Nutrition, Obesity and Asthma Inception in Children. The Role of Lung Function.
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ABSTRACT:
SUBMITTER: Manuel SS
PROVIDER: S-EPMC8624093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The association of early-onset wheezing with common viral and bacterial infections has raised significant interest in the role of infections in childhood asthma inception. This article serves to review these relationships among infections, host factors, and asthma inception in childhood.
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Project description:Human Respiratory Syncytial Virus and Human Rhinovirus are the most frequent cause of respiratory tract infections in infants and children and are major triggers of acute viral bronchiolitis, wheezing and asthma exacerbations. Here, we will discuss the application of the powerful tools of systems biology to decode the molecular mechanisms that determine risk for infection and subsequent asthma. An important conceptual advance is the understanding that the innate immune system is governed by a Bow-tie architecture, where diverse input signals converge onto a few core pathways (e.g., IRF7), which in turn generate diverse outputs that orchestrate effector and regulatory functions. Molecular profiling studies in children with severe exacerbations of asthma/wheeze have identified two major immunological phenotypes. The IRF7hi phenotype is characterised by robust upregulation of antiviral response networks, and the IRF7lo phenotype is characterised by upregulation of markers of TGF? signalling and type 2 inflammation. Similar phenotypes have been identified in infants and children with severe viral bronchiolitis. Notably, genome-wide association studies supported by experimental validation have identified key pathways that increase susceptibility to HRV infection (ORMDL3 and CHDR3) and modulate TGF? signalling (GSDMB, TGFBR1, and SMAD3). Moreover, functional deficiencies in the activation of type I and III interferon responses are already evident at birth in children at risk of developing febrile lower respiratory tract infections and persistent asthma/wheeze, suggesting that the trajectory to asthma begins at birth or in utero. Finally, exposure to microbes and their products reprograms innate immunity and provides protection from the development of allergies and asthma in children, and therefore microbial products are logical candidates for the primary prevention of asthma.
| S-EPMC7503410 | biostudies-literature
Project description:Excess adipose tissue predisposes to an enhanced inflammatory state and can contribute to the pathogenesis and severity of asthma. Vitamin D has anti-inflammatory properties and low-serum levels are seen in children with asthma and in children with obesity. Here we review the intersection of asthma, obesity, and hypovitaminosis D in children. Supplementation with vitamin D has been proposed as a simple, safe, and inexpensive adjunctive therapy in a number of disease states. However, little research has examined the pharmacokinetics of vitamin D and its therapeutic potential in children who suffer from obesity-related asthma.
| S-EPMC8341445 | biostudies-literature
Project description:IntroductionIt is not clear whether asthma, the most frequent chronic disease in childhood, is a risk for severe SARS-CoV-2 infection in the pediatric population and how SARS-CoV-2 infection affects the lung functions in these patients.PurposeWe aimed to investigate the course and the consequences of SARS-CoV-2 infection among children with asthma and determine the risk factors for the decline in lung function tests (LFTs).MethodsIn this retrospective study, asthmatic children with coronavirus disease 2019 (COVID-19) were compared with a random control group of asthmatic patients without COVID-19. In addition, the clinical course and the effect on LFTs of COVID-19 among children with asthma were also evaluated.ResultsOne hundred eighty-nine patients who had COVID-19, and 792 who did not were included in the study. Fever, fatigue, and cough were the most frequent symptoms during COVID-19. Regarding the severity of COVID-19, 163 patients (87.6%) had a mild clinical condition, 13 (7%) had moderate disease, 1 (0.5%) had severe disease, and 2 had (1.1%) critically ill disease. Two patients were diagnosed with multisystem inflammatory syndrome in children (MIS-C), one patient suffered from pneumothorax. LFTs of the patients before and after COVID-19 infection were analyzed; no significant differences were found in FEV1 % (91.7% vs. 90.9%, p = 0.513), FVC% (89.8% vs. 90.8%, p = 0.502) and FEV1 /FVC (103.1% vs. 100.6%, p = 0.056), while FEF25%-75% values (107.6% vs. 98.4%, p < 0.001) were significantly lower after the COVID-19 infection. Obesity (odds ratio [OR]: 3.785, 95% confidence interval [CI]: 1.152-12.429, p = 0.028] and having a family history of atopy (OR: 3.359, 95% CI: 1.168-9.657, p = 0.025] were found to be the independent risk factors for ≥25% decrease in FEF25-75 after COVID-19 infection.ConclusionCOVID-19 infection leads to dysfunction of the small airways in asthmatic children and obesity is an independent risk factor for a ≥25% decrease in FEF25-75. The long-term effects of COVID-19 infection especially on small airways require close monitoring in children with asthma.
