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.

[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.

Proteinase 3 mRNA expression is induced in monocytes but not in neutrophils of patients with cystic fibrosis.

Proteinase 3 (PR3), a serine proteinase which can degrade lung tissue, is present in the cystic fibrosis (CF) sputum. In the present study, PR3 protein and mRNA expression was determined in circulating neutrophils and monocytes. CF neutrophils contained similar PR3 concentrations as healthy controls and poorly expressed PR3 mRNA. In contrast, CF monocytes showed significantly higher PR3 concentrations than controls, together with an upregulation of PR3 mRNA expression especially during pulmonary exacerbation. Interestingly, antibiotic treatment fully abrogated PR3 mRNA expression and decreased PR3 protein in monocytes. Our findings highlight a potential role of monocyte-derived PR3 in CF-associated airway inflammation.

Expandable prosthesis in right postpneumonectomy syndrome in childhood and adolescence.

Right pneumonectomy can lead to severe respiratory impairment due to stenosis of the left main bronchus. This syndrome is usually treated by inserting a fixed-volume prosthesis but, in children, expandable prostheses have the advantage of being adaptable to growth and permit progressive recentering of the mediastinum. We report 3 such cases, with the results of pulmonary function tests. The patients were aged 11, 17, and 22 years at the time of implantation and had undergone pneumonectomy during childhood for either bronchiectasis or complete pulmonary sequestration. All 3 patients are doing well, with a follow-up of 1 to 3 1/2 years. Pulmonary function tests have shown a substantial improvement in the obstructive syndrome in 2 patients whereas, in the third patient, in whom the contralateral lung was not perfectly healthy, the functional improvement was only moderate.

Cutaneous acquired immunodeficiency syndrome-associated Kaposi's sarcoma in pediatric patients.

Kaposi's sarcoma has only rarely been reported in children with acquired immunodeficiency syndrome. In contrast to adult patients, in whom the disease is predominantly cutaneous, among pediatric patients with acquired immunodeficiency syndrome, Kaposi's sarcoma is primarily limited to the lymphadenopathic form. We describe two children with the acquired immunodeficiency syndrome who developed diffuse nodular skin lesions of Kaposi's sarcoma.

Activation of alveolar macrophages from children with the acquired immunodeficiency syndrome-related complex.

The ability of alveolar macrophages (AM) to release hydrogen peroxide (H2O2), an indicator of AM function, was studied in five children with the acquired immunodeficiency syndrome (AIDS) related complex and, for comparison, in 11 children without disorders of the lung parenchyma. In the AIDS-related complex group, pulmonary manifestations were mild, and lung involvement was suspected by moderate clinical and/or radiological features. None had a past history of opportunistic infections; neither did any have lymphopenia. Cytologic study of the bronchoalveolar lavage (BAL) fluid revealed increased cellularity with increased percentage of lymphocytes. The study of H2O2 release was performed on unstimulated AM and on AM stimulated by phorbol myristate acetate (PMA). Under both experimental conditions, the amount of H2O2 accumulated in the medium was significantly increased in the group with AIDS-related complex (P less than 0.001). As no enhanced oxidative activity has been reported in AM from patients with full-blown AIDS, an increased ability of AM to release oxygen metabolites from children with AIDS-related complex may reflect an initial and temporary step in the course of the LAV/HTLV-III pulmonary disease. Determining AM activation might be a reliable method of assessing the evolution of lung disorder in AIDS.

Pulmonary sarcoidosis in children: serial evaluation of bronchoalveolar lavage cells during corticosteroid treatment.

The clinical course of sarcoidosis in children has not been well defined. Eight children with symptomatic sarcoidosis included in this study underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and during steroid therapy. At the start of therapy, functional parameters, mostly dynamic lung compliance and lung transfer factor for CO, were impaired. This was associated with abnormalities of BAL cell populations: increased total cell number with a high proportion of lymphocytes, modifications of lymphocyte subpopulation with an elevated CD4+/CD8+ ratio, and enhanced ability of alveolar macrophages to release hydrogen peroxide. Although respiratory abnormalities seemed to be similar at the initial stage of sarcoidosis in children and adults, the course of the disease appeared to be different. Despite the absence of respiratory symptoms and disappearance of chest radiographic abnormalities on prolonged steroid treatment, we found slow improvement of pulmonary functions associated with persistence of BAL lymphocytosis and elevated CD4+/CD8+ ratios. However, the ability of alveolar macrophages to release hydrogen peroxide was significantly reduced after 6 months of steroid treatment, and it remained identical to the control group. Therefore, the evaluation of disease activity appears to be critical for therapy in pediatrics, and for this purpose studies of alveolar macrophage activation may be of particular interest.

