Preoperative Screening for Lung Volume Reduction Surgery: Usefulness of Combining Thin-Section CT with Physiologic Assessment

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1 Andetta Hunsaker1 Edward Ingenito2 gur TopaI1 Robert Pugatch1 John Reilly2 Received June 9, 1997; accepted afterrevision August27, Department of Radiology,Brigham and Women s Hospital, 75 Francis St., Boston, MA Address correspondence to A. Hunsaker. 2Deparanent of Pulmonary Medicine, Brigham and Women s Hospital,Boston, MA AJR 1998;170: X198/ American Roentgen Ray Society Preoperative Screening for Lung Volume Reduction Surgery: sefulness of Combining Thin-Section CT with Physiologic Assessment OBJECTIVE. This study was performed to assess the usefulness of preoperative thin-seetion CT alone and in combination with physiologic measurements in emphysema patients being evaluated for lung volume reduction surgery. SBJECTS AND METHODS. Six 1-mm collimation sections through the chest were obtamed in 20 patients being evaluated for lung volume reduction surgery. Extent and severity of emphysema were assessed by visually scoring the images. CT scores ranged from 0 to 144. Inspiratory resistance was measured in 12 of 20 patients and was also used to discriminate between responders (change in forced expiratory volume in I see, 150 ml after surgery) and nonresponders (change in forced expiratory volume in 1 sec, <150 ml after surgery). RESLTS. Four of 20 patients with mild emphysema as revealed by thin-section CT (scores of <50) did not improve lung function after lung volume reduction surgery. Eight of the remaining 16 patients with moderate to severe emphysema as revealed by thin-section CT (scores of >50) underwent inspiratory resistance measurement. Those seven patients whose inspiratory resistance measurement exceeded 8.5 cm H20/l per second did not respond favorably to lung volume reduction surgery (change in forced expiratory volume in I sec, <150 ml). The remaining five patients whose inspiratory resistance measurement was less than 8.5 cm H20/l per second responded favorably to lung volume reduction surgery. Thus, only five of the 20 patients showed improvement in forced expiratory volume in 1 sec after surgery. CONCLSION. Our data suggest that among patients with moderate to severe emphysema who are being examined for lung volume reduction surgery, the combination of radiologic and physiologic assessment is more accurate for predicting a favorable response to lung volume reduction surgery than radiologic assessment alone. However, in patients with chronic obstructive pulmonary disease by the American Thoracic Society criteria, mild emphysema as revealed on thin-section CT virtually precludes further workup because these patients are unlikely to re- of disease is likely to optimize functional out- spond favorably to lung volume reduction surgery. R adiologic studies, including come among the subset of patients with focal standard chest radiography, CT disease, most patients with chronic obstruc- scanning, and quantitative ventilation-perfusion scanning, have been established as standard preoperative tests for examining patients for lung volume reduction surgery [I]. These studies provide information about the extent and distribution of tissue destruction. In three series [2-4], directed unifocal or multifocal resection of emphysematous lung tissue based on presurgical radiologic studies has produced results superior to results obtained by undirected surgery or surgery in patients with diffuse disease in whom a directed surgical approach is not deemed applicable. Although resection directed at specific foci tive pulmonary disease screened for lung volume reduction surgery have diffuse disease, and in many centers such patients are not considered candidates for surgery [2-4]. Thus, most individuals may be excluded from potentially beneficial therapy based on radiographic studies alone, with little consideration given to the physiology that governs lung dysfunction in emphysema. Surgical therapy was initially proposed by Brantigan et al. [5] on the basis of the hypothesis that the underlying pathophysiology of emphysema was caused by decreased elastic recoil and the decreased tethering open of airways by adjacent parenchyma as a result of destruction of elastin fi- AJR:170, February

