Safety and efficacy of direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) remains an underdiagnosed disease. Anticoagulation is essential in its therapy to prevent recurrent venous thromboembolism (VTE). According to some international guidelines, vitamin K antagonists (VKA) remain the gold standard. Nevertheless, direct oral anticoagulants (DOAC) are widely used, partly because of numerous advantages. The objective of this study was to determine if DOAC is an effective and safe alternative to VKA in CTEPH patients. MATERIALS AND METHODS: A retrospective observational study was conducted between 2001 and 2021 in a CTEPH Clinic of a tertiary care hospital. We recorded demographic characteristics, anticoagulant therapies and pulmonary hypertension treatments received. Safety outcomes were bleeding events and deaths while efficacy outcomes were recurrent VTE events. RESULTS: Among the study population (N = 205), the distribution of anticoagulant used transitioned from majority on VKA to majority on DOAC. In 2020, 23 (19 %) were on VKA and 97 (78 %) on DOAC. Among 11 VTE events occurring during follow-up, 7 were in the VKA group (1.10 %/person-year) and 1 in the DOAC group (0.32 %/person-year). Rates of VTE recurrence were not significantly different in those treated with DOAC compared to VKA (P = 0.21). Total bleeding rate on VKA (2.52 %/person-year) and DOAC (2.52 %/person-year) were the same (P = 1.00). Among 27 patients who died, no deaths occurred as a consequence of bleeding or VTE events. CONCLUSION: Bleeding and VTE events were not higher in CTEPH patients receiving DOAC compared to VKA which adds confidence to considering DOAC as an effective and safe alternative for long term anticoagulation in CTEPH patients.

Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study.

BACKGROUND: The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown. OBJECTIVE: To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation. DESIGN: Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818). SETTING: Eighteen sites between February 2011 and February 2021. PATIENTS: Patients with isolated subsegmental pulmonary embolism. INTERVENTION: At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy. MEASUREMENTS: The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period. RESULTS: Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism. LIMITATION: The study was restricted to patients with low-risk subsegmental pulmonary embolism. CONCLUSION: Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability.

BACKGROUND: Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP. METHODS: We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism. RESULTS: A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9). CONCLUSIONS: A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).

Contributions of protein and milled chitin extracted from domestic cricket powder to emulsion stabilization.

Interfacial and emulsifying properties of fractionated cricket powder were assessed to identify whether emulsification properties originate from protein or chitin particles. Fractions extracted in alkaline water, containing high protein and mineral contents, increased the surface pressure of heptane-water interfaces with near-saturation equilibrium surface pressure of 31 mN/m. Dynamic surface pressure profiles indicated adsorption of protein clusters to the interface. Emulsification capacity of protein fraction was 50% greater than that of the source cricket flour, although oil-in-water emulsions prepared with 1-2% (w/w) protein fraction formed a cream layer within one day of storage. Emulsified layers persisted for up to 20 days, and light scattering measurements described a stable population with surface-volume-mean diameter of approximately 3 µm. Chitin-rich fractions milled to a particle size of 0.5-200 µm contributed negligible surface pressure, and its emulsification capacity was 5% of the value for the source cricket flour. Emulsions prepared with chitin-rich fractions coexisted with an unstable precipitate layer comprising 60% of the added solid, which was attributed to larger particles with poor emulsifying capability. Stable chitin-stabilized emulsion phases were resistant to creaming, yet volume-mean droplet diameter surpassed 50 µm within 24 h of storage. Both protein and chitin fractions have emulsifying capabilities but would require further processing or secondary additives to achieve desirable storage stability.

Serial imaging after pulmonary embolism and correlation with functional limitation at 12 months: Results of the ELOPE Study.

