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Biomedical subjects

J Just

Publications and source records attributed to J Just.

At least 19 recordsLinked to original sources

[Air pollution and asthma in children].

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.

Air Pollutants↗

[Recurrent respiratory tract infections: how should we investigate and treat?].

Recurrent respiratory tract infections are a common reason for visits to primary care practitioners or hospital physicians. They are placed at the junction of several medical specialities: paediatrics, ENT, pneumology, allergology, immunology, infectiology. The great diversity of the laboratory tests requested and on the other hand the proposed treatments, are the consequences of the diversity of the patients encountered and the paucity of the evidence based-medicine studies in this setting. The dilemma is how to identify the child for which recurrent respiratory tract infections are the witness of underlying condition, without performing repeated medical examinations, laboratory tests and treatments for normal children for which immunologic development occurs normally. The essential tools are the history analysis, physical examination and few laboratory tests. The other questions are how to include, for these patients, influenza and pneumococcal vaccines in the immunization program and how to assess the benefit/risk ratio and the cost of surgical treatments. This paper presents the thought of an expert group trying to define the situations where biological tests or treatments are useful.

Child↗

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma.

In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24-p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22-q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24-p14, 9p22 and 9q22-q34 are more likely to harbor genetic factors specific to AR.

Asthma↗

[Flexible bronchoscopy in children. Experience at French centers of pediatric pneumology].

INTRODUCTION: Fibreoptic bronchoscopy (FB) is an important diagnostic examination in paediatric pulmonology. In 2002 the Paediatric Pulmonology and Allergy Club undertook a retrospective study to establish the current status of fibreoptic bronchoscopy among its members. METHODS: In 2001 sixty five paediatric pulmonologists carried out an average of 116 examinations (+/- 111) in 35 paediatric centres. FB was performed either in an operating theatre (15 centres), a dedicated bronchoscopy suite (6 centres) or an endoscopy suite shared with gastro-enterologists (7 centres). Other examinations were performed in areas dedicated to, or associated with intensive care. General anaesthesia was routinely used in 18 centres. The others used sedation including an equimolar mixture of oxygen and nitrous oxide in 14 centres. Ten centres performed less than 50 examinations, 12 between 51 and 100, 4 between 101 and 200 and 8 centres more than 200 in the year. Seventy two per cent of the children were less than 6 years old. The washing and disinfection procedures were manual in 20 centres and automatic in 15. RESULTS: Three principal indications were reported: persistent wheezing, suspicion of a foreign body and ventilatory difficulties. Cough, desaturation and fever were the most frequently reported side effects. CONCLUSIONS: This is the first survey in paediatric pulmonology in France. It shows a wide variation in the practice of fibreoptic bronchoscopy in children.

Bronchoscopes↗

[Past and future of allergen immunotherapy].

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.

Administration, Sublingual↗

Traffic related air pollution and incidence of childhood asthma: results of the Vesta case-control study.

STUDY OBJECTIVE: The Vesta project aims to assess the role of traffic related air pollution in the occurrence of childhood asthma. DESIGN AND SETTING: Case-control study conducted in five French metropolitan areas between 1998 and 2000. A set of 217 pairs of matched 4 to 14 years old cases and controls were investigated. An index of lifelong exposure to traffic exhausts was constructed, using retrospective information on traffic density close to all home and school addresses since birth; this index was also calculated for the 0-3 years age period to investigate the effect of early exposures. MAIN RESULTS: Adjusted on environmental tobacco smoke, personal and parental allergy, and several confounders, lifelong exposure was not associated with asthma. In contrast, associations before age of 3 were significant: odds ratios for tertiles 2 and 3 of the exposure index, relative to tertile 1, exhibited a positive trend (1.48 (95%CI = 0.7 to 3.0) and 2.28 (1.1 to 4.6)), with greater odds ratios among subjects with positive skin prick tests. CONCLUSIONS: These results suggest that traffic related pollutants might have contributed to the asthma epidemic that has taken place during the past decades among children.

Age Factors↗

Contribution of indoor and outdoor environments to PM2.5 personal exposure of children--VESTA study.

Several studies among adult populations showed that an array of outdoor and indoor sources of particles emissions contributed to personal exposures to atmospheric particles, with tobacco smoke playing a prominent role (J. Expo. Anal. Environ. Epidemiol. 6 (1996) 57, Environ. Int. 24 (1998) 405, Arch. Environ. Health 54 (1999) 95). The Vesta study was carried out to assess the role of exposure to traffic emissions in the development of childhood asthma. In this paper, we present data on 68 children aged 8-14 years, living in the metropolitan areas of Paris (n = 30), Grenoble (n = 15) and Toulouse (n = 23), France, who continuously carried, over 48 h, a rucksack that contained an active PM2.5 sampler. Data about home indoor sources were collected by questionnaires. In parallel, daily concentrations of PM10 in ambient air were monitored by local air quality networks. The contribution of indoor and outdoor factors to personal exposures was assessed using multiple linear regression models. Average personal exposure across all children was 23.7 microg/m3 (S.D. = 19.0 microg/m3), with local means ranging from 18.2 to 29.4 microg/m3. The final model explains 36% of the total between-subjects variance, with environmental tobacco smoke contributing for more than a third to this variability; presence of pets at home, proximity of the home to urban traffic emissions, and concomitant PM10 ambient air concentrations were the other main determinants of personal exposure.

