A Grimfeld

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (126)151.34 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Persistent asthma in adults starts often early in childhood and is associated with alterations in respiratory function that occur early in life. The aim of this study was to evaluate the importance of innate and environmental factors associated with occurrence of asthma during childhood in a population of recurrent wheezing infants followed prospectively. 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 and environmental risk factors. At the age of 6 years, they were reevaluated with respect to remission or persistence of wheezing over the previous 12-month period. Data were available for 219 subjects aged 15 +/- 5 months. In 27% of the infants with recurrent wheeze, wheezing persisted until the age of 6 years. In multivariate analysis, stepwise logit analysis showed that the risk factors for persistent wheezing are eosinophilia >or=470/mm(3), allergenic sensitization, and a father with asthma. Environmental factors present during the first year of life that protect from persistence of wheezing are ( 1 ) breastfeeding for longer than 3 months, ( 2 ) pets at home, and ( 3 ) >or=3 siblings. The detection rate for persistent wheezing in this model is 72%. The persistence score showed good specificity 91% but low sensitivity 35%. This study confirms the role of atopic host factors on wheezing persistence during childhood and detected protective environmental factors.
    Journal of Asthma 05/2010; 47(4):412-6. · 1.85 Impact Factor
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    ABSTRACT: 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. 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. 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. Passive smoking lowers FeNO, and might be a major determinant of FeNO levels in nontreated allergic asthmatic children.
    Allergy 10/2009; 65(4):491-7. · 5.88 Impact Factor
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    ABSTRACT: 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. 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. 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. 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. 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.
    Clinical & Experimental Allergy 06/2008; 38(5):767-73. · 4.79 Impact Factor
  • Yacine Laoudi, Alain Grimfeld
    La Revue du praticien 11/2007; 57(16):1770-1.
  • Revue des Maladies Respiratoires 11/2007; 24(8 Pt 3):7S41-51. · 0.50 Impact Factor
  • Source
    J Just, F Sahraoui, V Le Gros, A Grimfeld
    Allergy 05/2007; 62(4):453-4. · 5.88 Impact Factor
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    ABSTRACT: The prevalence of asthma and allergic diseases doubled during the last quarter of the 20th century, particularly among children and adolescents. Given this fact, we cannot attribute this increase exclusively to genetic factors. Environmental factors to which it has been attributed include exposure to allergens and to airborne physicochemical pollutants, and changes in the characteristics of respiratory infections in young infants. In this review, we will point out the role of exposure to air pollutants and their interaction with other environmental factors. Whereas concentrations of the ‘classical’ air quality indicators (SO2, CO) have more or less decreased steadily in developed countries, asthma prevalence has increased during the same period. However, the relation between the increase incidence of asthma and atmospheric pollution should be examined with the knwoledge that there has been an increase in new forms of pollution, in particular, ultrafine particles. There are at present many experimental studies which show that urban pollution (especially that associated with diesel exhaust particles) elicits chronic oxidative stress, bronchial hyperreactivity and allergic inflammation. Several epidemiological studies suggest that there is an association between the density of automobile traffic and the prevalence of respiratory symptoms, especially asthma and allergic rhinitis. Exposure to automobile traffic-related pollutants during early infancy may accelerate or even provoke, among genetically susceptible subjects, bronchial inflammatory processes which could contribute to the increase in the incidence of asthma in industrialized countries.
    Revue Française d'Allergologie et d'Immunologie Clinique. 01/2007;
  • Revue Des Maladies Respiratoires - REV MAL RESPIR. 01/2007; 24(8):41-51.
  • Soins. Pediatrie, puericulture 11/2006;
  • J Just, L Nisakinovic, Y Laoudi, A Grimfeld
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    ABSTRACT: 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.
    Archives de Pédiatrie 08/2006; 13(7):1055-60. · 0.36 Impact Factor
  • A Grimfeld, J Just
    La Revue de Médecine Interne 07/2006; 27 Suppl 2:S64-5. · 0.90 Impact Factor
