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Resumen: Introducción y objetivo: El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método: Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados: En el análisis univariado, la recidiva tumoral (p

Background and objective: Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods: Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results: In the univariate analysis, tumor recurrence (P

The Water Framework Directive (WFD) was adopted in 2000 and is a common framework for water policy, management and protection in Europe. The WFD assesses specific parameters; however, it ignores indicators of ecosystem functioning and sub-individual performance. Reservoirs are strongly influenced by anthropogenic activities that promote their imbalance. Bioassays and biomarkers are useful tools to link the chemical, ecological and toxicological assessments in water quality assessments. These approaches can be complementary to WFD methodologies, allowing the detection of impacts on the ecosystem. This study evaluated if the biochemical parameters can improve the sensitivity of the biomonitoring strategy using bioassays with the standard species Daphnia magna, in the assessment of the ecological quality of water reservoirs. To this end, water samples of Portuguese reservoirs were analysed in three sampling periods (Autumn 2018 and Spring, Autumn 2019). In parallel, a physicochemical characterization of waters was performed. D. magna feeding rate assays were performed for 24 h. After exposure, metabolism, oxidative stress and lipid peroxidation biomarkers were evaluated. Feeding rate assays showed sensitivity to different reservoirs. Biomarkers showed a higher sensitivity and can therefore improve the sensitivity of the biomonitoring strategy using bioassays. Bioassays and biomarkers approach allowed to highlight potential sources of stress, more related to the quality of the seston than to chemical contamination. This work highlights the complementarity between bioassays and biomarkers to identify ecotoxicological effects of surface waters, and can be extremely useful, especially in cases where the biotic indices are difficult to establish, such as reservoirs.

To assess the ecological potential (EP), the Water Framework Directive (WFD) uses specific parameters but ignores ecosystem functioning and individual/subindividual biological responses. The heavily modified water bodies (reservoirs) are strongly influenced by human activities that promote their imbalance, with a loss or compromise the biodiversity and the functioning of these ecosystems. This work aims to determinate the EP according physical, chemical and biological parameters of WFD and evaluate the functionality and sensitivity of ecotoxicological tools in the evaluation of water quality of Aguieira reservoir. Four sampling sites were defined in Aguieira reservoir and sampling was conducted in autumn 2018, spring and autumn 2019. WFD showed overall that Aguieira reservoir presented moderate EP. The autumn samples and the two reservoir upstream sites had the worst classification. These results were complemented by a set of ecotoxicological assays (growth inhibition of Raphidocelis subcapitata and Spirodela polyrhiza, and feeding rate of Daphnia longispina) using three natural water treatments. R. subcapitata was the most sensitive species, indicating the presence of a risk that is not detected by chemical analysis, nor by organisms of different trophic levels. D. longispina only showed sensitivity in A3 and A4 in autumn, however this results was difficult to interpret since no reason can be observed to respond the F1 lower feeding rate observed in almost sites. S. polyrhiza, as well as the total chlorophyll, lipid peroxidation, and proline content did not show sensitivity, since no discrimination among the water treatments were recorded. The relevance of bioassays is associated with the fact that an integrated response to a complex mixture can be obtained, which can contain more substances than the measured ones. Thus, we may conclude that WFD are insufficient to draw conclusions about water quality, and the growth inhibition of Raphidocelis subcapitata assay is an important parameter to complement the WFD. In addition, species of different trophic levels are recommended for ecotoxicological analyses due to differences in species sensitivities.

Chemical cleaning is routinely performed in reverse osmosis (RO) plants for the regeneration of RO membranes that suffer from biofouling problems. The potential of urea as a chaotropic agent to enhance the solubilization of biofilm proteins has been reported briefly in the literature. In this paper the efficiency of urea cleaning for RO membrane systems has been compared to conventionally applied acid/alkali treatment. Preliminary assessment confirmed that urea did not damage the RO polyamide membranes and that the membrane cleaning efficiency increased with increasing concentrations of urea and temperature. Accelerated biofilm formation was carried out in membrane fouling simulators which were subsequently cleaned with (i) 0.01M sodium hydroxide (NaOH) and 0.1M hydrochloric acid (HCl) (typically applied in industry), (ii) urea (CO(NH2)2) and hydrochloric acid, or (iii) urea only (1340 g/Lwater). The pressure drop over the flow channel was used to evaluate the efficiency of the applied chemical cleanings. Biomass removal was evaluated by measuring chemical oxygen demand (COD), adenosine triphosphate (ATP), protein, and carbohydrate content from the membrane and spacer surfaces after cleaning. In addition to protein and carbohydrate quantification of the extracellular polymeric substances (EPS), fluorescence excitation−emission matrix (FEEM) spectroscopy was used to distinguish the difference in organic matter of the remaining biomass to assess biofilm solubilization efficacy of the different cleaning agents. Results indicated that two-stage CO(NH2)2/HCl cleaning was as effective as cleaning with NaOH/HCl in terms of restoring the feed channel pressure drop (>70% pressure drop decrease). One-stage cleaning with urea only was not as effective indicating the importance of the second-stage low pH acid cleaning in weakening the biofilm matrix. All three chemical cleaning protocols were equally effective in reducing the concentration of predominant EPS components protein and carbohydrate (>50% reduction in concentrations). However, urea-based cleaning strategies were more effective in solubilizing protein-like matter and tyrosine-containing proteins. Furthermore, ATP measurements showed that biomass inactivation was up to two-fold greater after treatment with urea-based chemical cleanings compared to the conventional acid/alkali treatment. The applicability of urea as an alternative, economical, eco-friendly and effective chemical cleaning agent for the control of biological fouling was successfully demonstrated. Keywords: Reverse osmosis, Biofouling, Membrane fouling simulator, Chemical cleaning, Urea

