B. Desrues

Impaired Functions of Macrophage from Cystic Fibrosis Patients: CD11b, TLR-5 Decrease and sCD14, Inflammatory Cytokines Increase

Background Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions. Objectives In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF). Results In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression. Conclusions Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.

Necrotizing Sarcoid Granulomatosis with and without Extrapulmonary Involvement

Three cases of necrotizing sarcoid granulomatosis (NSG) are reported. All 3 patients had pulmonary lesions; one of them had additional extrapulmonary lesions which were ophthalmologic (dacryoadenitis) and digestive (ulcerative colitis). This patient was followed for 5 years and developed several respiratory, ophthalmologic and digestive recurrences. In 2 cases the diagnosis of NSG had been initially overlooked and the authors emphasize the difficulties of this histologic diagnosis in terms of the differential diagnosis with other necrotic and granulomatous pulmonary diseases such as tuberculosis and Wegeners granulomatosis. They stress the possibility of extrapulmonary lesions in NSG and discuss the relationship between NSG and sarcoidosis.

Azygos vein aneurysm: contribution of transesophageal echography.

We report a case of idiopathic aneurysm of the azygos vein associated with lung cancer. This abnormality is exceptional because we could find only 8 previous published cases. Computed tomographic scan and especially transesophageal echography were of major importance in identifying the vascular nature of the radiographic abnormality and thus excluding extension of lung cancer.

Ambulatory Management of Large Spontaneous Pneumothorax With Pigtail Catheters

STUDY OBJECTIVE There is no consensus about the management of large spontaneous pneumothoraces. Guidelines recommend either needle aspiration or chest tube drainage and most patients are hospitalized. We assess the efficiency of ambulatory management of large spontaneous pneumothoraces with pigtail catheters. METHODS From February 2007 to January 2011, all primary and secondary large spontaneous pneumothoraces from Lorients hospital (France) were managed with pigtail catheters with a 1-way valve. The patients were discharged immediately and then evaluated every 2 days according to a specific algorithm. RESULTS Of the 132 consecutive patients (110 primary, 22 secondary), 103 were exclusively managed as outpatients, with full resolution of the pneumothorax by day 2 or 4, which represents an ambulatory success rate of 78%. Mean time (SD) of drainage was 3.4 days (1.8). Seven patients were initially hospitalized but quickly discharged and had full resolution by day 2 or 4, leading to a total success rate of 83%. The use of analgesics was low. The 1-year recurrence rate was 26%. If successful, this outpatient management is potentially cost saving, with a mean cost of

La protéinose alvéolaire pulmonaire

926, assuming up to 2 outpatient visits and 1 chest radiograph, compared with

Long-term nasal intermittent positive pressure ventilation (NIPPV) in sixteen consecutive patients with bronchiectasis: a retrospective study

4,276 if a chest tube was placed and the patient was admitted to the hospital for 4 days. CONCLUSION Ambulatory management with pigtail catheters with 1-way valves could be a reasonable first-line of treatment for large spontaneous pneumothoraces. Compared with that of other studies, our protocol does not require hospitalization and is cost saving.

Anti-Inflammatory Effect of Fluvastatin on IL-8 Production Induced by Pseudomonas aeruginosa and Aspergillus fumigatus Antigens in Cystic Fibrosis

Alveolar proteinosis (AP) is a rare disease characterized by alveolar accumulation of surfactant components, which impairs gas exchange. AP is classified into three groups: auto-immune AP defined by the presence of plasma autoantibodies anti-GM-CSF, the most frequent form (90% of all AP); secondary AP, mainly occurring as a consequence of haematological diseases, or following on from toxic inhalation or infections, and genetic AP, which affects almost exclusively children. AP diagnosis is suspected where chest CT-scan demonstrates interstitial lung disease with a crazy paving aspect; and confirmed by bronchoalveolar lavage, which has a milky appearance and contains periodic acid Schiff positive proteinaceous alveolar deposits. The use of surgical lung biopsy to confirm AP is less frequent nowadays. In this context, positive antibodies against GM-CSF indicates an auto-immune etiology of the AP. Concerning management, whole lung lavage is the gold standard therapy. In refractory AP, new treatments are available such as subcutaneous or inhaled GM-CSF supplementation, or rituximab infusions. The clinical course is unpredictable. Spontaneous improvement or even cure can occur, and the 5-year actuarial survival is 95%. The most frequent complications are infectious etiology.