INTRODUCTION: Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub-study of the prospective, multicenter ELOPE (Evaluation of Long-term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year. METHODS: In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university-affiliated hospitals. CT pulmonary angiography was performed at baseline and 12 months, perfusion scan at 6 and 12 months, and cardio-pulmonary exercise testing at 1 and 12 months. Imaging parameters included: on CT pulmonary angiography, CT obstruction index (CTO) (% clot burden in the pulmonary vasculature), and on perfusion scan, pulmonary vascular obstruction (PVO) (% perfusion defect). Abnormal cardio-pulmonary exercise test (primary outcome) was defined as percent of predicted peak oxygen uptake (VO2) <80%. RESULTS: Mean (median; SD) CT obstruction index was 28.1% (27.5%; 18.3%) at baseline, 1.2% (0%; 4.3%) at 12 months. Mean (median; SD) pulmonary vascular obstruction was 6.0% (0%; 9.6%) at 6 months, 5.6% (0%; 9.8%) at 12 months. Eighty-six patients had exercise testing at 12 months, and 46.5% had VO2 < 80% predicted. Mean (median; SD) CT obstruction index at 1 year was similar in patients with percent-predicted VO2 peak <80% vs >80% on 1-year cardio-pulmonary exercise testing (1.4% [0%; 5.7%] vs 1.0% [0%; 2.4%]; P = .70). Mean (SD) pulmonary vascular obstruction at 6 and at 12 months was similar in patients with percent-predicted VO2 peak <80% vs >80% (6 months: 5.9% [0%; 10.4%] vs 6.2% [4.5%; 9.0%]; P = .91; 12 months: 5.1% [0%; 10.2%] vs 6.0% [0%; 9.7%]; P = .71). CONCLUSIONS: Imaging findings after pulmonary embolism did not predict exercise limitation. Residual thrombus does not appear to explain long-term functional limitation after pulmonary embolism.

Temporal trends in outpatient management of incident pulmonary embolism and associated mortality.

INTRODUCTION: In clinical trial settings, outpatient management of pulmonary embolism (PE) is feasible and safe, but less is known on its use in routine care. We determined trends in outpatient management of PE and associated mortality in a large non-select patient population. METHODS: All residents of Quebec, Canada with a first-ever work-up for suspected PE in the emergency department (ED) over 10years were included. Patients could transition to outpatient management and from unconfirmed to confirmed PE in a time-varying fashion. Comparing the years 2005-9 with 2000-4, we assessed the odds ratio (OR) for outpatient management, and relative risk (RR) for all-cause mortality, readmissions for PE, and major bleeding in 30days. We adjusted the RR for a mortality risk score. RESULTS: Of 15,217 patients included, 7583 were outpatients (7.5% confirmed PE) and 7634 were inpatients (60.6% confirmed PE). In all, 10.9% of patients with confirmed PE were outpatients, but outpatient management of confirmed PE was more likely in the latter study period (OR 1.73, 95%CI 1.44-2.09). Among outpatients with confirmed PE, mortality (RR 0.84, 95%CI 0.15-4.61) and readmission (RR 1.25, 95%CI 0.45-3.48) rates were stable, and only 3 major bleeding events were noted. Inpatients with confirmed PE had stable mortality rates (RR 0.95, 95%CI 0.72-1.24). CONCLUSION: Outpatient PE management increased over 10years while remaining fairly uncommon. Nevertheless, stable mortality and readmission rates indicate this practice is safe in routine care, and add to the growing evidence in support of outpatient PE management.

Right ventricular ST-elevation myocardial infarction as a cause of death in idiopathic pulmonary arterial hypertension.

A 32-year-old woman with advanced idiopathic pulmonary arterial hypertension (PAH), treated with oral tadalafil and intravenous epoprostenol, presented with typical angina pectoris of one day's duration. Her electrocardiogram, previously typical of pulmonary hypertension, revealed an acute ST-elevation myocardial infarction in the anterior precordial leads. She had a prior coronary angiogram, in preparation for lung transplantation, that revealed normal coronary arteries. Urgent coronary angiography showed acute occlusion of several acute marginal coronary branches that feed the right ventricle (RV). Coronary angioplasty and stenting was unable to adequately restore coronary perfusion. Despite support, she developed progressive cardiogenic shock and died three days later. This is an unusual complication of PAH.

Quality of Life, Dyspnea, and Functional Exercise Capacity Following a First Episode of Pulmonary Embolism: Results of the ELOPE Cohort Study.

