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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

At least 37 records · Page 2Linked to original sources

Asthma and exercise-induced bronchoconstriction in amateur endurance-trained athletes.

High-level endurance training contributes to the development of asthma and exercise-induced bronchoconstriction but the effect of moderate endurance training on airway function remains to be determined. The aim of this study was to evaluate the prevalence of physician-diagnosed asthma and/or exercise-induced bronchoconstriction in moderately endurance-trained athletes. Ninety-five Mediterranean amateur endurance-trained athletes filled out a questionnaire about respiratory disorders and underwent a resting spirometry. Mean training volume was 10 h per week. The prevalence of asthma was found to be 4.2 %. All the athletes with asthma plus another one (5.3 %) reported having exercise-induced bronchoconstriction. These percentages are in the same range as those from the general population and much lower than those observed in elite endurance athletes. In contrast to elite athletes, our amateur endurance-trained athletes seem not exposed to a higher risk of asthma or exercise-induced bronchoconstriction than the general population. We suggest that 10 h per week of moderate endurance training in a temperate climate area does not lead to respiratory disease.

Adolescent↗

Inflammatory features of nasal mucosa in smokers with and without COPD.

BACKGROUND: To investigate whether nasal and bronchial inflammation coexists in chronic obstructive pulmonary disease (COPD), nasal and bronchial biopsy specimens from seven control subjects, seven smokers without COPD, and 14 smokers with COPD were studied. METHODS: Nasal and bronchial biopsy specimens were taken from the same patients during bronchoscopy and squamous cell metaplasia and the thickness of the epithelium and basement membrane were measured. The numbers of eosinophils (EG2), neutrophils (elastase), macrophages (CD68), and CD8 T lymphocytes (CD8/144B) were assessed by immunohistochemistry. RESULTS: Smokers with and without COPD had squamous metaplasia in the nasal and bronchial epithelium. In all groups the thickness of the nasal epithelium was greater than that of the bronchial epithelium. The thickness of the basement membrane was similar in nasal and bronchial biopsy specimens from smokers with and without COPD, but was greater in the bronchi than in the nasal epithelium of controls. Eosinophil number was higher in the nasal and bronchial mucosa of smokers without COPD than in smokers with COPD or controls. Neutrophil number was higher in the nasal and bronchial mucosa of smokers with COPD than in smokers without COPD or controls. CD8 T lymphocyte numbers were similar in smokers with and without COPD and higher than in controls. There were fewer macrophages in nasal and bronchial biopsy specimens from smokers without COPD than in those with COPD. CONCLUSION: Nasal and bronchial inflammation coexists in smokers and is characterised by infiltration of CD8 T lymphocytes. In smokers without COPD this feature is associated with an increased number of eosinophils, while in those with COPD it is linked to an increased number of neutrophils in both nasal and bronchial biopsy specimens.

Adult↗

Can endobronchial biopsy analysis be recommended to discriminate between asthma and COPD in routine practice?

BACKGROUND: International guidelines stress the importance of accurately discriminating between asthma and chronic obstructive pulmonary disease (COPD). Although characteristic pathological features have been described for both conditions, their discriminatory power has never been systematically assessed. METHODS: Endobronchial biopsy (EBB) specimens from patients with a clear clinical diagnosis of asthma and COPD (50 per group) were examined by three pathologists in a double blind manner. They were asked to propose a pathological diagnosis of either asthma or COPD and to analyse qualitatively the most frequent abnormalities reported in the literature. RESULTS: The sensitivity and specificity of EBB ranged from 36% to 48% and from 56% to 79%, respectively. Eosinophils strongly biased the pathological diagnoses in favour of asthma, whereas their estimated prevalence was similar (11-37% in asthma and 13-41% in COPD). Metaplasia (11-39% in COPD, 1-18% in asthma) and epithelial inflammation (28-61% in COPD, 11-38% in asthma) tended to be specific to COPD, whereas epithelial desquamation (80-98% in asthma, 61-88% in COPD) and basement membrane thickening (71-94% in asthma, 53-88% in COPD) tended to be associated with asthma. There was acceptable intra- and inter-observer agreement only for metaplasia and epithelial eosinophils. CONCLUSIONS: Specific histopathological features of asthma and COPD probably exist, but current routine analysis procedures to assess EBB specimens are not sufficiently discriminatory. This might be rectified by improving pathological definitions.

