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During the first wave of COVID-19, nearly 50% of France's fatalities occurred in nursing homes. Older people with mental health disorders are considered to be more prone to infections when epidemics arise. To test this hypothesis, we conducted a retrospective descriptive and comparative study of the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a cohort of elderly residents with or without severe mental illness (SMI) living in a French nursing home facility. This was done during the first lockdown from March 17th until May 11th, 2020. Our study included 72 participants of 75 residents, of whom 58 contracted COVID-19, 14 developed a severe form requiring hospitalisation, and 14 died. The disease was significantly less frequent in residents with SMI 15(62%) than those without SMI 43 (89.6%). In regression analysis, a higher level of autonomy was significantly associated with a lower disease incidence. Once contracted, residents with or without SMI differed significantly neither on morbidity nor mortality. The period of survival did not either significantly differ between the two groups. As a potential explanation, we suggested that pathological social withdrawal added to stigmatisation could have protected SMI residents from contracting the disease.

Grimfeld Alain. Information scientifique en matière médicale. In: Raison présente, n°188, 4e trimestre 2013. Croyance et connaissance. pp. 43-49.

Background 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. Objective The potential effect of short-term personal exposure to particulate matter with a diameter of less than 2.5 μm (PM2.5) on nasal inflammation was examined in children living in the Paris area. Methods 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, α1-antitrypsin, IL-6, and IL-8) mediators. Results 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 α1-antitrypsin concentrations after adjustment for confounders (age, sex, house dust mites, pollens, cat, environmental tobacco smoke through urinary cotinine, barometric pressure, and respiratory infection). Conclusion The association observed with the percentage of eosinophils supports recent speculations on fine particle involvement in allergic phenotype overexpression. Clinical implications 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.

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 (P0.0001). 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.

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.

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. Pediatr Pulmonol. 1998; 26:106–112. © 1998 Wiley-Liss, Inc.

Summary A 2-year-old male infant suffering from pulmonary alveolar proteinosis was treated by four unilateral bronchoalveolar lavages (BAL) in a 12-month period. The lavages were performed under general anaesthesia and controlled ventilation by introducing a fibrescope (3.6 mm external diameter) though either a tracheal tube (4.5 mm internal diameter) or a rigid bronchoscope. Each lobe of the lung was successively catheterized and the segments were washed separately with prewarmed saline solution injected through the side channel of the fibrescope. The described technique allows to perform BAL in safe conditions (i.e., controlled airways) in infants weighing more than 9 kg.

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 eosinophiliaor=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.

International audience; The precautionary principle has been the subject of a heated debate in recent months in France, not least because it was mentioned in the Environmental Charter discussed by the French Parliament in 2005, and included in the French constitution. In this context, the French Committee for Prevention and Precaution has issued a position paper-presented hereafter-in order to remind legislators and the public of the essential rationale of the precautionary principle, as the committee conceives it. The Committee for Prevention and Precaution (CPP) is an advisory body to the French Ministry of the Environment (now Ministry of Ecology and Sustainable Development), which was created by a Ministerial Decree on 30 July 1996 with the aim of contributing to giving sound foundations to the Ministry's policies in matters related to risk prevention and precaution; detecting, and providing warning and expertise on health issues related to disruptions in the environment; and creating a linkage between scientific research and knowledge on one hand, and regulatory action on the other. Its operational resources are provided by the Ministry's Department of Economic Studies and Environmental Assessment. The CPP is comprised of 19 scientific experts from the field of health and environment, and chaired by Professor Alain Grimfeld.

To evaluate the relationship between clinical parameters and differential cell counts, bronchoalveolar lavage was performed in 79 asthmatic infants and children with unusual asthma. Multivariate analysis showed significant associations between (1) allergic asthma and the presence of alveolar eosinophils and (2) persistent and longer asthma and an increased number of alveolar neutrophils. Our results provide the first evidence that in asthmatic infants and children eosinophilic inflammation is related to allergic sensitization.

Right pneumonectomy can lead to severe respiratory impairment due to stenosis of the left main bronchus. This syndrome is usually treated by inserting a fixed-volume prosthesis but, in children, expandable prostheses have the advantage of being adaptable to growth and permit progressive recentering of the mediastinum. We report 3 such cases, with the results of pulmonary function tests. The patients were aged 11, 17, and 22 years at the time of implantation and had undergone pneumonectomy during childhood for either bronchiectasis or complete pulmonary sequestration. All 3 patients are doing well, with a follow-up of 1 to 3 1 2 years. Pulmonary function tests have shown a substantial improvement in the obstructive syndrome in 2 patients whereas, in the third patient, in whom the contralateral lung was not perfectly healthy, the functional improvement was only moderate.

