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International audience; Background: There is a high prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS), sometimes associated with alveolar hypoventilation.Objective: To compare transcutaneous partial pressure of carbon dioxide (PtcCO2 ) and pulse oximetry (SpO2 ) in children with DS and in control children with OSA.Patients and methods: This retrospective case-control study involved children followed in Trousseau Hospital (Paris) Sleep Center. Polysomnography (PSG) recordings and clinical files of children with DS were reviewed to identify clinical signs of OSA and comorbidities associated with DS. Controls were children who presented with OSA of ENT origin without other comorbidities (exceptions: two overweight, one obese, and three with well-controlled asthma). DS subjects and controls were matched for age and apnea hypopnea index.Results: There were 28 children in each group. Mean PtcCO2 during sleep was significantly higher in patients with DS compared to controls (44 mm Hg vs 42 mm Hg, P = .001). Five (21%) patients with DS met the American Academy of Sleep medicine criteria for hypoventilation, compared to one (4%) in the control group. The mean PtcO2 during sleep was significantly lower in patients with DS (77 mm Hg vs 82 mm Hg, P = .003).Conclusions: This is the first study to compare nocturnal gas exchange in children with DS to a control group of children with similar OSA. Our data demonstrate that children with DS have increased PtcCO2 regardless of the presence of OSA and its severity. This may be due to respiratory muscle hypotonia and/or ventilatory control alteration in patients with DS.

International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)

Peripheral (or small) airway obstruction (PAO) is considered a marker of childhood asthma but the techniques able to directly measure it are rarely used in routine. Usual spirometry and plethysmography can detect a certain degree of PAO when reduced forced vital capacity (FVC) is associated to normal forced expiratory volume in 1 s (FEV1 ) to FVC ratio, and normal total lung capacity (TLC). The frequency of this functional pattern has never been studied in different pediatric respiratory conditions. To assess the prevalence and outcome of PAO in children with different diseases or symptoms, we retrospectively extracted from our database all files of Caucasian subjects encompassing spirometry and plethysmography measurements. Spirometry patterns (normal, airflow limitation [AFL; low FEV1 /FVC], low FVC [with normal FEV1 /FVC]) and final functional patterns (normal, AFL, PAO, restrictive [low TLC], or mixed) were described. We included 4394 files recorded in 1794 children (median [IQR] age: 10.7 [9.2-12.9] years). At inclusion, 125 (7%) children had low FVC of which 56 (44.8%, and 3.1% [95% CI 2.3-3.9] of the whole population) had PAO. PAO prevalence increased with age (OR (95% CI) per 2-year-increase: 2.26 (1.59-3.23); p < .001), and was more frequent in chronic bronchial diseases other than asthma (1.6% vs. 8.0%). On repeated tests, PAO frequently normalized (26.1%) or persisted (43.5%), but it less often progressed into AFL (13%) or restrictive (13%) patterns. PAO is an infrequent nonspecific and persistent functional pattern. Its prevalence increases with age and in diagnosis of chronic respiratory diseases other than asthma.

We report the case of a female patient aged 12 years referred to our pediatric sleep unit with a history of central sleep apnea associated with transient episodes of tachypnea on polysomnography recordings. The patient was otherwise healthy, with no personal or family medical history, and had a normal physical and neuropsychological examination. Brain magnetic resonance imaging showed signs of cerebellar vermis dysplasia but without the classical features of the molar tooth sign. The rest of the workup (genetic tests, blood tests, cardiac investigations) was normal except for an increased peripheral chemosensitivity to carbon dioxide and oxygen. The patient was successfully treated with bilevel positive airway pressure. This case report highlights the importance of performing brain magnetic resonance imaging in patients with central sleep apnea to study the cerebellum, beyond the brainstem area. Cerebellar malformations can be found even in the absence of any other neurological condition. CITATION: Taytard J, Valence S, Sileo C, et al. Severe central apnea secondary to cerebellar dysplasia in a child: look past Joubert syndrome. J Clin Sleep Med. 2020;16(12):2113–2116.

Introduction: Little is known on the effect of SARS-CoV-2 circulation on asthma daily symptoms in children. We compared asthma exacerbations, asthma symptom control and lung function before and after SARS-CoV-2 outbreak in children.Methods: Retrospective study of children with persistent asthma referred for lung function testing. The second quarter of 2020 being a period with nearly no activity, we compared the activity between the first, third and fourth quarters of 2019 and 2020 (Q1-2019 vs. Q1-2020, Q3-2019 vs. Q3-2020 and Q4-2019 vs. Q4-2020).Results: We retrieved 1,871 files in 2019 and 1,548 in 2020. The whole population [2,165 (63.3%) boys] had a median [IQR] age of 9.7 [6.8;13.1] years. There was no difference in age, sex, and ethnicity between 2019 and 2020 populations. Asthma was better controlled during Q4-2020 compared to Q4-2019 (P = 0.042), and there was a lower proportion of children with at least one exacerbation in the previous 3 months after the reopening, compared to the same period in 2019 (P < 0.0001). Baseline FEV1 (Z-score) recorded after the reopening was significantly higher (with less reversibility) compared to the same period before the epidemic (P < 0.0001). Baseline FEV1/FVC (Z-score) was significantly higher during Q3-2020 compared to Q3-2019 (P = 0.026), with fewer children having a significant reversibility (P = 0.035).Discussion: We demonstrated a trend toward increased exacerbations just before the recognition of the epidemic, and fewer exacerbations, better asthma symptom control and improvement in the lung function of asthmatic children after the reopening.

International audience; Bronchopulmonary infections are a major trigger of cardiac decompensation and are frequently associated with hospitalizations in patients with heart failure (HF). Adverse cardiac effects associated with respiratory infections, more specifically Streptococcus pneumoniae and influenza infections, are the consequence of inflammatory processes and thrombotic events. For both influenza and pneumococcal vaccinations, large multicenter randomized clinical trials are needed to evaluate their efficacy in preventing cardiovascular events, especially in HF patients. No study to date has evaluated the protective effect of the COVID-19 vaccine in patients with HF. Different guidelines recommend annual influenza vaccination for patients with established cardiovascular disease and also recommend pneumococcal vaccination in patients with HF. The Heart Failure group of the French Society of Cardiology recently strongly recommended vaccination against COVID-19 in HF patients. Nevertheless, the implementation of vaccination recommendations against respiratory infections in HF patients remains suboptimal. This suggests that a national health policy is needed to improve vaccination coverage, involving not only the general practitioner, but also other health providers, such as cardiologists, nurses, and pharmacists. This review first summarizes the pathophysiology of the interrelationships between inflammation, infection, and HF. Then, we describe the current clinical knowledge concerning the protective effect of vaccines against respiratory diseases (influenza, pneumococcal infection, and COVID-19) in patients with HF and finally we propose how vaccination coverage could be improved in these patients.

