[Self-sufficiency, needs, prescription and safety of blood products]. / Autosuffisance, besoins, prescription et sécurité des produits sanguins labiles.

The current issues debate will bring together experts around the themes of self-sufficiency (in its national and European aspects) and of needs in cellular blood products. The point of view of the manufacturer and prescribers of blood products will be confronted.

Passive smoking is a major determinant of exhaled nitric oxide levels in allergic asthmatic children.

BACKGROUND: Fraction of exhaled nitric oxide (FeNO) is considered, by some authors, to be a treatment follow-up parameter in allergic asthmatics. However, factors such as active smoking can influence NO production and must be taken into account in the interpretation of FeNO values. In children, the evidence in favour of an impact of passive smoking (PS) on FeNO values is controversial. The aim of this study was to evaluate the impact of chronic PS on FeNO in allergic asthmatic children. METHODS: Seventy nontreated allergic asthmatic children over 5 years of age, exposed and unexposed to PS, underwent measurement of FeNO, spirometry, and allergic tests (skin prick tests, total and specific serum IgE, and blood eosinophilia). Children were considered to be exposed to PS when at least 1 cigarette per day was declared to be smoked at home. RESULTS: Geometric mean FeNO value in 22 children exposed to PS was 26.3 +/- 1.5 ppb vs 56.3 +/- 1.7 ppb in 48 children unexposed (P < 0.001). After adjustment for age, blood eosinophilia, allergic sensitizations, total IgE, dust mite sensitization and asthma severity, multivariate analysis showed that PS exposure was negatively associated with FeNO values (P = 0.0001) and was the primary determinant of FeNO variations. CONCLUSION: Passive smoking lowers FeNO, and might be a major determinant of FeNO levels in nontreated allergic asthmatic children.

Lack of eosinophilia can predict remission in wheezy infants?

BACKGROUND: Early wheezing in infants is a potential risk factor for persistence of asthma into adulthood. Moreover, a personal or familial history of atopy are risk factors associated with persistence of pre-existing wheezing during childhood. However, their relative importance remains unclear. OBJECTIVES: Firstly to determine the critical thresholds of common biological markers of atopy in wheezy infants associated with persistence of wheezing into childhood and secondly to rank these biological markers together with clinical parameters according to the strength of their association with wheezing persistence. METHODS: A cohort of infants less than 30 months old with recurrent wheezing was established in order to assess severity of respiratory symptoms and to look for the presence of atopy. At the age of 6 years, they were re-evaluated regarding remission of wheezing over the previous 12-months period. RESULTS: Data were available for 219 subjects. In 27% of them, wheezing persisted at 6 years of age. Critical biological thresholds associated with the risk of wheezing persistence were: (1) a blood eosinophilia count >or=470/mm(3) (defining eosinophilia), and (2) a total serum IgE level >or=45 IU/mL (defining elevated IgE) during infancy. A multiple component factorial analysis identified a dimension associating eosinophilia, elevated IgE and allergic sensitization on the one hand with persistent wheezing at 6 years of age on the other (lambda=0.15). According to a segmentation analysis, the main discriminative parameter of wheezing persistence was eosinophilia. Thus a lack of eosinophilia alone could account for 91% of infants in remission, and when combined with absence of allergic sensitization, remission was correctly discriminated in 96.9% of the study population. CONCLUSION: Our data strongly suggest that the lack of eosinophilia in wheezy infants without ongoing infection could predict future remission of wheezing in a large majority of cases.

[Air pollution and asthma in children]. / Pollution et asthme de l'enfant.

The prevalence of asthma and allergic diseases has increased world-wide during the last quarter of the 20th century, particularly among children and adolescents. No change common to all sites where asthma has increased throughout the world has been identified, suggesting that this 'epidemic' phenomenon is likely due to multiple factors. The following have been most discussed: exposure to indoor and outdoor allergens, modification of the patterns of respiratory infections, decreasing trends of physical activity, evolution in the make-up of environmental irritants, including tobacco smoke and urban air toxicants. In this review, we point out the role of exposure to air pollutants, in addition to and in combination with other asthma enhancers or precipitators. Whereas concentrations of the 'classical' air quality indicators (SO2, CO) have more or less steadily decreased, asthma prevalence augmented in developed countries during the same period. However, the nature of the air pollution mix has deeply evolved, and should also be considered. Ambient air concentrations of industrial and house heating combustion sources of pollutants in the city have substantially decreased, but by contrast the concentrations of various ultrafine particles have increased. Now, there is in vitro and in vivo evidence that exposure to urban air particles, and particularly to diesel exhausts, elicits chronic oxidative stress and repeated inflammatory responses, so that they may enhance allergic inflammation and airway hyper-responsiveness. Several epidemiological studies suggested an association between traffic density close to places of children's residence and prevalence of respiratory symptoms, and more specifically of asthma or allergic rhinitis symptoms in them. Chronic exposure during infancy to traffic-related pollutants may accelerate or even provoke, among genetically sensitive subjects, disruption of the normal regulatory and repair processes eventually contributing to the increase of asthma incidence.

