for Bullectomy of Giant B da

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1 ORGNAL ARTCLES Functional ndications for Bullectomy of Giant B da Kazuya Nakahara, M.D., Kazuya Nakaoka, M.D., Kiyoshi Ohno, M.D., Yasumasa Monden, M.D., Masazumi Maeda, M.D., Akira Masaoka, M.D., Kenji Sawamura, M.D., and Yasunaru Kawashima, M.D. ABSTRACT Nineteen patients with giant bulla were followed for more than 1 year after bullectomy. They were divided into two groups according to their postoperative symptoms. Group 1 consisted of 16 patients who had no problems in their postoperative clinical course, while Group 2 included 3 patients who complained of severe dyspnea at 5 to 6 years of follow-up. Prior to operation, the forced expiratory volume in 1 sec over vital capacity (FEVl%) was 66.8? 21.8% in Group 1, and 27.6? 5.4% in Group 2. Following bullectomy, FEVl% was % in Group 1 and % in Group 2. Differences in preoperative and postoperative FEVl% were statistically significant within Group 1 and between the two groups. Postoperative FEVl% (Y) correlated significantly with preoperative FEV1% (X) (Y =.74X ; r =.836; p <.1). Thus, we were able to predict the postoperative FEVl% from the preoperative value. Regional ventilation over volume was computed from the washout curve of xenon 133 after reaching equilibrium with rebreathing in a closed circuit (VNdynamic). Group 2 had significantly lower regional ventilation over volume in all regions, both before and even after bullectomy, compared with normal subjects or Group 1 patients. Preoperative Vl VdF& was below.5 in all regions of Group 2. Furthermore, postoperative VNdynlmic (Y) correlated significantly with preoperative VNdymmic (x) in the upper region (Y =.46X +.4; r =.638;~ <.2) and in the lower region (Y =.7W +.33; r =.869; p <.1). From the First Department of Surgery, Osaka University Medical School, Osaka, Japan; the Second Department of Surgery, Nagoya City University, Nagoya, Japan; and the Department of Surgery, National Kink Central Hospital for Chest Diseases, Sakai, Japan. Accepted for publication July 15, Address reprint requests to Dr. Nakahara, First Department of Surgery, Osaka University Medical School, Fukushima-ku, Osaka, Japan. We conclude that functional indications of bullectomy for giant bulla are that FEV1% should be greater than 4%, and that regional V NdFdc should be greater than.5. On the other hand, symptomatic and functional improvement following bullectomy was reduced in patients whose FEV1% was less than 35% and whose VNdyna& was remarkably disturbed in all regions of the involved hemithorax. Bullectomy for giant bulla has been indicated for a number of reasons: (1) to relieve restrictive changes in the normal lung tissue in the vicinity of the giant bulla [l-51; (2) to increase both the elasticity of the remaining normal lung and the diameter of the airway caliber, thus increasing the expiratory force [3, 4, 61; (3) to increase the ventilation-perfusion ratio in the nonbullous region, thereby minimizing the effect of venous admixture [3, 7; and (4) on rare occasions, to decrease the physiological dead space that exists if the giant bulla ventilates substantially [3]. Based on this theoretical background, there has been almost no problem in performing bullectomy of well-demarcated, space-occupying bulla without other lung disease. However, there has been controversy over bullectomy for giant bulla with emphysematous changes in the remainder of the lungs. Some studies have shown that even in such situations bullectomy has a beneficial effect on patients' symptoms [4, 81, while others have claimed that operation for giant bulla with underlying generalized emphysema is not worthwhile [9]. We believe that this controversy has arisen because to date there has been no attempt to define physiological criteria for predicting a beneficial outcome following bullectomy for giant bulla [lo]. n the present study, we divided 19 patients into two groups according to degree of postoperative dyspnea. Preoperative and postoperative functional results were evaluated in order