Resume La surcharge ponderale chez l’enfant et l’adolescent se definit par un indice de masse corporelle (IMC) superieur au 97e percentile pour l’âge et le sexe selon des courbes etablies par l’International Obesity Task Force (IOTF). On estime qu’en France, elle toucherait 25 % des moins de 18 ans. Elle est d’origine multifactorielle, avec une influence importante de facteurs genetiques, modulee par des determinants precoces pre et post-nataux (tabagisme maternel, etc.), societaux et psychologiques. L’impact fonctionnel respiratoire de l’obesite chez l’enfant se traduit essentiellement par une diminution du rapport VEMS/CVF. Plusieurs etudes ont par ailleurs montre une association entre asthme et surpoids/obesite, avec un impact pejoratif de l’IMC sur le controle de l’asthme. Cependant, l’asthme est encore mal caracterise dans cette population et les determinants de l’obstruction bronchique semblent etre differents de ceux des enfants non obeses, avec notamment peu d’inflammation eosinophile. Le syndrome d’apnees obstructives du sommeil (SAOS) est une complication frequente du surpoids et toucherait jusqu’a 80 % des enfants et adolescents obeses. Il a une definition polysomnographique specifique chez l’enfant. La symptomatologie est globalement la meme que chez l’adulte, avec cependant des alterations cognitives et/ou neurocomportementales souvent plus marquees chez l’adolescent. Le traitement repose sur la chirurgie ORL lorsqu’elle est indiquee (avec realisation d’une polysomnographie postoperatoire), puis sur la ventilation par pression positive continue (PPC). Le syndrome d’obesite-hypoventilation (SOH), enfin, a la meme definition chez l’enfant que chez l’adulte et toucherait environ 20 % des patients. Son traitement repose sur la ventilation nocturne a deux niveaux de pression. Dans certains cas extremes chez l’adolescent, la chirurgie bariatrique peut etre proposee. L’indication devra etre posee dans un centre specialise a competence pediatrique.

Background Although bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management. Material and methods The study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included. Results In total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p, Bronchoalveolar lavage can help characterise severe asthma in children. However, it can be poorly tolerated and, in most cases, its impact on the patient's management remains limited. https://bit.ly/39XOlMt

Background: Ten months after its appearance in December 2019, SARS-CoV-2 has infected more than 25 million patients worldwide. Because children were first identified as potential spreaders of the virus, schools were closed in several countries. However, it rapidly became evident that the number of hospitalized children infected by SARS-CoV-2 was dramatically lower than that of adults. To date, only hypotheses have been raised to explain this difference, so it is of great importance to describe the presentation of this disease among children. Here, we describe a wide spectrum of COVID-19 manifestation in children in a dedicated pediatric unit in France. Methods: Patients hospitalized with COVID-19 who were diagnosed on the basis of either positive SARS-CoV-2 RT-PCR in nasopharyngeal swabs and/or typical aspects in chest-computed tomography (CT) were included between March and May 2020 in Paris. Results: Twenty-three patients were included on the basis of positive RT-PCR (n = 20) and/or typical aspects in CT (n = 4). The median age was 4.9 years [0.1&ndash, 17.6]. Patients were grouped by age (&lt, 2 years old: n = 14, 61%, 2&ndash, 10 years old: n = 2, 9%, &gt, 10 years old: n = 7, 30%). Overweight or obesity was reported in only three patients. At presentation, the most frequent symptom in the overall cohort was fever (n = 18, 78%), followed by acute rhinitis (n = 9, 64%) and cough (n = 7, 50%) in the under 2-year-old group and cough (n = 4, 57%), fatigue, dyspnea and abdominal pain (n = 3, 43% each) in the over 10-year-old group. Five patients required ICU treatment, four of whom were aged &gt, 10 years, two presented with acute myocarditis, and two were sickle cell disease patients who presented with acute chest syndrome. Discussion and conclusion: The youngest patients seem to present milder forms of COVID-19 without the need for ICU treatment and with a shorter length of hospitalization. More severe evolutions were observed in teenagers, with, however, favorable outcomes. Given the context of closed schools and confinement, the infection of these children suggests intra-familial transmission that needs to be further assessed. This description might help to understand the intriguing differences in COVID-19 severity across age-classes.

International audience; Nemaline myopathies are clinically and genetically heterogeneous muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Mutations in the KLHL40 (kelch-like family member 40) gene (NEM 8) are common cause of severe/lethal nemaline myopathy. We report an 8-year-old girl born to consanguineous Moroccan parents, who presented with hypotonia and poor sucking at birth, delayed motor development, and further mild difficulties in walking and fatigability. A muscle biopsy revealed the presence of nemaline bodies. KLHL40 gene Sanger sequencing disclosed a never before reported pathogenic homozygous mutation which resulted in absent KLHL40 protein expression in the muscle. This further expands the phenotypical spectrum of KLHL40 related nemaline myopathy.

Asthmatic children free of exacerbation with airway obstruction may have low partial pressure of oxygen (PaO2) which can be a marker for future risk, but PaO2 is scarcely measured during pulmonary function testing. We prospectively included asthmatic children with airway obstruction referred for pulmonary function testing, including blood gas analysis (n = 51). Hypoxaemia, defined as a value lower than − 2 z-score, was present in 15 (29%) children, and 37 (72%) children had a significant reversibility after bronchodilator administration. The multivariable model showed a positive influence of baseline forced expiratory volume in 1 s (FEV1) on PaO2 (β coefficient 0.69, [95% CI: 0.07; 1.30]; P = 0.03), whereas uncontrolled asthma and FEV1 reversibility negatively influenced it (β coefficient − 1.59 [95% CI: − 2.74; − 0.44]; P = 0.01; and − 0.07 [95% CI: − 0.13; − 0.02]; P = 0.01, respectively). As a consequence, children with uncontrolled symptoms of asthma and FEV1 reversibility ≥ 12% were significantly more at risk of having hypoxaemia compared to children with well/partly controlled asthma or no significant reversibility of FEV1. Conclusion: Among obstructive asthmatic children without current exacerbation, hypoxaemia is more likely to be seen in children with uncontrolled asthma and a significant post-bronchodilator FEV1 reversibility, in favour of different pathophysiology and treatment requirements of their airway obstruction.

Background: There is a high risk of obstructive sleep apnea (OSA) for children with Down Syndrome (DS), sometimes associated with alveolar hypoventilation. Aims and Objectives: The aim of this study was to compare trancutaneous CO2 (TcCO2) and Oxygen saturation (SpO2) in children with DS and in control children with clinical OSA. Methods: Retrospective case-control study including children followed in Trousseau Hospital sleep center(Paris, FRANCE). Polysomnography (PSG) recordings of children with DS were reviewed, alongside with clinical files to search for signs of clinical OSA and DS comorbidities. Controls were children presenting with clinical OSA of ENT origin without other comorbidities (except for obesity for 3 patients). Patients were matched on age and apnea hypopnea index. Results: 28 Children with DS and 28 control cases were included. The average TcCO2 during sleep was significantly increased in DS patients compared to controls (44.7 mmHg vs. 42.4 mmHg, p = 0.0089), along with the percentage of sleep time with a TcCO2 above 50 mmHg (9.1 vs. 1.4, p = 0.011). The average SpO2 during sleep was significantly decreased in DS patients (95.7% vs. 96.3%, p = 0.048). Conclusions: This is the first study comparing nocturnal gas exchange in children with DS to a control group of children with similar OSA measured during PSG recordings. It demonstrates that children with DS have an increased TcCO2, regardless of the presence of OSA and its severity. These findings could be explained by respiratory muscles hypotonia and/or ventilatory control dysfunction. A prospective study will be needed to explore these hypotheses.

