Joel D Cooper

University of Pennsylvania, Philadelphia, Pennsylvania, United States

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Publications (82)384.35 Total impact

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    ABSTRACT: Lung is a complex gas exchanger with interfacial area (where the gas exchange takes place) is about the size of a tennis court. Respiratory function is linked to the biomechanical stability of the gas exchange or alveolar regions which directly depends on the spatial distributions of the extracellular matrix fibers such fibrillar collagens and elastin fibers. It is very important to visualize and quantify these fibers at their native and inflated conditions to have correct morphometric information on differences between control and diseased states. This can be only achieved in the ex vivo states by imaging directly frozen lung specimens inflated to total lung capacity. Multiphoton microscopy, which uses ultra-short infrared laser pulses as the excitation source, produces multiphoton excitation fluorescence (MPEF) signals from endogenously fluorescent proteins (e.g. elastin) and induces specific second harmonic generation (SHG) signals from non-centrosymmetric proteins such as fibrillar collagens in fresh human lung tissues [J. Struct. Biol. (2010)171,189-196]. Here we report for the first time 3D image data obtained directly from thick frozen inflated lung specimens (~0.7- 1.0 millimeter thick) visualized at -60°C without prior fixation or staining in healthy and diseased states. Lung specimens donated for transplantation and released for research when no appropriate recipient was identified served as controls, and diseased lung specimens donated for research by patients receiving lung transplantation for very severe COPD (n=4) were prepared as previously described [N. Engl. J. Med. (2011) 201, 1567]. Lung slices evenly spaced between apex and base were examined using multiphoton microscopy while maintained at -60°C using a temperature controlled cold stage with a temperature resolution of 0.1°C. Infrared femto-second laser pulses tuned to 880nm, dry microscopic objectives, and non-de-scanned detectors/spectrophotometer located in the reflection geometry were used for generating the 3D images/spectral information. We found that this novel imaging approach can provide spatially resolved 3D images with spectral specificities from frozen inflated lungs that are sensitive enough to identity the micro-structural details of fibrillar collagens and elastin fibers in alveolar walls in both healthy and diseased tissues.
    Proc SPIE 02/2013;
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    ABSTRACT: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease consisting of emphysema, small airway obstruction, and/or chronic bronchitis that results in significant loss of lung function over time. METHODS: In order to gain insights into the molecular pathways underlying progression of emphysema and explore computational strategies for identifying COPD therapeutics, we profiled gene expression in lung tissue samples obtained from regions within the same lung with varying amounts of emphysematous destruction from smokers with COPD (8 regions x 8 lungs = 64 samples). Regional emphysema severity was quantified in each tissue sample using the mean linear intercept (Lm) between alveolar walls from micro-CT scans. RESULTS: We identified 127 genes whose expression levels were significantly associated with regional emphysema severity while controlling for gene expression differences between individuals. Genes increasing in expression with increasing emphysematous destruction included those involved in inflammation, such as the B-cell receptor signaling pathway, while genes decreasing in expression were enriched in tissue repair processes, including the transforming growth factor beta (TGF beta) pathway, actin organization, and integrin signaling. We found concordant differential expression of these emphysema severity-associated genes in four cross-sectional studies of COPD. Using the Connectivity Map, we identified GHK as a compound that can reverse the gene-expression signature associated with emphysematous destruction and induce expression patterns consistent with TGF beta pathway activation. Treatment of human fibroblasts with GHK recapitulated TGF beta-induced gene-expression patterns, led to the organization of the actin cytoskeleton, and elevated the expression of integrin beta1. Furthermore, addition of GHK or TGF beta restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD. CONCLUSIONS: These results demonstrate that gene-expression changes associated with regional emphysema severity within an individual¿s lung can provide insights into emphysema pathogenesis and identify novel therapeutic opportunities for this deadly disease. They also suggest the need for additional studies to examine the mechanisms by which TGF beta and GHK each reverse the gene-expression signature of emphysematous destruction and the effects of this reversal on disease progression.