The clinical course of sarcoidosis in children has not been well defined. Eight children with symptomatic sarcoidosis included in this study underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and during steroid therapy. At the start of therapy, functional parameters, mostly dynamic lung compliance and lung transfer factor for CO, were impaired. This was associated with abnormalities of BAL cell populations: increased total cell number with a high proportion of lymphocytes, modifications of lymphocyte subpopulation with an elevated CD4+/CD8+ ratio, and enhanced ability of alveolar macrophages to release hydrogen peroxide. Although respiratory abnormalities seemed to be similar at the initial stage of sarcoidosis in children and adults, the course of the disease appeared to be different. Despite the absence of respiratory symptoms and disappearance of chest radiographic abnormalities on prolonged steroid treatment, we found slow improvement of pulmonary functions associated with persistence of BAL lymphocytosis and elevated CD4+/CD8+ ratios. However, the ability of alveolar macrophages to release hydrogen peroxide was significantly reduced after 6 months of steroid treatment, and it remained identical to the control group. Therefore, the evaluation of disease activity appears to be critical for therapy in pediatrics, and for this purpose studies of alveolar macrophage activation may be of particular interest. Pediatr Pulmonol. 1993; 16:41–47. © 1993 Wiley-Liss, Inc.

A discussion between Paul-Henri Bourrelier (Ingenieur general des Mines), Alain Grimfeld, (chairman of the Comite Consultatif National d’Ethique), Yves le Bars (president of GRET, a professional association of solidarity and international cooperation) and Claudine Schmidt-Laine (scientific director of CEMAGREF).

Rationale As proteins are the ultimate effectors of gene expression, we have applied an innovative antibody-based approach to the identification of serum secreted protein markers in pediatric asthma. Methods In this asthmatic population we have analyzed various asthma phenotypes according to: i) asthma severity (persistent mild or persistent moderate); ii) asthma duration (less than 5 years or more); and iii) allergic phenotype (allergic sensitization or not). We have used: i) Milagen's collection of about 100,000 high affinity polyclonal antibodies raised against individual human proteins and their isoforms; ii) Milagen's proprietary matrix protein array technology (MPAT), comprising a multiplex protein immunoassay coupled to a readout and data analysis system. Results Asthma serum samples (up to 50 per group) and healthy controls were printed on a membrane, and allowed to interact with individual antibodies. Antibody-sample reaction was detected by chemiluminescence, and computer analysis of a CCD-acquired image quantified each spot. Statistical analysis of the data points thus generated, resulted in the selection of antibody panels that specifically recognize differentially secreted markers in asthma. Such antibodies are then used to identify corresponding protein antigens as molecular determinants of asthma. Among them, we have found proteins previously associated with asthma, as well as novel ones. Conclusions This approach enables us to: i) identify antibodies discriminating intermediate asthma phenotypes, and ii) discover proteins correlating with such phenotypes. These biomarkers offer potential application in prognosis, treatment response, and clinical trial follow-up.

Children are exposed to indoor and outdoor air pollution. Whereas normal children can suffer such air condition without long term sequellae, other children at risk can develop, since infancy, bronchopulmonary disease either because of bad conditions of life or congenital or hereditary causes.

Fourteen children aged between 6 months and 7 years (mean age = 3.5 years) were treated by CO2 broncholaser in the ENT Department of Trousseau Hospital. Three groups of diagnostic indication were identified: 1. Granulomas treated after mucosal trauma (tracheotomy, foreign body). 2. Granulomas due to pulmonary and/or lymph node tuberculosis. 3. Adhesions and stenosis secondary to neonatal ventilation. The operative and anesthetic technique is described in detail, together with any possible adverse events. The CO2 broncholaser appears to be a technique of choice in this age group, in which the narrowness of the airways makes any endoscopic procedure difficult. The broncholaser allows the early treatment of obstructive tracheobronchial pathology with its risks of severe ventilatory sequelae.

