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Joel D Cooper

Publications and source records attributed to Joel D Cooper.

16 recordsLinked to original sources
PubMed2025

Epigenome-Wide Analysis Identifies Pollution-Sensitive Loci in Fibrotic Interstitial Lung Disease.

Rationale: Particulate matter &#x2a7d;2.5 &#x3bc;m (PM2.5) adversely impacts patients with fibrotic interstitial lung disease (fILD). Objectives: We sought to determine whether PM2.5-associated epigenetic alterations contribute to the environmental pathogenesis of fILD. Methods: A retrospective two-cohort study applied satellite-derived PM2.5 and constituent exposure matching to the residential location of patients with fILD. Robust linear regressions were used to evaluate cohort-specific, epigenome-wide differential blood DNA methylation with increasing pollutant exposures (Illumina MethylationEPIC BeadChip). Cox and linear regressions were used to evaluate associations of cytosine-phosphate-guanine (CpG) loci with transplant-free survival and lung function. A Wilcoxon test was used to evaluate cartilage-associated protein (CRTAP) levels in fILD and control lungs. Measurements and Main Results: The University of Pittsburgh cohort (n&#x2009;=&#x2009;306) had 5-year median PM2.5 exposures of 12.1 &#x3bc;g/m3 compared with 5.1 &#x3bc;g/m3 in the University of British Columbia cohort (n&#x2009;=&#x2009;170). Higher pollutant exposures in the University of Pittsburgh cohort were associated with lower methylation at cg25354716, annotated to CRTAP, a critical extracellular matrix remodeling enzyme. Higher exposures in the University of British Columbia cohort were associated with higher methylation at cg01019301, annotated to TLN2 (talin-2), a cytoskeletal protein involved in fibroblast migration. A 10% increase in cg25354716 methylation was associated with a hazard ratio of 0.81 for death or lung transplantation in the meta-analyzed cohorts (95% confidence interval&#x2009;=&#x2009;0.69-0.96; P&#x2009;=&#x2009;0.01), whereas the same change in cg01019301 was associated with a hazard ratio of 1.36 (95% confidence interval&#x2009;= 1.07-1.74; P&#x2009;=&#x2009;0.01). CRTAP protein was more abundant in lungs from patients with fILD compared with those from donor controls (P&#x2009;<&#x2009;0.001). Conclusions: PM2.5 is associated with altered blood DNA methylation in fILD. This work identifies novel pollution-sensitive targets that hold potential for therapeutic modulation in fILD.

Humans↗
PubMed2003

Bronchial fenestration improves expiratory flow in emphysematous human lungs.

BACKGROUND: The crippling effects of emphysema are due in part to dynamic hyperinflation, resulting in altered respiratory mechanics, an increased work of breathing, and a pervasive sense of dyspnea. Because of the extensive collateral ventilation present in emphysematous lungs, we hypothesize that placement of stents between pulmonary parenchyma and large airways could effectively improve expiratory flow, thus reducing dynamic hyperinflation. METHODS: Twelve human emphysematous lungs, removed at the time of lung transplantation, were placed in an airtight ventilation chamber with the bronchus attached to a tube traversing the chamber wall, and attached to a pneumotachometer. The chamber was evacuated to -10 cm H2O pressure for lung inflation. A forced expiratory maneuver was simulated by rapidly pressurizing the chamber to 20 cm H2O, while the expiratory volume was continuously recorded. A flexible bronchoscope was then inserted into the airway and a radiofrequency catheter (Broncus Technologies) was used to create a passage through the wall of three separate segmental bronchi into the adjacent lung parenchyma. An expandable stent, 1.5 cm in length and 3 mm in diameter, was then inserted through each passage. Expiratory volumes were then remeasured as above. In six experiments, two additional stents were then inserted and forced expiratory volumes again determined. RESULTS: The forced expiratory volume in 1 second (FEV1) increased from 245 +/- 107 mL at baseline to 447 +/- 199 mL after placement of three bronchopulmonary stents (p < 0.001). With two additional stents, the FEV1 increased to 666 +/- 284 mL (p < 0.001). CONCLUSIONS: Creation of extra-anatomic bronchopulmonary passages is a potential therapeutic option for emphysematous patients with marked hyperinflation and severe homogeneous pulmonary destruction.

