Epidemiological studies have suggested an association between maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy in the offspring. However, prospective clinical studies ...on vitamin D measured in cord blood and development of clinical end-points are sparse.
To investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin D) level and investigator-diagnosed asthma- and allergy-related conditions during preschool-age.
Cord blood 25(OH)-Vitamin D level was measured in 257 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS), asthma, respiratory infections, allergic rhinitis, and eczema, at age 0-7 yrs were diagnosed exclusively by the COPSAC pediatricians strictly adhering to predefined algorithms. Objective assessments of lung function and sensitization were performed repeatedly from birth.
After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (<50 nmol/L) was associated with a 2.7-fold increased risk of recurrent TROLS (HR = 2.65; 95% CI = 1.02-6.86), but showed no association with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors.
Cord blood 25(OH)-Vitamin D deficiency associated with increased risk of recurrent TROLS till age 7 years. Randomized controlled trials of vitamin D supplementation during pregnancy are needed to prove causality.
Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to ...pregnant women is unknown.
To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring.
A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014.
Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care.
Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed.
Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group. table: see text.
The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.
clinicaltrials.gov Identifier: NCT00856947.
The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially ...cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.
Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with ...n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring.
We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood
(COPSAC
) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.
A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval CI, 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization.
Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).
Background
The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom ...development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood.
Methods
We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one‐month‐old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition.
Results
A neonatal airway immune profile particularly characterized by enhanced IL‐1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune‐associated markers, including IL‐1β and CXCL8, showed trend of association with development of early asthma endpoints.
Conclusions
Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre‐ and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.
This study examines whether the airway cytokine/chemokine profile is associated with development of asthma and allergy later in childhood. Twenty immune mediators were measured in the airway mucosal lining fluid of 620 one‐month‐old healthy neonates. Distinct airway immune profiles were associated with development of inhalant allergy (higher IL‐1β and lower CCL26) and asthma (lower IL‐1β and CXCL8), suggesting an early origin and different pathogenesis of childhood asthma and allergy. Abbreviations: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; CCL, C‐C motif chemokine ligand; CXCL, C‐X‐C motif chemokine ligand; IL, interleukin; INF, interferon; TNF, tumor necrosis factor.
Furry mammals kept as pets are important allergen sources. The prevalence of sensitization to dander from various animals appears to be increasing worldwide. Several mammalian allergens from diverse ...species and distinct protein families have been characterized, and some are available for component-resolved diagnostics (CRD). This review presents an overview of mammalian aeroallergens, with a focus on cat, dog, and horse allergens. The potential of CRD in fine-tuning the diagnostic workup following traditional methods based on whole- allergen extracts and allergen immunotherapy is discussed. The review highlights the clinical utility of CRD, particularly as a marker/predictor of increased asthma risk and disease severity. Finally, several perspectives of the future implications of CRD are offered in the context of furry animal allergens.
We aimed to explore the effect of multiple pre- and postnatal exposures on optic nerve status in young adults due to this critical period for development.
We analysed peripapillary retinal nerve ...fibre layer (RNFL) status and macular thickness at age 18 years in the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC
) cohort in relation to several exposures.
Of the 269 participants (median (IQR) age, 17.6 (0.6) years; 124 boys), 60 participants whose mothers had smoked during pregnancy had a thinner RNFL: adjusted mean difference -4.6 μm (95% CI -7.7; -1.5 μm, p = 0.004) compared with participants whose mothers had not smoked during pregnancy. A total of 30 participants who were exposed to tobacco smoke both during foetal life and childhood had thinner RNFL: -9.6 μm (-13.4; -5.8 μm, p < 0.001). Smoking during pregnancy was also associated with a macular thickness deficit: -4.7 μm (-9.0; -0.4 μm, p = 0.03). Higher indoor concentrations of particulate matter 2.5 (PM2.5) was associated with thinner RNFL: -3.6 μm (-5.6; -1.6 μm, p < 0.001) and a macular deficit: -2.7 μm (-5.3; -0.1 μm, p = 0.04) in the crude analyses, but not in the adjusted analyses. No difference was found among participants who smoked at age 18 years compared with non-smokers on RNFL or macular thickness.
