Pertussis immunisation in infancy and atopic outcomes: A protocol for a population-based cohort study using linked administrative data

Introduction The burden of IgE-mediated food allergy in Australian born children is reported to be among the highest globally. This illness shares risk factors and frequently coexists with asthma, one of the most common noncommunicable diseases of childhood. Findings from a case-control study suggest that compared to immunisation with acellular pertussis vaccine, early priming of infants with whole-cell pertussis vaccine may be associated with a lower risk of subsequent IgE-mediated food allergy. If whole-cell vaccination is protective of food allergy and other atopic diseases, especially if protective against childhood asthma, the population-level effects could justify its preferential recommendation. However, the potential beneficial effects of whole-cell pertussis vaccination for the prevention of atopic diseases at a population-scale are yet to be investigated. Methods and analysis Analyses of population-based record linkage data will be undertaken to compare the rates of admissions to hospital for asthma in children aged between 5 and 15 years old, who were born in Western Australia (WA) or New South Wales (NSW) between 1997 and 1999 (329,831) when pertussis immunisation in Australia transitioned from whole-cell to acellular only schedules. In the primary analysis we will estimate hazard ratios and 95% confidence intervals for the time-to-first-event (hospital admissions as above) using Cox proportional hazard models in recipients of a first dose of whole-cell versus acellular pertussis-containing vaccine before 112 days old (~4 months of age). Similarly, we will also fit time-to-recurrent events analyses using Andersen-Gill models, and robust variance estimates to account for potential within-child dependence. Hospitalisations for all-cause anaphylaxis, food anaphylaxis, venom, all-cause urticaria and atopic dermatitis will also be examined in children who received at least one dose of pertussis-containing vaccine by the time of the cohort entry, using analogous statistical methods. Presentations to the emergency departments will be assessed separately using the same statistical approach.

The link between atopic dermatitis and asthma- immunological imbalance and beyond

Atopic diseases are multifactorial chronic disturbances which may evolve one into another and have overlapping pathogenetic mechanisms. Atopic dermatitis is in most cases the first step towards the development of the atopic march and represents a major socio-economic burden in the industrialized countries. The treatment of atopic diseases is often long-lasting and in some cases with lower effectiveness than expected.In order to prevent the development of the atopic march, the links between the atopic diseases have to be understood. The aim of this review is to present some major points outlining the link between atopic dermatitis and asthma, through a research in the medical literature from recent years.Stratifying patient populations according to the clinical phenotype of their disease and according to specific measurable values (biomarkers) can help to establish the main etiopathogenetic mechanisms of the disease in these populations. This will add predictive value for the evolution of the disease, and will allow the use and research of more targeted therapy in order to stop this evolution and comorbidities.

BCG Vaccination in Early Childhood and Risk of Atopic Disease: A Systematic Review and Meta-Analysis

Background. Several large-scale studies suggest that Bacille Calmette–Guerin (BCG) vaccination in early childhood may reduce the risk of atopic diseases, but the findings remain controversial. Here, we aimed to investigate the potential correlation between early childhood BCG vaccination and the risk of developing atopic diseases. Methods. Eligible studies published on PubMed, EMBASE, and Cochrane CENTRAL were systematically sourced from 1950 to July 2021. Studies with over 100 participants and focusing on the association between BCG vaccine and atopic diseases including eczema, asthma, and rhinitis were included. Preliminary assessment of methods, interventions, outcomes, and study quality was performed by two independent investigators. Odds ratio (OR) with 95% confidence interval (CI) was calculated. Random effects of the meta-analysis were performed to define pooled estimates of the effects. Results. Twenty studies with a total of 222,928 participants were selected. The quantitative analysis revealed that administering BCG vaccine in early childhood reduced the risk of developing asthma significantly (OR 0.77, 95% CI 0.63 to 0.93), indicating a protective efficacy of 23% against asthma development among vaccinated children. However, early administration of BCG vaccine did not significantly reduce the risk of developing eczema (OR 0.94, 95% CI 0.76 to 1.16) and rhinitis (OR 0.99, 95% CI 0.81 to 1.21). Further analysis revealed that the effect of BCG vaccination on asthma prevalence was significant especially in developed countries (OR 0.73, 95% CI 0.58 to 0.92). Conclusion. BCG vaccination in early childhood is associated with reduced risk of atopic disease, especially in developed countries.

