Sean B. Smith

Early Anticoagulation Is Associated With Reduced Mortality for Acute Pulmonary Embolism

BACKGROUND Acute pulmonary embolism (PE) may be rapidly fatal if not diagnosed and treated. IV heparin reduces mortality and recurrence of PE, but the relationship between survival and timing of anticoagulation has not been extensively studied. METHODS We studied 400 consecutive patients in the ED diagnosed with acute PE by CT scan angiography and treated in the hospital with IV unfractionated heparin from 2002 to 2005. Patients received heparin either in the ED or after admission. Time from ED arrival to therapeutic activated partial thromboplastin time (aPTT) was calculated. Outcomes included in-hospital and 30-day mortality, hospital and ICU lengths of stay, hemorrhagic events on heparin, and recurrent venous thromboembolism within 90 days. RESULTS In-hospital and 30-day mortality rates were 3.0% and 7.7%, respectively. Patients who received heparin in the ED had lower in-hospital (1.4% vs 6.7%; P = .009) and 30-day (4.4% vs 15.3%; P < .001) mortality rates as compared with patients given heparin after admission. Patients who achieved a therapeutic aPTT within 24 h had lower in-hospital (1.5% vs 5.6%; P = .093) and 30-day (5.6% vs 14.8%; P = .037) mortality rates as compared with patients who achieved a therapeutic aPTT after 24 h. In multiple logistic regression models, receiving heparin in the ED remained predictive of reduced mortality, and ICU admission remained predictive of increased mortality. CONCLUSIONS We report an association between early anticoagulation and reduced mortality for patients with acute PE. We advocate further study with regard to comorbidities to assess the usefulness of modifications to hospital protocols.

Risk Factors Associated with Delayed Diagnosis of Acute Pulmonary Embolism

BACKGROUND Prompt diagnosis and treatment of acute pulmonary embolism (PE) is essential to reduce mortality. Risk factors for PE are well known, but factors associated with delayed diagnosis are less clear. OBJECTIVE Our objective was to identify clinical factors associated with delayed diagnosis of patients with acute PE presenting to a tertiary-care emergency department (ED). METHODS We studied 400 consecutive adults who presented to our ED with acute, symptomatic PE. All patients were diagnosed by computed tomography (CT) angiography. Early diagnosis was defined as CT diagnosis<12h from ED arrival, and delayed diagnosis as CT diagnosis>12h. Univariate and multiple logistic regression models were used to identify factors associated with delayed diagnosis. Odds ratios with 95% confidence intervals are reported. RESULTS The median time from arrival to diagnosis was 2.4h (interquartile range 1.4-7.6), and 73 (18.3%) patients had delayed diagnosis. Patients aged>65 years and those with coronary artery disease or congestive heart failure had longer times from ED arrival to CT diagnosis, whereas patients with recent immobility had shorter times. Patients diagnosed>12h were older and had higher rates of morbid obesity and coronary artery disease, whereas patients diagnosed<12h had higher rates of tachycardia. In multiple regression modeling, tachycardia and recent immobility remained associated with early diagnosis, whereas morbid obesity remained associated with delayed diagnosis. CONCLUSIONS Older patients with cardiovascular comorbidities had longer times from ED arrival to CT diagnosis. Our data suggest that these patients represent more of a diagnostic challenge than those presenting with traditional risk factors for PE, such as tachycardia and recent immobilization. Physicians should consider these factors to diagnosis acute PE promptly in the ED.

Up-regulation of MUC18 in airway epithelial cells by IL-13: implications in bacterial adherence.

Airway bacterial infections are a major problem in lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Increased Th2 cytokines, such as IL-13, are observed in lung diseases and may contribute to bacterial infections. How Th2 cytokines affect bacterial infection remains unknown. MUC18, an adhesion molecule shown to be involved in the pathogenesis of malignant melanoma, has been recently identified in airway epithelial cells of patients with COPD. We investigated MUC18 regulation by IL-13 and the role of MUC18 in bacterial adherence to epithelial cells. Human airway tissues, brushed bronchial epithelial cells from normal subjects and subjects with asthma, and epithelial cell lines (e.g., HEK293 cells) were used to study the regulation of MUC18 by IL-13 and the involvement of MUC18 in bacterial (e.g., Mycoplasma pneumoniae [Mp] and nontypeable Haemophilus influenzae [NTHi]) adherence to epithelial cells. Asthmatic bronchial epithelium expressed higher levels of MUC18 than normal bronchial epithelium. IL-13 increased MUC18 in cultured bronchial epithelial cells from normal subjects and particularly from subjects with asthma. IL-13-induced MUC18 expression may be modulated in part through transcription factor specificity protein 1. Overexpression of human MUC18 in HEK293 cells increased cell-associated Mp and NTHi levels. Moreover, MUC18 was shown to directly interact with Mp and NTHi. These results for the first time show that an allergic airway milieu (e.g., IL-13) increases MUC18 expression, which may contribute to increased bacterial infection/colonization in asthma and other lung diseases.