Plasma D-dimer measurement is used in the assessment of the clinical probability of pulmonary embolism (PE), in order to minimize the requirement for pulmonary computed tomography angiography (CTA).

Purpose : To evaluate whether doubling the threshold value of serum D-dimer from 500 µg/L to 1000 µg/L could safely reduce utilization of pulmonary CTA to exclude PE in our emergency department patient population.

Material and Methods : Emergency department patients evaluated for PE with a quantitative D-dimer assay and pulmonary CTA were eligible for inclusion. D-dimer values were retrospectively collected in all included patients. Pulmonary CT angiograms were reviewed and scored as positive or negative for PE. Receiver-operating characteristic (ROC) analysis was used to determine the accuracy of quantitative D-dimer measurements in differentiating between positive and negative PE patients as per CTA.

Results : A total of 237 consecutive patients underwent pulmonary CTA and had a D-dimer measurement performed. Median D-dimer level was 1007 µg/L and in 11 (5%) patients the pulmonary CT CTA was positive for PE. The ROC curve showed an area under the curve (AUC) of 0.91 (P < 0.0001). Increasing the D-dimer threshold value of 500 µg/L to 1000 µg/L increased the specificity from 8% to 52% without changing the sensitivity.

Conclusion : Adjusting the D-dimer cut-off value for the emergency department community population and patient age increases the yield and specificity of the ELISA D-dimer assay for the exclusion of PE without reducing sensitivity.

Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death world-wide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism - in the same way platelets do-to deliver drugs to obstructed blood vessels.

Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model.

This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.

Exhaled eicosanoids and biomarkers of oxidative stress in exacerbation of chronic obstructive pulmonary disease.

Arch Med Sci. 2012 May 9;8(2):277-85

Authors: Antczak A, Ciebiada M, Pietras T, Piotrowski WJ, Kurmanowska Z, Górski P

Abstract
INTRODUCTION: Eicosanoids and oxidants play an important role in inflammation, but their role in chronic obstructive pulmonary disease (COPD) is uncertain. In this study we hypothesized that levels of exhaled leukotrienes, prostaglandins and biomarkers of oxidative stress are increased in infectious exacerbations of COPD and that they decrease after antibiotic therapy.
MATERIAL AND METHODS: Cysteinyl-leukotrienes (LTs), leukotriene B(4) (LTB(4)), prostaglandin E(4), hydrogen peroxide (H(2)O(2)) and 8-isoprostane were measured in exhaled breath condensate (EBC) in 16 COPD patients with infectious exacerbations (mean age 64 ±12 years, 13 male) on day 1, during antibiotic therapy (days 2-4), 2-4 days after therapy and at a follow-up visit when stable (21-28 days after therapy).
RESULTS: There was a significant fall in concentration of cys-LTs, LTB(4) and 8-isoprostane at visit 3 compared to day 1 (cys-LTs: 196.5 ±38.4 pg/ml vs. 50.1 ±8.2 pg/ml, p < 0.002; LTB(4): 153.6 ±25.5 pg/ml vs. 71.9 ±11.3 pg/ml, p < 0.05; 8-isoprostane: 121.4 ±14.6 pg/ml vs. 56.1 ±5.2 pg/ml, p < 0.03, respectively). Exhaled H(2)O(2) was higher on day 1 compared to that at visits 2 and 3 (0.74 ±0.046 µM vs. 0.52 ±0.028 µM and 0.35 ±0.029 µM, p < 0.01 and p < 0.01, respectively). Exhaled PGE(2) levels did not change during exacerbations of COPD. Exhaled eicosanoids and H(2)O(2) in EBC measured at the follow-up visit (stable COPD) were significantly higher compared to those from healthy subjects.
CONCLUSIONS: We conclude that eicosanoids and oxidants are increased in infectious exacerbations of COPD. They are also elevated in the airways of stable COPD patients compared to healthy subjects.

PMID: 22662001 [PubMed - in process]

Pulmonary tuberculosis and delay in anti-tuberculous treatment are important risk factors for chronic obstructive pulmonary disease.

PLoS One. 2012;7(5):e37978

Authors: Lee CH, Lee MC, Lin HH, Shu CC, Wang JY, Lee LN, Chao KM

Abstract
OBJECTIVE: Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database.
MAIN OUTCOME MEASURES: Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment.
RESULTS: The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD.
CONCLUSIONS: Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients.

PMID: 22662259 [PubMed - in process]