Adolescent↗

Five epidemiological studies on transport and asthma: objectives, design and descriptive results.

A case-control study was conducted in five French metropolitan areas in order to assess the role of traffic-related air pollution in the occurrence of childhood asthma. This paper presents the study design and describes the distribution of key exposure variables. A set of 217 pairs of matched 4- to 14-year-old cases and controls were investigated (matching criteria: city, age, and gender). Current and past environmental smoke exposures, indoor allergens or air pollution sources, and personal and family atopy were assessed by standard questionnaires. When possible, direct measurements were done to check the validity of this information, on current data: skin prick tests, urine cotinine, house dust mites densities, personal exposures to, and home indoor concentrations of NO(x) and PM(2.5). Cumulative exposure to traffic-related pollutants was estimated through two indices: "traffic density" refers to a time-weighted average of the traffic density-to-road distance ratio for all home and school addresses of each child's life; "air pollution" index combines lifelong time-activity patterns and ambient air concentration estimates of NO(x), using an air dispersion model of traffic exhausts. Average current PM(2.5) personal exposure is 23.8 microg/m3 (SD=17.4), and average indoor concentrations=22.5 microg/m3 (18.2); corresponding values for NO(2) are 31.4 (13.9) and 36.1 (21.4) microg/m3. Average lifelong calculated exposures to traffic-related NO(x) emissions are 62.6 microg/m3 (43.1). The five cities show important contrasts of exposure to traffic pollutants. These data will allow comparison of lifelong exposures to indicators of traffic exhausts between cases and controls, including during early ages, while controlling for a host of known enhancers or precipitators of airway chronic inflammation and for possible confounders.

Adolescent↗

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.

Adolescent↗

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.

Adolescent↗

Genomic organization and chromosomal localization of mouse proteinase 3 (Myeloblastin).

Proteinase 3 (PR3), is a matrix-degrading serine proteinase expressed in different hematopoietic cell lineages. The PR3 protein appears to regulate the myeloid differentiation and was found to be the autoantigen associated with Wegener granulomatosis. We have isolated and characterized the gene for mouse PR3 (mPR3) and determined its chromosomal location. The gene has been localized to Chromosome (Chr) 10. Comparison of mouse PR3 genomic structure with that of its human counterpart indicates that: 1) the mPR3 gene spans 7 kb organized in 5 exons and 4 introns, 2) the codons of His-Asp-Ser of the catalytic site are conserved and spread out over different exons, similar to the human gene, and 3) the gene product encodes a pre-proform of the protein. Knowledge of the structure and chromosomal location of the mPR3 gene may help better the understanding of the temporal and cell-specific expression of mouse PR3.

Amino Acid Sequence↗

[Specific immunotherapy].

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.

Age Factors↗

Bacterial flora of the lower respiratory tract in children with bronchial asthma.

The aims of this retrospective study were to (i) determine the risk of contamination of lower respiratory tract samples obtained during fiberoscopy in children; (ii) determine the incidence and profile of the bacterial flora of the lower respiratory tract in a selected group of asthmatic children at high risk for bacterial infection; and (iii) identify risk markers for such findings. In 29 asthmatic children, comparison of bacterial cultures of specimens obtained from the upper and, lower respiratory tracts showed that contamination was a possibility in only 3.4% (1/29) of cases. The results from bacterial samples obtained via flexible bronchoscopy in a further 273 consecutively investigated physician-diagnosed asthmatic children were analysed. Patients were selected for bronchoscopy if they had severe chronic asthma or in order to exclude other diseases able to provoke wheezing. Their mean (SD) and median ages were 32.2 (38.3) and 17.5 mo, respectively. The incidence of positive bacterial cultures was 12.1% (33/273 patients). Bacterial flora included H. influenzae (39.5%, 15/38), B. catarrhalis (23.7%, 9/38), Neisseria species (7.9%, 3/38), M. pneumoniae (7.9%, 3/38), P. non-aeruginosa (5.3%, 2/38) and P. aeruginosa (2.6%, 1/38). No clinical or radiological markers were significantly associated with lower respiratory tract bacterial infection. Large quantities of bacteria were present in the lower respiratory tracts of a substantial number of children (1/8) in this selected group of asthmatics. For the moment, however, the clinical implications of this finding remain unclear.

Asthma↗

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.

Asthma↗