Lung function 5 yr after lung volume reduction surgery for emphysema

Current datum more than 2 yr after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline and 5-yr results in 26 symptomatic patients (mean age 67 +/- 6 yr) (mean +/- SD) who underwent bilateral, targeted upper lobe stapled LVRS using video-assisted thoracoscopy. Baseline forced expiratory volume in 1 s (FEV(1)) was 0.7 +/- 0.2 L (mean +/- SD), 29 +/- 10% predicted. Following LVRS, with none lost to follow-up, mortality due to respiratory failure at 0.5, 1, 2, 3, 4, and 5 yr was 4%, 4%, 19%, 31%, 46%, and 58%, respectively. Increase above baseline for FEV(1) > 200 ml and/or FVC > 400 ml at 1, 2, 3, 4, and 5 yr post-LVRS was noted in 73%, 46%, 35%, 27%, and 8% of all patients; decrease in dyspnea grade >/= 1 in 88%, 69%, 46%, 27%, and 15%; and elimination of initial oxygen dependence in 18 patients in 78%, 50%, 33%, 22%, and 0%, respectively. Expiratory airflow improved due to the increase in both lung elastic recoil and small airway intraluminal caliber. Five patients decreased FEV(1) 141 +/- 60 ml/yr and FVC 102 +/- 189 ml/yr over 3.8 +/- 1.2 yr post-LVRS, similar to their pre-LVRS rate of decline. In the 11 patients who survived 5 yr, at 0.5-1.0 yr post-LVRS peak increase in FEV(1) was 438 +/- 366 ml, with a decline of 149 +/- 157 ml the following year and 78 +/- 59 ml/yr over 4.0-4.5 yr. Bilateral LVRS provided palliative clinical and physiological improvement in 9 of 26 patients at 3 yr, 7 at 4 yr, and 2 at 5 yr.     

Lung elastic recoil does not correlate with pulmonary hemodynamics in severe emphysema

BACKGROUND: It has been postulated that right ventricular (RV) function may improve after lung volume reduction surgery (LVRS) for severe emphysema due to improvement in lung elastic recoil. Improved lung elastic recoil after LVRS is hypothesized to "tether" open extraalveolar vessels, thereby leading to a decrease in pulmonary vascular resistance (PVR) and improved RV function. Whether a relationship exists between static elastic lung recoil and pulmonary hemodynamics in severe emphysema, however, is unknown. METHODS: We prospectively studied 67 patients with severe emphysema (32 women; mean age, 65.3+/-6.6 years [SD]; mean FEV1, 0.79+/-0.25 L) who had hyperinflation (total lung capacity [TLC], 122.5+/-12.3% of predicted) and gas trapping (residual volume, 209.1+/-41.1% of predicted), and were referred to the National Emphysema Treatment Trial. Lung elastic recoil was measured both at TLC (coefficient of retraction [CR]) and at functional reserve capacity (CR at functional residual capacity [CRfrc]) in each patient. RESULTS: CR and CRfrc values were 1.3+/-0.6 cm H2O/L and 0.61+/-0.5 cm H2O/L, respectively. Hemodynamic measurements revealed a pulmonary artery (PA) systolic pressure of 35.9+/-8.9 mm Hg, mean PA pressure of 24.8+/-5.6 mm Hg, and PVR of 174+/-102 dyne*s*cm(-5). No significant correlations were found between CR and PVR (R=-0.046, p=0.71), PA systolic pressure (R=0.005, p=0.97), or mean PA pressure (R=-0.028, p=0.82). Additionally, no significant correlations were found between CRfrc and PVR (R=-0.002, p=0.99), PA systolic pressure (R=-0.062, p=0.62), or mean PA pressure (R=-0.041, p=0.74). CONCLUSIONS: We conclude there is no correlation between lung elastic recoil and pulmonary hemodynamics in severe emphysema, suggesting that elastic lung recoil is not an important determinant of secondary pulmonary hypertension in this group. Registered with www. clinicaltrials.gov, #NCT00000606.     

