Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.

Microbiomes have highly important roles for ecosystem functioning and carry out key functions that support planetary health, including nutrient cycling, climate regulation, and water filtration. Microbiomes are also intimately associated with complex multicellular organisms such as humans, other animals, plants, and insects and perform crucial roles for the health of their hosts. Although we are starting to understand that microbiomes in different systems are interconnected, there is still a poor understanding of microbiome transfer and connectivity. In this review we show how microbiomes are connected within and transferred between different habitats and discuss the functional consequences of these connections. Microbiome transfer occurs between and within abiotic (e.g., air, soil, and water) and biotic environments, and can either be mediated through different vectors (e.g., insects or food) or direct interactions. Such transfer processes may also include the transmission of pathogens or antibiotic resistance genes. However, here, we highlight the fact that microbiome transmission can have positive effects on planetary and human health, where transmitted microorganisms potentially providing novel functions may be important for the adaptation of ecosystems.

The rapid rise in atopy and asthma in industrialized nations has led to the identification of early life environmental factors that promote these conditions and spurred research into how such exposures may mediate the trajectory to childhood disease development. Over the past decade, the human microbiome has emerged as a key determinant of human health. This is largely due to the increasing appreciation for the myriad of non-mutually exclusive mechanisms by which microbes tune and train host immunity. Microbiomes, particularly those in early life, are shaped by extrinsic and intrinsic factors, including many of the exposures known to influence allergy and asthma risk. This has led to the over-arching hypothesis that such exposures mediate their effect on childhood atopy and asthma by altering the functions and metabolic productivity of microbiomes that shape immune function during this critical developmental period. The capacity to study microbiomes at the genetic and molecular level in humans from the pre-natal period into childhood with well-defined clinical outcomes, offers an unprecedented opportunity to identify early-life and inter-generational determinants of atopy and asthma outcomes. Moreover, such studies provide an integrative microbiome research framework that can be applied to other chronic inflammatory conditions. This review attempts to capture key studies in the field that offer insights into the developmental origins of childhood atopy and asthma, providing novel insights into microbial mediators of maladaptive immunity and chronic inflammatory disease in childhood.

Asthma prevalence estimates among adults are limited for urban-rural classification across sociodemographic characteristics.

This study examined current asthma prevalence and annual trends by 6-level urban-rural categories across sociodemographic characteristics among US adults.

Asthma prevalence for 2020 and annual trends for 2012-20 were estimated using Behavioral Risk Factor Surveillance System data. The 2013 National Center for Health Statistics urban and rural categories were used to define urban-rural status.

Current asthma prevalence was higher in medium (9.7%; prevalence ratio 1.103 [95% CI 1.037, 1.174]) and small (9.9%; 1.111 [1.031, 1.197]) metro than in large fringe metropolitan (8.6%), was higher in micropolitan (10.2%) than in both large fringe (8.6%; 1.115 [1.042, 1.194]) and large central metropolitan (8.8%; 1.080 [1.001, 1.066]) areas. Prevalence by sociodemographic characteristics varied between urban-rural scheme; the prevalence was significantly higher among adults aged 55-64 years in micropolitan (11.9%), women in small metro (12.8%), and other race non-Hispanic in noncore (most rural) (13.6%) areas, adults without a high school diploma in micropolitan areas (13.8%), household income <100% of federal poverty level in micropolitan areas (15.7%), and adults with insurance coverage in micropolitan areas (10.3%) compared to the corresponding populations in other urban-rural categories. During 2012-20, an increasing trend in prevalence was observed only in medium metro areas, with an annual percentage change of 0.81.

Asthma prevalence differed by 6-level urban-rural categories. These findings might be helpful in establishing effective asthma control programs and targeting resource allocation at the local level.

Prolonged occupational agricultural exposure is associated with an increase in asthma diagnosis. This study aimed to identify the prevalence and risk factors for asthma in dairy farmers.

