Impact on the medical decision-making process of multiplex PCR assay for respiratory pathogens.

The 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.

What the pulmonary specialist should know about the new inhalation therapies.

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.

The utility of a nebulised intra-tracheal rat model of invasive pulmonary aspergillosis.

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. 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 aerosolization of 100 microl of an Aspergillus fumigatus spore suspension through a MicroSprayer IA-1B. 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.

[Intra-alveolar pulmonary haemorrhage, an unusual manifestation of the primary antiphospholipid syndrome]. / L'hémorragie intra-alvéolaire, une complication rare du syndrome primaire des antiphospholipides.

Pulmonary embolism is the main pulmonary manifestation of primary antiphospholipid syndrome. Other pulmonary manifestations including intra-alveolar haemorrhage are less common. We report a 36-year-old man with a primary antiphospholipid syndrome who presented with an acute respiratory failure due to the association of pulmonary embolism and intra-alveolar haemorrhage. This diagnosis should be systematically considered as it is life threatening and requires a specific therapy.

[Nebulized corticosteroids and pediatricians: results of the NUAGES survey]. / Prescription des corticoïdes nébulisés par les pédiatres : résultats de l'enquête NUAGES.

INTRODUCTION: The aim of the study was to analyze the data of the NUAGES survey (a survey on the practice of nebulization in France), concerning the prescriptions of nebulized steroids from 514 pediatricians. MATERIAL AND METHODS: The reason why nebulization was chosen as a delivery route, the diseases motivating the prescription, the age of the patients, the kind of drug used, and the prescription and device modalities were studied. RESULTS: Efficacy in treating various respiratory diseases was the main reason cited for using nebulization, in particular severe persistent asthma (76%). Pediatricians prescribed nebulization mainly to infants (60%). The most frequently used drug was budesonide suspension (89%), but the intravenous route for steroids (18%) and drug admixtures (62%) were also proposed by nebulization. A specific prescription for the nebulizer was given in 75% of the cases, with the type of interface to use specified in 66%. DISCUSSION: Pediatricians consider that nebulization is well adapted to young children. Although the proper steroid is usually chosen, unfortunately, it is often prescribed with other drugs, with 1 prescription out of 4 not following the recommendations. Prescription of the device is not optimal and may compromise the efficacy of the treatment. CONCLUSION: Nebulization is a potential mode of delivery for steroids that is difficult to prescribe and warrants improved pediatrician training.

[Respiratory involvement in systemic lupus erythematosus]. / Atteinte respiratoire au cours du lupus érythémateux systémique.

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.

[Alveolo-interstitial pneumonia due to Temozolamide]. / Pneumonie alvéolo-interstitielle au témozolomide.

INTRODUCTION: Temozolomide is an alkylating agent approved for treatment of glioblastoma in association with radiotherapy. CASE REPORT: We report the case of a 56 year old woman presenting with alveolo-interstitial pneumonia after treatment with Temozolomide. Initially she received induction treatment with Temozolomide and concomitant radiotherapy for bifocal high grade glioblastoma. A month later she received, as scheduled, the first course of Temozolomide maintenance chemotherapy. Grade II dyspnoea developed a few days later. High resolution computed tomography showed alveolo-interstitial opacities with basal predominance, associated with alveolar nodules. Broncho-alveolar lavage showed a lymphocytosis. No bacteria were isolated from microbiological samples. A final diagnosis of drug-induced pneumonia was based on the time sequence and absence of other causes. CONCLUSION: There is little literature concerning the pulmonary toxicity of Temozolomide. However, our case report of drug-induced pneumonia and similar observations in the databases of regional pharmacovigilance centres suggest that this side effect should be included in the summary of product characteristics.

[Difficulties in the management of localised pulmonary Goodpasture's syndrome]. / Difficultés de la prise en charge d'une forme pulmonaire isolée du syndrome de Goodpasture.

INTRODUCTION: The diagnosis of the pulmonary forms of Goodpasture's syndrome is not easy and requires a renal biopsy when no anti-glomerular basement membrane antibodies are detected, since the disease can lead to spontaneous massive intra-alveolar haemorrhage that can be fatal. Treatment for the pulmonary-renal form combining corticosteroids, cyclophosphamide and plasmapheresis should be applied to the pulmonary form to control haemorrhage and prevent relapse. CASE REPORT: We report the case of a patient suffering from the localised pulmonary form of Goodpasture's syndrome in whom the diagnosis was delayed due to a negative indirect immunofluorescent antibody bioassay. After a serious early relapse remission was achieved with comprehensive treatment and a tobacco withdrawal programme. CONCLUSION: If there is no delay in diagnosis and comprehensive treatment is given, the prognosis for these patients is good with a recovery rate of 80 to 90%.