Feasibility Studies↗
PubMed2003

Effect of a cardiac-specific didactic course on thoracic surgery in-training examination performance.

BACKGROUND: The purpose of this study was to determine which factors influenced performance on the Thoracic Surgery In-Training Examination (TSITE) and whether the addition of a cardiac-specific didactic study course improved scores. METHODS: Between 1989 and 2002, 59 TSITE scores (overall, cardiac [C-TSITE], and thoracic [T-TSITE]) were collected from 33 residents (23 cardiac track, 10 thoracic). Factors assessed with univariate and multivariate analysis included calendar year, year of training (31 year I, 28 year II), standardized test-taking history (average National Board and American Board of Surgery in-training scores), subjective faculty assessment of cardiothoracic knowledge, months on cardiac versus thoracic service, clinical performance, and participation in a cardiac-specific didactic series with faculty lectures and board question reviews (12 residents). RESULTS: Cardiac-track residents had higher C-TSITE percentile scores (53% +/- 27% versus 38% +/- 27%, p < 0.05), whereas thoracic-track residents had higher T-TSITE scores (70% +/- 24% versus 51% +/- 25%, p < 0.01). Multivariate analysis identified 3 factors associated with higher overall TSITE scores: standardized test-taking history (p < 0.001), subjective faculty assessment of knowledge (p < 0.001), and year of training (p < 0.007). Inclusion in the cardiac-specific didactic series did not affect C-TSITE scores (50% +/- 30% versus 48% +/- 27%, p > 0.82) or overall TSITE scores (p > 0.23). CONCLUSIONS: Standardized test-taking history and subjective faculty assessment of knowledge were associated with higher TSITE scores, but implementation of a cardiac-specific didactic series had no influence. These findings suggest that independent study and reading may be the best way to improve TSITE scores.

Educational Measurement↗
PubMed2003

Comparison of open subxiphoid pericardial drainage with percutaneous catheter drainage for symptomatic pericardial effusion.

BACKGROUND: The optimal therapy for symptomatic pericardial effusions remains controversial. This paper compares outcomes after the two most commonly used techniques, percutaneous catheter drainage and operative subxiphoid pericardial drainage. METHODS: We performed a 5-year retrospective, single-institution study to analyze outcomes after either percutaneous catheter drainage or subxiphoid open pericardial drainage for symptomatic pericardial effusions. RESULTS: Symptomatic pericardial effusions in 246 patients were treated by open pericardiotomy and tube drainage (n = 150) or percutaneous catheter drainage (n = 96). Drainage duration, total drainage volume, and duration of follow-up (2.6 years) were similar in both groups. Effusions were classified malignant in 79 (32%) patients and benign in 167 (68%) patients. No direct procedural mortality occurred, but the hospital mortality was 16 patients (10.7%) in the open group and 22 (22.9%) in the percutaneous group (p = 0.01) The 5-year survival rate was 51% in the open group versus 45% in the percutaneous group, despite a greater percentage of the open group having a preoperative malignant diagnosis (35% versus 28%). Symptomatic effusions recurred in 16.5% of the percutaneous group compared with 4.6% in the open group (p = 0.002), and sclerosis did not appear to reduce recurrence rates (10.7% with sclerosis versus 15.6% without; p > 0.05). The diagnosis of malignancy was confirmed in 16 of 27 (59%) percutaneous procedures performed on patients with known malignancy. In the open group, cytologic and pathologic evaluation of the pericardial specimen revealed malignancy in 32 of 52 (62%) patients with known malignancy. CONCLUSIONS: Subxiphoid and percutaneous pericardial drainage of symptomatic pericardial effusions can be performed safely; however, death occurs from underlying disease. Open subxiphoid pericardial drainage with pericardial biopsy appears to decrease recurrence but does not improve diagnostic accuracy of malignancy over cytology alone.

Catheterization↗
PubMed2003

Feasibility and safety of the airway bypass procedure for patients with emphysema.