2 Hunsaker et al. bers within the lung interstitium. This process resulted in decreased expiratory recoil pressure and increased dynamic airway collapse during expiration with gas trapping and lung hyperexpansion [6, 7J. Removal of nonfunctioning emphysematous lung should, in theory, increase both elastic recoil and airway tethering, reduce gas trapping, and improve lung function independent of whether disease is diffuse, focal, or multifocal [81. Thus, one can argue that radiographic criteria alone fail to identify many patients who are potential candidates for this procedure. This study compares the usefulness of preoperative lung volume reduction surgery assessment by thin-section CT techniques alone with a combined CT plus physiologic approach. We hypothesize that a combined approach should serve as a superior method over CT analysis alone and identify both surgical candidates with unifocal and multifocal disease and those with more diffuse disease who have physiology amenable to correction by lung volume reduction surgery. We used inspiratory resistance as the physiologic index of choice on the basis of the argument that in chronic obstructive pulmonary disease, two patient populations exist: those with acute emphysema in whom lung dysfunction is primarily caused by parenchymal tissue destruction, decreased elastic recoil, and loss of airway tethering; and those in whom significant intrinsic airway disease related to airway narrowing supersedes the effects of pure emphysema. We concluded that lung resistance measured in inspiration should discriminate between these two groups. Subjects and Methods Patient Selection Twenty patients (nine men and 1 1 women years old), referred to our institution with a diagnosis of emphysema, participated in the present study under an institutionally approved human subjects research protocol. All patients had evidence of severe obstructive lung disease by standard spirometry criteria [91 at the time of presentation (forced expiratory volume in I sec ; predicted forced expiratory volume in I sec. 8-36%), were on maximal medical therapy as determined by their referring physician, and had diminished functional capacity. All participants underwent spirometry. lung resistance measurements during spontaneous breathing, chest CT scanning, cardiac echocardiography at baseline and during dobutamine hydrochloride challenge, and quantitative ventilation-perfusion scanning preoperatively. Each patient met established selection criteria for lung volume reduction surgery based on preoperative test results [10]. a Scanning We used a Somatom Plus CT scanner (Siemens, Iselin, NJ) and, for each patient, obtained six thinsection CT scans (1-mm collimation, 137 kvp ma, 1.0-sec scanning time). The scans were obtained during breath-hold at end inspiration: two scans of the upper lung zones at 3 and 6 cm above the carina; three scans of the lower lung zones at 3, 6, and 9 cm below the carina; and one scan at the level of the carina. The scans were reconstructed using a high-resolution bone algorithm and photographed at a window width (1500 H) and level (-600 H) appropriate for lung detail. CT Scoring Each thin-section scan was scored simultaneously for severity and extent of emphysema by two observers according to the direct observational method oflamers et al. [1 1], Sakai et al. [12], and Klein et al. [ 13]. Discrepancies were resolved by consensus. Severity was graded according to a fourpoint scale: 0, no emphysema; I, all low-attenuation areas smaller than 5 mm in diameter; 2, all circumscribed low-attenuation areas larger than 5 mm in diameter in addition to those circumscribed areas smaller than 5 mm in diameter. and 3, diffuse lowattenuation areas without intervening healthy lung or large, confluent low-attenuation areas. The cxtent of emphysema was also assessed using a fourpoint scale: 1, less than 25% lung involvement; 2, 25-50% lung involvement; 3, 50-75% lung involvement; and 4, more than 75% lung involvement. For each of the 12 lung sections, the score for severity of emphysema was multiplied by that for extent, and the scores were added together to give a total emphysema score. By the method of Sakai et a!., scores from 0 to 144 were possible. Mild disease corresponded to a score of 0-50; moderate disease. a score of ; and severe disease, a score of Heterogeneity was graded by taking the ratio of the sum of scores from the upper six lung zones to the sum of the scores from the lower six lung zones. Values greater than I indicate upper lobe predominant disease, whereas values less than I indicate lower lung disease. Pulmonary Function and Physiologic Evaluation Spirometry was recorded using a model 6000 portable system (Collins; Warren E. Collins, Braintree, MA). Preoperative results were recorded within 3 months of surgery. Postoperative results reported are those determined at 6 months follow-up. Spirometry was performed according to American Thoracic Society guidelines [10], and results represent the best of three measurements recorded. Lung resistance during inspiration was determined (in 12 of the 20 patients) as the transpulmonary pressure drop in phase with flow during inspiration while spontaneously breathing [14]. Transpulmonary pressure. the difference between mouth pressure and pleural pressure, was determined by measuring airway mouth pressure and esophageal pressure, which closely approximates