Oral tolerance induction in peanut allergy

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Peanut allergy is common, potentially severe and rarely resolves. Currently, there is no definitive therapy ("cure") for peanut allergy.

The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce tolerance to peanuts.

Four peanut-allergic children underwent OIT. The diagnosis was proven by pre-intervention oral challenges.

OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases.

All subjects tolerated immunotherapy "up dosing" to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (2.38 g protein) in post-intervention challenges.

The authors concluded that OIT was well tolerated and conferred protection against peanuts.

References:
Successful oral tolerance induction in severe peanut allergy. Clark AT, Islam S, King Y, Deighton J, Anagnostou K, Ewan PW. Allergy. 2009 Feb 17.

Specific oral tolerance (SOTI) cannot be recommended for routine clinical practice for food allergy treatment yet - JACI http://goo.gl/AKBy

Peanut oral immunotherapy is not ready for clinical use - From the experts in the field. JACI, 2010 http://goo.gl/YipT

Office-based oral immunotherapy for food allergy is safe and effective - according to Texas allergist group that use it http://goo.gl/S4N8W

Therapies for peanut allergy: Sustained oral tolerance over desensitization is the goal, we are not there yet. http://goo.gl/mXsyt

Peanut oral immunotherapy (20 peanuts) induces desensitization, however questions about long-term tolerance remain. JACI, 2011.

Oral immunotherapy for peanut allergy - interview with Dr. Wesley Burks: clearly 15-20% will not tolerate the treatment http://goo.gl/U45UB

Eosinophilic esophagitis after specific oral tolerance induction for egg protein http://goo.gl/fzmip
Peanut Allergy: An Evolving Clinical Challenge (review), 2011.
Image source: Roasted peanuts as snack food, Wikipedia, public domain.

High Levels of Apolipoproteins Associated with Wheezing, Asthma and Atopy

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There is an association between serum cholesterol and asthma, but little is known about the underlying mechanisms.

The study authors measured plasma concentrations of apolipoprotein AI (apoAI) and apolipoprotein B (apoB) of 462 10-year-old schoolchildren.

High apoAI concentrations were associated with high prevalence of wheeze and a trend was seen with asthma.

References:
Association of Apolipoproteins with Symptoms of Asthma and Atopy among Schoolchildren. Nagel G, Weiland SK, Rapp K, Link B, Zoellner I, Koenig W. Int Arch Allergy Immunol. 2009 Feb 12;149(3):259-266.

Interleukin-17 levels related to severity of allergic rhinitis

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T helper (Th)-17 cells are a subset of T helper lymphocytes that have regulatory activities.

The aim of this study was to investigate the relationship between serum IL-17 levels (measured by ELISA) and allergic rhinitis. 56 patients with pollen-induced allergic rhinitis were evaluated during the pollen season.

IL-17 levels were related to symptoms and peripheral eosinophil counts.

The authors concluded that IL-17 level assessment may be used to classify allergy severity.


Function of T helper cells: Antigen presenting cells (APCs) present antigen on their Class II MHC molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4 co-receptor (CD4+). The activation of a resting helper T cell causes it to release cytokines and other stimulatory signals (green arrows) that stimulate the activity of macrophages, killer T cells and B cells, the latter producing antibodies. Image source: Wikipedia, Mikael Häggström, public domain.

Which cytokines promote neutrophil tissue inflammation?

(A) IL-2

(B) IL-5

(C) IL-8

(D) IL-10

(E) IL-17

Answers: IL-8 and IL-17.

References:
Serum interleukin-17 levels are related to clinical severity in allergic rhinitis. Ciprandi G, De Amici M, Murdaca G, Fenoglio D, Ricciardolo F, Marseglia G, Tosca M. Allergy. 2009 Feb 17.
T helper cell, from Wikipedia, the free encyclopedia.

Cord Serum IgE Level Predicts Atopy up to Age 20

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Elevated level of umbilical cord serum immunoglobulin E (CS-IgE) is a risk factor for allergic disease in children and young adults.

The researchers followed a cohort of 190 newborns at birth and again at the ages of 5, 11 and 20 years.

At age 5, an elevated CS-IgE level was associated with allergic symptoms and positivity in skin prick testing. It was also associated with elevated serum total IgE at the ages of 11 and 20 years and with allergic rhinoconjunctivitis at the age of 20 years.

The sensitivity of elevated CS-IgE in predicting skin-prick verified atopy was 50% at the age of 5 years and 26% at the age of 20 years.

There was an opposing study published in 2011: Cord blood immunoglobulin E level is not a strong predictor of clinical allergic disorders http://goo.gl/HJJzy

Ig structures. Image source: Wikipedia.


Role of IgE and mast cells in allergy. Image source: Wikipedia.

References:

Cord Serum IgE Level Predicts Atopy up to Age 20. Medscape.
Pediatr Allergy Immunol 2009;20:12-18.
Both low and high levels of cord blood 25(OH) vitamin D were associated with increased aeroallergen sensitization. JACI, 2011.
Image source: Wikipedia, GNU Free Documentation License.

Horse treated for grass allergy with avoidance and antihistamines

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Thoroughbred Horse Has Allergy to Grass

References:
Horse treated for grass allergy. BBC.

Related:

Prevalence of horse allergy is underestimated - horse allergen should be in routine panel for skin testing (in Italy) http://goo.gl/KOGRp

Adipokines may not associated with asthma after all

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The prevalence of asthma and obesity is increasing concomitantly, but many aspects of this link are unclear.

