Thrombolytic therapy of pulmonary embolism: a meta-analysis

OBJECTIVES: We sought to assess the efficacy and safety of thrombolytic therapy in patients with an acute pulmonary embolism (PE). BACKGROUND: Thrombolytic therapy is approved for the treatment of acute PE; however, the safety and efficacy of this therapy remain debated. METHODS: A meta-analysis of randomized, controlled trials comparing thrombolytic agents with intravenous heparin in patients with acute PE was performed. Trials were identified through a combined search of the MEDLINE, EMBASE, and Current Contents databases. Three outcome measures were assessed: 1) mortality, 2) recurrence of PE, and 3) major hemorrhage. RESULTS: Nine trials including 461 patients were identified. Compared with intravenous heparin, thrombolytic therapy had no significant effect on mortality (relative risk [RR] 0.63, 95% confidence interval [CI] 0.32 to 1.23) or the recurrence of PE (RR 0.59, 95% CI 0.30 to 1.18), but was associated with an increased risk of major hemorrhage (RR 1.76, 95% CI 1.04 to 2.98). These results were homogeneous and largely unaffected by the formulation of thrombolytic agent, the clinical severity of PE, the extent of vascular obstruction determined radiologically, or the methodologic quality of the included trials. CONCLUSIONS: Compared with intravenous heparin, thrombolytic therapy does not appear to have therapeutic benefit in unselected patients with acute PE, but it is associated with an increased risk of major hemorrhage. Given the small number of patients included in the randomized trials thus far, the negative results in terms of the efficacy outcomes should be interpreted with caution. Definitive evidence of the utility of thrombolytic therapy in this setting requires a large, randomized, controlled trial.     

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

Respiratory complications: a major concern after right hepatectomy in living liver donors

BACKGROUND: One of the main concerns after living donor liver transplantation is the risk of morbidity and/or mortality that it imposes on the donors. Respiratory postoperative complications in living liver donors have already been reported but their frequency seems to be underestimated. We designed a prospective study to evaluate the rate and the nature of postoperative pulmonary complications in 112 consecutive donors. METHODS: The medical records of the 112 living liver donors operated on at our center from 1998 to 2003 were reviewed and all the cases of respiratory complications were retrieved. Moreover, since 2000, all patients had a computed tomography angiography of the thorax at day 7 on a prospective basis. RESULTS: In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or adult-to-child liver donation were performed in our center. No postoperative mortality was recorded. Fourteen major respiratory complications developed in of 11 of 112 donors (9.8%), in all cases after right hepatectomy, and included nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors (8.9%), who in the vast majority remained free of pulmonary complications. CONCLUSIONS: In our series, pulmonary complications are frequent in living liver donors. These complications are mainly observed after right hepatectomy. The particular prevalence of pulmonary embolism should lead to focus on its early diagnosis and prevention.     

Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis

OBJECTIVE: Although lung transplantation is viewed as an acceptable option for patients with end-stage idiopathic pulmonary fibrosis, the survival benefit of this approach is still debated. This study examined whether there was a survival benefit of lung transplantation in a cohort of patients referred to our transplant center with a diagnosis of idiopathic pulmonary fibrosis according to American Thoracic Society criteria. METHODS: Forty-six patients accepted for lung transplantation during a 12-year period with a diagnosis of idiopathic pulmonary fibrosis form the basis of this study. Survival benefit offered by lung transplantation was assessed using Cox proportional-hazards modeling, with patients on a waiting list as the control group. RESULTS: Twenty-eight patients underwent lung transplantation (27 single and 1 double), 16 patients died while waiting, and 2 patients remained on the active waiting list. Diagnosis of idiopathic pulmonary fibrosis was made on histologic examination of the explanted lung or lung biopsy before lung transplantation. There was a pattern of usual interstitial pneumonia in 31 cases (67%). The 15 remaining patients fulfilled all American Thoracic Society criteria for idiopathic pulmonary fibrosis. The median waiting time for organs was 51 days. Survival after lung transplantation was 79.4% at 1 year, 63.5% at 2 years, and 39% at 5 years. The multivariable analysis showed that lung transplantation reduced the risk of death by 75% (95% confidence interval, 8%-86%; P =.03) after adjustment on potential confounding variables. CONCLUSIONS: Lung transplantation is effective in improving the survival of selected patients affected by idiopathic pulmonary fibrosis.     

