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Biomedical subjects

Steven M Kawut

Publications and source records attributed to Steven M Kawut.

At least 19 recordsLinked to original sources
PubMed2006

Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction.

BACKGROUND: Acute lung injury is characterized by hypercoagulability and impaired fibrinolysis. We hypothesized that lower protein C and higher type 1 plasminogen activator inhibitor (PAI-1) levels in plasma would be associated with primary graft dysfunction (PGD) after lung transplantation. DESIGN: Prospective, multicenter cohort study. METHODS: We measured plasma levels of protein C and PAI-1 before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) 72 h after transplantation. Biomarker profiles were evaluated using logistic regression and generalized estimating equations. RESULTS: Patients who developed PGD had lower protein C levels 24 h posttransplantation than did patients without PGD (mean +/- SD [relative to control]: 64 +/- 27 vs. 92 +/- 41%, respectively; p = 0.002). Patients with PGD also had PAI-1 levels that were almost double those of patients without PGD at 24 h (213 +/- 144 vs. 117 +/- 89 ng/ml, respectively; p < 0.001). Throughout the 72-h postoperative period, protein C levels were significantly lower (p = 0.007) and PAI-1 levels were higher (p = 0.026) in subjects with PGD than in others. These differences persisted despite adjustment for potential confounders in multivariate analyses. Higher recipient pulmonary artery pressures, measured immediately pretransplantation, were associated with higher PAI-1 levels and increased risk of PGD. CONCLUSION: Lower postoperative protein C and higher PAI-1 plasma levels are associated with PGD after lung transplantation. Impaired fibrinolysis and enhanced coagulation may be important in PGD pathogenesis.

Biomarkers↗
PubMed2006

Six-minute-walk distance predicts waiting list survival in idiopathic pulmonary fibrosis.

RATIONALE: Functional studies may be useful to predict survival in idiopathic pulmonary fibrosis (IPF). Various cutoffs of 6-min-walk distance (6MWD) have been suggested to identify patients at a high risk of death. OBJECTIVES: To examine the association between 6MWD and survival in patients with IPF listed for lung transplantation, and to identify sensitive and specific cutoffs for predicting death at 6 mo. METHODS: We performed a retrospective cohort study of 454 patients classified as having IPF listed for lung transplantation with the United Network for Organ Sharing between June 30, 2004 and July 22, 2005. MEASUREMENTS AND MAIN RESULTS: Lower 6MWD was associated with an increased mortality rate (p value for linear trend < 0.0001). Patients with a walk distance less than 207 m had a more than fourfold greater mortality rate than those with a walk distance of 207 m or more, despite adjustment for demographics, anthropomorphics, FVC % predicted, pulmonary hypertension, and medical comorbidities (adjusted rate ratio, 4.7; 95% confidence interval, 2.5-8.9; p < 0.0001). 6MWD was a significantly better predictor of 6-mo mortality than was FVC % predicted (c-statistic = 0.73 vs. 0.59, respectively; p = 0.02). CONCLUSIONS: Lower 6MWD was strongly and independently associated with an increased mortality rate for wait-listed patients classified as having IPF. 6MWD was a better predictor of death at 6 mo than was FVC % predicted.