Background: A French national survey showed that 1447 children were treated with long-term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in 2019. Data about the ventilatory settings for children are scarce. The aim of the study was to report the CPAP/NIV settings from the survey according to the patients' age and disorders., Methods: CPAP and NIV settings were compared between 5 age groups (<1, 1-5, 6-11, 12-17 and ≥ 18 years), and 6 disease categories (upper airway disorders; neuromuscular disease, NMD; disorder of the central nervous system; cardiorespiratory disorder; congenital bone disease, CBD; and other)., Results: Age correlated positively with constant CPAP pressure (r = 0.364, p < 0.0001), and negatively with CPAP adherence (r = -0.173, p < 0.0001). Mean age at CPAP initiation, CPAP pressures and adherence did not differ between disorders. Regarding NIV, mean inspiratory positive airway pressure (IPAP) increased with age (r = 0.152, p = 0.0001), whereas respiratory rate (RR; r = -0.593, p < 0.0001) and adherence to NIV decreased with age (r = -0.154, p = 0.0002). NIV settings were quite similar between disease categories, with the CBD group having the highest IPAP, and NMD group having the lowest expiratory positive airway pressure and RR. Adherence tended to be higher with NIV than CPAP., Conclusions: CPAP pressure and IPAP increase with age, while settings seem quite similar between diseases. Even if our study provides some information about CPAP/NIV settings, they should always be individually adapted according to the severity of the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) is an ultra-rare autosomal recessive neurometabolic disorder caused by ALDH5A1 mutations presenting with autism and epilepsy. Here, we report the generation and characterization of human induced pluripotent stem cells (hiPSCs) derived from fibroblasts of three unrelated SSADHD patients - one female and two males with the CRISPR-corrected isogenic controls. These individuals are clinically diagnosed and are being followed in a longitudinal clinical study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Darius Ebrahimi-Fakhari reports a relationship with National Institutes of Health that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: While strong evidence supports adverse effects of pre-natal air pollution on child's lung function, previous studies rarely considered fine particulate matter (PM 2.5 ) or the potential role of offspring sex and no study examined the effects of pre-natal PM 2.5 on the lung function of the newborn., Aim: We examined overall and sex-specific associations of personal pre-natal exposure to PM 2.5 and nitrogen (NO 2 ) with newborn lung function measurements., Methods: This study relied on 391 mother-child pairs from the French SEPAGES cohort. PM 2.5 and NO 2 exposure was estimated by the average concentration of pollutants measured by sensors carried by the pregnant women during repeated periods of one week. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple breath washout (N 2 MBW) test, performed at 7 weeks. Associations between pre-natal exposure to air pollutants and lung function indicators were estimated by linear regression models adjusted for potential confounders, and then stratified by sex., Results: Mean exposure to NO 2 and PM 2.5 during pregnancy was 20.2 μg/m 3 and 14.3 μg/m 3 , respectively. A 10 μg/m 3 increase in PM 2.5 maternal personal exposure during pregnancy was associated with an adjusted 2.5 ml (2.3%) decrease in the functional residual capacity of the newborn (p-value = 0.11). In females, functional residual capacity was decreased by 5.2 ml (5.0%) (p = 0.02) and tidal volume by 1.6 ml (p = 0.08) for each 10 μg/m 3 increase in PM 2.5 . No association was found between maternal NO 2 exposure and newborns lung function., Conclusions: Personal pre-natal PM 2.5 exposure was associated with lower lung volumes in female newborns, but not in males. Our results provide evidence that pulmonary effects of air pollution exposure can be initiated in utero. These findings have long term implications for respiratory health and may provide insights into the underlying mechanisms of PM 2.5 effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The aim of the study was to analyze the weaning success, the type of weaning procedures, and weaning duration in consecutive infants hospitalized in a pediatric intensive care unit over a winter season., Methods: A retrospective observational study was conducted in a pediatric intensive care unit in a tertiary center. Infants hospitalized for severe bronchiolitis were included and the weaning procedure from continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or high-flow nasal cannula (HFNC) was analyzed., Results: Data from 95 infants (median age, 47 days) were analyzed. On admission, 26 (27%), 46 (49%), and 23 (24%) infants were supported with CPAP, NIV, and HFNC, respectively. Weaning failed in one (4%), nine (20%), and one (4%) infants while supported with CPAP, NIV, or HFNC, respectively (p = 0.1). In infants supported with CPAP, CPAP was stopped directly in five patients (19%) while HFNC was used as an intermediate ventilatory support in 21 (81%). The duration of weaning was shorter for HFNC (17 h, [IQR: 0-26]) than for CPAP (24 h, [14-40]) and NIV (28 h, [19-49]) (p < 0.01)., Conclusions: The weaning phase corresponds to a large proportion of noninvasive ventilatory support duration in infants with bronchiolitis. The weaning procedure following a "step-down" strategy may lead to an increase in the duration of weaning., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status., Objective: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations., Methods: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO 2 , PM 2.5 and PM 10 annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status., Results: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO 2 , PM 2.5 and PM 10 concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status., Conclusion: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations., Competing Interests: Declaration of competing interest MJA holds investigator initiated grants for unrelated research from Pfizer, Boehringer-Ingelheim, Sanofi and GSK. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi. He has also received a speaker's fee from GSK., (Copyright © 2022. Published by Elsevier B.V.)