At ages 24-39 years, body mass index (BMI) and female gender were independently associated with asthma.

Levels of leptin, adiponectin or any other obesity-related biomarker were not independently associated with asthma.

References:
Obesity, adipokines and asthma. Jartti T, Saarikoski L, Jartti L, Lisinen I, Jula A, Huupponen R, Viikari J, Raitakari OT. Allergy. 2009 Feb 10.

Decreased response to inhaled steroids in overweight and obese asthmatic children. JACI, 2011.
Image source: Wikipedia, public domain.

Characteristics of childhood peanut allergy

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A study of 778 children born in the Australian Capital Territory examined the clinical features of peanut allergy over 13 years:

- Most peanut allergy (90%) developed by age 72 months.

- Later age of first reaction was associated with an increased risk of anaphylaxis.

- Asthma was associated with increased risk of anaphylaxis.

- The incidences of peanut allergy and sensitization by age 72 months were 1.15% and 1.53%, respectively

- There was a rise in incidence during the 13-year study period.

References:
Characteristics of childhood peanut allergy in the Australian Capital Territory, 1995 to 2007. Mullins RJ, Dear KB, Tang ML. J Allergy Clin Immunol. 2009 Feb 12.
Image source: Roasted peanuts as snack food, Wikipedia, public domain.

Anti-acid drug sucralfate may increase risk for food allergy

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Aluminium (ALUM) is used as experimental and clinical adjuvant for parenteral vaccine formulation. It is also contained in anti-acid drugs like sucralfate (SUC).


Chemical structure of sucralfate. Source: Wikipedia, public domain.

Sucralfate is an oral gastrointestinal medication primarily used for control of heartburn symptoms. It is a sucrose sulfate-aluminium complex that binds to the hydrochloric acid in the stomach and acts like an acid buffer with cytoprotective properties. Sucralfate was approved by the Food and Drug Administration (FDA) in 1981.

Sucralfate is a locally acting substance that in an acidic environment (pH lower than 4), reacts with hydrochloric acid in the stomach to form a cross-linking, viscous, paste-like material capable of acting as an acid buffer for as long as 6 to 8 hours after a single dose.

The aim of this study was to assess the oral adjuvant properties of ALUM in a mouse model.

The highest OVA-specific immunoglobulin G1 (IgG1) and IgE antibody levels were found in mice fed with OVA/SUC, followed by OVA/ALUM-treated animals. Positive skin tests confirmed an allergic response.

The authors concluded that ALUM acts as a Th2-adjuvant via the oral route. This suggests that orally applied SUC leads to an enhanced risk for food allergy.

References:
Aluminium per se and in the anti-acid drug sucralfate promotes sensitization via the oral route. Brunner R, Wallmann J, Szalai K, Karagiannis P, Altmeppen H, Riemer AB, Jensen-Jarolim E, Pali-Schöll I. Allergy. 2009 Feb 5.

Anti-acid medications may be a risk factor for food allergy
Sucralfate, from Wikipedia, the free encyclopedia.

Onset of action of ciclesonide in the treatment of seasonal allergic rhinitis: 6 hours

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Ciclesonide is an intranasal corticosteroid (INS) approved for the treatment of allergic rhinitis (AR) in adults and children 6 years of age and older. The trade name in the U.S. is Omnaris.

Ciclesonide seems to have no significant effect on hypothalamic-pituitary-adrenal axis.

Why ciclesonide has no significant effect on hypothalamic-pituitary-adrenal axis?

The medication is "activated" locally in the lungs. Carboxylesterases in bronchial epithelial cells convert ciclesonide to des-CIC in the lungs. Low systemic levels of des-CIC are a result of the high metabolic clearance by the liver following CIC inhalation.

In a double-blind, randomized, placebo-controlled study, 509 adults with at least a 2-year history of SAR completed 1 to 5 priming sessions of ragweed pollen exposure. Patients with successful priming visits received a single dose of intranasal ciclesonide, 200 microg or placebo.

The change from baseline in TNSSs between the ciclesonide and placebo groups was measured hourly 1 to 12 hours.

The authors concluded that intranasal ciclesonide, 200 microg/d, has an onset of action of 6 hours in patients with SAR.

Ciclesonide is marketed under the brand name Alvesco for asthma and Omnaris/Omniair for hayfever in the US and Canada.



Treatment Options for Allergic Rhinitis (click to enlarge the image).

Ciclesonide mnemonic

C

Ciclesonide

Converted to active form (des-CIC)

Carboxyl-esterases in bronchial epithelial cells

Clearance by liver

References:

Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis. Couroux P, Kunjibettu S, Hall N, Wingertzahn MA. Ann Allergy Asthma Immunol. 2009 Jan;102(1):62-8.

New Dry Nasal Spray are on the Horizon for Perennial Allergic Rhinitis - Medscape, 2011.

Ciclesonide Aerosol (Alvesco) Approved for Asthma Treatment

Mind Maps: Allergic Rhinitis

Images source: Wikipedia, a free GNU license and public domain.

CNN video: Can a peanut allergy be cured?

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SLIT and budesonide are equally effective in mild persistent asthma due to grass pollen

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Few studies have compared the effects of immunotherapy and inhaled steroids. The main limitation is the long duration required to fully appreciate the effects of immunotherapy.

Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open randomized controlled trial.

They were randomized to either budesonide, 800 microg/d, in the pollen season or continuous grass SLIT for 5 years.