Exercise Test↗
PubMed2006

Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary vascular resistance which leads to right ventricular failure. Serotonin and the serotonin transporter play an important role in animal and human studies of PAH. We therefore hypothesized that PAH patients treated with high-affinity selective serotonin reuptake inhibitors (SSRIs) would have a reduced risk of death compared to PAH patients not treated with SSRIs. METHODS: We performed a retrospective cohort study of 84 consecutive adult PAH patients who underwent initial evaluation from January 1994 to June 2002 at the Pulmonary Hypertension Center of the New York Presbyterian Hospital. Patient-time while receiving high-affinity SSRIs (K(d)<1nmol) (paroxetine, sertraline, or fluoxetine) was considered "exposed". Patient-time while receiving tricyclic, atypical, or no antidepressants was considered "unexposed". RESULTS: Thirteen of the 84 patients (15%) used high-affinity SSRIs during the study period. Five patients were taking high-affinity SSRIs at baseline and 8 initiated high-affinity SSRIs during the follow-up period. The median time from baseline evaluation until initiation of high-affinity SSRIs was 125 (0-1227) days. The median duration of high-affinity SSRI use was 482 (110-1624) days and the total at-risk time on high-affinity SSRIs was 18.1 person-years. Seventy-nine (94%) patients were treated with warfarin; 38 (45%) received continuous intravenous epoprostenol; 12 (14%) received continuous subcutaneous treprostinil, and 23 (27%) were treated with oral bosentan. The median follow-up was 764 days. Twenty-four patients died and one underwent lung transplantation during the study period. There were no differences in age, gender, diagnosis, hemodynamics, or incidence of acute vasoreactivity between SSRI users and non-users. The risk of death for high-affinity SSRI users was lower but not statistically significantly different from that of non-users (hazard ratio=0.53, 95% CI 0.07 to 3.9, p=0.53). Adjustment for demographics, diagnosis, hemodynamics, or other therapies did not significantly change this result. CONCLUSIONS: SSRI use was associated with a 50% reduction in the risk of death in a cohort of PAH patients which was not statistically significant. Larger cohort studies may better define this relationship; an adequately powered trial of high-affinity SSRIs in PAH patients may be warranted.

Adult↗
PubMed2006

Immunoglobulin G levels before and after lung transplantation.

RATIONALE: The determinants of immunoglobulin G (IgG) level and the risk of hypogammaglobulinemia (HGG) in patients with severe lung disease before and after lung transplantation are unknown. OBJECTIVES: We aimed to identify predictors of low IgG levels before and after lung transplantation. METHODS: We performed a retrospective cohort study of 40 consecutive lung transplant recipients at our center. Total IgG levels were measured before and serially after transplantation. Mild HGG was defined as IgG levels from 400-699 mg/dl; severe HGG was defined as IgG levels<400 mg/dl. MEASUREMENTS AND MAIN RESULTS: Before transplantation, six (15%) patients had mild HGG, and none had severe HGG. Patients with chronic obstructive pulmonary disease had lower IgG levels compared with patients with other diseases (independent of corticosteroid use and age; p=0.001) and an increased risk of mild HGG (p=0.005). The cumulative incidences of mild and severe HGG significantly increased after transplantation (58 and 15%, respectively, both p<0.04 compared with pretransplant prevalences). Lower pretransplant IgG level and treatment with mycophenolate mofetil were associated with lower IgG levels after transplantation (both p<0.05). Only lower pretransplant IgG levels were significantly associated with an increased risk of severe HGG after transplantation (p=0.02). CONCLUSIONS: Mild HGG is common in patients with severe chronic obstructive pulmonary disease, and the incidences of mild and severe HGG increase significantly early after lung transplantation. Baseline IgG levels and treatment with mycophenolate mofetil affect post-transplant IgG levels.

Biomarkers↗
PubMed2006

Portopulmonary hypertension.

Portopulmonary hypertension is a common condition in patients who have portal hypertension. This article reviews the definition and clinical presentation of this disorder and outlines our current understanding of its pathophysiology. A diagnostic approach is provided , and novel medical therapies that are being investigated to treat this condition are discussed. Finally, the safety of liver transplantation in patients who have portopulmonary hypertension is reviewed.

Antihypertensive Agents↗
PubMed2006

Osteoporosis in diffuse parenchymal lung disease.