Kawasaki Disease and Atopic Diseases: A Systematic Review and Meta-Analysis of Observational Studies

<b><i>Introduction:</i></b> The etiology of Kawasaki disease (KD), an inflammatory and cardiovascular disorder, remains largely unexplained after more than 50 years of intensive research. In recent years, the association between KD and atopic diseases had been explored by some observational studies. We systematically reviewed and summarized the literature on the relationship between KD and atopic diseases. <b><i>Methods:</i></b> MEDLINE and EMBASE were searched to identify observational studies on the association between KD and atopic diseases from inception to May 2021. Odds ratio (OR) was pooled using random-effects models. Heterogeneity was assessed using the <i>I</i>² and Cochran Q statistics. Primary outcomes were to compare the prevalence of KD among individuals with atopic diseases to nonatopic disease controls and the prevalence of atopic diseases among individuals with KD to non-KD controls. <b><i>Results:</i></b> Thirteen studies, including 12,651 cases and 170,708 controls, were included in this meta-analysis. In cross-sectional studies, KD was associated with allergic rhinitis (<i>n</i> = 6; OR, 1.69; 95% CI, 1.52–1.87), asthma (<i>n</i> = 3; OR, 1.72; 95% CI, 1.38–2.14), allergic conjunctivitis (<i>n</i> = 2; OR, 1.95; 95% CI, 1.68–2.27), and atopic dermatitis (<i>n</i> = 3; OR, 1.35; 95% CI, 1.22–1.49). In case-control and cohort studies, KD was associated with allergic rhinitis (<i>n</i> = 3; OR, 1.35; 95% CI, 1.28–1.43), asthma (<i>n</i> = 8; OR, 1.40; 95% CI, 1.19–1.65), allergic conjunctivitis (<i>n</i> = 1; OR, 1.74; 95% CI, 1.45–2.09), and atopic dermatitis (<i>n</i> = 3; OR, 1.39; 95% CI, 1.26–1.53). <b><i>Conclusion:</i></b> KD diagnosed was associated with four common atopic diseases. Among the four allergic diseases, allergic conjunctivitis and asthma have the highest correlation with KD, which may provide a direction for exploring the etiology of KD.

Associations of Exposure to Nitrogen Oxides with Prevalent Asthma and Other Atopic Diseases in Israel

Childhood exposure to nitrogen oxides (NOx) is considered a risk factor for the onset of asthma. However, associations of this exposure with other atopic diseases and factors that modify this association are less clear. We aimed to study associations between exposure to NOx and the prevalence of atopic diseases in Israeli adolescents using a cross-sectional design. The study population comprised all Israeli-born adolescents whose medical status was evaluated for mandatory military recruitment during 1967–2017 (n = 2,523,745), of whom 5.9% had prevalent asthma. We based the exposure assessments on a land-use regression model and estimated associations using multivariable logistic regression models. Across all periods, mean exposure to NOx from birth to adolescence was associated with prevalent asthma at the examination in a dose-response manner, with an odds ratio for the upper quintile of 1.61 (95% CI: 1.56–1.67), in comparison to the lowest quintile. Associations were stronger in males and in lower socioeconomic strata. We found the strongest associations for asthma with comorbid rhinitis, with an almost twofold increase in the odds of upper versus lower quintile of exposure (odds ratio = 1.96, 95% CI: 1.82–2.11). Rhino-conjunctivitis and allergic atopic dermatitis suggested a possible threshold level with NOx. Capsule Summary: Research indicates that half of the global population will suffer from an allergic condition at some point in life. Childhood exposure to nitrogen oxides is a risk factor for the onset of asthma. The association between exposure and allergic diseases other than asthma is unclear. We demonstrate a strong, dose-response relationship between exposure and a group of allergic outcomes, using data comprising 2.5 million subjects over 50 years. The large health benefits from clean air should motivate governments to prioritize mitigation measures.

Exploring the Relation between Atopic Diseases and Lifestyle Patterns among Adolescents Living in Greece: Evidence from the Greek Global Asthma Network (GAN) Cross-Sectional Study

