Bibliographic updates

The Monthly choice - March 2016

Claude MOLINA & Jacques GAYRAUD

1. Aspirin – exacerbated resiratory disease: The pathogenic puzzle.
2. Effective treatment of HDM-induced Rhinitis with 2 doses of SLIT tablets. Results from a randomized DBPC phase III trial.
3. SLIT in HIV-positive patients.
4. Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL4: a randomized controlled trial.
5. Allergy to hen’s egg in infancy: Incidence and natural history.

1. Aspirin-Exacerbated Respiratory Disease: The Pathogenic Puzzle
T.M.Laidlaw :NEJM 2016 Feb 4 484-488

The Samter’s triad: Asthma, Chronic Rhinosinusitis with nasal polyposis and pathognomonic respiratory reactions to aspirin, is characterized by eosinophilic inflammation and mastocytes activation in the respiratory mucosa. All nonsteroidal anti-inflammatory drugs that inhibit both cyclooxygenase COX 1 and COX 2 may provoke the same reactions. In contrast the patients may tolerate the COX2-selective drugs such Celocoxib and high doses of aspirin induce a refractory state which has therapeutic benefits.

The hallmark of the syndrome is dysfunction of 5-lipoxygenase LTC4 synthase pathway which converts arachidonic acid to the cysteinyl leukotrienes responsible for bronchoconstriction, eosinophilic inflammation and platelets activation. Both Zileuton and Montelukast which block these mediators can improve or attenuate the symptoms of AERD.

But an ubiquitous product of cyclooxygenases, mainly COX 2 dependent: Prostaglandin E2 (PGE2), inhibits 5-lipoxygenase function, prevents cells activation and changes in lung function induced by aspirin. Moreover mast-cell activation reflects release of another mediator PGD2, potent chemotactic factor which elicits bronchoconstriction through T prostanoid receptors on the smooth muscle bronchial cells. The role of type 2 immune system, involvement of many cytokines, mediators and mucosal cells create a puzzle not yet solved. However clinical trials study possible efficacy of an antiplatelet drug: Prasugrel and an antagonist of T prostanoid receptors: Ifetroban.

2. Effective treatment of HDM-induced Rhinitis with 2 doses of SLIT tablets. Results from a randomized DBPC phase III trial.
P.Demoly et al JACI Feb 2016137 2 444-451

This trial conducted in 12 European countries including 992 adults with moderate to severe HDM induced Allergic Rhinitis (AR) demonstrated absolute reduction of symptoms and medication scores compared with placebo. The significant effect was evident from 14 weeks of treatment on ward and confirmed with the two doses : 6 SQ HDM or 12 SQ HDM. The treatment was well tolerated and the QOL was improved.
SLIT is from now on, a worldwide new option for HDM or Pollen-induced allergic rhinitis.

3. SLIT in HIV-positive patients
I.E Iemoly et al Allergy March 2016 71 3 412-415

If HIV infection is a relative contra-indication of Immunotherapy, in the last decade highly active anti-retroviral therapy has improved the immune function and life-expectancy in HIV-infected patients. The Italian authors evaluated the safety and clinical effectiveness of SLIT tablet (Oralair ®) in a group of 13 grass pollen allergic patients submitted to antiretroviral and symptomatic therapy, compared with 9 patients receiving symptomatic therapy alone. Clinical efficacy data showed a significant improvement in SLIT group compared to controls, without significant alteration of TCD 4 counts and viral load in any group. These preliminary studies show that SLIT therapy in viro-immunological controlled HIV positive patients, was efficacious safe and well tolerate.

4. Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL4: a randomized controlled trial.
A.M.Chaker et al JACI Feb 2016 137 2 452-461

To evaluate the induction of sustained tolerance to allergen when anti-IL4 was combined with a suboptimal course of grass pollen subcutaneous immunotherapy, (SCIT) the British authors enrolled 37 patients with seasonal allergic rhinitis. In a randomized double blind trial 3 parallel group were designed:
- one received suboptimal SCIT in combination with antiIL4(VAK694),
- the 2nd SCIT + placebo antibody,
- the 3rd double placebo,

all 13 weeks before the pollen season. The 1st primary end point was the size of late phase response (LPR) of the skin-test at 12 months, as surrogate of clinical efficacy. Exploratory end-points include the immunomodulatory activity of treatment. Both active arms led to a substantial and sustained reduction of LPR without additional suppression with association of anti-IL4. Addition IL4 to SCIT, compared to SCIT alone led to a reduction in allergen-specific IL4 producing cells counts. Both active arms led to induction of dual IL4/IL10 producing cells during the pollen season.

5. Allergy to hen’s egg in infancy: Incidence and natural history.
P.Xepapadaki : Allergy march 2016 71 3 50-357.

A large multinational cohort study (12 049 newborns, followed up to 2 years of age) on food allergy with gold-standard allergic methods showed that the mean incidence of egg allergy, usually perceived as a common food was considerably lower than previously documented : 1,23% ( 95% CI 0,98-1,51) with center-specific incidence ranged from 2,18% (UK) to 0,07% (Greece). Moreover, half of the children gained tolerance within 1 year post diagnosis.
On another point of view, it was shown that a technological process using a combination of enzymatic hydrolysis and heat treatment led to a strong decrease of hen’s egg allergenicity. Hydrolysed egg products may be beneficial for suspected allergic patients to extent their diet.
(B.K Ballmer-Weber Allergy 2 Feb 2016 Accepted article).

Your comments and questions can be sent to:

Claude Molina
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Jacques Gayraud
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Last updated 27 December 2016