Decreased phosphatidyl choline content in bronchoalveolar lavage fluids of children with bronchopulmonary dysplasia: a preliminary investigation.

Bronchoalveolar lavage (BAL) was performed on 12 infants who had recovered from neonatal acute respiratory failure and on 12 patients with bronchopulmonary dysplasia (BPD) in order to evaluate the concentration of phosphatidyl choline (PC) in BAL fluid. These two groups were similar at birth (mean birth weight: 1,980 and 1,750 g, respectively; mean gestational age: 33.4 and 32.1 weeks respectively). Mechanical ventilation based on oxygen requirement lasted longer in the group with BPD. BAL was performed at the end of the first year of life (at 8.5 and 10.3 months, respectively) and the results were compared to control values (from infants of the same age without neonatal disease). Whereas the protein concentration in BAL fluid was similar in the two groups, a dramatic decrease of the BAL PC was found in BPD: The mean values of BAL-PC over protein ratio were 0.9 in the group without pulmonary sequelae and 0.3 in the group with BPD. These preliminary results suggest an impairment of the pulmonary surfactant metabolism in this chronic lung disease following neonatal acute respiratory failure.

Prevalence of asthma or respiratory symptoms among children attending primary schools in Paris.

The objectives of this study were to determine the prevalence of chronic respiratory symptoms and asthma in 8- to 9-year-old children in Paris, and to analyze their medical management. This cross-sectional study was carried out in 1994 on a randomized sample of 3,756 pupils attending Paris public primary schools. The response rate by parents to an initial standardized self-administered questionnaire was 94.8%. This questionnaire identified 601 children (17%) as having recurrent respiratory symptoms. Of these children, 555 (92.3%) agreed to participate in a follow-up survey that evaluated their medical management; these children were examined by 73 school doctors of the city of Paris. Prevalence of parent-reported doctor-diagnosed asthma was 6.1%. In addition to these 211 children with asthma, 344 other children had recurrent respiratory symptoms: 120 children were "wheezers," and the remaining 224 children were "coughers." Among "chesty" pupils not identified as asthmatics, physical education teachers reported exercise-induced cough or respiratory discomfort in 13.7%, and nearly 14% had a peak expiratory flow 20% lower than the predicted values for age and height. In children identified as asthmatic, 25.3% were not under medical supervision, 55.5% had never performed lung function tests, 63.7% did not receive any prophylactic treatment, and 59.7% were receiving no treatment. Bronchodilator prophylactic medication before exercise was used by only 7% of asthmatics, although physical training teachers noted chest discomfort on exercise in 30.4% of these pupils. These results confirm that children with asthma and participating in this study were less than optimally investigated, were underdiagnosed and undertreated, and their medical management was not optimal. In addition to its epidemiologic value, the study has helped Paris school doctors to advise parents to refer their children to their general practitioner when asthma was suspected or undertreated.

Indications of the carbon dioxide laser in tracheobronchial pathology of the infant and young child: 14 cases.

Fourteen children aged between 6 months and 7 years (mean age = 3.5 years) were treated by CO2 broncholaser in the ENT Department of Trousseau Hospital. Three groups of diagnostic indication were identified: 1. Granulomas treated after mucosal trauma (tracheotomy, foreign body). 2. Granulomas due to pulmonary and/or lymph node tuberculosis. 3. Adhesions and stenosis secondary to neonatal ventilation. The operative and anesthetic technique is described in detail, together with any possible adverse events. The CO2 broncholaser appears to be a technique of choice in this age group, in which the narrowness of the airways makes any endoscopic procedure difficult. The broncholaser allows the early treatment of obstructive tracheobronchial pathology with its risks of severe ventilatory sequelae.

[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.

[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.

[Specific immunotherapy]. / Immunothérapie spécifique.

Increase of the prevalence of allergy these last 20 years is in part secondary to the modification of the allergenic charge of our environment. The specific immunotherapy (SIT) is the only etiologic treatment of the allergic disease and numbers of authors believe that, for the future, this treatment could change the natural history of the respiratory allergy, provided that it is realised early in the first years of life. Several experimental studies show that the process of the SIT could be the restoration of the Th1 cell/Th2 cell balance which is reversed in allergies. However, indications of SIT have to be carefully selected. The ideal indication is the single sensitized asthma, and treatment has to be started in the first years of life, at the onset of the asthmatic disease, before a definitive remodelling of the respiratory airways induced by inflammation. Subcutaneous SIT is for the moment the only effective route confirmed by several controlled trials, in particular for grass pollens, possibly for house dust, pet danders and mite allergens. Risk of syndromic effects, present all the time of the SIT protocol, can be prevented by rigorous use of the SIT according to the European consensus. The advent of recombinant allergens, in particular by complementary DNA (cDNA) modified by site-directed mutagenesis, could tip the immune response to a Th-1 like response instead of a Th-2 like response (IgE mediated) and result in a better tolerated and more efficacy immunomodulation.

