Potential Treatments for Food Allergy - 2015 update

This article from from Immunology and Allergy Clinics of North Ameica presents an overview of potential treatments of food allergy:

1. Various forms of immunotherapy:

- oral immunotherapy
- sublingual immunotherapy
- epicutaneous immunotherapy
- immunotherapy with modified food antigens
- immunotherapy with a recombinant peanut vaccine)

2. Allergen nonspecific treatments:

- Chinese herbal formulas
- probiotics/prebiotics
- helminths
- monoclonal antibodies
- toll-like receptor agonists

References:

Potential Treatments for Food Allergy - 2015 update from Immunology and Allergy Clinics http://buff.ly/1sOQL7u

Treating PASLI Immunodeficiency Disease - NIH video

From NIH/NIAD: Watch a video about a family’s experience with NIAID researchers who study rare disorders like PASLI disease.



Primary immune deficiency diseases (PIDDs) are rare, genetic disorders that impair the immune system. Without a functional immune response, people with PIDDs may be subject to chronic, debilitating infections, such as Epstein-Barr virus (EBV), which also can increase the risk of developing cancer. PIDDs may be diagnosed in infancy, childhood, or adulthood, depending on disease severity. They are estimated to affect more than 500,000 people in the United States.

In 2013, NIAID researchers identified a new PIDD called PASLI disease, named after the mutated gene and its symptoms (p110 delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency).

PASLI disease was initially detected in 6 patients who were referred to the NIAID PID Clinic. Upon further screening of the patients’ relatives, the disease was confirmed in 14 patients from 7 unrelated families of different ethnic and racial backgrounds. The patients have experienced recurring infections, including bacterial infections of the respiratory system and chronic viral infections with EBV, since childhood, and some have developed EBV-associated lymphoma.

By studying this group, the researchers found that the patients have a mutation in their PIK3CD gene, resulting in an overactive protein called PI3K-p110 delta. PI3K proteins are essential for directing the growth and activity of many types of immune cells, and p110 delta is specifically involved in B and T cells, which make antibodies and recognize and eliminate infected cells, respectively. The mutated, overactive p110 delta protein causes a chain reaction of problems. By sending the wrong signals at the wrong times, it disrupts the normal development of B and T cells, increasing susceptibility to infection.

The genetic information allowed the researchers to identify and target mTOR, an important signal that is excessively activated by p110 delta in PASLI patients. Drugs that block mTOR are already FDA-approved for the prevention of transplant rejection. One patient was treated with the drug rapamycin daily, which restored T cells to normal levels after 4 months. While the patient is not cured, normalization of T cells was adequate to improve disease symptoms.

References:

NIH Scientists Identify a New Immunodeficiency Disease http://1.usa.gov/1zmMsD9
New Variation of Genetic Immune Disorder Identified http://1.usa.gov/1zmMw61

Protocol for skin testing with levothyroxine

How to prepare the solution?

Thyroxin solution for skin testing can be prepared by crushing a tablet (50 mcg) and mixing with 1 mL of 0.9% phosphate-buffered saline for 2 hours.

The solution can be passed through a 0.2-micrometer-pore filter if future IV administration is indicated. This should be done by a pharmacist.

How to do the skin test?

Prick test with levothyroxine solutiion, 50 mcg/mL. If negative, do intradermal testing with 0.02 mL of the solution in concentrations of 1:100,000, 1:10,000, 1:1,000, 1:100, and 1:10.

If the tests are negative, a challenge with levothyroxine should be performed if indicated.



Drug allergy management in 5 steps (click to enlarge the image).

References:

IMMEDIATE-TYPE HYPERSENSITIVITY REACTION TO LEVOTHYROXINE AND DESENSITIZATION - Annals of Allergy, Asthma & Immunology http://buff.ly/1BHCa1C

Levothyroxine anaphylaxis? Vocal cord dysfunction mimicking an anaphylactic drug reaction - Annals of Allergy, Asthma & Immunology http://buff.ly/1FF8r6F

Image source: Wikipedia, public domain.

Severe Asthma in Children - free full text review in JACI: In Practice

Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of inhaled corticosteroids or oral corticosteroids. Severe asthma is divided into 2 categories:

- difficult-to-treat asthma - poor control due to an incorrect diagnosis or comorbidities, or poor adherence

- severe therapy-resistant asthma - poor control despite management of the factors above



Severe asthma: “What to do when asthma is not doing well?” (click to enlarge the image).

Severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes.

Guideline-based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. Children with severe asthma should be treated with higher-dose inhaled or oral corticosteroids combined with long-acting β-agonists and other add-on therapies, such as antileukotrienes and methylxanthines.

It is important to identify and address the influences that make asthma difficult to control, including reviewing the diagnosis and removing causal or aggravating factors.

Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future.

References:

Severe Asthma in Children. Theresa W. Guilbert, et al. The Journal of Allergy and Clinical Immunology: In Practice, Volume 2, Issue 5, Pages 489–500, September–October, 2014
(free full text)
http://www.jaci-inpractice.org/article/S2213-2198(14)00300-6/fulltext

16 VOCs could distinguish between healthy and asthma patients with a sensitivity of 100%, specificity of 91%

Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. VOC profiles in exhaled air could distinguish between asthma patients and healthy subjects. In this study from Switzerland, the researchers aimed to classify new asthma endotypes by combining inflammatory mechanisms investigated by VOC profiles in exhaled air and clinical information of asthma patients.

Breath samples were analyzed for VOC profiles by gas chromatography–mass spectrometry from 195 asthma patients and 40 healthy controls.

Out of 954 identified molecules, 16 VOCs could distinguish between healthy and asthma subjects with a sensitivity of 100% and a specificity of 91%. Cluster analysis based on VOCs in exhaled air, clinical parameters and FEV1, resulted in the formation of 7 different asthma endotype clusters.

This study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.

References:

Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air. Norbert Meyer et al. Respiratory Research 2014, 15:136 doi:10.1186/s12931-014-0136-8.
http://respiratory-research.com/content/15/1/136

Image source: OpenClipArt, public domain.

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