Sarcoïdose pulmonaire apparue sous étanercept

Life expectancy and quality of life are poor in patients with chronic respiratory failure due to bronchiectasis. The indication for nocturnal nasal intermittent positive pressure ventilation (NIPPV) remains controversial in chronic obstructive lung disease. The purpose of the present study was to determine whether some of the objectives of home mechanical ventilation, i.e. improvement in blood gas values and reduced length of hospitalization, were fulfilled by NIPPV and oxygen plus medical treatment in patients with chronic respiratory failure due to bronchiectasis. Sixteen consecutive patients (12 females and four males; mean age 57 +/- 11 yrs) with chronic respiratory failure due to bronchiectasis, treated at home with nocturnal NIPPV in addition to oxygen therapy, were retrospectively studied in terms of blood gas values and duration of hospitalization before and after NIPPV. Details of the therapy received by each patient were recorded. Nine patients agreed to complete a questionnaire to determine their perception of the benefits of the treatment. NIPPV was performed using a volumetric respirator and was applied with a customized nasal mask modelled with silicone paste. NIPPV was used for a mean of 26 months (range 0.5-60 months). Eleven patients were alive 12 months after use of NIPPV. No significant improvement in blood gas values was noted on room air during NIPPV, but arterial carbon dioxide tension (Pa,CO2) stabilized after the period of worsening observed before initiation of NIPPV. Duration of hospitalization, the year before and the year after NIPPV, was 19 (3-40) and 16 (8-37) days, respectively (NS). For the 11 patients who were alive 2 yrs after the start of NIPPV, duration of hospitalization the year before NIPPV and between 12 and 24 months after NIPPV were 17 (4-40) and 7 (2-27) days, respectively (p < 0.05). Nine patients who had received NIPPV for at least 12 months at the time of the study reported an improvement in their quality of life. The results suggest that home ventilatory support by nasal intermittent positive pressure ventilation offers an acceptable alternative to tracheotomy, with less discomfort, in the management of severe respiratory failure due to bronchiectasis, in order to allow the patient to return home. These results should be confirmed by controlled studies.

Immunohistochemical Expression of the Intracellular Component of Galectin-8 in Squamous Cell Metaplasiaof the Bronchial Epitheliumin Neoplastic and Benign Processes

Background Early in life, patients with cystic fibrosis (CF) are infected with microorganisms including bacteria and fungi, particularly Pseudomonas aeruginosa and Aspergillus fumigatus. Since recent research has identified the anti-inflammatory properties of statins (besides their lipid-lowering effects), we investigated the effect of fluvastatin on the production of the potent neutrophil chemoattractant chemokine, IL-8, in whole blood from CF patients, stimulated by Pseudomonas aeruginosa (LPS) and Aspergillus fumigatus (AFA) antigens. Results Whole blood from adult patients with CF and from healthy volunteers was collected at the Rennes University Hospital (France). Blood was pretreated for 1 h with fluvastatin (0–300 µM) and incubated for 24 h with LPS (10 µg/mL) and/or AFA (diluted 1/200). IL-8 protein levels, quantified by ELISA, were increased in a concentration-dependent manner when cells were stimulated by LPS or AFA. Fluvastatin strongly decreased the levels of IL-8, in a concentration-dependent manner, in whole blood from CF patients. However, its inhibitory effect was decreased or absent in whole blood from healthy subjects. Furthermore, the inhibition induced by fluvastatin in CF whole blood was reversed in the presence of intermediates within the cholesterol biosynthesis pathway, mevalonate, farnesyl pyprophosphate or geranylgeranyl pyrophosphate that activate small GTPases by isoprenylation. Conclusions For the first time, the inhibitory effects of fluvastatin on CF systemic inflammation may reveal the important therapeutic potential of statins in pathological conditions associated with the over-production of pro-inflammatory cytokines and chemokines as observed during the manifestation of CF. The anti-inflammatory effect could be related to the modulation of the prenylation of signalling proteins.

Association of pulmonary alveolar proteinosis and fibrosis: Patient with GATA2 deficiency

INTRODUCTION TNF blockers are widely used to treat inflammatory rheumatic diseases and also in the treatment of extrapulmonary sarcoidosis. TNFα plays a major role in the development and persistence of sarcoid granulomata. However, recent studies have reported the involvement of anti-TNF therapies in the development of granulomatosis associated with the clinical and radiological features of sarcoidosis. CASE REPORT A 54-years-old man with ankylosing spondylitis was treated with etanercept for two years. He was admitted with symptoms of bronchitis associated with radiological evidence of bilateral pulmonary nodules and a right upper lobe infiltrate. Anti-TNF therapy was stopped even though the patient had received 3 months of prophylactic treatment with rifampicin and isoniazid before starting etanercept. Bronchoalveolar lavage excluded infection, particularly tuberculosis. The chest CT-scan showed bilateral pulmonary nodules with peribronchovascular micronodules and enlarged mediastinal lymph nodes. Surgical lung biopsy was performed and revealed non-caseating granulomata. All the data were consistent with a diagnosis of pulmonary sarcoidosis. The patient remained symptomatic despite discontinuation of etanercept for ten months. Corticosteroids were then introduced, leading to a clinical, functional and radiological improvement. CONCLUSION This case report underlines the importance of studying the pulmonary complications of TNF blockers. The first priority is to exclude tuberculosis but a diagnosis of sarcoid-like granulomatosis has to be considered. Twenty-three cases have been described in the literature to date.