[Nocardia farcinica infection in a patient with cystic fibrosis]. / Infection à Nocardia farcinica chez un patient porteur d'une mucoviscidose.

Infections by Nocardia species are uncommon and generally affect immunocompromised patients. This bacteria has rarely been isolated from cystic fibrosis patients (CF), especially those who are not taking oral corticosteroids. We report a case of a patient with CF harbouring Nocardia farcinica. An 18-year-old male diagnosed with CF at the age of eight (F508 del/G85E) had been treated for allergic bronchopulmonary aspergillosis in 1998 with itraconazole, and a first colonization with Pseudomonas aeruginosa was eradicated in 2003. From May 2006, he presented with recurrent left- and right-sided pneumothorax. In June 2006, he presented with dyspnoea, fever, and nodular eruption on his ankles. Chest X-ray and CT scan revealed a right pneumothorax, severe bronchiectasis and bilateral alveolar consolidation. N. farcinica was idolated from his sputum without any other pathogens. Treatment with intravenous cotrimoxazole associated with imipenem and amikacin was initiated for three weeks followed by oral cotrimoxazole for a further nine months. The patient's symptoms and alveolar consolidation on CT scan improved. During 2007, his respiratory condition worsened and his FEV(1) declined from 50 to 26 % predicted. His pneumothorax recurred. He had chronic colonization with P. aeruginosa and was on the list for lung transplantation. Nocardia, a Gram positive bacillus, causes mainly pulmonary infection, usually in the context of immune suppression. The most frequent species is N. asteroides. In CF, very few cases have been reported; almost always N. asteroides, but exceptionally N. farcinica. In CF patients with worsening pulmonary condition, Nocardia should be considered, as well as other unusual pathogens.

Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey.

BACKGROUND: Invasive aspergillosis is an opportunistic infection that occurs mainly among patients with prolonged neutropenia. Few data are available on invasive aspergillosis in nonneutropenic patients. METHODS: The aim of this survey was to compare neutropenic and nonneutropenic patients who had received a diagnosis of invasive aspergillosis at our institution during a 6-year period. RESULTS: Among the 88 cases of invasive aspergillosis analyzed here, 12 were histologically proven, 52 were probable, and 24 were possible. Forty-seven percent of cases were diagnosed in the intensive care unit, and 40% were diagnosed in hematology units. Neutropenia was a risk factor for 52 patients (59%), most of whom had hematological or solid malignancies. Among the 36 nonneutropenic patients (41%), the main underlying conditions were steroid-treated chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, giant-cell arteritis, and microvascular disorders; 10 patients were recipients of solid-organ transplants, and 1 patient was seropositive for human immunodeficiency virus. The distribution of proven and probable invasive aspergillosis was similar for neutropenic and nonneutropenic patients. The mortality rate was 71.5% overall and was significantly higher among nonneutropenic patients than among neutropenic patients (89% vs. 60%; P<.05). Compared with neutropenic patients, nonneutropenic patients were significantly less likely to have symptoms of invasive aspergillosis and more likely to have frequent intercurrent pneumonia due to another microorganism. The sensitivity of mycological examination of bronchoalveolar lavage fluid specimens was higher for nonneutropenic patients than for neutropenic patients (85% vs. 58%; P<.05), whereas the sensitivity of antigenemia was the same for the 2 populations (65% vs. 64%). Findings on thoracic computed tomographs were similar, except that segmental areas of consolidation occurred more frequently among neutropenic patients. CONCLUSION: This survey at a whole institution underlines the high number of cases of invasive aspergillosis among nonneutropenic patients, with an overall mortality rate that was significantly higher than that for neutropenic patients.

Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease.

OBJECTIVE AND DESIGN: Chronic obstructive pulmonary disease (COPD) is characterized by an inflammatory process and airway remodeling involving matrix metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12 (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from COPD patients and control subjects. METHODS: Immunocytochemistry and immunochemistry were performed to analyze the expression of MMP-12 in BAL cells and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in BAL fluids. RESULTS: The number of MMP-12 expressing macrophages together with the staining intensity was higher in BAL samples from COPD patients than in controls subjects. Similar results were noted in bronchial biopsies with higher MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was also observed in BAL fluids from patient with COPD in comparison to control subjects. CONCLUSION: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.

The novel phosphodiesterase 4 inhibitor, CI-1044, inhibits LPS-induced TNF-alpha production in whole blood from COPD patients.