    Genome Medicine 08/2012; 4(8):67. · 4.94 Impact Factor
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    ABSTRACT: Adenoid cystic carcinoma is a rare malignancy that usually originates in the salivary glands of the head and neck but has rarely been known to originate in the trachea. This histology has a predilection for perineural invasion and a tendency for both local and distant recurrences. While surgical resection is the mainstay of treatment of tracheal adenoid cystic carcinoma, tumor size, location, and patient comorbidities may preclude surgery, and the optimal nonsurgical management remains undefined. In the absence of locoregional lymph node metastases, we recommend highly conformal radiotherapy alone to a dose of 80 Gy. We report on two patients with unresectable disease who were treated with definitive radiotherapy: one using conventional photons and one treated with a combination of photon and proton beams. Both patients were treated to a dose of 80 Gy with acceptable toxicities and objective clinical and radiographic response. The patient treated with conventional photons has no evidence of recurrent disease at 5 years; the patient treated with protons has continued evidence of response without evidence of disease recurrence 11 months after treatment.
    Chest 05/2012; 141(5):1323-6. · 5.85 Impact Factor
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    ABSTRACT: The major sites of obstruction in chronic obstructive pulmonary disease (COPD) are small airways (<2 mm in diameter). We wanted to determine whether there was a relationship between small-airway obstruction and emphysematous destruction in COPD. We used multidetector computed tomography (CT) to compare the number of airways measuring 2.0 to 2.5 mm in 78 patients who had various stages of COPD, as judged by scoring on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale, in isolated lungs removed from patients with COPD who underwent lung transplantation, and in donor (control) lungs. MicroCT was used to measure the extent of emphysema (mean linear intercept), the number of terminal bronchioles per milliliter of lung volume, and the minimum diameters and cross-sectional areas of terminal bronchioles. On multidetector CT, in samples from patients with COPD, as compared with control samples, the number of airways measuring 2.0 to 2.5 mm in diameter was reduced in patients with GOLD stage 1 disease (P=0.001), GOLD stage 2 disease (P=0.02), and GOLD stage 3 or 4 disease (P<0.001). MicroCT of isolated samples of lungs removed from patients with GOLD stage 4 disease showed a reduction of 81 to 99.7% in the total cross-sectional area of terminal bronchioles and a reduction of 72 to 89% in the number of terminal bronchioles (P<0.001). A comparison of the number of terminal bronchioles and dimensions at different levels of emphysematous destruction (i.e., an increasing value for the mean linear intercept) showed that the narrowing and loss of terminal bronchioles preceded emphysematous destruction in COPD (P<0.001). These results show that narrowing and disappearance of small conducting airways before the onset of emphysematous destruction can explain the increased peripheral airway resistance reported in COPD. (Funded by the National Heart, Lung, and Blood Institute and others.).
    New England Journal of Medicine 10/2011; 365(17):1567-75. · 51.66 Impact Factor
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    ABSTRACT: Tracheobronchopathia osteochondroplastica is a rare, benign disorder of upper airways characterized by multiple submucosal metaplastic cartilaginous and bony nodules arising from the tracheal cartilage. We report an unusual presentation of tracheobronchopathia osteochondroplastica as a single dominant nodule arising from the anterior tracheal rings in a young adult man who presented with wheezing and symptoms of airway obstruction. The differential diagnosis of cartilaginous and bony endotracheal lesions is discussed.
    Annals of diagnostic pathology 07/2011; 15(6):431-5.
