Environmental determinants of allergy and asthma in early life
TL;DR: The evidence supporting a relationship between key components of the external exposome in the prenatal and early‐life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures is explored.
Abstract: Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children.
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University of Amsterdam1, Ghent University2, University of Chicago3, University of Pennsylvania4, Lund University5, Auckland City Hospital6, University of Antwerp7, University of New South Wales8, Katholieke Universiteit Leuven9, Guy's and St Thomas' NHS Foundation Trust10, Queen's University11, University of Zagreb12, Northwestern University13, Medical University of Łódź14, University of Aberdeen15, Medical University of South Carolina16, University of North Carolina at Chapel Hill17, University of Southampton18, University of São Paulo19, National University of Singapore20, Flinders University21
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012 and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.
2,853 citations
TL;DR: Evidence is reviewed of how air pollutants can affect different immune cell types such as particle-clearing macrophages, inflammatory neutrophils, dendritic cells that orchestrate adaptive immune responses and lymphocytes that enact those responses, and of the capacity of air pollutants to stimulate pro-inflammatory immune responses across multiple classes of immune cell.
284 citations
TL;DR: Asthma is one of the main causes of hospitalization which are particularly common in children aged < 5 years with a prevalence that has been increased during the last two decades, mostly in LMICs.
Abstract: Asthma is the most common chronic disease in children, imposing a consistent burden on health system. In recent years, prevalence of asthma symptoms became globally increased in children and adolescents, particularly in Low-Middle Income Countries (LMICs). Host (genetics, atopy) and environmental factors (microbial exposure, exposure to passive smoking and air pollution), seemed to contribute to this trend. The increased prevalence observed in metropolitan areas with respect to rural ones and, overall, in industrialized countries, highlighted the role of air pollution in asthma inception. Asthma accounts for 1.1% of the overall global estimate of "Disability-adjusted life years" (DALYs)/100,000 for all causes. Mortality in children is low and it decreased across Europe over recent years. Children from LMICs particularly suffer a disproportionately higher burden in terms of morbidity and mortality. Global asthma-related costs are high and are usually are classified into direct, indirect and intangible costs. Direct costs account for 50-80% of the total costs. Asthma is one of the main causes of hospitalization which are particularly common in children aged < 5 years with a prevalence that has been increased during the last two decades, mostly in LMICs. Indirect costs are usually higher than in older patients, including both school and work-related losses. Intangible costs are unquantifiable, since they are related to impairment of quality of life, limitation of physical activities and study performance. The implementation of strategies aimed at early detect asthma thus providing access to the proper treatment has been shown to effectively reduce the burden of the disease.
238 citations
Cites background from "Environmental determinants of aller..."
...These indoor allergens play an important role in eliciting asthma exacerbations, by increasing airway inflammation and bronchial hyper-responsiveness (24)....
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TL;DR: Modulation of macrophage phenotypes through molecular intervention by targeting some of those potential macrophAGE regulators may have therapeutic potential in the treatment of allergic asthma and other allergic diseases.
214 citations
Cites background from "Environmental determinants of aller..."
...Allergic disease prevalence has increased significantly in recent decades.(1) The majority of school-age children and adults with asthma have concomitant allergic sensitization, which has been associated with asthma inception and severity....
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TL;DR: Associations between the timing and cause of early viral infections and the subsequent risk of childhood asthma were assessed in a cohort of children at high risk.
Abstract: Jackson DJ, Gangnon RE, Evans MD, et al. Am J Respir Crit Care Med. 2008;178(7):667–672
PURPOSE OF THE STUDY. Childhood asthma is often preceded by episodes of viral wheezing. Whether specific viral infections confer more risk for future development of asthma is incompletely understood. Associations between the timing and cause of early viral infections and the subsequent risk of childhood asthma were assessed in a cohort of children at high risk.
STUDY POPULATION. A total of 259 children were …
192 citations
References
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TL;DR: It is found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode.
Abstract: Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.
3,640 citations
TL;DR: This systematic review and meta-analyses confirmed the findings of a previous study published in “Rhinitis and Asthma: Causes and Prevention, 2nd Ed.” (2015) as well as new findings of “Mechanisms of Respiratory Disease and Allergology,” which confirmed the role of EMTs in the development of these diseases.
