAS in whole blood from 250 Puerto Rican and 148 Mexican American children and young adults with asthma. A total of five CpGs exceeded the genome-wide significance threshold of p = 1.17 × 10−7 in the combined analyses from Puerto Ricans and Mexican Americans: cg06035600 (MAP3K6, p = 6.13 × 10−8) showed significant association with pre-bronchodilator Tiffeneau–Pinelli index, the probes cg00914963 (TBC1D16, p = 1.04 × 10−7), cg16405908 (MRGPRE, p = 2.05 × 10−8), and cg07428101 (MUC2, p = 5.02 × 10−9) were associated with post-bronchodilator forced vital capacity (FVC), and cg20515679 (KCNJ6) with post-bronchodilator Tiffeneau–Pinelli index (p = 1.13 × 10−8). However, these markers did not show significant associations in publicly available data from Europeans (p > 0.05). A methylation quantitative trait loci analysis revealed that methylation levels at these CpG sites were regulated by genetic variation in Latinos and the Biobank-based Integrative Omics Studies (BIOS) consortium. Additionally, two differentially methylated regions in REXOC and AURKC were associated with pre-bronchodilator Tiffeneau–Pinelli index (adjusted p < 0.05) in Puerto Ricans and Mexican Americans. Moreover, we replicated some of the previous differentially methylated signals associated with lung function in non-Latino populations. Conclusions: We replicated previous associations of epigenetic markers with lung function in whole blood and identified novel population-specific associations shared among Latino subgroups. [ABSTRACT FROM AUTHOR]

Hospital emergency department (ED) visits by asthmatics differ based on race and season. The objectives of this study were to investigate season- and race-specific disparities for asthma risk, and to identify environmental exposure variables associated with ED visits among more than 42,000 individuals of African American (AA) and European American (EA) descent identified through electronic health records (EHRs). We examined data from 42,375 individuals (AAs = 14,491, EAs = 27,884) identified in EHRs. We considered associated demographic (race, age, gender, insurance), clinical (smoking status, ED visits, FEV1%), and environmental exposures data (mold, pollen, and pollutants). Machine learning techniques, including random forest (RF), extreme gradient boosting (XGB), and decision tree (DT) were used to build and identify race- and -season-specific predictive models for asthma ED visits. Significant differences in ED visits and FEV1% among AAs and EAs were identified. ED visits by AAs was 32.0% higher than EAs and AAs had 6.4% lower FEV1% value than EAs. XGB model was used to accurately classify asthma patients visiting ED into AAs and EAs. Pollen factor and pollution (PM2.5, PM10) were the key variables for asthma in AAs and EAs, respectively. Age and cigarette smoking increase asthma risk independent of seasons. In this study, we observed racial and season-specific disparities between AAs and EAs asthmatics for ED visit and FEV1% severity, suggesting the need to address asthma disparities through key predictors including socio-economic status, particulate matter, and mold. [ABSTRACT FROM AUTHOR]

Asthma is the most common chronic condition of childhood. Urban, minority children from families of lower socioeconomic status have disproportionately higher rates of asthma and worse outcomes. We investigated the association between the presence of asthma and asthma severity among American, urban, minority children and reported quality of life (QOL) of children and their families. We performed a prospective, cross-sectional study comparing QOL of urban, minority elementary school-age children with and without asthma. A convenience sample of children was enrolled from the pediatric emergency department (ED) and a specialized asthma clinic, at a large urban children's hospital. We measured child and parent QOL using the Pediatric Quality of Life Inventory Version 4 (PEDSQL4), and evaluated associations with asthma, parental educational attainment, and frequency of ED visits. We enrolled 66 children, 76% were African American, and 61% were female. Overall child QOL was higher for those without asthma (p = 0.017, d = 0.59). Children with asthma also visited the ED almost twice as frequently (t [64] = −3.505, p < 0.001, d = 0.8), and parents of children with asthma reported a lower overall QOL (p = 0.04, d = 0.53) than those without asthma. Among children with asthma, a higher overall child QOL was associated with decreased asthma severity, more ED visits, and higher parental educational attainment. Urban, minority elementary school-age children with asthma report a lower QOL than those children without asthma, and decreased asthma severity was associated with higher QOL. [ABSTRACT FROM AUTHOR]

