Both adverse early-life exposures and adult smoking can negatively influence adult lung function trajectory, but few studies consider how the impact of early-life exposures may be modified by ...subsequent smoking.
The Medical Research Council National Survey of Health and Development is a nationally representative cohort, initially of 5,362 individuals, followed since enrollment at birth in March 1946. Using data collected prospectively across life and multilevel modeling, we investigated how the relationships between early-life exposures (infant lower respiratory infection, manual social class, home overcrowding, and pollution exposure) and FEV
and FVC trajectories between ages 43 and 60-64 years were influenced by smoking behavior.
Among 2,172 individuals, there were synergistic interactions of smoking with infant respiratory infection (P = 0.04) and early-life home overcrowding (P = 0.009), for FEV
at 43 years. Within smoker-stratified models, there were FEV
deficits among ever-smokers associated with infant lower respiratory infection (-108.2 ml; P = 0.001) and home overcrowding (-89.2 ml; P = 0.002), which were not evident among never-smokers (-15.9 ml; P = 0.69 and -13.7 ml; P = 0.70, respectively). FVC modeling, including 1,960 individuals, yielded similar results. FEV
decline was greater in smokers (P < 0.001), but there was no effect of any early-life exposure on FEV
decline. Neither smoking nor early-life exposures were associated with FVC decline.
Besides accelerating adult FEV
decline, cigarette smoking also modifies how early-life exposures impact on both midlife FEV
and FVC. These findings are consistent with smoking impairing pulmonary development during adolescence or early adulthood, thereby preventing catch-up from earlier acquired deficits.
Chronic mucus hypersecretion (CMH) is common among smokers and is associated with chronic obstructive pulmonary disease development and progression.
To understand how the relationships between ...smoking, CMH, and chronic obstructive pulmonary disease develop during adult life, and facilitate earlier disease detection and intervention.
We analyzed data on CMH, smoking, and lung function prospectively collected by the Medical Research Council National Survey of Health and Development, a nationally representative British cohort followed since birth in 1946. We analyzed the longitudinal relationships between smoking and CMH, how symptoms during life related to airflow limitation at 60-64 years, and how CMH duration between ages 43 and 60-64 years related to concurrent FEV1 decline.
From 5,362 individuals enrolled at birth, 4,427 contributed data between ages 20 and 64 years (52% male; 63% ever-smoker). Among smokers CMH prevalence escalated between ages 36 and 43 from 7.6 ± 2.0% to 13.0 ± 2.6%. At these ages, symptoms were associated with a higher risk of subsequent airflow limitation (odds ratio 95% confidence interval, 3.70 1.62-8.45 and 4.11 1.85-9.13, respectively). Across adult life, CMH followed a dynamic remitting-relapsing course. Symptom prevalence following smoking cessation returned to levels seen among never-smokers. The longer CMH was present across three occasions (ages 43, 53, and 60-64 yr), the greater the concurrent FEV1 decline, corresponding to an additional decrement of 3.6 ± 2.5 ml/yr per occasion that CMH was present (P = 0.005).
CMH among middle-aged smokers represents an early developmental phase of chronic obstructive pulmonary disease. Smoking-related CMH usually resolves following smoking cessation but the longer its duration the greater the FEV1 lost, suggesting the course of CMH across adult life may reflect the underlying course of airway disease activity.
Epigenetic markings acquired in early life may have phenotypic consequences later in development through their role in transcriptional regulation with relevance to the developmental origins of ...diseases including obesity. The goal of this study was to investigate whether DNA methylation levels at birth are associated with body size later in childhood.
A study design involving two birth cohorts was used to conduct transcription profiling followed by DNA methylation analysis in peripheral blood. Gene expression analysis was undertaken in 24 individuals whose biological samples and clinical data were collected at a mean ± standard deviation (SD) age of 12.35 (0.95) years, the upper and lower tertiles of body mass index (BMI) were compared with a mean (SD) BMI difference of 9.86 (2.37) kg/m(2). This generated a panel of differentially expressed genes for DNA methylation analysis which was then undertaken in cord blood DNA in 178 individuals with body composition data prospectively collected at a mean (SD) age of 9.83 (0.23) years. Twenty-nine differentially expressed genes (>1.2-fold and p<10(-4)) were analysed to determine DNA methylation levels at 1-3 sites per gene. Five genes were unmethylated and DNA methylation in the remaining 24 genes was analysed using linear regression with bootstrapping. Methylation in 9 of the 24 (37.5%) genes studied was associated with at least one index of body composition (BMI, fat mass, lean mass, height) at age 9 years, although only one of these associations remained after correction for multiple testing (ALPL with height, p(Corrected) = 0.017).
DNA methylation patterns in cord blood show some association with altered gene expression, body size and composition in childhood. The observed relationship is correlative and despite suggestion of a mechanistic epigenetic link between in utero life and later phenotype, further investigation is required to establish causality.