Abstract: Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada
3,368 citations
TL;DR: The most important determinants of the gut microbiotic composition in infants were the mode of delivery, type of infant feeding, gestational age, infant hospitalization, and antibiotic use by the infant.
Abstract: OBJECTIVE.The aim of this study was to examine the contribution of a broad range of external influences to the gut microbiotic composition in early infancy. METHODS.Fecal samples from 1032 infants at 1 month of age, who were recruited from the KOALA Birth Cohort Study in the Netherlands, were subjected to quantitative real-time polymerase chain reaction assays for the enumeration of bifidobacteria, Escherichia coli, Clostridium difficile, Bacteroides fragilis group, lactobacilli, and total bacterial counts. Information on potential determinants of the gut microbiotic composition was collected with repeated questionnaires. The associations between these factors and the selected gut bacteria were analyzed with univariate and multivariate analyses. RESULTS.Infants born through cesarean section had lower numbers of bifidobacteria and Bacteroides, whereas they were more often colonized with C difficile, compared with vaginally born infants. Exclusively formula-fed infants were more often colonized with E coli, C difficile, Bacteroides, and lactobacilli, compared with breastfed infants. Hospitalization and prematurity were associated with higher prevalence and counts of C difficile. Antibiotic use by the infant was associated with decreased numbers of bifidobacteria and Bacteroides. Infants with older siblings had slightly higher numbers of bifidobacteria, compared with infants without siblings. CONCLUSIONS.The most important determinants of the gut microbiotic composition in infants were the mode of delivery, type of infant feeding, gestational age, infant hospitalization, and antibiotic use by the infant. Term infants who were born vaginally at home and were breastfed exclusively seemed to have the most “beneficial” gut microbiota (highest numbers of bifidobacteria and lowest numbers of C difficile and E coli).
2,006 citations
"Environmental determinants of aller..." refers background in this paper
...Vaginally delivered infants tended to be colonized with vaginal (Lactobacillus species) and fecal (Prevotella species) flora, whereas infants born by means of caesarean section tended to be colonized by skin flora (Staphylococcus and Corynebacterium species),(17) with increased abundance of Clostridium difficile and reduced Bifidobacterium and Bacteroides species.(16) Meta-analyses of studies examining the association between delivery mode and allergic disease in Western countries found an increased risk of childhood asthma,(18,19) allergic rhinitis,(18) and food allergy(18) in children born by means of caesarean section compared with vaginal births....
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TL;DR: A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.
Abstract: Background In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen. Methods Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children. Results Endotoxin levels in samples of dust from th...
1,740 citations
"Environmental determinants of aller..." refers background in this paper
...The Allergy and Endotoxin cross-sectional survey found that higher levels of endotoxin in child mattresses were associated with reduced risk of allergic sensitization, hay fever symptoms, and atopic asthma.(27) The precise mechanism for this effect is not known....
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...One theory suggests that increased exposure to environmental endotoxin leads to downregulation of inflammatory responses.(27) Others have suggested the protective effect is the result of polymorphisms within the CD14 gene, which encodes a coreceptor for Toll-like receptor 4 with high specificity for LPS, and in fact, a recent systematic review found a significant gene-environment interaction between CD14 polymorphisms and microbial exposure....
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TL;DR: In addition to genetic factors, exposure in early childhood to house-dust mite allergens is an important determinant of the subsequent development of asthma.
Abstract: Background and Methods. Children with asthma commonly have positive skin tests for inhaled allergens, and in the United Kingdom the majority of older children with asthma are sensitized to the house-dust mite. In a cohort of British children at risk for allergic disease because of family history, we investigated prospectively from 1978 to 1989 the relation between exposure to the house-dust mite allergen (Der p I) and the development of sensitization and asthma. Results. Of the 67 children studied in 1989, 35 were atopic (positive skin tests), and 32 were nonatopic. Of the 17 with active asthma, 16 were atopic (P<0.005), all of whom were sensitized to the house-dust mite, as judged by positive skin tests and levels of specific IgE antibodies (P<0.001). For house-dust samples collected from the homes of 59 of the children in 1979 and from 65 homes in 1989, the geometric means for the highest Der p I exposure were, respectively, 16.1 and 16.8 μg per gram of sieved dust. There was a trend toward an ...
1,645 citations