Increase in both angiogenic and angiostatic mediators in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a marked pulmonary vascular remodeling. The aim of this study was to investigate a potential imbalance between angiogenic and angiostatic factors in this disease. METHODS AND RESULTS: Sixty-four subjects with IPF and 10 healthy control subjects (60-70 years old) were prospectively included in this multicenter study. Plasma levels of vascular endothelial growth factor A (VEGF-A), thrombospondin-1 (TSP-1) and stem cell factor (SCF) were determined by Elisa. Comparisons between IPF and controls were made using the Mann-Whitney U test. We also analyzed these soluble mediators in relation with IPF severity (DLCO<40% or>40%) predicted or total lung capacity (TLC) and forced vital capacity (FVC) (both<55% or>55% predicted) using the same test. VEGF-A plasma levels were increased in IPF vs. controls (P=0.0008) as well as those of TSP-1 (P=0.008), irrespective of the severity of the disease as reflected by DLCO, TLC or FVC values. In contrast, SCF levels were similar in IPF and controls. CONCLUSIONS: Factors modulating angiogenic responses are dysregulated in patients with IPF with increases in VEGF-A and TSP-1. The serial assessment of VEGF-A and TSP-1 during the follow-up and the search for potential relationships with the outcome of the disease might give us hints to the clinical implication of these results.

[Pulmonary fibrosis associated with hereditary fibrosing poikiloderma caused by FAM111B mutation: A case report]. / Fibrose pulmonaire au cours de la poïkilodermie héréditaire sclérosante associée à la mutation du gène FAM111B : à propos d'un cas.

INTRODUCTION: Hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP) is a recently described, extremely rare, entity belonging to the spectrum of inherited poikilodermas. It is provoked by a mutation of the FAM111B gene. Respiratory involvement has never been fully described but usually involves a restrictive respiratory pattern. We present here a case of pulmonary fibrosis associated with POIKTMP and describe the clinical, functional, radiological and evolutionary characteristics. OBSERVATION: A 38 year-old patient with poikiloderma diagnosed in childhood was referred on account of dyspnoea. Initial evaluation showed a diffuse, fibrosing, interstitial pneumonitis with upper lobe predominance, associated with severe muscular involvement on imaging that remained sub-clinical during the evolution of the disease. Lung function impairment was severe and a rapid worsening of the pulmonary fibrosis and an acute exacerbation led to death after a follow-up of 21 months. CONCLUSION: This case illustrates the fibrosing pulmonary involvement associated with POIKTMP and confirms its extreme severity. It is found only in adults and is universally fatal after a variable time. It highlights the necessity for a systematic screening as soon as the diagnosis of POIKTMP is confirmed in order to establish specialised respiratory management.

Subcutaneous low-molecular-weight heparin fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomized pilot study.

Low-molecular-weight heparins have been extensively investigated in the treatment of deep venous thrombosis but limited data are available concerning their use in pulmonary embolism. In an open, pilot, randomized study, we compare the safety and efficacy of Fragmin, a low-molecular-weight heparin with those of unfractionated heparin in 60 patients with non massive pulmonary embolism (Miller Index < 20). Thirty one patients received unfractionated heparin intravenously and 29 received a fixed dose of 120 Anti-Xa IU/kg of Fragmin administered subcutaneously twice a day for 10 days. There was no pulmonary embolism recurrence nor major bleeding in either group during the treatment period. The decrease in pulmonary vascular obstruction on perfusion lung scan between day 0 and day 10 was 17 +/- 13% in the Fragmin group and 16 +/- 13% in the heparin group (NS). These results indicate that Fragmin may be a safe and effective treatment of submassive pulmonary embolism.

An uncommon etiology of isolated pleural effusion. The ovarian hyperstimulation syndrome.

We report three cases of pleural effusion in the context of ovarian stimulation for in vitro fertilization. The ovarian hyperstimulation syndrome usually causes pleural effusion and ascites. When the latter is lacking, an isolated pleural effusion in a pregnant patient can be mistaken for pulmonary embolism. Early recognition of the condition should allow for an appropriate diagnostic and therapeutic management. Except for some rare but life-threatening complications, such as major hypovolemia or respiratory distress syndrome, the spontaneous outcome is usually favorable. The pathogenesis of this condition may involve an increase of capillary permeability due to the release of vasoactive mediators.