BACKGROUND: We aimed to evaluate health-related quality of life (QOL), dyspnea, and functional exercise capacity during the year following the diagnosis of a first episode of pulmonary embolism. METHODS: This was a prospective multicenter cohort study of 100 patients with acute pulmonary embolism recruited at 5 Canadian hospitals from 2010-2013. We measured the outcomes QOL (by Short-Form Health Survey-36 [SF-36] and Pulmonary Embolism Quality of Life [PEmb-QoL] measures), dyspnea (by the University of California San Diego Shortness of Breath Questionnaire [SOBQ]) and 6-minute walk distance at baseline and 1, 3, 6, and 12 months after acute pulmonary embolism. Computed tomography pulmonary angiography was performed at baseline, echocardiogram was performed within 10 days, and cardiopulmonary exercise testing was performed at 1 and 12 months. Predictors of change in QOL, dyspnea, and 6-minute walk distance were assessed by repeated-measures mixed-effects models analysis. RESULTS: Mean age was 50.0 years; 57% were male and 80% were treated as outpatients. Mean scores for all outcomes improved during 1-year follow-up: from baseline to 12 months, mean SF-36 physical component score improved by 8.8 points, SF-36 mental component score by 5.3 points, PEmb-QoL by -32.1 points, and SOBQ by -16.3 points, and 6-minute walk distance improved by 40 m. Independent predictors of reduced improvement over time were female sex, higher body mass index, and percent-predicted VO2 peak <80% on 1 month cardiopulmonary exercise test for all outcomes; prior lung disease and higher pulmonary artery systolic pressure on 10-day echocardiogram for the outcomes SF-36 physical component score and dyspnea score; and higher main pulmonary artery diameter on baseline computed tomography pulmonary angiography for the outcome PEmb-QoL score. CONCLUSIONS: On average, QOL, dyspnea, and walking distance improve during the year after pulmonary embolism. However, a number of clinical and physiological predictors of reduced improvement over time were identified, most notably female sex, higher body mass index, and exercise limitation on 1-month cardiopulmonary exercise test. Our results provide new information on patient-relevant prognosis after pulmonary embolism.

Functional and Exercise Limitations After a First Episode of Pulmonary Embolism: Results of the ELOPE Prospective Cohort Study.

BACKGROUND: We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea. METHODS: One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) < 80% at 1-year CPET. RESULTS: At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak < 80% on CPET, which was associated with significantly worse generic health-related QoL (HRQoL), PE-specific HRQoL and dyspnea scores, and significantly reduced 6MWD at 1 year. Predictors of the primary outcome included male sex (relative risk [RR], 3.2; 95% CI, 1.3-8.1), age (RR, 0.98; 95% CI, 0.96-0.99 per 1-year age increase), BMI (RR 1.1; 95% CI, 1.01-1.2 per 1 kg/m2 BMI increase), and smoking history (RR, 1.8; 95% CI, 1.1-2.9), as well as percent predicted Vo2 peak < 80% on CPET at 1 month (RR, 3.8; 95% CI,1.9-7.2), and 6MWD at 1 month (RR, 0.82; 95% CI, 0.7-0.9 per 30-m increased walking distance). Baseline or residual clot burden was not associated with the primary outcome. Mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricular systolic function) at 1 year were similarly within normal limits in both patients with exercise limitations and those without such limitations. CONCLUSIONS: Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Pregnancy as a possible trigger for heritable pulmonary arterial hypertension.

It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease.

A multicenter prospective study of risk factors and treatment of unusual site thrombosis.

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism (VTE) with heterogeneity in pathophysiology and clinical features. While the need for anticoagulation treatment is generally accepted, there is little data on optimal USDVT treatment. The TRUST study aimed to characterize the epidemiology, treatment and outcomes of USDVT. From 2008 to 2012, 152 patients were prospectively enrolled at 4 Canadian centers. After baseline, patients were followed at 6, 12 and 24months. There were 97 (64%) cases of splanchnic, 33 (22%) cerebral, 14 (9%) jugular, 6 (4%) ovarian and 2 (1%) renal vein thrombosis. Mean age was 52.9years and 113 (74%) cases were symptomatic. Of 72 (47%) patients tested as part of clinical care, 22 (31%) were diagnosed with new thrombophilia. Of 138 patients evaluated in follow-up, 66 (48%) completed at least 6months of anticoagulation. Estrogen exposure or inflammatory conditions preceding USDVT were commonly associated with treatment discontinuation before 6months, while previous VTE was associated with continuing anticoagulation beyond 6months. During follow-up, there were 22 (16%) deaths (20 from cancer), 4 (3%) cases of recurrent VTE and no fatal bleeding events. Despite half of USDVT patients receiving <6months of anticoagulation, the rate of VTE recurrence was low and anticoagulant treatment appears safe. Thrombophilia testing was common and thrombophilia prevalence was high. Further research is needed to determine the optimal investigation and management of USDVT.

