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The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort.

ABSTRACT: Cluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However, while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised.To use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort.K-means cluster analysis was undertaken among 309 currently wheezing subjects at 18 years in the Isle of Wight birth cohort (N = 1456). Thirteen disease-characterising clustering variables at 18 years were used. Resulting clusters were then further characterised by severity indices plus potential risk factors for wheeze development throughout the 1st 18 years of life.Six wheeze clusters were identified. Cluster 1 (12.3%) male-early-childhood-onset-atopic-wheeze-with-normal-lung-function had male predominance, normal spirometry, low bronchodilator reversibility (BDR), intermediate bronchial hyper-responsiveness (BHR), high atopy prevalence and more admissions. Cluster 2 (24.2%) early-childhood-onset-wheeze-with-intermediate-lung-function had no specific sex association, intermediate spirometry, BDR, BHR, more significant BTS step therapy and admissions. Cluster 3 (9.7%) female-early-childhood-onset-atopic-wheeze-with-impaired-lung-function showed female predominance, high allergic disease comorbidity, more severe BDR and BHR, greatest airflow obstruction, high smoking prevalence, higher symptom severity and admissions. Cluster 4 (19.4%) female-undiagnosed-wheezers had adolescent-onset non-atopic wheeze, low BDR and BHR, impaired but non-obstructed spirometry, high symptom frequency and highest smoking prevalence. Cluster 5 (24.6%) female-late-childhood-onset-wheeze-with-normal-lung-function showed no specific atopy association, normal spirometry, low BDR, BHR and symptom severity. Cluster 6 (9.7%) male-late-childhood-onset-atopic-wheeze-with-impaired-lung-function had high atopy and rhinitis prevalence, increased BDR and BHR, moderately impaired spirometry, high symptom severity and higher BTS step therapy.Young adult wheeze is diverse and can be classified into distinct clusters. More severe clusters merit attention and are associated with childhood onset, atopy, impaired lung function and in some, smoking. Smoking-associated undiagnosed wheezers also merit recognition. Better understanding of young adult wheeze could facilitate better later adult respiratory health.

SUBMITTER: Kurukulaaratchy RJ

PROVIDER: S-EPMC4010938 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort.

Kurukulaaratchy R J RJ Zhang H H Raza A A Patil V V Karmaus W W Ewart S S Arshad S H SH

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20140101 5

<h4>Background</h4>Cluster analyses have enhanced understanding of the heterogeneity of both paediatric and adult wheezing. However, while adolescence represents an important transitional phase, the nature of young adult wheeze has yet to be clearly characterised.<h4>Objectives</h4>To use cluster analysis to define, for the first time, clinically relevant young adult wheeze clusters in a longitudinal birth cohort.<h4>Methods</h4>K-means cluster analysis was undertaken among 309 currently wheezin ...[more]

PMID: 24654674

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Project description:BackgroundRhinitis affects many young adults and often shows comorbidity with asthma.ObjectiveWe hypothesized that young adult rhinitis, like asthma, exhibits clinical heterogeneity identifiable by means of cluster analysis.MethodsParticipants in the Isle of Wight birth cohort (n = 1456) were assessed at 1, 2, 4, 10, and 18 years of age. Cluster analysis was performed on those with rhinitis at age 18 years (n = 468) by using 13 variables defining clinical characteristics.ResultsFour clusters were identified. Patients in cluster 1 (n = 128 [27.4%]; ie, moderate childhood-onset rhinitis) had high atopy and eczema prevalence and high total IgE levels but low asthma prevalence. They showed the best lung function at 18 years of age, with normal fraction of exhaled nitric oxide (Feno), low bronchial hyperresponsiveness (BHR), and low bronchodilator reversibility (BDR) but high rhinitis symptoms and treatment. Patients in cluster 2 (n = 199 [42.5%]; ie, mild-adolescence-onset female rhinitis) had the lowest prevalence of comorbid atopy, asthma, and eczema. They had normal lung function and low BHR, BDR, Feno values, and total IgE levels plus low rhinitis symptoms, severity, and treatment. Patients in cluster 3 (n = 59 [12.6%]; ie, severe earliest-onset rhinitis with asthma) had the youngest rhinitis onset plus the highest comorbid asthma (of simultaneous onset) and atopy. They showed the most obstructed lung function with high BHR, BDR, and Feno values plus high rhinitis symptoms, severity, and treatment. Patient 4 in cluster 4 (n = 82 [17.5%]; ie, moderate childhood-onset male rhinitis with asthma) had high atopy, intermediate asthma, and low eczema. They had impaired lung function with high Feno values and total IgE levels but intermediate BHR and BDR. They had moderate rhinitis symptoms.ConclusionClinically distinctive adolescent rhinitis clusters are apparent with varying sex and asthma associations plus differing rhinitis severity and treatment needs.

