Juan C Celedon

Juan C Celedon
Childrens Hospital of Pittsburgh, University of Pittsburgh

MD, DrPH

About

439
Publications
32,122
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17,650
Citations
Citations since 2016
207 Research Items
9059 Citations
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201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400

Publications

Publications (439)
Article
Full-text available
Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA meth...
Article
Background: Asthma is a heterogeneous common respiratory disease that remains poorly understood. The established genetic associations fail to explain the high estimated heritability, and the prevalence of asthma differs between populations and geographic regions. Robust association analyses incorporating different genetic ancestries and whole-geno...
Article
Full-text available
Background The current United States asthma management guidelines recommend usage of the Air Quality Index (AQI) for outdoor activity modification when air pollution is high. Little is known about parental knowledge and usage of air quality including the AQI in managing childhood asthma. Methods Forty parents (or legal guardians) of children with...
Article
Full-text available
Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal...
Article
Background Sex differences related to immune responses can influence atopic manifestations in childhood asthma. While genome-wide association studies have investigated a sex-specific genetic architecture of the immune response, gene-by-sex interactions have not extensively been analyzed for atopy-related markers including allergy skin tests, immuno...
Article
Full-text available
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. Ge...
Article
Full-text available
Introduction Bronchodilator response (BDR) is a measurement of acute bronchodilation in response to short-acting β2-agonists (SABA), with a heritability between 10–40%. Identifying genetic variants associated with BDR may lead to a better understanding of its complex pathophysiology. Methods We performed a genome-wide association study (GWAS) of B...
Preprint
Full-text available
Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesized that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA met...
Article
Full-text available
Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of geno...
Article
Increasing violence-related distress over time was associated with worse lung function and worse asthma-related quality of life in youth with asthma despite treatment with low-dose inhaled corticosteroids. Exposure to violence has been associated with lower lung function in cross-sectional studies. We examined whether increasing violence-related di...
Article
A growing body of evidence suggests a potential link between child maltreatment and asthma. Determining whether and how child maltreatment causes or worsens asthma would have major implications for disease prevention and treatment, as well as public health policy. In this article, we examine epidemiologic studies of child maltreatment and asthma an...
Article
Motivation Tissue-level omics data such as transcriptomics and epigenomics are an average across diverse cell types. To extract cell-type-specific (CTS) signals, dozens of cellular deconvolution methods have been proposed to infer cell-type fractions from tissue-level data. However, these methods produce vastly different results under various real...
Article
Full-text available
Asthma disproportionally affects Hispanic and/or Latino backgrounds; however, the relation between circulating metabolites and asthma remains unclear. We conducted a cross-sectional study associating 640 individual serum metabolites, as well as twelve metabolite modules, with asthma in 3347 Hispanic/Latino background participants (514 asthmatics, 1...
Article
Full-text available
MicroRNAs have been independently associated with asthma and COPD; however, it is unclear if microRNA associations will overlap when evaluating retrospective acute exacerbations. Objective: We hypothesized that peripheral blood microRNAs would be associated with retrospective acute asthma exacerbations in a pediatric asthma cohort and that such ass...
Article
Full-text available
Background: Epigenomic (e.g., DNA methylation [DNAm]) changes have been hypothesized as intermediate step linking environmental exposures with allergic disease. Associations between individual DNAm at CpGs and allergic diseases have been reported, but their joint predictive capability is unknown. Methods: Data were obtained from 240 children of...
Article
Objective: To first review and critically discuss published evidence on interactions between obesity and selected risk factors on asthma in children and adults, and then discuss potential future directions in this field. Data Sources: National Library of Medicine (via PubMed) Study Selection: A literature search was conducted for human studies on o...
Preprint
Variable number of tandem repeats (VNTRs) are major source of genetic variation in human. However due to their repetitive nature and large size, it is challenging to genotype them by short-read sequencing. Therefore, there is limited understanding of how they contribute to complex traits such as cystic fibrosis (CF) lung function. Genome-wide assoc...
Article
Background Child maltreatment is associated with asthma in adults. We examined whether lifetime major depressive disorder (MDD) or lifetime generalised anxiety disorder (GAD) mediate an association between child maltreatment and current asthma among 81 105 British adults in the UK Biobank who completed a mental health survey and had complete data o...
Article
Full-text available
Background: Children with severe asthma have substantial morbidity and healthcare utilization. Pediatric severe asthma is a heterogeneous disease, and a multidisciplinary approach can improve the diagnosis and management of these children. Methods: We reviewed the electronic health records for patients seen in the Severe Asthma Clinic (SAC) at U...
Article
Background Poor diet quality may contribute to the disproportionate asthma burden in Puerto Rican youth. Objective To examine whether an unhealthy diet at one or two study visits conducted over ∼5 years is associated with asthma, severe asthma exacerbations, and worse lung function in Puerto Rican youth. Methods Prospective study of 406 Puerto Ri...
Article
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 understa...
Article
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omi...