Adult↗

Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD.

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.

Adult↗

The analysis of asthma control under a Markov assumption with use of covariates.

In studies of disease states and their relation to evolution, data on the state are usually obtained at in frequent time points during follow-up. Moreover in many applications, there are measured covariates on each individual under study and interest centres on the relationship between these covariates and the disease evolution. We developed a continuous-time Markov model with use of time-dependent covariates and a Markov model with piecewise constant intensities to model asthma evolution. Methods to estimate the effect of covariates on transition intensities, to test the assumption of time homogeneity and to assess goodness-of-fit are proposed. We apply these methods to asthma control. We consider a three-state model and we discuss in detail the analysis of asthma control evolution.

Asthma↗

Medical Indoor Environment Counselor (MIEC): role in compliance with advice on mite allergen avoidance and on mite allergen exposure.

BACKGROUND: In order to improve patient compliance in allergen avoidance, a new occupational activity was created: Medical Indoor Environment Counselor (MIEC). The aim of this study was to assess the impact of an MIEC on compliance with advice for mite allergen reduction in patients sensitized and exposed to mite allergens, and on mite allergen levels. METHODS: The study included 378 patients from four centers (Marseilles, Montpellier, Paris, Strasbourg) in a randomized prospective study. Patients in group A received advice from doctors only, and those in group B from doctors and MIEC. Mite allergen levels were measured on mattresses, mattress bases, and floors. Compliance and mite allergen levels were assessed 5 months later. RESULTS: Compliance for changing the mattress bases, removing or treating the carpets, washing duvets, pillows and stuffed animals were significantly higher in group B than in group A. A significant decrease in mite allergen was obtained for group B in mattress bases (83.8-22.9 micro g/g) and in carpets (15.8-6.3 micro g/g), but not in group A. CONCLUSION: Our results suggest that the home visit by the MIEC 1) increased the compliance to mite reduction methods advised; 2) induced a significant difference in mite reduction levels on mattress bases and on carpets; 3) avoided nonestablished avoidance advice.

Adolescent↗

Glucocorticoid receptor-binding characteristics in severe asthma.

The cellular mechanisms associated with severe asthma are still poorly understood. This study investigated the association between glucocorticoid-receptor (GR) alterations and continuous oral glucocorticoid therapy requirement in severe asthma. GR-binding affinity (Kd) and receptor number (n) in peripheral blood monocytes (PBM) obtained from 10 normal subjects, 10 untreated, intermittent asthmatics and 10 severe asthmatics were assessed. Moreover, one ability of dexamethasone to inhibit regulated on activation, T-cells expressed and secreted (RANTES) release by these cells in vitro was investigated. GR-binding characteristics were studied in PBM using a 3H dexamethasone ligand-binding assay and Scatchard analysis. RANTES release was measured in the supernatant of PBM at 24 h using an enzyme-linked immunosorbent assay. No significant differences in Kd and n were found between the three groups of patients. Dexamethasone in vitro was able to inhibit RANTES release (mean+/-SEM), with the same concentration/response curve in intermittent, untreated asthmatics (0.47+/-0.22 versus 1.64+/-0.31 ng x mL(-1)) and severe asthmatics (1.49+/-0.64 versus 2.59+/-0.77 ng x mL(-1)). This study showed that, despite long-term treatment with oral glucocorticoids, there was no evidence of abnormalities in glucocorticoid receptor-binding characteristics in severe asthma, and moreover, it was demonstrated that glucocorticoid receptors were functional in vitro.