Chronic obstructive pulmonary disease (COPD) is a common, progressive respiratory disease that causes great morbidity and mortality despite treatment. Tumor necrosis factor alpha (TNF-alpha) plays a central role as a pro-inflammatory cytokine in COPD. TNF-alpha release is markedly inhibited by phosphodiesterase type 4 (PDE4) inhibitors that have proven efficacious in COPD clinical trials. The aim of this study was to compare the in vitro activities of the novel selective PDE4 inhibitors CI-1044 compared to well-known PDE4 inhibitors, rolipram and cilomilast, and to the glucocorticoid dexamethasone at reducing lipopolysaccharide (LPS)-induced TNF-alpha release in whole blood from COPD patients and healthy subjects. In the whole blood from COPD patients pre-incubation with PDE4 inhibitors or dexamethasone resulted in a dose-dependent inhibition of LPS-induced TNF-alpha release with IC(50) values of 1.3+/-0.7, 2.8+/-0.9 microM, higher to 10 microM and lesser than 0.03 microM for CI-1044, rolipram, cilomilast and dexamethasone, respectively. We observed a similar inhibition in the whole blood from healthy volunteers with, however, higher IC(50) values. These results indicate that CI-1044 inhibits in vitro LPS-induced TNF-alpha release in whole blood from COPD patients better than rolipram and cilomilast and suggested that it could be a useful anti-inflammatory therapy in COPD.

[Diffusing capacity for carbon monoxide (T(LCO)) and oxygen saturation during exercise in patients with cystic fibrosis]. / Capacité de transfert du monoxyde de carbone (TLCO) et saturation artérielle à l'exercice chez les patients atteints de mucoviscidose.

OBJECTIVES: To estimate the value of diffusing capacity for carbon monoxide (T(LCO)) in patients with cystic fibrosis and to evaluate its ability to predict arterial desaturation during exercise. METHOD: Fourty-four patients (9-30 years) with cystic fibrosis performed pulmonary function tests with measure of T(LCO) and a bicycle incremental exercise test. They represent a wide variation in disease severity: mean Shwachman score: 77.8 (range: 40-100), mean FEV1%: 72.8 (range: 17-131). This study investigated the relationship between T(LCO), lung volumes and exercise data. RESULTS: T(LCO) remained normal for a long time in patients with cystic fibrosis: 82% of them show a normal T(LCO) (mean value: 91.3% of predicted). T(LCO) was significantly correlated with FEV(1), residual volume, maximal work load and maximum oxygen uptake. A fall in arterial oxygen saturation was uncommon in our study (five patients) and not significantly correlated with T(LCO). CONCLUSIONS: T(LCO) is a good criter of severity of cystic fibrosis but remains unreliable to predict values above which physical activity is safe, without arterial desaturation. Exercise tests should be proposed in order to evaluate exercise adaptation of each patient and determine which factor limits maximal performance.

[Value of the association of D-dimer measurement and the evaluation of clinical probability in a non-invasive diagnostic strategy of pulmonary embolism]. / Intérêt de l'association du dosage des D-dimères et de l'évaluation de la probabilité clinique dans une stratégie diagnostique non invasive de l'embolie pulmonaire.

New diagnostic tools in suspected pulmonary embolism complete the classical diagnostic strategy of pulmonary scintigraphy and pulmonary angiography to limit the indications of these two invasive investigations. In a prospective series of 204 consecutive patients with suspected pulmonary embolism the association of D-dimer measurement and clinical probability was assessed for the exclusion of the diagnosis of pulmonary embolism. The D-DI Liatest is a new generation, unitary, rapid and quantitative latex test with a comparative diagnostic performance to that of the reference ELISA test, and well adapted to emergency situations.The clinical probability was assessed by a quantitative score based on past history, clinical symptoms and signs. The positive diagnosis of pulmonary embolism was made by spiral CT scanner and/or pulmonary angiography, associated with Duplex ultrasonography of the leg veins in nondiagnostic results. The prevalence of pulmonary embolism was 42.6% and the absence of anticoagulation in patients considered not to have pulmonary embolism was associated with a thrombo-embolic incidence of 0.9% at 3 months. Fifty-six patients had D-dimer concentrations equal or inferior to the threshold of 500 microg/L; the sensitivity was 99% and the specificity 47% with a negative predictive value of 98% to 100% in cases with a low clinical probability. D-dimer measurement is reliable and has a high cost-benefit value in ambulatory patients with suspected of pulmonary embolism and is even more valuable when the clinical probability of this diagnosis is low.

[Isoniazid-induced pleuro-pericarditis]. / Pleuro-péricardite induite par l'isoniazide.

We report a case of pleuro-pericarditis related to administration of isoniazid. Drug-induced lupus is well known; we recall the principle clinical, biological and immunological characteristics.

Phase II randomized multicenter study evaluating a treatment regimen alternating docetaxel and cisplatin-vinorelbine with a cisplatin-vinorelbine control group in patients with stage IV non-small-cell lung cancer: GFPC 97.01 study.