Operative and Functional Outcome After Pulmonary Endarterectomy for Advanced Thromboembolic Pulmonary Hypertension.

AIM: To evaluate the midterm hemodynamic and functional outcome of pulmonary endarterectomy (PEA) for patients with advanced chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirty-eight consecutive patients underwent PEA for CTEPH from May 2004 to March 2012. All patients were followed prospectively at six months postoperatively and annually thereafter. Each patient underwent serial cardiopulmonary exercise testing (CPET) and transthoracic echocardiography, and were followed for up to four years. RESULTS: Overall, 31.5% (12/38) of patients had Jamieson class II disease while 65.8% (25/38) had class III disease. There were three in-hospital mortalities (7.9%), all of which had baseline pulmonary vasculature resistance (PVR) greater than 1400 dynes-sec-cm(-5) . Preoperative PVR and mean pulmonary artery pressure were 1209 ± 723 dynes-sec-cm(-5) and 50 ± 14 mmHg, respectively, signifying a high-risk operative group. Ninety-seven percent of patients were in NYHA class III or IV preoperatively. At median follow-up of 29 months 89.5% (17/19) of patients were in NYHA class I or II. CPET revealed a progressive increase in peak oxygen consumption from 16.5 ± 4.1 ml/kg/min at first follow-up, to a plateau of 20.2 ± 5.6 ml/kg/min (p = 0.032) at two years. CONCLUSIONS: CPET can be used to quantify progress in functional capacity post-CTEPH, although improvements in peak oxygen consumption plateau at two years.

Implementation of a targeted screening program to detect airflow obstruction suggestive of chronic obstructive pulmonary disease within a presurgical screening clinic.

BACKGROUND: Targeted spirometry screening for chronic obstructive pulmonary disease (COPD) has been studied in primary care and community settings. Limitations regarding availability and quality of testing remain. A targeted spirometry screening program was implemented within a presurgical screening (PSS) clinic to detect undiagnosed airways disease and identify patients with COPD/asthma in need of treatment optimization. OBJECTIVE: The present quality assurance study evaluated airflow obstruction detection rates and examined characteristics of patients identified through the targeted screening program. METHODS: The targeted spirometry screening program was implemented within the PSS clinic of a tertiary care university hospital. Current or ex-smokers with respiratory symptoms and patients with a history of COPD or asthma underwent prebronchodilator spirometry. History of airways disease and smoking status were obtained during the PSS assessment and confirmed through chart reviews. RESULTS: After exclusions, the study sample included 449 current or ex-smokers. Abnormal spirometry results were found in 184 (41%) patients: 73 (16%) had mild, 93 (21%) had moderate and 18 (4%) had severe or very severe airflow obstruction. One hundred eighteen (26%) new cases of airflow obstruction suggestive of COPD were detected. One-half of these new cases had moderate or severe airflow obstruction. Only 34% of patients with abnormal spirometry results had reported a previous diagnosis of COPD. More than one-half of patients with abnormal spirometry results were current smokers. CONCLUSIONS: Undiagnosed airflow obstruction was detected in a significant number of smokers and ex-smokers through a targeted screening program within a PSS clinic. These patients can be referred for early intervention and secondary preventive strategies.

Long-term outcomes after pulmonary embolism: current knowledge and future research.