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    ABSTRACT: The clinical benefit of postoperative mediastinal radiation for completely resected Masaoka stage 2 thymoma remains controversial. Due to its indolent nature and infrequent recurrences, no study has definitively determined the optimal approach. We retrospectively reviewed 175 consecutive patients who underwent thymic resection from January 1990 to July 2008 at the University of Pennsylvania. The primary endpoint was local recurrence, defined as recurrence within the surgical bed, treated by resection alone versus resection plus radiation. Patients with high recurrence risk were referred for adjuvant radiotherapy. Seventy-four Masaoka stage 2 patients were resected; 62 underwent complete resections with adequate postsurgical follow-up. Thirty-seven patients received adjuvant radiotherapy and 25 patients were observed. The median radiation dose was 5040 cGy. The median follow-up for all patients was 52 months. The local recurrence rate was 3.2%. The proportion of recurrences in patients observed after surgery was 8% versus 0% in those who received adjuvant radiotherapy (P = .15). Size was not an independent predictor of recurrence (P = .81). The tumor-related death rate was 0%, and overall death rate was 3.2%. One death occurred in each group, observation, and radiation. There were no grade 3 or 4 complications with radiation. Recurrence rates were low following resection of stage 2 thymoma either with or without adjuvant radiotherapy. Adjuvant radiotherapy, although well-tolerated, did not significantly decrease the local relapse rate. Differences may be observed in future studies of patients who are at higher risk for local recurrence, based on completeness of resection, World Health Organization histology, and tumor size.
    Cancer 02/2011; 117(15):3502-8. · 5.20 Impact Factor
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    ABSTRACT: Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612). The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1 ≤ 50% of predicted or FEV1 < 1 liter, RV/TLC ≥ 0.65 at screening, marked dyspnea score ≥ 2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥ 12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥ 1 point at the 6-month follow-up visit. If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit. ClinicalTrials.gov: NCT00391612.
    BMC Pulmonary Medicine 01/2011; 11:1. · 2.76 Impact Factor
  • Joel D Cooper
    The Journal of thoracic and cardiovascular surgery 10/2010; 140(4):743-6. · 3.41 Impact Factor
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    ABSTRACT: To evaluate the use of inflation-fixed lung tissue for emphysema quantification with computed tomography (CT) and He magnetic resonance (MR) diffusion imaging. Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. Computed tomographic measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation. The mean (SD) CT emphysema indices were 56% (17%) before and 58% (19%) after fixation (P = 0.77; R = 0.76). Index differences correlated with differences in lung volume (R = 0.47). The mean (SD) 3He ADCs were 0.40 (0.15) cm/s before and 0.39 (0.14) cm/s after fixation (P = 0.03, R = 0.98). The CT emphysema index and the 3He ADC were correlated before (R = 0.89) and after fixation (R = 0.79). Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.
    Journal of computer assisted tomography 08/2010; 34(5):773-9. · 1.38 Impact Factor
  • Joel D Cooper
    Chest 08/2010; 138(2):243-5. · 5.85 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the accuracy of emphysema measurements obtained from systematic samples of evenly spaced CT images compared with measurements obtained from the entire scan. Evenly spaced transverse sections from the CT studies of 136 heavy smokers who underwent screening for lung cancer in the National Lung Screening Trial and of 112 subjects who underwent imaging before lung volume reduction surgery were sampled retrospectively. The samples were acquired both by selection of specific numbers of evenly spaced images and by selection of images at specific distance intervals. The percentage of lung pixels with attenuation below specific thresholds was used as an emphysema index. The image sample error was determined as the difference in emphysema index between the image samples and the entire scan. The largest absolute image sample errors in the National Lung Screening Trial cohort with image sample sizes of five, 10, and 20 were 2.2, 0.8, and 0.5 index percentage points, respectively, at 1-mm section thickness (-960 HU threshold), and 2.6, 1.1, and 0.5 index percentage points at 5-mm section thickness (-930 HU threshold). The largest errors in the lung volume reduction surgery cohort for image sample sizes of five and 10 were 5.6 and 2.3 index percentage points at 8- to 10-mm section thickness (-900 HU threshold). Image sample errors were equivalent for the two sampling methods. Systematic sampling resulted in very small errors in emphysema quantification and may be useful for decreasing radiation exposure in clinical research studies of emphysema.
