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Can CT Measurement of Emphysema Severity Aid Patient Selection for Lung Volume Reduction Surgery?
CHEST
editorials VOLUME 118 / NUMBER 5 / NOVEMBER, 2000
Can CT Measurement of Emphysema Severity Aid Patient Selection for Lung Volume Reduction Surgery? it seemed a paradox that the surgical I nitially, removal of lung tissue in patients with severe
emphysema resulted in improvement in pulmonary mechanics, symptoms, and exercise capacity. The data now emerging have explained this largely on the basis of an increase in lung elastic recoil and improvement in respiratory muscle function. Changes in lung structure due to emphysema leads to a “mismatch” in the size of the patient’s lung and chest wall. The lung is too large for the chest wall, placing the diaphragm in a flat and short position, which is suboptimal for force generation. Conversely, the chest wall is too small to allow the lung to expand to a volume at which elastic recoil pressures are high enough to maintain adequate flow rates and tether airways to avoid air trapping. The removal of lung tissue allows the remaining lung to expand enough to achieve a more normal recoil pressure, maintaining the patency of surrounding airways, and increasing the driving pressures for expiratory flow. FEV1, FVC, and measures of hyperinflation, most particularly the ratio of residual volume (RV) to total lung capacity (TLC), all improve. The smaller lung allows recovery to normal diaphragmatic curvature and force generation. Hidden in the group mean responses is the considerable variability of individual patient outcomes. Many important questions remain regarding patient selection, the duration and mechanisms of the observed improvement, and whether the benefit exceeds that observed from pulmonary rehabilitation alone. The National Emphysema Treatment Trial (NETT), a multicenter, randomized, controlled trial sponsored by the National Institutes of Health, will address these issues.1 Intuitively, it seems wise to target the most severe areas of emphysema for resection. These areas have little function and compress more normal, neighboring lung. Targeted removal of severe emphysema identified by imaging techniques has been the practice, and data suggest that patients with more heter-
ogeneous involvement of the lung have better outcomes after lung volume reduction surgery (LVRS). Others have suggested that much of the benefit of LVRS is purely the result of reducing hyperinflation, ie, matching the size of the lung and the chest wall, and could be accomplished by removing normal lung.2 In this issue of CHEST (see page 1240), Rogers and colleagues present their data showing that CT morphometry, an objective, computerized algorithm for partitioning the volume of the lung into three compartments based on density (severe emphysema, mild/moderate emphysema, and normal), predicts response to LVRS and suggests mechanisms leading to improvement. By using contiguous 10-mm slices, the volume of the lung in each of the three compartments can be measured. The primary outcome variable was improvement in exercise capacity, measured in watts on a cycle ergometer. The extent of improvement correlated with baseline total lung volume (TLV) and severe emphysema volume, measured by CT. Multiple regression analysis indicated that severe emphysema volume alone, without TLV, accounted for the response. This suggests that the higher the baseline severe emphysema, the greater the improvement in exercise capacity after LVRS. This may have a role in patient selection if confirmed in larger studies. In terms of mechanisms, the study indicated that the reduction in TLV was entirely due to a reduction in severe emphysema. This may seem obvious since the surgeon targets severe emphysema for removal. However, stapling techniques result in removal of some areas of mild/moderate emphysema (ME) and normal lung (NL) along with the severe emphysema. The lack of change in the volume of these compartments, despite some unavoidable resection, suggests reexpansion of NL and ME, and perhaps shifts of ME to severe emphysema. This study confirms others showing a mean improvement in lung mechanics. LVRS has resulted in a variable effect on diffusing capacity of the lung for carbon monoxide (Dlco), and this study showed no change in group mean Dlco. A low Dlco, when accompanied by reduced expiratory flow and hyperinflation, correlates well with overall emphysema severity. This has been explained by the loss of capillary bed by destruction in areas of emphysema. CHEST / 118 / 5 / NOVEMBER, 2000
1231