Obesity increases the risk of asthma throughout life but the underlying mechanisms linking these all too common threats to child health are poorly understood. Acute bouts of exercise, aerobic fitness, and levels of physical activity clearly play a role in the pathogenesis and/or management of both childhood obesity and asthma. Moreover, both obesity and physical inactivity are associated with asthma symptoms and response to therapy (a particularly challenging feature of obesity-related asthma). In this article, we review current understandings of the link between physical activity, aerobic fitness and the asthma-obesity link in children and adolescents (e.g., the impact of chronic low-grade inflammation, lung mechanics, and direct effects of metabolic health on the lung). Gaps in our knowledge regarding the physiological mechanisms linking asthma, obesity and exercise are often compounded by imprecise estimations of adiposity and challenges of assessing aerobic fitness in children. Addressing these gaps could lead to practical interventions and clinical approaches that could mitigate the profound health care crisis of the increasing comorbidity of asthma, physical inactivity, and obesity in children. [ABSTRACT FROM AUTHOR]

Asthma, a major cause of disability and reduced quality of life, has a high global prevalence and burden of death. Despite the propitious guidelines, a substantial portion of asthmatics reportedly have poorly controlled disease. In the current study, we have examined risk factors for uncontrolled asthma in specialty clinics and its association with impaired quality of life. A multicentre cross-sectional survey of asthma patients, 18 years and older, was conducted in Trinidad. Asthma Control Test (ACT) and the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ–J) were used to assess the disease control and quality of life, respectively. Data were analyzed using the Chi-square test and multivariable logistic regression controlling for gender. Of a total of 428 patients included, asthma was uncontrolled in 72.4% and asthma related quality of life was moderate to severely impaired in 86% of the studied population. In the multivariate regression models, poorly controlled asthma was associated with obesity (OR 2.25; 95% CI 1.30–3.39), late-onset asthma (OR 1.72; 95% CI 1.04–2.84), features of sleep apnea (OR 1.77; 95% CI 1.01–3.07) and depression (OR 2.01; 95% CI 1.04–3.86). Impaired quality of life was associated with Indo-Caribbean ethnicity (OR 3.19; 95% CI = 1.68–6.06). In this Caribbean population, uncontrolled asthma was independently associated with obesity, late-onset disease, and comorbidities of sleep apnea and depression. Poor asthma-related quality of life was independently associated with Indo-Caribbean ethnicity. [ABSTRACT FROM AUTHOR]

The association of asthma health outcome and air pollution has been widely investigated. Meanwhile, from a macro perspective, it cannot be ignored the enormous pressure on regional medical services resulting from a large number of hospitalization needs after the exposure to air pollution. This study is aimed at assessing the admission risk and excessive burden attributable to ambient air pollution in different unspecified asthma groups. We analyzed 6,663 medical claims of unspecified asthma patients from different levels of hospitals, air pollution, and meteorological conditions in Chengdu of China during 2014. The distinct impacts of air pollution on hospital admissions stratified by gender and age were revealed. When air pollution attacks, female patients and young and middle-aged patients (≤65) are more vulnerable to PM10 and SO2. In contrast to patients suffering from asthmatic bronchitis, the patients suffering from bronchial asthma are more susceptible to air pollution. And the percentage changes of admissions attributable to PM2.5, PM10, and SO2 reached by 1.046 (95%CI: 1.0088, 1.0846), 1.0419 (95%CI: 1.0117, 1.073), and 1.4049 (95%CI: 1.1011, 1.7925). Based on the WHO's air quality standards, the excessive admission burden of unspecified asthma due to overexposure to PM2.5, PM10, and SO2 were estimated by 15.42% (95%CI: 1.81%, 25.92%), 20.50% (95%CI: 6.80%, 30.92%), and 10.13% (95%CI: 1.67%, 14.96%), respectively. It is concluded that female patients and young and middle-aged patients suffering from bronchial asthma are susceptible to PM10, PM2.5, and SO2, causing the excessive admission burden in Chengdu of China. [ABSTRACT FROM AUTHOR]

