Books

BIBLIOGRAPHIC UPDATE IN ALLERGY

March 2018


1. Can Skin emollients decrease Atopic Dermatitis expression and modulate Atopic March?
2. Factors increasing the risk for a severe reaction in anaphylaxis.
3. Maternal Asthma severity during pregnancy and risk of offspring Asthma.
4. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.
5. Quadrupling Inhaled Glucocorticoid Dose to avoid Asthma Exacerbations

I. Can Skin emollients decrease Atopic Dermatitis expression and modulate Atopic March ?   
A.J.Lowe et al : Annals of All.Asthma.Immunol 2018 Feb 120 2 145-151

In this review, the authors recall the hypothesis that skin-barrier impairment and early-life atopic dermatitis (AD) could play a causal role in the development of sensitization and subsequent food allergies and allergic airways diseases (allergic asthma and rhinitis). They further discuss the potential to target the skin barrier as a means to lower the incidence of allergic disease.                              
There is a strong link between AD and sensitization, food allergy, asthma, and allergic rhinitis, particularly AD that is severe and commences in the first 6 months of life. There also is emerging evidence that regular use of prophylactic emollients can significantly decrease the expression of AD, at least while treatment continues. Although there is only indirect evidence that early-life emollient use might prevent AD and food allergy, early studies are encouraging. The results of high-quality prevention trials that are in progress are eagerly anticipated. If found to be effective, then neonatal emollient use could be a simple public health measure to lower the incidence of AD, food allergies, and allergic airways disease in future generations.

II. Factors increasing the risk for a severe reaction in anaphylaxis:
M.Worm et al  Allergy 2018 March Accepted article

To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis, data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms. The authors identified higher age and concomitant mastocytosis as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise, and psychological burden were more often associated with severe reactions. Additionally, intake of beta-blockers and ACE-I, in temporal proximity to allergen exposition were identified as important factors in logistic regression analysis These data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.
A similar investigation in a large population of adolescents (10-14 years) in Melbourne, (V.LMcWilliam et al JACI 2018 141 3 982-990) reveal an alarming high rate of adverse food reactions (547students, among them 93 anaphylaxis episodes). Peanut and tree nuts were the most common triggers, and those with nut allergy were the most at risk of anaphylaxis. Adolescents with asthma and more than 2 food allergies were at the greatest risk.

III. Maternal Asthma severity during pregnancy and risk of offspring Asthma.  
X.Liu et al JACI 2018 141 886-892

Severe and uncontrolled asthma during pregnancy has been linked to several unfavorable perinatal outcomes. The authors sought to investigate the extent to which offspring asthma is influenced by maternal asthma severity and control during pregnancy and performed a prospective population-based cohort study from Danish national registers, of which 15.014 children were born to asthmatic mothers. Among them, 7.188 children were born to mothers with active asthma during pregnancy. 4 groups were set up, based on dispensed antiasthma prescriptions and on use of medical services: mild controlled, mild uncontrolled, moderate-to-severe controlled, and moderate-to-severe uncontrolled asthma. The outcomes were offspring early-onset transient, early-onset persistent, and late-onset asthma. Prevalence ratios (PRs) of each phenotype of asthma, was estimated, using a log-binomial model with 95% CIs.              
Results: Higher prevalence of early-onset persistent asthma was observed among children of asthmatic mothers with mild uncontrolled (PR, 1.19), moderate-to-severe controlled (PR, 1.33), and moderate-to-severe uncontrolled asthma (PR, 1.37) compared with those of mothers with mild controlled asthma. Children of mothers uncontrolled asthma had a borderline increased prevalence of early-onset transient asthma.    
Overall maternal uncontrolled asthma increases the risk of early-onset persistent and transient asthma in offspring.  
 
IV.  Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations
D. J. Jackson,, N Engl J Med 2018; 378:891-901
Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.                        
254 children were studied, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. They were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control (“yellow zone”). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.
Results This rate did not differ significantly between groups. The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The difference in linear growth between high-dose and low dose group was -0.23cm per year (P=0.06).
Conclusions : In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control, did not reduce the rate of severe asthma exacerbations and may diminish linear growth or improve other asthma outcomes and may be associated with diminished linear growth.

V. Quadrupling Inhaled Glucocorticoid Dose to avoid Asthma Exacerbations
Tricia McKeever et al,. N Engl J Med 2018,March 8, 2018; 378:902-910

The authors tested the concept that a plan for patients to manage their asthma (which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate) would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.                   
They conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. They compared a self-management plan (that included quadrupling group) with the same plan (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.               
A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.          
In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased.
As suggested by an Australian researcher in his editorial (J.Bardin NEJMP 8March 2018 378 950-950-1) in real-life, clinicians are reluctant to an escalation by a factor of 4 or 5 , of ICS in their patients, due to the risks of severe side-effects.

Your comments and questions are welcome at the following addresses:

Claude Molina                                          
claude.nelly.molina@orange.fr 

Jacques Gayraud
Jacquesgm.gayraud@gmail.com