Background: We assessed the diagnostic performances of homeostasis model assessment indices (HOMA) of β-cell function (HOMA-%β) and of insulin resistance (HOMA-IR) for cystic fibrosis related diabetes (CFRD) screening., Methods: Data were collected from a prospective cohort of 228 patients with CF (117 adults and 111 children). Fasting insulin and glucose levels were measured to calculate HOMA-%β and HOMA-IR. HOMA-%β <100 indicated insulin secretion deficiency and HOMA-IR >1 insulin resistance. Both were used to calculate sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Two-hour oral glucose tolerance tests (2h-OGTT) defined CFRD. Analyses were conducted separately for children and adults. Performances of HOMA-%β and HOMA-IR were calculated at inclusion, for each year of follow-up and for pooled data over the follow-up period., Results: Sensitivity, specificity, NPV and PPV were respectively: 88%, 45%, 98% and 11% for HOMA-%β and 42%, 48%, 91% and 6% for HOMA-IR in the pooled data of children; and 83%, 18%, 90% and 10% for HOMA-%β, and 39%, 80%, 92% and 18% for HOMA-IR in the pooled data of adults. Combining HOMA-%β and HOMA-IR did not improve performances., Conclusion: Within both age groups, HOMA-%β <100 provided good sensitivity and NPV. HOMA-IR >1 had low sensitivity. Calculation of the HOMA-%β could be an interesting first-line screening approach to exclude CFRD and thus avoid unnecessary OGTT in patients for whom value is ≥100. However, HOMA-%β<100 does not support the diagnosis of CFRD and should be complemented by OGTT., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier B.V.)

Objective: To describe the characteristics of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) in France., Design: Cross-sectional national survey., Setting: Paediatric CPAP/NIV teams of 28 tertiary university hospitals in France., Patients: Children aged <20 years treated with CPAP/NIV since at least 3 months on June 1st, 2019., Intervention: An anonymous questionnaire was filled in for every patient., Results: The data of 1447 patients (60% boys), mean age 9.8 ± 5.8 years were analysed. The most frequent underlying disorders were: upper airway obstruction (46%), neuromuscular disease (28%), disorder of the central nervous system (13%), cardiorespiratory disorder (7%), and congenital bone disease (4%). Forty-five percent of the patients were treated with CPAP and 55% with NIV. Treatment was initiated electively for 92% of children, while 8% started during an acute illness. A poly(somno)graphy (P(S)G) was performed prior to treatment initiation in 26%, 36% had a P(S)G with transcutaneous carbon dioxide monitoring (PtcCO 2 ), while 23% had only a pulse oximetry (SpO 2 ) with PtcCO 2 recording. The decision of CPAP/NIV initiation during an elective setting was based on the apnea-hypopnea index (AHI) in 41% of patients, SpO 2 and PtcCO 2 in 25% of patients, and AHI with PtcCO 2 in 25% of patients. Objective adherence was excellent with a mean use of 7.6 ± 3.2 h/night. Duration of CPAP/NIV was 2.7 ± 2.9 years at the time of the survey., Conclusion: This survey shows the large number of children treated with long term CPAP/NIV in France with numerous children having disorders other than neuromuscular diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures., Objective: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach., Methods: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV 1 ) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV 1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation<0.70) identified in step 1., Results: The ExWAS identified 21 factors showing suggestive association with FEV 1 (none significant when controlling for multiple tests). The sBPR conducted on 15 uncorrelated exposures identified in step 1, revealed 3 clusters composed of 30, 115 and 454 individuals with a mean ± SD FEV 1 (%pred) of 79% ± 21, 90% ± 19 and 93% ± 16, respectively. Cluster 1 was composed of individuals with heavy smoking, poor diet, higher outdoor humidity and proximity to traffic, while cluster 2 and 3 included individuals with moderate/low levels of exposure to these factors., Discussion: This exposome study identified a specific profile of joint lifestyle and environmental factors, associated with a low FEV 1 in adults with asthma. None of the exposures revealed significant association when considered independently., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study aimed to assess how the emergence of high-flow nasal cannula (HFNC) has modified the demographic and clinical characteristics as well as outcomes of infants with bronchiolitis admitted to a pediatric intensive care unit (PICU)., Methods: This was a single-center retrospective study including infants aged 1 day to 6 months with bronchiolitis requiring HFNC, noninvasive ventilation (NIV), or invasive ventilation on admission., Results: A total of 252 infants (mean age 53±36 days) were included in the study. The use of HFNC increased from 18 (21.4%) during 2013-2014 to 53 infants (55.2%) during 2015-2016. The length of stay in the PICU decreased over time from 4.7±2.9 to 3.5±2.7 days (P<0.01) but the hospital length of stay remained similar (P=0.17). On admission, patients supported by HFNC as the first-line therapy were older. The PICU length of stay was similar according to the type of respiratory support (P=0.16), but the hospital length of stay was longer for patients supported by HFNC (P=0.01)., Conclusion: The distribution of respiratory support has significantly changed over time for patients with bronchiolitis and HFNC is increasingly used. The demographic and clinical characteristics of the have not changed over time. However, the PICU length of stay decreased significantly., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry., Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV 1 /FVC ≥ Lower Limit of Normal and a FVC<80% predicted in two population-based studies (ECRHS-III and SAPALDIA3). Physical activity was measured using the International Physical Activity Questionnaire. The odds of having low physical activity (<1st study-specific tertile) was evaluated using adjusted logistic regression models., Results: Subjects with a restrictive spirometry pattern (n = 280/4721 in ECRHS, n = 143/3570 in SAPALDIA) reported lower levels of physical activity than those with normal spirometry (median of 1770 vs 2253 MET·min/week in ECRHS, and 3519 vs 3945 MET·min/week in SAPALDIA). Subjects with a restrictive spirometry pattern were more likely to report low physical activity (meta-analysis odds ratio: 1.41 [95%CI 1.07-1.86]) than those with a normal spirometry. Obesity, respiratory symptoms, co-morbidities and previous physical activity levels did not fully explain this finding., Conclusion: Adults with a restrictive spirometry pattern were more likely to report low levels of physical activity than those with normal spirometry. These results highlight the need to identify and act on this understudied but prevalent condition., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hypophosphatasia (HPP) is a rare disease resulting from alterations of the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). Perinatal HPP is mainly characterized by bone hypomineralization and severe respiratory insufficiency. We describe a full-term boy diagnosed with perinatal HPP after birth, showing dramatic improvement after treatment with Asfotase Alfa, an enzyme-replacement therapy (ERT) prescribed in HPP cases. He initially presented with respiratory insufficiency due to bone hypomineralization, and severe pulmonary hypoplasia that required tracheostomy and invasive ventilation for 8 months. He was taken off ventilation at 41 weeks of age. He also presented complications including hypercalcemia, craniosynostosis, nephrocalcinosis, hypotonia, and a severe feeding disorder. He is still alive at 30 months of age, and his respiratory status and tonus is steadily improving. This case reflects the progression of HPP patients with specific therapy added to symptomatic management. Some aspects of the disease are now well known, such as nephrocalcinosis and craniosynostosis, related to the natural course of the disease, which persisted despite the ERT. The long-term prognosis and outcome for this newborn child remain unknown., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: To which extent serum cytokines may predict asthma control in adults remains understudied., Objectives: We investigated cross-sectional and longitudinal associations between cytokine profiles and asthma outcomes., Methods: Serum interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels were determined in 283 adults with current asthma from the 2nd survey of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2). Participants were followed-up seven years later. Asthma symptom control was assessed according to GINA 2015 guidelines. Cytokine profiles were identified by principal component (PC) analyses, and expressed as above/below the median., Results: The first two PCs captured 82.5% of the variability. While all seven cytokines scored high on PC1, only IL-1Ra and IL-10 scored high on PC2. At EGEA2, neither PC1 nor PC2 were related to exacerbations, asthma attacks, asthma symptom control, lung function, or allergic diseases. High level of PC1 (above the median) was associated with higher blood neutrophil counts (P = 0.02), while high level of PC2 was associated with lower IgE levels (P = 0.04). High level of PC2 at EGEA2 was associated with lower bronchial hyperresponsiveness (adjusted(a) OR[95%CI] = 0.46[0.23; 0.91]) and with subsequent lower risk of worsening asthma control and attacks (aOR[95%CI] = 0.24[0.09; 0.60]; 0.31[0.11; 0.85] respectively)., Conclusions: Serum cytokine profiles with high levels of IL-1Ra and IL-10 were associated with lower subsequent risks of worsening asthma control and attacks in adults. This study adds new findings for the role of serum cytokine profiles to help identifying adults with subsequent risk of asthma burden that could be targeted for specific therapies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The French Society of Research and Sleep Medicine (SFRMS) organized a meeting on obstructive sleep apnea syndrome (OSAS) in children. A multidisciplinary group of specialists (pulmonologists, ENT surgeons, pediatricians, neurophysiologists, sleep specialists) drew up a consensus document on the value of electrophysiological recordings in the diagnosis of OSAS in children. Technical considerations and recommended sensors, respiratory event definitions, and scoring criteria are presented according to the 2012 and 2014 recommendations of the American Academy of Sleep Medicine (AASM). Polysomnographic criteria for sleep-disordered breathing in children and the French National Authority for Health guidelines for indications of polysomnographic studies were reported. Relevance and limits of in-lab PSG, home PSG, and respiratory polygraphy were presented and guidelines were proposed to improve the diagnosis and follow-up of these children., (Copyright © 2016. Published by Elsevier SAS.)

