Little is known about early-life risk factors for food allergy in children.
We examined the association between perinatal characteristics and future risk of food allergy in offspring.
This nationwide ...Swedish cohort study of 1,086,378 children born in Sweden in 2001-2012 used prospectively recorded data from health care registers. Using Cox regression, we estimated hazard ratios (HRs) with 95% CIs for the association between perinatal characteristics (eg, cesarean delivery and preterm birth) and food allergy as defined by diagnoses in the National Patient Register, adjusting for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index, and asthma/pulmonary disease).
During the 13-year follow-up, 26,732 (2.5%) children were given a diagnosis of food allergy. Food allergy was positively associated with cesarean delivery (HR, 1.21; 95% CI, 1.18-1.25), large for gestational age (HR, 1.15; 95% CI, 1.10-1.19), and low 5-minute Apgar score (HR, 1.22; 95% CI, 1.10-1.36) but negatively associated with very preterm birth (<32 weeks of gestation: HR, 0.74; 95% CI, 0.56-0.98). No association was found between food allergy and moderately preterm birth, low birth weight, or small for gestational age. Risk estimates were similar when the outcome was restricted to 2 records of diagnosed food allergy. In 1,000 children undergoing cesarean delivery, an extra 5 developed food allergy compared with the reference group, suggesting that 17% of food allergy in children born by means of cesarean delivery can be explained by this exposure (attributable fraction).
Cesarean delivery was associated with increased risk of food allergy, whereas very preterm birth decreased risk.
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At present, there is no cure for asthma, and treatment typically involves therapies that prevent or reduce asthma symptoms, without modifying the underlying disease. A "disease-modifying" treatment ...can be classed as able to address the pathogenesis of a disease, preventing progression or leading to a long-term reduction in symptoms. Such therapies have been investigated and approved in other indications,
rheumatoid arthritis and immunoglobulin E-mediated allergic disease. Asthma's heterogeneous nature has made the discovery of similar therapies in asthma more difficult, although novel therapies (
biologics) may have the potential to exhibit disease-modifying properties. To investigate the disease-modifying potential of a treatment, study design considerations can be made, including: appropriate end-point selection, length of trial, age of study population (key differences between adults/children in physiology, pathology and drug metabolism) and comorbidities in the patient population. Potential future focus areas for disease-modifying treatments in asthma include early assessments (
to detect patterns of remodelling) and interventions for patients genetically susceptible to asthma, interventions to prevent virally induced asthma and therapies to promote a healthy microbiome. This review explores the pathophysiology of asthma, the disease-modifying potential of current asthma therapies and the direction future research may take to achieve full disease remission or prevention.
The traditional view of chronic obstructive pulmonary disease (COPD) as a self-inflicted disease caused by tobacco smoking in genetically susceptible individuals has been challenged by recent ...research findings. COPD can instead be understood as the potential end result of the accumulation of gene-environment interactions encountered by an individual over the life course. Integration of a time axis in pathogenic models of COPD is necessary because the biological responses to and clinical consequences of different exposures might vary according to both the age of an individual at which a given gene-environment interaction occurs and the cumulative history of previous gene-environment interactions. Future research should aim to understand the effects of dynamic interactions between genes (G) and the environment (E) by integrating information from basic omics (eg, genomics, epigenomics, proteomics) and clinical omics (eg, phenomics, physiomics, radiomics) with exposures (the exposome) over time (T)-an approach that we refer to as GETomics. In the context of this approach, we argue that COPD should be viewed not as a single disease, but as a clinical syndrome characterised by a recognisable pattern of chronic symptoms and structural or functional impairments due to gene-environment interactions across the lifespan that influence normal lung development and ageing.
Background
Peanut oral immunotherapy (pOIT) has showed good short‐term outcomes, but allergic reactions may prevent effective up‐dosing and is a major cause of stopping OIT. In placebo‐controlled ...trials, omalizumab has been shown to facilitate allergen immunotherapy and increase tolerance to peanut.
Objective
We hypothesized that by combining omalizumab with pOIT, and monitor treatment effects with basophil allergen threshold sensitivity tests (CD‐sens), peanut allergic patients could safely initiate pOIT and thereafter slowly withdraw omalizumab.
Methods
This is the 2nd part of a one‐armed open phase‐2 study where peanut allergic adolescents (n = 23) started pOIT after an individualized omalizumab treatment. The pOIT dose was increased from 280 to 2800 mg peanut protein in 8 weeks followed by an individualized step‐wise withdrawal of omalizumab, based on clinical symptoms and CD‐sens levels. pOIT continued for 12 weeks followed by an open peanut challenge. Peanut CD‐sens and allergen‐binding activity (ABA) and IgE‐ab, IgG‐ab and IgG4‐ab to peanut and its components were measured during the study.