STUDY OBJECTIVES: There are no studies focused on skeletal status in patients with diffuse parenchymal lung disease (DPLD). We hypothesized that patients with DPLD referred for lung transplantation would have a high prevalence of osteoporosis related to corticosteroid use or reduced pulmonary function and exercise capacity. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: Eighty-six patients with DPLD referred to our center for lung transplantation evaluation between March 1999 and April 2004. MEASUREMENTS AND RESULTS: Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and radius at the time of referral. Criteria developed by the World Health Organization were used to define osteopenia and osteoporosis. Fifty-five patients (64%) had usual interstitial pneumonia-pattern lung disease, 14 patients (16%) had nonspecific interstitial pneumonia-pattern lung disease, and 17 patients (20%) had other forms of DPLD. Sixty-four patients (74%) were receiving corticosteroids, and 43 patients (50%) were receiving preventive therapy for osteoporosis. Eleven patients (13%; 95% confidence interval [CI], 7 to 22%) met criteria for osteoporosis at any site, and 49 patients (57%; 95% CI, 46 to 68%) had osteopenia. Lower body mass index (BMI) [adjusted odds ratio (OR), 1.3; 95% CI, 1.1 to 1.6; p = 0.007] and Hispanic ethnicity (adjusted OR, 9.7; 95% CI, 1.8 to 52; p = 0.008) were independently associated with an increased risk of osteoporosis. Linear regression analysis confirmed that BMD at the femoral neck and hip was directly associated with BMI (p < 0.002). These findings were not affected by adjustment for the use of corticosteroids or osteoporosis prophylaxis, pulmonary function, or exercise performance. CONCLUSIONS: Reduced BMD was common in patients with DPLD who were referred for lung transplantation. Lower BMD was associated with lower BMI, whereas there was no association with other clinical factors in our cohort. Hispanic patients with DPLD had a higher risk of osteoporosis than non-Hispanic patients, independent of other variables. Given their increased risk of bone loss, patients with DPLD should undergo screening for osteoporosis and receive prophylaxis and treatment according to published guidelines.

Absorptiometry, Photon↗
PubMed2005

Risk factors and outcomes of hypogammaglobulinemia after lung transplantation.

BACKGROUND: Hypogammaglobulinemia (HGG) frequently occurs after solid organ transplantation; however, the prevalence and implications of HGG after lung transplantation are not well defined. The authors aimed to define the prevalence, risk factors, and outcomes of patients with severe HGG after lung transplantation. METHODS.: The authors performed a retrospective cohort study of 57 lung transplant recipients at their center. Quantitative total and subclass immunoglobulin (Ig) G levels were obtained from patients. RESULTS: Thirty-four (60%; 95% confidence interval [CI], 46%-72%) patients had low IgG levels (IgG <700 mg/dL); of these, eight (14%; 95% CI, 6%-26%) had severe HGG (IgG <400 mg/dL). Female patients had a higher risk of severe HGG than male patients (25% vs. 0%, P=0.007), and patients who underwent transplantation for emphysema had a higher risk of severe HGG than others (P=0.04). Patients with bronchiolitis obliterans syndrome had a higher risk of severe HGG than those without (50% vs. 10%, P=0.03). Severe HGG was associated with an increased risk of pneumonia (P=0.01) and worse survival (P=0.04) but with neither the incidence of cytomegalovirus disease (P=0.54) nor a subsequent diagnosis of bronchiolitis obliterans syndrome (P=0.70). CONCLUSIONS: The authors have documented a high prevalence of HGG after lung transplantation. Emphysema, female gender, and bronchiolitis obliterans syndrome are risk factors for severe HGG. Patients with severe HGG had a higher cumulative incidence of pneumonia and worse survival. Studies of the efficacy and safety of IgG supplementation after lung transplantation should be pursued.

Adolescent↗
PubMed2005

Outcomes of extended donor lung recipients after lung transplantation.

BACKGROUND: Lung transplantation is currently limited by the number of suitable donor organs. Many lung-transplant programs use lungs that do not meet the formal criteria for acceptability; however, the immediate and long-term consequences of this approach remain unclear. METHODS: We performed a retrospective cohort study of all patients who underwent lung transplantation at the Columbia University Medical Center from July 2001 to July 2003. We assessed the outcomes of recipients of extended donor lungs compared with those of recipients of optimal donor lungs after adjusting for confounding variables. RESULTS: Fifty-one patients underwent lung transplantation, of which 27 (53%) received extended donor lungs. Recipients of extended donor lungs had fewer intensive care unit-free days at 30 days (P=0.002) and a longer time to hospital discharge (P=0.007) than did recipients of optimal donor lungs. Extended donor recipients also had lower forced expiratory volume in 1 second % predicted at 1 year than did optimal donor recipients (P=0.03). There were no differences in the 30-day or longer-term survival of extended and optimal donor lung recipients. CONCLUSIONS: Recipients of extended donor lungs have a longer intensive care unit course, a prolonged hospital stay, and lower pulmonary function at 1 year than recipients of optimal lungs. Despite these differences, survival is similar between the two groups. The criteria for the optimal lung donor should be re-evaluated considering the current shortage of acceptable organs. Although some outcomes may differ with the use of extended donor lungs, the clinical impact of these differences should be assessed in future prospective multicenter studies.