2 481 Nakahara et al: Bullectomy of Giant Bulla to delineate predictable variables for symptomatic or functional relief, or both, after operation. Patients and Methods The cases of 19 patients with giant bulla occupying more than one-third of the hemithorax were reviewed. The mean age of this population was 47? 12 years (standard deviation [SD]); the range was 17 to 63 years. Eighteen of the patients were men. The degree of dyspnea before operation was classified according to the Hugh-Jones (H-J) criteria [ll]. Six patients were categorized as H-J Class, 4 were in H-J Class 11, 6 were in H-J Class 111, 2 were in H-J Class V, and 1 was in H-J Class V. Sixty percent of the patients had engaged for a long time in occupations in which they were likely to be exposed to dust, such as turners (6 patients) and sewer workers (2 patients). The study group also included a gilder, a railroad worker, and a sawmill worker. Two patients, 1 in H-J Class V and 1 in H-J Class V, had had pneumoconiosis. Another 2,l in H-J Class 11 and 1 in H-J Class 11, had generalized emphysematous changes secondary to cicatrization by old, healed tuberculosis. n 4 patients (21%), spontaneous pneumothorax was the result of previous illness. Simple bullectomy was performed for 15 upper lobe lesions and for 4 lower lobe lesions. n 5 patients with bilateral upper lobe lesions, bullectomies of both lungs were performed within a one-year interval. Pulmona y Function Tests Prior to and 1 to 7 years following the last bullectomy, pulmonary function tests were done in all 19 patients. Regional pulmonary functions were studied in 12 patients in Group 1 and in all 3 patients in Group 2. OVERALL PULMONARY FUNCTON TESTS. Vital capacity (VC) and timed forced expiratory volume in 1 second (FEV1) were measured using the conventional Benedict-Roth respirometer. Baldwin's equation was applied for predicted VC. Functional residual capacity (FRC) was measured by the helium dilution method. More than 15 minutes was provided for complete mixing of the inert gas, with monitoring by helium meter. The ratio of residual capacity (RV) and total lung capacity (TLC), or RV/TLC%, was calculated for each patient; TLC equalled the sum of inspiratory capacity and FRC, while RV was the difference between TLC and VC. Arterial blood gases and expiratory gases at rest were analyzed to calculate the alveolar-arterial oxygen difference (A-aDo2). REGONAL PULMONARY FUNCTON TESTS. The procedure was the same as in the original method of Ball and colleagues Six scintillation detectors with sodium iodide crystals (38 mm x 6.35 mm each) and photomultiplier tubes were used. The signals were fed through amplifiers, pulse height analyzers, and ratemeters connected to a six-channel recorder. These detectors properly collimated with cylindrical lead collimators (5 mm thick and.348 mm long). Six detectors were fitted at the middle line of the backs of the seated patients. The topmost parts of the upper detectors were positioned at the level of the clavicles in full inspiration, the central parts of the middle detectors were at the level of the seventh thoracic vertebra, and lower detectors at the level of the tenth thoracic vertebra. A Krogh-type respirometer with a full volume of 9 liters was filled with 4.5 mci of a mixture of xenon 133 gas and room air. This mixture was inhaled from maximum expiratory level up to maximum inspiratory level (TLC level). Counts of the upper, middle, and lower regions on both sides were obtained while the patients held their breaths for 4 seconds (V count). Vital capacities of the left and right sides were calculated from overall VC multiplied by the sum of the fractional distribution of the V count on each side. The patients continued to rebreathe in the closed circuit until the regional count rate reached equilibrium, at which point the patients held their breaths for 4 seconds at TLC level to obtain the TLC count. Thereafter, '33Xe was washed out of the airway under open circuit with steady breathing to obtain washout halftime. Mean clearance rate (MCR) was calculated according to the method of Streider and associates [13] and Miller and co-workers [14]. According to Fowler's group 1151, the concentration of the indicator at the nth breath (KN) is expressed as

3 482 The Annals of Thoracic Surgery Vol 35 No 5 May 1983 the function of the lung volume (VL), tidal volume (VT) and the concentration of the indicator just before washout (KO): KN = KO x (VLNL + V T)~ where N is the product of n (respiratory rate) and T (time). Therefore, KN = x (VLNL + VT)"~ n the washout half-time, KT,/KO =!h = (VLNL + VT)"=h. Th = -.693/n = 1 f Ln(VLNL + VT) Thus, KT is the concentration of '33Xe at wash-? out half-tune (Th). n the event that VL is far greater than VT, c, = X e X -(VT X ntnl)andkt,/ko = '/2 = e x -(VT x ntfll), so that VT x ~NL =.93Th (VT x ~NL = clearance rate). Since clearance rate was detected at six compartments in our study, MCR, which was the mean of six clearance rates weighted by each regional fractional volume (Vi), was