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma., Despite increased ICS use, only 34% of subjects with persistent asthma take ICSs on a regular basis

International audience; 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

Spirometry is the most common pulmonary function test (PFT) used to follow asthmatic patients. It is recommended to withhold Short-Acting Beta 2-Agonists (SABA) a few hours before PFTing, and to withhold Long-Acting Beta 2-Agonists (LABA) for diagnosis purpose but not for the assessment of response to a current treatment [1>]. In asthmatic children, the addition of LABA to inhaled corticosteroids (ICS) has no clear clinical benefit but it has proved to improve baseline Forced Expiratory Volume in 1 s (FEV1) [2]. The maximal increase in FEV1 after a single dose of formoterol was measured 3 h after administration but the remaining effect after 12 h would depend on the inhaled dose [3]. Finally, 25 µg or 50 µg of Salmeterol inhaled at 10 p.m. resulted in higher baseline pulmonary function and decrease in exercise induced bronchoconstriction 10 and 12 h later [4]. In routine practice, children are tested with various delays since last LABA inhalation, but LABA is usually inhaled on the morning of the test ( 12 h) or on the morning the previous day or before (>24 h). It is thought that children with the most recent inhalation should have the best pulmonary function and the lowest reversibility, but the latter has not been studied. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Taytard has nothing to disclose. Conflict of interest: Dr. Aupiais has nothing to disclose. Conflict of interest: Dr. Jovien has nothing to disclose. Conflict of interest: Dr. Assouline Kabla has nothing to disclose. Conflict of interest: Dr. Haziot has nothing to disclose. Conflict of interest: Dr. Fuger has nothing to disclose. Conflict of interest: Dr. Alberti has nothing to disclose. Conflict of interest: Dr. Beydon has nothing to disclose.

The objective of this study was to test the capacity of vibrotactile stimulation transmitted to the wrist bones by a vibrating wristband to awaken healthy individuals and patients requiring home mechanical ventilation during sleep. Healthy subjects (n = 20) and patients with central hypoventilation (CH) (Congenital Central Hypoventilation syndrome n = 7; non-genetic form of CH n = 1) or chronic obstructive pulmonary disease (COPD) (n = 9), underwent a full-night polysomnography while wearing the wristband. Vibrotactile alarms were triggered five times during the night at random intervals. Electroencephalographic (EEG), clinical (trunk lift) and cognitive (record the time on a sheet of paper) arousals were recorded. Cognitive arousals were observed for 94% of the alarms in the healthy group and for 66% and 63% of subjects in the CH and COPD groups, respectively (p < 0.01). The percentage of participants experiencing cognitive arousals for all alarms, was 72% for healthy subjects, 37.5% for CH patients and 33% for COPD patients (ns) (94%, 50% and 44% for clinical arousals (p < 0.01) and 100%, 63% and 44% for EEG arousals (p < 0.01)). Device acceptance was good in the majority of cases, with the exception of one CH patient and eight healthy participants. In summary this study shows that a vibrotactile stimulus is effective to induce awakenings in healthy subjects, but is less effective in patients, supporting the notion that a vibrotactile stimulus could be an effective backup to a home mechanical ventilator audio alarm for healthy family caregivers.

Introduction: Pulmonary hemosiderosis is a rare cause of interstitial lung disease in children. The French experience had previously highlighted that 20% of the 25 included children also had Down syndrome (DS). In this study populations, the main features of the patients with hemosiderosis were unspecific stigmata of autoimmune disease. This study aims to investigate the relationships between pulmonary hemosiderosis and DS. Material and methods: Patients with pulmonary hemosiderosis followed is one of RespiRare network and younger than 20 years old at diagnosis were selected. The following data were collected : DS status, clinical, biological, functional, and radiological findings. Results: Nine of the 34 included patients (26%) had DS. They were a girl predominance (72%) in the non-DS group, and a male predominance in the DS group (56%). The mean age at the diagnosis was 3.80±3.30 with no significant difference between DS and non-DS patients. DS patients tended to present a more severe form of the disease with more dyspnoea (p=0.03) and more pulmonary arterial hypertension (PAH) (p=0.0003). The 3 (9%) patients who died were DS patients (p=0.0003). Discussion and conclusions: DS seem to be a risk factor for hemosiderosis. Hemosiderosis in DS patients is more severe at presentation, and at follow-up. Several hypotheses can be proposed for such association: an increased fragility of the lung capillary, a higher susceptibility to autoimmune lesions, and a higher risk of chronic hypoxia, leading to PAH. In DS, hemosiderosis should be considered in patients with anaemia of unknown origin.

International audience; Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation. In CF, glucocorticoids (GC) are widely used, but their efficacy and benefit/risk ratio are still debated. In plasma, corticosteroid-binding globulin (CBG) binds 90% of GC and delivers them to the inflammatory site. The main goal of this work was to study CBG expression in CF patients in order to determine whether CBG could be used to optimize GC treatment. The expression of CBG was measured in liver samples from CF cirrhotic and non-CF cirrhotic patients by qPCR and Western blot and in lung samples from non-CF and CF patients by qPCR. CBG binding assays with H-3-cortisol and the measurement of the elastase/alpha 1-antitrypsin complex were performed using the plasmas. CBG expression increased in the liver at the transcript and protein level but not in the plasma of CF patients. This is possibly due to an increase of plasmatic elastase. We demonstrated that pulmonary CBG was expressed in the bronchi and bronchioles and its expression decreased in the CF lungs, at both levels studied. Despite the opposite expression of hepatic and pulmonary CBG in CF patients, the concentration of CBG in the plasma was normal. Thus, CBG might be useful to deliver an optimized synthetic GC displaying high affinity for CBG to the main inflammatory site in the context of CF, e.g., the lung.

ObjectiveTo evaluate the safety and clinical efficacy of nusinersen in patients older than 7 months with spinal muscular atrophy type 1 (SMA1).MethodsPatients with SMA1 were treated with nusinersen by intrathecal injections as a part of the Expanded Access Program (EAP; NCT02865109). We evaluated patients before treatment initiation (M0) and at 2 months (M2) and 6 months (M6) after treatment initiation. Survival, respiratory, and nutritional data were collected. Motor function was assessed with the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and physiotherapist scales adjusted to patient age (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and the Motor Function Measure 20 or 32).ResultsWe treated 33 children ranging in age from 8.3 to 113.1 months between December 2016 and May 2017. All patients were alive and were continuing treatment at M6. Median progress on the modified HINE-2 score was 1.5 points after 6 months of treatment (p < 0.001). The need for respiratory support significantly increased over time. There were no statistically significant differences between patients presenting with 2 and those presenting with 3 copies of the survival motor neuron 2 (SMN2) gene.ConclusionsOur results are in line with the phase 3 study for nusinersen in patients with SMA1 treated before 7 months of age and indicate that patients benefit from nusinersen even at a later stage of the disease.ClinicalTrials.gov identifier:NCT02865109.Classification of evidenceThis study provides Class IV evidence that for patients with SMA1 who are older than 7 months, nusinersen is beneficial.

