The heterogeneity of asthma phenotypes in children and young adults.
Ontology highlight
ABSTRACT:
SUBMITTER: Hesselmar B
PROVIDER: S-EPMC3332210 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
The heterogeneity of asthma phenotypes in children and young adults.
Hesselmar Bill B Enelund Anna-Carin AC Eriksson Bo B Padyukov Leonid L Hanson Lars Å LÅ Aberg Nils N
Journal of allergy 20120411
Objective. Genetic heterogeneity and risk factor distribution was analyzed in two previously proposed asthma phenotypes. Method. A sample of 412 subjects was investigated at 7-8, 12-13, and 21-22 years of age with questionnaires, skin prick tests, and genetic analysis of IL-4 receptor (IL4R) single-nucleotide polymorphisms. The sample was subdivided in one group with no asthma, and two groups with asthma separated by age of onset of symptoms, namely, early onset asthma (EOA) and late onset asthm ...[more]
Similar Datasets
Project description:BackgroundOlder adults have high rates of asthma morbidity and mortality. Asthma is now recognized as a heterogeneous disease, yet the distinct phenotypes among older adults are unknown.ObjectiveThe objective of this study was to identify asthma phenotypes in a diverse population of elderly patients with asthma.MethodsUsing cluster analysis, 180 older adults with persistent asthma were analyzed. Subjects completed detailed questionnaires, skin prick testing, and spirometry with reversibility. Twenty-four core variables were analyzed.ResultsFour groups were identified. Subjects in cluster 1 (n = 69) typically had asthma diagnosed after the age of 40 and the shortest duration of asthma. Cluster 2 (n = 40) had the mildest asthma defined by spirometry, Asthma Control test (ACT), and Asthma Quality of Life Questionnaire (AQLQ). They also had the lowest body mass index (BMI), lowest depression score, and least number of comorbidities. Cluster 3 (n = 46) had the longest duration of asthma (56 years) and the highest atopic skin test sensitization (74%). Cluster 4 (n = 25) had the most severe asthma, with extremely low FEV1% predicted (37.8%), lowest ACT, and lowest AQLQ scores. They were more likely to be black and had the highest comorbidities. Using BMI, posttreatment FEV1% predicted, and duration of asthma, 95.6% of subjects were able to be correctly classified.ConclusionsIn older adults with asthma, distinct phenotypes vary on key features that are more pronounced among the elderly, including comorbidities, fixed airway obstruction, and duration of asthma ≥40 years. Further work is required to determine the clinical and therapeutic implications for different asthma phenotypes in older adults.
| S-EPMC5897052 | biostudies-literature
Project description:BackgroundChildren with asthma in low-income urban areas have high morbidity. Phenotypic analysis in these children is lacking, but may identify characteristics to inform successful tailored management approaches.ObjectiveWe sought to identify distinct asthma phenotypes among inner-city children receiving guidelines-based management.MethodsNine inner-city asthma consortium centers enrolled 717 children aged 6 to 17 years. Data were collected at baseline and prospectively every 2 months for 1 year. Participants' asthma and rhinitis were optimally managed by study physicians on the basis of guidelines. Cluster analysis using 50 baseline and 12 longitudinal variables was performed in 616 participants completing 4 or more follow-up visits.ResultsFive clusters (designated A through E) were distinguished by indicators of asthma and rhinitis severity, pulmonary physiology, allergy (sensitization and total serum IgE), and allergic inflammation. In comparison to other clusters, cluster A was distinguished by lower allergy/inflammation, minimally symptomatic asthma and rhinitis, and normal pulmonary physiology. Cluster B had highly symptomatic asthma despite high step-level treatment, lower allergy and inflammation, and mildly altered pulmonary physiology. Cluster C had minimally symptomatic asthma and rhinitis, intermediate allergy and inflammation, and mildly impaired pulmonary physiology. Clusters D and E exhibited progressively higher asthma and rhinitis symptoms and allergy/inflammation. Cluster E had the most symptomatic asthma while receiving high step-level treatment and had the highest total serum IgE level (median, 733 kU/L), blood eosinophil count (median, 400 cells/mm3), and allergen sensitizations (15 of 22 tested).ConclusionsAllergy distinguishes asthma phenotypes in urban children. Severe asthma often coclusters with highly allergic children. However, a symptomatic phenotype with little allergy or allergic inflammation was identified.