The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups, but the improvement was greater in the SLIT patients at 3 and 5 years.

The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group.

The bronchial hyperresponsiveness improved significantly only in the SLIT group.

The authors concluded that in patients with grass pollen-induced asthma, in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness.

Comment: It may not be "fair" to compare the seasonal use of budesonide to the continuous use of SLIT.

References:
Long-term comparison of sublingual immunotherapy vs inhaled budesonide in patients with mild persistent asthma due to grass pollen. Marogna M, Spadolini I, Massolo A, Berra D, Zanon P, Chiodini E, Canonica GW, Passalacqua G. Ann Allergy Asthma Immunol. 2009 Jan;102(1):69-75.
Talking Points on Sublingual Immunotherapy (SLIT) for Physicians Practicing in the United States. ACAAI.
Image source: Fountain grass (Pennisetum setaceum) flowers in Waterloo, Ontario, Wikipedia,
Giligone, Creative Commons Attribution-ShareAlike 3.0 License.

Sublingual immunotherapy is an extremely complex issue in the U.S. - AAAAI http://goo.gl/wVOKr

Allergy history alone is not sufficient when assessing patients with asthma and rhinitis in general practice

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The authors defined formal allergy assessment as:

- allergy history
- skin prick tests to 5 common aeroallergens

The study objective was to estimate the extent to which a formal allergy assessment would improve the precision of allergy diagnosis compared with a patient's self-report or the allergy history alone.

The study included 127 patients with asthma and rhinitis from 4 general practices in the UK.

Self-reporting misclassified allergic status in many patients.

An allergy history alone was little better and resulted in false-positive rates for cat allergy of 32%, grass pollen of 48%, house dust mite of 75%, tree pollen of 54%, and dog of 27%.

Skin prick testing combined with a history was essential to reach a correct causative diagnosis.

References:
Is structured allergy history sufficient when assessing patients with asthma and rhinitis in general practice? Smith HE, Hogger C, Lallemant C, Crook D, Frew AJ. J Allergy Clin Immunol. 2009 Jan 7.
Image source: picturestation.net, free license.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

• ICS/LABA Have Changed Childhood Asthma: less oral steroids, higher FEV1, less albuterol, fewer intubations http://is.gd/nB03
  
  
• Most physicians who prescribe EpiPen have not told patients how to use them, unable to operate one successfully http://is.gd/nAP3
  
  
• Travel and food allergy: 80% of families with food allergies avoided cruises. Travel and food allergy: 90% of families with food allergies have not left the U.S http://is.gd/nB1r
  
  
• Headline of the day: "Sesame Allergies on the Rise in U.S.: Blame the hummus!"-- sesame allergy has increased more than any other food allergy over the past 10-20 years, now among the most common. "Sesame is now clearly one of the six or seven most common food allergens in the U.S." 70% of the patients allergic to sesame were also allergic to tree nuts, while 65% were allergic to peanuts http://is.gd/nyXU
  
  
• Baxter is testing subcutaneous IVIG with hyaluronidase to improve absorption in primary immunodeficiency http://is.gd/nz4I
  
  
• Differentiating COPD from asthma in clinical practice: why, why not and how? http://is.gd/nAHu and http://is.gd/nAHR

Image source: OpenClipArt.org, public domain.

Rhinitis medicamentosa: "Confessions of a Nasal Spray Addict"

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From The Island Med Student blog:

"Let me go back to the beginning. Several months ago, I became very sick, and one of the worst symptoms was rhinnorea (runny nose) and congestion. It was absolutely horrible, and I could barely breathe. Since I can’t take oral pseudoephedrine (makes me jittery and hallucinate), I decided to use the OTC nasal sprays available. After 2 quick squirts, my life was turned around! I could breathe effortlessly. My head wasn’t pounding and feeling like it was going to explode. All was well again!

However, now it’s been several months, and I can’t seem to get off the nasal spray. If I stop using it, my nose completely swells up with mucous. I can’t breathe at ALL through my nose. My head feels like it’s going to explode. My ears start popping painfully.

So, I started doing some research online, and it turns out that I am not alone. Millions of people suffer from nasal spray addiction, or “Rhinitis medicamentosa.”

The topical use of decongestant sprays leads to rebound hyperemia, producing progressively worse nasal obstruction and "rhinitis medicamentosa."

Although the most common agents implicated in "rhinitis medicamentosa" are topical decongestants, oral medications may also play a role, especially beta-blockers, clonidine, ACEi, and oral contraceptives.


Afrin - Costco.


Rhinitis types, pathological classification.

References:
Confessions of a Nasal Spray Addict. The Island Med Student, 2009.
Allergic Rhinitis: A Short Review

Pseudoephedrine used in allergic rhinitis improved stuffy nose but decreased sexual activity http://goo.gl/1uLxb

Oxymetazoline for 1 month adds to nasal steroid effect in perennial allergic rhinitis, without development of rhinitis medicamentosa. JACI, 2011.
WVU Health Report - Nasal Spray Addiction, 2011 (video).
Image source: Oxymetazoline, the active component of Afrin nasal spray, Wikipedia, public domain.

Twitter Updates from the 2009 Annual Meeting of the American Academy of Allergy Asthma and Immunology (AAAAI)

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Press releases from the annual AAAAI meeting (ongoing now) are available here: http://is.gd/nnGf

Twitter updates by some of the attendees can be found on Twitter search using the search term "AAAAI" or the hashtag #AAAAI. A few selected Twitter posts (also called tweets or updates) are listed below. I will update the list as more updates are added during the conference.

