Respiratory allergy caused by house dust mites: Inhaled mite aeroallergens are unusually virulent (2015 review)

The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic asthma. However, awareness of the condition remains generally low. Prevalence data for HDM allergen sensitization vary from 65 to 130 million persons in the general population worldwide to as many as 50% among asthmatic patients. Inhaled mite aeroallergens are unusually virulent: they are able to activate both the adaptive and innate immune responses. Translation of silent sensitization into symptomatic disease is still incompletely understood. Improved understanding of HDMs, their allergens, and their microhabitats will enable development of more effective outcomes for patients with HDM allergy.

References:

Respiratory allergy caused by house dust mites: What do we really know? Moisés A. Calderón et al. JACI 2015, free full text.
http://www.jacionline.org/article/S0091-6749(14)01482-1/fulltext

The next generation sequencing of microbiome of lower airways

For many years, the human lower airways were considered a sterile environment where the presence of microorganisms was interpreted as an abnormal health state. Not anymore.

High-throughput sequencing-based studies have led to a shift in this perception. Even in healthy conditions the lower airways show either a transient presence or a permanent colonization by microorganisms.

This review summarizes the methodology pertinent to high-throughput sequencing studies, based on amplicon sequencing, and discusses good practices and common pitfalls: http://www.waojournal.org/content/8/1/23

The study of the human lower airway microbiome is still in its infancy.

References:

The microbiome of the human lower airways: a next generation sequencing perspective.
Velma T. E. Aho et al. World Allergy Organization Journal 2015, 8:23, free full text.
http://www.waojournal.org/content/8/1/23

Image source: Lungs, Wikipedia, public domain.

As some of you know, I have been the Editor of the World Allergy Organization (WAO) Small Airways Working Group "What's New?" monthly summary since 2011. The summary features the top 3 asthma/small airways articles each month. The article above is part of the project. The archive is here: http://www.worldallergy.org/small_airways_group/reviews/archive.php

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 in 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.

References:

Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Victor E Ortega, Deborah A Meyers, and Eugene R Bleecker. Pharmgenomics Pers Med. 2015; 8: 9–22, free full text.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325626/

Assessment of Small Airways with Computed Tomography (CT) Leaves More to be Desired

Computed tomography (CT) assessment of air trapping has been considered useful as a measure of small airway disease. Mean lung density (MLD) and the percentage of the lung field occupied by low attenuation area (LAA%) can be evaluated automatically, and their expiratory/inspiratory (E/I) ratios correlate with asthma severity and spirometry parameters. However, mosaic attenuation, another indicator of air trapping, has been assessed visually, and its functional relevance remains controversial.

This retrospective study of 36 nonsmoking patients with stable asthma attempted to correlate mosaic attenuation, which was assessed visually and automatically, and the E/I ratios of MLD and LAA% with clinical and physiological variables, including impulse oscillometry (IOS) indices.

Only the E/I ratios of MLD and LAA% correlated with forced expiratory volume in 1 s/forced vital capacity of spirometry and the IOS indices of resistance from 5 to 20 Hz.

The automatic method for analysis of mosaic attenuation could be useful, but the results themselves may not be reflecting small airway involvement of asthma, unlike the E/I ratios of MLD and LAA%.

References:

Assessment of Small Airways with Computed Tomography: Mosaic Attenuation or Lung Density. Oguma T et al. Respiration. 2015 Apr 30. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/25924974

Real-Time Activation of One Mast Cell - NEJM video



Real-Time Activation of a Mast Cell by Substance P: Photomicroscopy of one human mast cell placed between two cover slips and perfused with the neuropeptide substance P shows degranulation in real time as observed with the use of Nomarski (three-dimensional) optics.

See the related NEJM article, "Mast Cells, Mastocytosis, and Related Disorders" http://www.nejm.org/doi/full/10.1056/NEJMra1409760
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