Recurrence of pulmonary emphysema in an alpha-1 proteinase inhibitor-deficient lung transplant recipient

Several types of primary disease may recur after lung transplantation, but recurrence of pulmonary emphysema has so far never been published. We report the case of a 49-year-old white male who underwent single lung transplantation for emphysema related to alpha-1 antitrypsin deficiency and to superimposed smoking. The postoperative course was complicated by several rejection episodes. Subsequently, the patient remained stable without evidence of graft dysfunction for more than 10 years, but he resumed light smoking at 8 years after transplant. At 11 years after transplant, although the patient was still asymptomatic and had a stable lung function, recurrence of emphysema on the grafted side was diagnosed on computerized tomography of the thorax. One year later, the patient began to experience a moderate decline in lung function. Two separate bronchoalveolar lavages performed after the onset of the recurrence disclosed a significant elastolytic activity related to neutrophil serine-elastase in lavage fluid. In summary, we describe a case of recurrence of pulmonary emphysema in a patient with alpha-1 antitrypsin deficiency. The resumption of smoking has probably played a central role in the presence of elastolytic activity in lavage fluid and in the recurrence of emphysema.     

Analysis of the different histologic lesions observed in transbronchial biopsy for the diagnosis of acute rejection. Clinicopathologic correlations during the first 6 months after lung transplantation

Acute rejection is an extremely common complication of lung transplantation. (1) To appreciate the interobserver variation in the interpretation of histologic findings and (2) to assess the efficacy of transbronchial biopsy (TBB) for acute rejection diagnosis and associated diseases, particularly infection, we performed a retrospective study including 53 consecutive patients who underwent at least one clinically indicated TBB during the first 6 months after lung transplantation. A total of 94 TBB was obtained. The following histologic features observed in TBB specimens-perivascular mononuclear infiltrates, lymphocytic bronchitis/bronchiolitis, and alveolar lesions, were reliably reproduced by 2 pathologists from the same transplant center, with kappa values ranging from 0.79 to 0.82. For identifying perivascular mononuclear infiltrates, discordance between the 2 observers was significantly associated with moderate/severe alveolar lesions. For the diagnosis of acute rejection, perivascular mononuclear infiltrates had a specificity of 96.5%, a positive predictive value of 97.5%, and a sensitivity of 67.7%, whereas lymphocytic bronchitis/bronchiolitis had a specificity of 56.3% and a sensitivity of 19.4%. Interestingly, there was a positive independent correlation between infection and moderate/severe alveolar histologic lesions ( P < .01). In conclusion, the interobserver agreement between experienced pathologists in TBB interpretation is good. Perivascular mononuclear infiltrates remain the cornerstone for acute rejection diagnosis. The presence of moderate/severe alveolar lesions should prompt to search for infection.     

Exhaled NO may predict the decline in lung function in bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) remains the leading cause of morbidity/mortality following lung transplantation. In recipients with BOS, markers predicting the decline in lung function are needed. The aim of this longitudinal study was to determine whether exhaled nitric oxide fraction (FeNO) measurements provide useful information for discriminating patients with unstable BOS from those with stable BOS. During a 14-month period, 145 FeNO measurements were performed in 50 lung transplant recipients. Among them, 16 recipients with BOS (32 FeNO measurements) were analysed. For each FeNO measurement, the patients were classified into three groups according to the decline in forced expiratory volume in one second (FEV1) within the following 6 months: 1) stable BOS free; 2) stable BOS (decline in FEV1 of <5%); and 3) unstable BOS (decline in FEV1 of > or =15%). The mean FeNO in patients with unstable BOS was significantly increased compared with that in stable BOS-free patients (18.4+/-5.7 versus 9.7+/-3.7 ppb) and that in patients with stable BOS (18.4+/-5.7 versus 9.7+/-3.3 ppb). The present findings suggest that, in patients with bronchiolitis obliterans syndrome, a raised exhaled nitric oxide fraction may predict the development of worrisome functional impairment during long-term follow-up.