From wheezemd:

• Major changes at the AAAAI meeting. One can tell the cutbacks by the pharma companies.
• Allergists in a state of funk-the economy and health care reform - it's the unknown that leads to stress.
• Is the Medical Home concept just another name for a new gatekeeper system?
• At AAAAI plenary session on food allergy. Few common allergens with high cross-reactivity. Example fish.
• #AAAAI peanut allergen Ara h 2 and 6 not affected by heat and heat increases antigenicity Ara h 1 in some patients.
• #AAAAI Ara h 1 doesn't lose antigenicity by gastic digestion.
• At World Allergy Journal meeting. Need for manuscripts for the online journal.
• Interesting study combining an intranasal steroid and an intranasal antihistamine showing added benefit in allergic rhinitis.
  
  

From JoyHCN:

• The AAAAI Saturday morning Plenary: Food Allergy: State of the Science is PACKED!!
• AAAAI press room is bare bones this year. But it's kind of cool to get all the materials on a thumb drive rather than a heavy conf book
• Dr. Bischoff: Future therapies for food allergy may include probiotics and intestinal therapies... #AAAAI
• Extrapolated FDA numbers show there r about 125K food allergy related visits to the ER annually, 14K of which r due 2 anaphylaxis #AAAAI
• Sampson: Skin prick tests and IgE tests alone wil likely way over diagnose food allergies. #AAAAI #food allergy
• Sampson: Without a complete or reliable medical history, a food challenge test is necessary to Dx food allergies #AAAAI
• As Sampson has said many times b4, yes, it is possible to outgrow food allergies, milk and egg most commonly outgrown #AAAAI
• Peanut, tree nut and shellfish allergies, though, are less commonly outgrown, thought it's still possible #AAAAI
• #AAAAI sitting among all these docs, furiously typing on my laptop to Tweet, I'm getting some funny looks LOL!
• As b4, the best food allergy therapy is still strict avoidance and carrying epinephrine. Sorry food allergy plp, same old same old #AAAAI
• Audio & video recording of educational sessions @ #AAAAI is prohibited; Assume that DOESN'T include blogging/tweeting
• For those who want 2 B research cool, a "murine model" just means research in mice
• The first state to have more than 25% of its adult pop obese was Mississippi in 2001. By 2007, the "thinnest" state was CO w/15%-20% obesity
• Have 2 admit that Tweeting live is a lil distracting. Paying more attention 2 what's happening on Twitter than 2 the speaker. Hmm...
• Overheard a doc 2 another doc "I'm looking for earth shattering. I want u to tell me something & I go wow! There's no wow this year" #AAAAI
• "Give me something I can take back to NY that I can use to help my patients. I haven't seen that yet here" #AAAAI
• Makes me wonder, what role do conferences serve now when people can get new info instantaneously on Twitter, RSS feeds, mag subs etc? #AAAAI
• Excellent point. There is no substitute for a face to face meeting, so I think conferences are still useful. @allergicgirl #AAAAI
• There are some successful, but small, studies being done on the use of traditional Chinese medicine on food allergies & eczema #AAAAI
• DO NOT try food allergy challenges at home! Can incredibly dangerous, Dr. A. Wesley Burks. Also see http://tinyurl.com/bpnpuo #AAAAI
• Burks: In the next few years, there will likely B "active treatment" 4 food allergies besides strict avoidance, today's only therapy #AAAAI
• So far, the most interesting things have bn early success of Mt. Sinai's trad Chinese med studies on food allergy, asthma, eczema #AAAAI
• FYI, the gold standard test for food allergies is a doctor supervised food challenge. Pretty scary gold standard #AAAAI
• Dr. Wood disagrees with Dr. Burks: he says an FDA-approved therapy for food allergies is well more than 10 years away #AAAAI
• Fish & Shellfish r most common food allergy in U.S. considering all ages. In children, milk & egg allergy r most common, NOT peanut #AAAAI
• U wanna prevent a deadly food allergy anaphylaxis rxn: "No epi, no eatie!" Always have an epi pen and know how to use it #AAAAI
• Study of 4 child asthma deaths: all overused rescue inhalers, none had asthma action plan, none consistently used controller meds #AAAAI
• 1 boy, 14 yo, African American, died WHILE USING his albuterol nebulizer! Had stayed home from school previous day b/c of asthma. #AAAAI
• Also, 33% of asthma-related fatalities happened in patients classified as having MILD disease (according to a 1992 Australian study) #AAAAI
• ER docs might be part of the food allergy fatality problem: many mistake anaphylaxis allergic rxns 4 asthma attacks & mistreat #AAAAI
• Take home notes: ER docs & PCP should B aware of any allergies their asthmatic patients have as a rxn may B anaphylaxis, not asthma #AAAAI
• Have food allergies, go nowhere & eat nothing w/o having an epi pen on u. Fatal rxns more likely in plp who had mild rxns B4 #AAAAI
• Uncontrolled asthma is #1 factor in fatal allergy shot rxns. Docs should reconsider admin of shots if pt's asthma isn't controlled #AAAAI
• What's your asthma personality? Your life may depend on it http://tinyurl.com/9wc8dw #AAAAI
• Take home note: Asthmatic kids (& adults) should have an asthma action plan at school. http://tinyurl.com/c5rych #AAAAI
• "Asthma is a nighttime disease b/c some protective effects, corticosteroids & adrenalin, diminish @ night," Busse #AAAAI

