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1.
Expert Rev Clin Immunol ; : 1-16, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31674254

RESUMO

Introduction: The development of childhood asthma is caused by a combination of genetic factors and environmental exposures. Epigenetics describes mechanisms of (heritable) regulation of gene expression that occur without changes in DNA sequence. Epigenetics is strongly related to aging, is cell-type specific, and includes DNA methylation, noncoding RNAs, and histone modifications.Areas covered: This review summarizes recent epigenetic studies of childhood asthma in humans, which mostly involve studies of DNA methylation published in the recent five years. Environmental exposures, in particular cigarette smoking, have significant impact on epigenetic changes, but few of these epigenetic signals are also associated with asthma. Several asthma-associated genetic variants relate to DNA methylation. Epigenetic signals can be better understood by studying their correlation with gene expression, which revealed higher presence and activation of blood eosinophils in asthma. Strong associations of nasal methylation signatures and atopic asthma were identified, which were replicable across different populations.Expert commentary: Epigenetic markers have been strongly associated with asthma, and might serve as biomarker of asthma. The causal and longitudinal relationships between epigenetics and disease, and between environmental exposures and epigenetic changes need to be further investigated. Efforts should be made to understand cell-type-specific epigenetic mechanisms in asthma.

2.
PLoS One ; 14(11): e0224448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693680

RESUMO

BACKGROUND: The mechanisms explaining multimorbidity between asthma, dermatitis and rhinitis (allergic multimorbidity) are not well known. We investigated these mechanisms and their specificity in distinct cell types by means of an interactome-based analysis of expression data. METHODS: Genes associated to the diseases were identified using data mining approaches, and their multimorbidity mechanisms in distinct cell types were characterized by means of an in silico analysis of the topology of the human interactome. RESULTS: We characterized specific pathomechanisms for multimorbidities between asthma, dermatitis and rhinitis for distinct emergent non-eosinophilic cell types. We observed differential roles for cytokine signaling, TLR-mediated signaling and metabolic pathways for multimorbidities across distinct cell types. Furthermore, we also identified individual genes potentially associated to multimorbidity mechanisms. CONCLUSIONS: Our results support the existence of differentiated multimorbidity mechanisms between asthma, dermatitis and rhinitis at cell type level, as well as mechanisms common to distinct cell types. These results will help understanding the biology underlying allergic multimorbidity, assisting in the design of new clinical studies.

3.
Eur Respir J ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31699840

RESUMO

About 40% of asthmatics experience remission of asthma symptoms. A better understanding of biological pathways leading to asthma remission may provide insight into new therapeutic targets for asthma. As an important mechanism of gene regulation, investigation of DNA methylation provides a promising approach. Our objective was to identify differences in epigenome wide DNA methylation levels in bronchial biopsies between subjects with asthma remission and subjects with persistent asthma or healthy controls.We analysed differential DNA methylation in bronchial biopsies from 26 subjects with persistent asthma, 39 remission subjects and 70 healthy controls, using the limma package. The comb-p tool was used to identify differentially methylated regions. DNA methylation of CpG-sites was associated to expression of nearby genes from the same biopsies to understand function.Four CpG-sites and 42 regions were differentially methylated between persistent asthma and remission. DNA methylation at two sites was correlated in cis with gene expression at ACKR2 and DGKQ, respectively. Between remission subjects and healthy controls 1163 CpG-sites and 328 regions were differentially methylated. DNA methylation was associated with expression of a set of genes expressed in ciliated epithelium.CpGs differentially methylated between remission and persistent asthma identify genetic loci associated with resolution of inflammation and airway responsiveness. Despite the absence of symptoms, remission subjects have a DNA methylation profile that is distinct from that of healthy controls, partly due to changes in cellular composition, with a higher gene expression signal related to ciliated epithelium in remission versus healthy controls.