The potential for bronchoscopic lung volume reduction using bronchial prostheses: a pilot study

STUDY OBJECTIVES: Significant morbidity and mortality offset the benefits of lung volume reduction surgery (LVRS) for emphysema. By contributing to distal lung collapse, bronchoscopic placement of valved prostheses has the potential to noninvasively replicate the beneficial effects of LVRS. The purpose of this study was to investigate the safety and feasibility of placing valves in segmental airways of patients with emphysema. DESIGN: Case series. SETTING: Tertiary hospital, severe airways disease clinic. PATIENTS: Ten patients aged 51 to 69 years with apical emphysema and hyperinflation, otherwise suitable for standard LVRS. Mean preoperative FEV(1) was 0.72 L (19 to 46% predicted), and 6-min walk distance was 340 m (range, 245 to 425 m). INTERVENTION: Apical, bronchoscopic, segmental airway placement of one-way valves (silicone-based Nitinol bronchial stent; Emphasys Medical; Redwood City, CA) under general anesthesia. Placement was over a guidewire under bronchoscopic and fluoroscopic control. RESULTS: Four to 11 prostheses per patient took 52 to 137 min to obstruct upper-lobe segments bilaterally. Inpatient stay was 1 to 8 days. No major complications were seen in the 30-day study period. Minor complications included exacerbation of COPD (n = 3), asymptomatic localized pneumothorax (n = 1), and lower-lobe pneumonia (day 37; n = 1). Symptomatic improvement was noted in four patients. No major change in radiologic findings, lung function, or 6-min walk distance was evident at 1 month, although gas transfer improved from 7.47 +/- 2.0 to 8.26 +/- 2.6 mL/min/mm Hg (p = 0.04) and nuclear upper-lobe perfusion fell from 32 +/- 10 to 27 +/- 9% (mean +/- SD) [p = 0.02]. CONCLUSION: Bronchoscopic prostheses can be safely and reliably placed into the human lung. Further study is needed to explore patient characteristics that determine symptomatic efficacy in a larger patient cohort.     

Effects of lung volume reduction surgery on sleep quality and nocturnal gas exchange in patients with severe emphysema

STUDY OBJECTIVES: We hypothesized that associated with improvements in respiratory mechanics, lung volume reduction surgery (LVRS) would result in an improvement in both sleep quality and nocturnal oxygenation in patients with severe emphysema. DESIGN: Prospective randomized controlled trial. SETTING: University hospital. PATIENTS: Sixteen patients (10 men, 63 +/- 6 years [+/- SD]) with severe airflow limitation (FEV(1), 28 +/- 10% predicted) and hyperinflation (total lung capacity, 123 +/- 14% predicted) who were part of the National Emphysema Treatment Trial.Interventions and measurements: Patients completed 6 to 10 weeks of outpatient pulmonary rehabilitation. Spirometry, measurement of lung volumes, arterial blood gas analysis, and polysomnography were performed prior to randomization and again 6 months after therapy. Ten patients underwent LVRS and optimal medical therapy, while 6 patients received optimal medical therapy only. RESULTS: Total sleep time and sleep efficiency improved following LVRS (from 184 +/- 111 to 272 +/- 126 min [p = 0.007], and from 45 +/- 26 to 61 +/- 26% [p = 0.01], respectively), while there was no change with medical therapy alone (236 +/- 75 to 211 +/- 125 min [p = 0.8], and from 60 +/- 18 to 52 +/- 17% [p = 0.5], respectively). The mean and lowest oxygen saturation during the night improved with LVRS (from 90 +/- 7 to 93 +/- 4% [p = 0.05], and from 83 +/- 10 to 86 +/- 10% [p = 0.03], respectively), while no change was noted in the medical therapy group (from 91 +/- 5 to 91 +/- 5 [p = 1.0], and from 84 +/- 5 to 82 +/- 6% [p = 0.3], respectively). There was a correlation between the change in FEV(1) and change in the lowest oxygen saturation during the night (r = 0.6, p = 0.02). In addition, there was an inverse correlation between the change in the lowest oxygen saturation during the night and the change in residual volume (- r = 0.5, p = 0.04) and functional residual capacity (- r = 0.6, p = 0.03). CONCLUSION: In patients with severe emphysema, LVRS, but not continued optimal medical therapy, results in improved sleep quality and nocturnal oxygenation. Improvements in nocturnal oxygenation correlate with improved airflow and a decrease in hyperinflation and air trapping.     