computed as: 6 MCR = Vi/Thi i=l where Vi was the percent distribution of V count on each region. Regional clearance rate (.693T~) over MCR was used as the indicator of the regional dynamic ventilation rate: VNdynamic =.693MCR x Th Terminally at the background level, 2 mci of '33Xe saline solution was rapidly injected intravenously while the patients held their breaths at end-tidal level until each regional count rate reached a plateau on the recorder. The patients were then forced to inspire to TLC level and again hold their breaths for 4 seconds. Regional count rate equivalent to regional perfusion was thus obtained (Q count). The percentage distribution of Q count was summed up on the left and right sides (Q index). Statistical Analysis Data were expressed as mean 2 SD. The paired t test was applied to compare the difference between preoperative and postoperative values in the same patients within a group, while the unpaired t test was used to compare the difference between groups. A p value less than.5 was regarded as statistically significant. Normal values of VNdynamic were sampled arbitrarily from the right hemithoraces of 11 normal volunteers (mean age, years), since there was no difference in VNdynamic between both hemithoraces for each region. All patients were included in computation of correlations. A p value less than.5 was considered statistically significant for each correlation coefficient (Y). To compare three unpaired groups, analysis of variance with the Newman-Keuls multiple range test was applied. The joint significance level for the Newman-Keuls tests was.5 [16]. Results Postoperative mprovement of Symptoms The time course for the degree of dyspnea is shown in Figure 1. Ten patients had no or only mild dyspnea (H-J Class or 11) prior to operation. There were no problems with clinical results following bullectomy in this group. Six of 9 patients with severe dyspnea (H-J Class 111 or V) preoperatively showed excellent postoperative symptomatic improvement (H-J Class 1 or ) over follow-up ranging from 5 to 7 years. These 16 patients were placed in Group 1. n Group 2 were 3 of 9 patients who had severe dyspnea prior to operation (H-J Class V, V, or 111) and who were still complaining of dyspnea (H-J Class 111) 5 to 6 years following bullectomy. n 2 of these patients, transient improvement was observed about 1 year postoperatively. Changes in Pulmonary Function Tests Results of overall pulmonary function tests are shown in Table 1. Figure 2 indicates that the %VC was above 8% in many instances preoperatively, except for 4 patients in Group 1 and 2 in Group 2. Following bullectomy, only 2 patients showed

4 ~ 483 Nakahara et al: Bullectomy of Giant Bulla + g -. preopl years Fig 1. The time course of the degree of dyspnea in 19 patients according to Hugh-Jones s criteria (-V). Asterisks (*) indicate bilateral bullectomies. postoperative % vc , B / oo % 8. 4 / preoperative % VC abnormal %VC. However, there was no statistically significant correlation between preoperative and postoperative %VC (r =.442; N = 19) (see Fig 2), nor were there significant differences of %VC within each group or between groups (see Table 1). Vital capacity and Q index of the operated hemithorax were measured in 12 patients in Group 1 and in all 3 patients in Group 2. The results are shown in Figure 3. n 5 patients with bilateral bullas, data from the more involved hemithoraces prior to operation were included. n Group 1 regional VC averaged 1.22?.66 liters preoperatively and 1.34 &.52 liters following bullectomy. n Group 2 it averaged.94?.32 liters prior to and.74 &.45 liters following bullectomy. The Fig 2. Preoperative vital capacity (%VC) did not correlate significantly with postoperative % VC. Open circles represent patients in Group 1 and closed circles are Group 2 patients. (Dotted line = unity.) Q index in Group 1 averaged.41?.13 preoperatively and.42 &.7 following bullectomy. n Group 2 it averaged.35 &.11 prior to and.36?.11 following bullectomy. There were no statistically significant differences in regional VC or Q index within each group or between groups. On the other hand, FEV% was below 7% in many patients (Fig 4). n Group 1 it was abnormal in 1 patients preoperatively and in 6 following bullectomy. n the 3 patients in Group 2, Table 1. Results of Overall Pulmonary Function Testing before and after Bullectomy (N = 19) Location of Bulla (No. of Patients) Pulmonary Function Variables Study Upper Lower %VC FEV% RVmLC Pa2 Pacoz A-aDq Group Age((yr) LFb LF (a) (%) (1% 1 (mm Hn) (mm HR) (mm Hn) Group 45 