The etiology of Kawasaki Disease (KD), the most common cause of acquired heart disease in children in developed countries, remains elusive, but could be multifactorial in nature as suggested by the numerous environmental and infectious exposures that have previously been linked to its epidemiology. There is still a lack of a comprehensive model describing these complex associations. We present a Bayesian disease model that provides insight in the spatiotemporal distribution of KD in Canada from 2004 to 2017. The disease model including environmental factors had improved Watanabe-Akaike information criterion (WAIC) compared to the base model which included only spatiotemporal and demographic effects and had excellent performance in recapitulating the spatiotemporal distribution of KD in Canada (98% and 86% spatial and temporal correlations, respectively). The model suggests an association between the distribution of KD and population composition, weather-related factors, aeroallergen exposure, pollution, atmospheric concentration of spores and algae, and the incidence of healthcare encounters for bacterial pneumonia or viral intestinal infections. This model could be the basis of a hypothetical data-driven framework for the spatiotemporal distribution of KD. It also generates novel hypotheses about the etiology of KD, and provides a basis for the future development of a predictive and surveillance model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown. OBJECTIVE: This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip. METHODS: Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (푛=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure. RESULTS: Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (푛=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate= -1:09, standard error (SE)=0:45, 푝=0:018) but not for AGER (cg09199225; estimate= -0:16, SE=0:21, 푝=0.44). DISCUSSION: Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. [ABSTRACT FROM AUTHOR]

In New York City, asthma prevalence is greater in Hispanics than non-Hispanics for both children (10.9% vs. 7.4%) and adults (9.0% vs. 6.3%). Disparities in asthma management among Hispanics are found to arise, in part, from a limited education about asthma. Using elements of Community Based Participatory Research (CBPR), we worked with the community to identify asthma priorities and misconceptions among Hispanics and used that information to develop a tailored asthma educational tool—the Asthma Training Modules (ATMs). Over the past 3 years (2016, 2017, and 2018), we conducted educational asthma workshops to collect and analyze information to develop the ATMs and a summary of the ATMs in an Asthma Educational Card (AEC). We trained 6 Asthma-Community-Leaders using the ATMs, who assembled community members for teaching sessions using the AEC. Participants completed a pre-and-post asthma knowledge questionnaire. We identified asthma priorities and misconceptions themed on: culturally relevant resources for Hispanics, symptom and trigger recognition, and treatments. A total of 104 participants attended the teaching sessions led by Asthma-Community-Leaders and participants' mean knowledge score increased from 64% pre-teaching to 85% post-teaching, (p < 0.01). Our community-led education, which included a tailored asthma educational tool and trained Asthma-Community-Leaders, successfully improved asthma knowledge among Hispanics. Further studies are warranted to determine whether these results are reproducible among a larger cohort and what the comparative effectiveness of our intervention as compared to other education-based interventions. [ABSTRACT FROM AUTHOR]