    American Journal of Roentgenology 03/2010; 194(3):585-91. · 2.90 Impact Factor
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    ABSTRACT: Computed tomography (CT) section thickness and reconstruction kernel each influence CT measurements of emphysema. This study was performed to assess whether their effects are related to the magnitude of the measurement. Low-radiation-dose multidetector CT was performed in 21 subjects representing a wide range of emphysema severity. Images were reconstructed using 20 different combinations of section thickness and reconstruction kernel. Emphysema index values were determined as the percentage of lung pixels having attenuation lower than multiple thresholds ranging from -960 HU to -890 HU. The index values obtained from the different thickness-kernel combinations were compared by repeated measures analysis of variance and Bland-Altman plots of mean versus difference in all subjects, and correlated with quantitative histology (mean linear intercept, Lm) in a subset of resected lung specimens. The effects of section thickness and reconstruction kernel on the emphysema index were significant (P < .001) and diminished as the index attenuation threshold was raised. The changes in index values from changing the thickness-kernel combination were largest for subjects with intermediate index values (10%-30%), and became progressively smaller for those with lower and higher index values. This pattern was consistent regardless of the thickness-kernel combinations compared and the HU threshold used. Correlations between the emphysema index values obtained with each thickness-kernel combination and Lm ranged from r = 0.55-0.68 (P = .007-.03). The effects of CT section thickness and kernel on emphysema index values varied systematically with the magnitude of the emphysema index. All reconstruction techniques provided significant correlations with quantitative histology.
    Academic radiology 11/2009; 17(2):146-56. · 2.09 Impact Factor
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    ABSTRACT: To characterize the effect of diffusion time on short-range hyperpolarized (3)He magnetic resonance imaging (MRI) diffusion measurements across a wide range of emphysema severity. (3)He diffusion MRI was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using three diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30-0.55 cm(2)/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects. The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm(2)/sec, respectively (P < 0.0001, analysis of variance [ANOVA]). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. The mean linear intercept correlated with ADC (r = 0.91-0.94, P < 0.001) and ADC index (r = 0.78-0.92, P < 0.01) at all diffusion times. Decreases in ADC with longer diffusion time were unrelated to emphysema severity. The strong correlations between the ADC at all diffusion times tested and quantitative histology demonstrate that ADC is a robust measure of emphysema.
    Journal of Magnetic Resonance Imaging 10/2009; 30(4):801-8. · 2.57 Impact Factor
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    ABSTRACT: The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized (3)He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii-parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials.
    Journal of Applied Physiology 09/2009; 107(4):1258-65. · 3.48 Impact Factor
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    ABSTRACT: Background: The smaller airways, < 2 mm in diameter, offer little resistance in normal lungs, but become the major site of obstruction in chronic obstructive pulmonary disease (COPD). Objective: To examine bronchiolar remodeling and alveolar destruction in COPD using micro-computed tomography (micro-CT). Methods: Micro-CT was used to measure the number and cross-sectional lumen area of terminal bronchioles (TB) and alveolar mean linear intercept (Lm) in 4 lungs removed from patients with very severe (GOLD-4) COPD and 4 unused donor lungs that served as controls. These lungs were inflated with air to a transpulmonary pressure (P(L)) of 30 cm H(2)O and held at P(L) 10 cm H(2)O while they were frozen solid in liquid nitrogen vapor. A high resolution CT scan was performed on the frozen specimen prior to cutting it into 2-cm thick transverse slices. Representative core samples of lung tissue 2 cm long and 1 cm in diameter cut from each slice were fixed at -80 degrees C in a 1% solution of gluteraldehyde in pure acetone, post-fixed in osmium, critically point dried, and examined by micro-CT. Results: A 10-fold reduction in terminal bronchiolar number and a 100-fold reduction in their minimal cross-sectional lumen area were measured in both emphysematous and non-emphysematous regions of the COPD lungs. Conclusions: The centrilobular emphysematous phenotype of COPD is associated with narrowing and obliteration of the terminal bronchioles that begins prior to the onset of emphysematous destruction.
    Proceedings of the American Thoracic Society 09/2009; 6(6):546-9.
