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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)

The Center Val de Loire region is particularly affected by the shortage of health professionals. The demographics of dentists are not immune to this situation and the retirement of a practitioner has become a real public health issue. For this purpose, bridges were created between the faculties of odontology of Nantes, Clermont-Ferrand and the Faculty of Medicine of Tours, to welcome short cycle students in Center Val de Loire region, to create a link with the liberal practitioners and to allow the students to confront the health issues of this territory.

International audience; No abstract available

High flow nasal cannula oxygen therapy (HFT) is increasingly used in intensive and emergency care departments. Patients suffering from respiratory failure, who are likely to benefit from HFT, may require aerosolized bronchodilators; therefore, combining nebulization with HFT may be relevant. This study aimed to identify the optimal settings for the implementation of nebulization within an adult HFT circuit.We assessed the mass and the particle size distribution of the aerosol emitted from the nasal cannula (inhalable mass) using mesh- and jet-nebulizers placed at various positions in the HFT circuit. Thereafter, the most relevant combination was used to evaluate the mass of salbutamol delivered downstream of an anatomical model reproducing aerosol deposition and leakage at the nasal and pharyngeal levels (respirable mass). The influence of HFT flow rate (30, 45, and 60 L/min), of breathing pattern (quiet and respiratory distress pattern) as well as of opened and closed mouth breathing was assessed.The most efficient position was that of a nebulizer placed upstream from the humidification chamber (inhalable mass ranging from 26% to 32% of the nebulizer charge). Using a mesh nebulizer, we observed a respirable mass ranging from 2% to 10% of the nebulizer charge. Higher HFT flow rates and open mouth breathing were associated with a lower efficiency. Simulating respiratory distress (i.e., increasing the simulated patient inspiratory flow) did not hamper drug delivery as compared to a quiet breathing pattern.Placing nebulizers within a HFT circuit upstream from the humidification chamber may enable to deliver clinically relevant masses of aerosol at the cannula outlet, but more importantly downstream of the nose and pharynx, even in case of high patients' inspiratory flow. This method of aerosol therapy is expected to produce a bronchodilatatory effect to be evaluated in the clinical settings.

IgG4 has recently been a subject of great interest in human pathology. No data are available about the characteristics of asthma patients with elevated IgG4 levels.An observational study was conducted from January 2006 to March 2015 in a difficult-to-treat population of asthma patients. Twenty-six difficult-to-treat asthma patients with elevated serum IgG4 levels (IgG4/IgG ratio up to 10%) were compared with a control population of 98 difficult-to-treat asthma patients with normal serum IgG4. Blood eosinophilia, total IgE and FeNO were compared between groups to better characterize asthma patients with elevated serum IgG4 levels.Median IgG4 concentrations were 1.72 g/l [1.19-2.36] and 0.22 g/l [0.10-0.49] in the elevated IgG4 group and normal Ig4 group, respectively. Median blood eosinophilia was more than three times higher in patients with elevated serum IgG4 levels than in controls (0.75 10(9)/L [IQR 0.54-1.78] vs 0.22 10(9)/L [IQR 0.09-0.54] respectively, p0.0001). Total IgE was twice as high (264.5 kUI/l [IQR 166.3-779] vs 126 kUI/l [IQR 26-350] respectively; p0.05) and FeNO was nearly twice as high (61 [IQR 41-111] ppb vs 35 [IQR 23-51] ppb, p0.001). Allergic broncho-pulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were observed in the asthma patients with elevated serum IgG4. Ten patients had unexplained increased blood eosinophilia.Asthma patients with elevated IgG4 levels have significantly higher blood eosinophilia, total IgE and FeNO. ABPA and EGPA are observed in patients with elevated serum IgG4.

Objectives Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported in healthy volunteers. Methods Six CF patients were included, CMS and colistin concentrations were measured in plasma, urine and sputum. Either after single intravenous administration of 2 Million International Unit (MIU) or after repeated nebulizations of 2 MIU of CMS. PK of CMS and colistin were assessed by a mixed effect modeling approach. Results Renal clearance of CMS was lower in CF patients compared to that previously reported in healthy volunteers (64.3 mL/min (RSE = 15%) vs. 103 mL/min (RSE = 8%)). However, apparent clearance of colistin was higher in CF patients compared to healthy volunteers (124 mL/min (RSE = 13%) vs. 48.7 mL/min (RSE = 15%)), resulting in reduced systemic exposure to colistin (dose normalized AUC (2 MIU) of 7.4 h.mg/L/MIU vs. 11.2 h.mg/L/MIU). After repeated nebulizations, colistin concentrations were very low in plasma ( Conclusions Although our study suggests a lower median dose normalized colistin plasma concentrations in CF patients compared with healthy controls, this difference was not significant and a larger study is needed to substantiate this.

