Genetic characterization of preschool wheeze phenotypes.

Rationale: Preschool wheeze is a heterogenous and poorly understood clinical syndrome. As a result, current treatments are insufficient, and prevention is not possible.

Objectives: To increase understanding of the genetic susceptibility and underlying disease mechanisms of wheeze phenotypes in early childhood through large-scale genome-wide association study (GWAS) analyses.

General population-based lung function trajectories over the life course: an accelerated cohort study.

Background: Lung function is a key determinant of health, but current knowledge on lung function growth and decline over the life course is based on fragmented, potentially biased data. We aimed to empirically derive general population-based life course lung function trajectories, and to identify breakpoints and plateaus.

Methods: We created an accelerated cohort by pooling data from eight general population-based child and adult cohort studies from Europe and Australia.

Maternal asthma and newborn DNA methylation.

Background: Prenatal exposure to maternal asthma may influence DNA methylation patterns in offspring, potentially affecting their susceptibility to later diseases including asthma.

Objective: To investigate the relationship between parental asthma and newborn blood DNA methylation.

Methods: Epigenome-wide association analyses were conducted in 13 cohorts on 7433 newborns with blood methylation data from the Illumina450K or EPIC array.

Trajectories of airflow limitation from childhood to early adulthood: an analysis of six population-based birth cohorts.

Background: Lung function during childhood is an important predictor of subsequent health and disease. Understanding patterns of lung function and development of airflow limitation through childhood is necessary to inform lung function trajectories in relation to health and chronic airway disease. We aimed to derive trajectories of airflow limitation from childhood (age 5-8 years) into early adulthood (age 20-26 years) using repeated spirometry data from birth cohorts.

Lung function trajectories from school age to adulthood and their relationship with markers of cardiovascular disease risk.

Rationale: Lung function in early adulthood is associated with subsequent adverse health outcomes.

Objectives: To ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function.

Methods: Using latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC).

Obstructive and restrictive spirometry from school age to adulthood: three birth cohort studies.

Background: Spirometric obstruction and restriction are two patterns of impaired lung function which are predictive of poor health. We investigated the development of these phenotypes and their transitions through childhood to early adulthood.

Methods: In this study, we analysed pooled data from three UK population-based birth cohorts established between 1989 and 1995.

Genome-wide association study of preserved ratio impaired spirometry (PRISm).

Background: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV) <80% predicted and FEV/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities.

A history of asthma may be associated with grandparents' exposures to stress and cigarette smoking.

Within human epidemiological studies, associations have been demonstrated between grandparental exposures during childhood and grandchildren's outcomes. A few studies have assessed whether asthma has ancestral associations with exposure to cigarette smoking, but results have been mixed so far. In this study we used four generations: (F0 great-grandparents, F1 grandparents, F2 parents, F3 study children) of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether there is evidence of associations between asthma in generations F2 or F3 and exposures to severe trauma in childhood and/or active cigarette smoking during the adolescence of grandmothers and grandfathers in generations F0 and F1 respectively, or of a history of a F0 or F1 grandmother smoking during pregnancy.

Prediction of adult asthma risk in early childhood using novel adult asthma predictive risk scores.

Background: Numerous risk scores have been developed to predict childhood asthma. However, they may not predict asthma beyond childhood. We aim to create childhood risk scores that predict development and persistence of asthma up to young adult life.

A meta-analysis of genome-wide association studies of childhood wheezing phenotypes identifies as a susceptibility locus for persistent wheezing.

Background: Many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of 'doctor-diagnosed asthma', thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes.

Lung function and cognitive ability in children: a UK birth cohort study.

Background: Decreased adult lung function is associated with subsequent impairment in cognition. A similar relationship in early life could be of great policy importance, since childhood cognitive ability determines key adult outcomes, including socioeconomic status and mortality. We aimed to expand the very limited data available on this relationship in children, and hypothesised that reduced lung function would be longitudinally associated with decreased cognitive ability.

Dietary patterns, lung function and asthma in childhood: a longitudinal study.

Background: Longitudinal epidemiological data are scarce examining the relationship between dietary patterns and respiratory outcomes in childhood. We investigated whether three distinct dietary patterns in mid-childhood were associated with lung function and incident asthma in adolescence.

Methods: In the Avon Longitudinal Study of Parents and Children, 'processed', 'traditional', and 'health-conscious' dietary patterns were identified using principal components analysis from food frequency questionnaires at 7 years of age.

Mid-childhood fat mass and airflow limitation at 15 years: The mediating role of insulin resistance and C-reactive protein.

Background: We previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV )/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years.

Early childhood wheezing phenotypes and determinants in a South African birth cohort: longitudinal analysis of the Drakenstein Child Health Study.

Background: Developmental trajectories of childhood wheezing in low-income and middle-income countries (LMICs) have not been well described. We aimed to derive longitudinal wheeze phenotypes from birth to 5 years in a South African birth cohort and compare those with phenotypes derived from a UK cohort.

Methods: We used data from the Drakenstein Child Health Study (DCHS), a longitudinal birth cohort study in a peri-urban area outside Cape Town, South Africa.

Early-life and health behaviour influences on lung function in early adulthood.

Rationale: Early-life exposures may influence lung function at different stages of the life course. However, the relative importance of characteristics at different stages of infancy and childhood are unclear.

Objectives: To examine the associations and relative importance of early-life events on lung function at age 24 years.

Evolution of Eczema, Wheeze, and Rhinitis from Infancy to Early Adulthood: Four Birth Cohort Studies.

The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. 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.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age.

Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), FEV/FVC, forced expiratory flow at 75% of FVC (FEF) and asthma at a median (range) age of 7 (4-15) years.