[Introduction of an anticholinesterase drug in the context of myasthenia, in a severe asthmatic patient]. / Introduction d'un anticholinestérasique dans le contexte d'une myasthénie, chez une patiente asthmatique sévère.

Association of asthma with myasthenia gravis presents a twofold peculiarity. First, as dyspnea characterizes both conditions, diagnostic orientation is difficult. Second, from a therapeutic standpoint, the initiation of anticholinesterase treatment requires a multidisciplinary approach due to possible contraindication for asthma. We report on the case of a patient monitored for severe asthma and treated with biotherapy, and also monitored for myasthenia gravis, and treated with anticholinesterase.

[Hamartochondroma: An unusual cause of endobronchial obstruction in smoking patients]. / L'hamartochondrome : cause inhabituelle d'obstacle endobronchique chez des patients fumeurs.

Endobronchial hamartochondroma is a rare benign tumor which differs from the parenchymal form in its symptomatology and also by its treatment which should be as conservative as possible. The endobronchial location is exceptional. Here we present the cases of two patients with endobronchial hamartochondroma associated with clinical manifestation, chest pain and repeated pulmonary infections, respectively. The diagnosis was made after performing a CT-scan, a PET-SCAN and histological analysis. After discussion in a multidisciplinary staff meeting, conservative treatment was chosen in both cases.

[Management of non-small cell lung cancer patients harboring activating mutations and CNS progression]. / Caractéristiques et prise en charge de l'évolutivité cérébro-méningée des cancers bronchiques dans un contexte de mutation activatrice.

The central nervous system (CNS), through carcinomatous meningitis or solid brain metastases, is the most common site of recurrence in non-small cell lung cancers (NSCLC) with activating mutations. Our retrospective study describes the population of patients with CNS metastases of NSCLC harboring activating mutation with targeted therapy (EGFR, ALK, BRAF, HER2) in 4 French regional reference hospitals. 60 patients were analyzed. The proposed treatments were heterogeneous and included combinations of chemotherapy, targeted therapy and radiotherapy±associated with topical treatments. Median overall survival following CNS metastasis in these patients was 15.8 months for meningitis carcinoma and 26 months for brain metastases. In patients with brain metastases, the addition of targeted therapy treatment allows a significant improvement in median progression free survival from 5.9 months to 10.6 months (HR 0.48 CI95 [0.24 to 0.97] P=0.035). These patients seem therefore benefit from systemic therapy and particularly targeted therapy with better survival than usual.

Pesticides Exposure by Air in Vineyard Rural Area and Respiratory Health in Children: A pilot study.

RATIONALE: Asthma, frequently associated with rhinitis, is the most common chronic disease in children, and a significant role is played by a range of environmental exposures. Among them, air pollution is of foremost concern. However, little is known about the impact of airborne pesticide exposure on children's respiratory health in rural areas. The objective of this study was to analyze the association between airborne pesticide exposure and asthma and rhinitis in children. METHODS: In a French vineyard rural area, children (3-10 years old) from 4 selected schools were invited to participate in this study over two periods: winter, with no or low air pesticide levels, and summer when fields are frequently treated with pesticides. Two health outcomes were considered: asthma and rhinitis symptoms (ISAAC questionnaire), and peak expiratory flow (PEF). A quantitative score of symptoms was built. Exposure to pesticides was evaluated 1) by measuring 56 pesticides in the ambient outdoor air around schools in the two periods and building a cumulative exposure index, and 2) by measuring ethylenethiourea (ETU) concentrations in urine in a subsample of children (n = 96), ETU being a urine biomarker of exposure to dithiocarbamates fungicides. Next, the association between pesticide exposure and respiratory health was studied using a logistic regression model, adjusted for confounders and respiratory status at baseline. RESULTS: 281 children participated in the study (47% girls, mean age: 7.5 yrs). 25% of the children were living on a farm. 22% had experienced wheezing at least once. 15.8% had asthma diagnosed by a doctor, 12% had current asthma and 35% had allergic rhinitis. The main pesticides detected in the ambient outdoor air around schools were fungicides (89,3%; mainly folpet and dithiocarbamates) and insecticides (10.6%). No association was found between the symptom score and pesticides in the outdoor air around schools during summer, when pesticides were applied to vineyards. However, an association was found between ETU urinary concentration (>0.974 µg/g creatinine) and asthma and rhinitis symptoms (OR=3.56; IC 95% 1.04-12.12). This result could be explained by extracurricular exposure, which was not considered in our air measurements in the schools. No association was found between peak expiratory flow and exposure to pesticides in the air. CONCLUSIONS: Children living in vineyard rural areas are at a higher risk of airborne dithiocarbamates exposure during the summer period. Despite the limited size of our sample, our results suggest possible links between some pesticide measurements and respiratory and allergic symptoms such as rhinitis.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.

OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

Dyspnea: a strong independent factor for long-term mortality in the elderly.

