Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation.
Ontology highlight
ABSTRACT:
SUBMITTER: Fitzpatrick AM
PROVIDER: S-EPMC6401237 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundDaily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.MethodsWe studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.ResultsThe daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.ConclusionsA daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).
| S-EPMC3247621 | biostudies-literature
Project description:Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population. We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n=16; no sensitization, n=36). Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid (poly(I:C)) as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation. 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (i.e., more myeloperoxidase and extracellular DNA) and less neutrophil pro-inflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (i.e., M2) phenotype in sensitized children and a more pro-inflammatory (i.e., M1) phenotype in non-sensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled healthcare were also higher in children without aeroallergen sensitization after enrollment. Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at T2-high inflammation.
2024-01-29 | GSE254019 | GEO
Project description:Recurrent wheezing in the preschool children is a common clinical problem, often associated with significant morbidity related to acute episodes. The management of these children has been complicated by a paucity of high-quality clinical trials in this age group. To fill this knowledge gap, National Heart, Lung, and Blood Institute's asthma research networks have performed a series of clinical trials in an effort to provide practitioners with guidance on appropriate management strategies. These studies establish daily inhaled corticosteroid (ICS) therapy in toddlers at high risk for subsequent asthma as an effective approach for the prevention of exacerbations and symptom reduction, but without evidence of disease-modifying properties. Additional studies have confirmed substantial heterogeneity in ICS response, in terms of both efficacy and effect on linear growth. Treatment with intermittent high-dose ICS was demonstrated to be an alternative approach to daily low-dose ICS for preventing severe exacerbations in toddlers with intermittent but significant wheeze and a positive modified asthma predictive index. This review details the findings and clinical implications derived from these studies, discuss the utility of biomarkers and the role of oral corticosteroids during acute exacerbations, and summarizes ongoing clinical trials in this age group.
| S-EPMC4715860 | biostudies-literature
Project description:BackgroundFactors responsible for asthma exacerbations in children are complex and may differ from those that drive asthma severity.ObjectiveTo identify latent classes of children at risk for asthma exacerbation and determine whether latent class assignment is useful in the prediction of future exacerbation.MethodsLatent class analysis was performed on 513 children aged 6 to 17 years at risk for asthma exacerbation, with 31 variables encompassing demographics, medical history, treatment, symptoms, lung function, sensitization, and type 2 inflammation. Primary and secondary outcomes included exacerbation occurrence by 12 months and time to first exacerbation, respectively.ResultsFour latent classes were identified with differing demographic features, sensitization and type 2 inflammatory markers, prior exacerbation severity and health care utilization, and lung function. Exacerbations occurred in 22.4% of class 1 ("lesser sensitization with normal lung function"), 27.9% of class 2 ("lesser sensitization with prior severe exacerbation and normal lung function"), 45.3% of class 3 ("multiple sensitization with reversible airflow limitation"), and 64.3% of class 4 ("multiple sensitization with partially reversible airflow limitation") (P < .001). Time to exacerbation also followed similar trends and was shortest in the latent classes with multiple sensitization and airflow limitation (P < .001). Outcomes were driven largely by children with exacerbation-prone asthma (defined as ≥3 exacerbations in the prior year), who were present in each class but most strongly represented in classes 3 and 4.ConclusionsChildren at risk for asthma exacerbation are a heterogeneous group. Sensitization, prior exacerbation severity, and lung function variables may be particularly useful in identifying children at greatest risk for future exacerbation.
| S-EPMC7338257 | biostudies-literature
Project description:IntroductionPreschool wheezers are at high risk of recurrent attacks triggered by respiratory viruses, sometimes exacerbated by exposure to allergens and pollution. Because of the COVID-19 infection, the lockdown was introduced, but the effects on preschool wheezers are unknown. We hypothesized that there would be an improvement in outcomes during the lockdown, and these would be lost when the lockdown was eased.Materials and methodsPatients underwent medical visits before and after the COVID-19 lockdown. We recorded the childhood Asthma Control Test (cACT) and a clinical questionnaire. Data on symptoms, the need for medications and the use of healthcare resources were recorded. We compared these data with retrospective reports from the preceding year and prospectively acquired questionnaires after lockdown.ResultsWe studied 85 preschool wheezers, mean age 4.9 years. During the lockdown, cACT score was significantly higher (median 25 vs. 23); families reported a dramatic drop in wheezing episodes (51 vs. none), significant reductions in the day and nighttime symptoms, including episodes of shortness of breath (p < .0001); the use of salbutamol and oral corticosteroids (OCS) dropped significantly (p < .0001) and 79 (95%) patients needed no OCS bursts during the lockdown. Finally, patients had significantly fewer extra medical examinations, as well as fewer Emergency Room visits (p < .0001). All were improved compared with the same time period from the previous year, but outcomes worsened significantly again after lockdown (cACT median: 22).ConclusionsDuring the national lockdown, children with persistent preschool wheeze showed a significant clinical improvement with reduction of respiratory symptoms, medication use for exacerbations, and use of healthcare resources. This trend reversed when lockdown restrictions were eased.
