Carla Grabianowski

Circulating Tissue Factor Procoagulant Activity is Elevated in Stable Moderate to Severe Chronic Obstructive Pulmonary Disease

INTRODUCTION Chronic obstructive pulmonary disease (COPD) patients have increased risk for cardiovascular mortality and venous thromboembolism. Tissue factor (TF) is the physiological initiating mechanism for blood coagulation and is pro-inflammatory. METHODS We have studied circulating blood-borne TF-procoagulant activity (TF-PCA), plasma coagulation factors (F) VIIa and FVIII, and thrombin-antithrombin (TAT) complexes in 11 stable, moderate-severe COPD patients, 10 free of exacerbation for >3 weeks. RESULTS TF-PCA was increased in COPD patients (52.3+/-5.6 U/ml, (SE)) compared to control subjects (20.7+/-1.5, n=45, p<0.0001). TAT levels were increased (COPD patients: 2.99+/-0.65 ug/l; control subjects: 1.31+/-0.13, n=53, p<0.0001), indicating enhanced thrombin generation. Plasma FVIIa (the activated form of FVII) was higher in COPD (83+/-11 mU/ml; controls, 64+/-5 mU/ml, n=20) but did not reach statistical significance. Plasma FVIIc and FVIII were not increased. TF-PCA levels were inversely related to plasma FVIIa (r=-0.80, p=0.003) and FVIIc (r=-0.76, p=0.007). CONCLUSIONS Blood-borne TF-PCA is elevated and constitutes a prothrombotic and proinflammatory state in stable but moderate-severe COPD, and may contribute to the increased risk for vascular events.

The Effect of Chronic Sputum Production on Respiratory Symptoms in Severe COPD

Background: Chronic sputum production is a significant but variable complaint in COPD; its effect on symptom burden has not been comprehensively described. We sought to characterize the daily burden of chronic sputum production in severe COPD and the phenotype of those with chronic sputum symptoms. Methods: We studied 50 outpatients with severe COPD who used an electronic diary to document peak expiratory flow (PEF) and respiratory symptoms daily for up to 2 years. A sputum index was derived based on complaints of sputum quantity, color, and consistency, and patients were divided into groups based on average daily sputum index (Low, Medium, High). The presence and severity of respiratory symptoms were scored by a novel method using daily changes in symptoms and PEF from baseline and were categorized into mild, moderate, and severe. Percent emphysema was measured using quantitative CT. Results: In the 14,500 observation days, severe symptom days were greater in the Medium and High groups (379/6089, 1609/4091, and 2624/4317 observation days in Low, Medium, and High, p < 0.0001). The same trend was found even when sputum complaints were removed from the symptom severity score. Observed/predicted PEF ratio was lower in the High group (0.56 ± 0.24, 0.55 ± 0.19, and 0.42 ± 0.12 in each group, p < 0.05 for High compared to Medium and Low). Percent emphysema inversely correlated with average sputum index and quantity (r = −0.449 and r = −0.584, respectively, p < 0.05). Conclusions: Increased sputum production in severe COPD is frequently encountered daily and is associated with more respiratory symptoms, worse airflow obstruction, and less emphysema.

Use of a SmartPhone/Tablet-Based Bidirectional Telemedicine Disease Management Program Facilitates Early Detection and Treatment of COPD Exacerbation Symptoms

INTRODUCTION Early treatment of worsening chronic obstructive pulmonary disease (COPD) symptoms speeds recovery, improves quality of life, and reduces the need for hospitalization. Patients may fail to recognize worsening symptoms leading to delays in treatment. A telemedicine application could facilitate detection and treatment of worsening symptoms. To work, such an application requires consistent use by patients and quick responses from healthcare providers. We conducted a quality assurance assessment of our system to see if we were meeting these goals. MATERIALS AND METHODS Thirty patients were provided a smartphone application for daily COPD symptom reporting. Reports between November 2012 and September 2013 were reviewed. Symptoms reports and interventions were time-stamped by the application. Adherence reporting was calculated as the number of reports made divided by the number of days enrolled in the program for each patient. Time to intervention was calculated as the time a report was submitted to the time a treatment recommendation was sent to the patient. RESULTS There were 4,434 symptom reports made over 5,178 patient-days of observation for an average reporting compliance of 85.6%. Median reporting compliance was 90.7% (interquartile range, 83.8-98%). Four hundred seventy-five symptom reports resulted in an alert. The average response time for all alerts was 6.64 h, with a median response time of 5.75 h. CONCLUSIONS From this quality assessment we were able to conclude that patient adherence to the reporting system exceeded 90% for over half of the participants. Furthermore, over 50% of worsening COPD symptom reports were responded to in less than 6 h with patient-specific treatment recommendations.

Outcomes of COPD Exacerbations Treated with Corticosteroids, Antibiotics, or Both

Background. The outcomes for outpatient treatment of acute exacerbations of COPD (AECOPD) are poorly described. Design. The results of a daily diary recording symptoms and peak flows were compiled into a severity score to trigger algorithm-based treatments and a symptom index to follow treatment response. Treatment failure (symptom index failing to return to baseline for 2 consecutive days or hospitalization within 21 days) was the main outcome. Results. Twenty-two patients (FEV1 0.81 ± 0.26 L) were treated for 115 AECOPDs (corticosteroids = 36, antibiotics = 41, corticosteroids/antibiotics = 38). Treatment failure was 50% for the corticosteroid/antibiotic compared to 28% (𝑃=0.006) for the corticosteroid and 34% (𝑃<0.0001) for the antibiotic group. Patients suffering from AECOPDs treated with corticosteroids had dyspnea, wheezing, and decreased peak flow; those treated with antibiotics had sputum symptoms; those treated with corticosteroids/antibiotics had dyspnea, wheezing, sputum symptoms, and decreased peak flows. Conclusions. AECOPDs with both dyspnea and sputum symptoms are more refractory to standard treatment and likely require closer monitoring.