Successful lung volume reduction surgery in a child with severe airflow obstruction and hyperinflation due to constrictive bronchiolitis

Lung volume reduction surgery (LVRS) may improve pulmonary function in patients with severe emphysema. However, its effects in other types of obstructive lung disease are unknown. To delay the need for lung transplantation, we performed LVRS in a 14-year-old boy with disabling airflow obstruction/hyperinflation secondary to postinfectious bronchiolitis nonresponsive to medical therapy. Within days after LVRS, a major improvement of symptoms and lung function occurred and persisted for > 1 year. Our observation suggests that LVRS may be a novel treatment option in selected patients with extreme hyperinflation even if the underlying disease is not emphysema.     

Lung function after bilateral lower lobe lung volume reduction surgery for alpha1-antitrypsin emphysema.

This study explores the mechanism(s) of airflow limitation following lung volume reduction surgery (LVRS) in patients with emphysema due to homozygous alpha1-antitrypsin (AT) deficiency. Bilateral targeted lower lobe stapled LVRS using video thoracoscopy was performed in six patients (five males) aged 61+/-9 yrs (mean+/-SD) with alpha1-AT emphysema. Two patients received only a 6-month follow-up. However, four patients, at 22, 24, 27 and 36 months post-LVRS, noted relief from dyspnoea and increased walk tolerance. At 27+/-6 months (mean+/-SD) post-LVRS, their forced expiratory volume in one second improved only from 30+/-2% of the predicted value (mean+/-SEM) before surgery to 33+/-1% pred after surgery. Yet, total lung capacity (TLC) decreased from 151+/-13 to 127+/-10% pred; diffusing capacity increased from 35+/-9 to 59+/-9% pred; and vital capacity increased from 68+/-10 to 88+/-5% pred. In three patients, static lung elastic recoil at TLC increased from 1.1+/-0.15 to 1.2+/-0.10 kPa. Using flow/pressure curves, the mechanism for expiratory airflow limitation pre-LVRS and the improvement noted post-LVRS could be primarily accounted for by the initial loss and subsequent increase in lung elastic recoil. Bilateral lung volume reduction surgery provides modest physiologic improvement for 2-3 yrs in patients with alpha1-antitrypsin emphysema due to increases in lung elastic recoil.     

Successful lung transplantation following lung volume reduction surgery

BACKGROUND: Lung volume reduction surgery (LVRS) is an accepted treatment modality for patients with advanced emphysema. Recently, successful lung transplantation (LTX) has been reported following LVRS. We assess the pulmonary functions in lung transplant recipients after LVRS. METHODS: 8 patients - 5 males and 3 women--aged 53-66 years with advanced emphysema underwent LVRS. Following clinical deterioration and decline of pulmonary function, patients underwent single LTX. Post transplantation follow-up included pulmonary function, 6 minute walk distance (6 MWD) and recording perioperative complications. RESULTS: Median forced expiratory in one second (FEV 1) before and after LVRS were 24 % with 31 % predicted, respectively. All but one showed improvement in lung function and 6 MWD following LVRS. Median maximal 6 MWD before and after LVRS was 222 and 316 meters, respectively. Median time from LVRS to LTX was 46 months (range 10-83). All patients survived and were discharged after LTX. Median FEV1 before and after LTX was 23 % with 57 % predicted, respectively. Median 6MWD before and after LTX was 240 and 462 meters, respectively. NYHA classes improved from 3-4 to 1-2 in 7 surviving patients. At transplantation, bleeding due to pleural adhesions was observed in 4 patients; two required blood transfusions. One patient developed acute respiratory distress syndrome and one had unilateral vocal cord paralysis. At nine-month follow-up, 7 patients are doing remarkably well, while one patient died 6 months after LTX due to bronchiolitis obliterans syndrome (BOS). CONCLUSIONS: LVRS is a therapeutic option in patients with end-stage emphysema. When emphysema deteriorates, LTX can be successfully performed with significant improvement of quality of life without significant additional risk.     