Background: Bleach is widely used for household cleaning. Although it is recognized that occupational use of bleach may have adverse respiratory health effects, it is unknown whether common domestic use of bleach may be a risk factor for asthma., Aim: To assess whether the domestic use of bleach for home cleaning is associated with asthma and other respiratory outcomes., Methods: Questionnaire-based information on respiratory symptoms and cleaning habits and data from skin prick-tests, bronchial responsiveness challenge and white blood cells were analyzed in 607 women participating in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). Bleach use was evaluated in 3 categories (<1 day/week; 1-3 days/week; 4-7 days/week "frequent")., Results: Overall, 37% of the women reported using bleach weekly. Women using bleach frequently (11%) were more likely to have current asthma as compared to non-users (adjusted Odds-Ratio (aOR) = 1.7; 95% Confidence Interval (95%CI) 1.0-3.0). Among women with asthma, frequent use of bleach was significantly associated with higher blood neutrophil cell counts. Bleach use was significantly associated with non-allergic asthma (aOR 3.3; 95%CI 1.5-7.1), and more particularly with non-allergic adult-onset asthma (aOR 4.9; 95%CI 2.0-11.6). Consistently, among women without allergic sensitization, significant positive associations were found between use of bleach and bronchial hyperresponsiveness, asthma like-symptoms and chronic cough. No association was observed for allergic asthma., Conclusions: Frequent use of bleach for home-cleaning is associated with non-allergic adult-onset asthma, elevated neutrophil counts and lower-airway symptoms in women., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Mycobacterium massiliense is closely related to Mycobacterium abscessus and is also a frequent cause of mycobacterial lung disease in patients with cystic fibrosis (CF). There has been no previous investigation of possible differences between M. massiliense and M. abscessus infections in the setting of CF., Methods: We studied a prospective cohort of 16 M. massiliense and 27 M. abscessus lung infection cases with CF, with a mean follow-up of 6 years., Results: M. massiliense cases were younger than M. abscessus cases (mean age: 12.8 vs 17.1 years; p=0.02) at the time of the first mycobacterial isolation and also had lower body mass index values (mean: 16.4 vs 19.3 kg/m(2), p=0.002). All M. massiliense cases, except one, had negative BMI Z-score values at the time of the first mycobacterial isolation (11/12 vs 16/23 M. abscessus cases, p=0.04). Clarithromycin-based combination therapies led to mycobacterial eradication in 100% of M. massiliense cases but only in 27% of M. abscessus cases (p=0.009)., Conclusion: Our data show a particular link between M. massiliense and malnutrition specifically in CF patients. Unlike M. abscessus, the bacteriological response of M. massiliense to combination antibiotic therapies containing clarithromycin was excellent. Distinguishing between M. massiliense and M. abscessus has major clinical implications for CF patients., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Catheter venous thrombosis may result in life-threatening embolic complications. Recently, a thrombophilic tendency was described in cystic fibrosis (CF), the significance of which remains unclear. The aims of this study were to (1) document the frequency of catheter venous thrombosis detected by colour-Doppler-ultrasound (Doppler-US), (2) assess genetic and acquired thrombophilia risk factors for catheter venous thrombosis and hypercoagulability status and (3) provide recommendations on laboratory screening when considering insertion of a totally implantable vascular access device (TIVAD) in CF patients., Methods: We designed a multicentre prospective study in patients selected at the time of catheter insertion. Doppler-US was scheduled at 1 and 6months after insertion and before insertion in case of a previous central line. Blood samplings were drawn at insertion and at 1 and 6months later., Results: One-hundred patients received a TIVAD and 90 completed the 6-month study. Prevalence of thrombophilia abnormalities and hypercoagulability was found in 50% of the cohorts. Conversely, catheter venous thrombosis frequency was low (6.6%)., Conclusion: Our data do not support biological screening at the time of a TIVAD insertion. We emphasise the contribution of a medical history of venous thromboembolism and prospective Doppler-US for identifying asymptomatic catheter venous thrombosis to select patients who may benefit from biological screening and possible anticoagulant therapy., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma., Methods: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006-2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1-7) and the generic SF-36 (scores range: 0-100) were used., Results: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (-1, p = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains., Conclusion: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recommendations for acute and long-term oxygen therapy (needs assessment, implementation criteria, prescription practices, and follow-up) in children were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP2A). The Haute Autorité de Santé (HAS) methodology, based on the Formalized Consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text (arguments+recommendations) is available at the website of the French Paediatric Society: www.sfpediatrie.com., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: The association between smoking and asthma remains unclear and has mostly been assessed in cross-sectional studies, with potential selection bias ("healthy smoker effect")., Aims: Using a longitudinal approach, the aims were to assess whether 1) childhood asthma modifies smoking initiation, 2) active smoking influences asthma incidence in adults and 3) active smoking among subjects with asthma influences the persistence of the disease or the 12-year evolution in lung function in children and adults., Methods: Subjects (513 children and 1190 adults) were recruited and followed-up for 12 years in the context of the EGEA study (Epidemiological study on the Genetics and Environment of Asthma)., Results: Childhood asthma was not associated with a decreased probability of starting active smoking (Hazard Ratio, HR = 0.96; 95% confidence interval (CI): 0.72, 1.27). Smoking at baseline was associated with a higher risk for asthma incidence in adulthood (HR = 1.95, 95% CI: 1.00, 3.77). Among subjects with asthma, smoking was unrelated to lung function evolution; however, among children with moderate to severe asthma at inclusion, smoking tended to slow down the lung function growth (P = 0.04)., Conclusion: These findings support the hypothesis that childhood asthma does not prevent smoking initiation and confirm that active smoking has a deleterious role on asthma. Altogether this study emphasizes the importance of active smoking as a serious public health problem particularly for children and women., (Copyright © 2011. Published by Elsevier Ltd.)