We previously reported that treatment with the prototypical antidepressant imipramine induced a dose-dependent reduction of the ingestion of a 10% sucrose solution, due to reduction of the licking burst number, thus suggesting reduced motivation and/or increased satiation. Importantly, the experimental sessions were performed in an alternate order, either 1-h or 24-h after imipramine administration. The observation that imipramine effect was more pronounced in the "1-h after-treatment" sessions, i.e. at the time of the brain drug Cmax, led us to suggest that it was likely related to brain drug levels at testing time. However, such an experimental design does not allow to rule out the alternative possibility that the observed effect might be due to post-session administration, as previously observed with memantine. To determine whether imipramine-induced decrease of sucrose ingestion could be observed even in absence of post-session administration, we examined the effect of a daily 22 day treatment with imipramine (5, 10 and 20 mg/kg). In the first half of the treatment period all behavioural tests were performed 1-h after administration. In the second half of the treatment period, tests were performed alternatively either 1-h or 24-h after imipramine administration. The results confirm that imipramine reduces sucrose ingestion due to a reduction of the licking burst number. Most importantly, these results demonstrate that this effect does not require imipramine post-session administration, since it was present before the beginning of post-session administrations. This supports the interpretation of the reduction of sucrose ingestion as a consequence of reduced motivation and/or increased satiation. Thus, these findings, taken together with the results of our previous study, might be relevant in explaining the effects of imipramine in models of drug-seeking and in body weight gain reduction in rats, but not in accounting for the antidepressant therapeutic effect. At variance with the results of our previous study, an increase in burst size was present in the first half of the treatment period, which might be interpreted as a prohedonic effect and/or as a compensatory effect. [ABSTRACT FROM AUTHOR]

Background: Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective: Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma. Methods: Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing. Results: Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions: We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group. [ABSTRACT FROM AUTHOR]

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Asthma is a chronic respiratory condition characterized by airway inflammation and hyperreactivity. Prevalence has continued to rise in recent decades as Western dietary patterns have become more pervasive. Evidence suggests that diets emphasizing the consumption of plant-based foods might protect against asthma development and improve asthma symptoms through their effects on systemic inflammation, oxidation, and microbial composition. Additionally, increased fruit and vegetable intake, reduced animal product consumption, and weight management might mediate cytokine release, free radical damage, and immune responses involved in the development and course of asthma. The specific aim of this review paper is to examine the current literature on the associations between dietary factors and asthma risk and control in children and adults. Clinical trials examining the mechanism(s) by which dietary factors influence asthma outcomes are necessary to identify the potential use of nutritional therapy in the prevention and management of asthma. [ABSTRACT FROM AUTHOR]

There is strong evidence for gut-taste bud interactions that influence taste function, behavior and feeding. However, the effect of gut inflammation on this axis is unknown despite reports of taste changes in gastrointestinal (GI) inflammatory conditions. Lipopolysaccharide (LPS), an inflammatory stimulus derived from gram-negative bacteria, is present in the normal GI tract and levels increase during high-fat feeding and gut infection and inflammation. Recordings from the chorda tympani nerve (CT), which transmits taste information from taste buds on the anterior tongue to the brain, previously revealed a transient decrease in sucrose responses in mice that ingest LPS during a single overnight period. Here we test the effect of acute or chronic, weekly LPS gavage on licking behavior and CT responses. Using brief-access testing, rats treated with acute LPS and mice receiving acute or chronic LPS decreased licking responses to sucrose and saccharin and to NaCl in mice. In long-term (23 h) tests chronic LPS also reduced licking responses to saccharin, sucrose, and NaCl in mice. Neurophysiological recordings from the CT supported behavioral changes, demonstrating reduced responses to sucrose, saccharin, acesulfame potassium, glucose and NaCl in acute and chronic LPS groups compared to controls. Chronic LPS significantly elevated neutrophils in the small intestine and colon, but LPS was not detected in serum and mice did not display sickness behavior or lose weight. These results indicate that sweet and salt taste sensitivity could be reduced even in asymptomatic or mild localized gut inflammatory conditions such as inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence of overweight and obesity in urban adolescents with asthma and to investigate the relationships between anthropometric measures and asthma outcomes including quality of life, asthma control and lung function. Methods: Adolescents with an asthma diagnosis, 12–20 years-old, were recruited from three urban communities in the United States. Spirometry and anthropometric data including height, weight and waist circumferences were collected along with questionnaire data measuring quality of life, asthma control, and medication adherence. Body mass index (BMI) and waist–height ratio (WHtR) were computed. Results: The sample (N = 294) included 48% female and 80% African American. About 50% of the sample were either overweight or obese, and 41% had central obesity. No significant gender interactions with either BMI or WHtR on asthma outcomes were found. Neither BMI nor WHtR predicted quality of life, asthma control or medication adherence, while females had poorer quality of life and asthma control regardless of weight status (p < 0.001). Higher BMI or WHtR predicted higher spirometry values. Regardless of weight status, females had greater percent predicted spirometry values, while raw values (L) were significantly greater in males. Conclusions: High BMI is a common comorbidity among poor, primarily African American, urban adolescents with asthma. The negative impact of being overweight or obese on quality of life or asthma control is yet to be manifested in adolescents. The findings underscore adolescence as an ideal period to safely intervene to reduce excessive body weight, which can prevent the potentially harmful effects of obesity on future asthma outcomes. [ABSTRACT FROM AUTHOR]

Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma. [ABSTRACT FROM AUTHOR]

Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure. Objectives: To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination. Methods: A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS. Results: Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS. Conclusions: This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described. [ABSTRACT FROM AUTHOR]

Background: Childhood asthma management is an environmental justice concern for immigrant Latino parents. Photovoice methods have empowered our community-based participatory research (CBPR) team of Latino parents of children with asthma to investigate and educate others about indoor environmental threats in our community. Methods: Data collection and management in evaluating interventions in such settings is under-described in the literature. We developed a culturally tailored educational intervention, guided by social cognitive theory, using photographs from our archive. We pilot tested this intervention with a convenience sample of Latino parents (n = 19) attending an English language literacy class. We designed and implemented a pre- and post-evaluation survey on self-efficacy and knowledge and collected observational notes. However, we found that the responses to the knowledge questions were of limited value. Lessons Learned: We describe the lessons we learned regarding data collection, management and evaluation. Conclusions: We provide suggestions for improving survey design and data management for culturally tailored educational interventions. [ABSTRACT FROM AUTHOR]

Population substructure within human populations is globally evident and a well-known confounding factor in many genetic studies. In contrast, admixture mapping exploits population stratification to detect genotype–phenotype correlations in admixed populations. Southern Africa has untapped potential for disease mapping of ancestry-specific disease risk alleles due to the distinct genetic diversity in its populations compared to other populations worldwide. This diversity contributes to a number of phenotypes, including ancestry-specific disease risk and response to pathogens. Although the 1000 Genomes Project significantly improved our understanding of genetic variation globally, southern African populations are still severely underrepresented in biomedical and human genetic studies due to insufficient large-scale publicly available data. In addition to a lack of genetic data in public repositories, existing software, algorithms and resources used for imputation and phasing of genotypic data (amongst others) are largely ineffective for populations with a complex genetic architecture such as that seen in southern Africa. This review article, therefore, aims to summarise the current limitations of conducting genetic studies on populations with a complex genetic architecture to identify potential areas for further research and development. [ABSTRACT FROM AUTHOR]

The genetic control of gene expression is a core component of human physiology. For the past several years, transcriptome-wide association studies have leveraged large datasets of linked genotype and RNA sequencing information to create a powerful gene-based test of association that has been used in dozens of studies. While numerous discoveries have been made, the populations in the training data are overwhelmingly of European descent, and little is known about the generalizability of these models to other populations. Here, we test for cross-population generalizability of gene expression prediction models using a dataset of African American individuals with RNA-Seq data in whole blood. We find that the default models trained in large datasets such as GTEx and DGN fare poorly in African Americans, with a notable reduction in prediction accuracy when compared to European Americans. We replicate these limitations in cross-population generalizability using the five populations in the GEUVADIS dataset. Via realistic simulations of both populations and gene expression, we show that accurate cross-population generalizability of transcriptome prediction only arises when eQTL architecture is substantially shared across populations. In contrast, models with non-identical eQTLs showed patterns similar to real-world data. Therefore, generating RNA-Seq data in diverse populations is a critical step towards multi-ethnic utility of gene expression prediction. Author summary: Advances in RNA sequencing technology have reduced the cost of measuring gene expression at a genome-wide level. However, sequencing enough human RNA samples for adequately-powered disease association studies remains prohibitively costly. To this end, modern transcriptome-wide association analysis tools leverage existing paired genotype-expression datasets by creating models to predict gene expression using genotypes. These predictive models enable researchers to perform cost-effective association tests with gene expression in independently genotyped samples. However, most of these models use European reference data, and the extent to which gene expression prediction models work across populations is not fully resolved. We observe that these models predict gene expression worse than expected in a dataset of African-Americans when derived from European-descent individuals. Using simulations, we show that gene expression predictive model performance depends on both the proportion of genetic variants shared between population-specific prediction models as well as the genetic relatedness between populations. Our findings suggest a need to carefully select reference populations for prediction and point to a pressing need for more genetically diverse genotype-expression datasets. [ABSTRACT FROM AUTHOR]