pleural pressure. Esophageal pressures were determined using esophageal balloon catheters inserted after application of topical anesthesia ( 1 % atomized lidocaine) to the nares. Balloons were passed to 40-cm depth, and correct positioning was documented by showing reproducible negative pressure fluctuations during inspiration and minimal fluctuation in transpulmonary pressure during panting against a closed aperture. Flow was measured at the mouth using a Fleisch pneumotachograph (OEM Medical; Rusch, Duluth, GA), and tidal volumes were determined from integration of the flow signal. Calculations of inspiratoty resistance were performed by linear regression fit of transpulmonary pressure, flow, and tidal volume recordings to the equation of motion during inspiration [15]. All recordings were made at 20 breaths per minute, and breathing frequency was controlled by having participants synchronize with a metronome. Reported resistance values represent the average results of recorded breaths during the trial period. Trials were performed in duplicate to ensure reproducibility. Surgical Technique Lung volume reduction surgery was performed using bilateral sequential thoracoscopic plication. Most patients underwent unilateral procedures performed 4-6 weeks apart, separated by a period of rehabilitation and reconditioning. The lung with the least perfusion, as revealed by quantitative ventilation-perfusion scanning. was reduced first. Statistical Anal ysis Comparison between groups was performed by analysis of variance for unpaired samples. Contingency table analysis was performed using Fisher s exact test because sample size precluded chi-square analysis. Relationship dependence analysis was performed using the linear regression method of Pearson [16]. Statistical significance was defined as a p value less than.05. Results CT scores and spirometry measurements were available for all patients, whereas measurements of inspiratory resistance were available for only a subset ( 12/20). Despite differences in emphysema score distribution, all patients had forced expiratory volume in I sec less than 36% predicted by spirometry. For the group as a whole, forced expiratory volume in I sec improved 0.09 ± in response to lung volume reduction surgery. Five of 20 patients showed a significant improvement (>150 ml and >15% increase in forced expiratory volume in 1 sec; change in forced expiratory volume in 1 sec = 0.42 ± ), whereas most patients did not show an improvement (n = 15, change in forced expiratory volume in 1 sec = ± ). Disease severity by CT scoring did not correlate with 310 AJR:170, February 1998

3 Thin-Section CT for Preoperative Screening for Lung Volume Reduction Surgery I Fig year-old woman with severe emphysema. Thin-section CT through upper lobes and superior segments of lower lobes shows diffuse emphysema with minimal visible healthy lung tissue. CT score = 135, preoperative forced expiratory volume in 1 sec = 25% of predicted, inspiratory resistance = 16.4,heterogeneity score = 1.143, and postoperative change in forced expiratory volume in 1 sec = -230 ml. Fig year-old woman with severe emphysema. Thin-section CT shows diffuse emphysema with essentially no residual healthy lung. CT score = 126, preoperative forced expiratory volume in 1 sec = 28% of predicted, inspiratory resistance = 8.9, heterogeneity score = 1.333, and postoperative change in forced expiratory volume in 1 sec = 90 ml. improvement in forced expiratory volume in I sec (ii = 20, r =.30, p =.20). Among patients with mild emphysema shown on CT scans (CT score, 6-40) (ii = 4), none had an improved forced expiratory volume in I sec (change in forced expiratory volume in I sec. <90 nil). In fact. two of these patients had lower forced expiratory volume in I -sec values after lung volume reduction surgery. Although CT scans showed only mild emphysema. these four patients had severe obstructive airways disease as manifested by forced expiratory volume in I sec less than or equal to.57 1 and percentage of predicted forced expiratory volume in I sec less than or equal to 23%. All patients showing a favorable response to lung volume Fig year-old man with severe emphysema. Thinsection CT through upper lobes shows diffuse disease with virtually no healthy residual lung. CT score = 136, preoperative forced expiratoryvolume in 1 sec = 14% of predicted, inspiratory resistance = 4.6, heterogeneity score = 1.125, and postoperative change in forced expiratory volume in 1 sec = 580 ml. Fig year-old man with very mild emphysema and severe dyspnea. Thin-section CT shows minimal centrilobular emphysema and subpleural bullae. CT score = 19, preoperative forced expiratory volume in 1 sec = 18% of predicted, inspiratory resistance = 15.1, heterogeneity score = 2.167, and postoperative change in forced expiratory volume in 1 sec = -60 ml. high