f 12 13(3) 3 (91.1 f 15.5) (66.8 f 21.8)),) (42.3 f 13.2) (85.6 f 14.7) (38.9 f 3.6) (21 f 14) (N = 16) 91.4 f f 19.2 d 36.8 f f f f 9 Group (2) 1 (N = 3) 8.3 f 18.1 (58.8 f 1.2) (73.3 f 11.7) (44.3 f 2.5) 43.8 f f f 5.6 Age and pulmonary function test results are expressed as mean f standard deviation. bnumbers in parentheses indicate patients with bilateral bullas. cvalues in parentheses are preoperative pulmonary function test results. Open brace ({) denotes statistical significance between groups postoperatively; close brace ) indicates statistical significance between or within groups preoperatively. dsignificance:.5 C p C.1. Significance:.1 < p <.2. Significance:.2 < p <.5. LF = lung field; %VC = percentage of normal vital capacity; FEVlS = ford expiratory volume at 1 second over vital capacity; RVmC = ratio of residual capacity to total lung capacity (see text for details); Pam = partial arterial oxygen tension; Pam2 = partiil arterial carbon dioxide tension; A-aDq = alveolar-arterial oxygen diffeference. 3of 4

5 484 The Annals of Thoracic Surgery Vol 35 No 5 May 1983 =.O-k f % kj -.o - - Fig 3.. Changes in vital capacity (VC) and of perfusion index (Q index) at the bullous hemithorax. There were no statistirally sign$cant differences within Group 1 (open circles), within Group 2 (closed circles), or between groups. postoperative FEVi. i 2 a / / /' / OM'/ Y =.74X r =.836 P<O.oo Preoperative FEVlo Fig 4. Preoperative forced expiratory volume in one second (FEV) correlated significantly with postoperative FEVl. Open circles represent Group 1 and closed circles are Group 2 patients. (Solid line = regression line; dotted line = unity.) FEV1% was 33.3%, 28.2%, and 29.6% preoperatively and 35%, 5.9%, and 54.1% following bullectomy. There was a statistically significant correlation between preoperative and postoperative FEVl% (postop. FEVl% =.74 x preop. FEV% ; r =.836; p <.1) for all 19 patients. mprovement of FEVl 76 following bullectomy was statistically significant in Group 1. Possibly because of the small size of the patient sample, there was no statistically significant change in FEV% in Group 2 (see Table 1). Differences of FEVl% between Groups 1 and 2 were statistically significant both preoperatively and postoperatively (see Table 1). The RV/TLC% ratio was generally high, especially in Group 2. However, there were no significant changes either between the groups or within each group prior to and following operation (see Table 1). Partial arterial oxygen tension (Paoz) in Group 1 was above 8 mm Hg, except in 5 patients (range, 66. mm Hg to 75. mm Hg) preoperatively and in 3 patients (range, 73. mm Hg to 79. mm Hg) following bullectomy. n the 3 patients in Group 2, Pao2 values were 82. mm Hg, 78. mm Hg, and 6. mm Hg preoperatively and 79.2 mm Hg, 72. mm Hg, and 74. mm Hg following bullectomy. There were no statistically significant changes in Paoz within each group or between groups (see Table 1). Partial arterial carbon dioxide tension (Paco2) ranged from 35. mm Hg to 47. mm Hg both prior to and following bullectomy. There were no statistically significant differences between groups or within each group (see Table 1). The A-aDo2 value was abnormally high in many patients (Fig 5). n 11 patients in Group 1, it was greater than 1 mm Hg. n 8 patients it was still high even after bullectomy. n the 3 patients in Group 2, A-aDo2 was 21 mm Hg, 28 mm Hg, and 36 mm Hg preoperatively and 3 mm Hg, 34 mm Hg, and 27 mm Hg following bullectomy. Differences in A-aDo2 within each group were not statistically significant. Postoperatively, differences in A-aDo2 between Group 1 and Group 2 were statistically significant (see Table l), indicating that oxygenation in alveoli was more disturbed following bullectomy in Group 2 than in Group 1. However, there was no statistically significant correlation between preoperative and postoperative A-aDo2 (r =.448; N = 19) (see Fig 5). Table 2 shows the regional ventilation over volume calculated from '=Xe washout half-time during steady breathing (VN+,amic), which was measured in 11 normal volunteers, 12 patients in Group 1 and the 3 in Group 2. The same data

