[Drug-induced pneumonitis due to sirolimus: an interaction with atorvastatin?]. / Pneumopathie médicamenteuse sous sirolimus: interaction avec l'atorvastatine?

INTRODUCTION: Sirolimus is an immunosupressant used in renal transplantation because of its lack of nephrotoxicity. We report four cases of pneumonitis due to sirolimus, possibly revealing an interaction with atorvastatin. CASE REPORT: Four patients (previously on long-term treatment with atorvastatin) presented with respiratory symptoms between 3 and 56 months after starting treatment with sirolimus following renal transplantation. Thoracic CT scans showed bilateral areas of peripheral alveolar consolidation. Bronchial lavage showed a lymphocytic alveolitis. Open-lung biopsy showed organizing pneumonia associated with diffuse alveolar damage and caseating granulomata. We attributed the pneumonitis to sirolimus on account of clinical and radiological resolution within 1 to 6 months of stopping treatment. We raise the possibility of an association between sirolimus and atorvastatin by competition for their hepatic degradation pathway via cytochrome P450 3A4. CONCLUSION: Sirolimus causes drug-induced pneumonitis that is predominantly an organizing pneumonia. Atorvastatin may encourage its development by competition with sirolimus in the liver.

[Characteristics and management of acute exacerbations of COPD in hospital. EABPCO-CPHG study by the college of general hospital respiratory physicians]. / Caractéristiques et prise en charge des exacerbations aiguës de BPCO hospitalisées. Etude EABPCO-CPHG du Collège des pneumologues des hôpitaux généraux.

INTRODUCTION: A cohort was formed to explore the evolution of COPD patients treated in general hospitals for acute exacerbations (AE). The present article describes and compares patient characteristics according to whether COPD was diagnosed before the AE or not. METHODS: Data were analyzed for 1,824 patients admitted between October 2006 and June 2007 to 68 departments of respiratory medicine. RESULTS: Population characteristics were: male, 77%; mean age, 70.3+/-11.3 years; current smokers, 33%; baseline grade 3-4 dyspnoea, 47%; FEV1

[Acute exacerbations of COPD admitted to hospital: predictive factors of 3 year mortality]. / Exacerbations aiguës de BPCO hospitalisées: facteurs prédictifs de mortalité à trois ans.

INTRODUCTION: COPD is a disease whose gravity is underestimated by doctors and patients. The development of acute exacerbations (AE) accelerates the progression of the disease and leads to increased financial costs, notably on account of hospitalisation. MATERIALS AND METHODS: An observational prospective study will be undertaken based on a cohort of consecutive patients hospitalised in departments of respiratory medicine in general hospitals. The main objective is to study the factors predictive of mortality at 3 years after one admission for AE. The secondary objectives are to describe the characteristics of the AE on arrival and 3 months after discharge from hospital. A register will be set up and a questionnaire will be completed for each patient, consisting of items concerning COPD, the AE and the condition of the patient and his treatments 3 months after discharge. The level of mortality at 3 years and the predictive factors will be calculated from the data in the register. EXPECTED RESULTS: Identification the characteristics of the AE and determination of a predictive score for mortality should allow optimisation of the management of patients suffering from COPD.

[Cohort KBP-2000-CPHG: Evaluation of factors influencing survival in lung cancer]. / Cohorte KBP-2000-CPHG: évaluation des facteurs pronostiques de la survie du cancer bronchique primitif à 2 et 5 ans.

INTRODUCTION: Lung cancer continues to have a poor prognosis despite some therapeutic advances. BACKGROUND: The last fifteen years has seen a dramatic increase in the incidence of lung cancer in women and an increased proportion of adenocarcinomas in both sexes. A study of overall survival as a function of gender and other prognostic factors has been established using the cohort of patients from the study KBP-2000-CPHG. METHODS: KBP-2000-CPHG is an epidemiological study carried out throughout the year 2000 looking at histologically confirmed primary lung cancers managed in general hospitals. 5,667 patients have been included. The study of survival looks at 2 and 5-year outcomes. The date and cause of death are recorded for each patient. In the absence of these data the date of the last contact is noted. If this is less than 4 months the patient is considered to be alive. If more than four months have elapsed a graduated strategy for establishing vital status is pursued which involves reviewing records from various different sources. RESULTS AWAITED: A preliminary review of the data was undertaken between September 2004 and March 2005 which obtained data on 5 567 patients. The analysis of survival according to sex and other forecast prognostic factors is underway.

