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R M Kotloff

Publications and source records attributed to R M Kotloff.

At least 19 recordsLinked to original sources
PubMed2006

Association of clinical risk factors with functional status following lung transplantation.

A fundamental goal of lung transplantation is the regaining of functional capacity, yet little is known about what factors are associated with the achievement of this goal. The aim of this study is to test the association of clinical risk factors with functional status 1 year following lung transplantation. We conducted a cohort study of 321 lung transplants and assessed functionality by the distance achieved during a standard 6-min walk test (6MWT). Preoperative recipient risk factors were evaluated for association with functional status and adjusted for confounding using multivariable linear regression models. In these multivariable analyses, recipient female gender (p<0.001), recipient pretransplant body mass index (BMI) of greater than 27 kg/m2 (p=0.017) and shorter pretransplant 6MWT distances (p=0.006) were independently associated with shorter distances achieved during 6MWT after lung transplant, while cystic fibrosis (CF) (p=0.003), and bilateral lung transplant (p=0.014) were independently associated with longer distances achieved. Approximately 51% of the variance in 6MWT distance was explained by these risk factors in the linear regression models (R2=0.51). These findings may have implications in patient counseling, selection, procedure choice, and may lead to interventions aimed at improving the functional outcomes of lung transplantation.

Adolescent↗
PubMed2004

Medical complications of lung transplantation.

Surgical advances, in conjunction with more effective immunosuppressive strategies, have propelled the field of lung transplantation forward and have made intermediate-term survival an achievable goal. Nonetheless, the post-transplant course is often marked by complications that threaten both the quality and duration of the recipient's life. Many of the medical complications that arise are the direct consequence of the need to administer potent immunosuppressive agents, with their attendant risks of infection, malignancy and drug toxicity. This article will review the major medical complications, excluding allograft rejection, which may be encountered in the lung transplant recipient. Familiarity with, and vigilance for, these problems should facilitate earlier recognition, more expeditious intervention and more favourable outcomes.

Cause of Death↗
PubMed2001

Emergent lung retransplantation after discovery of two primary malignancies in the donor.

A 50-year-old woman underwent single lung transplantation for advanced chronic obstructive pulmonary disease. Shortly after the procedure, it was discovered that the donor suffered from both a renal cell carcinoma and a spindle-cell sarcoma of the ascending aorta, which had metastasized to the spleen. The patient was emergently listed for a retransplantation and underwent bilateral lung transplantation after a new donor became available 4 days after the initial transplantation procedure. After 24 months, the patient is without evidence of malignancy. This case illustrates the role of immediate retransplantation for patients who have inadvertently received thoracic organs from donors harboring occult malignancies.

Adult↗
PubMed2001

Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is an Epstein-Barr virus-associated malignancy that occurs in the setting of pharmacologic immunosuppression after organ transplantation. With the increased use of organ transplantation and intensive immunosuppression, this disease is becoming more common. We explore reduction in immunosuppression as an initial therapy for PTLD. METHODS: We analyzed our organ transplant patient database to identify patients with biopsy-proven PTLD who were initially treated with reduction of their immunosuppressive medications with or without surgical resection of all known disease. RESULTS: Forty-two adult patients were included in this study. Thirty patients were treated with reduction in immunosuppression alone. Twelve patients were treated with both reduction in immunosuppression and surgical resection of all known disease. Thirty-one of 42 patients (73.8%) achieved a complete remission. Of those patients who were treated with reduction in immunosuppression alone, 19 of 30 (63%) responded with a median time to documentation of response of 3.6 weeks. Multivariable analysis showed that elevated lactate dehydrogenase (LDH) ratio, organ dysfunction, and multi-organ involvement by PTLD were independent prognostic factors for lack of response to reduction in immunosuppression. In patients with none of these poor prognostic factors, 16 of 18 (89%) responded to reduction in immunosuppression in contrast to three of five (60%) with one risk factor and zero of seven (0%) with two to three factors present. The analysis also showed that increased age, elevated LDH ratio, severe organ dysfunction, presence of B symptoms (fever, night sweats, and weight loss), and multi-organ involvement by PTLD at the time of diagnosis are independent prognostic indicators for poor survival. With median follow-up of 147 weeks, 55% of patients are alive with 50% in complete remission. CONCLUSIONS: Reduction in immunosuppression is an effective initial therapy for PTLD. Clinical prognostic factors may allow clinicians to identify which patients are likely to respond to reduction in immunosuppression.