Resume La pentoxifylline (PTX) semble avoir des effets sur les cellules immunitaires en inhibant le tumor necrosis factor alpha (TNFα). Son role en tant qu’epargneur de corticoides dans le traitement de la sarcoidose reste a definir. Nous presentons le cas d’une patiente atteinte d’une sarcoidose corticodependante malgre l’utilisation d’azathioprine. Elle s’etait finalement amelioree cliniquement, fonctionnellement et scannographiquement avec l’adjonction du PTX. Lorsque la tolerance de la PTX est bonne et en absence de risque hemorragique, son rapport benefice/risque a long terme pourrait etre interessant chez certains patients atteints de sarcoidose corticodependante.

International audience; Nebulized antibiotic therapy directly targets airways and lung parenchyma resulting in high local concentrations and potentially lower systemic toxicities. Experimental and clinical studies have provided evidence for elevated lung concentrations and rapid bacterial killing following the administration of nebulized antibiotics during mechanical ventilation. Delivery of high concentrations of antibiotics to infected lung regions is the key to achieving efficient nebulized antibiotic therapy. However, current non-standardized clinical practice, the difficulties with implementing optimal nebulization techniques and the lack of robust clinical data have limited its widespread adoption. The present review summarizes the techniques and clinical constraints for optimal delivery of nebulized antibiotics to lung paren-chyma during invasive mechanical ventilation. Pulmonary pharmacokinetics and pharmacodynamics of nebulized antibiotic therapy to treat ventilator-associated pneumonia are discussed and put into perspective. Experimental and clinical pharmacokinetics and pharmacodynamics support the use of nebulized antibiotics. However, its clinical benefits compared to intravenous therapy remain to be proved. Future investigations should focus on continuous improvement of nebulization practices and techniques. Before expanding its clinical use, careful design of large phase III randomized trials implementing adequate therapeutic strategies in targeted populations is required to demonstrate the clinical effectiveness of nebulized antibiotics in terms of patient outcomes and reduction in the emergence of antibiotic resistance.

Despite recent advances in targeted therapy of non-small cell lung cancer (NSCLC), many patients do not benefit from these therapies. Inhibition of PD1/PDL1 is an interesting therapeutic target which restores the immune system against tumor cells. PD1 is located on lymphocytes and PDL1 on the antigen presenting cells. PD1 and PDL1 are co-inhibition molecules and their interaction results in immune tolerance against tumor cells. Anti-PD1 and anti-PDL1 antibodies have been developed to restore immune system in solid cancer including NSCLC. In phase I, studies assessing nivolumab, an anti-PD1 antibody, objective responses were observed in 13 to 18% of NSCLC patients failing previous treatment. The data obtained with anti-PDL1 antibodies is similar with objective responses ranging from 6 to 22%. The encouraging results of phase I/II studies must be confirmed in ongoing phase III studies. Anti-PD1 and anti-PDL1 antibodies exposed to new adverse events including auto-immune diseases whose support is not codified. Questions about treatment duration and criteria evaluation are not resolved. These treatments pave the way for immunomodulation in NSCLC treatment.

Background: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP. Objectives: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses. Methods: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24). Results: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03). Conclusions: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.

SUMMARYThe objective of this study was to determine how clinicians make use of the modern multiplex PCR assays (MPAs) to manage patients hospitalized for community-acquired pneumonia (CAP). We studied the use of MPAs in 1648 patients hospitalized for CAP over a 3-year period at the moment of the setup of the new PCR assay. We observed that the use of MPAs for the identification of multiple respiratory pathogens marks a radical change in the investigation of CAP etiology. Surprisingly, the contribution of MPAs to the medical decision-making process varies drastically according to the units of care.