References:
Science Conference Coverage with Twitter
Twitter Updates from the Severe Asthma Workshop at the 2008 Annual Meeting of American College of Allergy, Asthma & Immunology (ACAAI)
Photos: 2008 Annual ACAAI Meeting in Seattle, Washington, November 6-11

Updated: 03/16/2009

JACI: Advances in basic and clinical immunology in 2008

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- Modulation of T(H)2 responses by specific transcription factors and receptors associated with the innate immunity - for example a TLR-9 agonist

- HIV-infected individuals who receive antiviral treatment develop a high incidence of asthma, resembling the inflammatory processes associated with immunoreconstitution

- Correlation of molecular diagnosis and clinical presentation was analyzed in 4 rare primary immunodeficiencies (PID): hyper-IgE syndrome; immune dysfunction, polyendocrinopathy, enteropathy, X-linked disease; cartilage-hair hypoplasia; and nuclear factor-kappaB essential modulator deficiency

- Long-term outcomes from patients with severe combined immunodeficiency (SCID) who received bone marrow transplants (BMT) considered successful


Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).

References:
Advances in basic and clinical immunology in 2008. Chinen J, Shearer WT. J Allergy Clin Immunol. 2009 Feb;123(2):328-332.

Advances in Allergy and Immunology. JACI.
Image source: Wikipedia, GNU Free Documentation License.

High-dose desloratadine (4-times the standard dose) is effective and safe in cold urticaria

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CNN: Woman is allergic to cold

Increased dosing of nonsedating antihistamines is recommended by the current European guidelines for acquired cold urticaria (ACU) who do not respond satisfactorily to the standard dose.

The authors compared the effects of 5 and 20 mg of desloratadine and placebo on cold-induced urticarial reactions in patients with ACU in a prospective, randomized, double-blind, 3-way crossover trial of 30 patients.


Desloratadine (trade names NeoClarityn, Claramax, Clarinex and Aerius) is an active metabolite of loratadine. Image source: Wikipedia, public domain.

At the end of each treatment, patients underwent cold provocation with the TempTest 2.0/2.1 system, and urticarial reactions were assessed.

Desloratadine at 20 mg/d significantly reduced cold-induced wheal volume versus desloratadine at 5 mg/d.

High-dose desloratadine (20 mg) was well tolerated, with no increased rate of somnolence.

The authors concluded that desloratadine at standard (5 mg) and high doses (20 mg) significantly improved objective signs of ACU provoked by cold exposure.

Desloratadine at 4 times the standard dose was better than 5 mg of desloratadine without an increase in AEs. Therefore, the increased desloratadine dosing might benefit patients with urticaria who do not respond to standard doses.

References:
High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: A randomized, placebo-controlled, crossover study. Siebenhaar F, Degener F, Zuberbier T, Martus P, Maurer M. J Allergy Clin Immunol. 2009 Feb 5.
Urticaria: A Short Review
CNN Video: Cold Urticaria
Cold Urticaria on Flickr

Consumer Reports "Best Buy Drugs" for Allergic Conditions and Asthma

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Consumer Reports is an American magazine with 4 million subscribers and an annual testing budget of approximately $21 million U.S. It publishes reviews and comparisons of consumer products and services based on reporting and results from its in-house testing laboratory. It also publishes general buying guides.

This is their list of "Best Buy Drugs" for Allergic Conditions and Asthma:

Consumer Reports "Best Buy Drugs" - Antihistamines http://is.gd/j2zS

• Loratadine 10mg tablets
• Loratadine dissolving 10mg tablets
• Loratadine syrup 10mg
• Alavert tablets 10mg
• Alavert dissolving 10mg tablets
• Alavert syrup 10mg
• Tavist ND 10mg tablets

Consumer Reports "Best Buy Drugs" - Inhaled Steroids http://is.gd/j2Ai

• Beclomethasone (QVAR) 80mcg— for adults and children age 5 and over with asthma
• Budesonide (Pulmicort Turbuhaler) 200mcg — for adults with asthma who may prefer a dry powder inhaler and for children with asthma age 6 and over
• Fluticasone (Flovent HFA) 110mcg — for children with asthma age 12 and over
• Fluticasone (Flovent HFA) 220mcg — for children age 12 and over and adults with asthma, and for adults with moderate to severe COPD
• Mometasone (Asmanex Twisthaler) 220mcg — for adults with asthma

References:
Consumer Reports, from Wikipedia, the free encyclopedia.
Image source: Wikipedia, public domain.

Patient information: Measures to control house dust mite exposure

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Allergy sufferers often have a difficult time getting a good night rest. This is often due to the fact that allergens (mostly dust mites and their products) may be present in the very bed that you are sleeping in. Dust mites "hide" in your bed linings and mattress and can result in itchy skin, sneezing, running nose, and coughing.


Yellow mite. Image source: Wikipedia, public domain.

How do you protect your bed from dust mites? One of approaches is to use a hypoallergenic mattress cover or pad.

Hypoallergenic mattress covers can reduce the amount of dust mite allergens in your bedroom. While a hypoallergenic mattress cover will help reduce the amount of allergens in your bedroom, it is important to remember that this is not a cure by any means. Another way to combat allergies in your bedroom is to make sure that you keep the room as clean as possible and wash your bedding frequently.