Adolescent↗
PubMed2001

Bronchogenic carcinoma complicating lung transplantation.

BACKGROUND: Malignancy is a well-recognized complication of solid-organ transplantation. Although a variety of malignancies have been reported in lung transplant recipients, a paucity of information exists regarding the incidence and clinical course of bronchogenic carcinoma in this patient population. METHODS: We conducted a retrospective cohort study of our lung transplant experience at the University of Pennsylvania. RESULTS: We identified 6 patients with bronchogenic carcinoma detected at the time of, or developing after, transplantation. The incidence of bronchogenic carcinoma was 2.4%. All patients with lung cancer had a history of smoking, with an average of 79 +/- 39 pack-years. A total of 5 patients had chronic obstructive pulmonary disease, and 1 had idiopathic pulmonary fibrosis. Lung cancers were all of non-small-cell histology and first developed in native lungs. Three patients had bronchogenic carcinoma at the time of surgery. The remaining 3 patients were diagnosed between 280 and 1,982 days post-transplantation. Of the 6 patients, 4 presented with a rapid course suggestive of an infectious process. The 1- and 2-year survival rates after diagnosis were 33% and 17%, respectively. CONCLUSION: Lung transplant recipients are at risk for harboring or developing bronchogenic carcinoma in their native lungs. Rapid progression to locally advanced or metastatic disease commonly occurs, at times mimicking an infection. Bronchogenic carcinoma should be considered in the differential diagnosis of pleuroparenchymal processes involving the native lung.

Carcinoma, Bronchogenic↗
PubMed2001

Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation: preliminary findings.

This study was undertaken to evaluate the efficacy of high resolution computed tomography (HRCT) in predicting the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Fifty lung transplant patients who were clinically stable and without evidence of BOS were evaluated for the presence of four HRCT features reported to be associated with bronchiolitis obliterans: mosaic attenuation on inspiratory CT (mosaic perfusion), mosaic attenuation on expiratory CT (air trapping), bronchiectasis, and tree-in-bud opacities. CT exams were part of an annual surveillance process with the hope of predicting subsequent development of BOS. Diagnosis of BOS was made in 9 of 50 patients as indicated by a fall in FEV1 of greater than 20% of a stable baseline. None of the radiographic features associated with clinically established BOS were both sensitive and specific in the prediction of BOS. Air trapping demonstrated moderate sensitivity (56%, 5/9) and moderate specificity (76%, 35/46) for prediction of BOS in the year following the CT exam. Bronchiectasis, the most reliable indicator of the presence of BOS was a poor predictor of subsequent BOS with an 11% (1/9) sensitivity but had high specificity (96%, 44/46). No high resolution CT features accurately predicted the development of BOS.

Adult↗
PubMed2001

Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation.

STUDY OBJECTIVES: To characterize the course of patients with advanced sarcoidosis who have been listed for lung transplantation and to identify prognostic factors for death while they are on the waiting list. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENTS: Forty-three patients with sarcoidosis who have been listed for lung transplantation at the University of Pennsylvania Medical Center. METHODS: A multivariable explanatory analysis using a Cox proportional hazards model was performed to determine risk factors that are independently associated with mortality while patients await transplantation. RESULTS: Twenty-three of the 43 patients (53%) died while awaiting transplantation. The survival rate of listed patients (as determined by the Kaplan-Meier method) was 66% at 1 year, 40% at 2 years, and 31% at 3 years. In a univariate analysis, the following factors were significantly associated with death on the waiting list: PaO(2) < or = 60 mm Hg (relative risk [RR], 3.4; 95% confidence interval [CI], 1.2 to 9.3); mean pulmonary artery pressure > or = 35 mm Hg (RR, 3.2; 95% CI, 1.1 to 9.5); cardiac index < or = 2 L/min/m(2) (RR, 2.8; 95% CI, 1.2 to 6.6), and right atrial pressure (RAP) > or = 15 mm Hg (RR, 7.6; 95% CI, 3.0 to 19.3). Multivariable analysis revealed that RAP > or = 15 mm Hg was the only independent prognostic variable (RR, 5.2; 95% CI, 1.6 to 16.7; p = 0.006). Twelve patients underwent lung transplantation. Survival after transplantation determined by the Kaplan-Meier method was 62% at both 1 and 2 years, and 50% at 3 years. CONCLUSIONS: Patients with advanced sarcoidosis awaiting lung transplantation have a high mortality rate with a median survival of < 2 years. Mortality is most closely linked to elevated RAP. While earlier referral may diminish the mortality rate of patients on the waiting list for transplantation, further improvements in posttransplantation outcomes will be necessary to ensure that this procedure truly bestows a survival benefit.