Summary Primary endobronchial tumors are rare in children and they include a broad spectrum of lesions. The aim of this study was to determine the characteristic features, treatments and outcomes of these tumors. We report a retrospective analysis of all patients treated for endobronchial tumor in nine French hospitals between 1990 and 2010 and a comparison of the results with those reported in the medical literature. Twelve tumors were reported: five low grade muco epidermoid carcinomas, two inflammatory myofibroblastic tumors, two hemangiomas, one anaplastic large cell lymphoma, one carcinoid tumor, and one juvenile xanthogranuloma. The mean age of the patients was 7.5 ± 3.5 years. The most common sign revealing the disease was persistent atelectasis or recurrent pneumonia (eight cases). The other revealing signs were a persistent bronchospasm (three cases) and hemoptysis (one case). The clinical presentation, biology, serum tumor markers, and chest X-ray abnormalities were not specific to a particular histological diagnosis. Chest CT scan revealed the presence of an endobronchial tumor in 11 cases. Nine tumors could be diagnosed from a biopsy obtained by video endoscopy. Complete surgical resection was performed in seven patients. Bronchoscopic removal was performed in five cases and was successful in three. There were no deaths. Endobronchial tumors are rare in childhood and their histology is diverse. Chest CT scan and per-endoscopic endobronchial biopsies are required for diagnosis, when possible. Surgical or endoscopic treatment should be discussed by a multidisciplinary team. Despite the multiple etiologies, the prognosis of these tumors is good if diagnosis is early and if resection is complete. Long-term recurrences have been described, so long-term follow-up of these children is recommended. Pediatr Pulmonol. 2014; 49:E121–E125. © 2014 Wiley Periodicals, Inc.

Chronic infections of respiratory tracts are suspected to promote the development of IgA nephropathy. From the study of one case, we discuss the hypothesis that infections by pseudomonas aeruginosa might promote an increased bronchial production of IgA1, which could pass in the serum and settle into immune complexes in the kidney. A 67 years old woman presented simultaneously IgA nephropathy and diffuse panbronchiolitis. The evolution was marked by repeated infections by pseudomonas aeruginosa. The study of lung biopsy by immunohistochemistry showed intense expression of IgA1 in bronchioles, increased when compared to large bronchi. In contrast, expression of the transport receptor (pIgR) was decreased in inflamed bronchioles and preserved in bronchi. The BAL during an infection by pseudomonas aeruginosa showed increased secretory (S-) IgA with predominance of S-IgA1 (28.6 µg/mL versus S-IgA2 8.4µg/mL). In the sera collected during two infectious episodes and compared with an inter-critical sample, we found an increased IgA1 (776 and 549µg/mL versus 455µg/mL), associated with increased polymeric IgA (estimated at 40-50%, versus normally  10%). The increased expression of IgA1 in bronchiolar tissue, BAL and serum in the case of our patient further suggests a putative link between IgA nephropathy and diffuse panbronchiolitis, through exuberant production of IgA1 induced by pseudomonas aeruginosa infections.

International audience; By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately. Extrapulmonary comorbidities are common in COPD and influence prognosis; we propose an exhaustive comorbidities review

La Presse Medicale - In Press.Proof corrected by the author Available online since samedi 20 decembre 2014

International audience; PurposeIntranasal deposition of aerosols is often studied using in vitro nasal cavity models. However, the relevance of these models to predict in vivo human deposition has not been validated. This study compared in vivo nasal aerosol deposition and in vitro deposition in a human plastinated head model (NC1) and its replica constructed from CT-scan (NC2).MethodsTwo nebulizers (Atomisor Sonique® and Easynose®) were used to administer a 5.6 μm aerosol of 99mTc-DTPA to seven healthy volunteers and to the nasal models. Aerosol deposition was quantified by γ-scintigraphy in the nasal, upper nasal cavity and maxillary sinus (MS) regions. The distribution of aerosol deposition was determined along three nasal cavity axes (x, y and z).ResultsThere was no significant difference regarding aerosol deposition between the volunteers and NC1. Aerosol deposition was significantly lower in NC2 than in volunteers regarding nasal region (p

To the Editor: Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia, accounting for 40% of all cases in individuals >65 years of age. Thoracic complications of CLL can be classified into three groups: 1) infectious complications, which are by far the most frequent and are directly related to the severity of immunodeficiency secondary either to leukaemia or therapy; 2) pleural effusions that are either in CLL localisation or related to venous or lymphatic compression caused by a mass or lymph node, and 3) specific bronchopulmonary involvement secondary to lymphocytic infiltration. Specific bronchopulmonary involvement due to chronic lymphocytic leukaemia (or pathologic leukaemic bronchopulmonary infiltration (LBPI)) is rare and there are few reports in the literature. We report the cases of six patients with CLL and bronchopulmonary leukaemic infiltrates who needed specific treatment due to the severity of respiratory symptoms. The patients’ characteristics are summarised in table S1 in the online supplementary material. All patients gave their written informed consent for inclusion in this report. The six patients were all males. Mean age was 70 years (range 64–74 years). Patient 1 was a current smoker (40 pack-years) and patients 4 and 6 were former smokers (10 PA). CLL had been diagnosed in all patients through a combination of blood hyperlymphocytosis, characteristic lymphocyte morphology and immunophenotyping carried out in the Haematology Department (Tours university Hospital, Tours, France), an average of 6.2 years previously (range 3–14 years). At diagnosis, none of the patients presented with respiratory symptoms or computed tomography (CT) scan abnormalities indicative of LBPI. Patients 1, 2, 4, 5 and 6 had a previous pulmonary history of infectious pneumonia. Only patient 1 had never received specific CLL treatment. All …

Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2).In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2).In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.