Heparin-induced thrombocytopenia with thrombotic complications during prophylactic treatment with low-molecular-weight heparin.

Heparin-induced thrombocytopenia is very uncommon with low-molecular-weight heparin, especially when given for prophylaxis of venous thromboembolism. In two of the four published cases, with thrombotic complications, thrombocytopenia may have been related to cross-reactivity between unfractionated heparin and low-molecular-weight heparin. We report one patient who received low-molecular-weight heparin for prophylaxis against venous thromboembolism without any previous injection of unfractionated heparin, and experienced thrombocytopenia with thrombotic complications. Heparin-induced thrombocytopenia was confirmed by several laboratory assays. This observation emphasizes the need for platelet count monitoring during low-molecular-weight heparin therapy.

[Talc therapy during thoracoscopy of pneumothorax due to rupture of the bullae in emphysema. A study of 71 cases]. / Le talcage sous thoracoscopie des pneumothorax par rupture de bulles d'emphysème. Etude de 71 cas.

The treatment of pneumothorax for large emphysematous bullae is classically surgical. We report a study of 71 patients treated by pleural talc therapy using thoracoscopy with good or excellent long term results in 93% of cases at a cost of some minor side effects. These results were compared with other forms of medical treatment which were always less effective and with surgical techniques which had more severe side effects. These results enable us to stress the value of talc therapy using pleuroscopy in patients with respiratory failure.

[Late presentation of a traumatic pulmonary arteriovenous malformation]. / Fistule artério-veineuse pulmonaire post-traumatique de révélation tardive.

INTRODUCTION: Pulmonary arteriovenous malformations (PAVM) are rare, and most often of congenital origin. Among secondary causes of PAVM, trauma is exceptional. CASE REPORT: We describe here one such case, discovered very late over twenty years after a thoracic perforing wound. Recent vascular imaging techniques (angio-CT scanning and -RMI) have largely contributed to their diagnosis, but direct pulmonary arteriography remains the reference technique preoperatively when surgery is required. In all cases, treatment is as conservative as possible, and embolization of small sized PAVM, even multiple, by coils has become the standard procedure. However, surgery is required when the PAVM is large and/or proximal, particularly when its feeding vessel is complex. Itwas the case of our patient, who has been cured by a lobectomy. CONCLUSIONS: PAVM are rare but should be sytematically searche for in case of hypoxemia along with a pulmonary nodule.

[Idiopathic pulmonary fibrosis: diagnosis and treatment in 2013]. / Fibrose pulmonaire idiopathique : prise en charge diagnostique et thérapeutique en 2013.

Idiopathic pulmonary fibrosis (IPF), the etiopathogeny of which is still unknown, is the most frequent and severe of idiopathic interstitial pneumonias. It progressively leads, sometimes more acutely when exacerbations occur, to a restrictive respiratory insufficiency. Its prognosis is very dark with a median survival of 3-5 years. No treatment so far has been curative. Its diagnostic and therapeutic management has been greatly improved due to the technical progress in terms of high-resolution tomodensitometry, to the availability of new drugs with a real antifibrotic potential and to the production of international recommendations. The diagnosis is reached in 2/3 of IPF patients presenting with a typical usual interstitial pneumonitis (UIP) CT-scan pattern. It requires a videothoracoscopic biopsy in the remaining patients. Multidisciplinary discussions are key to a proper diagnosis of IPF. Pirfenidone is presently the only drug with a real antifibrotic potential in mild to moderate forms of the disease (FVC>50% and DLCO>35% predicted). The other ones have proved either inefficient or toxic. It is highly recommended to include patients in innovative targeted protocols. Non-pharmacological management of these patients comprises long-term oxygen therapy, pulmonary rehabilitation and overall lung transplantation. Pulmonary hypertension, to be detected regularly during the follow-up, is associated to a dark prognosis. No specific treatment is efficient in this context. Several comorbidities, particularly frequent in IPF, should be treated when present: gastro-oesophageal reflux, obstructive sleep apnea, emphysema. The particular high frequency of bronchopulmonary cancer should be highlighted.

Outcome of patients with interstitial lung disease admitted to the intensive care unit.