We found that exposure to smoking during early life was associated with a thinner RNFL and macula at age 18 years. The absence of an association between active smoking at 18 years suggests that the vulnerability of the optic nerve is highest during prenatal life and early childhood.
Background
Mixed and non‐IgE‐mediated food allergy is a subset of immune‐mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. ...Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied.
Objective
As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non‐IgE‐mediated food allergy.
Design
In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein‐induced enterocolitis syndrome, food protein‐induced allergic proctocolitis, food protein‐induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis EoE, eosinophilic gastritis and eosinophilic colitis published until 14 October 2022.
Results
Twenty‐six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient‐reported dysphagia, usually using a non‐validated questionnaire. Twenty‐two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non‐validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient‐reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient‐reported outcomes.
Conclusions
Outcomes measured in clinical trials of EoE and non‐IgE‐mediated food allergy are heterogeneous and largely non‐validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non‐IgE‐mediated food allergies, core outcome development is needed to support the development of effective treatments.
Systematic review registration
OSF public registry DOI:10.17605/OSF.IO/AZX8S
Background
Blood eosinophil count is a well‐established biomarker of atopic diseases in older children and adults. However, its predictive role for atopic diseases in preschool children is not well ...established.
Objective
To investigate the association between blood eosinophil count in children and development of atopic diseases up to age 6 years.
Methods
We investigated blood eosinophil count at age 18 months and 6 years in relation to recurrent wheeze/asthma, atopic dermatitis, allergic rhinitis, and allergic sensitization during the first 6 years of life in the two Copenhagen Prospective Studies on Asthma in Childhood cohorts (n = 1111). Blood eosinophil count was investigated in association with remission of existing atopic disease, current atopic disease, and later development of atopic disease.
Results
Blood eosinophil count at 18 months was not associated with current wheezing/asthma or atopic dermatitis, while blood eosinophil count at age 6 years was associated with increased occurrence of current wheezing/asthma (OR = 1.1; 1.04–1.16, p = .0005), atopic dermatitis (OR = 1.06; 1.01–1.1, p = .02), and allergic rhinitis (OR = 1.11; 1.05–1.18, p = .0002). Blood eosinophil count at 18 months did not predict persistence or development of recurrent wheeze/asthma or atopic dermatitis at age 6 years.
Conclusion
Blood eosinophil count at 18 months was not associated with current wheezing/asthma or atopic dermatitis and did not predict persistence or development of disease. This implies a limited clinical role of blood eosinophil levels in early‐life atopic disease and questions the clinical value of blood eosinophil counts measured in toddlers as a predictive biomarker for subsequent atopic disease in early childhood.
Oral immunotherapy is an effective treatment for food allergies; however, its use in clinical practice is limited by resources and lack of standardized protocols for foods other than peanut. Previous ...studies have suggested that shrimp has a higher threshold for reaction than other allergenic foods, suggesting it may be safe to directly administer maintenance doses of immunotherapy.
Children aged 3–17 years who had 1) skin prick test ≥3 mm and/or specific IgE level ≥0.35 kU/L and convincing objective IgE-mediated reaction to shrimp, or 2) no ingestion history and specific IgE level ≥5 kU/L, underwent a low-dose oral food challenge to 300 mg shrimp protein, with the goal of continuing daily ingestion of the 300 mg maintenance dose as oral immunotherapy.
Between January 2020 and April 2023, 17 children completed the low-dose oral food challenge. Nine (53%) tolerated this amount with no reaction, and 8 (47%) had a mild reaction (isolated oral pruritis or redness on chin). Sixteen (94%) continued maintenance low-dose oral immunotherapy eating 300 mg shrimp protein daily. None of the patients developed anaphylaxis related to the immunotherapy.
Our case series suggests that some shrimp allergic patients being considered for oral immunotherapy should be offered a low-dose oral food challenge, to potentially bypass the build-up phase of immunotherapy.
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