4.
Clin Exp Allergy ; 49(10): 1352-1361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31336400

RESUMO

BACKGROUND: Pet and dampness or mould exposure are considered risk factors for asthma and sensitization. It is unclear whether timing of exposure to these factors is differentially associated with asthma risk and sensitization in adolescence. OBJECTIVE: We investigated the role of timing of pet and dampness or mould exposure in asthma and sensitization in adolescence. Understanding this role is essential to build targeted prevention strategies. METHODS: We used data from 1871 participants of the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. Residential exposure to pets, dampness or mould was assessed by repeated parental questionnaires. We used asthma data from the 17-year questionnaire and sensitization data from the 16-year medical examination. We characterized timing using longitudinal exposure patterns from pregnancy till age 17 using longitudinal latent class growth modelling. We used logistic regression models to analyse associations of exposure patterns with asthma at age 17 and sensitization at age 16. RESULTS: For none of the time windows, exposure to pets and dampness or mould was associated with asthma at age 17, but a lower sensitization risk at age 16 was suggested, for example the odds ratio (95% confidence interval) for sensitization was 0.63 (0.35-1.11) and 0.69 (0.44-1.08) for early life and persistently high pet exposure, respectively, compared with very low exposure. An inverse association was also suggested for sensitization and moderate early childhood dampness or mould exposure (0.71 [0.42-1.19]). CONCLUSION AND CLINICAL RELEVANCE: Different timing of pet and dampness or mould exposure was not associated with asthma, but lower risk of sensitization in adolescence was suggested, which could be partly attributable to reversed causation. Current findings are not sufficient to recommend pet avoidance to prevent allergic disease. More prospective studies are needed to obtain insights that can be used in clinical practice.

5.
Nat Med ; 25(7): 1153-1163, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209336

RESUMO

Human lungs enable efficient gas exchange and form an interface with the environment, which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (TH2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identifies a shift from airway structural cell communication in healthy lungs to a TH2-dominated interactome in asthmatic lungs.


Assuntos
Asma/patologia , Pulmão/citologia , Adulto , Idoso , Linfócitos T CD4-Positivos/fisiologia , Comunicação Celular , Células Epiteliais/imunologia , Células Epiteliais/fisiologia , Feminino , Estudo de Associação Genômica Ampla , Células Caliciformes/metabolismo , Humanos , Pulmão/imunologia , Pulmão/patologia , Masculino , Metaplasia , Pessoa de Meia-Idade , Células Th2/fisiologia , Transcriptoma
7.
Dev Cell ; 49(1): 10-29, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30930166

RESUMO

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan.


Assuntos
Desenvolvimento Embrionário/genética , Redes Reguladoras de Genes/genética , Pediatria/tendências , Análise de Célula Única/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Distribuição Tecidual/genética
8.
J Expo Sci Environ Epidemiol ; 29(4): 539-547, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028280

RESUMO

OBJECTIVES: We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO2) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved. METHODS: We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV1 in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (i-GSEA4GWAS) to identify plausible pathways. RESULTS: Two SNPs near the EPHA3 (rs13090972 and rs958144) and one in TXNDC8 (rs7041938) showed significant interactions with NO2 in Caucasians but we did not replicate this locus in African-Americans. SNP-CO interactions did not reach genome-wide significance. The i-GSEA4GWAS showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV1 changes. For NO2-related FEV1 responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses. CONCLUSION: The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways.

10.
Am J Hum Genet ; 104(4): 665-684, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30929738

RESUMO

The extent to which genetic risk factors are shared between childhood-onset (COA) and adult-onset (AOA) asthma has not been estimated. On the basis of data from the UK Biobank study (n = 447,628), we found that the variance in disease liability explained by common variants is higher for COA (onset at ages between 0 and 19 years; h2g = 25.6%) than for AOA (onset at ages between 20 and 60 years; h2g = 10.6%). The genetic correlation (rg) between COA and AOA was 0.67. Variation in age of onset among COA-affected individuals had a low heritability (h2g = 5%), which we confirmed in independent studies and also among AOA-affected individuals. To identify subtype-specific genetic associations, we performed a genome-wide association study (GWAS) in the UK Biobank for COA (13,962 affected individuals) and a separate GWAS for AOA (26,582 affected individuals) by using a common set of 300,671 controls for both studies. We identified 123 independent associations for COA and 56 for AOA (37 overlapped); of these, 98 and 34, respectively, were reproducible in an independent study (n = 262,767). Collectively, 28 associations were not previously reported. For 96 COA-associated variants, including five variants that represent COA-specific risk factors, the risk allele was more common in COA- than in AOA-affected individuals. Conversely, we identified three variants that are stronger risk factors for AOA. Variants associated with obesity and smoking had a stronger contribution to the risk of AOA than to the risk of COA. Lastly, we identified 109 likely target genes of the associated variants, primarily on the basis of correlated expression quantitative trait loci (up to n = 31,684). GWAS informed by age of onset can identify subtype-specific risk variants, which can help us understand differences in pathophysiology between COA and AOA and so can be informative for drug development.