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    ABSTRACT: Patients who are offered concomitant surgery are highly selected and must satisfy the strict criteria set out for both LVRS and cancer surgery. Several evaluative processes have been reported for the selection of suitable patients. These various evaluative processes, together with the physical condition of the patient and the surgeon's experience, help to best select patients suitable for combined surgical resection. Several intraoperative strategies are available for dealing with a patient who has concomitant lung cancer and severe emphysema. The choice of technique depends on the location and size of the tumor, the severity and distribution of the emphysema, and the surgeon's experience and preference. Lung volume reduction surgery in well-selected patients who have severe emphysema results in postoperative improvement of symptoms and measured pulmonary function. The combination of lung cancer resection with LVRS offers selected patients who have concomitant early lung cancer and severe emphysema the opportunity to undergo resection of their cancer with improvement rather than further reduction in their pulmonary function. By traditional criteria these patients would otherwise be considered unsuitable surgical candidates because of the limited pulmonary function.
    Thoracic Surgery Clinics 06/2009; 19(2):209-16.
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    ABSTRACT: Airway bypass is being investigated as a new form of minimally invasive therapy for the treatment of homogeneous emphysema. It is a bronchoscopic catheter-based procedure that creates transbronchial extra-anatomic passages at the bronchial segmental level. The passages are expanded, supported with the expectation that the patency is maintained by paclitaxel drug-eluting airway bypass stents. The concept of airway bypass has been demonstrated in two separate experimental studies. These studies have shown that airway bypass takes advantage of collateral ventilation present in homogeneous emphysema to allow trapped gas to escape and reduce hyperinflation. It improves lung mechanics, expiratory flow, and volume. Airway bypass stent placements have been shown to be feasible and safe in both animal and human studies. Paclitaxel-eluting airway bypass stents were found to prolong stent patency and were adopted for clinical studies. A study evaluating the early results of the clinical application of airway bypass with paclitaxel-eluting stents found that airway bypass procedures reduced hyperinflation and improved pulmonary function and dyspnea in selected subjects who have severe emphysema. The duration of benefit appeared to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results supported further evaluation of the procedure and led to the EASE Trial. The EASE Trial is a prospective, multicenter, randomized, double-blind, sham-controlled study. The trial aims to evaluate the safety and effectiveness of the airway bypass to improve pulmonary function and reduce dyspnea in homogeneous emphysema subjects who have severe hyperinflation. The trial is presently ongoing worldwide, though enrollment was completed.
    Thoracic Surgery Clinics 06/2009; 19(2):239-45.
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    ABSTRACT: One century ago, thoracic surgery was in its infancy. Since then, advances in chest radiology have allowed for reliable and early detection of thoracic ailments. Refinements in anesthesiology and surgical technique have led to the development of a plethora of techniques for the diagnosis, staging, and treatment of mediastinal disease. As the disease processes we encounter have expanded and evolved, so too has our surgical armamentarium.
    Thoracic Surgery Clinics 03/2009; 19(1):1-5.
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    ABSTRACT: For patients with end-stage emphysema undergoing lung volume reduction surgery (LVRS), we have preferred a bilateral (BLVRS) approach to achieve maximum benefit with a single procedure. A unilateral (ULVRS) approach has been used in certain patients in whom BLVRS is contraindicated. Between January 1993 and December 2006, 43 consecutive patients underwent ULVRS. The study excluded patients undergoing giant bullectomy. Relative contraindications for BLVRS were unilateral emphysema, 21; unilateral emphysema plus other factors, 2; and other factors alone, 10. Preoperative pulmonary rehabilitation was required. Postrehabilitation data were used as the baseline for analyses. Outcome measurements for ULVRS were compared with BLVRS results. After ULVRS, the mean increase in forced expiratory volume in 1 second (FEV(1)) from postrehabilitation values was 32% at 6 months (p <or= 0.001) and 28% at 3 years (p = 0.036). The FEV(1) was not significantly improved at 5 years. The mean reduction in residual volume after ULVRS was 23% at 6 months (p <or= 0.001) and 38% at 5 years (p = 0.001). Supplemental oxygen requirements declined initially postoperatively. One patient (2%) died in the hospital. The 90-day mortality was 0%. Kaplan-Meier survival after ULVRS was 97.7%, 80.9%, and 45.5%, at 1, 3, and 5 years. ULVRS produces improvements in pulmonary function, exercise capacity, and quality of life with an acceptable morbidity and mortality in patients for whom BLVRS is contraindicated, but the benefits are of lower magnitude than those achieved with BLVRS.