OBJECTIVE: To determine the association between dyspnea at entry into the PAQUID cohort and 13-year mortality, taking into consideration BMI and other mortality-related factors. DESIGN: Longitudinal study. SETTING: In Dordogne and Gironde, South Western France. SUBJECTS: A total of 3646 French community dwellers aged 65 years old and over from the PAQUID study were included. MAIN OUTCOME MEASURES: dyspnea measured on 5-grades scale, mortality measured over 13 years of follow-up. Adjustment variables: age, gender, BMI (kg/m²), antecedent of ischemic heart disease, antecedent of stroke, hypertension, smoking history and diabetes. RESULTS: The study sample included 3646 subjects out of whom 54.11% died at 13 years of follow-up, 57.3% of participants were women and mean age was 75.3 (SD 6.8) years. Univariate analysis showed that dyspnea was associated with 13-year mortality. Death occurred in 45.6% of non-dyspneic subjects , 51.8% in those with level 1 of dyspnea, 65.6% in level 2 and 80.6% in level 3 and 4 (P<10⁻4). The median survival was at 13.26 (SD 0.20) years for level-0 of dyspnea, 12.33 (SD 0.31) years for level-1 of dyspnea, 9.28 (SD 0.44) years for level-2 and 6.43 (SD 0.45) years for level-3 and 4 (P=10⁻³). In the multivariate analysis, the risk of mortality for level1 compared to level-0 was HR=1.13 (CI95%=[1.01-1.26]); this risk increases to HR=1.42 (CI95%=[1.25-1.63]) for level-2 and to HR=1.90 (CI95%=[1.61-2.25]) for level-3 and 4. CONCLUSION: These findings suggest that the relationship between long-term mortality and dyspnea is strong, consistent and independent of other covariates in the elderly.

[Chronic central nervous system effects of pesticides: state-of-the-art]. / Effets chroniques des pesticides sur le système nerveux central : état des connaissances épidémiologiques.

BACKGROUND: Given the neurotoxic properties of pesticides, suggested by experimental results and clinical observations, many epidemiological studies have investigated neurological effects following acute or chronic exposure to pesticides. This review provides an overview of current knowledge about pesticide effects on the central nervous system: neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis), cognitive disorders, and psychiatric disorders (mood disorders, anxiety, depression and suicide). RESULTS: Parkinson's disease, the most widely studied in relation with pesticide exposure, particularly with insecticides and herbicides, was observed to be a risk factor of the disease. Evidence is scarce for Alzheimer's disease and amyotrophic lateral sclerosis, but quite consistent. Cognitive and psychiatric disorders were often observed in relation with organophosphate insecticide exposure. Cognitive disorders were found associated with acute and chronic exposures, and psychiatric disorders mostly with poisonings. These epidemiologic studies were limited by a lack of detailed and reliable exposure assessment. The role of genetic susceptibilities has been recently observed, but must be further investigated.

First data on direct costs of lung cancer management in Morocco.

BACKGROUND: Lung cancer is the leading cause of cancer morbidity and mortality. Its management has a significant economic impact on society. Despite a high incidence of cancer, so far, there is no national register for this disease in Morocco. The main goal of this report was to estimate the medical costs of lung cancer in our country. METHODS: We first estimated the number of annual new cases according to stage of the disease on the basis of the Grand-Casablanca-Region Cancer Registry data. For each sub-group, the protocol of treatment was described taking into account the international guidelines, and an evaluation of individual costs during the first year following diagnosis was made. Extrapolation of the results to the whole country was used to calculate the total annual cost of treatments for lung cancer in Morocco. RESULTS: Overall approximately 3,500 new cases of lung cancer occur each year in the country. Stages I and II account for only 4% of cases, while 96% are diagnosed at locally advanced or metastatic stages III and IV. The total medical cost of lung cancer in Morocco is estimated to be around USD 12 million. This cost represents approximately 1% of the global budget of the Health Department. According to AROME Guidelines, about 86% of the newly diagnosed lung cancer cases needed palliative treatment while 14% required curative intent therapy. The total cost of early and advanced stages lung cancer management during the first year were estimated to be 4,600 and 3,420 USD, respectively. CONCLUSION: This study provides health decision-makers with a first estimate of costs and the opportunity to achieve the optimal use of available data to estimate the needs of health facilities in Morocco. A substantial proportion of the burden of lung cancer could be prevented through the application of existing cancer control knowledge and by implementing tobacco control programs.

[Are there specific characteristics of COPD in women?]. / Existe-t-il des spécificités chez les femmes atteintes de BPCO ?

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a disorder resulting from an interaction between a genetic predisposition, still poorly understood, and the impact of environmental factors including tobacco smoke or professional or domestic air contaminants. BACKGROUND: The prevalence of COPD in the world concerns women as much as men, but it remains under diagnosed among women smokers. The mortality data show an increase in mortality among women compared to men. It thus seems that COPD in women presents more often a particular phenotype, characterized more by bronchial attacks than by emphysema, and by more marked functional effects on the quality of life. Anxiety and depression seem more marked with further repercussions on the quality of life. The effectiveness of treatment may be different, in particular with regard to nicotine weaning and respiratory rehabilitation. VIEWPOINT AND CONCLUSIONS: In the evaluation of chronic diseases in women little is known about COPD. Further studies, focusing specifically on these differences, are needed in order to improve the diagnosis and management of COPD in women.