Organizing pneumonia (OP), or bronchiolitis obliterans organizing pneumonia (BOOP), is rare, particularly in children. It affects the small airways and belongs to the group of interstitial lung diseases. Approximately 20 cases in children have been reported, the lack of knowledge of this disease making the diagnosis less likely. Contrary to the findings in adults, where the cryptogenic form is widely present, OP in pediatrics often occurs after a definite cause (infection, transplant, etc.) or in a specific context (dysimmune disease). We report on a teenager who presented with OP in the context of celiac disease, the first case of this association described in the literature., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

According to the definition (body mass index>97 degrees percentile), overweight and obesity concern 15% of French children. The parallel trends in the increase in asthma and obesity may indicate a potential link between these two conditions. The purpose of this study was to review the epidemiological data indicating a relationship between asthma and obesity, to evaluate the consequences of obesity on asthma and to assess the mechanisms of this association. We conclude with the implications for treatment strategies.

In France, an annual seasonal influenza vaccination has been recommended since 2000 for patients suffering from chronic respiratory diseases, including asthma. Each year, a free influenza vaccination voucher is sent by the French Public Health Insurance authorities to patients with chronic respiratory disease, including severe asthma. In November 2006, this measure was extended to all asthmatic patients, irrespective of asthma severity. The present paper examines the 2006-2007 influenza vaccination coverage rate in 433 asthmatic children aged six to 17 years (mean age: 9.5 years; male: 61%) who consulted a pediatric pulmonologist between March and September 2007 in eight hospitals throughout France. The influenza vaccination coverage rate was 15.7% for the 2006-2007 season (13.9% for the 2005-2006 season and 10.9% for the 2004-2005 season). General practitioners vaccinated 72.1% of the children. Lack of information (42%) was the most frequently reported reason for non-vaccination. Free vouchers (received by 39.6% of the children) significantly increased the vaccination coverage rate (31% versus 5.9%; p < 0.001). In France, in 2006-2007, the influenza vaccination coverage rate in asthmatic children was far below the national public health objective to achieve for the year 2008 (at least 75%). Concerted action is needed to improve the influenza vaccination coverage rate in asthmatic children.