Article
Rationale: Outdoor air pollution causes emergency department (ED) visits and hospitalizations for childhood asthma. In the U.S., 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 exacerbati...
Article
Background: Whether persistent overweight or obesity impacts lung function or asthma morbidity in youth is unclear. Objective: To examine overweight or obesity that persists between school age and adolescence and change in lung function and total IgE, and severe asthma exacerbations in Puerto Rican youth. Methods: Prospective study of 340 Puerto Ri...
Article
Rationale: Current guidelines do not sufficiently capture the heterogeneous nature of asthma; a more detailed molecular classification is needed. Metabolomics represents a novel and compelling approach to derive asthma endotypes, i.e., subtypes defined by functional/pathobiological mechanisms. Objective: To validate metabolomic-driven endotypes...
Article
Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of TH2 cells depends on membrane-associated RING-CH-1 (MARCH...
Article
Objective: Coffee intake has been inversely associated with asthma in adults. We examined the relation between urinary levels of caffeine or caffeine metabolites and asthma, lung function, and fractional exhaled nitric oxide (FeNO) in adults. Methods: Cross-sectional study of 2,832 adults aged 18-79 years in the US National Health and Nutrition Exa...
Article
Full-text available
Background Genome-wide association studies (GWASs) have identified thousands of variants associated with asthma and other complex diseases. However, the functional effects of most of these variants are unknown. Moreover, GWASs do not provide context-specific information on cell types or environmental factors that affect specific disease risks and o...
Article
Full-text available
Background: Well-designed clinical research needs to obtain information that is applicable to the general population. However, most current studies fail to include substantial cohorts of racial/ethnic minority populations. Such underrepresentation may lead to delayed diagnosis or misdiagnosis of disease, wide application of approved interventions w...
Article
Motivation: Allele specific differences in molecular traits can be obtained from next generation sequencing data and could potentially improve testing power, but such information is usually overlooked in association studies. Furthermore, the variation of molecular quantitative traits (e.g., gene expression) could result from the interaction effect...
Article
Background Observational studies have yielded inconsistent findings for the relation between vitamin D level and total IgE or allergic sensitization. Objective To determine whether vitamin D supplementation reduces levels of total IgE and IgE to each of two common indoor allergens in children with asthma and low vitamin D levels. Methods Total Ig...
Article
Recent advances in next-generation sequencing technology have yielded huge amounts of transcriptomic data. The discreteness and the high dimensions of RNA-seq data have posed great challenges in biological network analysis. Although estimation theories for high-dimensional modified Poisson-type graphical models have been proposed for the network an...
Article
Full-text available
Genome-wide association studies (GWAS) of response to asthma medications have primarily focused on Caucasian populations, with findings that may not be generalizable to minority populations. We derived a polygenic risk score (PRS) for response to albuterol as measured by bronchodilator response (BDR), and examined the PRS in a cohort of Hispanic sc...
Article
Background Age- and sex-related differences in asthma may be due to changes in sex hormone levels. Objective To examine whether change in free testosterone or free testosterone to estradiol ratio is associated with changes in lung function and eosinophils in Puerto Rican youth. Methods We tested for association between change in sex hormone level...
Preprint
Full-text available
Current guidelines do not sufficiently capture the heterogeneous nature of asthma; a detailed molecular classification is needed. Metabolomics represents a novel and compelling approach to derive asthma endotypes, i.e., subtypes defined by functional/pathobiological mechanisms. In two cohorts of asthmatics, untargeted metabolomic profiling and Simi...
Article
Exposure to environmental factors can affect DNA methylation at a 5'-cytosine-phosphate-guanine-3' (CpG) site or a genomic region, which can then affect an outcome. In other words, environmental effects on an outcome could be mediated by DNA methylation. To date, single CpG-site-based mediation analysis has been employed extensively. More recently,...
Article
Background Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms. Methods Epigenome‐wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9–20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans...
Article
Background: While infant bronchiolitis contributes to substantial acute (e.g., severity) and chronic (e.g., asthma development) morbidities, its pathobiology remains uncertain. We examined the integrated relationships of local (nasopharyngeal) and systemic (serum) responses with bronchiolitis morbidities. Methods: In a multicenter prospective co...
Article
Full-text available
Background: Occupational exposures at the WTC site after September 11, 2001 have been associated with presumably inflammatory chronic lower airway diseases. Aims: In this study we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of those trajectories with quantit...
Article
Background Insulin-like growth factor-1 (IGF-1) plays a key role in the pathogenesis of metabolic syndrome (MS), which is in turn associated with asthma. Whether IGF-1 contributes to asthma causation or asthma severity is largely unknown. Objective To examine the relation between serum IGF-1 and asthma, asthma outcomes, and lung function in adults...
Preprint
Background Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms. Methods Epigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EV...
Preprint
Exposure to environmental factors can affect DNA methylation at a CpG site or a genomic region, which can then affect an outcome of interest. In other words, environmental effects on an outcome could be mediated by DNA methylation. To date, single CpG site-based mediation analysis has been employed extensively. More recently, however, there has bee...
Article