Functional and reversible loss of regional pulmonary perfusion may also result from compression of lung in areas adjacent to severe emphysema. In addition, an overall reduction in lung perfusion due to cardiopulmonary interaction, partially caused by intrinsic positive end-expiratory pressure associated with dynamic hyperinflation, may also reduce Dlco. In this study, the proportion of the lung in the severe emphysema and ME partitions accounted for individual patient changes in Dlco. The higher the baseline severe emphysema fraction of lung, the greater the increase in Dlco after LVRS. This suggests that surgical removal of severe emphysema results in excision of few capillaries, and the recruitment of previously compressed, neighboring lung and its vascular bed predominates. By contrast, the higher the baseline ME fraction of lung, the greater the decrease in Dlco. This suggests that net removal of capillaries predominates in such patients. In this study, the change in severe emphysema volume best accounted for the improvement in exercise capacity, FEV1, RV, and TLC. This suggests that the better the surgery achieves its goal of removing severe emphysema, the better the resulting functional result. Perhaps other CT approaches that incorporate regional distribution of the emphysema would better predict response and provide a map for the surgeon. Using another quantitative CT technique, Gierada and colleagues3 found that better outcomes after LVRS were associated with a higher severe emphysema index, upper-lobe predominance, more heterogeneity, and volume of normal-attenuation lung ⬎ 1 L. This latter feature suggests that adequate amounts of normal or near-normal lung need to be present for optimal results. McKenna and associates4 report that the best outcomes were found with a bilateral heterogeneous pattern of emphysema with upper-lobe predominance on CT and perfusion scans. Weder and colleagues5 used a simplified subjective classification of CT and found that degree of heterogeneity predicted outcome, but emphasize that even patients with homogenous patterns improved after LVRS, although to a smaller extent. In another study from the same group, multiple regression analysis found that functional improvement after LVRS was most closely correlated with preoperative hyperinflation (RV/TLC) and heterogeneity measured by CT.6 Heterogeneity on CT predicted improvement better than heterogeneity on lung perfusion scans. However, the perfusion scans were still used to guide target areas for resection in those with homogenous CT patterns. The two techniques may provide complementary information, since CT is an anatomic technique and perfusion scanning is a functional technique. Some measure of heterogeneity is likely to be 1232
important in patient selection given a model in which decompression of normal and less-diseased lung is an important mechanism for improvement. Global pulmonary function testing measurements do not capture this, and imaging techniques are well suited to this role. It is likely that no single parameter will adequately identify the ideal candidate for LVRS, as correlation coefficients have only been in the moderate range. It appears today that degree of hyperinflation and a heterogeneous pattern of severe emphysema are the best predictors of improvement. A consensus on the best method for describing CT severity and heterogeneity has yet to emerge. Data from the NETT trial should be helpful. Steve H. Salzman, MD, FCCP New York, NY Dr. Salzman is Director, Pulmonary Function Laboratories, Beth Israel Medical Center, and Associate Professor of Clinical Medicine, Albert Einstein College of Medicine, New York, NY. Correspondence to: Steve H. Salzman, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Beth Israel Medical Center, First Ave at 16th St, New York, NY 10003; e-mail: [email protected]
References 1 NETT Research Group. Rationale and design of the National Emphysema Treatment Trial: a prospective randomized trial of lung volume reduction surgery. Chest 1999; 116:1750 –1761 2 Fessler HE, Permutt S. Lung volume reduction surgery and airflow limitation. Am J Respir Crit Care Med 1998; 157:715– 722 3 Gierada DS, Slone RM, Bae KT, et al. Pulmonary emphysema: comparison of preoperative quantitative CT and physiologic index values with clinical outcome after lung-volume reduction surgery. Radiology 1997; 205:235–242 4 McKenna RJ Jr, Brenner M, Fischel RJ, et al. Patient selection criteria for lung volume reduction surgery. J Thorac Cardiovasc Surg 1997; 114:957–967 5 Weder W, Thurnheer R, Stammberger U, et al. Radiologic emphysema morphology is associated with outcome after surgical lung volume reduction. Ann Thorac Surg 1997; 64:313–320 6 Thurnheer R, Engel H, Weder W, et al. Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery. Am J Respir Crit Care Med 1999; 159:301–310
How Much Adult Asthma Can Be Attributed to Occupational Factors (Revisited)? asthma (OA) is a disease characterO ccupational ized by variable airflow limitation and/or airway hyperresponsiveness due to causes and conditions