Results
All 23 patients successfully reached the 2800 mg maintenance dose. Moderate/systemic allergic reactions were rare while receiving full‐dose omalizumab. Eleven of 23 (48%) successfully continued with pOIT after omalizumab was stopped. Compared to treatment failures, median baseline IgE‐ab to peanut components Ara h 1‐3 and CD‐sens to peanut were significantly lower among successfully treated patients and IgG4‐ab to peanut, Ara h 2 and 6 increased significantly more during treatment.
Conclusions and clinical relevance
This study indicates that omalizumab is an effective adjunctive therapy for initiation and rapid up‐dosing of pOIT; however, adverse events from pOIT become more frequent as omalizumab doses are decreased.
Clinical trials registration: ClinicalTrials.gov; NCT02402231. EudraCT; 2012‐005625‐78.
Objective
Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide ...association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans.
Design
Structured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment.
Data Sources
We searched PubMed and Embase databases from 2005 to 2019.
Eligibility Criteria
Epigenome‐wide association studies testing association between differential methylation and asthma in humans.
Results
Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples.
Conclusion
Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.
Post coronavirus disease-19 (post COVID-19) is mainly studied in clinical populations and less is known about post COVID-19 in a young general population. The aim of the study is to investigate the ...prevalence and symptoms of post COVID-19 and its potential risk factors in young adults. Participants from the Swedish population-based birth cohort BAMSE were included (n = 2022, mean age 26.5 years). Post COVID-19 was assessed through a questionnaire and defined as symptoms after confirmed COVID-19 (registry-based or self-reported positive test) lasting for ≥ 2 months. In total, 681 participants had had confirmed COVID-19. Among them, 112 (16.5%) fulfilled the definition of post COVID-19 (17.8% in females, 14.5% in males, p = 0.26). The most common post COVID-19 symptoms were altered smell and taste (68.8%), dyspnea (33.7%) and fatigue (30.4%). Overall, no major risk factors for post COVID-19 were identified except for being bedbound during COVID-19. However, asthma and rhinitis were associated with the post COVID-19 symptom dyspnea, migraine with altered smell and taste, and lower self-rated health with fatigue. In conclusion, post COVID-19 symptoms are common, also among young adults in the general population. Although not life-threatening, it could have a considerable impact on public health due to the high prevalence and long-term symptoms.
To examine the role of prenatal and postnatal second-hand tobacco smoke (SHS) exposure on asthma, rhinitis, and eczema development up to 16 years of age.
A birth cohort of 4089 children was followed ...for 16 years. Information on parental smoking habits, lifestyle factors, and symptoms of allergic disease was gathered using repeated parental questionnaires. Generalized estimating equations assessed the overall and age-specific associations between SHS exposure and allergic disease at ages 1 to 16 years.
Exposure to SHS in utero was associated with an overall elevated risk of developing asthma up to 16 years (odds ratio OR = 1.45; 95% confidence interval CI, 1.15-1.83) but not for rhinitis or eczema. After additional adjustment for parental smoking throughout childhood, excess overall risks for asthma remained statistically significant. Moreover, a dose-dependent pattern with SHS was observed. Exposure to SHS during infancy was associated with an overall elevated risk of asthma (OR = 1.23; 95% CI, 1.01-1.51), rhinitis (OR = 1.18; 95% CI, 1.01-1.39), and eczema (OR = 1.26; 95% CI, 1.09-1.45) up to 16 years. When age-specific associations were examined, the elevated risks related to SHS exposure in utero or during infancy were mostly confined to early childhood for asthma and rhinitis, whereas the excess risk of eczema appeared greatest at later ages.
Our findings indicate that early SHS exposure, in utero or during infancy, influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages.
Obesity-related inflammation is associated with cardiovascular, metabolic, and pulmonary diseases. The aim of this study was to demonstrate associations between adiposity measurements and levels of ...inflammation-related plasma proteins in a population of young adults. Subjects from a population-based birth cohort with a mean age of 22.5 years were included in the study population (n = 2074). Protein levels were analyzed using the Olink Proseek Multiplex Inflammation panel. Percentage body fat (%BF) and visceral fat rating (VFR) measurements were collected using Tanita MC 780 body composition monitor. Linear regression of standardized values was used to investigate associations. Potential effect modifications by sex and BMI category were assessed. Of 71 investigated proteins, 54 were significantly associated with all adiposity measurements %BF, body mass index (BMI), VFR and waist circumference. Among proteins associated with %BF, seven showed a larger or unique association in overweight/obese subjects and three showed a significant effect modification by sex. Fourteen proteins more strongly associated with VFR in females compared to males. Adipose-associated systemic inflammation was observed in this young adult population. Sex and adiposity localization influenced some of the associations. Our results highlight specific proteins as suitable biomarkers related to adiposity.
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