[A survey of nebulization practices in France conducted in 2004 by the GAT]. / NUAGES: une enquête sur la pratique de la nébulisation en France.

METHODS: A questionnaire was sent to 50 000 general practicioners (GP) and specialists. RESULTS: 4,898 physicians (9.4%) responded, including 59.1% GP, 16.9% pneumologists, 13% pediatricians and about 10% other specialists, ENT, allergologists, and intensivists. The main reason for pneumologists to prescribe nebulization was the efficiency on long term of approved drugs. GP prescribe nebulization for its local effects, using unapproved drugs, on short periods of time, especially in COPD, asthma, bronchitis and tracheitis/laryningitis. Although pneumologists have been trained during their fellowship and do not ask for further education, MG have learned by their own experience and are asking for further education. CONCLUSION: This study should help to develop teaching programs on nebulization with the aim to optimize its practice.

[The pentoxifylline, a corticosteroid sparing in the treatment of sarcoidosis: A case report]. / La pentoxifylline, un épargneur de corticoïdes dans le traitement de la sarcoïdose : à propos d'une observation.

INTRODUCTION: The pentoxifylline seems to have some effects on immune cells by inhibiting tumor necrosis factor alpha (TNFα). Its role as a sparing corticosteroids in the treatment of sarcoidosis remains to be defined. CLINICAL CASE: We present the case of a patient with sarcoidosis corticodependent despite the use of azathioprine. It was finally improved clinically, functionally and by a thoracic computed tomography with addition of pentoxifylline. CONCLUSION: When the tolerance of the pentoxifylline is good and there is not a bleeding risk, the benefit-risk in the long term might be interesting in some patients with sarcoidosis corticodependent.

Insights on animal models to investigate inhalation therapy: Relevance for biotherapeutics.

Acute and chronic respiratory diseases account for major causes of illness and deaths worldwide. Recent developments of biotherapeutics opened a new era in the treatment and management of patients with respiratory diseases. When considering the delivery of therapeutics, the inhaled route offers great promises with a direct, non-invasive access to the diseased organ and has already proven efficient for several molecules. To assist in the future development of inhaled biotherapeutics, experimental models are crucial to assess lung deposition, pharmacokinetics, pharmacodynamics and safety. This review describes the animal models used in pulmonary research for aerosol drug delivery, highlighting their advantages and limitations for inhaled biologics. Overall, non-clinical species must be selected with relevant scientific arguments while taking into account their complexities and interspecies differences, to help in the development of inhaled medicines and ensure their successful transposition in the clinics.

N.U.A.G.E.S: a survey of nebulisation practice in France with regard to ERS guidelines.

UNLABELLED: 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.

[Association of tracheobronchopathia osteochondroplastica and ozène]. / Association trachéobronchopathie chondro-ostéoplastique et ozène.

INTRODUCTION: We report a case of tracheobronchopathia osteochondroplastica associated with Ozena (atrophic rhinitis). OBSERVATION: Fibreoptic bonchoscopy showed irregular tracheal stenosis and histopathological examination displayed zones of bone metaplasia in the tracheal submucosa. We isolated the bacteria Klebsiella pneumoniae sp ozaenae from bronchial aspirate. CONCLUSION: This organism is frequently isolated in both conditions suggesting some link between the two diseases.

[Carrington's disease without eosinophils in the bronchial lavage]. / Une maladie de Carrington sans éosinophilie au lavage broncho-alvéolaire.

INTRODUCTION: Idiopathic chronic eosinophilic pneumonia (ICEP) or Carrington's disease is an infiltration of the lung parenchyma by eosinophils without known cause. The diagnosis of ICEP is based on well defined clinical and radiological characteristics associated with blood and/or alveolar eosinophilia. Alveolar hypereosinophilia is marked and regarded as a constant feature. CASE REPORT: We report the case of a 57 year old man seen on account of a cough and deterioration of general health associated with radiographic peripheral pulmonary infiltrates, blood hypereosinophilia but no hypereosinophilia in the bronchial lavage (BL). The diagnosis of ICEP was made after histological examination of a surgical lung biopsy. CONCLUSION: Absence of alveolar hypereosinophilia in ICEP remains exceptional and in this case confirmation of the diagnosis may depend on examination of a lung biopsy.

