Claude MOLINA & Franz MARRACHE

1.    The allergen specificity of the late asthmatic reaction
2.    Doing away with the risks of long-acting β-agonists
3.    Chronic urticaria (CU) and 2nd generation antihistamines
4.    Sensitization to horse allergen : what it means
5.    Infant weight gain and asthma

The allergen specificity of the late asthmatic reaction

Allergen inhalation challenge (AIC) in asthma typically triggers a dual bronchospastic reaction : an early one (EAR), which is IgE-dependent, with mastocyte mediation, and, in some cases, a late one (LAR) whose mechanism is ill defined.

The Southampton group (M.Hatzivlassiou et al : Allergy 2010 65 355-358) submitted 6 asthmatic volunteers, with dual sensitization to grass pollen (GP) and house dust mite (HDM), to a couple of single allergen AICs on two occasions separated by 14 days. Lung function, bronchial reactivity and induced sputum differential cell count were checked 24hr pre- and post-allergen challenge.

EAR was characterized for each inhaled allergen by a statistically similar drop in FEV1. On the contrary, LAR after house dust mite challenge revealed a significantly larger drop in FEV1 than after the grass pollen test, as well as a significant airway eosinophil recruitment non observed with GP.
The authors conclude therefore that LAR is  allergen specific, can be dissociated from  EAR and that other factors, independent of IgE,  contribute to its development (possible role of T cell recruitment, or stimulation of bronchial epithelial cells by means of Toll-like  receptors, or chemical composition of the allergen : chitine for HDM).

Although the number of cases was small and only two allergens, albeit the most frequent, were involved in the test, this clinical and patho-physiological distinction between EAR and LAR is worth taking into account and has definite therapeutic implications.

Key words: provocative challenge; early allergic reaction; late allergic reaction; bronchial hyper reactivity; eosinophils; house dust mite; grass pollen


Doing away with the risks of long-acting β-agonists

The FDA has, at last, just recognised the harmlessness of Long acting β-agonists (LABA) when reasonably used and associated with inhaled corticosteroids (ICS) in the treatment of asthma (NEJM 9 March 2010). Such precautions with β2mimetics, to which French clinicians have drawn attention since the beginning of the last century, make it possible to serenely study the possibility of stepping-up the classical therapy for children or teenagers with uncontrolled asthma receiving ICS (R.F Lemanske et al NEJM .2 March 2010 ahead of print).

182 children (6 to 17 years of age), whose moderate asthma was not enough improved by inhaling 100µg of ICS (Fluticasone : Flixotide ®) twice a day for 2 to 8 weeks, with an  80% adhesion rate, were randomised in three groups : double-dose ICS (1st group), regular dose ICS plus a leukotriene-receptor antagonist LTRA (Montelukast : Singulair ®) for the 2nd group or a long-acting beta-agonist LABA (Salmeterol Serevent ®) for the 3rd group.

The best response was significantly obtained in the 3rd group (45%) and was only 30% in the other two. But individual responses were variable and the authors conclude on the need to regularly monitor each child and appropriately adjust their asthma therapy, thus rediscovering an old medical adage.
In their comment on this paper “The choice of a step-up therapy in the treatment of asthma”, E.Von Mutius and J-M.Drezen rightly insist on these criteria, in this order : harmlessness, price and convenience.

At last ,whereas  pharmacogenetic studies suggested that the  polymorphism of the β2-adrenergic receptor gene (for the Arginine allel at codon 16,  particularly  for Arg/Gly genotype)  may account for a negative response to LABA or adverse outcomes in some asthmatics, a  recent work of E.R.Bleecker et al (AJRCCM 2010  april 181 676-687) refute these previous retrospective studies and  confirm the efficacy  of LABA-CI association

Key-words: long-acting beta-agonists; inhaled corticosteroids; asthma, step-up therapy; leukotriene-receptor antagonist; pharmacogenetics β2-adrenergic receptor gene


Chronic urticaria (CU) and 2nd generation antihistamines

In a multicenter Bulgarian-English-German study (M.Staevska et al : JACI 2010 March 676-682), 80 patients (age range : 16-67 years), 27 men and 53 women, with CU were randomised for 40/40 treatment with levocetirizine L (Xyzall ®) or desloratadine D Aerius ®, following European Academy of Allergology and Clinical Immunology  (EAACI) guidelines, i.e. : 5mg daily orally at first, with a weekly increase of 5mg in the case of non-response up to the maximum dose of 20mg.

As early as the 1st week, 13 patients became symptom-free : 9 with L and 4 with D. Of the 28 patients nonresponsive to 20mg D, 7 became totally symptom-free with 20mg L, Thus, increasing doses  improves the quality of life. However none of the 18 non-responders to 20mg L could get the same result with D ! There were no side effects leading to discontinuation of treatment and neither drug increased somnolence.