Air pollution particulate matter ,2.5 mm (PM2.5) exposure is associated with poor respiratory outcomes. Mechanisms underlying PM2.5-induced lung pathobiology are poorly understood but likely involve cellular and molecular changes to the airway epithelium. We extracted and chemically characterized the organic and water-soluble components of air pollution PM2.5 samples, then determined the whole transcriptome response of human nasal mucociliary airway epithelial cultures to a dose series of PM2.5 extracts. We found that PM2.5 organic extract (OE), but not water-soluble extract, elicited a potent, dose-dependent transcriptomic response from the mucociliary epithelium. Exposure to a moderate OE dose modified the expression of 424 genes, including activation of aryl hydrocarbon receptor signaling and an IL-1 inflammatory program. We generated an OE-response gene network defined by eight functional enrichment groups, which exhibited high connectivity through CYP1A1, IL1A, and IL1B. This OE exposure also robustly activated a mucus secretory expression program (.100 genes), which included transcriptional drivers of mucus metaplasia (SPDEF and FOXA3). Exposure to a higher OE dose modified the expression of 1,240 genes and further exacerbated expression responses observed at the moderate dose, including the mucus secretory program. Moreover, the higher OE dose significantly increased the MUC5AC/MUC5B gel-forming mucin expression ratio and strongly downregulated ciliated cell expression programs, including key ciliating cell transcription factors (e.g., FOXJ1 and MCIDAS). Chronic OE stimulation induced mucus metaplasia-like remodeling characterized by increases in MUC5AC1 secretory cells and MUC5AC mucus secretions. This epithelial remodeling may underlie poor respiratory outcomes associated with high PM2.5 exposure. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jakob Disease (CJD) is a rapidly progressive neurodegenerative disease caused by the misfolded version of the cellular prion protein. Here we report four cases of sporadic CJD (sCJD) and describe the diagnostic methods available in order avoid missed or delayed recognition of CJD in China. Case presentation: We report four patients diagnosed with sCJD between March 2018 and December 2019 at Xiangya Hospital and the Second Xiangya Hospital of Central South University. All patients were admitted to the hospital because of a progressive cognitive decline. Although their routine tests and biochemical indicators in the cerebrospinal fluid (CSF), as well as computed tomography (CT) imaging, did not reveal any apparent abnormalities, the presence of "cortical ribboning" was incidentally found on diffusion-weighted imaging (DWI). The patients were subsequently diagnosed with CJD based on positive testing for 14-3-3 protein in their CSF, and the presence of periodic sharp and slow wave complexes (PSWCs) on their electroencephalograms (EEG). Additionally, two of patients was confirmed pathological examination of cerebral biopsies demonstrating neuronal loss, gliosis, and spongiform changes. Conclusions: CJD is a rare disease and is easily misdiagnosed by clinician in China due to a lack of recognition and awareness of CJD. Based on our experience described in this report, enhanced vigilance for CJD is required for patients with rapidly progressive dementia in China and other developing countries. DWI, EEG and detection of 14-3-3 protein in CSF should be performed in order to achieve a timely diagnosis of CJD. [ABSTRACT FROM AUTHOR]