Introduction: Diet and physical activity might be associated with the risk of allergic diseases in childhood. However, evidence in literature is sparse and diverse. We aim to examine the associations between four healthy dietary consumption pattern drinks, plus the adherence to a physically active lifestyle with atopic diseases (asthma, allergic rhinitis and eczema) in adolescence and their relative importance. Methods: A total of 1934 adolescents (921 boys, 47.5%) and their parents completed a validated questionnaire assessing atopic diseases’ symptoms prevalence in the past 12 months, as well as nutritional and physical activity information. Four healthy dietary and one physical active lifestyle patterns were identified and logistic regression was applied to assess their relation with allergic diseases. Results: A high weekly consumption of fruits, vegetables and pulses and low consumption of unhealthy foods was negatively associated with all atopic symptoms while adherence to a physical active lifestyle was inversely associated with asthma and allergic rhinitis symptoms and dairy products with asthma and eczema symptoms in the past 12 months after adjustment for several confounders (all p < 0.05). Fruits, vegetables and pulses consumption per week emerged as the most important lifestyle pattern negatively associated for all atopic diseases, after the adjustment for all the remaining lifestyle patterns and confounders (all p < 0.05) Conclusions: Our findings suggest that a high fruit, vegetable and pulse intake should be the first lifestyle intervention every clinician and public health care worker evolving in the management of atopic adolescents should encourage and promote.

The role of cutaneous T-cell attracting chemokine in the development of different phenotypes of atopic dermatitis in children

The goal of this study was to detect the risk of developing different atopic dermatitis (AD) phenotypes in children (isolated or combined with other comorbid atopic diseases (AtD)) depending on serum concentrations of cutaneous T-cell attracting chemokine (CTACK)/CCL27. The main group comprised 39 children aged 3 to 18 years old suffering from different AD phenotypes – isolated (18 patients) and combined with comorbid AtD – AR/ARC and/or bronchial asthma (21 patients). The control group comprised 47 children aged 3 to 18 years old, suffering from diseases of the gastrointestinal tract (GIT). Serum CTACK/CCL 27 concentrations were detected in all children. In the full main group, the average level of CTACK/CCL27 was significantly higher compared to the patients of the control group: 4403.6 pg/ml (95% CI: 3726.2; 5148.7, p<0.001) and 3495.9 pg/ml (95% CI: 3197.8; 4186.8, p<0.001), respectively. Mean serum CTACK/CCL27 levels in patients of the main group with different AD phenotypes were higher than those in the full main group: with isolated AD – 4549.4 pg/ml (LQ; HQ: 3923.5; 5175.2, p<0.05), with AD associated with other AtD – 5116.6 pg/ml (LQ, HQ: 4062.8; 6170.5, p<0.05). In phenotypes of overall and isolated AD, the cut-off value of serum CTACK/ CCL27 is 3586.5 pg/ml (76.9% and 77.8%, respectively, and 38.3% in the control group). The risk of development at this concentration is 5.37 (95% CI: 2.05; 14.07, p<0.001) for the total AD phenotype and 5.64 (95% 1.56; 20.32, p<0.05) for the isolated AD phenotype. In AD phenotype combined with comorbid AtD, the cut-off value of serum CTACK/CCL27 is 4308.8 pg/ml (66.7% of the main and 21.3% in the control group). The risk of developing this AD phenotype at this concentration is 7.40 (95% CI: 2.30; 23.76, p<0.001). Serum CTACK/CCL27 levels are the reliable biomarker of the risk for developing different AD phenotypes in children. In the serum level of CTACK/CCL27=3658.5 pg/ml, the significant risk of developing total AD phenotype is 5.37, and isolated – AD=5.64. In the serum concentration of CTACK/CCL27=4308.8 pg/ml, the significant risk of developing AD phenotype combined with comorbid AtD is 7.40.

Very Elevated IgE, Atopy, and Severe Infection: A Genomics-Based Diagnostic Approach to a Spectrum of Diseases

Elevated IgE has been long recognized as an important clinical marker of atopy but can be seen in a myriad of conditions. The discovery of autosomal dominant STAT3 deficiency marked the first recognition of hyper-IgE syndrome (HIES) and the first primary immunodeficiency linked to elevated IgE. Since then, genomic testing has increased the number of defects with associated mutations causing hyper-IgE syndrome and atopic diseases with FLG, DOCK8, SPINK5, and CARD11, among others. A spectrum of recurrent infections and atopy are hallmarks of elevated IgE with significant phenotypic overlap between each underlying condition. As treatment is predicated on early diagnosis, genomic testing is becoming a more commonly used diagnostic tool. We present a 6-year-old male patient with markedly elevated IgE and severe atopic dermatitis presenting with staphylococcal bacteremia found to have a heterozygous variant in FLG (p.S3247X) and multiple variants of unknown significance in BCL11B, ZAP70, LYST, and PTPRC. We review the genetic defects underpinning elevated IgE and highlight the spectrum of atopy and immunodeficiency seen in patients with underlying mutations. Although no one mutation is completely causative of the constellation of symptoms in this patient, we suggest the synergism of these variants is an impetus of disease.