[Asthma in infants]. / L'asthme du nourrisson.

Infant asthma is a newly individualised entity, underdiagnosed and undertreated. The physiological and anatomical features in infancy, the particular frequency of respiratory viral infections at this age can explain clinical aspects of asthma in infant. Some risk and prognostic factors, however, have been established. These include allergy, viral infections, neonatal respiratory illness. An early diagnosis of the disease makes possible adequate preventive means to be carried on. Treatment, based firstly on environmental control must be started soon to preserve pulmonary growth.

[Role of inhalation therapy in the management of childhood asthma]. / Place des thérapeutiques inhalées dans la prise en charge de l'asthme de l'enfant.

Inhaled drugs became of great interest in the treatment of childhood asthma. They must be adapted now to age and each form of the disease. The primarily interest of an organ therapy is to lead to a maximal efficacy by bringing locally an optimal quantity of drug without or with very few side effects. The choice of the device depends upon age which determines drug tolerance and quality of the inhalation technique. In infants and young children the use of nebulizers appears to be the most suitable technique; preschool children are capable to use metered-dose inhalers (MDI) with spacers; in older children the use of MDI, without spacers, or dry powder inhalers is allowed. During attacks of asthma, inhaled therapy appears to be effective in most cases using either B2 agonists alone in moderate forms, or B2 agonists associated with oral or parenteral corticoids in more severe forms. For the preventive treatment of asthma, in order to prevent attacks, some inhaled drugs also belong to a first line therapy against either allergy or on specific bronchial hyperreactivity: cromolyn or nedocromil are often used in mild to moderate forms (in association with oral anti-histamine drugs in some cases); in more severe forms we can start with a bronchodilator B2 agonist long-term treatment (associated with sustain-released theophylline in some cases), except in infants before twelve or eighteen months of age; in the most severe forms of chronic asthma an anti-inflammatory long-term treatment with inhaled corticosteroids may be prescribed even in young children.

[Comparative study of the performance and ergonomics of nebulizers in cystic fibrosis]. / Etude comparative sur les performances et l'ergonomie de nébuliseurs dans la mucoviscidose.

This study had, as its aim, to test twelve nebulizers (6 jet, 6 ultrasonic) which are used in the treatment of cystic fibrosis. Devices were connected to a respirator in order to mimic the ventilation of a child and of an adult suffering from cystis fibrosis. Three medications: tobramycine, colistine and amiloride were nebulised. The volume of the recommended solution varied between 1.5 and 13 ml according to the manufacturer. During a session of ten minutes the ultrasonic nebulizer delivered an inhaled volume which was significantly greater than the jet (2.72 +/- 0.98 ml vs 1.22 +/- 0.59 ml, p < 0.0001) for the three drugs. Regarding granulometry, the fraction of particles between 0.5 and 5 microns, was higher with ultrasonic than with pneumatic nebulizer for tobramycine (67.1 +/- 10.7 vs 55.5 +/- 11.5%, p < 0.001) and amiloride (66.4 +/- 9.2% vs 58.1 +/- 15%, p < 0.05%). The variation of concentration due to nebulisation were independent of the type of apparatus but influenced by the drug since concentration was increased for tobramycine (+10.5 +/- 18.6%) and amiloride (+13.4 +/- 8/9%). In summary the effective fraction resulting from the inhalable fraction, from granulometry and from changes in concentration was significantly greater for ultrasonic than for jet nebrulizer (17.3 +/- 6.7% vs 9.7 +/- 9.6%, p < 0.001). This study underlines the great variability of the performance of aerosols generators and therefore the need for an accurate evaluation of nebulizer performances in order to prescribe the best nebulizer/drug association in clinical practice.

[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.

[Inferior turbinectomy in asthmatic children]. / Turbinectomie inférieure chez l'enfant asthmatique.

Nineteen children with asthma underwent bilateral inferior turbinectomy from 1990 to 1995. Mean age was 11.5 years (range 8-17). All had obstructive allergic rhinitis and were resistant to long-term local corticosteroids. All operations were done under general anesthesia and endoscopic control. Mean hospital stay was 3 days. The postoperative period was uneventful and mean follow-up is 21 months (10-44). The patients described outcome as a clear improvement (n = 15), partial improvement (n = 3) and unilateral improvement (n = 1). The effect on asthma was more difficult to ascertain due to the number of cofactors. It can be noted however that asthma was not aggravated and that in 9 cases episodes decreased in frequency. Inferior turbinectomy provides considerable improvement in the comfort of patients with asthma, especially in terms of nasal ventilation.