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    ABSTRACT: Outdoor and indoor air pollutants are suspected to induce harmful effects on respiratory health, raising the question of their involvement in allergic asthma and rhinitis. The potential effect of short-term personal exposure to particulate matter with a diameter of less than 2.5 microm (PM2.5) on nasal inflammation was examined in children living in the Paris area. Forty-one children with allergic asthma and 44 healthy children participated in this study. They were monitored during 48 hours for their personal exposure to PM2.5. At the end of the measurement period, children underwent one nasal lavage. Nasal lavage fluid was investigated for cellular (neutrophils and eosinophils) and soluble (albumin, urea, elastase, alpha1-antitrypsin, IL-6, and IL-8) mediators. Pollutant concentrations did not differ between the 2 groups. In asthmatic subjects, but not in healthy children, personal PM2.5 levels were correlated to nasal percentage of eosinophils and to albumin, urea, and alpha1-antitrypsin concentrations after adjustment for confounders (age, sex, house dust mites, pollens, cat, environmental tobacco smoke through urinary cotinine, barometric pressure, and respiratory infection). The association observed with the percentage of eosinophils supports recent speculations on fine particle involvement in allergic phenotype overexpression. This study highlights the link between personal fine particle exposures and nasal inflammation in asthmatic allergic children living in urban areas. Because the view of united airways is still not completely understood, the question of pulmonary inflammation in such a situation deserves further investigation.
    Journal of Allergy and Clinical Immunology 07/2006; 117(6):1382-8. · 12.05 Impact Factor
  • Revue Des Maladies Respiratoires - REV MAL RESPIR. 01/2006; 23:11-11.
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    ABSTRACT: 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. 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. 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.
    Archives de Pédiatrie 11/2005; 12(10):1487-91. · 0.36 Impact Factor
  • J. Just, A. Grimfeld
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease especially in anatomic features and in disease severity. The only proven genetic factor so far identified in its pathogenesis is alpha1-antitrypsin deficiency, although this accounts for less than 1% of individuals with COPD. Exposure to deleterious environmental factors is equally significant but only 15% of smokers develop COPD. The prevalence of COPD is increased in industrialized countries and, as with asthma, this suggests a genetic influence with modification of phenotype expression secondary to interaction between genetic and environmental factors. The childhood origin of adult COPD is supported by a number of epidemiologic studies. This hypothesis is based on: (1) an increased prevalence of asthma, especially in children and young adults; (2) persistence of infantile asthma into adolescence and adulthood; (3) the risk of progression of childhood viral respiratory infections to COPD; and (4) familial transmission of a functional phenotype of certain forms of adult COPD.
    Revue Française d'Allergologie et d'Immunologie Clinique. 01/2005; 45(1):42-46.
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    ABSTRACT: 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.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2005; 12(10):1487-1491.
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    ABSTRACT: 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. 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. 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</=24 months of age) or placebo. Phase II was a double-blind follow-up period without study medication. Of the 412 children enrolled, 342 and 310 completed Phase I and Phase II, respectively. The results showed a significant decrease in the number of infections in the whole population of children. However, no difference was observed between the loratadine and placebo group. When considering secondary end-points, loratadine was shown to reduce the number of respiratory exacerbations during the treatment phase. None of the 204 children who received loratadine discontinued the study because of drug-related events. Loratadine treatment was not more sedative than placebo and was not associated with cardiovascular events. The strong decrease in the rate of infections in the children at risk of recurrent infections, while not being influenced by loratadine treatment, should encourage future reflection in terms of prophylactic management. This study also confirms the long-term safety of loratadine and its metabolites in young children.
    Clinical & Experimental Allergy 11/2004; 34(11):1665-72. · 4.79 Impact Factor
  • Acta bioquímica clínica latinoamericana 09/2004; 38(3):319-327. · 0.09 Impact Factor
  • J Just, E Goudard, A Grimfeld
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    ABSTRACT: 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.
    Archives de Pédiatrie 07/2004; 11 Suppl 2:74s-79s. · 0.36 Impact Factor
  • J Just, E Goudard, A Grimfeld
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2004; 11.

Publication Stats

709 Citations
151.34 Total Impact Points

Institutions

  • 2006–2009
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Université René Descartes - Paris 5
      • Faculty of Pharmaceutical Sciences and biology
      Paris, Ile-de-France, France
  • 1992–2007
    • Hôpital Armand-Trousseau (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2003–2006
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2004
    • Centre de Pneumologie et d'Allergologie
      Avinyó, Provence-Alpes-Côte d'Azur, France
  • 1998–1999
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France