Background Pulmonary hemosiderosis is a rare and complex disease in children. A previous study from the French RespiRare® network led to two important findings: 20% of the children presented with both pulmonary hemosiderosis and Down syndrome (DS), and at least one tested autoantibody was found positive in 50%. This study investigates the relationships between pulmonary hemosiderosis and DS. Methods Patients younger than 20 years old and followed for pulmonary hemosiderosis were retrieved from the RespiRare® database. Clinical, biological, functional, and radiological findings were collected, and DS and non-DS patients’ data were compared. Results A total of 34 patients (22 girls and 12 boys) were included, among whom nine (26%) presented with DS. The mean age at diagnosis was 4.1 ± 3.27 years old for non-DS and 2.9 ± 3.45 years old for DS patients. DS patients tended to present a more severe form of the disease with an earlier onset, more dyspnoea at diagnosis, more frequent secondary pulmonary hypertension, and an increased risk of fatal evolution. Conclusions DS patients have a higher risk of developing pulmonary hemosiderosis, and the disease seems to be more severe in this population. This could be due to the combination of an abnormal lung capillary bed with fragile vessels, a higher susceptibility to autoimmune lesions, and a higher risk of evolution toward pulmonary hypertension. A better screening for pulmonary hemosiderosis and a better prevention of hypoxia in DS paediatric patients may prevent a severe evolution of the disease. Electronic supplementary material The online version of this article (10.1186/s13023-018-0806-6) contains supplementary material, which is available to authorized users.

International audience; Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail bronchiectasis and pulmonary impairment as measured using spirometry, during childhood. We aimed at looking whether blood gas exchanges progressed differently between CF and PCD children in a retrospective study of repeated measurements. Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a mixed linear model, adjusted for age, evaluated associations between diseases and PaO2, PaCO2, or PaO2-PaCO2 ratio.Among 42 PCD and 73 CF children, 62% and 59% had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were similar at inclusion (PaO2 median [IQR] PCD −1.80 [−3.40; −0.40]; CF −1.80 [−4.20; 0.60] z-scores; P = 0.72). PaO2 and PaO2-PaCO2 ratio similarly and significantly decreased with age in both groups (P

Objectives Osteogenesis imperfecta (OI) is the most common genetic skeletal disorder. Extraskeletal findings are common but an association with sleep-disordered breathing (SDB) has never been described. The aim of this study was to investigate clinical features of children with OI and suspected SDB. Methods A retrospective study of clinical records, signs of SDB and polysomnographic recordings of children with OI was performed. We paid particular attention to symptoms that could be associated with SDB in this population – scoliosis, kyphosis, vertebral arthrodesis, chest wall deformities, basilar impression, autonomy – as well as data already known to be associated with obstructive sleep apnea such as body mass index and upper-airway impairment. Results We reviewed the clinical charts of 188 patients referred to our genetic skeletal disorders reference center for OI. Among the 15 patients (8%) with polysomnographic recordings, 12 (6.4%) had sleep-disordered breathing. We found a negative correlation between the Brief Assessment of Motor Function score and Apnea Hypopnea Index (r = −0.68; p = 0.01) and Desaturation Index (r = −0.62; p = 0.02). The Apnea Hypopnea Index was higher for non-walkers than walkers (mean [SD]: 6.5 [3.6] vs. 2.4 [1.5]; p = 0.02) and with type III versus IV OI. Two patients were started on continuous positive airway pressure ventilation, with clinical improvement. Conclusion For OI children, symptoms suggesting obstructive sleep disorders should be searched for systematically, especially in children with compromised autonomy, high body mass index, trunk deformations, and severe OI type.

Introduction: Studies on first-degree relatives of non-obese patients suggest that genetics play a role in Obstructice Sleep Apnea Syndrome (OSAS). Aim: To study familial aggregation of OSAS and tonsillar hypertrophy. Methods: Prospective monocentre cohort study in non-obese children referred for suspected OSAS, classified as presenting or not a clinical OSAS according to national recommendations criteria. At inclusion, parents completed the Berlin questionnaire, and familial history of tonsillectomy was recorded. Polysomnography (PSG) were performed as recommended. The clinical persistence of OSAS was assessed 1 year later. Results: Seventy three non-obese children (25 girls) median [Q1;Q3] 5.1 [3.3;7.0] years old, were included. Clinical OSAS was present in 62 (85%) of them, 27 (38%) had a familial history of tonsillectomy, and 21 (29%) had at least one parent with a positive Berlin questionnaire. Fifty six children underwent PSG recording, with an Apnea Hypopnea Index, available in 52 children, of 2.9 [1.3;7.5]/h. Children were divided into two groups: no or mild OSAS (n=34 (65%)), and moderate to severe OSAS (n=18 (35%)). There was no difference between groups for the familial history of tonsillectomy (p=0.14) or the frequency of positive Berlin questionnaire (p=0.51). The size of the children’s tonsils was not related to Berlin questionnaire result (p=1). Residual clinical OSAS was detected in 17/37 (46%) children followed-up. It was more frequent in children without tonsillectomy after inclusion compared to these with tonsillectomy (p=0.001) but was not influenced by the Berlin questionnaire (p=0.72). Conclusion: This sudy did not evidence familial aggregation of OSAS and tonsil hypertrophy.

Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P Conclusions: Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.

International audience; BACKGROUND: Although the negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known, the effect of ETS on allergic sensitization is still debated. OBJECTIVE: To evaluate how maternal allergies modulate the effect of tobacco exposure on allergic sensitization in childhood. METHODS: Of 9000 children in grades 4 and 5 selected in 6 cities in France, 7798 participated in a survey that consisted of an epidemiologic questionnaire, skin prick testing to common allergens, and skin examination for eczema. Tobacco exposure was obtained from parent questionnaires. RESULTS: Twenty-five percent of the children had allergic sensitization, 25.2% had eczema, 11.6% had allergic rhinitis, 9.9% had asthma, and 8.3% had exercise-induced asthma. Twenty percent of the children were exposed to tobacco in utero. Maternal exposure had a greater impact than paternal exposure on children's allergic sensitization. Prenatal exposure was more associated with sensitization than postnatal exposure. Children with maternal allergies and exposure to maternal ETS during pregnancy were at higher risk for sensitization to house dust mite (25.7% vs. 14.0%; odds ratio, 1.95; 95% confidence interval, 1.19-3.18; P = .006). In contrast, sensitization to food allergens was not associated with tobacco exposure. CONCLUSIONS: Children exposed to maternal smoking had a higher risk of sensitization to house dust mite, especially when the mothers were allergic.