11.
Environ Int ; 128: 63-69, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31029980

RESUMO

BACKGROUND: It has been suggested that adults who use cleaning agents in their homes have a higher risk of asthma and allergic symptoms. The associations of asthma and allergic symptoms with household use of cleaning agents in adolescents have not been investigated yet. OBJECTIVES: To examine the associations of household cleaning agents use with the prevalence of asthma, rhinitis and eczema in adolescents. METHODS: In this cross-sectional analysis, we included participants of the PIAMA birth cohort study with data on household use of 10 types of cleaning agents and information on asthma, rhinitis and/or eczema from parent-completed questionnaires at age 14 (N = 2333). For the cleaning agents, we developed a composite score ranging from 0 (no exposure) to 30 points (household use on 4-7 days per week for all 10 types of cleaning agents). Logistic regression was used to analyse associations between household cleaning agents use (composite score and specific cleaning agents) and outcomes, adjusting for potential confounders. RESULTS: Seven, 13 and 11% of the participants had asthma, rhinitis and eczema, respectively, at age 14. The composite score for household use of cleaning agents was not associated with asthma, rhinitis and eczema. For instance, adjusted odds ratios (95% confidence interval) for the prevalence of asthma, rhinitis and eczema comparing those with the highest use of cleaning agents (≥10 points) to those with never/seldom use (0-4 points) were 0.95 (0.56, 1.63), 1.23 (0.82, 1.82) and 0.95 (0.56, 1.63), respectively. For individual cleaning agents, we only found the use of ammonia to be significantly associated with a lower risk of rhinitis [0.60, (0.44, 0.82)]. CONCLUSIONS: There was no indication of an increased prevalence of asthma, rhinitis or eczema among adolescents living in households within the highest category of cleaning agents use.


Assuntos
Detergentes , Exposição Ambiental/estatística & dados numéricos , Hipersensibilidade Respiratória/epidemiologia , Adolescente , Estudos Transversais , Eczema/epidemiologia , Humanos
12.
Am J Respir Cell Mol Biol ; 61(1): 31-41, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30995076

RESUMO

Lung disease accounts for every sixth death globally. Profiling the molecular state of all lung cell types in health and disease is currently revolutionizing the identification of disease mechanisms and will aid the design of novel diagnostic and personalized therapeutic regimens. Recent progress in high-throughput techniques for single-cell genomic and transcriptomic analyses has opened up new possibilities to study individual cells within a tissue, classify these into cell types, and characterize variations in their molecular profiles as a function of genetics, environment, cell-cell interactions, developmental processes, aging, or disease. Integration of these cell state definitions with spatial information allows the in-depth molecular description of cellular neighborhoods and tissue microenvironments, including the tissue resident structural and immune cells, the tissue matrix, and the microbiome. The Human Cell Atlas consortium aims to characterize all cells in the healthy human body and has prioritized lung tissue as one of the flagship projects. Here, we present the rationale, the approach, and the expected impact of a Human Lung Cell Atlas.