Correlation of changes in quality of life after lung volume reduction surgery with changes in lung function, exercise, and gas exchange

STUDY OBJECTIVES: To evaluate correlations between improvement in quality of life (QOL) in patients with severe COPD before and after they undergo lung volume reduction surgery (LVRS) with changes in pulmonary function tests, gas exchange, exercise performance, and alterations in medical management. DESIGN: Case-series analysis. SETTING: University hospital. PATIENTS: Forty-two patients (mean [+/- SD] age, 56+/-8 years; 53% women) with severe airflow obstruction (FEV(1), 0.62+/-0.2 L), and moderate to severe hyperinflation (total lung capacity [TLC], 6.9+/-1.7 L). INTERVENTION AND MEASUREMENTS: All patients underwent bilateral LVRS via median sternotomy. Measurements of lung function, symptom-limited cardiopulmonary exercise testing, the total distance the patient was able to walk in 6 min in a corridor, and sickness impact profile (SIP) scores were made before and 3 months after LVRS. SIP scores are inversely proportional to the level of function and QOL. RESULTS: Compared to baseline, FEV(1) increased (0.87+/-0.3 vs. 0.62+/-0.2 L, respectively; p<0.01) while residual volume significantly decreased (3.2+/-1.8 vs. 6.3+/-1.2 L, respectively; p<0.004) at 3 months post-LVRS. On cardiopulmonary exercise testing, values increased from baseline to post-LVRS for total exercise time (9.0+/-2.2 vs. 6.0+/-1.5 min, respectively; p = 0.045), maximum oxygen uptake (VO(2)) (16+/-3 vs. 11+/-2 mL/kg/min, respectively; p = 0.01), and maximum minute ventilation (VE) (33+/-9 vs. 28+/-5 L/min, respectively; p = 0.03). The percentage change in the oxygen cost of breathing (VO2/VE ratio) from low to high workloads during exercise was significantly lower after LVRS (p = 0.002). There was no significant change in oxygenation after LVRS (PaO(2)/fraction of inspired oxygen, 331+/-27 vs. 337+/-39, respectively; p = 0.76), but PaCO(2) tended to be lower (41+/-9 vs. 48+/-6 mm Hg, respectively; p = 0.07). Overall SIP scores were significantly lower after LVRS than before (8+/-4 vs. 15+/-2, respectively; p = 0.002). Changes in SIP scores correlated with the change in VO2/VE ratio from low to high workloads, with patients having the smallest changes in VO2/VE ratio having the smallest changes in SIP scores after LVRS (r = 0.6; p = 0.01). Improved or lower SIP scores also tended to correlate with a reduction in residual volume/TLC ratio (r = 0.45; p = 0.09), and there was a linear correlation with a statistically significant Pearson r value with decreased steroid requirements (r = 0.7; p = 0.001). Moreover, changes in psychological SIP subscore tended to correlate with diminished oxygen requirements post-LVRS (r = 0.45; p = 0.09). However, there was no significant correlation between changes in SIP scores and routine measurements of lung function, exercise performance, or gas exchange. CONCLUSION: There is an association between an improvement in QOL and reduced hyperinflation after LVRS. Reduced hyperinflation may lead to more efficient work of breathing during exercise and, therefore, to an increased ability to perform daily activities. Changes in QOL scores correlate best with behaviorally based variables that directly affect the patient's well-being, such as systemic steroid administration.     

Lung volume reduction surgery vs medical treatment: for patients with advanced emphysema

OBJECTIVE: To contribute to the knowledge on the therapeutic value of lung volume reduction surgery (LVRS). DESIGN: Two similar, independently conceived and conducted, multicenter, randomized clinical trials. SETTING: The Canadian Lung Volume Reduction (CLVR) study and the Overholt-Blue Cross Emphysema Surgery Trial (OBEST). METHODS: Using a fixed-effects meta-analysis, the 6-month results produced by the addition of LVRS to optimal medical therapy were compared to those obtained from optimal medical therapy alone. Patients were required to have severe emphysema, marked airflow limitation (ie, FEV(1), 15 to 40% predicted), hyperinflation (total lung capacity [TLC], > 120% predicted), CO(2), < 55 mm Hg, and measurable dyspnea (chronic respiratory disease questionnaire [CRDQ] scores /= 1 for the OBEST). Optimal medical therapy included pulmonary rehabilitation in both arms of both studies. RESULTS: The CLVR study randomized 58 patients and the OBEST randomized 35 patients for a total of 93 patients. Of these, 54 patients were randomized to undergo surgery, and 39 patients were randomized to receive medical treatment. The 6-month mortality rate (including operative mortality) in the surgical and medical cohorts was similar (5.6% vs 5.1%, respectively). A comparison of the medical and surgical arms of the combined CLVR study/OBEST population showed that LVRS was associated with a higher FEV(1) (167 mL or 24% predicted; 95% confidence interval [CI], 29 to 304; p = 0.017), lower residual volume (-1,342 mL or 24.5% predicted; 95% CI, -1,844 to -840; p < 0.001), lower TLC (-1,044 mL or 13% predicted; 95% CI, -1483 to -605; p < 0.001), and higher 6-min walk distance (148.8 feet; 95% CI, 24.3 to 273.2; p = 0.019). Each domain of the CRDQ showed statistically significant improvement in the surgical arm of the study, but not in the medical arm. The summary physical component scale of the Medical Outcomes Study 36-item short form (SF-36) was also more favorable in the LVRS cohort (6.9; 95% CI, 2.86 to 10.90; p < 0.001). The summary mental component scale of the SF-36 did not show a statistically significant difference between the two groups. CONCLUSION: Six months after randomization, LVRS produced better palliation than optimal medical therapy in patients with advanced emphysema.     