International audience; BackgroundLow-dose azithromycin has beneficial effects on severity of the lung disease in cystic fibrosis (CF) patients for a period of 6–12 months after initiation of the treatment. Although its impact in the longer term is uncertain, this treatment is frequently used chronically. The aim of this retrospective study was to investigate the effects of low-dose azithromycin treatment on the progression of CF lung disease in patients treated for more than 12 months.MethodsAll of the CF patients followed in our pediatric center and who had been on low-dose azithromycin for more than 12 sequential months were included. The clinical data were collected for one year before and three years after the initiation of the azithromycin treatment. These data comprised lung function analyses, rates of exacerbations and of antibiotic courses, and changes in the airways' bacterial colonization.ResultsA total of 68 patients were included (mean age: 9.95 yrs (3.61)). After 12 months, significant reductions in the numbers of pulmonary exacerbations and antibiotic courses were present. However, this effect was not maintained in the subsequent periods, during which increased rates of both pulmonary exacerbations and antibiotic courses were observed. The lung function decline was not modified during the treatment, and a decreasing time-dependent trend typical of CF was observed for the various parameters. No differences in the airway colonization by pathogens such as P. aeruginosa and methicillin-sensitive and/or -resistant Staphyloccocus aureus were observed during the treatment. However, isolated Staphyloccocus aureus strains became resistant to macrolides after 6 months of azithromycin and remained resistant thereafter.ConclusionsNo clinical benefits of low-doses azithromycin were present after one year of treatment in young CF patients. Selection for macrolide-resistant strains of bacteria occurred, which should lead to a reconsideration of the duration of azithromycin treatment in CF.

International audience; Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by single or multiple benign lung nodules mimicking lung neoplasma. Histologic analysis reveals homogenous hyaline lamellae, usually surrounded by collection of plasma cells, lymphocytes and histiocytes in a perivascular distribution. The clinical and radiological findings have been described in small series, but the long-term outcomes have rarely been reported. The objectives were to describe the clinical, radiological and outcomes of PHG in new cases and through a literature review. Patients with PHG were found by a multicenter search among French departments of internal medicine, pulmonology and anatomo-pathology. Review of the literature was made through the National Library of Medicine’s MEDLINE database using keywords “hyalinizing granuloma.” Five news cases and 135 cases of the literature were found. There were 82 men and 57 women, mean age at the diagnosis 44.6 years (15–83). Patients were frequently asymptomatic (n = 39, 27.4 %). The nodule was unique in 37 cases (28.9 %) and multiple in 91 cases (71.1 %). 18FDG PET scan revealed hypermetabolism of the nodule in 9/15 cases (60 %). A systemic disease was associated in 65 cases (mainly mediastinal and retroperitoneal fibrosis, autoimmune, tumoral or infectious disease or thromboembolism). The outcomes were evaluated in 73 patients when follow-up was available: 14 patients had a surgical resection of the nodule. Forty-five patients did not receive any immunosuppressive drug. Among these patients, 2 improved, 29 were stable and 14 worsened. Corticosteroids were used as a monotherapy in 19 patients and led to radiological improvement in 8 cases, stabilization in 8 cases and worsening in 3 cases. Five patients were treated with corticosteroids and at least one immunosuppressive drug and 4 patients improved. PHG is a rare benign disease, mimicking lung neoplasma, frequently associated with systemic diseases.

Objectives Osteogenesis imperfecta (OI) is the most common genetic skeletal disorder. Extraskeletal findings are common but an association with sleep-disordered breathing (SDB) has never been described. The aim of this study was to investigate clinical features of children with OI and suspected SDB. Methods A retrospective study of clinical records, signs of SDB and polysomnographic recordings of children with OI was performed. We paid particular attention to symptoms that could be associated with SDB in this population – scoliosis, kyphosis, vertebral arthrodesis, chest wall deformities, basilar impression, autonomy – as well as data already known to be associated with obstructive sleep apnea such as body mass index and upper-airway impairment. Results We reviewed the clinical charts of 188 patients referred to our genetic skeletal disorders reference center for OI. Among the 15 patients (8%) with polysomnographic recordings, 12 (6.4%) had sleep-disordered breathing. We found a negative correlation between the Brief Assessment of Motor Function score and Apnea Hypopnea Index (r = −0.68; p = 0.01) and Desaturation Index (r = −0.62; p = 0.02). The Apnea Hypopnea Index was higher for non-walkers than walkers (mean [SD]: 6.5 [3.6] vs. 2.4 [1.5]; p = 0.02) and with type III versus IV OI. Two patients were started on continuous positive airway pressure ventilation, with clinical improvement. Conclusion For OI children, symptoms suggesting obstructive sleep disorders should be searched for systematically, especially in children with compromised autonomy, high body mass index, trunk deformations, and severe OI type.

Case report: We present the case of a 13 years old patient admitted to our center for repeated pneumonia with pleural effusion. This patient was initially treated in September 2014 for pneumonia with pleural effusion. The infection was successfully treated with antibiotics, but cough, fever and inflammatory syndrome reappeared within a month. He was referred to us in November. The CT scan showed right lung pneumonia and pleural effusion, associated with multiple necrotic mediastinal adenopathies. Bronchoscopy showed extrinsic compression of the right mainstem bronchus. Considering the evolution and the voluminous and necrotic adenopathies, mycobacterial infection appeared to be the best diagnostic hypothesis, and he was treated accordingly. After initial improvement, the recurrence of symptoms led us to perform another CT scan. This time it showed a voluminous and compressive pleural mass. Biopsy demonstrated undifferentiated tumor cells. Chromosome analysis identified a t(15;19) pattern. Nuclear protein of the testis (NUT) immunohistochemistry and fluorescence in situ hybridization confirmed NUT rearrangement. Discussion: NUT midline carcinoma (NMC) is a rare and extremely aggressive tumor. It is characterized by the presence of acquired chromosomal rearrangements usually involving bromodomain-containing protein 4-NUT fusion gene. Immunohistochemical expression of NUT in the nuclei of non-germ cell tumor is theoretically diagnostic (French CA. Annu Rev Pathol 2012; 7:247-65). NMCs are frequently unrecognized. Association of surgery and radiotherapy seems to give the best chances of survival (Bauer DE et al. Clin Cancer Res. 2012; 15:18(20):5773-9).

To evaluate the prevalence of nocturnal symptoms in a large sample of asthmatic patients, and to assess the agreement between patients' complaints and general practitioners' (GPs') reports in primary care.Cross-sectional survey involved 3,526 GPs and 751 specialists (pulmonologists and allergists) and included 13,493 patients with persistent asthma. Symptoms, treatment, and social and medical data were collected in real time by the patients and their GPs.France.Prevalence of nocturnal symptoms was 60%. A total of 7,989 patients with nocturnal symptoms had complete data for both patients and GPs; 3,849 (48.1%) had perfect agreement between GP and their complaints for nocturnal symptoms (agreement group; [kappa = 1]); 3,376(42.2%) declared having no symptoms during the night, but these were detected by the GP during the visit (underestimated by patients and detected by GPs); 773(9.6%) declared having nocturnal symptoms, but these were not detected by GPs. Patients with a good agreement with their GP's opinion were significantly more frequently followed-up by a specialist than other patients (p = 0.002).Nocturnal symptoms appear to be underdeclared by patients. GPs should therefore systematically ask their patients about nocturnal symptoms to increase control of asthma and to adequately manage its treatment.