BACKGROUND: The potential absence of cross-resistance between cisplatin and docetaxel in non-small-cell lung cancer (NSCLC) suggests that alternating regimens of cisplatin-based chemotherapy and docetaxel might increase the activity of chemotherapy in stage IV NSCLC. PATIENTS AND METHODS: Randomized, multicenter, non-comparative phase II study in patients with stage IV NSCLC (Eastern Cooperative Oncology Group performance status of 0-2). Patients randomized to alternating treatment group (A) received docetaxel 100 mg/m2 on days (D) 1 and 43 alternating with cisplatin 100 mg/m2 on D22 and vinorelbine 30 mg/m2 on D22, D29 and D36. Those randomized to the control group (B) received cisplatin 80 mg/m2 on D1, D22 and D43 and vinorelbine 30 mg/m2 once a week from D1 to D57. Treatment was continued for a further 6 weeks in the event of objective response or stabilization. RESULTS: Seventy patients were enrolled (group A: 38, group B: 32). More premature treatment discontinuations due to toxicity were observed in group A (median number of cycles: 3) than in group B (median number of cycles: 5). The intention-to-treat objective response rate was 10.8% [95% confidence interval (CI) 0.8% to 20.8%] in group A compared with 25% (95% CI 10% to 40%) in group B, the median time to treatment failure being 10.2 weeks and 17.3 weeks, respectively. The median survival and 1-year survival were 29.1 weeks and 39% in group A compared with 41.6 weeks and 42% in group B. Febrile neutropenia occurred in 5.9 and 4.9% of the cycles in group A and group B, respectively. Non-hematological toxicity was moderate in the two groups. CONCLUSIONS: The addition of docetaxel alternating with cisplatin-vinorelbine did not enhance the activity of this combination. The development of sequential regimens might be a more promising way of exploiting the absence of cross-resistance between these two drugs.

Involvement of gelatinases (MMP-2 and MMP-9) in the development of airway inflammation and pulmonary fibrosis.

Pulmonary fibrosis has an aggressive course and is usually fatal an average of 3 to 6 years after the onset of symptoms. Pulmonary fibrosis is associated with deposition of extracellular matrix (ECM) components in the lung interstitium. Matrix metalloproteinases (MMPs) are a major group of proteinases known to regulate the ECM remodeling and so they are hypothesized to be important in the process of lung fibrosis. These led to the concept that modulation of airway remodeling including excessive proteolytic damage of the tissue may be of interest for future treatment. The excessive airway remodeling as a result of an imbalance in the equilibrium of the normal processes of synthesis and degradation of extracellular matrix components could argue in favor of antiprotease treatments. Moreover, these observations emphasize that effective therapies for these disorders must be given early in the natural history of the disease, prior to the development of expensive lung destruction and fibrosis.

[Treatment of tracheobronchomegaly with an Ultraflex prosthesis. A case report]. / Traitement de la trachéobronchomégalie par la mise en place d'une prothèse Ultraflex.

Tracheobronchomegaly is defined as a dilatation of the trachea and the large bronchi. It may occur as a familial condition or in association with a connective tissue disease, e.g. Ehlers-Danlos syndrome. Tracheobronchomegaly occurs late in adults. The predominant symptoms are bronchial irritation and recurrent bronchopulmonary infections (because of ineffective cough). Diagnosis is provided by thoracic imaging, particularly computed tomography that enables measuring the precise diameter of the trachea. We report the case of one patient with tracheobronchomegaly who was greatly improved after implantation of Ultraflex tracheobronchial prostheses.

[Tracheobronchial amyloidosis: apropos of 2 cases]. / Amylose trachéobronchique: à propos de deux cas.

INTRODUCTION: Tracheo-bronchial amyloidosis is an uncommon localized form of amyloidosis. We report two new cases. EXEGESIS: Two patients had developed expiratory dyspnea for several months. CT-scan and flexible bronchoscopy confirmed tracheal narrowing and a diagnosis of tracheo-bronchial amyloidosis was made by tissue biopsies. The immunohistochemical type was AL in one case, undetermined in the other case. There was no argument for systemic involvement. The two patients benefited from bronchoscopic dilatation. This treatment improved clinical symptoms and pulmonary function tests with a follow up of 12 and 18 months respectively. CONCLUSION: Tracheo-bronchial amyloidosis is a localised form of amyloidosis with various respiratory symptoms. Diagnosis is made by CT-scan and flexible bronchoscopy that allows biopsies. Immunohistochemical type is more often AL. Recurrence, respiratory insufficiency and tracheo-bronchial metaplasia are the most important complications. Treatment consists of bronchoscopic dilatation or excision, and bronchoscopic laser-YAG. Pulmonary function testing allows precise follow-up.

