Chest
Volume 139, Issue 5, May 2011, Pages 1165-1171
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Translating Basic Research into Clinical Practice
Interaction Between Adaptive and Innate Immune Pathways in the Pathogenesis of Atopic Asthma: Operation of a Lung/Bone Marrow Axis

https://doi.org/10.1378/chest.10-2397Get rights and content

Atopic asthma is the most common form of asthma, particularly during childhood, and in many cases it persists into adult life. Although atopy is clearly a risk factor for development of this disease, only a small subset of subjects sensitized to aeroallergens express persistent symptoms, suggesting that additional pathogenic mechanisms are involved. Recent studies have implicated respiratory viral infections as key cofactors in asthma development in atopic patients. In relation to initial expression of the asthma phenotype in early childhood, it has been shown that although both atopic sensitization and early severe lower respiratory tract infections can operate as independent asthma risk factors, the persistence of asthma is most frequent among children who experience both insults, suggesting that the relevant inflammatory pathways interact to maximally drive disease pathogenesis. Importantly, it has been established that both these factors must be operative contemporaneously for these interactions to occur (ie, the interactions are likely to be direct). Recent studies on viral-induced asthma exacerbations in atopic children have provided a plausible mechanism for these interactions. Notably, it has been demonstrated that signals triggered during the innate immune response to the virus can lead to the release of large numbers of migrating high-affinity IgE receptor-bearing bone marrow-derived precursors of mucosal dendritic cells into the blood. The subsequent trafficking of these cells to the infected airway mucosa where dendritic cell turnover is very high provides a potential mechanism for recruitment of underlying aeroallergen-specific T-helper 2 immunity into the already inflamed milieu in the infected airway mucosa.

Section snippets

Asthma-Associated Phenotypes in Early Life

Studies conducted in longitudinal birth cohorts, such as the Tucson Children's Respiratory Study6 and Western Australian Pregnancy Cohort (Raine study)7 have defined a number of asthma phenotypes based on when children wheeze, how long wheezing persists, and what triggers the wheeze. Wheezing in infancy is common, with up to 30% having at least one episode of wheeze. The Tucson group defined transient infantile wheeze as a condition in which children wheezed in the first 3 years of life, often

Development of the Persistent Atopic Asthmatic Phenotype

The broad association between atopy and asthma symptoms during childhood has been recognized for many years,24 and the strength of this relationship during the school years has been confirmed via the results of recent prospective cohort studies. The particular issue of whether the atopic phenotype per se can alone account for this association (eg, by increasing risk for development of inappropriate proinflammatory T helper [Th] 2-associated immunity against any class of inhaled antigen) is

Acute Asthma Exacerbations: Similar Interactions at Play?

The importance of respiratory viral infections as triggers of acute severe asthma exacerbations has been recognized for many years,2, 34 particularly in children. However, the underlying mechanisms are incompletely understood, partly because of the logistic and ethical difficulties associated with obtaining relevant clinical material for study at the time of acute symptoms. The development of highly sensitive genomics-based techniques for expression profiling, which require only nanogram levels

Conclusions and Speculation

The findings presented here are derived principally from studies focusing on atopic asthma and demonstrate the potential for amplification of airways inflammation initiated locally by a microbial pathogen through effects induced in myeloid precursor populations at a distal site (the bone marrow). This may be mediated either via soluble cytokines/mediators secreted into the blood and/or via cytokine-secreting cells (notably activated Th cells) migrating from the inflammatory site into bone

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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    Funding/Support: The authors are supported by the National Health and Medical Research Council of Australia.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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