Le diagnostic de pneumopathie medicamenteuse (PM) est un diagnostic d’elimination reposant sur des criteres chronologiques et semiologiques (imputabilite intrinseque) et des criteres bibliographiques (imputabilite extrinseque). En reanimation, la frequence de survenue des PM graves est difficile a evaluer, principalement du fait d’une difficulte pour obtenir un diagnostic de certitude. Dans les situations de pneumopathies hypoxemiantes bilaterales et apres avoir elimine les causes les plus communes (infection et œdeme pulmonaire cardiogenique), la PM doit etre evoquee systematiquement, car elle serait impliquee dans environ 10 % des syndromes de detresse respiratoire aigue (SDRA). Parmi les 400 medicaments connus comme « pneumotoxiques » et cites sur le site pneumotox.com, une centaine d’entre eux ont ete decrits comme pouvant donner des SDRA, parmi lesquels les plus frequemment en cause sont l’amiodarone, les chimiotherapies et les therapies ciblees.

Gastro-oesophageal reflux has long been suspected of implication in the genesis and progression of idiopathic pulmonary fibrosis (IPF). We hypothesised that hiatal hernia may be more frequent in IPF than in other interstitial lung disease (ILD), and that hiatal hernia may be associated with more severe clinical characteristics in IPF.We retrospectively compared the prevalence of hiatal hernia on computed tomographic (CT) scans in 79 patients with IPF and 103 patients with other ILD (17 scleroderma, 54 other connective tissue diseases and 32 chronic hypersensitivity pneumonitis). In the IPF group, we compared the clinical, biological, functional, CT scan characteristics and mortality of patients with hiatal hernia (n=42) and without hiatal hernia (n=37).The prevalence of hiatal hernia on CT scan at IPF diagnosis was 53%, similar to ILD associated with scleroderma, but significantly higher than in the two other ILD groups. The size of the hiatal hernia was not linked to either fibrosis CT scan scores, or reduction in lung function in any group. Mortality from respiratory causes was significantly higher among IPF patients with hiatal hernia than among those without hiatal hernia (p=0.009).Hiatal hernia might have a specific role in IPF genesis, possibly due to pathological gastro-oesophageal reflux.

Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence “MAbImprove,” the GDR 3260 “Antibodies and therapeutic targeting,” and the Grant Research program ARD2020 “Biotherapeutics” invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 – April 1, 2016 in Tours, France.

Ribavirin is an old drug that was developed and approved in the late 1980s to treat respiratory syncitial virus infections. It can be administered orally, intravenously, or by inhalation using a nebulizer. At the time it was developed, continuous nebulization was considered a valuable method to

Ulcerative colitis (UC) is an inflammatory bowel disease that can on rare occasions affect the respiratory tract. We report the case of a 32-year-old woman suffering from UC, for whom 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography (18F-FDG PET) was useful, both for diagnosis and management of tracheal involvement. She presented with severe cough and fever, and bronchoscopy revealed inflammation of the trachea. Infection, vasculitis and relapsing chondritis were first ruled out. Lymphoma was then suspected, and 18F-FDG PET was performed, but revealed only a moderately increased uptake on the posterior wall of the trachea. Histological findings revealed non-specific inflammation. Systemic corticosteroids were prescribed and symptoms improved rapidly. After 3 months, bronchoscopy showed a significant reduction of the local inflammation, and 18F-FDG PET did not reveal the previous abnormal tracheal 18F-FDG uptake. Management of tracheal involvement of UC requires close monitoring. However, repeated bronchoscopies can be harmful in these inflammatory situations, and non-invasive techniques could be useful. 18F-FDG PET is used for the follow-up of digestive involvement of UC, but extra-intestinal locations have not been evaluated. Our case highlights the potential interest of 18F-FDG PET for tracheal involvement of UC, allowing a non-invasive assessment of local inflammation.