Background: Young children with rhinovirus (RV) infection-particularly bronchiolitis-are at high risk for developing childhood asthma. Emerging evidence suggests clinical heterogeneity within RV bronchiolitis. However, little is known about these biologically-distinct subgroups (endotypes) and their relations with asthma risk. Objective: We aime...
Article
Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Background Maternal depression has been linked to health care use for asthma in cross-sectional or short-term follow-up studies of school-aged children. Objective To examine whether increased or persistent maternal depressive symptoms over approximately 5 years are associated with severe asthma exacerbations or worse lung function in youth. Metho...
Article
Background: Few studies have examined concurrent exposure to household endotoxin and traffic-related air pollution (TRAP) in relation to childhood asthma, yet both factors are associated with asthma outcomes. Objective: We examined whether proximity to a major roadway (a TRAP proxy) modifies the estimated effects of indoor endotoxin on asthma ou...
Conference Paper
Full-text available
Introduction: Although overweight or obesity have been linked to reduced lung function, no study has estimated the effects of lung function on weight in adults. Aim: We investigated the relation between expiratory flow and body size, and vice versa, in a cohort of adults. Methods: Prospective study in 1,329 former World Trade Center (WTC) workers...
Article
Background: Little is known about genetic determinants of severe asthma exacerbations. Objectives: We aimed to identify genetic variants associated with asthma hospitalizations. Methods: Genome-wide association study of asthma hospitalizations in 34,167 white British adults with asthma, of whom 1,658 (cases) had at least one asthma-related hos...
Article
Background Most children diagnosed with asthma suffer from respiratory symptoms such as cough, dyspnea, and wheezing which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated the genetic susceptibility of asthma diagnosis itself, but few have focused on important respirato...
Article
Importance Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear. Objective To determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. Design, Setting, and Parti...
Article
Background Latinos are heavily affected with childhood asthma. Little is known about epigenetic mechanisms of asthma in Latino youth. Methods We conducted a meta-analysis of two epigenome-wide association studies (EWAS) of asthma, using DNA from white blood cells (WBCs) from 1,136 Latino children and youth aged 6 to 20 years. Genes near the top Cp...
Article
The Coronavirus infectious disease 2019 (COVID-19) pandemic has disproportionally impacted historically disadvantaged populations, with infection and mortality rates among Black and Latinx Americans far exceeding the proportion of the population that these groups represent. We, as researchers, educators, and critical care and pulmonary providers on...
Article
Objective To first review and critically discuss published evidence on psychosocial stressors, stress, and asthma in adolescents, and then discuss potential future directions in this field. Data Sources National Library of Medicine (Pubmed). Study Selections A literature search was conducted for human studies on stressors or stress and asthma bet...
Poster
Full-text available
This poster investigates how relationships between analytes (genes, metabolites) are linked with clinical markers of asthma severity across two cohorts. Integrated Linear Modeling (IntLIM) and Relational Database of Metabolomics (RaMP) are leveraged to uncover pathways enriched for analyte-analyte relationships specific to asthma severity.
Poster
Full-text available
Background: Workers and volunteers who participated in the rescue and recovery of the World Trade Center (WTC) disaster site in 2001-2002 manifest a heterogenous group of chronic lower airway diseases, with variable spirometric patterns. We examined systematically the observed transitions among those spirometric patterns. Methods: from the WTC Ches...
Article
Full-text available
Background The most common abnormal spirometric pattern reported in WTC worker and volunteer cohorts has consistently been that of a nonobstructive reduced forced vital capacity (low FVC). Low FVC is associated with obesity, which is highly prevalent in these cohorts. We used quantitative CT (QCT) to investigate proximal and distal airway inflammat...
Article
Background A reduced forced vital capacity without obstruction (low FVC) is the predominant spirometric abnormality reported in workers and volunteers exposed to dust, gases, and fumes at the World Trade Center (WTC) disaster site in 2001–2002. While low FVC has been associated with obesity and metabolic syndrome, its association with WTC occupatio...
Article
Background Nasal (airway) epithelial methylation profiles have been associated with asthma, but the effects of such profiles on expression of distant cis-genes are largely unknown. Research question To identify genes whose expression is associated with proximal and distal CpG probes (within 1 Mb), and to assess whether and how such genes are diffe...
Article
Background Insulin resistance and metabolic dysfunction have been associated with asthma risk and asthma severity. Objective To examine the association between glycated hemoglobin A1c (HbA1c), asthma-related hospitalizations, and lung function measures among adults in the United Kingdom (U.K.). Methods Cross-sectional study of 47,606 adults aged...
Article
Background Little is known about risk factors for atopic and non‐atopic asthma among children in Puerto Rico. We aimed to identify modifiable risk factors for atopic and non‐atopic asthma in this vulnerable population. Methods Case‐control study of children with (n=305) and without (n=327) asthma in San Juan (PR). Asthma was defined as physician‐d...
Article
Full-text available
Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma. Studies in adults are rare, and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study of blood DNA methylation in adults in relation to non-atopic and atopic asthma. We measured DNA methylation in blood usin...
Conference Paper
Background: Workers and volunteers who participated in the rescue and recovery of the World Trade Center (WTC) disaster site in 2001-2002 manifest a heterogenous group of chronic lower airway diseases, with variable spirometric patterns. We examined systematically the observed transitions among those spirometric patterns. Methods: from the WTC Ches...