[Oxidatif-stress and COPD. Role of infection. Prevention]. / Stress oxydatif et BPCO. Rôle des infections. Prévention.

For the next decade, COPD will become the third cause of mortality in the world. COPD is mainly due to cigarette smoking and presents different levels of severity according to people, probably linked to environmental and genetic factors, which are not well documented. Recent publications pointed out bacterial bronchial colonization and exacerbations of infectious origin as worsening factors through a pro-inflammatory effect and oxidative stress. This should lead to a comprehensive review of anti-infectious prevention tools and to discuss the role of prophylactic antibiotherapy and antioxidants.

[Oxidative stress in bronchopulmonary disease: contribution of N-acetylcysteine (NAC)]. / Le stress oxydatif en pathologie broncho-pulmonaire: apport de la N-acétyl-cystéine (NAC).

Oxidative stress is a frequent mechanism involved in the pathogenesis of bronchopulmonary disease. The cause can be exogenous, in particular related to to atmospheric pollution and tobacco smoke, or endogenous, related to mobilization of inflammatory cells (macrophages and polymorphonuclear neutrophils). In this general review, we present work demonstrating this oxidative stress and activation of inflammatory cells. We discuss the effect of oxidative stress on the bronchial tree and the need to maintain an adequate balance between oxidants and anti-oxidants. This reviews focuses on experimental studies proving the anti-oxidant effect of NAC on glutathione synthesis and on different pharmacological models. We then discuss human trials, initially experimental then in different bronchopulmonary pathologies related to oxidative stress. Acetaminophen intoxication and pulmonary fibrosis are models for use of NAC. Recent work on COPD appears to show a decrease in exacerbations, improvement in symptoms and quality-of-life, and perhaps a reduction in the alteration of ventilatory function.

[Efficacy of rituximab in lymphomatoid granulomatosis]. / Efficacité du Rituximab au cours d'une granulomatose lymphomatoïde.

INTRODUCTION: Lymphomatoid Granulomatosis is a rare and serious disease, now considered to be a B-cell lymphoma, which is frequently associated with Epstein-Barr virus infection. There is no consensus on treatment, which is usually based on steroid therapy, either alone or combined with cyclophosphamide and combination chemotherapy. CASE REPORT: We report the case of an asymptomatic patient diagnosed after the incidental discovery of bilateral nodular opacities on their chest x-ray. Physical examination and bronchoscopy were normal. The diagnosis of Lymphomatoid Granulomatosis was made on the basis of surgical lung biopsy. Immunohistochemical studies confirmed the B phenotype of the lymphoma with the identification of atypical large CD 20 positive cells. In situ hybridisation confirmed the presence of EBV. In this case the course of the disease was slow. Treatment with anti CD 20 monoclonal antibodies (rituximab) led initially to a reduction in parenchymal abnormalities and mediastinal adenopathy. CONCLUSION: This treatment, recently used in Lymphomatoid Granulomatosis with pulmonary involvement, has shown promising results. Rituximab can be used in combination chemotherapy as standard treatment for aggressive B-cell lymphoma.

[Pneumopathies caused by inhalation of hydrocarbons: apropos of 3 cases]. / Les pneumopathies par inhalation d'hydrocarbures. A propos de trois observations.

We report three personal cases of hydrocarbide aspiration pneumonia. High-viscosity non-volatile hydrocarbides (paraffin oil, for instance) cause often pseudotumoral exogenous fat-aspiration lung disease. Low-viscosity volatile hydrocarbides (petroleum, gasoline, white spirit, for instance) cause acute pseudo-infectious lung disease with dyspnea and fever which usually resolves within a few weeks but which may also be life-threatening. Purely symptomatic treatment has greatly progressed with advances in intensive ventilatory assistance. Gastric emptying with emetic agents or lavage procedures is dangerous and must be avoided except for exceptional cases. When required, the airways must be protected with tracheal intubation. Volatile hydrocarbides should be stored in protected areas in containers with safety stoppers which children cannot open.

The addition of cisplatin to cyclophosphamide-doxorubicin-etoposide combination chemotherapy in the treatment of patients with small cell lung carcinoma: A randomized study of 457 patients. "Petites Cellules" Group.