Weight gain after lung volume reduction surgery is not correlated with improvement in pulmonary mechanics

STUDY OBJECTIVES: Malnutrition and low body weight are common in patients with emphysema. Previous work has demonstrated correlation between severity of airflow obstruction and body weight. Lung volume reduction surgery (LVRS) is a recent advance in the treatment of patients with severe emphysema that results in improved pulmonary function. We formed the hypothesis that improved lung mechanics after LVRS would result in body weight gain. DESIGN: Retrospective chart review. PATIENTS: All patients who underwent bilateral LVRS for severe emphysema at the University of Michigan between January 1995 and April 1996 were eligible for the study. MEASUREMENTS AND RESULTS: Pulmonary function and body weight were measured preoperatively and at 3, 6, and 12 months postoperatively for patients who underwent bilateral LVRS between January 1995 and April 1996. The average weight gain in 38 patients returning for 12 months of follow-up was 3.8 +/- 0.9 kg, or 6.2% of the preoperative weight. Women gained significantly more weight than men (9.2 vs 2.2%, respectively) at 1 year. Interestingly, there was no correlation between change in weight and postoperative change in FEV(1), FVC, residual volume (RV), total lung capacity (TLC), or RV/TLC at 12 months. However, there was a statistically significant correlation between weight gained and improvement in diffusion of carbon monoxide measured 12 months postoperatively. CONCLUSIONS: This study shows that patients with severe emphysema gain weight after LVRS. These changes were independent of changes in pulmonary mechanics but may be a result of improved gas exchange. These findings provide further information about benefits of LVRS in patients with advance emphysema that are beyond simple changes in pulmonary function.     

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.     

Interpreting improvement in expiratory flows after lung volume reduction surgery in terms of flow limitation theory

Spirometry and pulmonary mechanics were measured pre- and postoperatively in 37 patients undergoing bilateral lung volume reduction surgery (LVRS). The relative contributions of changes in compliance (CL), recoil pressures (PTLC), small airway conductance (Gu), and airway closing pressures (Ptm') to changes in expiratory flows were examined with a Taylor series expansion of the Pride- Permutt model of flow limitation. The resulting variational expression, deltaVmax = GudeltaPel + PeldeltaGu - GudeltaPtm' - Ptm'deltaGu - deltaGudeltaPtm', was then used to describe how the peak flow rate (Vmax) depends on preoperative Gu, P TLC, Ptm', and on changes (delta) in these parameters after surgery. After LVRS, both FEV(1) and Vmax increased significantly ( DeltaFEV(1) = 28 +/- 44%; DeltaVmax = 78 +/- 132%), and changes in FEV(1) and Vmax correlated closely (r = 0.74, p < 0.001). Among responders (DeltaFEV(1) > or = 12%; n = 19; DeltaFEV(1) = 60 +/- 38%), PTLC increased (8.8 +/- 2.8 to 12.2 +/- 4.7 cm H2O) and the time constant for expiration (tau = CL/Gu) decreased (2.67 +/- 0.62 to 2.35 +/- 0.55 s), while Ptm', CL, and Gu did not change. GudeltaPel, the change in recoil weighted by preoperative conductance upstream of the flow-limiting site, accounted for 72% of the improvement in Vmax. Among nonresponders ( DeltaFEV(1) = -6 +/- 15%, n = 18), tau increased significantly, contributing to a decline in FEV(1)/FVC ratio. PeldeltaGu decreased (-0.25 +/- 0.68, p = 0.013), accounting for all of the decline in Vmax. This analysis suggests that (1) improvement in expiratory flows after LVRS is largely due to increases in recoil pressure; (2) large improvements in FEV(1) can occur without changes in Gu or Ptm', arguing that LVRS has little effect on airway resistance or closure; and (3) large changes in PTLC can occur without changes in CL, supporting arguments of Fessler and Permutt (Am J Respir Crit Care Med 1998;157:715-722) that "resizing of the lung to chest wall" is the primary mechanism by which LVRS improves lung function.     

