Food hypersensitivity: an examination of factors influencing symptoms and temporal changes in the prevalence of sensitization in an adult sample.

BACKGROUND/OBJECTIVES: Food hypersensitivity (FHS) is common, but little is known about the factors associated with severe reactions, age of onset and whether sensitization persists. This study examines the factors associated with self-reported severe food reactions, onset age and the changes in prevalence of sensitization to foods over time in an adult sample. SUBJECTS/METHODS: We used data from adults taking part in the European Community Respiratory Health Survey (ECRHS) III (2010-2014) who provided information on food hypersensitivity, including symptoms, suspected culprit food and onset age (n = 4865). A subsample from six countries had serum food-specific IgE tested for 25 core foods and also in 10 years earlier (ECRHS II). We applied logistic regression and McNemar's test for analyses. RESULTS: The prevalence of self-reported FHS was 13.5% at ECRHS III. Of those providing information on symptoms (n = 611), 26.4% reported severe reactions. About 80% of 1033 reported food-specific reactions (reported by 596 participants) began after age 15. History of asthma (odds ratio OR 2.12 95% confidence interval CI 1.13-3.44) and a younger age of onset of FHS (OR 1.02, 95% CI 1.01-1.03, per year) were associated with higher risks of a lifetime experience of severe food reactions. In the subsample with IgE tested in both surveys (n = 1612), the overall prevalence of sensitization to foods did not change over 10 years. CONCLUSION: Our findings support previous observations of more severe food reactions in people with asthma and that most FHS reported by this sample started after age 15. We found no evidence of changes in the prevalence of sensitization to food in adults followed for 10 years.

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 (FEV1 )/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C-reactive protein (CRP) at 15 years partially mediate this association. METHODS: We included 2263 children from the UK Avon Longitudinal Study of Parents and Children population-based cohort (ALSPAC). Four fat mass index (FMI) trajectories ("low," "medium-low," "medium-high," "high") from 9 to 15 years were previously identified using Group-Based Trajectory Modeling. Data on CRP, glucose, insulin, and post-bronchodilator FEV1 /FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment-estimated insulin resistance index (HOMA-IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA-IR and CRP. RESULTS: Compared to children in the "low" FMI trajectory, children in the "medium-high" and "high" FMI trajectories had lower FEV1 /FVC at 15 years. The percentage of the total effect explained by HOMA-IR was 19.8% [-114.1 to 170.0] and 20.4% [1.6 to 69.0] for the "medium-high" and "high" trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP. CONCLUSION: The association between mid-childhood fat mass and FEV1 /FVC ratio at 15 years may be partially mediated by insulin resistance.

The Association of Self-Reported Birthweight with Lung Function and Respiratory Diseases: Results from a Multi-Centre, Multi-Case Control Study in Italy.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene-Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (<2500 g), and this proportion was greater in women than men (7.8% vs. 5.1%; p = 0.006). Both men and women with low BW were shorter than those with normal BW (mean ± SD: 160.2 ± 5.5 vs. 162.6 ± 6.5 cm in women, p = 0.009; 172.4 ± 6.1 vs. 174.8 ± 7.2 cm in men, p < 0.001). Although FEV1 and FVC were reduced in individuals with low BW, this was explained by associations with sex and height. In multivariable analysis, BW was not associated with respiratory diseases in adulthood. However, those with low BW had a higher risk of self-reported hospitalisation for lung disease before the age of two (10.3% vs. 4.1%; p < 0.001), severe respiratory infection before the age of five (16.9% vs. 8.8%; p = 0.001) and hypertension in adulthood (29.9% vs. 23.7%; p = 0.001); however, they had a lower risk of arrhythmia (2.7% vs. 5.8%; p = 0.027).

Parental Prepuberty Overweight and Offspring Lung Function.

In a recent study we found that fathers' but not mothers' onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring's adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents' overweight on adult offspring's lung function within the paternal and maternal lines. We included 929 offspring (aged 18-54, 54% daughters) of 308 fathers and 388 mothers (aged 40-66). Counterfactual-based multi-group mediation analyses by offspring's sex (potential moderator) were used, with offspring's prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers' overweight before puberty had a negative indirect effect, mediated through sons' height, on sons' forced expiratory volume in one second (FEV1) (beta (95% CI): -144 (-272, -23) mL) and forced vital capacity (FVC) (beta (95% CI): -210 (-380, -34) mL), and a negative direct effect on sons' FVC (beta (95% CI): -262 (-501, -9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers' overweight before puberty had neither direct nor indirect effects on offspring's lung function. Fathers' overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons' adult height but not through sons' prepubertal overweight.

Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study.

BACKGROUND: Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation. METHODS: We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV1, FVC, and FEV1/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2. RESULTS: In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs. CONCLUSIONS: To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.

Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study.

BACKGROUND: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). METHODS: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. RESULTS: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV1 declines. We found no association between weight change profiles and FEV1/FVC decline. CONCLUSION: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.

Age at menopause and lung function: a Mendelian randomisation study.

In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.We included 94 742 naturally post-menopausal women from the UK Biobank and performed MR analyses on the effect of age at menopause on forced expiratory volume in 1 s (FEV1), FVC, FEV1/FVC, spirometric restriction (FVC

Author Correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.

In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.