Editorials
editorials VOLUME 118 / NUMBER 5 / NOVEMBER, 2000
Can CT Measurement of Emphysema Severity Aid Patient Selection for Lung Volume Reduction Surgery? it seemed a paradox that the surgical I nitially, removal of lung tissue in patients with severe
emphysema resulted in improvement in pulmonary mechanics, symptoms, and exercise capacity. The data now emerging have explained this largely on the basis of an increase in lung elastic recoil and improvement in respiratory muscle function. Changes in lung structure due to emphysema leads to a “mismatch” in the size of the patient’s lung and chest wall. The lung is too large for the chest wall, placing the diaphragm in a flat and short position, which is suboptimal for force generation. Conversely, the chest wall is too small to allow the lung to expand to a volume at which elastic recoil pressures are high enough to maintain adequate flow rates and tether airways to avoid air trapping. The removal of lung tissue allows the remaining lung to expand enough to achieve a more normal recoil pressure, maintaining the patency of surrounding airways, and increasing the driving pressures for expiratory flow. FEV1, FVC, and measures of hyperinflation, most particularly the ratio of residual volume (RV) to total lung capacity (TLC), all improve. The smaller lung allows recovery to normal diaphragmatic curvature and force generation. Hidden in the group mean responses is the considerable variability of individual patient outcomes. Many important questions remain regarding patient selection, the duration and mechanisms of the observed improvement, and whether the benefit exceeds that observed from pulmonary rehabilitation alone. The National Emphysema Treatment Trial (NETT), a multicenter, randomized, controlled trial sponsored by the National Institutes of Health, will address these issues.1 Intuitively, it seems wise to target the most severe areas of emphysema for resection. These areas have little function and compress more normal, neighboring lung. Targeted removal of severe emphysema identified by imaging techniques has been the practice, and data suggest that patients with more heter-
ogeneous involvement of the lung have better outcomes after lung volume reduction surgery (LVRS). Others have suggested that much of the benefit of LVRS is purely the result of reducing hyperinflation, ie, matching the size of the lung and the chest wall, and could be accomplished by removing normal lung.2 In this issue of CHEST (see page 1240), Rogers and colleagues present their data showing that CT morphometry, an objective, computerized algorithm for partitioning the volume of the lung into three compartments based on density (severe emphysema, mild/moderate emphysema, and normal), predicts response to LVRS and suggests mechanisms leading to improvement. By using contiguous 10-mm slices, the volume of the lung in each of the three compartments can be measured. The primary outcome variable was improvement in exercise capacity, measured in watts on a cycle ergometer. The extent of improvement correlated with baseline total lung volume (TLV) and severe emphysema volume, measured by CT. Multiple regression analysis indicated that severe emphysema volume alone, without TLV, accounted for the response. This suggests that the higher the baseline severe emphysema, the greater the improvement in exercise capacity after LVRS. This may have a role in patient selection if confirmed in larger studies. In terms of mechanisms, the study indicated that the reduction in TLV was entirely due to a reduction in severe emphysema. This may seem obvious since the surgeon targets severe emphysema for removal. However, stapling techniques result in removal of some areas of mild/moderate emphysema (ME) and normal lung (NL) along with the severe emphysema. The lack of change in the volume of these compartments, despite some unavoidable resection, suggests reexpansion of NL and ME, and perhaps shifts of ME to severe emphysema. This study confirms others showing a mean improvement in lung mechanics. LVRS has resulted in a variable effect on diffusing capacity of the lung for carbon monoxide (Dlco), and this study showed no change in group mean Dlco. A low Dlco, when accompanied by reduced expiratory flow and hyperinflation, correlates well with overall emphysema severity. This has been explained by the loss of capillary bed by destruction in areas of emphysema. CHEST / 118 / 5 / NOVEMBER, 2000
1231
