Claude MOLINA and Franz MARRACHE
• Severe asthma in children and bronchial remodelling
• Justification for Sub-Lingual Immunotherapy (SLIT)
• IgE, atopic eczema and food allergy
• The various facets of asthma in Olympic athletes
• Impact of stress upon asthmatic adolescents
Severe asthma in children and bronchial remodelling:
A French hospital-university team (Lille/Paris) compared structural changes in bronchi after the occurrence (or not) of a bronchial obstructive syndrome in children with severe Asthma (according to American Thoracic Society criteria). (Airway remodeling is correlated with obstruction in children with severe asthma : I.Tillie-Leblond et al Allergy 2008 63 May 533-541). For this study, 25 children aged between 5 and 14 years were recruited : 15 had bronchial obstruction (FEV1 lower than 80% of predicted and not responding to bronchodilators) and 10 did not have bronchial obstruction. A bronchial biopsy was taken and thoroughly examined using immuno-histochemistry . It was concluded that a large number of features were the same in the 2 groups : that applied to basal membrane thickening, epithelial integrity (analysed using EGF and EGF-R markers), collagen I and III deposition in the mucosa (using TGF-â as a marker), the number of eosinophils or neutrophils in the bronchi or gland thickness.In contrast, there was a statistically significant correlation between bronchial obstruction, the thickness of the smooth muscle wall (with increased expression of the MLCK: Muscular Light Chain Kinase enzyme, which reflects contractility) and the extension of the vascular network within the bronchi (as determined by expression of CD31) .Thus, the hypothesis of bronchial remodelling as a consequence of chronic inflammation remains uncertain, given that the age of Asthma in these children did not affect the results. It should also be stressed that structural changes predominantly involving smooth muscle and vascular factors develop early in the natural course of this form of asthma and explain the low efficacy of corticosteroids. It is therefore adequate to envisage a revision of classical therapeutic targets in these severe forms of asthma in children (and subsequently in adults).
Justification of Sub-Lingual Immunotherapy (SLIT):
Three recent articles dedicated to SLIT justify its definitive adoption by the European allergic community, followed by the anglo-saxon one. In a general New England Journal of Medicine review on this issue, A.J. Frew (Sublingual Immunotherapy: NEJM 2008 22 May 358 2259-2264) discusses the indications, the mode of action and the effects of such therapy with its dosage, duration of treatment, its minor secondary effects, its yearly cost, but also its uncertainties concerning, among others, allergen standardisation in line with the absence of an international consensus. Nevertheless, although FDA has not yet approved this form of therapy, the British Society for Allergy and Clinical Immunology has acknowledged, since January 2008, its efficacy and safety for the treatment of pollen-induced allergic rhinitis and asthma. This method, which was initiated in Italy, is currently widely used in Europe. Authors from Madrid have had the idea of comparing the immunological effects of 2 immunotherapy methods: SLIT (11 patients) and SCIT (sub-cutaneous: 12 patients) in 23 house dust allergic children, after a 2 year-long follow up period : Antunez C. et al…2 years follow-up of immunological response in mite-allergic children ; comparaison with sub-cutaneous administration Pediatr.Allergy Immunol 2008 19 3 210-218. Clinical improvement was similar and a decrease in specific IgE /IgG4 ratio was observed from the 1st month onwards with SCIT, after 2 years with SLIT. The authors also observed, in the long run, an increase in CD4/CD8 ratio as well as a decrease in the production of TNF-á and IL-2.
In contrast, an increase in the CD4+CD25+ subpopulation and a decrease in CD8+CD25 subpopulation were only observed with SCIT, with a slight change in the INF-ã/IL-4 ratio, reflecting a re-orientation from a Th2 response to a Th1 one.
There seems to be a slight difference in the immunological response in the peripheral blood during SCIT. In contrast, is there a mucosal protection with SLIT? That is what the authors suggest. And the recent observation by K.C. Bergmann et H. Wolf: Effect of Pollen-specific SLIT on Oral Allergy Syndrome: an observational study WAO Journal May 2008 1(5) 79-84 seems to confirm this hypothesis. For this study, 102 patients with pollen-induced allergic rhinitis, 9 out 10 had a more or less intense oral syndrome to food allergens associated with pollen allergens (such as apple-birch, Artemisia - celery, tomato – grass pollen). They were treated with SLIT for 1 year. The oral allergy syndrome improved in 3/4 of the cases concurrently with an improvement of rhinitis. According to J. Ring (journal editor) this is encouraging in terms of foreseeing a possible future treatment of food allergies by SLIT.