| S-EPMC9347415 | biostudies-literature
Project description:Changes in dietary patterns may partly explain the epidemic of asthma in industrialized countries. The objective of this study was to examine the relationship between dietary patterns and lung function and asthma exacerbations in Puerto Rican children. This is a case-control study of 678 Puerto Rican children (ages 6-14 years) in San Juan (Puerto Rico). All participants completed a respiratory health questionnaire and a 75-item food frequency questionnaire. Food items were aggregated into 7 groups: fruits, vegetables, grains, protein, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group and asthma. Based on the results, a dietary score was created [range from -2 (unhealthy diet: high consumption of dairy and sweets, low consumption of vegetables and grains) to 2 (healthy diet: high consumption of vegetables and grains and low consumption of dairy and sweet)]. Multivariable linear or logistic regression was used to assess the relationship between dietary score and lung function or asthma exacerbations. After adjustment for covariates, a healthier diet (each 1-point increment in dietary score) was associated with significantly higher %predicted forced expiratory volume in the first second (FEV1) and %predicted forced vital capacity (FVC) in control subjects. Dietary pattern alone was not associated with asthma exacerbations, but children with an unhealthy diet and vitamin D insufficiency (plasma 25(OH)D <30?ng/mL) had higher odds of ?1 severe asthma exacerbation [odds ratio (OR)?=?3.4, 95% confidence interval (CI)?=?1.5-7.5] or ?1 hospitalization due to asthma (OR?=?3.9, 95% CI?=?1.6-9.8, OR?=?3.4, 95% CI?=?1.5-7.5) than children who ate a healthy diet and were vitamin D sufficient. A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with higher lung function (as measured by FEV1 and FVC). Vitamin D insufficiency, together with an unhealthy diet, may have detrimental effects on asthma exacerbations in children.
| S-EPMC5733741 | biostudies-literature
Project description:Although our previous GWAS failed to identify SNPs associated with pulmonary function at the level of genomewide significance, it did show that the heritability for FEV1/FVC was 41.6% in a Japanese population, suggesting that the heritability of pulmonary function traits can be explained by the additive effects of multiple common SNPs. In addition, our previous study indicated that pulmonary function genes identified in previous GWASs in non-Japanese populations accounted for 4.3% to 12.0% of the entire estimated heritability of FEV1/FVC in a Japanese population. Therefore, given that many loci with individual weak effects may contribute to asthma risk, in this study, we created a quantitative score of genetic load based on 16 SNPs implicated in lower lung function in both Japanese and non-Japanese populations. This genetic risk score (GRS) for lower FEV1/FVC was consistently associated with the onset of asthma (P = 9.6 × 10(-4)) in 2 independent Japanese populations as well as with the onset of COPD (P = 0.042). Clustering of asthma patients based on GRS levels indicated that an increased GRS may be responsible for the development of a particular phenotype of asthma characterized by early onset, atopy, and severer airflow obstruction.
