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.     

Collecting 48,000 CT Exams for the Lung Screening Study of the National Lung Screening Trial

From 2002–2004, the Lung Screening Study (LSS) of the National Lung Screening Trial (NLST) enrolled 34,614 participants, aged 55–74 years, at increased risk for lung cancer due to heavy cigarette smoking. Participants, randomized to standard chest X-ray (CXR) or computed tomography (CT) arms at ten screening centers, received up to three imaging screens for lung cancer at annual intervals. Participant medical histories and radiologist-interpreted screening results were transmitted to the LSS coordinating center, while all images were retained at local screening centers. From 2005–2007, all CT exams were uniformly de-identified and delivered to a central repository, the CT Image Library (CTIL), on external hard drives (94%) or CD/DVD (5.9%), or over a secure Internet connection (0.1%). Of 48,723 CT screens performed, only 176 (0.3%) were unavailable (lost, corrupted, compressed) while 48,547 (99.7%) were delivered to the CTIL. Described here is the experience organizing, implementing, and adapting the clinical-trial workflow surrounding the image retrieval, de-identification, delivery, and archiving of available LSS–NLST CT exams for the CTIL, together with the quality assurance procedures associated with those collection tasks. This collection of CT exams, obtained in a specific, well-defined participant population under a common protocol at evenly spaced intervals, and its attending demographic and clinical information, are now available to lung-disease investigators and developers of computer-aided-diagnosis algorithms. The approach to large scale, multi-center trial CT image collection detailed here may serve as a useful model, while the experience reported should be valuable in the planning and execution of future equivalent endeavors.     

Gadolinium as a CT contrast agent: assessment in a porcine model

PURPOSE: To investigate the use of gadolinium as a computed tomographic (CT) contrast agent. MATERIALS AND METHODS: In vitro attenuation measurements of multiple dilutions of gadodiamide and ioversol were compared. In three pigs, 50-mL boluses of undiluted gadodiamide were injected intravenously at 2 mL/sec, and repeated single-level scans were obtained through the lung bases, liver, and kidneys. The doses of 0.8-1.0 mmol of gadolinium per kilogram of body weight were approximately three times the highest doses currently used in patients. Enhancement was determined from attenuation measurements in the aorta, pulmonary arteries, liver, and kidneys. RESULTS: In vitro, the attenuation of undiluted gadodiamide (3,069 HU) was equivalent to that of ioversol diluted to 106 mg of iodine per milliliter and at equimolar concentrations was 50% greater than that of ioversol. The magnitude of and time to peak enhancement were 141 HU and 27 seconds (n = 3) for the aorta; 168 HU and 21 seconds (n = 3) for the pulmonary arteries; 23 HU and 65 seconds (n = 2) for the liver; and 63 HU and 32 seconds (n = 1) for the kidneys. Time-attenuation curves revealed a useful duration of enhancement of 20-30 seconds for the aorta and pulmonary arteries. CONCLUSION: Gadolinium produces good vascular enhancement, adequate renal enhancement, and suboptimal hepatic enhancement. Further study is needed to determine the safety of the gadolinium dose required to produce similar enhancement in patients.     

Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening.     

Radiologic assessment of emphysema for lung volume reduction surgery

Radiologic imaging is vital to determining whether lung volume reduction surgery (LVRS) is a potential therapeutic option for patients with severe chronic obstructive pulmonary disease. The importance of imaging in patient selection for LVRS has been emphasized by numerous studies relating preoperative imaging features to postoperative outcomes. This article reviews the radiologic features assessed in the LVRS evaluation, summarizes the relationships between preoperative radiologic features and postoperative outcomes, and addresses the limitations of imaging in guiding patient selection.     

Repeatability of quantitative CT indexes of emphysema in patients evaluated for lung volume reduction surgery

PURPOSE: To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS). MATERIALS AND METHODS: Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests. RESULTS: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83). CONCLUSION: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.     

The role of collateral paths in long-range diffusion of 3He in lungs

RATIONALE AND OBJECTIVES: The hyperpolarized (3)He long-range diffusion coefficient (LRDC) in lungs is sensitive to changes in lung structure due to emphysema, reflecting the increase in collateral paths resulting from tissue destruction. However, no clear understanding of LRDC in healthy lungs has emerged. Here we compare LRDC measured in healthy lungs with computer simulations of diffusion along the airway tree with no collateral connections. MATERIALS AND METHODS: Computer simulations of diffusion of spatially modulated spin magnetization were performed in computer-generated, symmetric-branching models of lungs and compared with existing LRDC measurements in canine and human lungs. RESULTS: The simulations predict LRDC values of order 0.001 cm(2)/sec, approximately 20 times smaller than the measured LRDC. We consider and rule out possible mechanisms for LRDC not included in the simulations: incomplete breath hold, cardiac motion, and passage of dissolved (3)He through airway walls. However, a very low density of small (micron) holes in the airways is shown to account for the observed LRDC. CONCLUSION: It is proposed that LRDC in healthy lungs is determined by small collateral pathways.