1. Evaluation of inhaler techniques in asthma
2. Risk of food allergy: perinatal conditions of its development
3. Airway pathologic phenotypes in adult asthma
4. Clinical phenotypes and endotypes in children asthma
5. Oral desensitization to peanut
Evaluation of Inhaler techniques in asthma
To evaluate the method of inhalation techniques and study the correlation with patient characteristics, the Tunisian authors, in a prospective trial, sought to appreciate individual educational method, measure its impact for improving the technique and optimize treatment efficacy 54 patients adults, 41 asthmatic , 13 COPD were followed 4 months.
The therapeutic educational program included 3 levels of action: identify the errors, demonstrate correct technique by direct or indirect methods (video ,internet ) and evaluate the therapeutic education. The most devices used were metered –dose inhalers (66,6%). All patients were treated with inhaled corticoids. The average error was 4,43/patient, 5,1/patient for dry powder inhaler (diskus or turbuhaler). The misuse of devices was significantly correlated with age, female sex and lower level of education and socio-economic status, disturbances of lung function, seriousness of disease. The therapeutic education allowed to reduce the frequency of errors from 5, 11 to 0,8 after one month 0,45 after 3months and for the diskus: 5,9 to 0,57. At the same time the control of asthma was improved P≤ 0.06 with decrease of exacerbations. This is a very interesting report which may help clinicians in adequate prescription of inhalers and patients who, sometimes need advices of nurse or physiotherapist.
N.Mitselou et al JACI 20180142050 1510-1514 e2
Following-up a cohort of more than one million children (1,086,378) during 13 years, the Swedish authors sought to examine the association between perinatal characteristics and future risk of F.A. Major findings are:
1) Cesarean delivery was significantly associated with increased risk of food allergy. It is likewise proposed as risk factor for asthma
2) Large for gestational age status and low 5-minute Apgar score were associated with a greater risk of food allergy
3) Infants born very preterm (≤32 weeks of gestation) were at a lower risk of food allergy.
4) Unlike for asthma or atopic diseases, there was no association between moderately pre-term birth, low birth weight or small for gestational age and FA
Airway Pathologic Phenotypes in Adult Asthma
S.Siddiqui et al JACI November 2018 142 5 1457-1468
Using topological data analysis (TDA) applied to bronchial biopsy specimens from 202 adult patients :142 asthmatic 60 healthy subjects, the British and American authors undertook a large pathologic, immunologic and genetic study to investigate whether distinct pathologic phenotypes of asthma contribute to its clinical heterogeneity and severity. The results are as follows:
4 pathologic asthma phenotypes were identified: each enriched for micro-clusters and/or physiologic parameters.
- group 1 :mild-moderate asthma/healthyCONTINUUM, the most frequent 40%, representing a topological continuum connecting healthy subjects to patients with mild asthma, low hyperresponsiveness high percentage of submucosal glands, Th17 high gene expression, tissue eosinophilia.
- group 2 reticular basement membrane thicknessHIGH, 31% with 2clusters epithelial area” high”, Th17 high tissue neutrophils and epithelial area “low” with sputum eosinophils (clinically: late onset disease and hyperresponsiveness which need inhaled and/or oral corticosteroids).
- group 3 : airway smooth muscle mass HIGH, 19% with mast cells (corresponding to exacerbations and low lung function justifying thermoplasty to reduce muscle mass).
- group 4 remodelingLOW), with high sputum neutrophils, high epithelial area and frequent exacerbations .
Mutually exclusive TH2 and TH17 gene expression signature was demonstrated across the pathologic phenotypes and the spectrum of asthma severity. An external replication population (59 patients with severe asthma) was evaluated with the same technique and showed similar pathological data.
In conclusion, airway pathology in asthmatic patients demonstrates distinct phenotypes with differing features of cellular inflammation, remodeling, TH2/TH17 inflammation, and airway function.
Clinical Phenotypes and Endotypes in Children Asthma
J.Just Bulletin Acad Natio.Med June 2018 in press
The heterogeneity of asthma and allergic diseases in childhood is characterized by multiple phenotypes related to different pathophysiologic pathways or endotypes. (Age, Male or Female Sex, Early multiple sensitizations to crude but also molecular allergens, conveys a higher risk of severe asthma phenotype especially in terms of asthma exacerbations. Early-onset asthma with multiple allergic symptoms such fruit-pollen syndrome, multiple sensitization with moulds (Alternaria) had a risk of poor lung function pattern and asthma persistence during the life. Eosinophilic endotypes linked to atopy are correlated with blood and alveoli cells and usually well controlled by inhaled corticoids. Conversely, neutrophilic asthma was infrequent in children and not stable on time.
Oral Desensitization to Peanut
The PALISADE Group of Clinical Investigators (B.P Vickery et al)
NEJM 18 Nov 2018 DOI 10.1056
The patients allergic to Peanut are at risk for unpredictable and occasionally life-threatening reactions. The American group undertook a new oral desensitization with a peanut-derived biologic drug: AR 101, in screening participants 4 to 55 years of age in a double-blind, placebo-controlled food challenge, Those who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a new challenge at trial exit. The primary efficacy end point was the proportion of participants who could ingest a challenge dose of 600 mg: ( 4 peanuts) or more, without dose-limiting symptoms.
Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, were able to ingest a dose of 600 mg or more during the exit food challenge, . Adverse events affected more than 95% of the participants. They are graded as severe only in 4.3% of the active group and 0.8%, in placebo. Efficacy was not shown in the participants 18 years of age or older. This phase 3 trial with an immunomodulatory drug AR101 result in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure, than placebo.
The drawbacks underlined in the editorial of NEJM, by M.R Perkin, who conducted the Cambridge group is multiple:1) the equivalent defatted peanut flour AR101 in protein content used in the trial is difficult to translate to actual peanuts and to the content used by the Cambridge group 2) There is no effect in the participants older than 17 years of age 3) the tolerance induced by AT 101 is temporary and lost if regular consumption ceases 4) the treatment is difficult to start at home, given the risks of side-effects 5) 1/3 of participants do not tolerate the cumulative dose of 4 peanuts . That is to say that the products like AR 101 and similar CA 002 have a modest role in immunotherapy but their potential market is believed to be billions of dollars.
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