Uncontrolled proteolysis by neutrophil serine proteases (NSPs) in lung secretions is a hallmark of cystic fibrosis (CF). We have shown that the active neutrophil elastase, protease 3, and cathepsin G in CF sputum resist inhibition in part by exogenous protease inhibitors. This resistance may be due to their binding to neutrophil extracellular traps (NETs) secreted by the activated neutrophils in CF sputum and to genomic DNA released from senescent and dead neutrophils. Treating CF sputum with DNase dramatically increases its elastase activity, which can then be stoichiometrically inhibited by exogenous elastase inhibitors. However, DNase treatment does not increase the activities of protease 3 and cathepsin G, indicating their different distribution and/or binding in CF sputum. Purified blood neutrophils secrete NETs when stimulated by the opportunistic CF bacteria Pseudomonas aeruginosa and Staphylococcus aureus. The activities of the three proteases were unchanged in these conditions, but subsequent DNase treatment produced a dramatic increase in all three proteolytic activities. Neutrophils activated with a calcium ionophore did not secrete NETs but released huge amounts of active proteases whose activities were not modified by DNase. We conclude that NETs are reservoirs of active proteases that protect them from inhibition and maintain them in a rapidly mobilizable status. Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions.

Summary Background Bronchogenic carcinoma (BC) is a worldwide health public problem with a parallel but delayed development to smoking. The prognosis of BC in young patients is poorly known mainly because of few studies that have looked at this group of patients. The hypothesis of our study is that ‘young’ patients with BC have a better prognosis than others. Methods We conducted a retrospective epidemiologic study of all patients aged 45 and under (n = 73) followed for BC between 2002 and 2007 in two hospitals in the central region in France, compared with patients over 45 years random (n = 73). We evaluated the clinical characteristics (sex, smoking habits, WHO status, clinical presentation, histology, TNM stage), the management and prognosis of these patients. Results The median survival of patients aged 45 and under was 13.4 months against 8.9 months for patients over 45 years. In multivariate analysis, age is not an independent prognostic factor (P = 0.41) in contrast to the WHO status (P = 0.002) and initial TNM stage (P Conclusion In our study, the better prognosis of the “young” patient group is not directly related to age but in good condition and lower TNM stage of these patients.

Resume Objectifs Le nebuliseur Respirgard II ® recommande pour l’administration de pentamidine vient d’etre retire du marche. Notre etude recense les pratiques actuelles pour la nebulisation de pentamidine dans le secteur hospitalier pediatrique. Patients et methodes Un questionnaire a ete envoye aux differents services d’hemato-oncologie et pneumologie pediatriques des CHU de France. Etaient recherches : les indications de traitement, le nombre d’enfants traites en 2010, les effets secondaires observes et le materiel utilise pour la nebulisation. Resultats Sur 62 services interroges, 36 reponses (58 %) ont ete obtenues. La pentamidine etait surtout prescrite chez des enfants immunodeprimes suivis en hematologie pediatrique âges de cinq a 15 ans ( ® , Respiromed CR01 ® , MicroCirrus ® ). Conclusion La nebulisation de pentamidine reste une pratique peu repandue en pediatrie. Une meilleure information sur le type de nebuliseurs a utiliser est necessaire.

COPD is a slowly progressive chronic respiratory disease causing an irreversible decrease in air flow. The main cause is smoking, which provokes inflammatory phenomena in the respiratory tract. COPD is a serious public health issue, causing high morbidity, mortality and disability. Related comorbidities are linked to ageing, common risk factors and genetic predispositions. A combination of comorbidities increases healthcare costs. For instance, patients with more than two comorbidities represent a quarter of all COPD sufferers but account for half the related health costs. Our review describes different comorbidities and their impact on the COPD prognosis. The comorbidities include: cardiovascular diseases, osteoporosis, denutrition, obesity, ageing, anemia, sleeping disorders, diabetes, metabolic syndrome, anxiety-depression and lung cancer. The prognosis worsens with one or more comorbidities. Clinicians are faced with the challenge of finding practical and appropriate ways of treating these comorbidities, and there is increasing interest in developing a global, multidisciplinary approach to management. Managing this chronic disease should be based on a holistic, patient-centred approach and smoking cessation remains the key factor in the care of COPD patients.

We investigated the biodistribution, pharmacokinetics, safety profile, and feasibility of aerosolized gemcitabine (GCB) in patients with lung carcinoma.Eleven patients with carcinoma localized in the lungs were studied in a dose escalation study of aerosolized GCB administered 1 day/week for 9 consecutive weeks. Safety data, scintigraphic assessment of the delivered dose and pharmacokinetic monitoring were analyzed. Patients were treated with doses of between 1 mg/kg and 4 mg/kg (dose in the nebulizer), using a new inhaler device (Aeroneb Pro with an Idehaler Chamber).The total dose of GCB delivered to the patient's lung was 42±16% of the initial amount of dose in the nebulizer. Safety data showed no hematologic toxicity, nephrotoxicity or neurotoxicity. At 4 mg/kg, one patient experienced grade 4 pulmonary toxicity (bronchospasm), which was the dose-limiting toxicity. Grade 2 and 3 toxic effects included fatigue, vomiting, dyspnea, and cough. Overall response: minor response in one patient, stable disease in four patients, progressive disease in four patients. Pharmacokinetic data showed very low plasma GCB levels. Maximal plasma concentration was observed at the end of nebulization. Aerosolized gemcitabin was safe, with minimal toxicity, for patients with lung carcinoma.