In this article, we provide the rationale for the ELOPE (Evaluation of Long-term Outcomes after Pulmonary Embolism) Study, a prospective, observational, multicenter cohort study of patients with a newly diagnosed, first episode of pulmonary embolism (www.clinicaltrials.govNCT01174628) that aims to identify clinical, anatomic, physiologic and biomarker determinants of poor outcome after pulmonary embolism.Pulmonary embolism, the most serious form of venous thromboembolism (VTE), leads to the hospitalization or death of over 30,000 Canadians, 225,000 Americans and 300,000 Europeans each year, numbers that have risen over the past decade. Although numerous studies have evaluated optimal approaches to the diagnosis and treatment of pulmonary embolism, their focus has primarily been on short-term outcomes such as mortality and recurrent VTE in the days, weeks or months after pulmonary embolism diagnosis. However, it is increasingly recognized that pulmonary embolism may have long-lasting sequelae that impact on patients' health. The objective of this article was to review the available evidence on long-term clinical, functional, anatomic and physiologic outcomes after pulmonary embolism, and discuss avenues for research in this field, including the ELOPE Study. Residual pulmonary vascular abnormalities on follow-up imaging and echocardiogram are frequent in pulmonary embolism patients, but the clinical significance of these abnormalities is poorly understood. Whether initial and/or residual clot burden, recurrent pulmonary embolism, altered pulmonary artery or right ventricular hemodynamics or other prognostic factors such as biomarker levels contribute to long-term morbidity after pulmonary embolism is as yet unknown. The ELOPE Study will describe and identify the predictors of long-term outcomes after pulmonary embolism in the setting of a rigorous, multicenter cohort study in which long-term clinical, anatomic, physiologic and functional sequelae such as quality of life, return to work and loss of productivity after pulmonary embolism are systematically evaluated.

Integrated interdisciplinary care for patients with chronic obstructive pulmonary disease reduces emergency department visits, admissions and costs: a quality assurance study.

BACKGROUND: Dedicated programs for the management of chronic obstructive pulmonary disease (COPD) can reduce hospitalizations and improve quality of life. OBJECTIVE: To investigate whether health care utilization could be reduced by a newly developed integrated, interdisciplinary initiative that included a COPD nurse navigator who educates patients and families, transitions patients through various points of care and integrates services. METHODS: The present quality assurance, pre-post study included patients followed by a COPD nurse navigator from January 25, 2010 to November 5, 2011. Information regarding emergency department visits and hospitalizations, including lengths of stay, were obtained from hospital databases. Diagnoses were classified as respiratory or nonrespiratory, and used primary and secondary hospitalization diagnoses to identify acute exacerbations of COPD (AECOPD). Paired sign tests were performed. RESULTS: The sample consisted of 202 patients. Following nurse navigator intervention, significantly more patients experienced a decrease in the number of respiratory-cause emergency department visits (P<0.05), number of respiratory hospitalizations (P<0.001), total hospital days for respiratory admissions (P<0.001), number of hospitalizations with AECOPD (P<0.001) and total hospital days for admissions with AECOPD (P<0.001). Financial modelling estimated annual savings in excess of $260,000. CONCLUSION: The present quality assurance study indicated that the implementation of an integrated interdisciplinary program for the care of patients with COPD can improve patient outcomes despite the tendency of COPD to worsen over time.

Comparison of different measures of diffusing capacity for carbon monoxide (DLCO) in systemic sclerosis.

In systemic sclerosis (SSc), impaired diffusing capacity for carbon monoxide (DLCO) can indicate interstitial lung disease (ILD), pulmonary hypertension (PH), and/or other disease manifestations, including anemia. We undertook this study to compare the various measures of DLCO in the setting of a complex disease like SSc. We analyzed the pulmonary function tests of a cohort of SSc subjects, as a whole and among subjects with isolated PH and ILD separately. Associations were assessed using Spearman correlation coefficients, Student's t tests, and F tests by one-way ANOVA. P values <0.05 were considered statistically significant. This study included 225 subjects (mean age, 57 years; 88 % women; mean disease duration, 9.6 years; 32 % with diffuse disease, 44 % with ILD, and 17 % with PH). Mean percent predicted DLCO values were 75 % for DLCOsb and 83 % for DLCOrb. Adjustment for alveolar volume (VA) resulted in near normalization of both DLCOsb/VAsb (91 %) and DLCOrb/VArb (91 %). Subjects with ILD had significantly lower DLCOsb but not DLCOsb/VAsb, whereas those with PH had significantly lower DLCOsb and DLCOsb/VAsb. Among the various measures of DLCO, DLCOsb had the strongest and most consistent associations with clinical outcomes of interest. Adjusting for alveolar volume dampened the associations except with PH, with which DLCOsb/VAsb was more strongly associated than DLCOsb. Low DLCOsb is the most sensitive measure to detect abnormalities in gas exchange in SSc but reflects both parenchymal lung disease and pulmonary vascular disease. Low DLCOsb/VAsb is more specific for pulmonary vascular disease and should be the preferred measure of gas exchange in SSc.