| S-EPMC5104222 | biostudies-literature
Project description:Several studies have shown that the airways of asthma patients contain higher diversity of bacteria and are enriched in pathogenic species. However, sampling the airways in children is challenging. Here we aimed to identify differences in the salivary bacterial composition between African Americans children with and without asthma. Saliva samples from 57 asthma cases and 57 healthy controls were analyzed by means of 16S ribosomal RNA amplicon profiling. Measurements of bacterial diversity and genus relative abundance were compared between cases and controls using the nonparametric Wilcoxon test and multivariate regression models. A total of five phyla and a mean of 56 genera were identified. Among them, 15 genera had a relative abundance greater than 1%, being Prevotella, Haemophilus, Streptococcus, and Veillonella the most abundant genera. Differences between cases and controls were found in terms of diversity, as well as in relative abundance for Streptococcus genus (13.0% in cases vs 18.3% in controls; P?=?.003) and Veillonella genus (11.1% in cases vs 8.0% in controls; P?=?.002). These differences remained significant after correction for multiple comparisons and when potential confounders were taken into account in logistic regression models. In conclusion, we identified changes in the salivary microbiota associated with asthma among African Americans.
| S-EPMC6851413 | biostudies-literature
Project description:Importance:Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. Objective:To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. Design, Setting, and Participants:This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed-at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular diagnosis of patients. Each patient's neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. Main Outcomes and Measures:Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. Results:Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities on magnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and very rare homozygous and compound heterozygous mutations were identified that led to the absence of the protein and complex I disassembly as well as mild mitochondrial network fragmentation. Conclusions and Relevance:A broad clinical spectrum of neurologic features, ranging from isolated optic atrophy to severe early-onset encephalopathies, is associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening in both syndromic neurologic presentations and nonsyndromic recessive optic neuropathies.
| S-EPMC5833489 | biostudies-literature
Project description:BackgroundFood allergy (FA) appears early in the atopic march, a progression that may lead to the development of asthma. The association between FA and pulmonary function in children with and without asthma remains unknown.ObjectiveTo investigate the association between FA and lung function in children with and without asthma.MethodsWe enrolled 1,068 children as a part of a family-based FA cohort. We then categorized children as having FA by physician diagnosis, evidence of specific IgE, and typical symptoms within 2 hours of food ingestion. We categorized asthma by physician diagnosis. We used American Thoracic Society criteria for spirometry measurements. We assessed the effects of asthma classification and FA number on lung function using mixed-effect models.ResultsWe enrolled 1,068 children: 417 (39%) had asthma, 402 (38%) had at least 1 FA, and 162 (15%) had 2 or more FAs. Unstratified analyses found no significant association between FA number and lung function. In children with asthma, we detected statistically significant differences in predicted forced expiratory flow at 25% to 75% between children with 2 or more FAs compared with those with none (mean [SE] β = -7.5 [3.6]; P = .04). This effect lost significance after adjusting for aeroallergen sensitization. We detected no significant associations between FA number and predicted forced expiratory volume in 1 second, forced vital capacity, and ratio of forced expiratory volume in 1 second to forced vital capacity.ConclusionHaving 2 or more FAs is a potential risk factor for greater small airway airflow obstruction among children with asthma, highlighting the need for close clinical follow-up and improved intervention strategies for these patients.