The possible role of maternal consumption of free sugar during pregnancy in the inception of respiratory and atopic diseases has not been studied. We aimed to study the relationship between maternal ...intake of free sugar during pregnancy and respiratory and atopic outcomes in the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children.We analysed associations between maternal intake of free sugar in pregnancy (estimated by a food frequency questionnaire), and current doctor-diagnosed asthma, wheezing, hay fever, eczema, atopy, serum total IgE and lung function in children aged 7-9 years (n=8956 with information on maternal diet in pregnancy and at least one outcome of interest).After controlling for potential confounders, maternal intake of free sugar was positively associated with atopy (OR for highest
lowest quintile of sugar intake 1.38, 95% CI 1.06-1.78; per quintile p-trend=0.006) and atopic asthma (OR 2.01, 95% CI 1.23-3.29; per quintile p-trend=0.004). These associations were not confounded by intake of sugar in early childhood, which was unrelated to these outcomes.Our results suggest that a higher maternal intake of free sugar during pregnancy is associated with an increased risk of atopy and atopic asthma in the offspring, independently of sugar intake in early childhood.
Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing. We examined the effect of prenatal vitamin D on childhood wheezing in an interventional ...study.
We randomised 180 pregnant women at 27 weeks gestation to either no vitamin D, 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol, in an ethnically stratified, randomised controlled trial. Supplementation improved but did not optimise vitamin D status. Researchers blind to allocation assessed offspring at 3 years. Primary outcome was any history of wheeze assessed by validated questionnaire. Secondary outcomes included atopy, respiratory infection, impulse oscillometry and exhaled nitric oxide. Primary analyses used logistic and linear regression.
We evaluated 158 of 180 (88%) offspring at age 3 years for the primary outcome. Atopy was assessed by skin test for 95 children (53%), serum IgE for 86 (48%), exhaled nitric oxide for 62 (34%) and impulse oscillometry of acceptable quality for 51 (28%). We found no difference between supplemented and control groups in risk of wheeze no vitamin D: 14/50 (28%); any vitamin D: 26/108 (24%) (risk ratio 0.86; 95% confidence interval 0.49, 1.50; P = 0.69). There was no significant difference in atopy, eczema risk, lung function or exhaled nitric oxide between supplemented groups and controls.
Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level, was not associated with decreased wheezing in offspring at age three years.
Controlled-Trials.com ISRCTN68645785.
Abstract Sugar sweetened beverage consumption has been suggested as a risk factor for childhood asthma symptoms. We examined whether the UK Soft Drinks Industry Levy (SDIL), announced in March 2016 ...and implemented in April 2018, was associated with changes in National Health Service hospital admission rates for asthma in children, 22 months post-implementation of SDIL. We conducted interrupted time series analyses (2012-2020) to measure changes in monthly incidence rates of hospital admissions. Sub-analysis was by age-group (5-9,10-14,15-18 years) and neighbourhood deprivation quintiles. Changes were relative to counterfactual scenarios where the SDIL wasn’t announced, or implemented. Overall, incidence rates reduced by 20.9% (95%CI: 29.6-12.2). Reductions were similar across age-groups and deprivation quintiles. These findings give support to the idea that implementation of a UK tax intended to reduce childhood obesity may have contributed to a significant unexpected and additional public health benefit in the form of reduced hospital admissions for childhood asthma.
In this population-based cohort of 7538 adults, combined immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) anti-spike titers measured after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure, including household overcrowding, public transport use, and visits to indoor public places. Anti-spike IgG/A/M titers showed positive correlation with neutralizing antibody titers (rs = 0.80 95% confidence interval, .72-.86; P < .001) and S peptide-stimulated interferon-γ concentrations (rs = 0.31 .13-.47; P < .001).
Evidence for associations between Mediterranean diet during pregnancy and childhood asthma, allergy and related outcomes is conflicting. Few cohorts have followed children to school age, and none ...have considered lung function.In the Avon Longitudinal Study of Parents and Children, we analysed associations between maternal Mediterranean diet score during pregnancy (estimated by a food frequency questionnaire, using an
defined score adapted to pregnant women; score ranging from 0 (low adherence) to 7 (high adherence)) and current doctor-diagnosed asthma, wheeze, eczema, hay fever, atopy and lung function in 8907 children at 7-9 years. Interaction between maternal Mediterranean diet and maternal smoking in pregnancy was investigated.The maternal Mediterranean diet score was not associated with asthma or other allergic outcomes. Weak positive associations were found between maternal Mediterranean diet score and childhood maximal mid-expiratory flow (forced expiratory flow at 25-75% of forced vital capacity (FEF
)) after controlling for confounders. Higher Mediterranean diet scores were associated with increased FEF
z-scores adjusted for age, height and sex (β 0.06, 95% CI 0.01-0.12; p=0.03, comparing a score of 4-7
a score of 0-3). Stratifying associations by maternal smoking during pregnancy showed that associations with FEF
were only seen in children of never-/passive-smoking mothers, but no evidence for a statistically significant interaction was found.Results suggest adherence to a Mediterranean diet during pregnancy may be associated with increased small airway function in childhood, but we found no evidence for a reduced risk of asthma or other allergic outcomes.
PDF
