Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study.

PURPOSE: To evaluate a diagnostic strategy for pulmonary embolism that combined clinical assessment, plasma D-dimer measurement, lower limb venous ultrasonography, and helical computed tomography (CT). METHODS: A cohort of 965 consecutive patients presenting to the emergency departments of three general and teaching hospitals with clinically suspected pulmonary embolism underwent sequential noninvasive testing. Clinical probability was assessed by a prediction rule combined with implicit judgment. All patients were followed for 3 months. RESULTS: A normal D-dimer level (<500 microg/L by a rapid enzyme-linked immunosorbent assay) ruled out venous thromboembolism in 280 patients (29%), and finding a deep vein thrombosis by ultrasonography established the diagnosis in 92 patients (9.5%). Helical CT was required in only 593 patients (61%) and showed pulmonary embolism in 124 patients (12.8%). Pulmonary embolism was considered ruled out in the 450 patients (46.6%) with a negative ultrasound and CT scan and a low-to-intermediate clinical probability. The 8 patients with a negative ultrasound and CT scan despite a high clinical probability proceeded to pulmonary angiography (positive: 2; negative: 6). Helical CT was inconclusive in 11 patients (pulmonary embolism: 4; no pulmonary embolism: 7). The overall prevalence of pulmonary embolism was 23%. Patients classified as not having pulmonary embolism were not anticoagulated during follow-up and had a 3-month thromboembolic risk of 1.0% (95% confidence interval: 0.5% to 2.1%). CONCLUSION: A noninvasive diagnostic strategy combining clinical assessment, D-dimer measurement, ultrasonography, and helical CT yielded a diagnosis in 99% of outpatients suspected of pulmonary embolism, and appeared to be safe, provided that CT was combined with ultrasonography to rule out the disease.

Albuterol delivery in an in vitro pediatric ventilator lung model: comparison of jet, ultrasonic, and mesh nebulizers.

OBJECTIVE: : To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. DESIGN: : In vitro, laboratory study. SETTING: : Research laboratory of a university hospital. INTERVENTIONS: : Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. MEASUREMENTS AND MAIN RESULTS: : The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39-2.70 µm) reached the end of the endotracheal tube. CONCLUSIONS: : Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator-lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer.

Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis.

RATIONALE: Lung injury leads to pulmonary inflammation and fibrosis through myeloid differentiation primary response gene 88 (MyD88) and the IL-1 receptor 1 (IL-1R1) signaling pathway. The molecular mechanisms by which lung injury triggers IL-1beta production, inflammation, and fibrosis remain poorly understood. OBJECTIVES: To determine if lung injury depends on the NALP3 inflammasome and if bleomycin (BLM)-induced lung injury triggers local production of uric acid, thereby activating the NALP3 inflammasome in the lung. Methods: Inflammation upon BLM administration was evaluated in vivo in inflammasome-deficient mice. Pulmonary uric acid accumulation, inflammation, and fibrosis were analyzed in mice treated with the inhibitor of uric acid synthesis or with uricase, which degrades uric acid. MEASUREMENTS AND MAIN RESULTS: Lung injury depends on the NALP3 inflammasome, which is triggered by uric acid locally produced in the lung upon BLM-induced DNA damage and degradation. Reduction of uric acid levels using the inhibitor of uric acid synthesis allopurinol or uricase leads to a decrease in BLM-induced IL-1beta production, lung inflammation, repair, and fibrosis. Local administration of exogenous uric acid crystals recapitulates lung inflammation and repair, which depend on the NALP3 inflammasome, MyD88, and IL-1R1 pathways and Toll-like receptor (TLR)2 and TLR4 for optimal inflammation but are independent of the IL-18 receptor. CONCLUSIONS: Uric acid released from injured cells constitutes a major endogenous danger signal that activates the NALP3 inflammasome, leading to IL-1beta production. Reducing uric acid tissue levels represents a novel therapeutic approach to control IL-1beta production and chronic inflammatory lung pathology.

Heterogeneity of atherosclerotic plaque phenotypes and composition in four different arterial beds: an intravascular ultrasound virtual histology study

Purpose: The purpose of this study was to compare the plaque morphology between coronary and peripheral arteries using intravascular ultrasound (IVUS). Methods: IVUS was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Results: Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P=NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P=0.02) was observed in all arteries. Compared to coronary arteries, VH-FA was less frequently observed in renal (P<0.001) and iliac arteries (P<0.006), while VH-PIT and VH-FC were prevalent in both of these peripheral arteries. Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary, carotid, and renal arteries compared to those with intermediate/negative remodeling (all P<0.01). There was positive relationship between RI and percent necrotic core area in all four arteries. Conclusions: Atherosclerotic plaque phenotypes were heterogeneous among four different arteries. In contrast, the associations of remodeling mode with plaque phenotype and composition were similar among the various arterial beds.

Filariopsis barretoi (travassos, 1921) (Nematoda: metastrongyloidea) lung parasite of primates from South America - taxonomy, synonyms and pathology

Nematodes and fragments of lungs from Cebus ssp., Callithrix jacchus (l.) and Saimiri sciureus (L.) were studied. The worms from Cebus and Callithrix must be called Filariopsis barretoi (Travassos, 1921). The names Filariopsis arator Chandler, 1931 and Filaroides cebi Gebauer, 1933 are synonymized to F. barretoi. The status of Filariopsis gordius (Travassos, 1921) remains uncertain. The pathology is described. The parasites are located in the pulmonary paranchyma, near the pleural surface, constituting nodules.

Ex vivo ultrasound control of resection margins during partial nephrectomy.