OBJECTIVE: We have proposed that direct passages created between pulmonary parenchyma and large airways (airway bypass) could take advantage of the extensive collateral ventilation present in emphysematous lungs to provide improvement in expiratory flow and respiratory mechanics. A critical step in the safe performance of these procedures is to create passages through the airway wall into lung parenchyma while avoiding injury to adjacent blood vessels. METHODS: The procedure consists of selection of a target site bronchoscopically, use of a Doppler catheter to detect and avoid peribronchial blood vessels, and creation of a passage through the airway wall with a cautery probe. To evaluate the safety of airway bypass, 10 patients were treated during prescheduled lobectomies for neoplasm. The procedure was done after thoracotomy and immediately before resection and was confined to airways in the lung identified for removal. Airway bypass was subsequently performed in 5 patients undergoing lung transplantation for emphysema just before lung excision to evaluate the procedure in emphysematous patients. RESULTS: Twenty-nine passages (1-5 per subject) were created in the patients undergoing lobectomy. Eighteen passages were created (3-4 per subject) in the patients undergoing transplantation. There were 2 instances of mild bleeding in the patients undergoing lobectomy and no bleeding in the patients undergoing transplantation. Both instances were treated with suction and topical application of epinephrine and resolved without incident. CONCLUSION: The results of this study confirm that passages can be made safely through the airways of human subjects. These clinical results support further investigation of the efficacy of the airway bypass procedure in patients with emphysema.

Adult↗
PubMed2003

Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema.

OBJECTIVE: Numerous reports have confirmed the early benefits of lung volume reduction surgery for selected patients with emphysema. This report documents the long-term survival and functional results after lung volume reduction surgery. METHODS: Between January 1993 and June 2000, a total of 250 consecutive patients underwent bilateral lung volume reduction surgery through median sternotomy at our institution. All patients had disabling dyspnea, thoracic hyperinflation, and a heterogeneous pattern of emphysema with suitable target areas for resection. Preoperative pulmonary rehabilitation was required and post-rehabilitation data were used as the baseline for data analysis. Follow-up ranged from 1.8 to 9.1 years (median 4.4 years). RESULTS: Prolonged air leaks (>7 days) were the most common complication (45.2%, n = 113). Reexploration rates for air leak and bleeding were 3.2% (n = 8) and 1.2% (n = 3), respectively. Eighteen patients (7.2%) required reintubation and mechanical ventilation. The in-hospital mortality in this series was 4.8% (n = 12). The median length of hospitalization was 9 days (range 4-168 days). Kaplan-Meier survivals after lung volume reduction surgery were 93.6%, 84.4%, and 67.7% at 1, 3, and 5 years, respectively. Eighteen patients (7.2%) have subsequently undergone lung transplantation after a median interval of 4.3 years (range 2.1-6.4 years). Spirometric values, lung volumes, and gas exchange parameters improved after surgery. The forced expiratory volume in 1 second and the residual volume showed statistically significant improvements between preoperative values and each time point of follow-up. Health-related quality of life showed significant postoperative improvement and with time correlated well with the improvement in forced expiratory volume in 1 second. CONCLUSIONS: Lung volume reduction surgery produces significant functional improvement for selected patients with emphysema. For most of these patients, benefits appear to last at least 5 years.

Aged↗
PubMed2003

A prospective evaluation of lung volume reduction surgery in 200 consecutive patients.

