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Biomedical subjects

A Grimfeld

Publications and source records attributed to A Grimfeld.

At least 19 recordsLinked to original sources

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.

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↗

Use of personal passive samplers for measurement of NO(2), NO, and O(3) levels in panel studies.

We measured personal exposure to nitrogen dioxide (NO(2)), nitrogen monoxide (NO), and ozone (O(3)), using personal passive samplers during three 4-day periods, in a panel study of asthmatics continuing the normal activities of everyday life. Fifty-five adults, mean age 42 years, 53% men, and 39 children, mean age 11 years, 67% boys, wore two Ogawa passive samplers simultaneously: one for O(3), the other for NO(2) and NO. Mean outdoor pollution was measured at a regional monitoring network. Personal exposure levels were scattered; they were (on average) higher than stationary-site levels for NO and lower for NO(2) and O(3). In adults, 41% of the variance of personal exposure to NO(2) was explained by mean stationary-site measurement levels (P<0.0001). Twenty-one percent additional variance was explained by living near a main road, not having an extractor fan over the cooker, older age, and male sex. NO and O(3) personal exposures correlated poorly with stationary-site measurements. In panel studies of the health effects of air pollution, personal exposure to NO(2) and NO can be measured satisfactorily by passive samplers: such measurements are necessary for NO but not for NO(2). For O(3), accurate personal exposure measurement remains a challenge and further technical development is required.

Activities of Daily Living↗

[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↗

EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy)-- descriptive characteristics.

The Epidemiological study on the Genetics and Environment of Asthma (EGEA) was planned to assess genetic, environmental risk factors and their interactions for asthma and for the two related traits of bronchial hyperresponsiveness and atopy. The population examined includes 348 nuclear families ascertained by one asthmatic (213 adult and 135 paediatric probands) and 416 controls, totalling 1,847 subjects (EGEA I). Prevalences of asthma, skin prick test response, high IgE and bronchial hyperresponsiveness were for parents, siblings, and offspring of cases intermediate between cases and spouses or controls, both in adults and children, confirming the familial resemblance for asthma and related traits. With an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II), a total of 119 families with two asthmatic siblings has been ascertained for a genome screening.

Adolescent↗

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↗

Short-term effect of winter air pollution on respiratory health of asthmatic children in Paris.

There is controversy as to whether low levels of air pollution affect the symptoms and lung function in asthma. We addressed this by examining the short-term effects of winter air pollution on childhood asthma in Paris. We performed a 6 month follow-up of 84 medically diagnosed asthmatic children classified into two groups of severity. The outcomes included incidence and prevalence of asthma attacks, symptoms and use of supplementary beta2-agonists, peak expiratory flow (PEF) value and its variability. The statistical analysis controlled the lack of independence between daily health outcomes, trends and meteorology. Air pollution was associated with an increase in reports and duration of asthma attacks and asthma-like symptoms in mild asthmatic children. The strongest association was the risk of asthma attack for an increase of 50 microg x m(-3) of sulphur dioxide (SO2) on the same day (odds ratio (OR)=2.86). Maximum reduction in morning peak expiratory flow (PEF) (5%) and maximum increase in PEF variability (2%) were observed at a lag of 3 days for an increase of 50 microg x m(-3) of SO2 in the subgroup of mild asthmatics receiving no regular inhaled medication. In moderate asthmatic children, the duration of supplementary beta2-agonist use was strongly associated with air pollution. The general pattern of our results provides evidence of the effect of the low levels of air pollution encountered in Western Europe on symptoms and lung function in childhood asthma.

Administration, Inhalation↗

[The wheezing child and pediatric respiratory infections].

Given that the respiratory and immunity systems are still in development up to the age of 3 years, viral infections and exposure to environmental factors such as passive smoking in babies and young children may alter these systems, so favouring the development of allergic rhinitis and asthma. This may explain the correlation between viral respiratory infections or exposure to environmental factors and later development of wheezing and asthma. Prevention of respiratory infections may thus reduce the risks of pneumonopathy in the long term. For greatest efficacy however, the preventative measures must be in place before the age of 3 years, i.e. before lung development has been completed.

Child↗

[Inferior turbinectomy in asthmatic children].

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.

Adolescent↗