AIRBAg was a cross-sectional study including 1203 representative dairy farmers. They completed a self-administered questionnaire and underwent a health respiratory check-up. Referral to a pulmonologist was made for any participant with wheezing, dyspnoea, chronic bronchitis, a chronic cough or a FEV₁/FEV₆ ratio<80%. They underwent further examinations such as spirometry with a reversibility test. Controls (non-asthmatic dairy farmers and non-farm employees) were matched to each asthma case for sex and age (±5 years). The odds ratios (OR) between asthma and different risk factors were estimated using conditional multivariate logistic regression models.

Active asthma was diagnosed in 107 (8.9%) farmers. Compared with control dairy farmers, there was a positive association with family history of allergy (OR = 8.68; 95% CI [4.26-17.69]), personal history of eczema (OR = 3.39; 95% CI [1.61-7.13]), hay manipulation (OR = 5.36, 95% CI [1.59-18.01]), and a negative association with farm area (OR = 0.92; 95% CI [0.85-0.99]) and handling treated seeds (OR = 0.47; 95% CI [0.23-0.95]). Compared with control non-farm employees, there was a positive association between asthma and family history of allergy (OR = 95.82, 95% CI [12.55-731.47]).

The prevalence of active asthma in dairy farmers was somewhat higher than the rate observed in the general population but may be controlled by reducing exposure to airborne organic contaminants through occupational adaptions on farms.

Introduction: Asthma is among the most common chronic conditions in children. The aim of this publication is to describe prevalence rates and factors associated with asthmatic or wheezing preschoolers and to evaluate medical care and treatment with regard to urban-rural differences.Methods: Data for this cross-sectional study were collected through a questionnaire, which was distributed to parents within the Health Monitoring Units in Bavaria (HMU), Germany. Data from 4767 children were available (2016/17). Those children were classified into four diagnostic groups: Unremitting Wheeze, International Study of Asthma and Allergies in Children (ISAAC) Asthma, Physician-diagnosed Asthma, and healthy control group. Urban-rural differences were tested by Pearson's chi-squared test or by Fisher's exact test. Independent variables were factors associated with health outcomes, for example, residency or migrant status. To examine associations between independent and outcome variables multivariate logistic regression analysis was performed.Results: Prevalence rates were 6.3% for 'Unremitting Wheeze', 5.2% for 'ISAAC Asthma', and 1.2% for 'Physician-diagnosed Asthma'. Factors associated with health outcomes were the occurrence of asthma in first-degree relatives, male sex, and migrant status. Generally, higher rates of doctor's visits, positive allergy tests, and corticosteroids intake in the diagnostic groups in rural compared to urban areas were observed. Rates of performed allergy tests were 55.6% for 'ISAAC Asthma' and 74.6% for 'Physician-diagnosed Asthma'.Conclusions: Prevalence rates of the diagnostic groups decreased compared to the HMU 2014/15. According to previous studies, factors associated with asthmatic or wheezing health outcomes could be confirmed. Children in rural areas generally received more medical care.Key pointsChildren's prevalence rates of asthma or wheezing disorders decreased in the past 2 years within Bavaria.This study is consistent with risk factors for asthma from the literature: asthma in the family, male gender, and migrant status.Children in rural areas receive more medical care than children in urban areas.There should me more allergy tests among children with medical diagnosis in Bavaria as low rates indicate gaps in care.

Background: Research in early childhood allergy prevention (ECAP) is flourishing and new intervention strategies have proven to be promising. Due to the dynamic nature of ECAP, gaps between what is known and how guidelines inform practice are likely. A living systematic review (LSR) can narrow this gap by incorporating new evidence as it becomes available. No efficacy comparisons across various ECAP interventions for similar outcomes have been carried out. Networks of randomised clinical trials can be evaluated in the context of a network meta-analysis (NMA). We aim to establish a LSR on the efficacy and safety of any intervention investigated in randomised controlled trials (RCT) to prevent the occurrence of allergic sensitisation (AS), symptoms or diagnoses of allergic diseases in infancy and early childhood (0-3 years). Methods: A baseline SR will synthesise the evidence from existing SRs of RCTs as well as RCTs not yet considered in these. After completion of the baseline SR we propose to conduct a LSR. Using this methodology, we aim to undertake constant evidence surveillance, three-monthly search updates, and review updates every three months, should new evidence emerge. Conclusions: The ECAP evidence landscape has undergone dramatic transformations and this process is likely to continue. As a response to this, a LSR offers the potential to allow more timely synthesis of new evidence as it emerges. Long gaps between updates of SRs makes it harder for guidelines and recommendations to be up to date. Users of information, such as parents, may be confused if they encounter new evidence that is not part of a trusted guideline. A LSR approach allows us to continuously search the literature and update the evidence-base of existing ECAP interventions resulting in a decreased timespan from evidence accrual to informing clinical practice.