BACKGROUND: To assess whether the addition of cisplatin (100 mg/m(2) administered intravenously on Day 1) to CDE (cyclophosphamide [1000 mg/m(2) on Day 1], doxorubicin [45 mg/m(2) on Day 1], and etoposide [150 mg/m(2) on Days 1 and 2] combination is useful in the treatment of patients with small cell lung carcinoma (SCLC). METHODS: In a multicenter clinical trial, 457 patients were randomized from May 1988 to March 1993 to receive either CDE (n = 228) or cisplatin-CDE (PCDE, n = 229) chemotherapy every 4 weeks for 6 cycles. As patients with limited SCLC were included in a concomitant trial assessing thoracic radiotherapy, the current study mainly included patients with extensive stage (79%) or limited stage disease and a contraindication for thoracic radiotherapy. RESULTS: The objective response rate was higher in the cisplatin-CDE group (72%) than in the CDE group (53%) (P = 0.0001). The median overall survival was similar for the groups that received CDE (266 days) and PCDE (271 days) (P = 0.93, log rank test). A higher fatal neutropenia rate was observed in the PCDE group (n = 23) than in the CDE group (n = 4) (P < 0.001, log rank test), mainly for patients with extensive disease (n = 26; P = 0.015, log rank test). CONCLUSIONS: The addition of cisplatin to a CDE regimen is toxic to patients with extensive SCLC and does not improve overall survival. The PCDE combination must be avoided for patients with extensive SCLC; CDE or cisplatin-etoposide combinations remain standard chemotherapy for these patients. The PCDE combination associated with granulocyte-colony stimulating factors could only be assessed in patients with good prognoses.

A randomized clinical trial comparing concurrent and alternating thoracic irradiation for patients with limited small cell lung carcinoma. "Petites Cellules" Group.

BACKGROUND: Although thoracic radiotherapy is considered to be useful for the treatment of patients with small cell lung carcinoma (SCLC), its optimal administration schedule is still controversial. METHODS: In a multicenter clinical trial, 164 patients with limited SCLC (of whom 156 were eligible for the study) were randomized to receive either concurrent thoracic irradiation, initiated immediately after the second cycle of chemotherapy (Days 30-64) at a dose of 50 grays in 20 fractions, or alternating thoracic irradiation, scheduled in 3 courses between the second, third, fourth, and fifth cycles of chemotherapy with a 7-day rest period after and before chemotherapy at a dose of 20 grays in 8 fractions (Days 36-47 and Days 64-75) and then 15 grays in 6 fractions (Days 92-101). The same chemotherapy regimen (cyclophosphamide-doxorubicin or vindesine-etoposide) was administered every 4 weeks in both groups. RESULTS: Concurrent radiotherapy-induced lung toxicity led to early termination of this trial when a significant difference was observed (6 cases vs. 1, P = 0.05, 2-sided log rank test). Objective response rates were 89% in the 82 patients of the concurrent radiotherapy group and 95% in the 74 patients of the alternating radiotherapy group. Median survival periods were 13.5 and 14.0 months, respectively, with no significant difference between the two survival distributions (P = 0.15, 2-sided log rank test). Toxic deaths due to bone marrow hypoplasia were similar in both groups (3 vs. 2), but mortality due to lung toxicity (pulmonary fibrosis) was more frequent with concurrent radiotherapy (6 patients) than with alternating radiotherapy (1 patient) in long term analysis (P = 0.05, 2-sided log rank test). CONCLUSIONS: Although no statistically significant overall survival difference was observed between the two radiation therapy schedules, the better tolerance of the alternating schedule justifies the choice of this schedule with this chemotherapy regimen, although it may not be applicable to other chemotherapy regimens.

[Pulmonary malacoplakia caused by Rhodococcus equi in AIDS: a case report]. / Malacoplasie pulmonaire à Rhodococcus equi au cours du SIDA: à propos d'un cas.

We describe the observation of a right upper lobe consolidation with cavitation produced by Rhodococcus equi in a patient suffering from AIDS. The inefficacy of a prolonged antimicrobial therapy adapted against R. equi led to a right upper lobectomy. The histopathology showed a pseudotumoral mass, with dense infiltration of macrophages containing Michaelis-Gutmann bodies, which was positive for the culture of R. equi. Pulmonary malacoplakia with Rhodococcus equi was diagnosed. This pathology should be evoked when a R. equi pneumonia persists despite a right management of treatment for several months. The features of pneumonia with Rhodococcus equi and of pulmonary malacoplakia are taken from a literature review.