    The Annals of thoracic surgery 08/2008; 86(1):204-11; discussion 211-2. · 3.45 Impact Factor
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    ABSTRACT: To evaluate the safety of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. Local institutional review board approval and informed consent were obtained. Physiologic monitoring data were obtained before, during, and after hyperpolarized (3)He MR imaging in 100 consecutive subjects (57 men, 43 women; mean age, 52 years +/- 14 [standard deviation]). The subjects inhaled 1-3 L of a gas mixture containing 300-500 mL (3)He and 0-2700 mL N(2) and held their breath for up to 15 seconds during MR imaging. Heart rate and rhythm and oxygen saturation of hemoglobin as measured by pulse oximetry (Spo(2)) were monitored continuously throughout each study. The effects of (3)He MR imaging on vital signs and Spo(2) and the relationship between pulmonary function, number of doses, and clinical classification (healthy volunteers, patients with asthma, heavy smokers, patients undergoing lung volume reduction surgery for severe emphysema, and patients with lung cancer) and the lowest observed Spo(2) were assessed. Any subjective symptoms were noted. Except for a small postimaging decrease in mean heart rate (from 78 beats per minute +/- 13 to 73 beats per minute +/- 11, P < .001), there was no effect on vital signs. A mean transient decrease in Spo(2) of 4% +/- 3 was observed during the first minute after gas inhalation (P < .001) in 77 subjects who inhaled a dose of 1 L for 10 seconds or less, reaching a nadir of less than 90% at least once in 20 subjects and of less than 85% in four subjects. There was no correlation between the lowest Spo(2) and pulmonary function parameters other than baseline Spo(2) (r = 0.36, P = .001). The lowest mean Spo(2) varied by 1% between the first and second and second and third doses (P < .001) and was unrelated to clinical classification (P = .40). Minor subjective symptoms were noted by 10 subjects. No serious adverse events occurred. Hyperpolarized (3)He MR imaging can be safely performed in healthy subjects, heavy smokers, and those with severe obstructive airflow limitation, although unpredictable transient desaturation suggests that potential subjects should be carefully screened for comorbidities.
    Radiology 08/2008; 248(2):655-61. · 6.34 Impact Factor

Publication Stats

2k Citations
384.35 Total Impact Points

Institutions

  • 2007–2012
    • University of Pennsylvania
      • • Department of Medicine
      • • Division of Cardiothoracic Surgery
      Philadelphia, Pennsylvania, United States
  • 2011
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
    • Imperial College London
      Londinium, England, United Kingdom
  • 2009
    • Hospital of the University of Pennsylvania
      • Division of Cardiothoracic Surgery
      Philadelphia, Pennsylvania, United States
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom
  • 1997–2009
    • Washington University in St. Louis
      • • Department of Physics
      • • Department of Surgery
      • • Division of Cardiothoracic Surgery
      Saint Louis, MO, United States
  • 2006
    • University of Southern California
      • Department of Cardiothoracic Surgery
      Los Angeles, CA, United States
  • 1995–2006
    • Barnes Jewish Hospital
      San Luis, Missouri, United States
  • 1992–2006
    • University of Washington Seattle
      • • Division of Cardiothoracic Surgery
      • • Department of Surgery
      Seattle, WA, United States
  • 2003
    • Sapienza University of Rome
      • Department of Biology and Biotechnology "Charles Darwin" BBCD
      Roma, Latium, Italy