Project description:BackgroundAn estimated 40% of cancer cases in the UK in 2015 were attributable to cancer risk behaviours. Tobacco smoking, alcohol consumption, obesity, and unprotected sexual intercourse are known causes of cancer and there is strong evidence that physical inactivity is associated with cancer. These cancer risk behaviours co-occur however little is known about how they pattern longitudinally across adolescence and early adulthood. Using data from ALSPAC, a prospective population-based UK birth cohort study, we explored patterns of adolescent cancer risk behaviours and their associations with cancer risk behaviours in early adulthood.MethodsSix thousand three hundred fifty-one people (46.0% of ALSPAC participants) provided data on all cancer risk behaviours at one time during adolescence, 1951 provided data on all cancer risk behaviours at all time points. Our exposure measure was quartiles of a continuous score summarising cumulative exposure to cancer risk behaviours and longitudinal latent classes summarising distinct categories of adolescents exhibiting similar patterns of behaviours, between age 11 and 18 years. Using both exposure measures, odds of harmful drinking (Alcohol Use Disorders Identification Test-C ≥ 8),daily tobacco smoking, nicotine dependence (Fagerström test ≥4), obesity (BMI ≥30), high waist circumference (females: ≥80 cm and males: ≥94 cm, and high waist-hip ratio (females: ≥0.85 and males: ≥1.00) at age 24 were estimated using logistic regression analysis.ResultsWe found distinct groups of adolescents characterised by consistently high and consistently low engagement in cancer risk behaviours. After adjustment, adolescents in the top quartile had greater odds of all outcomes in early adulthood: nicotine dependency (odds ratio, OR = 5.37, 95% confidence interval, CI = 3.64-7.93); daily smoking (OR = 5.10, 95% CI =3.19-8.17); obesity (OR = 4.84, 95% CI = 3.33-7.03); high waist circumference (OR = 2.48, 95% CI = 1.94-3.16); harmful drinking (OR = 2.04, 95% CI = 1.57-2.65); and high waist-hip ratio (OR = 1.88, 95% CI = 1.30-2.71), compared to the bottom quartile. In latent class analysis, adolescents characterised by consistently high-risk behaviours throughout adolescence were at higher risk of all cancer risk behaviours at age 24, except harmful drinking.ConclusionsExposure to adolescent cancer risk behaviours greatly increased the odds of cancer risk behaviours in early adulthood. Interventions to reduce these behaviours should target multiple rather than single risk behaviours and should focus on adolescence.