Adult↗
PubMed2001

Apical perfusion fraction as a predictor of short-term functional outcome following bilateral lung volume reduction surgery.

STUDY OBJECTIVES: To examine whether relative hypoperfusion to the apical one third of the lungs as determined by lung scintigraphy predicts a favorable functional outcome following bilateral lung volume reduction surgery (LVRS). METHODS: We performed a retrospective analysis of 128 patients who underwent bilateral LVRS. An apical perfusion fraction (AP%), defined as the percentage of total lung perfusion to the apical one third of both lungs, was derived for each patient by quantitative scintigraphy technique. Pulmonary function testing and 6-min walk test (6MWT) data were obtained preoperatively and 3 to 6 months postoperatively. RESULTS: The mean (+/- SD) improvement in FEV(1) was 309 +/- 240 mL, 209 +/- 293 mL, and 116 +/- 224 mL for patients with an AP% of 20%, respectively (p = 0.01, analysis of variance [ANOVA]). The likelihood of experiencing an increase in FEV(1) >or= 200 mL was 68% for those with an AP% 20%. Preoperative and postoperative 6MWT data were available for 109 of 128 patients. Improvement was 250 +/- 252 feet, 205 +/- 299 feet, and 77 +/- 200 feet for patients with AP% 20%, respectively (p = 0.04, ANOVA). While 50% of those with an AP% or= 180 feet, only 21% of those with an AP% > 20% did so. CONCLUSION: This retrospective analysis suggests that quantification of apical perfusion by nuclear scintigraphy assists in predicting the likelihood of short-term functional improvement after LVRS.

Exercise Test↗
PubMed2000

Fatal hyperammonemia after orthotopic lung transplantation.

BACKGROUND: A case of fatal hyperammonemia complicating orthotopic lung transplantation was previously reported. OBJECTIVE: To describe the incidence, clinical features, and treatment of hyperammonemia associated with orthotopic lung transplantation. DESIGN: Retrospective cohort analysis. SETTING: Academic medical center and lung transplantation center in Philadelphia, Pennsylvania. PATIENTS: 145 sequential adult patients who underwent orthotopic lung transplantation. MEASUREMENTS: Plasma ammonium levels. RESULTS: Six of the 145 patients who had had orthotopic lung transplantation developed hyperammonemia, all within the first 26 days after transplantation. The 30-day post-transplantation mortality rate was 67% for patients with hyperammonemia compared with 17% for those without hyperammonemia (P = 0.01). Development of major gastrointestinal complications (P = 0.03), use of total parenteral nutrition (P < 0.001), and lung transplantation for primary pulmonary hypertension (P = 0.045) were associated with hyperammonemia. CONCLUSIONS: Hyperammonemia is a potentially fatal event occurring after orthotopic lung transplantation. It is associated with high nitrogen load, concurrent medical stressors, primary pulmonary hypertension, and hepatic glutamine synthetase deficiency.

Adult↗
PubMed2000

Bilateral versus single lung transplantation for chronic obstructive pulmonary disease: intermediate-term results.