Model-based versus clinical prediction of the spirometric response to lung volume reduction surgery

BACKGROUND: Lung volume reduction surgery (LVRS) improves symptoms and lung function in selected patients with severe emphysema. OBJECTIVES: We investigated whether models based on physiologic and radiologic predictors discriminated patients with a favorable from those with a poor spirometric response to LVRS. METHODS: Data of a derivation cohort of 70 patients who had previously undergone LVRS served to develop two types of prediction models, lookup functions and logistic regression equations. Presence or absence of improvement in forced expiratory volume in 1 s (FEV1) > or =300 ml and forced vital capacity (FVC) > or =500 ml represented dichotomous outcomes. The residual volume/total lung capacity ratio, CT-radiological emphysema heterogeneity scores and diffusing capacity, a marker of emphysema severity, were the predictors. Models were used to predict spirometric outcomes for a validation cohort of 60 emphysema patients referred for LVRS. Furthermore, the surgeon preoperatively estimated outcomes based on all available clinical data but blinded to model predictions. Spirometric changes within 6 months following surgery were compared to predictions. RESULTS: Median FEV1 in the validation cohort increased from 0.69 to 1.00 liters (+41%), and FVC from 2.07 to 2.78 liters (+29%; p < 0.05 for changes). Lookup functions and logistic regression equations identified patients experiencing major increases in FEV1 > or =300 ml and FVC > or =500 ml with an accuracy quantified by areas under the receiver-operating characteristic curves of 0.72 to 0.76 (all areas >0.5, p < 0.05). Predictions by the surgeon had an accuracy of 0.71 to 0.78 (p = NS vs. models). CONCLUSIONS: The accuracy of models based on three predictors was fair and similar to assessment by an experienced surgeon based on all available clinical information. Prediction models may contribute to the consistent assessment of LVRS candidates.     

Lung volume reduction surgery as a bridge to lung transplantation

Lung volume reduction surgery (LVRS) improves lung function, exercise capacity, and quality of life in patients with advanced emphysema. In some patients with emphysema who are candidates for lung transplantation, LVRS is an alternative treatment option to lung transplantation, or may be used as a bridge to lung transplantation. Generally accepted criteria for LVRS include severe non-reversible airflow obstruction due to emphysema associated with significant evidence of lung hyperinflation and air trapping. Both high resolution computed tomography (CT) scan of the chest and quantitative ventilation/perfusion scan are used to identify lung regions with severe emphysema which would be used as targets for lung resection. Bilateral LVRS is the preferred surgical approach compared with the unilateral procedure because of better functional outcome. Lung transplantation is the preferred surgical treatment in patients with emphysema with alpha1 antitrypsin deficiency and in patients with very severe disease who have homogeneous emphysema pattern on CT scan of the chest or very low diffusion capacity.     