In fact, L even makes up for a possible somnolence by improving the symptoms thus reducing CU-induced insomnia.  75% of the patients observed that their comfort was greater than that obtained with 1st generation antihistamines (cholinergic). It should be noted that the risks linked to the latter are pinpointed again in a recommendation from the EAACI (M/K Church Allergy  2010 65 459-466) which advises against over-the-counter use.

Finally, levocetirizine L comes out as the best treatment for symptoms of chronic urticaria, but does not rule out etiologic research and/or searching for illness-provocative factors.

Key-words: chronic urticaria; levoceterizine, desloratadine; 1st and 2nd generation antihistamines.


Sensitization to horse allergen : what it means

Two teams wondered if the absence of direct or indirect contact with this animal was enough to avoid the development of a sensitization and/or an allergy.

E.November et al conducted a survey of 2 to 16-year old children (J Invest Allergol Clin Immunol 2009 ; Vol 19(3) : 237-252). On a panel of 17 skin prick tests (SPT) to respiratory allergens, the prevalence of horse dander sensitization was 2.7% (624 positive PTs within a population of 23460 patients having consulted an allergy unit over the past 8 years) : among the 184 sensitized children, 64 presented allergic symptoms (in order of frequency : rhinitis – asthma – urticaria – rhinitis + urticaria) while they had not had any direct contact with horses.

At the same time, with adults, Liccardi G et al announce in their paper (J Investig Allergol Clin Imunol 2010, Vol 20(1)) the results of a study conducted on 1822 subjects, in 2005 and 2006. They find 1201 positive PTs with a prevalence of 3.43% for horse dander. Among the 35 horse-positive PTs, there were 6 direct and 10 indirect contacts. 19 cases had had no contact at all. There were more women than men, and most had some family allergy history as well as a concomitant allergy to cat and dog (respectively 23/35 and 25/35).

Returning to the 19 horse allergy cases which appeared de novo, they point to a cross-reaction between horse allergen and the major allergen of several mammalian species, including cats, dogs, cows, guinea pigs, rats, all those allergens belonging to the large family of lipocalins, composed of small molecules prone to bind hydrophobic molecules such as steroids. They also evoke the possible role of a serum albumin, a 68-kDa panallergen common to several epithelia.

As a conclusion, the authors insist therefore on the existence of horse allergy in the absence of previous contact with the animal, and underline the underestimated role of indirect contact (through dander-bearing clothes) in the development of sensitisation unknown to some patients. Hence the need to introduce horse allergen into the routine panel and to warn these subjects against the dangers of an overexposure to that allergen, equally responsible for severe systemic reactions.

Key-words: horse, respiratory allergy, lipocalins, animal allergens


Infant weight gain and asthma

For several decades, obesity and asthma have been constantly increasing, hence the interest borne by Ian M Paul et al to a possible linkage between asthma and weight gain during early childhood (Pediatr Allergy Immunol 2010: 21: 82-89).

From a cohort of 2 to 3-year old children, highly at-risk for asthma, with intermittent wheezing, in remission, the authors sought to gather the criteria of a persisting asthma indicator. Birth weight, growth curve, pulmonary function, and asthma symptoms were collected for hypothesis testing. In a first stage, a 2-year treatment with inhaled corticosteroids or placebo was prescribed at random, followed by a 1-year observation period. Between birth and study enrollment, patterns of infant weight gain were categorised in 3 types : accelerated, average, or decelerated. Regression analyses were used to test the effects of those patterns on outcomes during the observation year : symptom severity, drug treatment, and atopic indicators.

At the end of the study, for pre-school children, neither daily asthma symptoms nor lung function abnormalities could be associated with a particular infant weight gain pattern. However, a significant association was observed between the decelerated pattern and fewer exacerbations, contrary to the accelerated pattern which scored the most adverse effects.

Despite these partial results, asthma-obesity co-morbidity seems a prominent fact. Much research indeed shows that asthma, atopia and obesity markers do coexist, among which body mass index (BMI), not counting the importance among children of the association between obesity, gastro-oesophagus reflux, bronchial hypersensitivity and asthma.

The relationship between BMI and response to treatment is well established by Carlos A. Camango et al in a recent paper (Body Mass Index and Response to Asthma Therapy : Fluticasone Propionate/Salmeterol versus Montelukast. J of Asthma, February 2010 Vol 42  n°1 pp76-82 ) : they assess and compare asthmatic patients’ responses to 2 kinds of treatment Fluticasone-Salmeterol versus Montelucast in relation with BMI levels (normal, obese1, obese2, obese3). Whatever the treatment, they observe a less satisfactory treatment response among obese3 patients than with normal BMI ones, thus confirming the importance of prevention and treatment, given the public health problem represented by children’s overweight and obesity.

Key-words: asthma, weight gain, childhood


Source: CEFCAP
You may send comments on these brief news to: cme.inallergy.online@wanadoo.fr

Back to top