Background: A close relation between asthma and allergic rhinitis has been reported by several epidemiological and clinical studies. However, the nature of this relation remains unclear. We used the follow-up data from the European Community Respiratory Health Survey to investigate the onset of asthma in patients with allergic and non-allergic rhinitis during an 8.8-year period., Methods: We did a longitudinal population-based study, which included 29 centres (14 countries) mostly in western Europe. Frequency of asthma was studied in 6461 participants, aged 20-44 years, without asthma at baseline. Incident asthma was defined as reporting ever having had asthma confirmed by a physician between the two surveys. Atopy was defined as a positive skin-prick test to mites, cat, Alternaria, Cladosporium, grass, birch, Parietaria, olive, or ragweed. Participants were classified into four groups at baseline: controls (no atopy, no rhinitis; n=3163), atopy only (atopy, no rhinitis; n=704), non-allergic rhinitis (rhinitis, no atopy; n=1377), and allergic rhinitis (atopy+rhinitis; n=1217). Cox proportional hazards models were used to study asthma onset in the four groups., Findings: The 8.8-year cumulative incidence of asthma was 2.2% (140 events), and was different in the four groups (1.1% (36), 1.9% (13), 3.1% (42), and 4.0% (49), respectively; p<0.0001). After controlling for country, sex, baseline age, body-mass index, forced expiratory volume in 1 s (FEV(1)), log total IgE, family history of asthma, and smoking, the adjusted relative risk for asthma was 1.63 (95% CI 0.82-3.24) for atopy only, 2.71 (1.64-4.46) for non-allergic rhinitis, and 3.53 (2.11-5.91) for allergic rhinitis. Only allergic rhinitis with sensitisation to mite was associated with increased risk of asthma independently of other allergens (2.79 [1.57-4.96])., Interpretation: Rhinitis, even in the absence of atopy, is a powerful predictor of adult-onset asthma.

Unlabelled: Several studies have reported an increasing incidence of childhood parapneumonic empyemas in various countries., Aim of the Study: The aim of our study was to estimate the annual incidence of complicated community-acquired pneumonias in children during a 9-year period in a French area and to describe the epidemiological and clinical characteristics of these complications., Population and Methods: We have listed the children from 28 days to 15 years old, hospitalized in the 2 children hospitals of the Isere district for a community-acquired pneumonia complicated with a pleural empyema or a pulmonary abscess from 1995 to 2003., Results: During the study period, 90 children were hospitalized for a complicated pneumonia including 83 pleural empyemas and 7 isolated lung abscess. The average number of cases was 4 per year from 1995 to 1998 then increased since 1999 to reach 34 cases in 2003, according to a linear model (P<0,001). The incidence of the complicated pneumonia, plotted to the paediatric population of the area has gone up from 0.5 per 100000 to 13 per 100000 children between 1995 and 2003., Conclusion: The incidence of the complicated pneumonias in children increased since 1999 in a French area. Additional investigations are necessary to identify the causes of this increase.

Carcinoid tumors are the most common endobronchial tumor in the pediatric population, and represent a rare cause of airway obstruction. The authors report two cases of boys aged 10 and 11 years old, who presented with a 12-month history of recurrent pneumonia. Bronchial endoscopy showed an endobronchial tumor. Chest CT-scan identified local extension and lung-associated lesions; octreoscan was performed to detect distant metastases. Histopathological study concluded in typical carcinoid tumor. The outcome after surgical conservative resection is uneventful with a follow-up of 7 and 26 months. Bronchial tumors must be considered in children with recurrent pneumonia or persistant respiratory symptoms, and require CT scan and bronchial endoscopy for their diagnosis.

Background: A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort., Methods: A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990-94) and ECRHS-II (1998-2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants., Results: The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was -2% (95% CI: -9.5, 5.5), 7.5% (-2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08-10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11-3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed., Conclusions: Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication.

Reduced pulmonary function is an important predictor of cardiovascular morbidity and mortality. The mechanisms underlying this association are unknown but may involve systemic inflammation. We assessed the cross-sectional and longitudinal relationships between C-reactive protein (CRP) levels and forced expiratory volume in 1s (FEV1) and its decline in the general population, over a period of 8.5 years. The analyzes were based on 531 subjects (mean age at baseline: 37+/-7 years, 50% women and 42% non-smokers), recruited at two French centers participating in the European Community Respiratory Health Survey. Lung function was expressed as a percentage of predicted FEV1. CRP was measured centrally, by means of a highly sensitive assay. In cross-sectional analysis, FEV1 as a % of predicted values was negatively associated with serum CRP concentration (P=0.002). Multivariate adjustment did not alter these results (P=0.002). In longitudinal analysis, annual FEV1 decline tended to increase from the lower to the upper tertile for baseline CRP concentration but the association was borderline significant (P=0.14). Mean values of annual FEV1 decline were 26+/-32, 31+/-32, and 34+/-32 ml/year for the lower, middle and upper tertiles of baseline CRP concentration, respectively, after adjusting for potential confounders (P=0.09). Changes in CRP levels during follow-up were associated with annual FEV1 decline. The mean annual FEV1 declines in subjects with increasing CRP, in those with stable CRP and in those with decreasing CRP were 36+/-31, 30+/-31 and 24+/-31 ml/year, respectively (P<0.001). These findings were not affected by adjustment for potential confounders (P=0.002). In conclusion, increases in CRP levels over time were associated with a steeper FEV1 decline.