Risk factors for near-fatal asthma

BACKGROUND: There is a paucity of lung function data in patients, both before and after episodes of near-fatal asthma (NFA), requiring transient endotracheal intubation and mechanical ventilation. METHODS: Lung function was initially measured in 43 asthmatic patients (age range, 16 to 49 years), who were observed and treated in a tertiary referral asthma clinic and were clinically stable at the time of study. Subsequently, clinical and physiologic follow-up studies were obtained over > 5 years. The primary outcomes were to determine (1) the integrity of lung elastic recoil and (2) the severity of expiratory airflow limitation, and (3) to correlate these outcomes with adverse clinical complications. RESULTS: Fourteen of 26 asthmatic patients (54%) [age range, 30 to 49 years] had significantly reduced lung elastic recoil pressures at all lung volumes compared to 3 of 17 asthmatic patients (18%); p = 0.02 [chi(2) test and Fisher exact test] [age range, 16 to 26 years]. In asthmatic patients between the ages of 30 and 49 years, significant loss of lung elastic recoil was noted in 4 of 10 patients with mild reduction in FEV(1) (FEV(1), > 79% predicted), 6 of 12 patients with moderate reduction in FEV(1) (FEV(1), 61 to 79% predicted), and all 4 patients with severe reduction in FEV(1) (FEV(1), < 61% predicted). In asthmatic patients between the ages of 16 and 26 years, significant loss of lung elastic recoil was noted in 0 of 11 patients with mild reduction in FEV(1), 2 of 5 patients with moderate reduction in FEV(1), and 1 of 1 patient with severe reduction in FEV(1). A subgroup of 10 asthmatic patients (7 men) [mean (+/- SD) age, 37 +/- 11 years] were studied when clinically stable, both before and after an episode of NFA in 8 cases and only after an episode of NFA in 2 additional cases. In 1 of 10 cases, the FEV(1) was mildly reduced, in 4 cases it was moderately reduced, and in 5 cases it was severely reduced, both before and after an episode of NFA. The sensitivity was 90%, the specificity was 61%, the positive predictive value was 41%, and the negative predictive value was 95% for NFA with an FEV(1) < or = 79% predicted or FEV(1)/FVC ratio of < 75%. Prior to an episode of NFA, all 8 asthmatic patients had significant loss of lung elastic recoil pressure, and afterward all 10 had significant loss of lung elastic recoil pressure (ie, less than the predicted normal mean minus 1.64 SD at a total lung capacity [TLC] of 100 to 70% predicted). The sensitivity was 100%, the specificity was 79%, the positive predictive value was 59%, and the negative predictive value was 100% for NFA with the loss of lung elastic recoil. The mean TLC measured with a plethysmograph in 10 patients with NFA was 7.2 +/- 1.41 (124 +/- 16% predicted). The sensitivity for TLC of > 115% predicted was 70%, the specificity was 70%, the positive predictive value was 88%, and the negative predictive value was 41% for NFA. CONCLUSION: A persistent reduction in FEV(1) of < or = 79% predicted or an FEV(1)/FVC ratio of < 75%, and, especially, the loss of lung elastic recoil and hyperinflation at TLC are risk factors for NFA. The loss of lung elastic recoil in asthmatic patients was associated with increased age, duration of disease, and progressive expiratory airflow limitation.     

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.     

Functional and morphological heterogeneity of emphysema and its implication for selection of patients for lung volume reduction surgery.

Lung volume reduction surgery (LVRS) in patients with advanced pulmonary emphysema aims to alleviate symptoms and enhance quality of life by improving respiratory mechanics. The theoretical concepts of the operation predict the greatest functional benefit in patients with marked hyperinflation, and with airflow obstruction due to loss of elastic recoil. Consistent observations in several centres, have confirmed these expectations. To achieve maximal reduction in lung volume at the least cost of functional tissue, resection is targeted to the lung zones with the most severe destruction by emphysema, leaving zones with relatively well-preserved tissue intact. Heterogeneity in emphysema distribution as assessed by visual scoring of the chest computed tomography scan according to a simple grading system has been shown to correlate with LVRS outcome variables. Therefore, evaluation of lung volume reduction surgery candidates has to include the functional and morphological characteristics of the emphysema as well as a general assessment of perioperative risk. However, the knowledge of potential predictive factors of lung volume reduction surgery outcome is so far based on retrospective analysis of highly selected patients. Therefore, many questions in respect of the selection of ideal candidates for this procedure remain unanswered at the present time.     

Densitometry for assessment of effect of lung volume reduction surgery for emphysema.