scores improved their forced expiratory volume in I sec by 180 ml or more. The remainder improved minimally (<100 ml) or actually experienced a decline in forced expiratory volume in I sec after surgery. Although CT revealed that a 55-year-old woman and a 59-year-old man both had severe disease (Figs. I and 2), their objective responses manifested by postoperative change in forced expiratory volume in I sec were different. The 55-year-old woman (Fig. I) showed worsening of forced expiratory volume in I sec. and the 59-year-old man (Fig. 2) showed significant improvement. Likewise, a 58-year-old man and a 48-year-old woman both had severe emphysema with lung de- Fig yearold man with extensive emphysema. Thin-section CT shows diffuse emphysema involving upper lobes and superior segments of lower lobes. CT score = 132, preoperative forced expiratory volume in 1 sec = 36% of predicted, inspiratory resistance = 5.7, heterogeneity score = 1.045, and postoperative change in forced expiratory volume in 1 sec = 940 ml. volume in I sec by nearly I I and the 48-yearold woman (Fig. 3) improved forced expiratory volume by only 90 ml. CT of a 69-year-old man revealed mild centrilobular emphysema (CT score, 19) (Fig. 5). Despite this condition, the patient. who had no clinical history of asthma. had a forced expiratory volume in I sec consistent with severe airflow obstruction (forced expiratory volume in 1 sec. I 8% of predicted). Among patients with evidence of moderate to severe emphysema, disease heterogeneity expressed as the ratio of upper lobe to lower lobe disease I I I correlated linearly with improvernent in forced expiratory volume in 1 sec after lung volume reduction surgery, although the relationship did not achieve statistical significance (a = 16, r =.47, p =. 067) (Fig. 6). None of the five patients in our group with a heterogeneity score of less than.95 improved after lung volume reduction surgery. Contingency table analysis was performed for patients with moderate to severe disease to determine whether preoperative assessment of the heterogeneity score among mdividuals with significant emphysema might be useful in predicting response to surgery. where a favorable response was defined as an improvement of 150 ml or more in forced cxpiratory volume in I sec after surgery [91. Statistical significance was assessed using Fishers exact test because results from only I 6 patients ( I 6 of the 20 patients with moderate to severe emphysema) were available for analysis. sing a cutoff value of I.0, we found that a heterogeneity score was I 00% reduction surgery had moderate to severe emphysema shown by thin-section CT scanning. However, responders represented a subset of this group because only five of 12 patients with struction that appeared similar (Figs. 3 and 4, respectively)-in fact, similar CT scores-but likewise responded differently; the 58-yearold man (Fig. 2) improved forced expiratory sensitive (5/5) but only 45% specific (5/I I) for identifying candidates for lung volume reduction surgery (p =.19). The positive predictive value of a heterogeneity score of I.0 AJR:170, February

4 Hunsaker et al. was 45% (5/1 1 ), and the negative predictive value was 100% (5/5). A heterogeneity score cutoff of 1. I was I 00% sensitive (5/5) in selecting responders for lung volume reduction surgery and 82% specific (9/1 1 ) in identifying nonresponders. Response rates among patients in the two heterogeneity score groups defined using this criterion were significantly different (p =.005). The positive predictive value of a heterogeneity score of I. I was 7 1% and the negative predictive value was 100% (9/9). Higher heterogeneity score cutoff values resulted in a loss of sensitivity and a negative predictive value. In the subset of 12 patients for whom physiologic results were available, preoperative lung resistance measured during inspiration showed a strong inverse relationship to postoperative improvement in forced expiratory volume in 1 sec after lung volume reduction surgery (r =.72, p =.0081) (Fig. 7). Four of the patients in this group with markedly elevated inspiratory resistance were among those patients with mild emphysema (inspiratory resistance = I 6.6 ± 1.7 cm H2O/1 per second) who failed to improve in response to surgery. Only among patients with moderate to severe emphysema by CT scoring did inspiratory resistance significantly correlate with postoperative outcome. Contingency table analysis by Fisher s cxact test using inspiratory resistance as the mdcpendent predictive parameter showed that a cutoff of 8.5 cm H,O/l per second significantly discriminated between lung volume reduction surgery responders and nonresponders. This physiologic index was 100% sensitive (6/6) and 100% specific (2/2) in identifying a favorable outcome to surgery and had positive and negative predictive values of 100% in