Adult↗
PubMed2005

New predictors of outcome in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use. We performed a retrospective cohort study of 84 consecutive patients with PAH who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. Survival at 1, 3, and 5 [corrected] years was 87%, 75%, and 61%, respectively. Multivariate analysis showed that being of African-American or Asian descent was associated with an increased risk of death. Warfarin use was associated with a reduced risk of death. Higher serum albumin and cardiac index and acute vasoreactivity were independently associated with improved survival. These data suggest that the determinants of outcome have changed. Race is identified as a new risk factor, which may be attributable to biologic or socioeconomic differences. Cardiac function and acute reactivity of the pulmonary vascular bed remain strong independent predictors of outcome.

Adult↗
PubMed2005

Hemodynamics and survival of patients with portopulmonary hypertension.

It is not known whether patients with pulmonary arterial hypertension associated with portal hypertension (portopulmonary hypertension (PPHTN) have different disease characteristics from those of patients with other forms of pulmonary arterial hypertension. We performed a retrospective cohort study of patients with PPHTN and patients with pulmonary arterial hypertension that was idiopathic, familial, or associated with anorexigen use (IPAH) to determine whether hemodynamics or survival were different between these groups. We included consecutive patients who underwent initial pulmonary artery catheterization and vasodilator testing at our center between January 1997 and May 2001 and who were followed until January 2004. Patients with PPHTN (N = 13) had a higher cardiac index and lower pulmonary vascular resistance than patients with IPAH (N = 33) (P < or = 0.001). Right atrial pressure and pulmonary artery pressure were similar between the groups. Patients with PPHTN had a higher risk of death in multivariate analysis (hazard ratio: [HR] = 2.8, 95% CI 1.04-7.4; P = 0.04). These findings were not affected by adjustment for differences in laboratory values, hemodynamics, or therapy. In conclusion, patients with PPHTN have a higher risk of death than that of patients with IPAH, despite having a higher cardiac index and lower pulmonary vascular resistance. Future studies of the specific mechanisms of and therapy for pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease.

Adult↗
PubMed2005

Noninfectious pulmonary complications after lung transplantation.

This article reviews several important noninfectious pulmonary complications that threaten survival, pulmonary function, and quality of life after lung transplantation. Topics reviewed include primary graft dysfunction (PGD), native lung hyperinflation, anastomotic complications, phrenic nerve injury, pleural complications, lung cancer, pulmonary toxicity associated with immunosuppressive medications, and exercise limitation.

Humans↗
PubMed2005

Successful bilateral lung transplantation for pulmonary fibrosis associated with the Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, a bleeding diathesis, and in a subset of patients, pulmonary fibrosis. Lung transplantation, the only curative therapy for pulmonary fibrosis, has not been previously reported as a successful treatment strategy for patients with HPS because the bleeding diathesis was thought to contraindicate major thoracic surgery. We successfully performed bilateral sequential lung transplantation in a patient with pulmonary fibrosis and HPS after transfusion of 6 units of platelets. Lung transplantation is a viable therapeutic option in patients with pulmonary fibrosis and only a mild bleeding diathesis associated with HPS.

Adult↗
PubMed2005

Exercise testing determines survival in patients with diffuse parenchymal lung disease evaluated for lung transplantation.