BACKGROUND: There is controversy regarding the transplant procedure of choice in chronic obstructive pulmonary disease. We reviewed our intermediate-term outcomes with single lung transplantation (SLT) versus bilateral lung transplantation (BLT). METHODS: We retrospectively reviewed 130 patients with chronic obstructive pulmonary disease: 84 underwent SLT, 46 BLT. The mean age was 51.1 +/- 1.2 years for those who underwent BLT and 56.2 +/- 0.7 years for those who underwent SLT (p < 0.0001). Male patients represented 65% of the BLT group and 46% of the SLT group (p = 0.04). Spirometry and 6-minute walk tests were obtained preoperatively and at 3- to 6-month intervals. Posttransplant survival and survival from time of onset of bronchiolitis obliterans syndrome were calculated by Kaplan-Meier method. The mean follow-up was 32.4 months. RESULTS: The 90-day mortality rate was 13.0% For BLT and 15.5% for SLT (p = 0.71). Actuarial survival rates at 1, 3, and 5 years were 82.6%, 74.6%, and 61.9% for BLT and 72.2%, 63.4%, and 57.4% for SLT; the favorable survival trend with BLT did not achieve statistical significance. There were no differences in preoperative spirometry or 6-minute walk tests. The improvements in forced expiratory volume in one second, forced vital capacity (FVC), and 6 MWT were significantly greater following BLT. The incidence of bronchiolitis obliterans syndrome was 22.4% in SLT and 22.2% in BLT; survival following onset of bronchiolitis obliterans syndrome was similar. CONCLUSIONS: For patients with chronic obstructive pulmonary disease, BLT is associated with superior lung function, exercise tolerance, and a trend toward enhanced survival. Younger candidates may be best suited for BLT. Given the limited donor lungs, SLT remains the preferred alternative for all other patients.

Bronchiolitis Obliterans↗
PubMed2000

An overview of pulmonary host defense.

In response to a constant barrage of inhaled and aspirated material, the lung has evolved a sophisticated multi-tiered system of defense. Components of this system include mechanical and biochemical barriers, phagocytic scavengers, and specific cellular and humoral immune responses. A breakdown of individual components of this system is frequently associated with the inability to maintain a sterile milieu and the consequent development of respiratory tract infection.

Antibody Formation↗
PubMed1999

Advanced emphysema: preoperative chest radiographic findings as predictors of outcome following lung volume reduction surgery.

PURPOSE: To determine whether preoperative chest radiographic findings alone can reliably predict which patients will achieve the best functional outcome of lung volume reduction surgery. MATERIALS AND METHODS: The preoperative chest radiographs obtained in 57 patients who had undergone lung volume reduction surgery were retrospectively scored by five blinded readers for severity and distribution of emphysema, evidence of lung compression, disease heterogeneity, and other features. Comparisons were made with the 3-6-month postoperative functional outcome for each patient. RESULTS: High disease heterogeneity (score > 2) and unequivocal lung compression (score 1) both were 100% predictive of a favorable outcome (FEV1 increase, > or = 30%). Low heterogeneity (score < 1) was 94% predictive of an unfavorable outcome (FEV1 increase < 30%), as was a lack of lung compression, which was 92% predictive of an unfavorable outcome. These two features also correlated with an improved 6-minute walk test result, although this correlation was weaker. CONCLUSION: Chest radiography alone may be sufficient for initial screening. High disease heterogeneity and lung compression on chest radiographs are highly predictive of a favorable functional outcome.

Aged↗
PubMed1998

Effect of volume reduction on lung transplant timing and selection for chronic obstructive pulmonary disease.

BACKGROUND: End-stage chronic obstructive pulmonary disease has traditionally been treated with lung transplantation. For 2 years, our lung transplantation program has placed patients with appropriate criteria for lung transplantation and volume reduction into a prospective management algorithm. These patients are offered the lung volume reduction option as a "bridge" to "extend" the eventual time to transplantation. We examine the results of this pilot program. METHODS: From October 11, 1993, to April 17, 1997, 31 patients were evaluated for lung transplantation who also had physiologic criteria for volume reduction (forced expiratory volume in 1 second < or = 25%; residual volume > 200%; significant ventilation/perfusion heterogeneity). All patients completed 6 weeks of pulmonary rehabilitation and then had baseline pulmonary function and 6-minute walk tests. These patients were then offered volume reduction as a "bridge" and were simultaneously listed for transplantation. Postoperatively, these 31 patients were then divided into two groups: Those with satisfactory results at 4 to 6 months after volume reduction and those with unsatisfactory results. Volume reduction was performed through a video thoracic approach in 87% of the patients and bilateral median sternotomy in the remaining 13%. The condition of the patients was monitored after the operation with repeated pulmonary function tests and 6-minute walk tests at 3-month intervals. RESULTS: Twenty-four of 31 patients (77.4%) had primary success (at 4 to 6 months) results after lung volume reduction and 7 patients (22.6%) had primary failure, including 1 patient who died in the perioperative period (3.2%). Four patients (16.7%) from the primary success cohort had significant deterioration in their pulmonary function during intermediate-term follow-up and were then reconsidered for lung transplantation. Two of them have subsequently undergone transplantation with good postoperative pulmonary function results. Interestingly, three patients had alpha 1-antitrypsin deficiency; two had a poor outcome of lung volume reduction and primary failure. CONCLUSIONS: Lung volume reduction in these patients is safe. Seventy-seven percent of otherwise suitable candidates for lung transplantation achieved initial good results from volume reduction and were deactivated from the list (placed on status 7). Most patients entering our prospective management algorithm have either significantly delayed or completely avoided lung transplantation after volume reduction. Lung volume reduction has substantially affected the practice, timing, and selection of patients for lung transplantation. Our waiting list now has a reduced percentage of patients with a diagnosis of chronic obstructive pulmonary disease compared with 3 years ago. Our experience suggests that lung volume reduction may be limited as a "bridge" in alpha 1-antitrypsin deficiency.