| S-EPMC8251173 | biostudies-literature
Project description:BackgroundOral corticosteroids (OCSs) are recommended for severe wheezing episodes in children. However, limited evidence supports this intervention in preschool children with outpatient wheezing illnesses.ObjectiveWe sought to investigate whether OCSs reduce symptom scores during acute lower respiratory tract illnesses (LRTIs) in preschool children with recurrent wheeze.MethodsWe performed post hoc and replication analyses in 2 outpatient cohorts of children aged 1 to 5 years with episodic wheezing participating in clinical trials. We compared symptom scores during LRTIs that were or were not treated with OCSs, adjusting for differences in disease and episode severity covariates. We stratified episodes by severity by using a propensity model. The primary outcome was the area under the curve (AUC) of total symptom scores among the more severe episodes.ResultsTwo hundred fifteen participants from the Acute Intervention Management Strategies trial experienced 798 acute LRTIs, 112 of which were defined as severe based on propensity scores. The AUCs of total symptom scores did not differ between the episodes that were (n = 70) and were not (n = 42) treated with OCSs (P = .46) nor was there an OCS treatment effect on individual symptom scores. Similar analyses of the Maintenance Versus Intermittent Inhaled Corticosteroids in Wheezing Toddlers trial, involving 278 participants with 133 severe LRTIs, confirmed the above findings (P = .46 for AUC of total symptoms score comparison).ConclusionIn 2 separate cohorts of preschool children with episodic wheezing, OCS treatment during clinically significant LRTIs did not reduce symptom severity during acute LRTIs, despite asthma controller medication use during most episodes. These findings need to be confirmed in a prospective randomized controlled trial.
| S-EPMC3810170 | biostudies-literature
Project description:AimsThis study sought to determine whether clinical clusters exist in takotsubo cardiomyopathy. Takotsubo cardiomyopathy (TCM) is a heterogeneous disorder with a complex, poorly understood pathogenesis. To better understand the heterogeneity of TCM, we identified different clinical phenotypes in a large sample of TCM patients by using latent class analysis (LCA).Methods and resultsUsing the National Inpatient Sample (NIS) database, we identified 3139 patients admitted to hospitals in 2016-2017 with a primary diagnosis of TCM. We performed LCA based on several patient demographics and comorbidities: age, sex, hypertension, hyperlipidaemia, diabetes mellitus, obesity, current smoking, asthma, chronic obstructive pulmonary disease (COPD), and anxiety and depressive disorders. We then repeated LCA separately with the NIS 2016 and 2017 data sets and performed a robust test to validate our results. We also compared in-hospital outcomes among the different clusters identified by LCA. Four patient clusters were identified. C1 (n = 1228, 39.4%) had the highest prevalence of hyperlipidaemia (93.4%), hypertension (61.6%), and diabetes (34.3%). In C2 (n = 440, 14.0%), all patients had COPD, and many were smokers (45.8%). C3 (n = 376, 11.8%) largely comprised patients with anxiety disorders (98.4%) and depressive disorders (80.1%). C4 (n = 1097, 34.8%) comprised patients with isolated TCM and few comorbidities. Among all clusters, C1 had the lowest in-hospital mortality (1.0%) and the shortest length of stay (3.2 ± 3.1 days), whereas C2 had the highest in-hospital mortality (3.4%).ConclusionsUsing LCA, we identified four clinical phenotypes of TCM. These may reflect different pathophysiological processes in TCM. Our findings may help identify treatment targets and select patients for future clinical trials.
| S-EPMC7835582 | biostudies-literature
Project description:Young children can experience violence directly or indirectly in the home, with some children exposed to multiple forms of violence. These polyvictims often experience violence that is severe, chronic, and multifaceted. The current study used latent class analysis to identify and examine the pattern of profiles of exposure to family violence (i.e., violence directed towards the child and between caregivers) among a sample of 474 children ages 3-6 year who were drawn from the Multidimensional Assessment of Preschoolers Study (Wakschlag et al., 2014). The data yielded 3 classes: a polyvictimized class (n = 72; 15.2%) with high probability of exposure to all forms of violence, a harsh parenting class (n = 235; 49.5%), distinguished mainly by child-directed physical discipline in the absence of more severe forms of violence, and a low-exposure class (n = 167; 35.2%). Classes were differentiated by contextual factors, maternal characteristics, and mother-reported and observational indicators of parenting and child functioning with most effect sizes between medium and large. These findings add to emerging evidence linking polyvictimization to impaired caregiving and adverse psychological outcomes for children and offer important insight for prevention and intervention for this vulnerable population.