PURPOSE: To quantify the amount of aerosol deposited in different parts of the airways with a commercially available nasal sonic jet nebulizer (NJN) using a sound effect, and to compare its performance with a new nasal mesh nebulizer (NMN). METHODS: Seven healthy non-smoking male volunteers aged 21-36 years with a mean weight of 77±10 kg were included in this single-center study. Both nebulizer systems were loaded with (99m)Tc-DTPA and scintigraphies were performed with a gamma camera. Particle size distribution of the aerosols produced by the two nebulizer systems was measured. RESULTS: There was no statistical difference between the two nebulizers in terms of fraction of particles smaller than 5 μm (44±4% vs 45±2%) (p>0.9). Aerosol deposition in the nasal region was 73±10% (% of aerosol deposited in airways) with the NJN, and 99±3% with the NMN (p=0.01). Total nasal deposition was 9.6±1.9% of the nebulizer charge with the NJN and 28.4±8.9% with the NMN (p=0.01). 0.5±0.3% of the nebulizer charge was deposited in the maxillary sinuses with the NJN, compared to 2.2±1.6% with the NMN (p=0.01). CONCLUSION: Although the two nebulizers had the same particle size, NMN significantly improved aerosol deposition in nasal cavity and prevents deposition into the lungs.

Background Jet nebulizers are commonly used to administer aerosolized tobramycin to CF patients. The aim of this study was to assess the performance of disposable jet nebulizers as an alternative to reusable nebulizers such as the Pari LC Plus. Method From a survey conducted in 49 CF centers in France, 18 disposable jet nebulizer systems were selected. An in vitro study was performed with 20 jet nebulizer/air source combinations (18 disposable and 2 reusable) to determine their performance with tobramycin solution (300mg/5mL). A scintigraphic deposition study in baboons was performed to validate the in vitro data. Results In vitro and in vivo results correlated. There was no overall relationship between the compressed air source and nebulizer performance, but the nebulizer interface was responsible for significantly different results. Conclusions None of the disposable nebulizers tested in this study can be recommended as an alternative to the Pari LC Plus nebulizer for tobramycin.

Melioidosis is a disease that is endemic in North Australia and Southeast Asia, caused by Burkholderia pseudomallei. This Gram-negative organism can affect all organs, but presents most commonly as severe pneumonia. We report a 58-year-old man who presented with a B. pseudomallei pneumonia on his return from Thailand. Radiography revealed a complete disappearance of symptoms after a 3-week therapy with ceftazidime and doxycycline followed by 4 months of combined amoxicillin-clavulanic acid and doxycycline therapy. No relapse had occurred 18 months later.

International audience; Invasive pulmonary aspergillosis (IPA) is of particular concern to immunodeficient patients, whose mortality rates may exceed 80%. The development of an animal model that faithfully reproduces the pathophysiology of IPA would improve the studies on diagnostic and therapeutic modes, and the use of rats as a possible model for IPA seems to have been largely overlooked. Such a model could be established with the MicroSprayer IA-1B Ò. Male Sprague-Dawley rats (6-8 weeks old) were rendered immunodeficient by cyclophosphamide injections and a protein-deficient diet. On day D0, they were anaesthetised by inhalation of 5% isoflurane and infected by the intra-tracheal aerosolisation of 100 ll of an Aspergillus fumigatus spore suspension through a MicroSprayer IA-1B Ò. This inoculation process was simple and rapid, with no deaths observed during or immediately after the procedure. The rats regained consciousness within 1 min. Follow-up data including those for clinical factors (weight changes, mortality rate), biological factors (Aspergillus antigens) and histological factors were consistent with previous studies. The advantages of this model include the ease of animal manipulation, the reproducibility of infection and the potential for repeated blood sampling.