13.
Environ Health ; 18(1): 39, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023382

RESUMO

BACKGROUND: Spirometric lung function measurements have been proven to be excellent objective markers of respiratory morbidity. The use of different types of spirometers in epidemiological and clinical studies may present systematically different results affecting interpretation and implication of results. We aimed to explore considerations in the use of different spirometers in epidemiological studies by comparing forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) measurements between the Masterscreen pneumotachograph and EasyOne spirometers. We also provide a correction equation for correcting systematic differences using regression calibration. METHODS: Forty-nine volunteers had lung function measured on two different spirometers in random order with at least three attempts on each spirometer. Data were analysed using correlation plots, Bland and Altman plots and formal paired t-tests. We used regression calibration to provide a correction equation. RESULTS: The mean (SD) FEV1 and FVC was 3.78 (0.63) L and 4.78 (0.63) L for the Masterscreen pneumotachograph and 3.54 (0.60) L and 4.41 (0.83) L for the EasyOne spirometer. The mean FEV1 difference of 0.24 L and mean FVC difference of 0.37 L between the spirometers (corresponding to 6.3 and 8.4% difference, respectively) were statistically significant and consistent between younger (< 30 years) and older volunteers (> 30 years) and between males and females. Regression calibration indicated that an increase of 1 L in the EasyOne measurements corresponded to an average increase of 1.032 L in FEV1 and 1.005 L in FVC in the Masterscreen measurements. CONCLUSION: Use of different types of spirometers may result in significant systematic differences in lung function values. Epidemiological researchers need to be aware of these potential systematic differences and correct for them in analyses using methods such as regression calibration.

14.
Eur Respir J ; 53(4)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30846474

RESUMO

The aim was to investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatmentWe performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe chronic obstructive pulmonary disease (COPD) patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls.Treatment with ICS for both 6 and 30 months significantly altered the expression of four miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor-κB.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.

16.
Cell Rep ; 26(7): 1701-1708.e3, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759382

RESUMO

In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner.

17.
Br J Nutr ; 121(8): 905-913, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30728088

RESUMO

Observational studies suggest that breast-feeding is associated with a more favourable BMI and cardio-metabolic markers, but potential underlying mechanisms are unclear. As serum adiponectin has an important function in adults for glucose and lipid metabolism, we assessed 251 participants of the Prevention and Incidence of Asthma and Mite Allergy birth cohort whether breast milk adiponectin is associated with childhood BMI and cardio-metabolic markers. We measured adiponectin levels in breast milk collected around 3 months after birth of the child and subsequently obtained weight and height repeatedly up to the age of 17 years. A medical examination (including blood pressure, glycated Hb and cholesterol) was performed at the age of 8, 12 and 16 years. We used multivariable mixed models to assess the association between breast milk adiponectin and BMI and cardio-metabolic markers at these ages. In models adjusted for exact age of breast milk collection, maternal age, presence of siblings, maternal BMI, pregnancy weight gain and child's birth weight, each unit increase in log breast milk adiponectin (in ng/ml) was associated with a 0·28 lower BMI z score (95 % CI -0·56, 0·00) at 3 months. After the age of 1 year, there was a tendency towards a higher BMI z score with increased breast milk adiponectin at some ages, but this pattern was not consistent throughout childhood. There were no associations between breast milk adiponectin and any of the cardio-metabolic markers in childhood. We conclude that in our study with follow-up until 17 years of age, breast milk adiponectin has no long-term effect on BMI and cardio-metabolic health during childhood.

18.
Curr Opin Allergy Clin Immunol ; 19(2): 141-147, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30649013

RESUMO

PURPOSE OF REVIEW: Childhood asthma is a heterogeneous disease and many children have uncontrolled disease. Therefore an individualized approach is needed to improve asthma outcomes in children. Precision medicine using clinical characteristics, biomarkers, and the rapidly involving field of genomics and pharmacogenomics aims to achieve asthma control and reduce future risks with less side-effects in individual children with asthma. RECENT FINDINGS: It is not yet possible to select treatment options on clinical characteristics. Novel monoclonal antibodies are efficacious in patients with severe, eosinophilic asthma. Reduced lung function growth and early decline is a prevalent finding in children with persistent asthma. Pharmacogenetic studies have identified children at risk for cortisol suppression when using inhaled corticosteroids. SUMMARY: Clinical characteristics and simple biomarkers like eosinophils, IgE, and the fraction of exhaled nitric oxide may be used in clinical practice for a basic precision medicine approach, deciding which children will have the best chance to respond to inhaled corticosteroids and to the biologicals omalizumab and mepolizumab.Further application of pharmacogenomics and breathomics needs additional studies before they can be applied as tools for precision medicine in individual children with asthma.