Use of the low-dose corticotropin stimulation test for the monitoring of children with asthma treated with inhaled corticosteroids.

OBJECTIVE: Subnormal hypothalamic-pituitary-adrenal (HPA) function and rare cases of adrenal crisis have been reported in asthmatic children treated with inhaled corticosteroids. We investigated subnormal HPA activity and followed up affected patients until recovery of normal HPA functions. STUDY DESIGN: 100 children with persistent asthma underwent low-dose corticotropin testing, with the administration of 1 microg of 1-24 ACTH intravenously. Treatments were beclomethasone dipropionate as a metered-dose inhaler, n = 14, budesonide as a dry-powder inhaler, n = 16, fluticasone propionate as a metered-dose inhaler n = 31 or a dry-powder inhaler n = 39. The mean commercially labelled dose was 520 +/- 29 microg/day (mean +/- SEM, range: 160-1,000) and the equipotent dose (which compares the efficiency of these drugs for treating asthma and their responsibility for systemic effects) was 890 +/- 55 microg/day (range: 200-2,000). RESULTS: The mean stimulated cortisol level +/- SEM (and range) of the patient was 482 +/- 12 (148-801), and that of 40 age-matched controls was 580 +/- 12.5 (439-726), (SD = 79). The result was subnormal (more than 2 SD below the mean of the controls) in28 of the 100 patients. One-four stepwise decreases of 10-100% in the daily equipotent doses received by the patients with abnormal low-dose corticotropin testing results led to normal results in subsequent low-dose corticotropin testing in 27 retested patients. The mean time interval between two tests was 5 months (range: 2-6 months) and the mean period required for normalization of the test was 13 months (range: 2-21). Only one case of asthma exacerbation and no adrenal crisis were observed over these periods. CONCLUSIONS: Decreasing daily equipotent doses led to recovery of normal HPA function without asthma exacerbation. Thus, a revision of the doses of inhaled corticosteroids used in asthmatic children with a progressive decrease to the consensus-recommended doses should decrease the systemic effects of inhaled corticosteroids, while minimizing the risk of asthma exacerbation.

[Interest of lung scintigraphy for the follow-up of cystic fibrosis (CF) and other chronic obstructive pulmonary disease (COPD). Two case reports in children]. / Intérêt de la scintigraphie pulmonaire dans le suivi de la mucoviscidose et de la bronchite chronique obstructive chez l'enfant: à propos de 2 cas cliniques.

INTRODUCTION: Lung scintigraphy provides a regional, functional test of pulmonary ventilation and perfusion. It allows an early detection of pulmonary damage or dysfonction, in particular in cystic fibrosis (CF) and other chronic obstructive pulmonary disease (COPD) in childhood. CASE REPORTS: We report two cases in children suffering from CF and COPD (of undefined aetiology), who had a major localized ventilation disorder. They have been detected by lung scintigraphy before the development of clinical or radiological symptoms. An obstructive bronchial cast in the corresponding lobar bronchus was then revealed and withdrawn by bronchial fiberscopy. CONCLUSION: Lung scintigraphy allows early detection of local pulmonary abnormalities, sometimes undetectable with a chest X-ray or even with a chest tomodensitometry. It can reveal bronchial obstructive plugs, avoiding thus the development of bronchectasies thanks to a quick suitable treatment.

Prophylactic management of children at risk for recurrent upper respiratory infections: the Preventia I Study.

BACKGROUND: Given the morbidity and mortality of asthma and the recent dramatic increase in its prevalence, pharmacologic prophylaxis of this disease in children at risk would represent a major medical advance. OBJECTIVES: The Preventia I Study was designed to evaluate the efficacy and long-term safety of loratadine in reducing the number of respiratory infections in children at 24 months. A secondary objective was to investigate the benefit of loratadine treatment in preventing the onset of respiratory exacerbations. METHODS: Preventia I was a randomized placebo-controlled study involving 22 countries worldwide. The children were 12-30 months of age at enrollment and had experienced at least five episodes of ENT infections, and no more than two episodes of wheezing during the previous 12 months. Phase I was a 12-month double-blind period during which the children were treated with loratadine 5 mg/day (2.5 mg/day for children

[Past and future of allergen immunotherapy]. / Immunothérapie spécifique: acquis et avenir.