Comparative analysis of different scintigraphic approaches to assess pulmonary ventilation.

A study was carried out to investigate the predictive value of 81-metastable-krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the correlation between the 81mKr distribution, the 99mTc aerosols deposition, and the respiratory parameters of patients with chronic obstructive pulmonary disease (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol lung scintigraphies were successively carried out. The 81mKr distribution and 99mTc deposition were compared to the 133Xe distribution at equilibrium and to the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to detect alterations in ventilation revealed by 133Xe were defined. The 81mKr distribution and 99mTc deposition according to respiratory parameters were described using a principal component analysis. Compared to 133Xe distribution, a significantly higher distribution of 81mKr in the upper parts of the lungs in the more severe patients (p = 0.05), a significantly higher deposition of Technegas in the lower parts of the lungs (p = 0.0008), and a significantly higher deposition in the central parts of the high-size 99mTc aerosol were observed (p = 0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54 and 0.55 for Technegas. There was a significant negative correlation between 81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta-acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr peripheral distribution and Technegas peripheral deposition correlated negatively with increased obstruction, as measured by forced expiratory volume in 1 sec (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and 99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary ventilation as measured by 133Xe scintigraphy.

What are the characteristics of asthma patients with elevated serum IgG4 levels?

INTRODUCTION: 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. POPULATION AND METHODS: 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. RESULTS: 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, p < 0.0001). Total IgE was twice as high (264.5 kUI/l [IQR 166.3-779] vs 126 kUI/l [IQR 26-350] respectively; p < 0.05) and FeNO was nearly twice as high (61 [IQR 41-111] ppb vs 35 [IQR 23-51] ppb, p < 0.001). 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. CONCLUSION: 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.

[Paraneoplastic pemphigus revealing dendritic cell sarcoma originating from Castleman's disease of the neck]. / Pemphigus paranéoplasique révélateur du développement d'un sarcome à cellules dendritiques à partir d'une tumeur de Castleman pulmonaire.

INTRODUCTION: Paraneoplastic pemphigus is associated with Castleman's disease. We report a case of paraneoplastic pemphigus at the stage of the sarcomatous transformation of Castleman's disease, present for many years but without concomitant paraneoplastic pemphigus. The pemphigus was manifested by the most unusual, exclusive, involvement of the mucosa of the mouth and lung. OBSERVATION: A 32 year-old man suffering from extensive ulceration of the oral mucosa was hospitalized in December 2000 for alteration in his general status of health and acute respiratory failure. The search for intercellular anti-substance antibodies on rat spleen was positive, corresponding to anti-envoplakin IgG and leading to the diagnosis of paraneoplastic pemphigus. The thoracic x-ray and scan revealed a hilum tumor, the histological examination of which confirmed the diagnosis of Castleman's disease concomitant to sarcomatous transformation. Following surgical treatment, the respiratory failure worsened. The patient improved with systemic corticosteroids at the dose of 2 mg/kg/d and chemotherapy was initiated. The patient died suddenly within the context of acute respiratory failure, three months after surgery. DISCUSSION: This is a case of paraneoplastic pemphigus of unusual clinical and biological expression: exclusively mucosal involvement with obliterating bronchiolitis, explained by the isolated presence of antibodies recognizing envoplakin, without anti-desmoglein. The transformation of the Castleman tumor into a sarcoma may have unmasked intra-cellular antigens (plakins), initiating the specific immune reaction.

[Immunotherapy in non-small cell lung cancer: inhibition of PD1/PDL1 pathway]. / Immunothérapie dans le cancer bronchique non à petites cellules: inhibition de la voie PD1/PDL1.

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.

Pulmonary manifestations revealing Rosai-Dorfman disease.

Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis, mainly involving cervical nodes. We present the case of a patient with a pulmonary form of Rosai-Dorfman disease without peripheral or intra-thoracic lymph nodes, characterized by the presence of pulmonary nodules and cysts associated with bilateral pleural effusions.