Project description:BackgroundGlobally, the rapid increase of obesity is reaching alarming proportions. A new approach to reduce obesity and its comorbidities involves tackling the built environment. Environmental influences seem to play an important role, but the environmental influences in early life on adult body composition have not been thoroughly investigated. This study seeks to fill the research gap by examining early-life exposure to residential green spaces and traffic exposure in association with body composition among a population of young adult twins.MethodsAs part of the East Flanders Prospective Twin Survey (EFPTS) cohort, this study included 332 twins. Residential addresses of the mothers at time of birth of the twins were geocoded to determine residential green spaces and traffic exposure. To capture body composition, body mass index, waist-to-hip ratio (WHR), waist circumference, skinfold thickness, leptin levels, and fat percentage were measured at adult age. Linear mixed modelling analyses were conducted to investigate early-life environmental exposures in association with body composition, while accounting for potential confounders. In addition, moderator effects of zygosity/chorionicity, sex and socio-economic status were tested.ResultsEach interquartile range (IQR) increase in distance to highway was found associated with an increase of 1.2% in WHR (95%CI 0.2-2.2%). For landcover of green spaces, each IQR increase was associated with 0.8% increase in WHR (95%CI 0.4-1.3%), 1.4% increase in waist circumference (95%CI 0.5-2.2%), and 2.3% increase in body fat (95%CI 0.2-4.4%). Stratified analyses by zygosity/chorionicity type indicated that in monozygotic monochorionic twins, each IQR increase in land cover of green spaces was associated with 1.3% increase in WHR (95%CI 0.5-2.1%). In monozygotic dichorionic twins, each IQR increase in land cover of green spaces was associated with 1.4% increase in waist-circumference (95%CI 0.6-2.2%).ConclusionsThe built environment in which mothers reside during pregnancy might play a role on body composition among young adult twins. Our study revealed that based on zygosity/chorionicity type differential effects of prenatal exposure to green spaces on body composition at adult age might exist.

Project description:The term "atopic march" has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time. Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts.The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (? 7% of those with symptoms) follow trajectory profiles resembling the atopic march. Please see later in the article for the Editors' Summary.

Project description:PurposeThe South Australian Aboriginal Birth Cohort (SAABC) is a prospective, longitudinal birth cohort established to: (1) estimate Aboriginal child dental disease compared with population estimates; (2) determine the efficacy of an early childhood caries intervention in early versus late infancy; (3) examine if efficacy was sustained over time and; (4) document factors influencing social, behavioural, cognitive, anthropometric, dietary and educational attainment over time.ParticipantsThe original SAABC comprised 449 women pregnant with an Aboriginal child recruited February 2011 to May 2012. At child age 2 years, 324 (74%) participants were retained, at age 3 years, 324 (74%) participants were retained and at age 5 years, 299 (69%) participants were retained. Fieldwork for follow-up at age 7 years is underway, with funding available for follow-up at age 9 years.Findings to dateAt baseline, 53% of mothers were aged 14-24 years and 72% had high school or less educational attainment. At age 3 years, dental disease experience was higher among children exposed to the intervention later rather than earlier in infancy. The effect was sustained at age 5 years, but rates were still higher than general child population estimates. Experiences of racism were high among mothers, with impacts on both tooth brushing and toothache. Compared with population estimates, levels of self-efficacy and self-rated oral health of mothers at baseline were low.Future plansOur data have contributed to a better understanding of the environmental, behavioural, dietary, biological and psychosocial factors contributing to Aboriginal child oral and general health, and social and emotional well-being. This is beneficial in charting the trajectory of cohort participants' health and well-being overtime, particularly in identifying antecedents of chronic diseases which are highly prevalent among Aboriginal Australians. Funding for continued follow-up of the cohort will be sought.Trial registration numberACTRN12611000111976; Post-results.

Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.

Project description:Rationale: The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. Objectives: To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. Methods: We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (filaggrin [FLG] mutations and 17q21 variants), increase the risk of multimorbidity. Measurements and Main Results: Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema+wheeze+rhinitis was rare but significantly overrepresented (three to six times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern. FLG mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (FLG by 2- to 3-fold, rs7216389 risk variant by 1.4- to 1.7-fold). Latent Markov modeling revealed five latent states (no disease/low risk, mainly eczema, mainly wheeze, mainly rhinitis, multimorbidity). The most likely transition to multimorbidity was from eczema state (0.21). However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity. Conclusions: Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.

Dataset Information

The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort.

Publications

The diversity of young adult wheeze: a cluster analysis in a longitudinal birth cohort.

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