| S-EPMC4709100 | biostudies-literature
Project description:BACKGROUND:The development of novel therapeutics and treatment regimens for the management of asthma is hindered by an incomplete understanding of its heterogeneous nature and pathophysiology. Metabolomics can provide an integrated and global profile of a biological system in a dysregulated state, making it a valuable tool to identify biomarkers along the disease development pathway and to understand the biological mechanisms driving that pathway. METHODS:Liquid chromatography-mass spectrometry metabolomic profiling was conducted on plasma samples provided at recruitment for 380 children with asthma from the 'Genetic Epidemiology of Asthma in Costa Rica Cohort'. Metabolites associated with three clinical characteristics of asthma severity (i) airway hyper-responsiveness (AHR) (ii) percent-predicted forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and (iii) FEV1/FVC post-bronchodilator were identified and their discriminatory ability assessed. Metabolite set enrichment analyses was applied to explore the biology underlying these relationships. RESULTS:AHR was associated (p<0.05) with 91 of 574 metabolites (15.9%), FEV1/FVC pre-bronchodilator with 102(17.8%), and FEV1/FVC post-bronchodilator with 155 (27.0%). The findings suggest that these characteristics capture some common and some distinct phenotypic aspects of lung function; glycerophospholipid, linoleic acid and pyrimidine metabolism were common to all three characteristics. The corresponding metabolomic profiles showed moderate but robust discriminatory ability. CONCLUSIONS:The results confirm the existence of an asthma severity metabolome. However, differences in the metabolomic profiles of the three lung function characteristics studied, suggest that refinement of both phenotype classification and metabolite selection should be a priority as the field of asthma metabolomics progresses.
| S-EPMC5474172 | biostudies-literature
Project description:BackgroundWhether persistent overweight or obesity affects lung function or asthma morbidity in youth is unclear.ObjectiveTo evaluate overweight or obesity that persists between school age and adolescence and change in lung function and total immunoglobulin (Ig)E and severe asthma exacerbations in Puerto Rican youth.MethodsProspective study of 340 Puerto Rican youth assessed at 2 visits, the first at ages 6 to 14 years and the second at ages 9 to 20 years. Persistent overweight or obesity was defined as a body mass index z-score greater than or equal to 85th percentile at both visits. Outcomes of interest were change in percent predicted (%pred) lung function measures and total IgE between study visits and severe asthma exacerbations in the year before visit 2. Logistic or linear regression was used for multivariable analysis.ResultsIn multivariable analysis, persistently overweight or obese subjects had changes in %pred forced expiratory volume in 1 second (FEV1) (β = -5.07%; 95% confidence interval, -1.51% to -8.62%; P < .01) and %pred FEV1 to forced vital capacity (FVC) ratio (β = -2.85%; 95% confidence interval, -0.18% to -5.51%; P = .04) which were lower than those observed in subjects with normal weight at both study visits (control subjects). Compared with control subjects, those who were persistently overweight or obese and those who became overweight or obese at visit 2 had increased odds of more than or equal to 1 severe asthma exacerbation in the year before visit 2. There was no significant association between persistent overweight or obesity and change in %pred FVC or total IgE (P > .20 for both instances).ConclusionIn a prospective study of Puerto Rican youth, persistently overweight or obese subjects had lower changes in FEV1 or FEV1 to FVC ratio and higher odds of severe asthma exacerbations than subjects of normal weight.
| S-EPMC8977258 | biostudies-literature
Project description: Not available
| S-EPMC8556333 | biostudies-literature
Project description:BackgroundSingle omic analyses have provided some insight into the basis of lung function in children with asthma, but the underlying biologic pathways are still poorly understood.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify modules of coregulated gene transcripts and metabolites in blood among 325 children with asthma from the Genetic Epidemiology of Asthma in Costa Rica study. The biology of modules associated with lung function as measured by FEV1, the FEV1/FVC ratio, bronchodilator response, and airway responsiveness to methacholine was explored. Significantly correlated gene-metabolite module pairs were then identified, and their constituent features were analyzed for biologic pathway enrichments.ResultsWGCNA clustered 25,060 gene probes and 8,185 metabolite features into eight gene modules and eight metabolite modules, where four and six, respectively, were associated with lung function (P ≤ .05). The gene modules were enriched for immune, mitotic, and metabolic processes and asthma-associated microRNA targets. The metabolite modules were enriched for lipid and amino acid metabolism. Integration of correlated gene-metabolite modules expanded the single omic findings, linking the FEV1/FVC ratio with ORMDL3 and dysregulated lipid metabolism. This finding was replicated in an independent population.ConclusionsThe results of this hypothesis-generating study suggest a mechanistic basis for multiple asthma genes, including ORMDL3, and a role for lipid metabolism. They demonstrate that integrating multiple omic technologies may provide a more informative picture of asthmatic lung function biology than single omic analyses.
| S-EPMC6689076 | biostudies-literature