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Translating Basic Research into Clinical PracticeInteraction Between Adaptive and Innate Immune Pathways in the Pathogenesis of Atopic Asthma: Operation of a Lung/Bone Marrow Axis
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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2018, Journal of Allergy and Clinical ImmunologyCitation Excerpt :In light of the association of nonatopic systemic inflammation with disease burden in obese asthmatic adults38 and children,6,11 we speculate that CDC42 activation in T cells from obese asthmatic patients might play several roles, including skewing of T-cell differentiation to a TH1/TH17 profile, increased T-cell tissue recruitment by facilitating transmigration, and T-cell activation. Because these pathways are distinct from those activated in patients with atopic asthma,39 our findings begin to identify immune pathways associated with nonatopic immune responses in patients with the obese asthma phenotype. Activation of Rho GTPases, including CDC42, has been proposed to underlie T-cell activation in patients with TH1-mediated autoimmune diseases, such as lupus.40
Rhinovirus-induced first wheezing episode predicts atopic but not nonatopic asthma at school age
2017, Journal of Allergy and Clinical ImmunologyCitation Excerpt :We suggest that the investigation of virus etiology, sensitization, and eczema status, and especially the combination of these 3, might enable the asthma risk assessment already at the time of the first wheezing episode because rhinovirus-sensitive viral diagnostics are widely available.1,2,4,7,19,21,33 The underlying susceptibility to atopic disorders and viral triggers might be the true asthma risk factor, and thus interplay between sensitization and viral infections is likely to be involved.2,5,15,34,35 The Childhood Origins of Asthma study group showed the chronological order of causality in a statistical model (ie, early-life aeroallergen sensitization precedes rhinovirus illnesses and asthma).2
Vitamin D over the first decade and susceptibility to childhood allergy and asthma
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Funding/Support: The authors are supported by the National Health and Medical Research Council of Australia.
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