SCIENCE

February 2020

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Electronic cigarette (e-cigarette) and asthma

P.W Clapp et al   JACI 2020 145 97 9

The e-cigarette has definitely acquired the right place in the arsenal of smoking cessation. Its development is accompanied by a notable drop in smoking in spite, in France, price increases. To tell the truth “vaping” persists more than one year after smoking cessation. This is to say it is necessary to pay attention to inhalation risks, as mentioned by the French National Academy, already in 2015 and more recently ( G. Dubois: Bulletin de l’ANM 2019 in press Commission V).
In USA, vaping is responsible in 2019 of 2409 hospitalizations particularly in young asthmatics, whereas usually this sensitive population is little inclined to smoking. Among the multiple substances, probably involved and detected in bronco-alveolar lavages the diacetyl, vitamin E oil and foam cells (however nonspecific, V.Guerini Lancet Feb 2020), were identified. Nevertheless, e-cigarette attracts adolescents (5 million in USA). It must be monitored and regulated, with a ban in promotion and to minors, given the frequency of chronic pulmonary diseases, such asthma with risks of exacerbations, status asthmaticus, and life threatening.



 


Epitopes of major peanut allergen Ara h 2 and promising hypoallergen for immunotherapy

Tscheppe et al JACI 2020 145 229-238

In 48 patients with peanut allergy, the sera tested with IgE-binding and basophil activation assays showed that both types of epitopes contributed to allergic reactions to Ara h 2 in a patient-specific manner.
A set of Ara h 2 derivatives with removed linear and/or conformational epitopes was produced after reduction and alkylation leading to an Ara h2 mutant.
The hypo-allergens so produced showed abolished IgE binding and highly reduced basophil activation but retained their ability to activate allergen-specific T cells.
This hypo-allergen did not induce anaphylactic reactions in a mouse model of peanut allergy.
The observation that both types of IgE epitopes had to be removed to produce an efficacious hypo-allergen should inform immunotherapy trials. Future animal studies will assess further safety and effectiveness to help direct these trials in allergic patients.

 

 


Nemolizumab (N): Hope confirmed in moderate or severe atopic dermatitis with pruritus

J.I.Silverberg et al JACI 2020145 1 173-182

 In a preliminary study published in 2018 by the Japanese authors N had shown efficacy in the treatment of Atopic Dermatitis (AD) More recently an Euro-American group took over this study which now concerns 226 patients compared with placebo (55) by this monoclonal antibody which blocks alpha subunit of IL 31 receptor, a key pathway of skin lesions and pruritus.
In a randomized double blind trial phase 2 B lasting 24 weeks with subcutaneous injection every 4 weeks, 3 dosages were compared: 10mg, 30mg and 90mg. All doses reduced AD severity but the best effectiveness was observed with the 30mg dose, as judged with 4 scores among them Eczema Area and severity index and Physician’s global assessment.
One third 33% achieved clear skin by week 16 versus 12% in placebo group. Itch was rapidly reduced at the 1st week with maximum at week 16, (69% versus 35% placebo) with an acceptable safety profile (few episodes of pharyngitis and respiratory involvement). N deserves a major place among all biotherapies of AD.

 


Sexual hormones and asthma

Y-Y Han et al AJRCCM 2020 201 2 15 January 

The role of hormones may explain sex differences in asthma. The team of Pittsburg sought to examine sex hormone levels of free testosterone and estradiol and asthma in adults by cross-sectional study in 7,615 adults (3,953 men and 3,662 women) aged 18-79 years who participated in the 2013-2014 and 2015-2016 U.S. NHN Survey. Logistic regression was conducted separately in women and men.
Results: Free testosterone levels in the fourth quartile were associated with lower odds of current asthma in women. Given an interaction between obesity and sex hormones on current asthma, these results were stratified by obesity. In this analysis, elevated free testosterone and estradiol levels were associated with reduced odds of current asthma in obese women, and an elevated serum estradiol was associated with lower odds of current asthma in nonobese men.
Conclusions: These findings confirm that sex hormones play a role in known sex differences in adult asthma, suggest that obesity modifies their effects but must be interpreted with caution.



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Paraphenylene-diamine, hair dye, hair dresser and skin damage without a contact allergy

Meisser, Sanne S. et al. JACI Volume 145, Issue 2, 619 - 631.e2

Phenylenediamine (PPD) is a strong contact allergen used in hair dye that is known to cause allergic contact dermatitis (ACD). Both private and occupational exposure to PPD is frequent, but the effect of PPD exposure in nonallergic occupationally exposed subjects is unknown.
Results :
RNA sequencing demonstrated downregulation of tight junction and stratum corneum proteins in the skin of patients with severe ACD after PPD exposure. Claudin-1 (CLDN-1), CLDN8, CLDN11, CXADR-like membrane protein (CLMP), occludin (OCLN), membrane-associated guanylate kinase inverted 1 (MAGI1), and MAGI2 mRNA expression was downregulated in patients with severe ACD. CLDN1 and CLMP expression were downregulated in nonresponding hairdressers and patients with mild ACD. Filaggrin 1 (FLG1), FLG2, and loricrin (LOR) expression were downregulated in patients with ACD. Conclusion: PPD-exposed skin is associated with extensive changes, including downregulation of tight junction and stratum corneum proteins, even in the absence of clinical symptoms.

 

Your comments and questions are welcome at the following addresses:
Claude Molina - claude.nelly.molina@orange.fr                                                     
Jacques Gayraud - gayraud65@wanadoo.fr

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Last updated 17 February 2020
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