To explore if change in the extent of emphysema correlated with change in lung function, the effect of resection of emphysematous tissue was studied by computed tomography (CT) densitometry. In addition, the current authors studied how surgery-induced change in emphysema related to lung density in control subjects. In total, 30 patients (14 females; mean+/-sd age 59+/-10 yrs) with severe emphysema before and 3 months after lung volume reduction surgery (LVRS), 48 patients with moderate emphysema and 76 control subjects were investigated. Lung density (15th percentile point) of both lungs and heterogeneity of lung density between 12 isovolumetric partitions in each lung were calculated from chest CT images. The 15th percentile point and its heterogeneity could distinguish controls from subjects with moderate emphysema with a sensitivity and specificity of >95%. LVRS significantly increased lung density by 5.0+/-10.9 g.L(-1) (n=30). Improvement in the diffusing capacity of the lung for carbon monoxide and in residual volume significantly correlated with an increase in lung density (n=20 and 28, respectively). Change in forced expiratory volume in one second did not correlate with change in lung density. In conclusion, lung density 15th percentile point is a valuable surrogate marker for detection of both the extent of and reduction in emphysema.     

Preoperative severity of emphysema predictive of improvement after lung volume reduction surgery: use of CT morphometry

STUDY OBJECTIVE: To determine how the volume and severity of emphysema measured by CT morphometry (CTM) before and after lung volume reduction surgery (LVRS) relates to the functional status of patients after LVRS. DESIGN: A histologically validated CT algorithm was used to quantify the volume and severity of emphysema in 35 patients before and after LVRS: total lung volume (TLV), normal lung volume (< 6.0 mL gas per gram of tissue), volume of mild/moderate emphysema (ME; 6.0 to 10.2 mL gas per gram of tissue), volume of severe emphysema (> 10.2 mL gas per gram of tissue), surface area/volume (SA/V; meters squared per milliliter), and surface area (SA; meters squared). Outcome parameters included maximal cardiopulmonary exercise (CPX) performance in 21 patients and routine pulmonary function in all patients. We hypothesized that baseline CTM parameters predict response to LVRS and that the change in these parameters may offer insight into mechanisms of improvement. PATIENTS AND INTERVENTION: Thirty-five patients with severe emphysema who had successful LVRS. RESULTS: The significant decrease in TLV following LVRS was entirely accounted for by a decrease in severe emphysema. The SA/V and the SA both increased significantly following LVRS. The change in maximal CPX in watts following surgery correlated significantly with baseline values of severe emphysema (r = 0.60), which was collinear with TLV, and SA/V. The change in diffusing capacity of the lung for carbon monoxide revealed a significant positive linear relationship with preoperative severe emphysema (r = 0.37) and a negative relationship with ME (r = -0.37). Change in watts revealed a strong relationship with changes in severe emphysema (r = -0.75) and weaker but significant relationships with change in TLV, ME, SA/V, and SA. Other measures of pulmonary function revealed significant albeit less dominant relationships with baseline CTM and change in these indexes. CONCLUSION: Using CTM, we have identified a close relationship between baseline severe emphysema, or change in severe emphysema, and the improvement in CPX after LVRS. These observations support a potential role of CTM in future clinical trials for predicting responders to LVRS and identifying mechanisms of improvement.     

The relationship between pulmonary function tests, thorax HRCT, and quantitative ventilation-perfusion scintigraphy in chronic obstructive pulmonary disease

We have evaluated the relationship between pulmonary function tests (PFT), thorax high resolution computed tomography (HRCT) images and quantitative ventilation-perfusion (V/Q) scintigraphic studies in 16 male patients (mean age 65.6 +/- 5.5 years) with chronic obstructive pulmonary disease (COPD). The mean forced vital capacity (FVC) value of the patient group was 2352 +/- 642 mL (65.4 +/- 15.8%), whereas mean forced expiratory volume in one second (FEV(1)) was found to be 1150 +/- 442 mL (40.8 +/- 14.9%). The ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) was 3.17 +/- 0.88 mL/min/mmHg/L, and the mean partial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) pressures were 68.5 +/- 11.04 mmHg and 38.9 +/- 5.8 mmHg respectively. For each patient, thorax HRCT and V/Q scintigraphic images of both lungs were divided into upper, mid and lower zones during examination. Visual scoring for the assessment of emphysema on thorax HRCT were used and images were graded from mild to severe (< or = 25% - > or = 76%). Emphysema scores were found to be higher on upper zones with accompanying lowest V/Q ratios. DLCO/VA, DLCO, total emphysema scores, and individual emphysema scores of the upper, mid and lower zones were found to be correlated. As a conclusion, it can be stated that emphysematous changes in COPD patients are more apparent in the upper lung zones, which also have the lowest V/Q ratios.