Administration, Oral↗

Assessment of variations in control of asthma over time.

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Adolescent↗

[Value of thoracic CT in the management of severe hemoptysis].

PURPOSE: To assess the value of thoracic CT in the management of patients with severe hemoptysis. PATIENTS AND METHODS: Between January 1997 and January 2001, 62 patients were investigated for severe hemoptysis (>300 ml/24H). The protocol, performed before angiography and embolization, included bronchial fiberoptic examination (BFE) followed by thoracic spiral CT-angiography. Data recorded at CT and BFE were the presence and location of bleeding, the etiology of hemoptysis and the therapeutic modality. RESULTS: Nine patients with life-threatening hemoptysis directly underwent bronchial embolization. CT was available in the 53 remaining patients. No abnormality was found in 4 patients. CT assessed the presence (n=49) and the location (n=38) of the bleeding. The etiology was determined in 49 patients. BFE was feasible in 38/53 patients. BFE assessed the presence (n=38) and location (n=15) of the bleeding. The etiology was determined in 12 cases of bronchial tumour. The available findings of CT and BFE for the presence and the location of the bleeding were concordant. Comparing fiberoptic examination and thoracic CT, the percentages of localized bleedings (39% and 72%) and demonstrated etiologies (32% and 92%), were significantly different (p<0,005 and p<0.0001 respectively). CONCLUSION: Although retrospective and limited by the small number of cases, our study provides arguments to perform thoracic CT before bronchial fiberoptic examination for the management of severe hemoptysis.

Adolescent↗

[Smoking habits, attitudes and knowledges of medical students of Medicine, Pharmacy and Odonto-Stomatology's Faculty of Dakar, Senegal].

INTRODUCTION: Smoking is a public health problem that does not spare the medical profession. We set out to determine the prevalence of smoking in medical students in Dakar and to assess their attitudes and knowledge in the face of this problem. METHODS: A cross sectional study was conducted by means of an auto-questionnaire among 1547 medical students between 3 and 31 May 2001. There were 1061 males (68.6%) and 486 females (31.4%). RESULTS: The overall prevalence of regular or occasional smoking was 34.6%, with 42.8% in the first cycle, 38% in the second and 19% in the third. It was significantly higher among males at 76.4%. The average age of starting smoking ranged from 10 to 22 years and average duration from 5 to 26 years. The influence of fashion was the most frequent initiating factor at 37.4% and 96.6% smoked commercial cigarettes. Nicotine dependence, assessed by the Fagerstrom score, was average in 59.3%, strong in 14% and very strong in 4.7%. 58.8% smoked in public places and 78.2% thought they could give up smoking within the next 5 years. 8.4% were unaware of the effects of tobacco on health and 20.5% of the relationship between tobacco and the diseases quoted. 37.7% of future doctors would not systematically avoid smoking in the presence of patients but 79% wished to ban advertising and 70.4% to ban the use of tobacco in hospitals. 94.4% of students wanted health care workers to be educated about the effects of smoking. CONCLUSIONS: Tobacco smoking among medical students has increased between 1989 (28.7%) and 2001 (35.6%). This observation should stimulate the establishment of a course on the pathology of tobacco smoking and the integration of education and prevention within the medical curriculum, increase the awareness of smokers and above all help them stop.

Adolescent↗

Endogenous anti-inflammatory mediators from arachidonate in human neutrophils.