INTRODUCTION: The outcome of acute respiratory failure (ARF) affecting patients with various interstitial lung diseases (ILD) is poorly defined particularly in those with drug-induced ILD (DI-ILD). We investigated this issue focusing on fibrosing idiopathic interstitial pneumonitis (FIIP) and DI-ILD. METHODS: We carried out a retrospective study of patients with ILD admitted in a single center ICU. The primary end-point was in-hospital mortality. RESULTS: We included 72 subjects who fell into 3 diagnostic groups: DI-ILD (n=20), FIIP (n=28) and miscellaneous (M-ILD) (n=24). In-hospital mortality rates were 40% (n=8/20), 68% (n=19/28), and 25% (n=6/24) for DI-ILD, FIIP and M-ILD, respectively, (p=0.006). It reached, 64% (n=7/11), 100% (n=17/17) and 60% (n=6/10), respectively, in subjects on mechanical ventilation (p=0.007). In multivariate analysis, the need for mechanical ventilation (OR= 35; [95% CI, 5-255]), the type of ILD (FIIP vs miscellaneous) (OR=22; [95% CI, 3-147]) and high-dose steroids during ICU stay (OR=0.19; [95% CI, 0.04-0.99]) were independent determinants of in-hospital mortality. CONCLUSION: This study, while confirming the poor prognosis of FIIP patients in ICU, highlights the better prognosis of DI-ILD and M-ILD even though severity criteria on admission are similar in these 3 groups. These data impact on the management of these patients in ICU in whom a proper diagnostic of the underlying condition is crucial.

A highly unusual combination of pulmonary pathogens in an HIV infected patient.

We report on a case with an unusual combination of pulmonary pathogens including Pneumocystis carinii, Rhodococcus equi and Toxoplasma gondii in an HIV infected patient. The multiple microbiological procedures required to ascertain the etiological diagnoses of pneumonitis in HIV-seropositive subjects are discussed.

Role of bronchoalveolar lavage in predicting survival of patients with human immunodeficiency virus infection.

In this multicenter study, we investigated the prognostic factors that influence the risk of death in patients with human immunodeficiency virus (HIV) infection. Clinical and laboratory indices obtained from 161 HIV-seropositive patients who underwent a detailed morphologic and immunophenotypic evaluation of bronchoalveolar lavage (BAL) and peripheral blood cell populations were retrospectively analyzed. In 155 patients, death occurred within the 48-mo follow-up (mean follow-up: 14.8 mo; range: 1 to 48 mo). In the univariate analysis, the patient's age (> 30 yr), HIV disease status, HIV transmission category, number of opportunistic pathogens isolated from the BAL, percentage of BAL neutrophils, and low number of BAL CD4 T cells were predictive of increased mortality. In contrast, the presence of an alveolitis or an increase in the numbers of alveolar macrophages and CD3 T cells was associated with a decreased mortality. In the multivariate analysis, significant independent predictors were age, risk factor for HIV, and presence of an alveolitis. Furthermore, patients with a low number of BAL CD4 T cells had a particularly poor prognosis while the CD4 T-cell count in the peripheral blood (< 50 cells/mm3 in the majority of our patients) had a negligible effect on predicting survival. Our findings suggest the clinical utility of BAL analysis in patients infected with HIV.

Site-directed bronchoalveolar lavage and transbronchial biopsy in HIV-infected patients with pneumonia.

We have assessed the diagnostic value of site-directed bronchoalveolar lavage (BAL) and combined transbronchial biopsy (TBB) in 29 HIV-infected patients with localized pneumonia, in whom a previous BAL was nondiagnostic and in whom improvement did not occur with empiric antibiotic therapy. All patients but three had a CD4 cell count < 100/microliters. A definite diagnosis could be reached in 26 of 29 (90%) individuals, including 24 pathogens. Neither the radiologic pattern nor the type of Pneumocystis carinii (PC) prophylaxis could predict the positivity of either one of these two diagnostic procedures. Site-directed BAL alone allowed a diagnosis in infection in eight (28%) cases. TBB alone led to diagnosis in eight (28%) cases, including three PC and two toxoplasma gondii, undiagnosed by the site-directed BAL. Both techniques were positive and in agreement in 10 (34%) cases. The majority of the diagnosis led to a specific treatment. Therefore, the patients' survival was positively altered by the procedure. In conclusion, the performance of site-directed BAL and combined TBB markedly optimizes the diagnostic yield of each of these procedures performed separately in HIV-infected patients with localized pneumonia.