| S-EPMC6215513 | biostudies-literature
Project description:Literature is limited regarding the COVID-19 pandemic's impact on health services use in younger Canadian populations with asthma. We utilized health administrative databases from January 2019-December 2021 for a population-based cross-sectional study to identify Ontario residents 0-25 years old with physician-diagnosed asthma and calculate rates of healthcare use. Multivariable negative binomial regression analysis was used to adjust for confounders. We included 716,690 children and young adults ≤25 years. There was a sharp increase of ICS and SABA prescription rates at the start of the pandemic (March 2020) of 61.7% and 54.6%, respectively. Monthly virtual physician visit rates increased from zero to 0.23 per 100 asthma population during the pandemic. After adjusting for potential confounders, rate ratios (RR) with 95% confidence intervals (CI) showed that the pandemic was associated with significant decrease in hospital admissions (RR = 0.21, 95% CI: 0.18-0.24), emergency department visits (RR = 0.35, 95% CI: 0.34-0.37), and physician visits (RR = 0.61, 95% CI: 0.60-0.61). ICS and SABA prescriptions filled also significantly decreased during the pandemic (RR = 0.58, 95% CI: 0.57-0.60 and RR = 0.47, 95% CI: 0.46-0.48, respectively). This Canadian population-based asthma study demonstrated a dramatic decline in physician and emergency department visits, hospitalizations, and medication prescriptions filled during the COVID-19 pandemic. An extensive evaluation of the factors contributing to an 80% reduction in the risk of hospitalization may inform post-pandemic asthma management.
| S-EPMC9838850 | biostudies-literature
Project description:BackgroundThe polymorphism Arg16 in β2 -adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long-acting β2 -agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27.ObjectiveWe assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA.MethodsThe study was undertaken using data from 10 independent studies (n = 5903) participating in the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma-related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta-analysed using the inverse variance weighting method assuming random-effects.ResultsIn subjects treated with ICS and LABA (n = 832, age: 3-21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05-1.87, I2 = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05-1.94, I2 = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71-1.39, I2 = 0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2 haplotypes and asthma exacerbations in the other treatment categories, namely as-required short-acting β2 -agonists (n = 973), ICS monotherapy (n = 2623), ICS plus leukotriene receptor antagonists (LTRA; n = 338), or ICS plus LABA plus LTRA (n = 686).Conclusion and clinical relevanceThe ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype-guided treatment which might improve clinical outcomes in asthmatic patients.
| S-EPMC8503671 | biostudies-literature
Project description:BACKGROUND:Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications. METHODS:The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response. RESULTS:Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/?L or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments. CONCLUSIONS:In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.
| S-EPMC5148729 | biostudies-literature
Project description:We review the imaging findings of pediatric gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using contemporary anatomic and molecular imaging techniques. A low index of suspicion can result in significant delays in diagnosis of pediatric GEP-NETs. A multimodality imaging approach, using both anatomic and functional imaging, is essential in the diagnosis, staging, and surveillance of these potentially malignant tumors.
| S-EPMC2292492 | biostudies-other
Project description:BACKGROUND:Asthma phenotypes are currently not amenable to primary prevention or early intervention because their natural history cannot be reliably predicted. Clinicians remain reliant on poorly predictive asthma outcome tools because of a lack of better alternatives. OBJECTIVE:We sought to develop a quantitative personalized tool to predict asthma development in young children. METHODS:Data from the Cincinnati Childhood Allergy and Air Pollution Study (n = 762) birth cohort were used to identify factors that predicted asthma development. The Pediatric Asthma Risk Score (PARS) was constructed by integrating demographic and clinical data. The sensitivity and specificity of PARS were compared with those of the Asthma Predictive Index (API) and replicated in the Isle of Wight birth cohort. RESULTS:PARS reliably predicted asthma development in the Cincinnati Childhood Allergy and Air Pollution Study (sensitivity = 0.68, specificity = 0.77). Although both the PARS and API predicted asthma in high-risk children, the PARS had improved ability to predict asthma in children with mild-to-moderate asthma risk. In addition to parental asthma, eczema, and wheezing apart from colds, variables that predicted asthma in the PARS included early wheezing (odds ratio [OR], 2.88; 95% CI, 1.52-5.37), sensitization to 2 or more food allergens and/or aeroallergens (OR, 2.44; 95% CI, 1.49-4.05), and African American race (OR, 2.04; 95% CI, 1.19-3.47). The PARS was replicated in the Isle of Wight birth cohort (sensitivity = 0.67, specificity = 0.79), demonstrating that it is a robust, valid, and generalizable asthma predictive tool. CONCLUSIONS:The PARS performed better than the API in children with mild-to-moderate asthma. This is significant because these children are the most common and most difficult to predict and might be the most amenable to prevention strategies.
| S-EPMC6504569 | biostudies-literature