Eicosanoids have been historically involved in the pathogenesis of various inflammatory diseases. Lipoxins (LXs) and epi-LXs show physiological effects relevant to inflammation regulation. In this study, we focused on LX precursors based on the hypothesis that their entrance and metabolism into the cell may facilitate their targeting at the inflammation site. Because compound chirality is of considerable importance in the efficacy of therapeutic agents, our aim was to study the anti-inflammatory effects of various epimers of LXA(4) precursors compared to LXA(4). Blood polymorphonuclear cells (PMNs) were incubated with 15(S)- or 15(R)-hydroxyeicosatetraenoic acid (HETE), 14(R)-,15(S)-, or 14(S),15(S)-diHETE, and LXA(4) and then stimulated with the calcium ionophore A23187. We found that 15(R)-HETE rather than 15(S)-HETE was preferentially metabolized and that 15-epi-LXs were produced in larger amounts than LXs. In contrast, when PMNs were incubated with the diastereoisomers of 14,15(S)-diHETE, 14-epi-LXB(4) was produced in lower amounts than LXB(4). Enantiomers of 15-HETE and diastereoisomers of 14,15-diHETE and LXA(4) were able to significantly decrease LTB(4) release by PMNs. These results suggest a potential resolution of the inflammatory process through endogenous anti-inflammatory mediators released by the way of trans-cellular metabolism.

Anti-Inflammatory Agents↗

The accuracy of the diagnosis of suspected paracetamol (acetaminophen) hypersensitivity: results of a single-blinded trial.

BACKGROUND: Hypersensitivity to paracetamol (acetaminophen) is rare and very few clinical data are available in the literature. MATERIALS AND METHODS: Eighty-four patients (28 males and 56 females, 5-70 years old) with a suspicion of paracetamol hypersensitivity were referred to our drug allergy clinic between May 1996 and May 2000. The reaction had occurred 1-96 months prior to the consultation. Single-blinded placebo-controlled oral challenges were carried out in 82 patients, under strict hospital surveillance. RESULTS: Most of the patients experienced skin eruptions 82/84 (97.6%), with 10 cases of anaphylactic shock (11.9%). Twenty-six (30.9%) reactions were immediate (occurring within the first hour after drug intake), 53 (63.1%) non-immediate and five could not remember. Oral provocation tests (OPT) demonstrated drug hypersensitivity in 11 patients only. The two patients not tested (due to a history of life-threatening reaction) were included in the positive group. Thus, 13 (15.5%) patients had paracetamol hypersensitivity and 71 (84.5%) had not. All the 13 positive patients had skin eruptions, five with anaphylactic shock. 9/13 had immediate reactions. Using OPT, 10 out of 11 had the same clinical reaction but more delayed. In both groups, whether hypersensitive to paracetamol or not: atopy was similar (7/13-53.8% and 31/71-43.7%), sex ratio was not different (M/F 0.3 and 0.5), 3/13 (23.1%) and 0/71 (0%) had aspirin/ibuprofen hypersensitivity. CONCLUSION: The clinical history of paracetamol (acetaminophen) hypersensitivity is rarely sufficient to set a firm diagnosis and only OPT can confirm this. Careful OPT reproduces the same symptoms (not more severe in our hands) with the same or slightly more delayed chronology. Atopy and sex are not risk factors.

Acetaminophen↗

Regulation of E-cadherin expression by dexamethasone and tumour necrosis factor-alpha in nasal epithelium.

Asthma and rhinitis often coexist and share many clinical features. The extent of epithelial alteration in nasal inflammation is controversial. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is mediated by the cadherin family. In human bronchial epithelial cells the authors have shown that tumour necrosis factor (TNF)-alpha induced a significant decrease of E-cadherin and beta-catenin expression. The addition of dexamethasone inhibited this decrease. The aim of the present study was to investigate the effect of TNF-alpha and dexamethasone on the regulation of E-cadherin, gamma-catenin and beta-catenin in human nasal epithelial cells (HNEC). A primary culture of HNEC, obtained from human nasal turbinates after surgery, was used. The quantitative and qualitative modulation of E-cadherin, gamma-catenin and beta-catenin expression was assessed by Western blot and immunofluorescence analysis. In order to assess the TNF-alpha-induced activation of HNEC, interleukin-8 and RANTES (regulated on activation, normal T-cell expressed and secreted) release was assessed by enzyme-linked immunosorbent assay. The results showed that TNF-alpha induced, a decrease in gamma-catenin and beta-catenin expression, but had no effect on E-cadherin expression. Immunofluorescence showed that TNF-alpha induced cytoplasmic localisation of E-cadherin, gamma-catenin and beta-catenin. Dexamethasone inhibited the effect of TNF-alpha and induced a three-fold increase in E-cadherin expression. These results suggest that the difference in nasal and bronchial epithelial cohesion may be due to the differential effect of tumour necrosis factor-alpha and dexamethasone on E-cadherin expression.