Objectives: To evaluate the additional information provided by pulse transit time (PTT), a noninvasive tool, when using during polysomnography for the diagnosis of sleep breathing disorders in a pediatric population., Main Findings: Respiratory and microarousals events were scored twice. The first scoring was performed using nasal pressure, thermistors, thoracic and abdominal movements, and oxygen saturation. The second scoring, blinded to the first scoring, was performed using PTT in combination with all the other signals. Microarousals were scored once visually on the EEG trace (cortical arousals [CAs]) and once using the PTT signal (autonomic arousals [AAs]) blinded to EEG. For the whole group of 16 children studied (mean age, 9.5 years), there was no significant difference between the respiratory disturbance index (RDI) with or without PTT analysis (22.4 +/- 13.5/h vs 20.4 +/- 14.3/h; not significant [mean +/- SD]). Among the children exhibiting a "without PTT" RDI < 30/h, 5 of 12 children (41.66%) showed a clinically significant >/= 5/h increase in RDI when using PTT. AAs detected by PTT were significantly more frequent than CAs during rapid eye movement (REM) sleep (7.4 +/- 3.9/h vs 3.2 +/- 2.3/h; p < 0.001) and slow wave sleep (SWS) [6.0 +/- 4.3/h vs 0.6 +/- 0.5/h; p < 0.0001]., Conclusions: The quantification of respiratory effort using PTT improves the detection of respiratory events in children. The detection of microarousals is improved particularly in REM and SWS.

The increase in asthma prevalence over the past 20 years could be due to modification of exposure to environmental factors (environmental theory) or to the lost of protective factors (hygienist theory). Among environmental factors this paper reviewed the controversial role of exposure to house dust mite (HDM). If exposure to HDM is deleterious in asthmatics known to be sensitised to this allergen, the effect of HDM exposure on asthma incidence has been challenged recently, based on longitudinal studies showing no correlation between level of exposure to HDM and asthma incidence. Exposure to animal dander may have protective effects. This review has shown that, even if some studies have shown potential protective effect of early exposure, the protection seems to be better in families with a low risk of atopy; almost all studies tend to show a deleterious effect of current exposure; exposure to dog dander may be more protective than cat. These studies cannot give definite conclusions to change current advices of early eviction of HDM and animal dander, especially in families with a high risk of atopy. The deleterious effect of passive smoking on asthma prevalence and severity is undisputable and our efforts should concentrate on obtaining effective eviction of passive smoking.

Basic and clinical research in cystic fibrosis have led to several new hypothesis to improve the management of the disease. The numerous tracks for new therapies may be explained by the lack of firm patho-physiological explanations for the disease and of knowledge of the best targets to get a significant improvement of the patients. After initial great hopes, there has been important limitations and slow down of gene therapy, imposing to go back to research programs on new vectors. New hopes have arisen with protein therapies, including chaperones molecules that can activate mutated CFTR proteins within the cells. New anti-inflammatory therapies are developed, including proteases inhibitors. The prevention of airway colonisation with Pseudomonas aeruginosa is fundamental and could go through the development of specific vaccines, cellular therapies or molecules directly acting on the virulent factors of the bacteria.

Bronchial foreign body inhalation is a frequent and potentially serious accident in children. It can provoke long-term complications such as bronchiectasis. These complications occur especially if the delay between inhalation and extraction is long (above 7 days) and in case of vegetal foreign body. To decrease the risk of complications, one must emphasize the importance of early diagnosis and the potential role of fiberoptic bronchoscopy to help the diagnosis in case of suspected inhalation without clinical or radiological signs. Rigid bronchoscopy is the only procedure that allows diagnosis and removal of the foreign body.

Background: Bronchiolitis obliterans syndrome (BOS) is a common complication of lung transplantation (LT), associated with a tremendous mortality and morbidity. Recent innovative research has focused on bronchoalveolar lavage (BAL) analysis, assuming that neutrophilia might be a marker of chronic rejection., Patients and Methods: To address this issue, we retrospectively analyzed 258 sequential BAL from 44 lung transplant recipients, having survived for more than 3 months after surgery., Results: At the end of the follow-up, 22, 7, 7 and 8 patients had BOS stage 0, 1, 2 and 3, respectively. The total cell count and neutrophilia increased with BOS severity (P < 0.01). BOS occuring before and after the 12th month of LT were associated with early and more delayed increases of BAL neutrophils, respectively. Finally, the various kinetic profiles of neutrophil progression were identified, allowing for an earlier identification of BOS stages 2 and 3, by 3 and 6 months, respectively. Conversely, neutrophilia associated to BOS stage 1 remained low, and could not be distinguished from that of stage 0., Conclusions: These results support the possible role of neutrophils in BOS pathogenesis, and may be of interest for an earlier detection and management of chronic rejection.

Although when an infant or a young child presents with persistent or recurrent wheezing, the probability of asthma is high, one must remain very careful in order not to miss an other etiology. Except for the chest X ray with inspiratory and expiratory studies that is mandatory, the other evaluations should be based on a careful interview and clinical examination. Fiberoptic bronchoscopy may be indicated each time there is a doubt on foreign body aspiration or tracheobronchomalacia.

In order to understand the epidemiological aspects of chronic cough, we analysed 100 patients' files referred for chronic cough in five pediatric-pulmonology consultations. The patients had a chronic cough for more than 3 weeks. The distribution of causes was: asthma, 56%; upper airway disorders, 16%; psychogenic, 4%; whooping cough, 4%; Mycoplasma pneumoniae pulmonary infection, 3%; Chlamydia pneumoniae pulmonary infection, 1%; bronchiectasis, 1%. In 15% of cases two or more causes were associated; In most cases, the clinical characteristics of the cough are evident enough to establish a diagnosis with few secondary explorations. The prognosis is on the whole favourable.