Respiratory involvement in systemic lupus erythematosus D. Carmier, S. Marchand-Adam, P. Diot, E. Diot Respiratory involvement in systemic lupus erythematosus (SLE) is not as well known as the cutaneous, rheumatological and renal manifestations. It occurs frequently but the diagnosis may be difficult because of the heterogeneity of the anatomical and clinical presentations. A precise diagnosis is crucial as new immunosuppressive drugs have considerably improved the prognosis. The pathology involves genetic, endocrine, environmental, pharmacological and immunological factors with a cytotoxic reaction of auto antibodies against complement, a circulating immune complex reaction and a hyperactivity of B lymphocytes. Respiratory involvement in SLE can be classified in 5 groups based on the anatomy: pleural involvement, infiltrating pneumonia (lymphoid interstitial pneumonia, bronchiolitis obliterans with organizing pneumonia and acute lupus pneumonitis), airways involvement (upper airways, bronchi), vascular involvement (pulmonary hypertension, acute reversible hypoxaemia, alveolar haemorrhage, and antiphospholipid syndrome), muscular and diaphragmatic involvement (shrinking lung syndrome). Treatment is based, depending upon the type of involvement and its severity, on steroids which may be combined with immunosuppressants and plasmapheresis.

Une enquete sur la pratique de la nebulisation en France a ete conduite en 2004 par le GAT (Groupe AerosolTherapie de la Societe de Pneumologie de Langue Francaise). Methodes un questionnaire a ete envoye a 50 000 medecins generalistes (MG) et specialistes. Les reponses ont ete exploitees par Analyse des Correspondances Multiples. Resultats Quatre mille huit cent quatre-vingt-dix-huit medecins (9,4 %) ont repondu, dont 59,1 % de MG, 16,9 % de pneumologues, 13 % de pediatres et environ 10 % d’autres specialistes, ORL, allergologues, urgentistes et reanimateurs. La raison principale pour laquelle les pneumologues prescrivent la nebulisation est l’efficacite de l’administration a long terme (1 semaine a > 1 mois) de medicaments valides. Les MG qui prescrivent la nebulisation pour son action locale, utilisent des substances non validees, sur de courtes periodes ( Conclusion Cette etude devrait aider au developpement de programmes de formation a la nebulisation afin d’optimiser sa prescription en terme d’indications, de choix d’appareils et de medicaments.

Summary A survey of nebulisation practice in France was conducted under the aegis of the French respiratory society in 2004. Methods Analysis of a questionnaire was obtained from 3674 physicians. Results A total of 2439 physicians were general practitioners (GPs), 698 were chest physicians, and 537 paediatricians. The main reasons to use nebulisation are (1) for chest physicians efficacy in treating various pathologies with long-term administration (1 wk to ⩾1 month) of approved drugs, and (2) for GP's local action properties. While chest physicians learned about nebulisation during their university training and do not ask for additional information, GPs learned by practical experience or from colleagues and ask for further information. Conclusion This study will help to develop targeted educational programmes on nebulisation practice.

Despite an increasing interest in the use of inhalation for local delivery of molecules for respiratory diseases and systemic disorders, methods to deliver therapy through airways has received little attention for lung cancer treatment. However, inhalation of anticancer drugs is an attractive alternative route to systemic administration which results in limited concentration of the medication in the lungs, and triggers whole-body toxicity. In this study, we investigated the feasibility of nebulization for therapeutic antibodies, a new class of fully-approved anticancer drugs in oncology medicine. Cetuximab, a chimeric IgG1 targeting the epidermal growth factor receptor (EGFR), was nebulized using three types of delivery devices: a jet nebulizer PARI LC+®, a mesh nebulizer AeronebPro® and an ultrasonic nebulizer SYST’AM® LS290. Aerosol size distribution was measured using a cascade impactor and aerosol droplets were observed under optical microscopy. The immunological and pharmacological properties of cetuximab were evaluated following nebulization using A431 cells. The aerosol particle clouds generated with the three nebulizers displayed similar aerodynamical characteristics, but the IgG formed aggregates in liquid phase following nebulization with both the jet and ultrasonic devices. Flow cytometry analyses and assays of EGFR-phosphorylation and cell growth inhibitions on A431 demonstrated that both the mesh and the jet nebulizers preserved the binding affinity to EGFR and the inhibitory activities of cetuximab. Altogether, our results indicate that cetuximab resists the physical constraints of nebulization. Thus, airway delivery represents a promising alternative to systemic administration for local delivery of therapeutic antibodies in lung cancer treatment.

Resume Introduction Les auteurs rapportent un cas de tracheobronchopathie chondro-osteoplastique (TBCO) responsable d’une stenose tres serree et etendue de la trachee, associee a un ozene. Observation Une etiopathogenie commune de type infectieux est suspectee devant la presence de la bacterie Klebsiella pneumoniae subsp ozaenae chez ce patient et dans la litterature consacree a ces deux pathologies. Conclusion Cette observation de TBCO se distingue par ailleurs par son caractere peu evolutif et par la bonne tolerance de la stenose tracheale avec cinq ans de recul.