IgE, atopic eczema and food allergy
An international group of paediatric allergists (Early Prevention of Asthma and Allergy in Child study group) investigated IgE responses in young children with atopic eczema (IgE antibody responses in young children with atopic dermatitis U.Wahn et al Pediatr.Allergy Immunol 2008 19 332-336). In this study, 2184 infants, between 13 and 24 months of age, with atopic eczema (Scorad 5-59, representing a moderate eczema score) were tested with the 8 most common allergens. Results showed that 18.7% were sensitised to a single allergen, and 36.8% were polysensitised. The frequency of positive IgE responses to aeroallergens and foodallergens (>0.35 kU/l) correlated with the severity of the cutaneous manifestations. Among these young children, a minority had elevated food allergen-specific IgE levels, which would suggest that there is an increased risk of acute clinical reactions to these allergens (7% to egg, 3% to cow’s milk, 4% to peanut). These observations confirm classical data namely the prevalence of IgE responses to food allergens which is highest during the first year of life whereas respiratory allergens develops between 1 and 2 years of age or later. The approach of this association between atopic eczema /food allergy is discussed in the review about this issue by F. Rancé, from Toulouse (France) (Food Allergy in children suffering from atopic eczema Rancé F. Pediatr.Allergy Immunol.2008 19 279-284) ; 2 cases are discussed as an example: one of the cases is a young child with early onset and severe eczema in whom a food diet excluding suspected allergens improved cutaneous lesions; the second case is that of an older child in whom such diet might have deleterious effects on growth without any improvement of the cutaneous state.
This article is followed by a MCQ type questionnaire such as those build-up for Continuous Medical Education (CME).
The various facets of asthma in Olympic athletes
The experience of the athletes of the Finnish Olympic team was analysed in the publication by Haahtela T. et al (Mecanisms of asthma in Olympic athletes – Practical implication. Allergy. 2008 Jun;63(6):685-9).
Extreme exercise conditions among elite athletes may be the source of respiratory manifestations. So, in short duration speed and power efforts or endurance tests in swimmers and long distance skiers, hyperventilation (≥ 200 l/m) has a cooling and drying effect on the airways, and also stimulates vagal nerve endings and bronchoconstriction. Among swimmers, aspiration of a large number of droplets of water full of chemical products (chlorinated products, in particular) induces, by irritation, a vagally-mediated bronchoconstriction as well as bronchial hyperreactivity. Hyperventilation is also associated with the inhalation of important amounts of allergens, domestic aeroallergens and/or pollens depending on the environment (indoor or outdoor exercise), and constitutes, a risk factor for atopy and asthma as reflected by the increase in prevalence of IgE-dependent manifestations among young athletes. The mechanisms vary according to the sport and individual athlete, depending on the aetiology but also on clinical phenotypes. At least two phenotypes are evident, thereby reflecting the existence of distinct mechanisms : the phenotype of early onset infant asthma, which is atopic and combines hyperreactivity to metacholine and an eosinophilic inflammation of the airways with an increase in exhaled NO ; and the other phenotype which includes late onset manifestations (developing during the sports career), bronchial hyperreactivity with the isocapneic hyperventilation test, and not necessarily with metacholine challenge, and which is not associated with markers of atopy.
A mixed type of bronchial inflammation, both eosinophilic and neutrophilic seems to specifically affect swimmers, ice hockey players and long distance skiers. In this case, inflammation may be both allergic and irritant.
It should be stressed that asthma in athletes is under- or over-diagnosed and is therefore an important source of therapeutic problems.
In general, in order to assess the temporal link between asthma and competition sports practise, one must take into account individual predisposition, environmental factors, and the intensity of training.
See at www.cefcap.com the file on Allergy and Sport and the file on Asthma in 2005 Updates.
Impact of stress on asthmatic adolescents
Recent studies suggesting that psychosocial factors may have an impact on asthma, account for the work of Turyk ME et al (Stressful life events and asthma in adolescent. Pediatr. Allergy Immunol. 2008 19:255-263).
The 2026 participants, high school students from Catholic Private Schools of Chicago as well as from State public schools, were aged between 12 and 14 years. Diagnosis of asthma and information on types and number of stressful events, during the previous 12 months, were the object of an anonymous questionnaire.
This questionnaire included a 15-item stressful life events inventory that encompassed traditional items featuring in established life event instruments, family life elements, sources of ill being, relationship and school difficulties and items relating to inner city youths such as gang violence, stabbings and shootings.
Anonymity of the questionnaire, facilitated the collection of information regarding drug use. Of all the participants, there were 315 asthmatic adolescents 1711 non-asthmatic, served as a control group. Overall, asthma was significantly associated with the number of stressful events faced by urban adolescents. Similar results were observed for respiratory symptoms and the other markers of morbidity : school absenteeism, hospitalisations, and physician visits due to asthma.
These associations were independent of exposure to tobacco smoking in the family, use of inhaled substances, sociodemographic factors, or home dampness.
On their own, these results do not allow to conclude to a formal cause-effect link between asthma and stress. However, by analysing and listing the effects of stressful events, the clinician may be helped in terms of preventive and therapeutic approach to the disease among these adolescents.
These texts has been translated by L.TABORDA Covilha (Portugal).
Source: CEFCAP
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