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What Is New In Small Airways Research

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Author: Ves Dimov, M.D.
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine
Small Airways Working Group

Asthma and its relation with microbes: 2015 review

High-resolution microbiota sequencing and translational models of lung disease are providing new insight into the roles of microorganisms in asthma pathogenesis and exacerbation. Bacteria have roles to play in the disease progress and clinical outcome of asthma but also appear to play protective functions in certain cases. Asthma can be viewed as a chronic inflammatory disease that can be initiated and modulated by the airway microbiota. These interactions with the host immune system can involve commensal bacteria as well as pathogens. Increase in asthma prevalence worldwide could be due in part to a changing relation with microbes in the lower respiratory tract. Understanding the molecular basis and biological effect the airway microbiota has on the host immune response may lead to the discovery of microbial or immunological targets that are amenable to manipulation for the development of new treatments.

Source: Earl CS, An S, and Ryan RP. The changing face of asthma and its relation with microbes. Trends in Microbiology 2015; published online before print, 31 March. (doi:http://dx.doi.org/10.1016/j.tim.2015.03.005)

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Image Source: Wikipedia, Staphylococcus aureus; public domain

Genetic profiles for personalized and precision medicine in asthma

Pharmacogenetic approaches have already become useful in other pulmonary diseases to identify individuals most likely to respond to costly biologic therapies. One example is the discovery of ivacaftor for treatment of cystic fibrosis related to CFTR Gly551Asp gene. Is asthma next? It is possible that variants in an IL4RA gene could serve as biomarkers for biologic drugs currently under development such as dupilumab.

DNA should be collected in drug trial cohorts and made available for pharmacogenetic studies. In time, the costs of high-throughput genotyping and DNA sequencing will continue to decrease, while the expanding volume of genetic data will be deciphered by different analytic methods that take into account genetic ancestry, gene–gene interactions, and rare variant effects. An integrated approach will be critical for the development of genetic profiles based on the complex molecular mechanisms underlying treatment responses to eventually deliver truly precise and personalized medicine to an individual asthmatic.

Source: Ortega VE, Meyers DA, Bleecker ER. Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Journal of Pharmacogenomics and Personalized Medicine 2015; 8: 9-22. (doi:10.2147/PGPM.S52846)

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Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma, could be used as add-on treatment

Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms.

This double-blind, randomized, placebo-controlled trial investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (³53%) and/or eosinophilic (³3%) airway inflammation.

In patients with eosinophil levels of 26% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41% to 11.8% after vitamin D treatment. It also resulted in slightly better Asthma Control Questionnaire scores (P = .08).

Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation but did not affect sputum neutrophils. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

Source: de Groot JC, van Roon ENH, Storm H, Veeger NJGM, Zwinderman AH et al. Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma. Journal of Allergy and Clinical Immunology March 2015; 135(3): 670-675. (doi:http:dx.doi.org/10.1016/j.jaci.2014.11.033)

Abstract

Last updated: Monday, May 18th, 2015