Background: Research in early childhood allergy prevention (ECAP) is flourishing and new intervention strategies have proven to be promising. Due to the dynamic nature of ECAP, gaps between what is known and how guidelines inform practice are likely. A living systematic review (LSR) can narrow this gap by incorporating new evidence as it becomes available. No efficacy comparisons across various ECAP interventions for similar outcomes have been carried out. Networks of randomised clinical trials can be evaluated in the context of a network meta-analysis (NMA). We aim to establish a LSR on the efficacy and safety of any intervention investigated in randomised controlled trials (RCT) to prevent the occurrence of allergic sensitisation (AS), symptoms or diagnoses of allergic diseases in infancy and early childhood (0-3 years). Methods: A baseline SR will synthesise the evidence from existing SRs of RCTs as well as RCTs not yet considered in these. After completion of the baseline SR we propose to conduct a LSR. Using this methodology, we aim to undertake constant evidence surveillance, three-monthly search updates, and review updates every three months, should new evidence emerge. Conclusions: The ECAP evidence landscape has undergone dramatic transformations and this process is likely to continue. As a response to this, a LSR offers the potential to allow more timely synthesis of new evidence as it emerges. Long gaps between updates of SRs makes it harder for guidelines and recommendations to be up to date. Users of information, such as parents, may be confused if they encounter new evidence that is not part of a trusted guideline. A LSR approach allows us to continuously search the literature and update the evidence-base of existing ECAP interventions resulting in a decreased timespan from evidence accrual to informing clinical practice.

Asthma and allergies are complex, chronic inflammatory diseases in which genetic and environmental factors are crucial. Protection against asthma and allergy development in the context of farming environment is established by early animal contact, unpasteurized milk consumption and gut microbiota maturation. The human β-defensin 2 (hBD-2) is a host defense peptide present almost exclusively in epithelial tissues, with pronounced immunomodulatory properties, which has recently been shown to ameliorate asthma and IBD in animal models. We hypothesized that adequate hBD-2 secretion plays a role in the protection against asthma and allergy development and that genetic variations in the complex gene locus coding for hBD-2 may be a risk factor for developing these diseases, if as a consequence, hBD-2 is insufficiently produced. We used MALDI-TOF MS genotyping, sequencing and a RFLP assay to study the genetic variation including mutations, polymorphisms and copy number variations in the locus harboring both genes coding for hBD-2 (DEFB4A and DEFB4B). We administered hBD-2 orally in a mouse model of house dust mite (HDM)-asthma before allergy challenge to explore its prophylactic potential, thereby mimicking a protective farm effect. Despite the high complexity of the region harboring DEFB4A and DEFB4B we identified numerous genetic variants to be associated with asthma and allergy in the GABRIELA Ulm population of 1,238 children living in rural areas, including rare mutations, polymorphisms and a lack of the DEFB4A. Furthermore, we found that prophylactic oral administration of hBD-2 significantly curbed lung resistance and pulmonary inflammation in our HDM mouse model. These data indicate that inadequate genetic capacity for hBD-2 is associated with increased asthma and allergy risk while adequate and early hBD-2 administration (in a mouse model) prevents atopic asthma. This suggests that hBD-2 could be involved in the protective farm effect and may be an excellent candidate to confer protection against asthma development.