| S-EPMC5140743 | biostudies-literature
Project description:Atopic sensitization (ie, atopy) is the most commonly reported risk factor for asthma. Recent studies have begun to suggest that atopy, as conventionally defined, might be an umbrella term that obfuscates more specific allergic disease types.We sought to determine whether distinct and meaningful atopic phenotypes exist within a racially diverse birth cohort using 10 allergen-specific serum IgE (sIgE) measurements from children aged 2 years.Using the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (62% black), we analyzed sIgE data on 10 allergens (Dermatophagoides farinae, dog, cat, timothy grass, ragweed, Alternaria alternata, egg, peanut, milk, and German cockroach) obtained from 594 children at age 2 years. Conventional atopy was defined as at least 1 sIgE level of 0.35 IU/mL or greater.A 4-class solution (latent class model) was the best fit. Class types were labeled "low to no sensitization" (76.9% of sample), "highly sensitized" (2.7%), "milk and egg dominated" (15.3%), and "peanut and inhalant(s)" (5.1%). Almost one third (32.2%) of the low to no sensitization group met the criteria for conventional atopy. The highly sensitized group was significantly associated with a doctor's diagnosis of asthma after age 4 years (odds ratio [OR], 5.3; 95% CI, 1.6-17.4), whereas the milk and egg dominated and peanut and inhalant(s) groups were not (ORs of 1.6 [95% CI, 0.8-3.0] and 1.8 [95% CI, 0.6-4.9], respectively). Children of black race were more likely to be in the 3 multisensitized groups (P = .04).Classification by sIgE patterns defined groups whose membership is more strongly associated with atopic dermatitis, wheeze, and asthma compared with conventional atopy.
| S-EPMC4149949 | biostudies-literature
Project description:BackgroundFrailty is an important concept in the care of older adults although controversy remains regarding its defining features and clinical utility. Both the Fried phenotype and the Rockwood deficit accumulation approaches cast frailty as a "burden" without exploring the relative salience of its cardinal markers and their relevance to the patient. New multifactorial perspectives require a reliable assessment of frailty that can validly predict postoperative health outcomes.MethodsIn a retrospective study of 2828 unselected surgical patients, we used item response theory to examine the ability of 32 heterogeneous markers capturing limitations in physical, functional, emotional, and social activity domains to indicate severity of frailty as a latent continuum. Eighteen markers efficiently indicated frailty severity and were then subject to latent class analysis to derive discrete phenotypes. Next, we validated the obtained frailty phenotypes against patient-reported 30-day postoperative outcomes using multivariable logistic regression. Models were adjusted for demographics, comorbidity, type and duration of surgery, and cigarette and alcohol consumption.ResultsThe 18 markers provided psychometric evidence of a single reliable continuum of frailty severity. Latent class analyses produced 3 distinct subtypes, based on patients' endorsement probabilities of the frailty indicators: not frail (49.7%), moderately frail (33.5%), and severely frail (16.7%). Unlike the moderate class, severely frail endorsed emotional health problems in addition to physical burdens and functional limitations. Models adjusting for age, sex, type of anesthesia, and intraoperative factors indicated that severely frail (odds ratio, 1.89; 95% confidence interval, 1.42-2.50) and moderately frail patients (odds ratio, 1.31; 95% confidence interval, 1.03-1.67) both had higher odds of experiencing postoperative complications compared to not frail patients. In a 3-way comparison, a higher proportion of severely frail patients (10.7%) reported poorer quality of life after surgery compared to moderately frail (9.2%) and not frail (8.3%) patients (P < .001). There was no significant difference among these groups in proportions reporting hospital readmission (5.6%, 5.1%, and 3.8%, respectively; P = .067).ConclusionsSelf-report frailty items can accurately discern 3 distinct phenotypes differing in composition and their relations with surgical outcomes. Systematically assessing a wider set of domains including limitations in functional, emotional, and social activities can inform clinicians on what precipitates loss of physiological reserve and profoundly influences patients' lives. This information can help guide the current discussion on frailty and add meaningful clinical tools to the surgical practice.
| S-EPMC6931904 | biostudies-literature