Resume Il existe dans la region bordelaise un tres grand nombre de Pinus pinaster (pin maritime) responsables au printemps d'une forte pollinisation. Nous avons etudie prospectivement la sensibilisation a ce pollen dans une population de malades adresses en consultation de pneumoallergologie. On retrouvait chez 1,9 % de la population etudiee une sensibilisation au pollen de P. pinaster , soit une sensibilisation de 3 % parmi les sujets atopiques. Aucun d'entre eux n'avait de monosensibilisation, les tests cutanes positifs au pin maritime etant le plus souvent associes a une sensibilisation a d'autres pneumallergenes. Ces patients presentaient essentiellement des symptomes d'asthme et de rhinite, avec parfois des symptomes de conjonctivite. Nous n'avons pas mis en evidence de caracteristiques particulieres parmi les patients sensibilises. Cette etude confirme le faible pouvoir allergisant des pollens de pin dans une region ou leur concentration atmospherique est l'une des plus elevees.

Resume Introduction Le niveau de connaissances du patient sur sa maladie et son traitement est un element essentiel du diagnostic educatif. Il est donc utile de disposer d’un moyen rapide, aise et valide afin de collecter les informations necessaires a l’elaboration d’un programme educatif adapte aux besoins du patient. Le but de ce travail est de valider un questionnaire de connaissances sur la BPCO (BronchoPneumopathie Chronique Obstructive) selon une methode structuree. Methodes A partir d’une revue de la litterature, un questionnaire initial a ete construit. Il comportait 4 domaines : aspect biomedical, symptomes et signes de gravite, connaissances generales et traitements. L’auto-questionnaire a ete teste par 35 porteurs de BPCO afin d’evaluer sa clarte et sa comprehensibilite. Il a ete revu sur le fond et la forme par 11 experts francais puis modifie. La reproductibilite est etudiee par une procedure de test et retest. Resultats La premiere version du questionnaire elaboree par le groupe de travail comporte 50 items. Ce questionnaire est reduit a 41 items apres les entretiens cognitifs avec 35 porteurs de BPCO et l’evaluation par 11 experts. Le questionnaire est reproductible : pourcentage de concordance (moyenne : 79,5 % ; minimum : 53,3 % ; maximum : 100 %) et coefficient de correlation intra classe = 0,53. Conclusion Ce travail a permis le developpement d’un questionnaire de connaissances sur la BPCO en langue francaise.

Background: Quality of life (QOL) is an important component of evaluation in oncology. Usually, QOL is used in phase III studies to compare two treatments. The aim of this trial was to evaluate the impact of the disclosure of the diagnosis of cancer on QOL by using the European Organisation for Research and Treatment of Cancer core Quality of Life Questionnaire (EORTC QLQ)-C30 questionnaire and the supplemental lung cancer-specific module QLQ-LC13. Patients and methods: Patients hospitalised for exploration of an abnormal chest X-ray, with no previous history of cancer, a performance status ≤2, and able to fulfil the questionnaire were eligible. The patients answered the questionnaire two times: before (Q1) and after (Q2) the disclosure of the diagnosis. Results: Seventy patients answered at Q1 and Q2. After the disclosure, some scores deteriorated: arm pain ( P =0.009), physical functioning ( P =0.01), role functioning ( P =0.008), emotional functioning ( P =0.0001) and social functioning ( P =0.012), whereas the patients' own assessment of global QOL (item global QOL in functioning scales) did not show the same evolution. Conclusion: Disclosure of the diagnosis had an impact on social and emotional QOL. Patients with lung cancer need psychological support at the beginning of their disease.

Background: The AIR II study is a prospective multicentre assessing management of lower respiratory tract infections (LRTIs) in adults by general practitioners (GPs). Epidemiological studies generally address the prescriptions of antibiotics. To our knowledge, little is known about the real impact of non-antibiotic therapeutic prescriptions (defined here as co-prescriptions) in LRTI. Therefore, the aim of the study was to evaluate non-antibiotic prescriptions in LRTIs. Methods: Two thousand general practitioners (GPs) were randomly selected and asked to participate in each of 30 predefined areas covering mainland France. The patient's sociomedical record was completed by the GP during the consultation and sent to the data processing centre at the same time as an anonymous copy of his prescription. The GP also had to report the inclusion by telephone and agree to a telephone appointment with an interviewer. Results: GPs (n=3144) reported 5469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. Antibiotics were prescribed to 96.5% of patients. In addition to the 5270 prescriptions of antibiotics, co-prescriptions proved to be twice as numerous as prescriptions of antibiotics (10,027 prescriptions for 5115 patients). Mucomodifiers, steroidal anti-inflammatory drugs and bronchodilators were significantly more prescribed in AECB than others. Non-steroidal anti-inflammatory drugs and antitussives were significantly more prescribed in acute bronchitis than AECB or CAP. Conclusions: Our results suggest that recommendations of management in LRTIs need to take into account co-prescriptions.

International audience; BACKGROUND: Allergic sensitization to Alternaria has been related to asthma in various studies, but its association with allergic rhinitis is still controversial. OBJECTIVES: The aim of this study was to assess at the population level the relationships in childhood between Alternaria sensitization and 'past-year rhinoconjunctivitis' (PYRC), 'ever hay fever' (EHF) and 'ever allergic rhinitis caused by allergens other than pollens' (EAR) according to the presence or the absence of asthma. METHODS: This study is part of the Six Cities Study, the French contribution to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II. Children underwent skin prick test (SPT) to Alternaria and parents filled a standardized medical questionnaire. RESULTS: Some 6726 children with a mean age of 10 years were examined. The overall prevalence of Alternaria sensitization was 2.8%, 0.8% for monosensitization. Prevalences of symptoms in sensitized children were 27.7% for PYRC, 27.0% for EHF and 30.4% for EAR. Adjusted Odds Ratios (OR) between Alternaria sensitization and allergic rhinitis phenotypes were 2.34 (95% confidence interval: 1.51-3.63) for PYRC, 2.40 (1.65-3.50) for EHF and 2.95 (2.05-4.23) for EAR. The relationship still remained in the case of monosensitization to Alternaria for both PYRC and EAR when excluding the asthmatic children [OR = 3.87 (1.54-9.78) and 2.88 (1.10-7.55) respectively]. CONCLUSION: In our population-based sample of children, we found a link between Alternaria sensitization and allergic rhinitis, independently of asthma, which is compatible with the mechanisms of deposition of Alternaria in the upper airways.