19.
Ann Am Thorac Soc ; 16(1): 1-16, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30592451

RESUMO

High-throughput, "next-generation" sequencing methods are now being broadly applied across all fields of biomedical research, including respiratory disease, critical care, and sleep medicine. Although there are numerous review articles and best practice guidelines related to sequencing methods and data analysis, there are fewer resources summarizing issues related to study design and interpretation, especially as applied to common, complex, nonmalignant diseases. To address these gaps, a single-day workshop was held at the American Thoracic Society meeting in May 2017, led by the American Thoracic Society Section on Genetics and Genomics. The aim of this workshop was to review the design, analysis, interpretation, and functional follow-up of high-throughput sequencing studies in respiratory, critical care, and sleep medicine research. This workshop brought together experts in multiple fields, including genetic epidemiology, biobanking, bioinformatics, and research ethics, along with physician-scientists with expertise in a range of relevant diseases. The workshop focused on application of DNA and RNA sequencing research in common chronic diseases and did not cover sequencing studies in lung cancer, monogenic diseases (e.g., cystic fibrosis), or microbiome sequencing. Participants reviewed and discussed study design, data analysis and presentation, interpretation, functional follow-up, and reporting of results. This report summarizes the main conclusions of the workshop, specifically addressing the application of these methods in respiratory, critical care, and sleep medicine research. This workshop report may serve as a resource for our research community as well as for journal editors and reviewers of sequencing-based manuscript submissions in our research field.

20.
Lancet Respir Med ; 7(4): 336-346, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30584054

RESUMO

BACKGROUND: Epigenetic mechanisms could alter the airway epithelial barrier and ultimately lead to atopic diseases such as asthma. We aimed to identify DNA methylation profiles that are associated with-and could accurately classify-atopy and atopic asthma in school-aged children. METHODS: We did a genome-wide study of DNA methylation in nasal epithelium and atopy or atopic asthma in 483 Puerto Rican children aged 9-20 years, recruited using multistage probability sampling. Atopy was defined as at least one positive IgE (≥0·35 IU/mL) to common aeroallergens, and asthma was defined as a physician's diagnosis plus wheeze in the previous year. Significant (false discovery rate p<0·01) methylation signals were correlated with gene expression, and top CpGs were validated by pyrosequencing. We then replicated our top methylation findings in a cohort of 72 predominantly African American children, and in 432 children from a European birth cohort. Next, we tested classification models based on nasal methylation for atopy or atopic asthma in all cohorts. FINDINGS: DNA methylation profiles were markedly different between children with (n=312) and without (n=171) atopy in the Puerto Rico discovery cohort, recruited from Feb 12, 2014, until May 8, 2017. After adjustment for covariates and multiple testing, we found 8664 differentially methylated CpGs by atopy, with false discovery rate-adjusted p values ranging from 9·58 × 10-17 to 2·18 × 10-22 for the top 30 CpGs. These CpGs were in or near genes relevant to epithelial barrier function, including CDHR3 and CDH26, and in other genes related to airway epithelial integrity and immune regulation, such as FBXL7, NTRK1, and SLC9A3. Moreover, 28 of the top 30 CpGs replicated in the same direction in both independent cohorts. Classification models of atopy based on nasal methylation performed well in the Puerto Rico cohort (area under the curve [AUC] 0·93-0·94 and accuracy 85-88%) and in both replication cohorts (AUC 0·74-0·92, accuracy 68-82%). The models also performed well for atopic asthma in the Puerto Rico cohort (AUC 0·95-1·00, accuracy 88%) and the replication cohorts (AUC 0·82-0·88, accuracy 86%). INTERPRETATION: We identified specific methylation profiles in airway epithelium that are associated with atopy and atopic asthma in children, and a nasal methylation panel that could classify children by atopy or atopic asthma. Our findings support the feasibility of using the nasal methylome for future clinical applications, such as predicting the development of asthma among wheezing infants. FUNDING: US National Institutes of Health.

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