Early life origins of chronic obstructive pulmonary disease.

BACKGROUND: Early life development may influence subsequent respiratory morbidity. The impact of factors determined in childhood on adult lung function, decline in lung function and chronic obstructive pulmonary disease (COPD) was investigated. METHODS: European Community Respiratory Health Survey participants aged 20-45 years randomly selected from general populations in 29 centres underwent spirometry in 1991-3 (n = 13 359) and 9 years later (n = 7738). Associations of early life factors with adult forced expiratory volume in 1 s (FEV(1)), FEV(1) decline and COPD (FEV(1)/FVC ratio <70% and FEV(1) <80% predicted) were analysed with generalised estimating equation models and random effects linear models. RESULTS: Maternal asthma, paternal asthma, childhood asthma, maternal smoking and childhood respiratory infections were significantly associated with lower FEV(1) and defined as "childhood disadvantage factors"; 40% had one or more childhood disadvantage factors which were associated with lower FEV(1) (men: adjusted difference 95 ml (95% CI 67 to 124); women: adjusted difference 60 ml (95% CI 40 to 80)). FEV(1) decreased with increasing number of childhood disadvantage factors (> or =3 factors, men: 274 ml (95% CI 154 to 395), women: 208 ml (95% CI 124 to 292)). Childhood disadvantage was associated with a larger FEV(1) decline (1 factor: 2.0 ml (95% CI 0.4 to 3.6) per year; 2 factors: 3.8 ml (95% CI 1.0 to 6.6); > or =3 factors: 2.2 ml (95% CI -4.8 to 9.2)). COPD increased with increasing childhood disadvantage (1 factor, men: OR 1.7 (95% CI 1.1 to 2.6), women: OR 1.6 (95% CI 1.01 to 2.6); > or =3 factors, men: OR 6.3 (95% CI 2.4 to 17), women: OR 7.2 (95% CI 2.8 to 19)). These findings were consistent between centres and when subjects with asthma were excluded. CONCLUSIONS: People with early life disadvantage have permanently lower lung function, no catch-up with age but a slightly larger decline in lung function and a substantially increased COPD risk. The impact of childhood disadvantage was as large as that of heavy smoking. Increased focus on the early life environment may contribute to the prevention of COPD.

Do childhood respiratory infections continue to influence adult respiratory morbidity?

The aim of the present study was to examine the influence of childhood respiratory infections on adult respiratory health. In 1992-1994, the European Community Respiratory Health Survey recruited community based samples of 20-44-yr-old people from 48 centres in 22 countries. Study participants completed questionnaires and underwent lung function testing. On average, 8.9 yrs later, 29 centres re-investigated their samples using similar methods. Mixed effects models comprising an estimate for the random variation between centres were used to evaluate the relevant associations. In total, 9,175 patients participated in both studies, of whom 10.9% reported serious respiratory infections (SRI) before 5 yrs of age and 2.8% reported hospitalisation for lung disease (HLD) before 2 yrs if age. SRI was associated with current wheeze (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.7-2.2), asthma (OR 2.5, 95% CI 2.2-3.1), and lower forced expiratory volume in one second (FEV(1); 89 mL; 95% CI 54-126), forced vital capacity (FVC; 49 mL; 95% CI 8-90) and FEV(1)/FVC ratio (-1.2%; 95% CI -1.8- -0.6). Childhood respiratory infections were also associated with new asthma (OR 1.5, 95% CI 1.03-2.0), new wheeze (OR 1.5, 95% CI 1.0-2.4) and persistent wheeze (OR 2.2, 95% CI 1.4-3.6) but not with a decline in lung function. Similar findings were observed for HDL. These associations were significantly consistent across centres. SRI was associated with lower FEV(1) when excluding ever asthmatics and current wheezers. The impact of early infections was significantly larger in subjects exposed to maternal or active smoking. The impact of childhood respiratory infections on the respiratory system may not only last into adulthood but also influence development and persistence of adult respiratory morbidity.

Epidemiology of COPD.

Chronic obstructive pulmonary disease (COPD) is responsible for early mortality, high death rates and significant cost to health systems. The projection for 2020 indicates that COPD will be the third leading cause of death worldwide (from sixth in 1990) and fifth leading cause of years lost through early mortality or handicap (disability-adjusted life years) (12th in 1990). Active smoking remains the main risk factor, but other factors are becoming better known, such as occupational factors, infections and the role of air pollution. Prevalence of COPD varies according to country, age and sex. This disease is also associated with significant comorbidities. COPD is a disorder that includes various phenotypes, the continuum of which remains under debate. The major challenge in the coming years will be to prevent onset of smoking along with early detection of the disease in the general population.