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The relationships between environmental bacterial exposure, airway bacterial colonization, and asthma.

Curr Opin Allergy Clin Immunol. 2014 Jan 21;

Authors: Beigelman A, Weinstock GM, Bacharier LB

Abstract
PURPOSE OF REVIEW: Recent application of advanced culture-independent molecular techniques for the identification of microorganisms has contributed to our knowledge on the role of early-life microbial exposure and colonization in health and disease. The purpose of this review is to present the current perspectives regarding the role of microbial exposure and airway bacterial colonization on the development and the activity of asthma.
RECENT FINDINGS: Recent findings continue to support the protective role of early-life diverse microbial exposure against the development of atopic diseases. However, airway bacterial colonization early in life serves as a risk factor for the development of asthma. Culture-independent molecular techniques for the identification of microorganisms have challenged the traditional paradigm that the lower airway is a sterile compartment. Asthmatics, compared with nonasthmatics, appear to have a different lung microbiome composition and some of these differences might contribute to asthma activity, severity, and corticosteroid response.
SUMMARY: Bacterial presence in the airway appears to influence the inception and may affect the activity of asthma. Complex interactions between different types and routes of bacterial exposures, the airway, and the immune system early in life may determine whether these exposures augment or reduce the risk of asthma development.

PMID: 24451910 [PubMed - as supplied by publisher]

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Early weight gain and the development of asthma and atopy in children.

Curr Opin Allergy Clin Immunol. 2014 Jan 21;

Authors: Wandalsen GF, Chong-Neto HJ, de Souza FS, Solé D, Bacharier LB

Abstract
PURPOSE OF REVIEW: To provide perspective to the most recent evidence regarding the association between early weight gain in infancy and the development of asthma and atopy during childhood, and highlight the potential mechanisms involved.
RECENT FINDINGS: Recently, several birth cohort studies involving more than 25 000 children have found a consistent association between early weight gain in the first 2 years of life and incident asthma during school age. Methodology differs substantially between the studies and complicates the establishment of definite conclusions. Specific mechanisms for this association have been proposed, including impairment in lung development and elevated levels of growth factors and cytokines associated with airway inflammation and remodeling. A limited number of studies indicate that early weight gain in infancy is also associated with recurrent wheezing during preschool age but not with the development of atopy.
SUMMARY: A consistent association between early weight gain in infancy and incident asthma during school age has been observed in several cohort studies. The identification of this modifiable risk factor for the development of asthma opens the possibility of preventive intervention. Additional studies are necessary to clarify the involved mechanisms and some pending questions, such as the influence of early weight gain in asthma phenotypes and severity.

PMID: 24451911 [PubMed - as supplied by publisher]

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Asthma is a heterogeneous disease with numerous clinical phenotypes. Severe asthma constitutes about 10 % of all cases of asthma. There is significant geographic and regional variation in the incidence and severity of asthma.

Other important factors include gender, ethnicity, living environment, lifestyle, socioeconomic class, and pathophysiology. These factors can often be identified as either genetic or environmental influences on asthma severity. The immune system derangements in severe asthma are poorly understood. Many molecules and cell types have been implicated in severe asthma, including neutrophils, airway epithelial cells, thymic stromal lymphopoietin, and even filaggrin.

Recently, vitamin D has been thought to have a role in the severity of asthma. Aspirin exacerbated respiratory disease is an example of a phenotype that includes severe asthma as a feature. This suggests a role of leukotrienes or prostaglandins in the pathogenesis of severe asthma. Both the innate and adaptive immune system may play a role in the development of severe asthma. Besides filaggrin, other factors of the innate immune system, including TLR4 and TLR9 have been implicated in asthma. Airway epithelial cells possess pattern recognition receptors that recognize danger or pathogen-associated molecular patterns, and the result of binding of the ligand is the triggering of a signaling pathway that ultimately can lead to an activation of inflammatory mediators through the action of calcineurin and NF-κB. Components of the adaptive immune system, including TH2 and Th17 cells, have been implicated in the pathogenesis of asthma. The fact that so many molecules and cells may be variably involved in asthma patients, coupled with the presence of redundant pathways that lead to secretion of inflammatory mediators, make the development of effective drugs for the treatment of asthma extremely difficult.

A better understanding of the heterogeneity and what drives this diversity on a genetic and epigenetic level will help to develop strategies for novel therapeutic agents or methods.