• Kaposi's sarcoma has only rarely been reported in children with acquired immunodeficiency syndrome. In contrast to adult patients, in whom the disease is predominantly cutaneous, among pediatric patients with acquired immunodeficiency syndrome, Kaposi's sarcoma is primarily limited to the lymphadenopathic form. We describe two children with the acquired immunodeficiency syndrome who developed diffuse nodular skin lesions of Kaposi's sarcoma. ( Arch Dermatol. 1990;126:791-793)

International audience; The ability of alveolar macrophages (AM) to release O2 metabolites was studied in 8 children with interstitial lung disease (ILD), and in 11 children without lung parenchyma disorder. AM were collected by bronchoalveolar lavage. The experiments were performed on unstimulated AM and on AM stimulated by phorbol myristate acetate (PMA) or zymosan. Our results indicated that, with or without triggering agent, the amount of O2 metabolites release was a linear function pattern with time. The accumulation of superoxide anion (O2-) and hydrogen peroxide (H2O2) into the extracellular medium differed depending on the triggering agent used: with PMA, the amount of O2- released was threefold the amount of H2O2 detected in the medium, whereas with zymosan the O2- accumulation was tenfold higher than the amount of H2O2 measured. In patients with ILD, a significant increase in the amount of H2O2 release was observed for both unstimulated and stimulated AM (p less than 0.001). In this group, the measurement was repeated after a 2-month steroid treatment: prednisone had markedly improved the clinical, radiologic, and functional status of the patients, and this improvement was in good correlation with the decrease of O2 metabolite production. The amount of H2O2 release in each case was within the range of control values. Evaluation of O2 metabolite release by AM could be a useful parameter in the assessment of the activity of ILD.

The ability of alveolar macrophages (AM) to release hydrogen peroxide (H2O2), an indicator of AM function, was studied in five children with the acquired immunodeficiency syndrome (AIDS) related complex and, for comparison, in 11 children without disorders of the lung parenchyma. In the AIDS-related complex group, pulmonary manifestations were mild, and lung involvement was suspected by moderate clinical and/or radiological features. None had a past history of opportunistic infections; neither did any have lymphopenia. Cytologic study of the bronchoalveolar lavage (BAL) fluid revealed increased cellularity with increased percentage of lymphocytes. The study of H2O2 release was performed on unstimulated AM and on AM stimulated by phorbol myristate acetate (PMA). Under both experimental conditions, the amount of H2O2 accumulated in the medium was significantly increased in the group with AIDS-related complex (P less than 0.001). As no enhanced oxidative activity has been reported in AM from patients with full-blown AIDS, an increased ability of AM to release oxygen metabolites from children with AIDS-related complex may reflect an initial and temporary step in the course of the LAV/HTLV-III pulmonary disease. Determining AM activation might be a reliable method of assessing the evolution of lung disorder in AIDS.

Bronchoalveolar lavage (BAL) was performed on 12 infants who had recovered from neonatal acute respiratory failure and on 12 patients with bronchopulmonary dysplasia (BPD) in order to evaluate the concentration of phosphatidyl choline (PC) in BAL fluid These two groups were similar at birth (mean birth weight: 1,980 and 1,750 g, respectively; mean gestational age: 33.4 and 32.1 weeks respectively). Mechanical ventilation based on oxygen requirement lasted longer in the group with BPD. BAL was performed at the end of the first year of life (at 8.5 and 10.3 months, respectively) and the results were compared to control values (from infants of the same age without neonatal disease). Whereas the protein concentration in BAL fluid was similar in the two groups, a dramatic decrease of the BAL PC was found in BPD: The mean values of BAL-PC over protein ratio were 0.9 in the group without pulmonary sequelae and 0.3 in the group with BPD These preliminary results suggest an impairment of the pulmonary surfactant metabolism in this chronic lung disease following neonatal acute respiratory failure. Pediatr Pulmonol 1987; 3:67–70.

T he Epidemiologic Study on the Genetics and Environment of Asthma (EGEA) was planned to assess genetic and environmental risk factors and their interactions in patients with asthma and for the two related traits of bronchial hyperresponsiveness and atopy. The study was performed from 1991 to 1995 and combined a case control study and a study of the families of the asthmatic patients. A synthesis of the results already obtained is presented. Smoking was related to IgE levels, even in asthma patients. Smoking was clearly related to the clinical severity of the asthma, which is clinically insufficiently taken into account. The relationships of occupational exposures to asthma have been assessed using a job exposure matrix. Segregation analyses of IgE have shown, after correction for the mode of ascertainment, the existence of a dominant major gene and a familial residual correlation. A systematic genome screen used in families with two asthmatic siblings showed a linkage of various regions in the genome that are related to asthma or related phenotypes (ie, 1p, 11p, 11q, 12q, 13q, 17q, and 19q), results that are in agreement with those of genome screens used in other studies. Regarding candidate genes, no association was shown between asthma and the F508 mutation of the cystic fibrosis gene. The analysis is still in progress with studies on the heterogeneity of asthma, with refined genetic studies, and by searching to integrate the results regarding environmental and genetic factors and studying their interactions.

International audience; 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.