OBJECTIVES: Though numerous studies have demonstrated the short-term efficacy of lung volume reduction surgery (LVRS) in select patients with emphysema, the longer-term follow-up studies are just being reported. The primary objectives of this study were to assess long-term health-related quality of life, satisfaction, physiologic status, and survival of patients following LVRS. DESIGN: We used a prospective cohort study design to assess the first 200 patients undergoing bilateral LVRS (from 1993 to 1998), with follow-up through the year 2000. Each patient served as his own control, initially receiving optimal medical management including exercise rehabilitation before undergoing surgery. Preoperative postrehabilitation data were used as the baseline for comparisons with postoperative data. The primary end points were the effects of LVRS on dyspnea (modified Medical Research Council dyspnea sale), general health-related quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]), patient satisfaction, and survival. The secondary end points were the effects of LVRS on pulmonary function, exercise capacity, and supplemental oxygen requirements. SETTING: A tertiary care urban university-based referral center. PATIENTS: Eligibility requirements for LVRS included disabling dyspnea due to marked airflow obstruction, thoracic hyperinflation, and heterogeneously distributed emphysema that provided target areas for resection. Patients were assessed at 6 months, 3 years, and 5 years after surgery. INTERVENTIONS: Preoperative pulmonary rehabilitation and bilateral stapling LVRS. MEASUREMENTS AND RESULTS: The 200 patients accrued 735 person-years (mean +/- SD, 3.7 +/- 1.6 years; median, 4.0 years) of follow-up. Over the three follow-up periods, an average of > 90% of evaluable patients completed testing. Six months, 3 years, and 5 years after surgery, dyspnea scores were improved in 81%, 52%, and 40% of patients, respectively. Dyspnea scores were the same or improved in 96% (6 months), 82% (3 years), and 74% (5 years) of patients. Improvements in SF-36 physical functioning were demonstrated in 93% (6 months), 78% (3 years), and 69% (5 years) of patients. Good-to-excellent satisfaction with the outcomes was reported by 96% (6 months), 89% (3 years), and 77% (5 years) of patients. The FEV(1) was improved in 92% (6 months), 72% (3 years), and 58% (5 years) of patients. Changes in dyspnea and general health-related quality-of-life scores, and patient satisfaction scores were all significantly correlated with changes in FEV(1). Following surgery, the median length of hospital stay in survivors was 9 days. The 90-day postoperative mortality was 4.5%. Annual Kaplan-Meier survival through 5 years after surgery was 93%, 88%, 83%, 74%, and 63%, respectively. During follow-up, 15 patients underwent subsequent lung transplantation. CONCLUSIONS: In stringently selected patients, LVRS resulted in substantial beneficial effects over and above those achieved with optimized medical therapy. The duration of improvement was at least 5 years in the majority of survivors.

Dyspnea↗
PubMed2002

Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI.

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

Diffusion↗
PubMed2002

Lung transplantation for pulmonary vascular disease.

BACKGROUND: Pulmonary hypertension (PHT) is a lethal condition resulting in markedly diminished life expectancy. Continuous prostaglandin I2 infusion has made an important contribution to symptom management, but it is not a panacea. Lung or heart-lung transplantation remains an important treatment option for end-stage PHT patients unresponsive to prostaglandin I2. This study reviews the outcomes after transplantation for PHT in our program. METHODS: A retrospective chart review was performed for 100 consecutive patients with either primary PHT (48%) or secondary PHT (52%) transplants since 1989. Living recipients were contacted to confirm health and functional status. RESULTS: Fifty-five adult and 45 pediatric patients underwent 51 bilateral lung transplants, 39 single lung transplants, and 10 heart-lung transplants. Mean age was 23.7 years (range, 1.2 months to 54.8 years) and mean pre-transplant New York Heart Association class was 3.2. Pre-transplant hemodynamics revealed a mean right atrial pressure of 9.6+/-5.4 mm Hg and mean pulmonary artery pressure of 64+/-14.4 mm Hg. Hospital mortality was 17% with early death predominantly because of graft failure and infection. With an average follow-up of 5.0 years, 1- and 5-year actuarial survival was 75% and 57%, respectively. Mean pulmonary artery pressure on follow-up catheterization was 22+/-6.0 mm Hg, and mean follow-up New York Heart Association class was 1.3 (p < 0.001 for both compared with pre-transplant). Diagnosis and type of transplant did not confer a significant difference in survival between groups. CONCLUSIONS: Whereas lung or heart-lung transplant for PHT is associated with higher early mortality than other pulmonary disease entities, it provides similar long-term outcomes with dramatic improvement in both quality of life and physiologic aspects.

Adolescent↗
PubMed2002

Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival.