this small subset of patients. Discussion The present study suggests that preoperative screening for lung volume reduction surgery combining CT scanning and airway resistance measurements performed during inspiration may be more accurate than CT scanning alone for identifying patients with emphysema who will respond favorably to surgery. CT scanning, particularly thin-section scanning, is an important part of a screening approach using two procedures that can be used to identify a subset of patients in whom lung volume reduction surgery is likely to be ineffective, without the need for additional studies. CT scanning has been shown to be a more sensitive predictor of emphysema than > w 0 0).c 0 0) j 0.4 O.2 o.0-.: W O3-. Heterogeneity Score Inspiratory Resistance (cm H20/l per second) simple spirometry because physiologic changes similar to those of emphysema can occur in small airways disease even in the absence of centrilobular emphysema I 17-20j. Furthermore, visual scoring systems for quantifying emphysema. similar to that employed here, have been shown to correlate well with pathologic grade of disease assessed at autopsy and with densitometry measurements of parenchymal destruction [ I I, 20-25]. But the limitation of CT scanning is that, even though moderate to severe emphysema may be present and the criteria for disease heterogeneity met, those individuals who have a significant component of airway disease cannot be examined adequately with CT alone. In such patients, intrinsic airway disease may be their primary physiologic problem. not the emphysema seen on CT. However, CT scanning alone can eliminate that subset of patients with chronic obstructive pulmonary disease who, despite low forced expiratory volume in 1-sec values (30%), have negligible to mild emphysema (on CT), thus precluding further unnecessary workup. Although our approach relies on preoperative CT assessment, the data also suggest that among patients with more severe emphysema. Fig. 6.-Scatter plot assesses response to surgery in patients with moderate to severe emphysema (n = 16, r =.47, p =.067). Postoperative change in forced expiratoryvolume in 1 sec (FEV1) is plotted against hetero- geneity score. Patients with low het- erogeneity score (<1.1) generally had either no change or a lower forced I expiratory volume in 1 sec postoperatively. Patients with improved forced expiratory volume in 1 sec generally had heterogeneity scores greater than or equal to 1.1. Fig. 7.-Scatter plot compares post- operative improvement in forced expiratory volume in 1 sec (FEV1) with inspiratory resistance (n= 12, r=.72, p =.0081). Improvement is seen in patients with low inspiratory resistance (<8.5 cm H20/l per second). (CT score > 50), physiologic studies can better discriminate between responders and nonresponders than radiologic criteria alone. This finding is likely due to the fact that. whereas CT is sensitive for identifying emphysema in patients with chronic obstructive pulmonary disease, it is not a useful method for detecting coexistent intrinsic airway narrowing or extensive airway destruction and fibrosis, which may be a significant determinant of lung dysfunction in this setting and thus preclude a favorable response to lung volume reduction surgery. In patients with pure emphysema, lung dysfunction is caused by loss of tissue elasticity, with marked reduction in the ability to empty the lungs during expiration as a result of a decrease in lung recoil pressure pushing air out and compression of floppy airways during expiration as intrathoracic pressures become positive. In the absence of significant airway destruction, narrowing due to wall thickening and smooth muscle constriction, or mucous plugging, airflow during inspiration (when intrathoracic pressures are negative and airways are not compressed) should be relatively normal. Thus, measurements of lung physiology during inspiration should identify individuals with significant obstruction re- 312 AJR:170, February 1998

5 Thin-Section CT for Preoperative Screening for Lung Volume Reduction Surgery lated primarily to airway disease rather than to emphysema that is not as readily amenable to equal to 8.5 cm H2O/l per second identified all loss of tethering as a result of parenchymal unifocal or multifocal resection techniques. emphysema patients with moderate to severe emphysema, even if radiologic studies show Our data seem to indicate that among pa- CT scores who responded to lung volume re- evidence of emphysema. The fact that no tients with moderate to severe emphysema by duction surgery with a greater than l50-ml significant dift erence in preoperative forced CT scoring, two patient populations exist: improvement (>15% increase) in forced expi- expiratory volume in I -sec values between those with lung dysfunction primarily as a re- ratory volume in 1 sec. A value