Dust mite allergen avoidance. The main allergen is in the dust mite feces. Use 3 control measures for 3-6 months to see an effect on the allergy symptoms (click to enlarge the image).


Measures Used for Dust Mite Control

Physical barriers for dust mite control

Covers:

- pillows
- mattresses
- box springs
- comforters
- furniture cushions

The simplest covers are made of plastic but they may be uncomfortable to use. Gas permeable fabrics are an alternative to plastic covers.

Benefit of bedding covers (as only intervention) on asthma control has not been well-documented. House dust mite impermeable bedding as an isolated intervention is unlikely to offer benefit (Allergy, 2011).

Decreasing humidity to below 50% reduces mite growth. The best method is air conditioning in a humid climate. Upper floors are less humid. Patients allergic to HDM have less symptoms on 2nd floor.

After washing, bedding should be dried in a dryer on a hot setting.

In 50% of the reported trials, dust mite avoidance failed -- the measures did not decrease allergen exposure for a significant period of time.

You need at least 3 methods for 3 months minimum:

Physical measures for 3-6 months:

- pillow covers
- mattress covers
- washing bedding in hot water/dryer
- carpet removal

References:

Indoor Allergen Avoidance

There's an entire industry making asthma and allergy products - but do they work? http://goo.gl/KkUqW

House dust mite impermeable bedding as an isolated intervention is unlikely to offer benefit (Allergy, 2011).
The efficacy of dust mite covers and hot water wash environmental control procedures http://goo.gl/CvIIk
Where are highest concentrations of dust mites found in home? Pillows, stuffed animals, mattress, bedding? http://goo.gl/l6KtR -- A: Mattress.
Dust mite-impermeable mattress covers alone are not very helpful - a complex approach with 3-4 measures is needed http://goo.gl/nr3TW

Traditional Chinese medicines may be effective for treating asthma and allergy

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Corticosteroids and beta(2)-agonists are effective in managing asthma symptoms but a curative therapy for asthma is lacking. Traditional Chinese medicine (TCM), used in Asia for centuries, may have a role in Western health care for asthma treatment.

Possible mechanisms include anti-inflammation, inhibition of airway smooth muscle contraction, and immunomodulation.

Evidence from clinical studies supports beneficial effects of TCM herbal therapy on asthma.

Data suggest the potential efficacy of food allergy herbal formula-2 for food allergy.

In a review of the current experimental therapies for food allergy, Nature claims that the Mount Sinai research group hopes to bring Chinese herbal formula to the market in 2013, bypassing the FDA approval process (http://goo.gl/h7hL8).

However, I ran a search for "Chinese formula for food allergy" and there is not much new in Pubmed, apart from a review in the Mount Sinai's own journal, Mt Sinai J Med. 2011 Sep-Oct;78(5):697-716.

The search for "herbal formula food allergy" brings better results, including a small phase I study, again by the Mount Sinai group, that did not evaluate clinical efficacy, which is typical of the phase I trials.

The use of parasitic worms for treating allergic diseases was also disappointing in a recent study.

References:

Efficacy and mechanisms of action of traditional Chinese medicines for treating asthma and allergy. Li XM, Brown L. J Allergy Clin Immunol. 2009 Feb;123(2):297-306.
Chinese herbs for treatment of asthma and food allergy
Acupuncture for treatment of allergic rhinitis
Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-gamma-producing CD8+ T cells. Srivastava KD, Qu C, Zhang T, Goldfarb J, Sampson HA, Li XM. J Allergy Clin Immunol. 2009 Feb;123(2):443-51.

"Don't knock Chinese medicine. It's been around for more than 3,000 years and there's a lot we don't understand yet." http://goo.gl/TNjxy

No Chinese manufacturer has successfully registered herbal medicinal products in the EU - all will be banned in May. The Lancet, 2011.
The quest to find the "magic" Chinese herbal formula continues: Danggui Buxue Tang helps asthmatic MICE http://goo.gl/Bdfle
Image source: Wikipedia, public domain.

Plastic Surgeon Discusses Suture Allergies

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A plastic surgeon blogger discusses suture allergies in Suture Allergies Revisited.

"Allergic reactions to suture materials are rare and have been specifically associated with chromic gut. However, Johnson and Johnson mention known triclosan allergy as a contraindication for use of certain sutures. Contact allergy to triclosan is uncommon.

Surgical gut suture (Plain and Chromic) is contraindicated in patients with known sensitivities or allergies to collagen or chromium, as gut is a collagen based material, and chromic gut is treated with chromic salt solutions.

Surgical Stainless Steel Suture may elicit an allergic response in patients with known sensitivities to 316L stainless steel, or constituent metals such as chromium and nickel. Skin staples are surgical steel so should be used with the same precautions."

References:
Suture Allergies Revisited. Suture for a Living, 04/2008.
Image source: Surgical suture on a needle holder. Packaging shown above. Wikipedia, public domain.

Atlases of Allergy and Immunology

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A list of a few books from my Twitter page:

AllergyNotes Atlas of Allergic Diseases: http://tinyurl.com/6dts38, see a fellow's review here: http://tinyurl.com/6qnus6 1:38 PM Dec 5th from web

AllergyNotes Color Atlas of Allergic Diseases: http://tinyurl.com/6fg99x 1:43 PM Dec 5th from web

AllergyNotes Atlas of Allergies and Clinical Immunology: http://tinyurl.com/69okza 1:43 PM Dec 5th from web

Dietary exclusions do not improve atopic eczema in adults and children

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Atopic eczema is the most common inflammatory skin disease of childhood in developed countries.