The Analyse Infections Respiratoires (AIR) II study is a prospective, multicentre survey of the management of lower respiratory tract infections in patients aged 15-65 yrs by general practitioners (GPs) in France. To obtain real-time data recording, practitioners were required to submit an anonymous copy of their drug prescriptions. They were then interviewed over the telephone about the patients' sociodemographic data, signs and symptoms, as well as their presumptive diagnosis and the investigations they had decided upon. GPs (n=3,144) reported 5,469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. The symptomatology covered an extremely wide range of clinical features, which, although statistically different in terms of incidence, overlapped to a large extent across diagnoses. By contrast, hospitalization, investigations or referral to a specialist were much more prevalent in pneumonia, although still very infrequent in general terms (0.5, 1.2 and 10.8%, respectively). Antibiotics were prescribed in 96.5% of patients, with minor differences between diagnoses. However, other medications such as nonsteroid, anti-inflammatory drugs, steroids, nonspecific antitussives and bronchial liquefiers accounted for two-thirds of the prescriptions. This study demonstrates the lower respiratory tract infections encountered by general practitioners are usually mild. However, antibiotic prescription was more systematic than in previous studies and the prescription of nonspecific symptomatic treatments was twice as frequent. General practitioners did not perform additional examinations or refer on a regular basis. There was a high prescription rate for symptomatic treatment.

We prospectively considered 65 patients admitted for a spontaneous pneumothorax (SP) to describe the pragmatic management of SP, the first recurrence-free interval after medical therapeutic procedure and to specify the first recurrence risk factors over a 7-year period in these patients treated medically. The treatment options were observation alone (9%), needle aspiration (6%), small calibre chest tube (Pleurocatheter) drainage (28%) or thoracic tube drainage (49%), and pleurodesis with video-assisted thoracic surgery procedure (8%). Duration of the drainage and length of hospital stay were shorter in the Pleurocatheter group than in the thoracic tube group (P < 0.01). Among the 47 patients (72%) with a first SP and treated medically, nine patients (19%) had a first homolateral recurrence (FHR) during a mean follow-up of 84+/-13 months. Recurrence-free intervals ranged from 1 to 24 months (mean +/- SD: 9.3+/-8.4 months). FHR cases were more frequent in the Pleurocatheter group (P < 0 04). Analysis of potential risk factors showed that the patient's height and a previous homolateral SP episode are independent recurrence risk factors.

International audience; BACKGROUND: Fine particulate matter has been linked to allergies by experimental and epidemiological data having used aggregated data or concentrations provided by fixed-site monitoring stations, which may have led to misclassification of individual exposure to air pollution. METHODS: A semi-individual design was employed to relate individual data on asthma and allergy of 5338 school children (10.4 +/- 0.7 years) attending 108 randomly chosen schools in 6 French cities to the concentrations of PM2.5 (fine particles with aerodynamic diameter 2.5 microm) assessed in proximity of their homes. Children underwent a medical visit including skin prick test (SPT) to common allergens, exercise-induced bronchial (EIB) reactivity and skin examination for flexural dermatitis. Their parents filled in a standardised health questionnaire. RESULTS: After adjustment for confounders and NO2 as a potential modifier, the odds of suffering from EIB and flexural dermatitis at the period of the survey, past year atopic asthma and SPT positivity to indoor allergens were significantly increased in residential settings with PM2.5 concentrations exceeding 10 microg/m3 (WHO air quality limit values). The relationships were strengthened in long-term residents (current address for at least 8 years). CONCLUSIONS: Findings support the hypothesis that changes in allergy prevalence observed in recent decades might be partly related to interactions between traffic-related air pollution and allergens. Further longitudinal investigations are needed to corroborate such results.

International audience; Among early-life environmental factors, parental smoking (ETS) has been associated with adverse respiratory outcomes in children. The aim of the study was to evaluate whether parental smoking might lead to asthma and allergies taking into account family history of asthma, personal atopy, breast feeding as confounders and owing pets and day-care during the first 6 months of life as modifiers. About 9000 children of fourth and fifth grade were selected in six cities of France. About 7798 answered an epidemiological questionnaire, underwent a medical examination including skin prick test positivity to common allergens, skin examination for eczema, and run test to assess exercise-induced asthma (EIA). Prevalence of allergies was, respectively, 25.2% for eczema, 12.9% for rhinitis, 9.9% for asthma and 25% for atopy. About 8.3% had an EIA. About 21.6% of children were exposed to maternal tobacco smoking during pregnancy. Maternal smoking, in utero and later, was significantly related to lifetime wheezing (odds ratio (OR): 1.24[1.10-1.56]) and asthma (OR: 1.22[1.04-1.66]). There was no association between atopy, rhinitis, eczema and parental smoking, respectively. ETS remains a risk factor of wheezing in childhood. Counselling parents of children to quit smoking still remains a public health policy.

Criteria for the prescription of long-term oxygen therapy (LTOT) have been published by academic societies and regulatory bodies, but many prescriptions for LTOT do not fulfil these criteria. Demographic, functional data and survival were compared in chronic obstructive pulmonary disease (COPD) patients with different levels of oxygenation, i.e. arterial oxygen tension (Pa,O2) < 8 kPa or > or = 8 kPa (60 mmHg), at the time of initial registration in the ANTADIR Observatory. Data were collected between 1984-1995. Selection criteria were a diagnosis of COPD or emphysema with forced expiratory volume in one second (FEV1) < 80% pred, FEV1/vital capacity (VC) < 70% and age between 18-75 yrs. Of 7,700 patients prescribed LTOT 18.5% had stable Pa,O2 > or = 8 kPa. While the FEV1 was the same they differed from the patients with more severe hypoxaemia in having a higher rate of diagnosis of primary emphysema and a lower arterial carbon dioxide tension (Pa,CO2). In this group of patients LTOT was more frequently administered as liquid oxygen than in other patients on LTOT. The survival of these patients was reduced compared to the general population of the same age and sex but comparable to that of patients with a Pa,O2 between 6.7-8 kPa (50-60 mmHg). Patients prescribed long-term oxygen therapy with an arterial oxygen tension > or = 8 kPa (60 mmHg) in the ANTADIR network were shown to have severe chronic obstructive pulmonary disease on the basis of spirometry and their survival was similar to that of more hypoxaemic patients. Randomized controlled trials of the effect of long-term oxygen therapy in patients with arterial oxygen tension > or = 8 kPa are needed.

Resume La sensibilisation a Alternaria alternata est frequente dans les environnements chauds et secs, ou cette moisissure represente un des pneumallergenes majeurs. Sa prevalence varie de 7,5 a 17 % dans la population generale de certaines regions d'Australie ou des Etats-Unis alors qu'elle depasse rarement 5 a 7 % en Europe. Cette sensibilisation est plus frequente chez les malades asthmatiques pour qui clle pourrait representer un facteur de risque particulier. Dans des environnements propices a une forte sensibilisation, Alternaria pourrait ainsi multiplier le risque d'asthme, surtout chez l'enfant. En Europe et sous des climats plus humides, cette association est plus difficile a etablir, les autres pneumallergenes semblant jouer un role predominant.