of greater than patients with mild, moderate, or severe emphysema by CT scoring is seen supports the argument that, among patients with chronic obstructive pulmonary disease referred for consideration for lung volume reduction surgery, factors other than loss of elastic recoil contribute to airflow obstruction. One can argue that radiologic assessment of disease distribution may provide an additional method for predicting responsiveness to lung volume reduction surgery therapy [ I 1. Surgery directed specifically at unifocal or multifocal resection of regions of emphysema has been shown to produce better physiologic and functional outcomes among patients than undirected surgery. On the basis of these arguments, we examined the relationship between distribution of disease assessed by heterogeneity scoring of CT scans (heterogeneity score >1 = predominant upper lung zone emphysema, heterogeneity score < I = lower lung zone emphysema) and improvement in forced expiratory volume in I sec after lung volume reduction surgery. When only patients with moderate or severe emphysema scores were considered (n = 16). a linear correlation that approached statistical significance was observed (Fig. 7). These findings are consistent with published results I I I and suggest a better physiologic outcome among patients with disease distributed primarily in the upper lung zones. Contingency table analysis suggests that in our cohort, a heterogeneity score greater than or equal to I. I is a statistically significant discriminator of patients with surgically responsive disease (p =.0048). This criterion proved to be 100% sensitive (all five patients with moderate to severe disease who responded favorably to surgery had heterogeneity scores I. I ) and 8 1% specific (of the remaining 1 1 patients, nine had heterogeneity scores < I. I ), with a heterogeneity score of greater than or equal to 1. I having a predictive value for a favorable surgical outcome of 7 1% among this small group of lung volume reduction surgery patients. Although this preoperative assessment algo- sult of parenchymal tissue destruction, decreased lung elastic recoil, and loss of airway tethering; and those with evidence of emphysema who also have significant intrinsic airway disease related to airway narrowing, mucous plugging, and destruction of parallel conducting pathways [7]. The former group, which includes the 58-year-old man (Fig. 3) and the 59-year-old man (Fig. 2), responds favorably to lung volume reduction surgery, whereas the latter group, which includes the 48-year-old woman (Fig. 4) and the 55-yearold woman (Fig. 1), does not respond favorably despite similar radiologic appearances on CT scanning. In theory, lung resistance measured during inspiration should discriminate between these two groups. During expiration, resistance to airflow in patients with emphysema is limited by airway collapse because expiration is generally active and intrathoracic pressures are positive [14]. During inspiration, intrathoracic pressures are subatmospheric, tending to pull airways open, and thus dynamic airway collapse does not occur. Increased resistance to flow during inspiration in the setting of a markedly reduced forced expiratoty volume in 1 sec suggests significant intrinsic airway disease and a decreased likelihood of responding favorably to lung volume reduction surgery, even if emphysema is detected radiologically. Lower resistance to airflow during inspiration in the setting ofa markedly reduced forced expiratory volume in 1 sec suggests airflow limitation as a result of dynamic airway compression related to decreased airway tethering from emphysema and a greater likelihood of responding favorably to lung volume reduction surgery. Measurements of inspiratory resistance were obtained in 12 of the 20 patients in our study. A significant negative linear relationship between inspiratory resistance and improvement in forced expiratory volume in 1 sec after lung volume reduction surgery was observed in this group (r = -0.72, p = ) (Fig. 7), supporting the aforementioned hypothesis. When patients with only moderate to 8.5 cm H,O/l per second identified all patients who failed to improve after lung volume reduction surgery. In this small subset of patients, inspiratory resistance of less than 8.5 cm H-,O/l per second proved to be 100% sensitive (5/5), 100% specific (3/3), and highly predictive (5/5). Although the results presented here are promising, they must be confirmed in a large cohort. CT scoring was available for 20 bilateral lung volume reduction surgery patients, and physiologic studies were available for only a subset (n = 12) of this group. In addition, only five of the 20 patients studied here showed a favorable response to lung volume reduction surgery, and thus cutoffs used in the contingency table analysis to determine preoperative