The study authors performed a systematic review of 9 randomized controlled trials to assess the effects of dietary exclusions in atopic eczema:

- 6 studies of egg and milk exclusion
- 1 study of few foods
- 2 studies of an elemental diet

There was no benefit of either diet in unselected cases of atopic eczema

There may be some benefit of egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs (51% improvement in body surface area).

The authors concluded that despite their frequent use, there was little evidence to support the use of exclusion diets in atopic eczema.

References:
Dietary exclusions for improving established atopic eczema in adults and children: systematic review. Bath-Hextall F, Delamere FM, Williams HC. Allergy. 2009 Feb;64(2):258-64.

Image source: OpenClipArt.org, public domain.

Twitter Conference: CCR4 Receptor as a Potential Treatment Target in Asthma?

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Twitter updates:

• Attending a lecture about the role of IL 13 and CCR5 in asthma, anti-CCR5 drugs inhibit downstream effects of IL 13
  
  
• CCR5 receptor is present on CD4 lymphocytes and is used by the HIV virus to enter the cell along with the CD4 receptor
  
  
• Anti-CCR5 drugs could be used to treat both HIV and asthma, Maraviroc is an example
  
  
• 1% of European population carries a CCR5 mutation making such people "resistant" to HIV. Are they at lower risk of asthma?
  
  
• The same CCR5 mutation supposedly protected its carriers agains bubonic plague in middle ages. It was therefore 'promoted' in the evolution process.
  
  
• CCR5-delta32 mutation reduces risk of nonatopic asthma http://www.ncbi.nlm.nih.gov...

Evidence for the cure of HIV infection by CCR5 delta 32/delta 32 stem cell transplantation http://j.mp/gwDMH5 and http://j.mp/fQJAlM

SNPs associated with atopic diseases

Filaggrin gene

Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.

17q12-21 gene

ORMDL3 protein defects associated with asthma.

5q22-32 gene

CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.

3p21-22 gene

CCR5 is a chemokine receptor. SNP can be protective against asthma.

Xp22 gene

TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.

5q31 gene

IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.

ADRB2 gene

ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.

ADAM33 gene

Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.

References:
A small-molecule compound targeting CCR5 and CXCR3 prevents the development of asthma. Eur Respir J 2007, doi:10.1183/09031936.00111507.
Association of CCR5-delta32 mutation with reduced risk of nonatopic asthma in Slovenian children. J Asthma. 2008 Nov;45(9):780-4.

Thrombomodulin (CD141) - a new marker for atopy and asthma?

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Dendritic cells (DCs) are important in allergic diseases because they induce TH2-polarized responses in atopic individuals.

Thrombomodulin (CD141 or blood dendritic cell antigen 3 [BDCA-3]) is a membrane protein expressed on the surface of endothelial and dendritic cells. Thrombomodulin functions as a co-factor in the thrombin-induced activation of protein C in the anticoagulant pathway.

The antigen described as BDCA-3 turned out to be identical to thrombomodulin.

Thrombomodulin (CD141) expression was higher on house dust mite (HDM) allergen-stimulated DCs from atopic individuals.

In vivo, thrombomodulin+ circulating DCs were significantly more frequent in subjects with HDM allergy and asthma, compared with controls.

Thrombomodulin expression on DCs may be involved in the pathogenesis of atopy and asthma.

References:
Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response. Stephanie T. Yerkovich et al. JACI, Volume 123, Issue 1, Pages 209-216.e4 (January 2009).
Thrombomodulin in exercise-induced asthma. Kanazawa H, Kurihara N, Hirata K, Kamimori T, Takeda T. Intern Med. 1995 Mar;34(3):158-62.
Image source: Thrombomodulin, Wikipedia, public domain.

Allergy and Immunology News of the Day

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Health News of the Day is a daily summary made from the selected links I post on Twitter. It is in a bullet points format with links to the original sources which include 350 RSS feeds that produce about 2,500 items per day.

• Too much TV linked to higher asthma risk, if you can believe that. Children who watch television for more than two hours a day have twice the risk of developing asthma. Asthma affects more than 300 million people worldwide and is the most common children's chronic illness. Asthma accounts for one in 250 deaths globally each year, linked to obesity and lack of exercise http://is.gd/lxDF
  
  
• Hospitalizations for respiratory problems rise on hot, humid days. Hospital admissions rose by 4% for each degree increase in temperature beyond the 90-percent threshold http://is.gd/lFwx
  
  
• A Dallas TV station is describing immunotherapy (allergy shots) as "fighting fire with fire" http://is.gd/lHAo
  
  
• Children who've been infected with measles are less likely to develop allergies http://is.gd/lR2O
  
  
• Severe Insulin Allergy Treated with Rituximab and Omalizumab http://is.gd/lR9A
  
  
• HFA asthma inhalers can interfere with breath alcohol analyzer readings. The new propellant of asthma inhalers consists of HFAs, with some also containing alcohol -- ethanol. Transient increase in breath ethanol concentr. (BEC) after use of HFA-ethanol inhaler, returned to baseline within 5 min http://is.gd/lRcw
  
  
• 4.5% rate of cleft palate observed in rodents receiving doses equivalent to maximal recommended human dose of albuterol http://is.gd/lReK
  
  
• Spraying Combivent into eyes may result in narrow-angle glaucoma, mydriasis, increased intraocular pressure http://is.gd/lReK

Image source: OpenClipArt.org, public domain.