Purpose: Surgery remains the treatment of choice for localized renal neoplasms. While radical nephrectomy was long considered the gold standard, partial nephrectomy has equivalent oncological results for small tumors. The role of negative surgical margins continues to be debated. Intraoperative frozen section analysis is expensive and time-consuming. We assessed the feasibility of intraoperative ex vivo ultrasound of resection margins in patients undergoing partial nephrectomy and its correlation with margin status on definitive pathological evaluation.Materials and Methods: A study was done at 2 institutions from February 2008 to March 2011. Patients undergoing partial nephrectomy for T1-T2 renal tumors were included in analysis. Partial nephrectomy was done by a standardized minimal healthy tissue margin technique. After resection the specimen was kept in saline and tumor margin status was immediately determined by ex vivo ultrasound. Sequential images were obtained to evaluate the whole tumor pseudocapsule. Results were compared with margin status on definitive pathological evaluation.Results: A total of 19 men and 14 women with a mean +/- SD age of 62 +/- 11 years were included in analysis. Intraoperative ex vivo ultrasound revealed negative surgical margins in 30 cases and positive margins in 2 while it could not be done in 1. Final pathological results revealed negative margins in all except 1 case. Ultrasound sensitivity and specificity were 100% and 97%, respectively. Median ultrasound duration was 1 minute. Mean tumor and margin size was 3.6 +/- 2.2 cm and 1.5 +/- 0.7 mm, respectively.Conclusions: Intraoperative ex vivo ultrasound of resection margins in patients undergoing partial nephrectomy is feasible and efficient. Large sample studies are needed to confirm its promising accuracy to determine margin status.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.

Alveolar macrophages and lung dendritic cells sense RNA and drive mucosal IgA responses.

The mechanisms regulating systemic and mucosal IgA responses in the respiratory tract are incompletely understood. Using virus-like particles loaded with single-stranded RNA as a ligand for TLR7, we found that systemic vs mucosal IgA responses in mice were differently regulated. Systemic IgA responses following s.c. immunization were T cell independent and did not require TACI or TGFbeta, whereas mucosal IgA production was dependent on Th cells, TACI, and TGFbeta. Strikingly, both responses required TLR7 signaling, but systemic IgA depended upon TLR7 signaling directly to B cells whereas mucosal IgA required TLR7 signaling to lung dendritic cells and alveolar macrophages. Our data show that IgA switching is controlled differently according to the cell type receiving TLR signals. This knowledge should facilitate the development of IgA-inducing vaccines.

Trends in lung cancer among young European women: the rising epidemic in France and Spain.

Lung cancer mortality in young women in the European Union (EU) has steadily increased until the mid 1990 s and has levelled off thereafter, but trends have been heterogeneous in various countries. We analyzed therefore age-standardized trends in lung cancer mortality in young women (20-44) for the 6 major European countries, using joinpoint regression. In the early 1970s the highest lung cancer mortality in young women was in the UK (2.1/100,000). UK rates, however, steadily declined and in 2000-2004 they were the lowest of all 6 major EU countries (1.2/100,000). The second lowest rate in 2000-2002 was in Italy, whose rates remained around 1.1/100,000 between 1970 and 1994, and increased to 1.4 thereafter. In Germany and Poland, lung cancer rates in young women rose from 0.8-1.0/100,000 in the early 1970s to 1.7-1.9 in the mid 1990 s and levelled off during the last decade. Major rises over recent years were observed in France (from 0.8/100,000 in 1985-1989 to 2.2 in 2000-2003) and in Spain (from 0.8 in the 1985-1989 to 1.7 in 2000-2004). Thus, France showed both the highest rate observed over the last 3 decades and the largest rise over the last 2 decades. Since recent trends in the young give relevant information to the likely future trends in middle age, the female lung cancer epidemic is likely to expand in southern Europe from the current rates of 5.0/100,000 in Spain and 7.7 in France to approach 20/100,000 within the next 2-3 decades. Urgent interventions for smoking cessation in women are therefore required.

Evaluation of tumour vascularisation in two rat sarcoma models for studying isolated lung perfusion. Injection route determines the origin of tumour vessels.

Isolated cytostatic lung perfusion (ILP) is an attractive technique allowing delivery of a high-dose of cytostatic agents to the lungs while limiting systemic toxicity. In developing a rat model of ILP, we have analysed the effect of the route of tumour cell injection on the source of tumour vessels. Pulmonary sarcomas were established by injecting a sarcoma cell suspension either by the intravenous (i.v.) route or directly into the lung parenchyma. Ink perfusion through either pulmonary artery (PA) or bronchial arteries (BA) was performed and the characteristics of the tumour deposits defined. i.v. and direct injection methods induced pulmonary sarcoma nodules, with similar histological features. The intraparenchymal injection of tumour cells resulted in more reliable and reproducible tumour growth and was associated with a longer survival of the animals. i.v. injected tumours developed a PA-derived vascular tree whereas directly injected tumours developed a BA-derived vasculature.

Host-microorganism interactions in lung diseases.

Until recently, the airways were thought to be sterile unless infected; however, a shift towards molecular methods for the quantification and sequencing of bacterial DNA has revealed that the airways harbour a unique steady-state microbiota. This paradigm shift is changing the way that respiratory research is approached, with a clear need now to consider the effects of host-microorganism interactions in both healthy and diseased lungs. We propose that akin to recent discoveries in intestinal research, dysbiosis of the airway microbiota could underlie susceptibility to, and progression and chronicity of lung disease. In this Opinion article, we summarize current knowledge of the airway microbiota and outline how host-microorganism interactions in the lungs and other tissues might influence respiratory health and disease.