International audience; BACKGROUND: Whereas effects on allergic and respiratory health have been established for passive tobacco smoking, contradictory results still exist for active tobacco smoking. OBJECTIVE: Whether adolescents with asthma and allied diseases have higher rates of active smoking compared with adolescents without asthma was assessed after controlling for environmental tobacco smoking exposure. METHODS: A population-based sample of 14,578 adolescents was enrolled in an epidemiological survey on allergies in France. RESULTS: After controlling for age, sex, geographic region, familial allergy and passive smoking, current (in the past year) wheezing (12.4%), current asthma (5.6%), lifetime asthma (12.3%), current rhinoconjunctivitis (13.9%), lifetime hayfever (14.4%) and current eczema (9.3%) but not lifetime eczema (22.5%) were all significantly related to active smoking (>1 cigarette/day) (9.3%). A higher risk of current wheezing, current and lifetime asthma or current eczema was seen in smokers exposed to passive smoking compared with smokers not exposed to it using a polychotomous logistic regression model, in which the different modalities of exposure to active and passive smoking constituted the response variable. Passive smoking was significantly associated only with current diseases. Active smoking was also highly related to both severe asthma (OR=4.02; 95% confidence interval: 1.37, 11.79) and severe rhinoconjunctivitis (OR=2.95; 1.58, 5.49). The highest rate of adolescents suffering from the co-morbidity of lifetime asthma and hayfever (3.6%) was also seen in active smokers compared with passive and non-smokers (5.5% vs. 3.6% and 3.1%, respectively; P=0.001). CONCLUSIONS: Being asthmatic or allergic does not seem to act as a deterrent towards starting active smoking or continuing to smoke in adolescence. Results suggest the need for considering individual allergic status in programming health educational activities aimed at reducing smoking among adolescents.

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca alkaloid. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m 2 per day, and increased to 15 mg/m 2 per day and 20 mg/m 2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62–66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40–45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m 2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time is 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m 2 per day of either a bolus or continuous infusion.

The authors are indebted to the collaborators in the participating centres and all parents, children, teachers and other school staff who participated in the surveys. There are many field workers and funding agencies who supported data collection and national, regional and international meetings, including the meetings of the ISAAC Steering Committee. Unfortunately, these are too numerous to mention (they are acknowledged elsewhere) but the authors particularly wish to thank the funders who supported the ISAAC International Data Centre including the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the National Child Health Research Foundation, the Hawke’s Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand and Astra New Zealand, as well as Glaxo Wellcome International Medical Affairs for finding the regional coordinating centres. The International Data Centre is now supported by a grant from the BUPA Foundation., The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit., peer-reviewed

Summary The uptake of the monoamine radiolabelled tracer 125I-meta-iodo-benzyl-guanidine (MIBG) was studied in vitro in platelets from 15 healthy volunteers and five allergic patients whose serum IgE concentration was 37 ± 33 and 650 ± 200 IU/ml, respectively. The MIBG uptake was determined by means of a gamma counter after incubation in a buffer. Binding of IgE to platelets significantly reduced MIBG uptake both in healthy subjects and in allergic patients. This reduction was significantly related to the action of IgE as it did not occur after binding of IgG. Moreover, MIBG uptake plotted versus increasing concentration of IgE (ranging from 10 to 3000 IU/ml) was fitted by a classical sigmoidal curve which was not significantly different between healthy subjects and allergic patients. Lastly, the effect of IgE on MIBG uptake was due to the binding of the sole IgE as it was not modified by subsequent addition of anti-IgE. It is concluded that the binding of the sole IgE to its specific receptor on platelets alters the transport of monoamines.

Pirarubicin (THP) (Roger Bellon Laboratory, France) is a new anthracycline under clinical development. In order to assess the efficacy and toxicity of the drug in small-cell lung carcinoma (SCLC), we have undertaken this trial in front-line therapy in patients with metastatic disease, PS less than 3 and at least one evaluable lesion. Responses were assessed after two cycles of THP (60 mg/m2 i.v. bolus every 3-4 weeks) and a further cross over to VP16 + CDDP (three cycles) was systematic whatever the response to THP. This crossover was performed after only one cycle in case of obvious progression. From June 1988 to April 1990, 32 patients were enrolled: 6 were ineligible (4 non-SCLC, 2 M0), 26 patients were fully evaluable for THP and 18 patients for VP16-CDDP. The characteristics of the patients were as follows: mean age 57.4 years (38-71); T4: 54%; T3: 27%; T2: 19%; N3: 62%; N2: 35%; No: 4%. The efficacy was as follows 1 complete response and 2 partial responses (confirmed by endoscopy); 12 patients received only one cycle because of obvious progression; the overall response rate is 12% (95% confidence interval 0-24%). The patient who had complete response after pirarubicin remained in CR after VP16-CDDP, whereas the 2 patients who had partial response achieved CR for one and PR for the other; among the 15 who did not respond 1 CR and 7 PR were observed. The only significant toxicity of THP was granulopenia without infection. THP seems to be an effective anthracycline in SCLC, and the study is continuing. A response could be reached in 50% of the nonresponders with standard therapy and 10 of 24 patients (42%) finally responded. Therefore, this schedule for testing new drugs in metastatic SCLC appears ethically acceptable.

Asthma-induced mortality increases especially among children; asthma induced morbidity impairs their day-to-day life as well as both their physical and psychological development. The treatment of asthma in children should reduce their symptoms. Although asthma medication appears to be efficient in clinical trials such is not the case in clinical practice and public health. The use of drugs and services depends upon the severity of the disease as well as upon cultural, personal and familial factors. These factors are crucial in the spontaneously inconsistent evolution of this disease. The management of asthmatic children should thus aim: 1) to alter behaviors--of both the patients and their parents who are often in charge of the treatment on a day-to-day basis and of the physician in order to organize a comprehensive therapeutic project for the sick children; 2) to enhance the collaboration between the different paramedical people involved in the treatment; 3) to improve the efficiency of the health system to allow it to achieve its goal of providing high-standard, accessible health care.

The most popular way to define asthma based on questionnaires is to use definitions taken from cross-sectional international studies on asthma. These definitions may not, however, be optimal for future studies focusing on risk factors of asthma. The current authors, therefore, compared the performance of different operational definitions of asthma. The European Community Respiratory Health Study I was a cross-sectional study of 21,924 subjects aged between 25-44 yrs in 18 countries. Operational definitions of asthma compared included different combinations of symptoms of asthma and bronchial hyperresponsiveness. A continuous asthma score, ranging from 0-8, was defined as the sum of positive answers to eight main symptom questions. There was no threshold in the associations of asthma symptoms with severity or risk factors of asthma, which would have suggested a dichotomous definition of asthma. Using dichotomous definitions requiring the presence of several asthma symptoms strengthened associations with studied risk factors, and also increased the estimated specificity and positive predictive value. Using a continuous asthma score also improved the power of the analyses. In conclusion, dichotomous definitions of asthma yielding higher odds ratios are achieved by requiring positive responses to several questions on symptoms. However, symptoms of asthma are possibly best analysed as a continuous asthma score.