Mepolizumab Useful in Refractory Eosinophilic Asthma, a Rare Subtype of Asthma

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Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma.

A study examined the prednisone-sparing effect of mepolizumab (proposed trade name Bosatria), a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone.


Eosinophil. Image source: Wikipedia.


Eosinophil. Image source: Wikipedia.

Eeosinophilic form of asthma represents less than 5% of cases of adult-onset asthma and is difficult to treat.


Crystal structure of human IL-5. Image source: Wikipedia, public domain.

Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment.

Mepolizumab therapy reduced exacerbations by 43% and improved Asthma Quality of Life Questionnaire (AQLQ) scores in patients with refractory eosinophilic asthma.

Eosinophils may have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in patients with eosinophilic asthma.


Cytokine targets for immunomodulators for allergic disorders.


Mediators from Eosinophils


Cytokine-based treatments of asthma and allergic diseases

What is the most potent chemokine (chemoattractant) for eosinophils?

(A) IL-5

(B) IL-8

(C) LTB4

(D) eotaxin

(E) IL-4

(F) IL-13

Answer: D.

Eosinophil chemotactic protein 2 (Eotaxin-2) is the most potent chemoattractant for eosinophils but IL-5 is the most specific stimulant of their production.

The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.

References:
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. NEJM, Volume 360:973-984 March 5, 2009 Number 10.
Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. NEJM, Volume 360:985-993 March 5, 2009 Number 10.
Immunomodulators for allergic respiratory disorders. Casale TB, Stokes JR. J Allergy Clin Immunol. 2008 Feb;121(2):288-96; quiz 297-8.
Eosinophils in Asthma — Closing the Loop or Opening the Door? NEJM, Volume 360:1026-1028 March 5, 2009 Number 10.
Mind Maps: Immunomodulators for allergic disorders
Severe asthma unresponsive to inhaled corticosteroids -- what treatment option is next?
Eosinophils

Monoclonal antibody reslizumab improves lung function in asthma subtype with eosinophilic airway inflammation - ACAAI, 2010 http://goo.gl/UJJHG

Anti-IL5 Antibody Reslizumb (mAb) Looks Promising for Severe Eosinophilic Asthma http://goo.gl/mlGkL

Gene therapy is a safe and effective treatment for SCID in patients with ADA deficiency

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Severe combined immunodeficiency (SCID), or "Boy in the Bubble" Syndrome, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are affected, due to a defect in one of several possible genes. Wisconsin and Massachusetts (as of February 1, 2009) screen newborns for SCID.

Severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA) is a fatal disorder of purine metabolism and immunodeficiency. ADA deficiency accounts for about 15% of all cases of severe combined immunodeficiency (SCID).


ADA irreversibly deaminates adenosine (left), converting it to the related nucleoside inosine (right) by the removal of an amino group (observe missing nitrogen in upper left). Image source: Wikipedia, public domain.

In ADA deficiency, there is an accumulation of deoxyadenosine, which causes an increase in S-adenosylhomocysteine; both substances are toxic to immature lymphocytes, which thus fail to mature. As a result, the immune system is severely compromised or completely lacking.

A multi-center study investigated the long-term outcome of gene therapy for SCID due to ADA deficiency.

How did they do it?

1. Enzyme-replacement therapy was given before the gene therapy.

2. CD34+ bone marrow cells were transduced with a retroviral vector containing the ADA gene.

3. Nonmyeloablative conditioning with busulfan.

4. The autologous CD34+ bone marrow cells transduced with a retroviral vector were infused.

All patients were alive after a follow-up of 4 years. Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA.

The authors concluded that gene therapy, combined with reduced-intensity conditioning, was a safe and effective treatment for SCID in patients with ADA deficiency.


Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).

References:
Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency. Alessandro Aiuti et al. NEJM, Volume 360:447-458 January 29, 2009 Number 5.

Neonatal screening for SCID caused by an adenosine deaminase defect: A reliable and inexpensive method http://goo.gl/mMSzZ
Severe combined immunodeficiency, from Wikipedia, the free encyclopedia.
Adenosine deaminase deficiency, from Wikipedia, the free encyclopedia.

Sensory attributes of olopatadine superior to azelastine nasal spray

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Patients differentiate intranasal treatments based on sensory attributes.

A study of 110 patients evaluated the sensory attributes of olopatadine nasal spray 0.6% (OLO) and azelastine nasal spray 0.1% (AZE).

OLO was superior to AZE in aftertaste, patient preference, and likelihood of extended use - on average, 60% versus 30% in all 3 categories.

54% and 32% of patients favored the taste and smell of OLO compared with 27.5 and 11.9% who favored AZE.


Olopatadine. Image source: Wikipedia, public domain.













Azelastine. Image source: Wikipedia, public domain.

The authors concluded that the sensory attributes of OLO are superior to AZE for immediate taste, aftertaste, patient preference, and likelihood of use. This outcome could lead to greater patient compliance and improved treatment effect.

References:
Comparative study of sensory attributes of two antihistamine nasal sprays: Olopatadine 0.6% and azelastine 0.1%. Meltzer, Eli et al. Allergy and Asthma Proceedings, Volume 29, Number 6, November/December 2008, pp. 659-668(10).

Olopatadine 0.6% nasal spray better than placebo for allergic rhinitis in children http://goo.gl/G4AYy - Is it better than nasal steroids?