The best delivery of a drug in ventilated neonates is obtained when using a small particle diameter solution administered via a spacer. Lung deposition of hydrofluoroalkane beclomethasone dipropionate (QVAR, 1.3 microm particles), delivered via an Aerochamber-MV15, was measured in piglets under conditions mimicking ventilated severely ill neonates (uncuffed 2.5 mm endotracheal tube; peak pressure 16 cm H2O; respiratory rate 40/min). After determining the mass and particle size distribution of the 99mTc-labeled and unlabeled drug, three lung deposition studies were performed: after 1 h of ventilation (controls, n = 18), after 48 h aggressive ventilation inducing an acute lung injury (nine piglets out of the controls), and after increasing the pressure to 24 cm H2O during drug delivery (five piglets out of the nine with acute lung injury). All piglets were then killed for lung histology. Results (median, range), expressed as a percentage of the delivered dose, were compared using an inferential or the Friedman test. While lung deposition was low, it was greater (p = 0.003) in controls (2.66%, 0.50-7.70) than in piglets with histologically confirmed acute lung injury (0.26%, 0.06-1.28) or under a high-pressure ventilation (1.01%, 0.30-2.15). Lung deposition of QVAR in an animal model of ventilated neonates is low, variable, and dramatically affected by lung injury.

The recent decade has witnessed a change of view about cancer mechanisms. Considerable evidence now suggests that the tumour microenvironment status is well correlated with disease outcome. The presence of particular immune cell types or molecules determines whether a pro- or antitumour immune response predominates within the microenvironment [1]. Accordingly, improved understanding of the factors that modulate the tumour microenvironment will be critical for the development of effective future strategies for cancer management. High expression of IL-22R1 in nonsmall cell lung cancer is an independent indicator of poor overall survival

The objective of this study was to evaluate the mass of salbutamol delivered by a pMDI or a mesh nebulizer using a spacer in a pediatric model of mechanical ventilation. For the use with pMDI (Ventoline, 100µg/puff, GlaxoSmithKline, France) the spacer (Combihaler, Laboratoire Protec9Som, France) was compared with a T-piece. For the nebulization of salbutamol (2.5mg/2.5ml), a mesh nebulizer (Aeroneb Solo, Aerogen, Ireland) was used with a T-adapter or a spacer. In this study, a respirator (Volume controlled, Vc = 155mL, f = 25/min, PEEP = 6, P max = 8, ratio between the inspiratory time and the expiratory time = 50/50) and a model of lung Dual TTL model 5600i (Michigan Instruments) were used. A filter was placed after the 5.0 mm endotracheal tube. The concentration of salbutamol was measured by spectrophotometry after the use of the pMDI and after nebulization Values, expressed as mean +/- SD, were compared using one-way ANOVA. With pMDI, the mass of salbutamol deposited on the filter was twice higher with the spacer compared with the T-piece (19 ± 1.5 µg vs 8.2 ± 1.7 µg). After nebulization, salbutamol aerosol delivery increased withspacer in comparison with the T-adapter (32.7 ± 3.5 % vs 22.1 ± 2.0 %). In addition, the use of a spacer reduces the mass of salbutamol deposited between the Y-piece and the endotracheal tube compared with the T-adapter. In pediatric conditions, the spacer increase the amount of salbutamol deposited by 2.3 compared with the T-piece. Concerning the nebulization, the deposition of salbutamol is increased by 1.5 with the spacer compared with T-adapter.

Chronic obstructive pulmonary disease (COPD) is punctuated by episodes of infection-driven acute exacerbations. Despite the life-threatening nature of these exacerbations, the underlying mechanisms remain unclear, although a high number of neutrophils in the lungs of COPD patients is known to correlate with poor prognosis. Interleukin (IL)-22 is a cytokine that plays a pivotal role in lung antimicrobial defence and tissue protection. We hypothesised that neutrophils secrete proteases that may have adverse effects in COPD, by altering the IL-22 receptor (IL-22R)-dependent signalling.Using in vitro and in vivo approaches as well as reverse transcriptase quantitative PCR, flow cytometry and/or Western blotting techniques, we first showed that pathogens such as the influenza virus promote IL-22R expression in human bronchial epithelial cells, whereas Pseudomonas aeruginosa, bacterial lipopolysaccharide or cigarette smoke do not. Most importantly, neutrophil proteases cleave IL-22R and impair IL-22-dependent immune signalling and expression of antimicrobial effectors such as β-defensin-2. This proteolysis resulted in the release of a soluble fragment of IL-22R, which was detectable both in cellular and animal models as well as in sputa from COPD patients with acute exacerbations.Hence, our study reveals an unsuspected regulation by the proteolytic action of neutrophil enzymes of IL-22-dependent lung host response. This process probably enhances pathogen replication, and ultimately COPD exacerbations.