Algorithms↗
PubMed1998

Lung transplantation for cystic fibrosis.

Lung transplantation currently stands as the only therapeutic option that carries the potential to restore patients with advanced cystic fibrosis to a more normal state of health. Nonetheless, the procedure carries significant risk and median survival following transplantation is only 5 years. This article discusses the currently achievable outcomes and the common short-comings of transplantation. Strategies to optimize outcomes through appropriate patient selection, use of living donors, and novel research initiatives are discussed.

Cystic Fibrosis↗
PubMed1998

Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in orthotopic lung transplant patients.

Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm. Previously they have not been described in lung transplant recipients. We report a high incidence of symptomatic giant gastric ulcers and identify the risk factors for ulcer development in these patients. We examined the records of all 95 patients who had undergone lung transplantation at our institution from November 1991 to July 1995. Fourteen of the patients who underwent lung transplantation developed symptoms that required esophagogastroduodenoscopy. Three of these patients (21%) were found to have giant gastric ulcers. The relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy after lung transplantation is over 40 times that of population controls. The patients who developed giant gastric ulcers, despite H2 antagonist use, had all received bilateral lung transplantation and had received nonsteroidal antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids. The risk of developing giant gastric ulcers is significantly increased in patients who have undergone bilateral orthotopic lung transplantation. Clinicians should be made aware of this complication in order to avoid use of ulcerogenic medications in this population. Avoidance of these medications could potentially minimize the risk of this complication.

Female↗
PubMed1998

Altered lung mechanics after double-lung transplantation.

We studied lung mechanics and small airways function in 15 patients after double-lung (DL) transplantation. Patients were classified as stable (DL-S, n = 11), or having obliterative bronchiolitis syndrome (DL-OBS, n = 4). We performed pulmonary function tests (PFT), measured slope of phase 3 of the single-breath nitrogen test (N2SP3), and obtained pressure-volume curves and values: chord compliance (Cst,L), specific chord compliance (SCst,L), and elastic recoil pressure at 90% TLC. PFT showed mild restrictive pattern in DL-S and severe obstructive lung disease in DL-OBS. The N2SP3 measurement indicated small airways dysfunction in 82% of DL-S and in all DL-OBS patients. The Cst,L was 0.24 +/- 0.08 L/cm H2O in DL-S and 0.16 +/- 0.05 L/cm H2O in DL-OBS, both lower than control subjects 0.34 +/- 0. 09 L/cm H2O (p < 0.01; p < 0.001). Moreover, SCst,L was 0.09 +/- 0. 03 cm H2O-1 in DL-S, and 0.05 +/- 0.02 cm H2O-1 in DL-OBS, significantly lower than control subjects 0.12 +/- 0.02 cm H2O-1 (p < 0.05; p < 0.001). Elastic recoil at 90% TLC was normal in 14 of 15 patients. We found a linear correlation between N2SP3 and FEV1, and between FEV1 and Cst,L and SCst,L for combined DL-S and DL-OBS. Reduced compliance near FRC with normal elastic recoil at high lung volumes does not suggest changes in lung parenchyma. We speculate that structural or functional alterations in small airways may have contributed to low compliance measurements. Of special concern are our findings that DL-S had significant small airways dysfunction and reduced compliance in a pattern similar to the DL-OBS, only smaller in magnitude.

Adult↗