Increased release of matrix metalloproteinase-9 in the plasma of acute severe asthmatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling. OBJECTIVE: We have compared the levels of MMPs, eotaxin and soluble interleukin 2 receptor (IL-2R) in the plasma of healthy subjects, atopic patients and asthmatic patients. METHODS: The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP-9, TIMP-1, IL-2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography. RESULTS: An increased basal level of MMP-9 and IL2-R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP-9 in the plasma of all groups of patients. However, the MMP-9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP-1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP-9 (92 kDa) but not MMP-2 (66 kDa) in the plasma of patients with acute asthma. CONCLUSION: The increased in MMP-9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP-9 as a non-invasive systemic marker of inflammation and airway remodelling in asthma.

Effects of PDE4 inhibitors on lipopolysaccharide-induced priming of superoxide anion production from human mononuclear cells.

AIMS: Phosphodiesterase 4 (PDE4) inhibitors have been described as potent anti-inflammatory compounds, involving an increase in intracellular levels of cyclic 3',5'-adenosine monophosphate (AMP). The aim of this study was to compare the effects of selective PDE4 inhibitors, rolipram and RP 73-401 with the cell permeable analogue of cyclic AMP, dibutyryl-cyclic AMP (db-cAMP) and the anti-inflammatory cytokine interleukin-10 (IL-10) on superoxide anion production from peripheral blood mononuclear cells preincubated with lipopolysaccharide (LPS). MAJOR FINDINGS: We report that, after incubation of the cells with LPS, a large increase in superoxide anion production was observed. Rolipram or RP 73-401 (10(-8) to 10(-5) M) induced significant reductions of fMLP-induced superoxide anion production in cells incubated with or without LPS. The db-cAMP (10(-5) to 10(-3) M) also elicited dose-dependent inhibitions of the fMLP-induced superoxide anion production. In contrast, IL-10 (1 or 10 ng/ml) did not elicit a reduction in fMLP-induced superoxide anion production in both conditions. PRINCIPAL CONCLUSION: These results suggest that the inhibitory activity of PDE4 inhibitors on fMLP-induced production of superoxide anion production is mediated by db-cAMP rather than IL-10.

[Pseudotumoral forms of sarcoidosis]. / Les formes pseudo-tumorales de la sarcoïdose.

We report 5 cases of sarcoidosis in 4 men and 1 woman who presented multinodular pulmonary lesions. Seldom described (1 to 4% of all cases of sarcoidosis), a multinodular pulmonary presentation is suggestive of metastatic disease. In our patients, the parenchymal opacities were multiple, peripheral and exhibited fuzzy limits, measuring 1 to 7 cm in size and frequently associated with mediastinal adenopathies. The radiographic pattern contrasted with the clinical manifestations (3 of the 5 cases were fortuitous discoveries). Pathological proof required to rule out other disease, especially tumor formation, was acquired; mediastinoscopy allowing the diagnosis in 3 out of 5 cases. The clinical course was favorable in all cases without treatment within 8 +/- 5 months and a mean follow-up of 5 years (range 9 months to 14 years).

[Prevention of infection transmitted by bronchial fibroscopes]. / Prévention des infections transmises par les endoscopes bronchiques.

A growing number of infectious complications are reported after bronchial fibroscopy procedures. The risk of nosocomial patient-to-patient or environment-to-patient infection is real via contaminated fibroscopes. Cross transmission can be caused by several microorganisms, the most frequently identified being Pseudomonas aeruginosa, Mycobacterium tuberculosis and other atypical mycobacteria. Fibroscopes can be contaminated via different mechanisms, generally related to poorly adapted cleaning and decontamination protocols. Identified errors include an insufficient cleaning phase, an inappropriate disinfecting agent (iodine derivatives, chlorhexidine), defective cleaning or disinfection of accessory equipment, or use of tap water for rinsing. Finally several episodes of Pseudomonas and atypical mycobacteria infections have been found to result from the use of automatic cleaning machines. Particular attention must be paid to the use of these devices. Official guidelines for the disinfection of endoscopic equipment must be rigorously applied in all centers. The personnel should have adequate training. It is also important to take regular samples and make regular bacteriology controls of the water and fibroscopic equipment.

[Spontaneous resolution of a giant pulmonary bulla]. / Disparition spontanée d'une bulle géante.

There are different causes leading to formation of pulmonary bullae, in particular tuberculosis. There is some debate concerning the pathophysiology of bullae extension although two mechanisms are put forward: partial obstruction of the airways and elastic recoil of adjacent lung parenchyma with a negative pressure in the bullae. Pulmonary function tests are highly perturbed in patients with giant bullae. The natural history of bullae is enlargement although spontaneous regression is rarely described. Bullae should be resected in selected patients, others require careful follow-up. We present the case of a man with tuberculosis who developed a giant pulmonary bulla that regressed spontaneously in a few years.