6 485 Nakahara et al: Bullectomy of Giant Bulla postoperative A-aDOz mmhg 25 1 o / 2 t /, O,,, / upper region middle region lower region r-63.9, P<OoOl 8 - u Fig 6. The correlation between regional dynamic ventila- tion per volume (VNdynamic) prior to and following bullectomy in different regions of the hemithorax. n the upper and lower lung fields, the preoperative and postoperative values correlated significantly. n Group 2 VVdynnmic was less than.5 preoperatively and less than.75 postoperatively in all lung fields. (Open circles = Group pal mmh tients; closed circles = Group 2 patients; ns = not preowrative A-aDO. significant.) Fig 5. Preoperative alveolar-arterial oxygen difference (A-aDo2) did not correlate significantly with postoperative A-aDq. Open circles indicate Group 2 and closed circles represent Group 2 patients. (Dotted line = unity.) from the normal subjects were used in the preoperative and postoperative data analysis. n 5 patients with bilateral bullas, data from the more involved hemithoraces prior to operation were selected. n Group 1 preoperative VNdynamic averaged.53?.24,.68?.38, and 1.12?.28 in the upper, middle, and lower lung fields, respectively. On the other hand, it averaged.2?.7,.25?.6, and.3?.13 in Group 2. n all regions, preoperative VNdynamic was below.5 in all 3 patients in Group 2. n each re- gion, preoperative VNdynamic in Group 2 was significantly lower than in individuals or in Group patients. Also, this variable was significantly lower in Group 1 than in normal individuals- for the upper- and middle lung fields. Following bullectomy VNdynamic was.66?.12 in the upper,.86?.16 in the middle, and 1.17 &.15 in the lower lung field; in Group 2 it was.4?.7,.56?.15, and.41 &.21, respectively. n all regions, V/ Vdynamic in Group 2 was significantly lower than in normal individuals or Group 1 patients. Postoperative VNdynamic in all regions was less than.75 in all 3 patients in Group 2. However, there was no statistically significant difference between normal subjects and Group 1 patients postoperatively. Table 2. Regional Ventilation ~V/Vd,,l,,,llljc~ before and after Bullectomy Lung Regions Study Group Upper Middle Lower Group 1 (.53 *.24) (.68 f.38) (N = 12) f.16 Group 2 (N = 3).56 f f.21 Control.76?.1 (N = 11) Values are expressed as mean 2 standard deviation. bvalues in parentheses are preoperative results. Open brace ({) denotes statistical significance between groups postoperatively; close brace (}) indicates statistical significance between or within groups preoperatively. Variation: : <.1. dvariation: a <.1. Variation: : <.2. Variation: a <.5.

7 486 The Annals of Thoracic Surgery Vol 35 No 5 May 1983 Figure 6 shows the correlation between preoperative and postoperative VNdynamic. They correlated significantly in the upper lung field (postop. VNdynamic =.46 x preop. VNdynamic +.4; T =.638; p <.2), and in the lower lung field (postop. VNdynamic =.72 x preop. VNdynamic +.33; T =.869; p <.1). The correlation for the lower region was most significant. However, the values did not correlate significantly for the middle lung field (T =.48; N = 15). Comment The most important point in determining indications for bullectomy of giant bulla is how to assess the state of the nonbullous lung field. Postoperative functional recovery, especially in giant bulla with generalized emphysema, has been reported to be less good than in welldemarcated bulla without underlying lung disease (3, 41. n fact, the patients in Group 2 revealed generalized emphysema secondary to pneumoconiosis (2 patients) and old, healed tuberculosis. However, the reliability of overall lung function testing in predicting generalized emphysema has not been evaluated. For example, Pride and associates [3] found that patients with lower pulmonary carbon dioxide diffusing capacity or higher compliance and larger TLC by body plethysmography were more likely to have generalized emphysema, and thus to benefit less from bullectomy. Gelb and coworkers [17] showed that airway resistance and pulmonary elastic recoil pressure were improved in relation to lung volume following bullectomy, and that postoperative airway resistance was still high in patients with progressive bronchitis. FitzGerald and colleagues [4] stressed the importance of FEVl% in predicting functional recovery following bullectomy. However, these authors did not provide precise criteria for operation with beneficial results. The present study was undertaken to clarify this point by correlating preoperative and postoperative values for pulmonary functions and by retrospectively observing 19 patients divided into two groups according to symptomatic change following bullectomy. Results clearly showed that although bullectomy almost always improves the symptoms, sustained improvement was more pronounced in patients whose FEVl% was above 4% preoperatively; those patients with an FEV% less than 35% did not show as much benefit from bullectomy. From the regression line for