STUDY OBJECTIVES: Diffuse parenchymal lung disease is associated with a high risk of mortality despite early referral and listing for lung transplantation. We hypothesized that cardiopulmonary exercise test results and the distance walked in 6min (6MWTD) would be associated with survival in patients with diffuse parenchymal lung disease referred for lung transplantation. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: We included 51 consecutive patients with diffuse parenchymal lung disease who underwent exercise testing after referral to the Lung Transplant Program at the New York Presbyterian Hospital between January 2000 and December 2002. Thirty-three patients were listed, and 7 underwent transplantation during the study period. There were 17 deaths with 1 death post-transplantation. RESULTS: A 6MWTD < 350 m was associated with an increased risk of death (HR = 4.6, 95% CI 1.5-14.2, P = 0.009). Oxygen saturation with unloaded exercise (HR = 0.91, 95% CI 0.84-0.98, P = 0.015) and oxygen consumption at peak exercise adjusted for weight (HR = 0.88, 95% CI 0.79-0.99, P = 0.039) were also associated with the risk of death. A patient with oxygen saturation <95% during unloaded exercise had a 75% chance of dying on the list for transplantation. A patient with 6MWTD < 350 m had a 67% chance of dying on the list. CONCLUSIONS: Cardiopulmonary exercise test parameters and the 6MWTD were associated with the risk of death. Measures during exercise may be useful for determination of prognosis and for prioritizing patients with diffuse parenchymal lung disease for lung transplantation.

Adult↗
PubMed2005

von Willebrand factor independently predicts long-term survival in patients with pulmonary arterial hypertension.

OBJECTIVES: We hypothesized that higher plasma levels of von Willebrand factor (vWF) and reduced ristocetin cofactor activity (RCA)/vWF ratios at baseline and follow-up would be associated with an increased risk of death in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Endothelial injury and dysfunction cause increased vWF levels in patients with cardiovascular disease. Increased vWF is associated with a higher risk of death in patients with coronary artery disease, congestive heart failure, and ARDS. In PAH, vWF is elevated and functions abnormally, resulting in reduced platelet binding. The ability of vWF to bind platelets is reflected by RCA. METHODS: We performed a retrospective cohort study of 66 PAH patients who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. RESULTS: vWF level was directly associated with Factor VIII activity, RCA, fibrinogen, and prothrombin time (p < or = 0.01). vWF levels at baseline and follow-up were associated with the risk of death (hazard ratio [HR] per 50% increase, 1.4; 95% confidence interval [CI], 1.1 to 1.8 [p = 0.02]; and HR per 50% increase, 1.5; 95% CI, 1.1 to 2.0 [p = 0.011]; n = 48, respectively). RCA/vWF ratios were not associated with outcome. These results were unaffected by adjustment for demographics, baseline hemodynamics, laboratory results, or PAH therapy in multivariate analyses. CONCLUSIONS: Increased vWF levels at baseline and follow-up are associated with worse survival in patients with PAH; however, RCA/vWF ratios are not. The hemostatic effects of vWF do not account for these findings. This suggests that endothelial injury and dysfunction may persist despite treatment and may impact on disease course. Therapies that target endothelial injury may therefore improve outcomes for patients with PAH.

Adult↗
PubMed2004

Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with nonsmall cell lung carcinoma.

BACKGROUND: Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens. METHODS: Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens. RESULTS: Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death. CONCLUSIONS: The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan-1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma.

Adenocarcinoma↗
PubMed2004

Surrogate end points for pulmonary arterial hypertension.

Pulmonary arterial hypertension is a rare disease that is characterized by increased pulmonary vascular resistance and right heart failure. Recent advances in the understanding of pulmonary arterial hypertension have been translated into effective therapies tested in clinical trials. These trials have used surrogate end points as the primary outcomes of interest. However, it is not clear which potential surrogate end points are reliable and valid for studying pulmonary arterial hypertension. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Hemodynamic, echocardiographic, neurohormone, and exercise measures hold some promise as potential surrogate end points for clinical trials of therapy for pulmonary arterial hypertension. Hemodynamic measures have the most evidence to support their use. Functional studies, such as the distance walked in 6 minutes, also may be meaningful. We present the available data as well as the strengths and weaknesses of each metric. Further studies should focus on validating the most promising of these surrogate end points, so that future investigators, subjects, and patients may benefit from the advantages they confer on clinical trials and patient care.

Biomarkers↗