Functional and reversible loss of regional pulmonary perfusion may also result from compression of lung in areas adjacent to severe emphysema. In addition, an overall reduction in lung perfusion due to cardiopulmonary interaction, partially caused by intrinsic positive end-expiratory pressure associated with dynamic hyperinflation, may also reduce Dlco. In this study, the proportion of the lung in the severe emphysema and ME partitions accounted for individual patient changes in Dlco. The higher the baseline severe emphysema fraction of lung, the greater the increase in Dlco after LVRS. This suggests that surgical removal of severe emphysema results in excision of few capillaries, and the recruitment of previously compressed, neighboring lung and its vascular bed predominates. By contrast, the higher the baseline ME fraction of lung, the greater the decrease in Dlco. This suggests that net removal of capillaries predominates in such patients. In this study, the change in severe emphysema volume best accounted for the improvement in exercise capacity, FEV1, RV, and TLC. This suggests that the better the surgery achieves its goal of removing severe emphysema, the better the resulting functional result. Perhaps other CT approaches that incorporate regional distribution of the emphysema would better predict response and provide a map for the surgeon. Using another quantitative CT technique, Gierada and colleagues3 found that better outcomes after LVRS were associated with a higher severe emphysema index, upper-lobe predominance, more heterogeneity, and volume of normal-attenuation lung ⬎ 1 L. This latter feature suggests that adequate amounts of normal or near-normal lung need to be present for optimal results. McKenna and associates4 report that the best outcomes were found with a bilateral heterogeneous pattern of emphysema with upper-lobe predominance on CT and perfusion scans. Weder and colleagues5 used a simplified subjective classification of CT and found that degree of heterogeneity predicted outcome, but emphasize that even patients with homogenous patterns improved after LVRS, although to a smaller extent. In another study from the same group, multiple regression analysis found that functional improvement after LVRS was most closely correlated with preoperative hyperinflation (RV/TLC) and heterogeneity measured by CT.6 Heterogeneity on CT predicted improvement better than heterogeneity on lung perfusion scans. However, the perfusion scans were still used to guide target areas for resection in those with homogenous CT patterns. The two techniques may provide complementary information, since CT is an anatomic technique and perfusion scanning is a functional technique. Some measure of heterogeneity is likely to be 1232
important in patient selection given a model in which decompression of normal and less-diseased lung is an important mechanism for improvement. Global pulmonary function testing measurements do not capture this, and imaging techniques are well suited to this role. It is likely that no single parameter will adequately identify the ideal candidate for LVRS, as correlation coefficients have only been in the moderate range. It appears today that degree of hyperinflation and a heterogeneous pattern of severe emphysema are the best predictors of improvement. A consensus on the best method for describing CT severity and heterogeneity has yet to emerge. Data from the NETT trial should be helpful. Steve H. Salzman, MD, FCCP New York, NY Dr. Salzman is Director, Pulmonary Function Laboratories, Beth Israel Medical Center, and Associate Professor of Clinical Medicine, Albert Einstein College of Medicine, New York, NY. Correspondence to: Steve H. Salzman, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Beth Israel Medical Center, First Ave at 16th St, New York, NY 10003; e-mail: [email protected]
References 1 NETT Research Group. Rationale and design of the National Emphysema Treatment Trial: a prospective randomized trial of lung volume reduction surgery. Chest 1999; 116:1750 –1761 2 Fessler HE, Permutt S. Lung volume reduction surgery and airflow limitation. Am J Respir Crit Care Med 1998; 157:715– 722 3 Gierada DS, Slone RM, Bae KT, et al. Pulmonary emphysema: comparison of preoperative quantitative CT and physiologic index values with clinical outcome after lung-volume reduction surgery. Radiology 1997; 205:235–242 4 McKenna RJ Jr, Brenner M, Fischel RJ, et al. Patient selection criteria for lung volume reduction surgery. J Thorac Cardiovasc Surg 1997; 114:957–967 5 Weder W, Thurnheer R, Stammberger U, et al. Radiologic emphysema morphology is associated with outcome after surgical lung volume reduction. Ann Thorac Surg 1997; 64:313–320 6 Thurnheer R, Engel H, Weder W, et al. Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery. Am J Respir Crit Care Med 1999; 159:301–310
How Much Adult Asthma Can Be Attributed to Occupational Factors (Revisited)? asthma (OA) is a disease characterO ccupational ized by variable airflow limitation and/or airway hyperresponsiveness due to causes and conditions
Editorials