Obliterative bronchiolitis remains the main cause of graft dysfunction and death after 1 year. Defined by an irreversible airway obstruction, bronchiolitis obliterans syndrome is usually recognized in the advanced stage of the disease, with histological evidence of fibrotic damage. Fibrosis represents the end-stage of an inflammatory process, leading to the postulate that chronic lung graft dysfunction is preceded by cellular and molecular events. This study was performed during the first year following lung transplantation, in the absence of histological or functional criteria of chronic rejection. Transbronchial biopsies from eight lung allografts were examined. Four developed a bronchiolitis obliterans syndrome (Group I), and 4 had good outcomes (Group II) at 2 years. Using immunohistochemistry, the aim of the study was to correlate early immunological events with graft outcomes at 2 years. An up-regulation of HLA class I antigen (P = 0.0001), an overexpression of Ki-67 (P = 0.006) on bronchial epithelium, and graft infiltration by CD45+, CD25+ cells (P = 0.003) were significantly associated with the development of chronic rejection. An overexpression of numerous adhesion molecules was observed. However, only very late antigen-4 had a discriminative value (P = 0.04), preceding chronic graft dysfunction. Our results suggest that graft dysfunction is associated with early molecular and cellular events, and raises the possibility that a fibroproliferative disorder is initiated shortly after transplantation. The recognition of such early immunological markers might facilitate improved graft management and prognosis.

Aims: Asthma is one of the most frequently encountered chronic illnesses in children. The aim of the present study was to investigate the problem of integration of asthmatic subjects at school by assessing the reactions of parents and teachers, and also by considering the medical aspects., Population and Methods: A cross-sectional random study was carried out during autumn 1994 including 4,251 primary school children aged between five and 14 years, and including teachers from 188 classes and 26 schools in Grenoble and its inner suburbs. The first screening questionnaire was completed by the parents, and data on 3,799 children were obtained; from this, 191 currently asthmatic children were identified. One hundred and forty-six parents of the identified asthmatics subsequently answered a second questionnaire on the severity of the illness and its effects on school attendance and educational activities. The 186 teachers from the schools involved were interviewed about their knowledge of the disorder, and about what they knew of the treatment and management of asthmatic children in school., Results: It was found that the cumulative prevalence of asthma amounted to 7.6%, and that the prevalence over the previous 12-month period was 4.3%. Sixteen percent of the asthmatic children reported an asthma-associated school absence of more than six days during the six preceding months. In 45.2% of cases, physical exercise was responsible for an asthmatic attack, but premedication was used in only 21% of cases. Nine percent of the children had obtained a medical certificate which exempted them from participating in sports activities and physical exercise. Seventy-three percent of the parents had informed the teachers of their child's illness, but the information communicated was incomplete. It was found that the teachers did not have a thorough knowledge of the disorder, but that many of them (92.7%) would appreciate further information on the subject and on its management. Eighty-three percent of the teaching staff were unaware that the ministerial circular No. 93-248 of 22 July 1993 had been issued on the proposed management of chronic disorders at school, advocating a combined effort on the part of the parents, the child's physician, the school doctors and the teachers in setting up a concerted plan of action., Conclusions: This study has demonstrated that the school integration of asthmatic children remains problematical both as regards treatment and the pursuit of indoor and outdoor school activities. Integration could be improved by using parent-doctor-teacher liaison forms, thereby maintaining closer communication regarding the child's needs. When this is not sufficient, an individualized asthma management plan could be introduced in collaboration with the parents, doctors and teachers, which might result in improved treatment and integration of asthmatic children in school.

Hemoptysis in children are infrequent and often self-limiting. They are a manifestation of the broader spectrum of pulmonary haemorrhage. Diffuse pulmonary haemorrhages are often associated with diseases of other organs (cardiopathies, systemic diseases). Focal haemorrhages have multiple aetiologies, dominated by bronchopulmonary infections and cystic fibrosis. Fiberoptic bronchoscopy allows one to localise the bleeding, look for local causes and diagnose pulmonary hemosiderosis by BAL. For local lesions and if the medical management fails, bronchial arteriography is indicated to perform the embolisation of the bleeding vessels.

Epidemiology of paediatric respiratory allergic disorders allows the approach to causal and preventive risk factors by studying groups or sub groups of children in different locations and under different conditions. This is, however, complicated by the lack of consensus on disease definitions, which renders comparisons between studies difficult. Atopy is usually defined by the presence of positive skin tests (wheal size of at least a mean diameter > or = 3 mm), by the presence of specific IgE, or by the presence of increased total IgE (> or = 100 UI/mL). Infantile asthma is not well defined, complicated by the high prevalence of bronchiolitis; one thus questions between wheezing or wheezy bronchitis. Prevalence is high: among early wheezers, two populations will be defined by the medium term evolution: transient wheezers and persistent wheezers. Risk factors for these two conditions are different. Childhood asthma may be defined by the diagnosis of asthma (specific but fairly non-sensitive), by asthmatic symptoms (wheezing, waking by an attack of shortness of breath) (sensitive but not very specific), or by the combination of symptoms and airway hyperresponsiveness. The ISAAC study has standardised a questionnaire to assess the prevalence of asthma. The preliminary results show that there are wide variations across the world. The prevalence is low in Africa and Asia, intermediate in Europe, and high in Anglo-Saxon countries. The prevalence of asthma has gradually increased over the past 20 years in developed countries. Asthma and atopy are closely associated in children. Risk factors are genetic, associated with sex and environmental factors. Among these, allergic sensitisation is associated with the degree of exposure to allergens. Westernization of way of life is associated with increased prevalence of atopy, allergic rhinitis and asthma. Atopy seems inversely correlated to certain infections. Passive smoking is clearly associated with early wheezing. This and atmospheric pollution aggravate childhood asthma. However, the inducing role of pollution on asthma is still controversial.