BACKGROUND: Revisions in the international system for the staging of lung cancer, adopted in 1997, assigned the T4 descriptor to separate tumor nodules in the same lobe and the M1 descriptor to tumor nodules in a different lobe. Consequently, these changes shifted the stage of patients with these lesions to stage IIIB or stage IV. The goal of this review was to determine the impact of multifocal non-small cell lung cancer on survival. METHODS: A database analysis of our cardiothoracic surgery tumor registry was performed to identify all patients who underwent surgical resection of non-small cell lung cancer (NSCLC), who were ultimately determined to have pathologically node-negative disease from 1994 to 1999. All pathology reports were individually reviewed. Survival data were collected on each patient from the date of surgery with a mean duration of follow-up of 46.3 months. Kaplan Meier actuarial survival was determined for all patients. RESULTS: Forty-four patients were identified who underwent complete resection of multiple NSCLC tumors. During this same period, 504 patients underwent complete resection of stage I NSCLC tumors. The 3-year actuarial survival for patients with T1/N0/M0 tumors was 79.6%. In comparison with patients with T1/N0/M0 tumors, the 3-year actuarial survival rates of patients with T2/N0/M0 tumors (72.3%, p = 0.056), T4/N0/M0 tumors (66.5%, p = 0.058), and T1 to T2/N0/M1 tumors (63.6%, p = 0.201) were lower. However, these differences did not achieve statistical significance. CONCLUSIONS: Although there was a trend toward decreased survival in patients with multifocal NSCLC compared with patients with stage I NSCLC, this did not achieve statistical significance. Importantly, survival in these subgroups of patients with stage IIIB or stage IV disease (stage determined solely on the basis of multifocal NSCLC) is better than the survival reported in the series that formed the foundation for these staging changes. These data support complete surgical resection of multifocal lung tumors in patients with node-negative NSCLC.

Adenocarcinoma↗
PubMed2002

Thirteen-year experience in lung transplantation for emphysema.

BACKGROUND: Emphysema is the most common indication for lung transplantation. Recipients include younger patients with genetically determined alpha-1 antitrypsin deficiency (AAD) and, more commonly, patients with chronic obstructive pulmonary disease (COPD). We analyzed the results of our single-institution series of lung transplants for emphysema to identify outcome differences and factors predicting mortality and morbidity in these two groups. METHODS: A retrospective analysis was undertaken of the 306 consecutive lung transplants for emphysema performed at our institution between 1988 and 2000 (220 COPD, 86 AAD). Follow-up was complete and averaged 3.7 years. RESULTS: The mean age of AAD recipients (49 +/- 6 years) was less than those with COPD (55 +/- 6 years; p < 0.001). Hospital mortality was 6.2%, with no difference between COPD and AAD, or between single-lung transplants and bilateral-lung transplants. Hospital mortality during the most recent 6 years was significantly lower (3.9% vs 9.5%, p = 0.044). Five-year survival was 58.6% +/- 3.5%, with no difference between COPD (56.8% +/- 4.4%) and AAD (60.5% +/- 5.8%). Five-year survival was better with bilateral-lung transplants (66.7% +/- 4.0%) than with single-lung transplants (44.9% +/- 6.0%, p < 0.005). Independent predictors of mortality by Cox analysis were single lung transplantation (relative hazard = 1.98, p < 0.001), and need for cardiopulmonary bypass during the transplant (relative hazard = 1.84, p = 0.038). CONCLUSIONS: AAD recipients, despite a younger age, do not achieve significantly superior survival results than those with COPD. Bilateral lung transplantation for emphysema results in better long-term survival. Accumulated experience and modifications in perioperative care over our 13-year series may explain recently improved early and long-term survival.

Adult↗
PubMed2002

Management of the solitary pulmonary nodule: directed resection.

The primary goals in management of a solitary pulmonary nodule are: 1) early detection and treatment of lung cancer at a curable stage; 2) avoidance of unnecessary surgery for benign lesions; 3) efficient, economic use of resources in distinguishing between benign and malignant lesions. Management depends on the nature of the nodule, the nature of the patient, and the approach of the physician or surgeon who assumes responsibility for further evaluation and treatment of the solitary pulmonary nodule. By combining appropriate diagnostic studies, and close personal attention, unnecessary excision of benign nodules can be kept to a minimum, patient anxiety allayed and excision of cancers undertaken with appropriate staging and without compromise of outcome.

