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Childhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization.

ABSTRACT: Inappropriate responses to respiratory viruses, especially rhinovirus, and early allergic sensitization are the strongest contributors to the inception and persistence of early onset asthma. The ORMDL3 asthma locus in chromosome 17q seems to exert its effects by increasing susceptibility to human rhinovirus in early life. Being raised on animal farms is highly protective against the development of asthma, and this protective effect is mediated by exposure to microbes. Two trials in high-risk young children, one to prevent wheezing lower respiratory tract illness using bacterial lyophilizates and another using anti-immunoglobulin E to prevent asthma progression, are already under way.

SUBMITTER: Martinez FD

PROVIDER: S-EPMC6613822 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Childhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization.

Martinez Fernando D FD

Immunology and allergy clinics of North America 20190501 2

Inappropriate responses to respiratory viruses, especially rhinovirus, and early allergic sensitization are the strongest contributors to the inception and persistence of early onset asthma. The ORMDL3 asthma locus in chromosome 17q seems to exert its effects by increasing susceptibility to human rhinovirus in early life. Being raised on animal farms is highly protective against the development of asthma, and this protective effect is mediated by exposure to microbes. Two trials in high-risk you ...[more]

PMID: 30954166

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Project description:BackgroundSpecific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and asthma risk.ObjectiveTo define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen-specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk.MethodsChildren at high-risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen-specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap(®) 100; Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years.ResultsSensitization to dog was strongly associated with increased asthma risk (P < 0.0001). Sensitization to perennial compared with seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (P = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (P = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (P = 0.05).Conclusions and clinical relevanceAnalysing specific patterns of an individual's allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as 'atopic' by the presence of any demonstrable sensitization alone. Furthermore, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of sensitization.

Project description:PURPOSE OF REVIEW:Asthma is a chronic respiratory condition with increasing domestic and worldwide prevalence that burdens individuals and the healthcare system with high costs associated with long-term treatments and acute emergency room (ER) visits. It can be triggered by ambient microbes, including bacteria, viruses, and fungi. In this review, we examine the outcomes of asthma patients in relation to environmental exposures to ambient microbe products, focusing on whether exposure leads to asthma development from birth to childhood and if particular microbes are associated with worsened asthma exacerbations. RECENT FINDINGS:Bacterial endotoxin is more prominent in homes with pets and may cause cytokine cascades that lead to asthma exacerbation. However, some studies have demonstrated a protective effect with early exposure. Patients with positive Aspergillus skin testing are more prone to moderate-severe or severe-uncontrolled asthma. Fungal sensitization is also associated with earlier onset of asthma and demonstrates a dose-dependent relationship of symptom severity and duration. Among viruses, rhinovirus has the greatest association with decreased lung function, severe asthma, and asthma-related hospital admissions. Distribution of microbial products and associated asthma symptoms depends on the geographical climate. Genetic variations among individuals also mitigate the effects of microbial products on asthma development and symptom severity. Microbial products of bacteria, fungi, and viruses are associated with the development of asthma, more severe asthma symptoms, and worse outcomes. However, some early exposure studies have also demonstrated a protective effect. Bacterial and fungal products are related to decreased lung function and earlier onset of asthma. Viral products are related to asthma-associated hospital admissions; and the climate and patient genetics can also temper or intensify the relationships between microbial products, asthma development, and asthma symptom severity. Further research should focus on the effects of early microbe exposure and its interaction with human immune systems and asthma-related outcomes.

Dataset Information

Childhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization.

Publications

Childhood Asthma Inception and Progression: Role of Microbial Exposures, Susceptibility to Viruses and Early Allergic Sensitization.

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