selection criteria may significantly change when more equal numbers of responders and nonresponders are considered. Despite these limitations, our results suggest that patients who are likely to respond favorably to lung volume reduction surgery therapy for emphysema can be identified before surgery by using a combination of thin-section CT and measurements of lung resistance during inspiration while patients breathe spontaneously. This combination appears to be better able to identify responders preoperatively than radiologic criteria alone, even when disease distribution Acknowledgment is considered. We thank Georgia Washington for preparation of this manuscript. References I. Slone RM, Gierada DS. Radiology of pulmonary emphysema and lung volume reduction surgery. Sen,in Thorac Cardiovasc Surg 1996:8: Cooper JD, Patterson GA. Lung volume reduction surgery for severe emphysema. Semin Thorac ( ardiovasc Surg 1996:8: Yusen RD, Trulock EP, PohI MS. Biggar DG. Resuits of lung volume reduction surgery in patients with emphysema: the Washington niversity Em- rithm, based solely on radiologic analysis, appears useful, direct comparison of CT images among patients with moderate to severe disease suggests that alternative approaches may be of greater use, especially among patients with more homogeneous, evenly distributed severe emphysema were considered, the negative relationship between inspiratory resistance and change in forced expiratory volume in 1 sec remained significant. Contingency table analysis revealed that an inspiratory resistance value of less than or physema Surgery Group. Semin Thorac Cardiovasc Surg 1996:8: Yusen RD. Lefrak SS. Evaluation of patients with emphysema for lung volume reduction surgery. Semin Thorac Cardiovasc Surg 1996;8: Brantigan OC, Mueller E, Kress MB. A surgical approach to pulmonary emphysema. Am Rev AJR:170, February

6 Hunsaker et al. Respir Dis 1959;80: Gaensler EA, Cugell DW, Knudson Ri, Fitzgerald MX. Surgical management of emphysema. C/in Chest Med 1983;4: Leaver Dci, Tatterfield AE, Pride NB. Contributions of loss of lung recoil and ofenhanced airways collapsibility to the airflow obstruction of chronic bronchitis and emphysema. J C/in Invest 1973;52: Sciurba FC. Rogers RM, Keenan RT, et al. Improvement in pulmonary function and elastic recoil after lung reduction surgery for diffuse emphysema. N Eng/ J Med 1996;334: American Thoracic Society. Statement standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Cr/i Care Med 1995;152[suppl]:S78-S American Thoracic Society. Statement standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;l52[suppl]:S108-Sl Lamers Ri, Thelissen GR, Kessels AG, et al. Chronic obstructive pulmonary disease: evaluation with spirometrically controlled CT lung densitometry. Radiology 1994;193:109-l Sakai F, Gamsu G, Im J, Ray CS. Pulmonary function abnormalities in patients with CT-determined emphysema. J Comput Assist Tomogr 1987;ll: Klein JS, Gamsu 0, Webb WR, et al. High resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity. Radiology 1992;l82: Hyatt RE. The interrelationships of pressure, flow, and volume during various respiratory maneuvers in normal and emphysematous subjects. Am Ret RespirDis 1961;83: Kaczka DW, Barnas GM, Suki B. Lutchen KR. Assessment of time-domain analysis for estimation of low-frequency respiratory mechanical properties and impedance spectra. Ann Biomed Eng 1995;23: Snedecor GW, Cochran WG, eds. Statistical methods, 8th ed. Ames: Iowa State niversity Press, 1989: Goddard PR, Nicholson EM, Laszlo G. Watt I. Computed tomography in pulmonary emphysema. C/in Radio/ 1982;33: Kuwano K. Matsuba K, Ikedal, Murakami J, et al. The diagnosis of mild emphysema: correlation of computed tomography and pathology scores. Am Ret Respir Dis 1990;l41: Thurlbeck WM, Mller NL. Emphysema: definition, imaging, and quantification. AiR 1994;163: Foster WL. Pratt PC. Roggli VL, et al. Centrilobular emphysema: CT pathologic correlation. Radio/- ogt 1986;l59: Bergin C. Mller N. Nichols DM. et al. The diagnosis of emphysema: a computed tomographicpathologic correlation. Am Rev Respir Dis 1986; 133: Bergin Ci, Mller NL, Miller RR. CT in the qualitative assessment of emphysema. J Thorac Imaging 1986;l: Miniati M, Filippi E, Falaschi F, et al. Radiologic evaluation of emphysema in patients with chronic obstructive pulmonary disease: chest radiography versus high resolution computed tomography. Am J RespirCrit Care Med 1995;151: Hruban RH, Meziane MA, Zerhouni EA, et al. High resolution computed tomography of inflation-fixed lungs: pathologic-radiologic correlation of centrilobular emphysema. Am Ret Respir Dis 1987;l36: Gurney JW. Jones KK, Robbins RA, ci al. Regional distribution of emphysema: correlation of high-resolution CT with pulmonary function tests in unselected smokers. Radiology 1992;l83: AJR:170, February 1998