Disease-Free Survival↗
PubMed2002

Impact of comorbidity on survival after surgical resection in patients with stage I non-small cell lung cancer.

OBJECTIVE: As the mean age in patients with non-small cell lung cancer increases, the proportion of patients with serious comorbidity who are considered for surgical resection also increases. Patients with non-small cell lung cancer have been shown to have a higher burden of comorbidity than do patients with tumors of other sites, such as breast, prostate, colon, and head and neck. The goal of this review was to determine the impact of comorbidity on postoperative and long-term survival after surgical resection in patients with stage I non-small cell lung cancer. METHODS: A database analysis of our hospital's tumor registry included 451 patients who underwent surgical resection for pathologic stage I non-small cell lung cancer between January 1, 1994, and December 31, 1999. Comorbidity severity was prospectively determined with the Kaplan-Feinstein Index. Survival data were collected for each patient from the date of operation, with a mean duration of follow-up of 35.7 months. Bivariate statistics and Cox proportional hazards model analyses were used. RESULTS: The mean age was 64.4 years, and 249 (55%) patients were male. The distribution of overall comorbidity severity was none, 142 (31.5%); mild, 150 (33.3%); moderate, 115 (25.5%); and severe, 44 (9.8%). The overall in-hospital mortality was 2.2% (n = 10/451). There was a nonsignificant trend toward higher hospital mortality with greater comorbidity: none, 0.7% (n = 1/142); mild, 3.3% (n = 5/150); moderate, 0.9% (n = 1/115); and severe, 6.8% (n = 3/44, P =.055). Kaplan-Meier estimated survivals at 3 years for each level of comorbidity were as follows: none, 85.6%; mild, 74.8%; moderate, 68.8%; and severe, 70.0% (P <.002). After adjustment for age, sex, T status, and tumor histologic type, the relative risks of death as a function of comorbidity were mild, 1.44 (95% confidence interval 0.89-2.34); moderate, 2.28 (95% confidence interval 1.43-3.65); and severe; 1.94 (95% confidence interval 1.023-3.70). CONCLUSIONS: Comorbidity has a significant impact on survival after surgical resection of patients with stage I non-small cell lung cancer. These data may help to explain the lower than expected survival results for patients after surgical resection for stage I non-small cell lung cancer.

Actuarial Analysis↗
PubMed2002

Does donor cause of death affect the outcome of lung transplantation?

BACKGROUND: Accumulating evidence suggests that the donor's cause of death may influence posttransplantation allograft function. We conducted a retrospective analysis of our adult lung transplant experience to investigate the influence of donor traumatic brain injury versus nontraumatic brain injury on posttransplantation outcome. METHODS: We retrospectively reviewed donor records and recipient medical charts for 500 consecutive lung transplants performed between July 1988 and December 1999. Recipient follow-up was complete, with a minimum follow-up of 1 year of survival. RESULTS: There were 295 and 205 donors in the traumatic and nontraumatic brain injury groups, respectively. Young male donors predominated in the traumatic brain injury group. Recipients receiving donor lungs from the traumatic and nontraumatic brain injury groups did not differ by age, sex, diagnosis, type of transplant (single-lung versus double-lung) or requirement for pretransplantation mechanical ventilatory assistance. Recipients did not differ in immediate or 24-hour PaO (2)/inspired oxygen ratio, ventilation time, hospital stay, hospital mortality, or overall survival. Recipients of organs from donors who died of traumatic brain injury showed a higher severity and frequency of rejection episodes during the first year after transplantation. Freedoms from bronchiolitis obliterans syndrome at 5 years were 34.5% and 50.8% for recipients of organs from donors who died of traumatic and nontraumatic brain injury, respectively (P =.002). CONCLUSIONS: The cause of donor brain death does not appear to influence early results of lung transplantation. Traumatic brain injury, or some phenomenon associated with it, may predispose a transplanted lung and its recipient toward more severe early rejection episodes and subsequent development of bronchiolitis obliterans syndrome.

Adult↗