Fluticasone propionate 50 micrograms BID versus 100 micrograms BID in the treatment of children with persistent asthma. Fluticasone Propionate Study Group.

The aim of this multicenter, double-masked study was to compare the efficacy and safety of two different doses of inhaled fluticasone propionate dry powder--50 micrograms and 100 micrograms--administered BID via a multidose powder inhaler with those of placebo in the treatment of children with persistent asthma. After a 2-week run-in period, 263 patients were randomized to treatment with twice-daily placebo (n = 92), fluticasone 50 micrograms (n = 85), or fluticasone 100 micrograms (n = 86) for 12 weeks. One hundred sixty-six (63%) patients were male, and 224 (85%) were white, with a mean age of 8 years. Two hundred twenty-one (84%) patients were atopic, and 167 (63%) had been asthmatic for 1 to 5 years. Baseline mean morning peak expiratory flow (PEF) values were 207 L/min, 199 L/min, and 194 L/min, and baseline percentages of predicted normal values were 86%, 80%, and 81% for the groups receiving placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the end of the first week of treatment, patients in both fluticasone groups had significantly greater improvements in morning PEF than did those receiving placebo. Patients experienced mean increases of 4 L/min, 22 L/min, and 26 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. At the end point (the last evaluable visit), patients in both fluticasone groups continued to have significantly greater improvements in morning PEF than did patients receiving placebo. Patients experienced mean increases of 17 L/min, 50 L/min, and 57 L/min with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. Changes in the percentage of predicted values by end point were 8%, 20%, and 26% with placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. The probability of remaining in the study, according to predefined withdrawal criteria, indicated a significant treatment difference in favor of fluticasone. Withdrawal criteria were met by 63%, 42%, and 29% of patients receiving placebo, fluticasone 50 micrograms, and fluticasone 100 micrograms, respectively. This study clearly demonstrates the superiority of fluticasone 50 and 100 micrograms BID over placebo in the treatment of persistent asthma in children.

Two cycles of cisplatin-vindesine and radiotherapy for localized nonsmall cell carcinoma of the lung (stage III). Results of a prospective trial with 149 patients.

One hundred forty-nine patients with localized nonsmall cell carcinoma of the lung (Stage III A and B) were treated with two monthly cycles of initial chemotherapy that included vindesine-cisplatin followed by 6000 cGy of thoracic irradiation. Patients with complete, partial, and minor response after initial chemotherapy were randomized into groups to receive either maintenance chemotherapy (four cycles) after radiotherapy or radiotherapy alone. The objective response rate was 24% after chemotherapy and 41% after combined chemoradiotherapy (complete response, 7.5%). The overall median survival was 9 months and the 2-year survival was 14%. Survival was identical with or without maintenance chemotherapy. The 2-year survival of patients with complete response was 75% compared with 9% for patients with partial or minor response. These results suggest that only the few patients (ten) who achieve complete response have a strong probability of survival. It is therefore essential to search for other therapeutic modalities that result in an increase of the complete response rate.

Cisplatin and vindesine for disseminated non-small cell lung cancer. Results of a prospective trial with 81 patients.

Eighty-one patients with disseminated non-small cell lung cancer (stage IV) were treated with 2 monthly cycles of initial chemotherapy combining cisplatin with vindesine. The initial chemotherapy-responding patients (CR, PR, MR) were randomized to 2 cycles or 4 cycles of maintenance chemotherapy. After initial chemotherapy, the response rate was 33% (CR, PR, MR) with 18.5% objective responses. The overall 1-year survival rate was 15% with 37% for responders as opposed to 2% for non-responders. Maintenance chemotherapy did not improve the response rate obtained after initial cycles. The small number of patients does not allow us to reach a definite conclusion on the optimum duration of maintenance chemotherapy. In the absence of large placebo versus chemotherapy randomized trials, no definite conclusion can be made on the benefit of chemotherapy in disseminated non-small cell lung cancer. This study suggests, however, that chemotherapy is associated with a significantly longer survival in responding patients.