Blotting, Western↗

Eosinophilic inflammation in sputum of poorly controlled asthmatics.

Despite full effective treatment, asthmatic patients often present with poorly controlled asthma. Airway eosinophilia is associated with asthma, but its relationship with asthma control is still undetermined. To investigate the relationship between airway eosinophilia and asthma control, cellular and biochemical markers of airway inflammation were measured in 19 subjects with poorly controlled asthma, 16 subjects with asthma under control and eight normal volunteers. The severity of asthma was mild-to-moderate persistent in 23 patients (14 poorly controlled) and severe prednisone-dependent in 12 subjects (five poorly controlled). Induced sputum was analysed for total and differential cell counts, leukotriene E4 (LTE4), eosinophil cationic protein (ECP), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin (IL)-8. Sputum eosinophils, LTE4, ECP and RANTES levels (but not IL-8) were significantly higher in patients with poorly controlled asthma as compared to patients with controlled asthma. By contrast, sputum cells and sputum inflammatory markers were not different among groups of patients with different severity of asthma. These results suggest that sputum eosinophilia is associated with poorly controlled asthma rather than with the severity of asthma.

Adult↗

Costs of asthma are correlated with severity: a 1-yr prospective study.

Asthma prevalence is increasing and asthma-related costs are likely to increase, but few studies have analysed the relationship of asthma costs and severity. The impact of severity on costs was quantified in a cohort of 318 asthmatic patients followed up prospectively for 1 yr. Patients presenting with a broad range of severity of the disease (intermittent, mild persistent, moderate persistent, severe persistent) were recruited by chest physicians throughout France and treated for 1 yr according to customary clinical practice and following international guidelines. Severity, direct and indirect costs, and quality of life (QoL) were assessed. A multivariate analysis was conducted to relate factors contributing to the costs measured. Mean direct costs for goods and services excluding hospitalization, numbers of consultations, supplementary examinations, and the use and cost of bronchodilators and corticosteroids, indirect costs of days lost from work, and adverse QoL parameters all increased significantly with increasing severity. This also applied to mean age, body weight, asthma duration, depression of forced expiratory volume in one second, and inhaled corticosteroid posology in the 234 patients completing the study. There was a significant relationship (r=0.614, p<0.001) between direct costs (hospitalization and cures were excluded) and three domains of the QoL questionnaire (mobility, pain and energy). Overall costs of asthma (including individual direct costs, indirect costs, and intangible quality of life costs) are clearly related to severity. This is the first study in asthma to combine rigorous independent classification of grades of severity in statistically valid numbers of patients of grades receiving "real-world" treatment and followed-up prospectively for 1 yr. It allowed severity to be accurately related to direct, indirect and intangible costs of asthma. Quality of life explained a significant part of these costs.

Adolescent↗

[Recommendations for the management of asthma].

Recommendations for the management of asthma have been proposed for the last 15 years around the world. These recommendations have been internationalised and the latest one, the Global Initiative for Asthma (GINA) is a World Health Organisation--National Institutes of Health initiative. Asthma recommendations were initially based on opinion of experts but the newest will be evidence-based. The GINA guidelines concern diagnosis, assessment of severity and treatment of asthma. They include all parts of asthma treatment: allergen avoidance, immunotherapy, pharmacotherapy and education. These guidelines are applied in over 100 countries worldwide, and, in countries where they are applied, morbidity and mortality due to asthma have decreased.

Anti-Inflammatory Agents↗