Background: Asthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables. Results: We evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 233 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to quantify interaction effects using an information-theory metric known as Information Gain (IG). We performed analyses in the full dataset and in sex-stratified subsets. Our analyses identified several interaction models significantly, and suggestively, associated with BDR. The strongest interaction significantly associated with BDR was a pairwise interaction between pre-natal smoke exposure and socioeconomic status (full dataset IG: 2.78%, p = 0.001; female IG: 7.27%, p = 0.004)). Sex-stratified analyses yielded divergent results for females and males, indicating the presence of sex-specific effects. Conclusions: Our study identified novel interaction effects significantly, and suggestively, associated with BDR in African American children with asthma. Notably, we found that all of the interactions identified by ViSEN were "pure" interaction effects, in that they were not the result of strong main effects on BDR, highlighting the complexity of the network of biological and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods, thus emphasizing the importance of employing statistical methods optimized to detect both additive and non-additive interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies. [ABSTRACT FROM AUTHOR]

Objective: There are racial and ethnic disparities in childhood asthma burden and outcomes. Although there have been comparisons between whites and minorities, there are few between minority groups. This study aimed to compare characteristics of asthma hospitalizations in African American and Hispanic children. Methods: A retrospective chart review was conducted to compare asthma characteristics between African American and Hispanic children aged 2–18 years hospitalized at an urban, tertiary care hospital for an acute asthma exacerbation. Length of stay (LOS), need for intensive care unit (ICU), and need for additional medications or respiratory support were compared between the groups. Results: Of the 925 children that met the inclusion criteria, 64% were Hispanic and 36% were African American. The groups were similar in age, gender, insurance status, and weight classification. African American children were more likely to have severe persistent asthma (12% vs. 7%, p =.02). They were also more likely to require magnesium sulfate (45% vs. 32%, p <.001) and admission to the ICU from the emergency department (ED) (14% vs. 8%, p =.01), which were independent of asthma severity. There was no significant difference in LOS or other characteristics of hospitalization. Conclusions: African American children hospitalized for asthma have more severe exacerbations compared to Hispanic children, which is independent of their asthma severity. However, this was not associated with longer LOS, which may indicate greater responsiveness to inpatient asthma management. Further investigation is needed to understand the mechanisms underlying asthma and exacerbation severity among minority groups. [ABSTRACT FROM AUTHOR]

Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight-based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment. [ABSTRACT FROM AUTHOR]

Rationale: Severe early-life respiratory illnesses, particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are strongly associated with the development of asthma in children. Puerto Rican children in particular have a strikingly high asthma burden. However, prior studies of the potential associations between early-life respiratory illnesses and asthma in Puerto Rican and other minority populations have been limited. Objectives: We sought to determine whether early-life respiratory illness was associated with asthma in Puerto Rican, Mexican American, and African American children. Methods: Using a logistic regression analysis, we examined the association between early-life respiratory illnesses (report of upper respiratory infection (URI), pneumonia, bronchitis, and bronchiolitis/RSV) within the first two years of life and physician-diagnosed asthma after the age of two in a large cohort of Puerto Rican, Mexican American, and African American children. Measurements and main results: While early-life respiratory illnesses were associated with greater asthma odds in Puerto Ricans, Mexican Americans, and African Americans, these associations were stronger among Puerto Rican children. Specifically, in Puerto Ricans, the odds was 6.15 (95% CI: 4.21–9.05) if the child reported at least one of the following respiratory illness: URI, pneumonia, bronchitis or bronchiolitis. The odds were also higher in Puerto Ricans when considering these conditions separately. Conclusions: We observed population-specific associations between early-life respiratory illnesses and asthma, which were especially significant and stronger in Puerto Ricans. Taken together with the known high burden of RSV in Puerto Rico, our results may help explain the high burden of asthma in Puerto Ricans. [ABSTRACT FROM AUTHOR]