Specific immunotherapy involves the administration of allergen extracts to achieve clinical tolerance of the allergens which cause symptoms in patients with allergic conditions. Immunotherapy has been shown to be effective in patients with mild forms of allergic diseases, specially in upper airway diseases. Recent studies suggest that specific immunotherapy may also modify the course of allergic disease, by reducing the risk of developing new allergic sensitizations, and also inhibiting the development of clinical asthma in children treated for allergic rhinitis. The traditional subcutaneous route is burdened with the risk of severe adverse events, therefore, local routes have been investigated and developed. The sublingual route is supported by numerous controlled trials showing its efficacy in rhinitis. The safety profile, assessed in clinical trials studies, is satisfactory. Several points still need to be elucidated, including mechanisms of action, optimal dosage, cost-effectiveness, and adherence. New approaches using mimic bacterial DNA vaccines alone or associated to modified allergen, which enhances immunogenicity in terms of eliciting a Th1-type response vaccines, are also undergoing serious consideration.

Short-term health effects of particulate and photochemical air pollution in asthmatic children.

In a previous panel study in Paris, France, detrimental effects of moderately high levels of winter air pollution on the symptoms and lung function of asthmatic children were demonstrated. A new study was conducted, with the aim of assessing the short-term effects of photo-oxidant and particulate air pollution on childhood asthma during spring and early summer in Paris. Eighty-two medically diagnosed asthmatic children were followed up for 3 months. Outcomes included the incidence and prevalence of asthma attacks, nocturnal cough, supplementary use of beta2-agonists, symptoms of airway irritation, and peak expiratory flow (PEF) value and its variability. The statistical methods controlled for the lack of independence between daily health outcomes, temporal trends and pollen and weather conditions. Black smoke and nitrogen dioxide (NO2) were associated with increases in the occurrence of nocturnal cough and respiratory infections. Ozone (O3) was associated with an increase in the occurrence of asthma attacks and respiratory infections and with changes in lung function, as shown by an increase in PEF variability and a decrease in PEF. Statistically significant interactions were demonstrated between O3 and temperature and between O3 and pollen count for asthma attacks. O3 levels had a greater effect on additional bronchodilator use and on irritations of the eyes, nose and throat on days on which no steroids were used. Particulate matter was associated with eye irritation only. This study showed that, although within international air quality standards, the prevailing levels of photo-oxidant and particulate pollution in spring and early summer had measurable short-term effects on children with mild-to-moderate asthma.

[Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) - First results of a multi-disciplinary study]. / Etude Epidémiologique sur les facteurs Génétiques et Environnementaux de l'Asthme, l'hyperréactivité bronchique et l'atopie (EGEA). Premiers résultats d'une étude multidisciplinaire.

The French co-operative epidemiological study EGEA realised in 1991/95 combines a case control study and a study of the families of asthmatic cases. A synthesis of the results already obtained is presented. Smoking was related to IgE, even in asthmatics and was clearly related to the clinical severity of asthma, an aspect insufficiently taken into account. The relationships of occupational exposures to asthma have been assessed using a job exposure matrix. Segregation analyses on IgE have shown, after correction for the mode of ascertainment, the existence of a dominant major gene and familial residual correlation. A systematic genome screen realised in families with 2 asthmatic siblings showed linkage of various regions in the genome implicated to asthma or related phenotypes (1p, 11p, 11q, 12q, 13q, 17q, 19q), coherent with genome screens realised in other studies. Regarding candidate genes, no association was evidenced between asthma and the AF508 mutation of the cystic fibrosis gene. The analysis is still in progress by studies on the heterogeneity of asthma with refined genetic studies and by searching to integrate results regarding environmental and genetic factors and studying their interactions.

[Epidemiological study of genetic and environmental factors in asthma, bronchial hyperresponsiveness and atopy. Protocol and potential selection bias]. / Etude épidémiologique des facteurs génétiques et environnementaux de l'asthme, l'hyperréactivité bronchique et l'atopie (EGEA). Protocole et biais de sélection potentiels.

BACKGROUND: The EGEA study combines a case-control study and a family study to assess genetic and environmental risk factors and their interactions for asthma, bronchial hyperresponsiveness and atopy. Information is scanty regarding potential selection biases, in particular regarding familial ressemblance in epidemiological surveys of this kind. METHODS: Asthmatic probands (adult and paediatric) were recruited in chest clinics of six clinical centres. Controls were mostly population-based (electoral rolls) for adults and recruited in surgery departments for children. RESULTS: The population examined includes 348 nuclear families ascertained by one asthmatic and 416 controls, totalling 1847 subjects (EGEA I) and an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II). Potential biases for the various types of analyses have been studied. Quantification of the consequences of the greater participation of probands with a parental history of asthma shows it does not introduce a major bias in the estimates of familial resemblance. Cases and controls showed a good comparability regarding sex, age, area of residence and familial geographical origin, allowing proper associations studies for environmental and candidate genetic factors. CONCLUSIONS: The case-control component of the study will allow to perform studies on environmental factors and association studies for various genetic polymorphisms. Using the family base collected, segregation and genetic linkage/association analyses with DNA markers may be performed.

Genome screen for asthma and related phenotypes in the French EGEA study.

A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.