preoperative and postoperative FEVl% values (postop. FEV1% =.74 x preop. FEV% ; r =.836; p <.1), we can predict that a patient whose preoperative FEVl% is less than 35% will show improvement in this function of 5%, at most, postoperatively. This value still indicates severe obstructive ventilatory impairment. Many patients with giant bulla showed low FEV1% values due to loss of pulmonary elastic recoil; the remaining lung could not be stretched enough to develop great retractive force, so the airway could not maintain its caliber on expiration [6, 161. Another reason is that over 6% of these patients had been engaged in dusty occupations for a long time, resulting in destructive and emphysematous change in the lung parenchyma. Pride and colleagues [3] showed from regional and overall pulmonary function studies that bulla causing substantial dead space ventilation was rare. Ting's group (181 studied an excised bulla and concluded that it had mechanical properties similar to those of a paper bag; in other words, there is little change in pressure up to near its maximum volume, at which point large pressure changes occur only with a small change in volume. These studies indicate that overall pulmonary function tests reflect predominantly the function of the nonbullous lung [lola High RVRLC ratios, which we and other groups [, 3, 41 have observed in many cases of emphysematous bulla, therefore, strongly suggest that many patients had emphysema in the remainder of the lung. On the other hand, %VC was greater than 8% in many patients, and there was no statistically significant change within each group preoperatively or postoperatively. Furthermore, VC and Q index of the involved hemithorax did not increase remarkably following operation, indicating that restrictive disturbance of the re-

8 487 Nakahara et al: Bullectomy of Giant Bulla maining lung was not a major cause of dyspnea. This also showed that VC was not a good predictor in selecting patients for bullectomy. Dynamic ventilation per volume (vndynamic) calculated from '33Xe washout half-time has been introduced as a good indicator of regional ventilatory efficiency [13, 141. n our study, VNdynamic in Group 2 was less than.5 in all regions of the involved hemithorax. From the regression line of the lower lung field, which was most significant (postop. vivdynamic =.72 x preop. \jndynamic +.33; r =.869; p <.1), we can predict that a patient whose preoperative VNdynamic is.5 will show functional improvement to.7 at most, which is 6% of normal. t has been proposed that ventilation and perfusion in the lower lung field are most significant, indicating that the lower lung field is the most important area in lung function [12, 141. On the other hand, the present study showed that patients who did not benefit from bullectomy had disturbed ventilatory function in all regions, regardless of the location of bulla. Thus, we are convinced that \jndynamic is a good predictor of function and symptomatic relief following bullect om y. References Foreman S, Weil H, Duke R, et a1 Bullous disease of the lung: physiologic improvement of the lung. Ann nt Med 69:757, 1968 Wesley JR, Macleod WM, Mullard KS: Evaluation and surgery of bullous emphysema. J Thorac Cardiovasc Surg 63:945, 1972 Pride NB, Barter CE, Hugh-Jones P: The ventilation of bullae and the effect of their removal on thoracic gas volume and tests of over-all pulmonary function. Am Rev Respir Dis 17:83, 1973 FitzGerald MX, Keelan PJ, Cugell DW, Gaensler EA Long-term results of surgery for bullous emphysema. J Thorac Cardiovasc Surg 48:566, Halkier E, Rasmusen E, Vejlsted H, et al: Surgical improvement of respiratory insufficiency. Scand J Thorac Cardiovasc Surg 12:75, Rogers Rh4, DuBois AB, Blakemore WS: Effect of removal of bullae on airway conductance and conductance volume ratios. J Clin nvest , Duffell GM: The role of surgery in COPD. Postgrad Med 54:197, Braun SR, dopico GA, Birnbaum ML, Pellett JR: Bullae and severe generalized disease: successful treatment with bullectomy. J Thorac Cardiovasc Surg 65:926, Gunstensen J, McCormack RJM: The surgical management of bullous emphysema. J Thorac Cardiovasc Surg 65:92, Hugh-Jones P, Whimster W: The etiology and management of disabling emphysema. Am Rev Respir Dis , Hugh-Jones P: A simple standard exercise test and its use for measuring exertion dyspnea. Br Med J 1:65, Ball WC, Stewart PB, Newsham LGS, Bates DV: Regional pulmonary function studied with '=Xe. J Clin nvest 41:519, Streider DJ, Barnes BA, Aronow S, et al: '33Xe study of ventilation and perfusion in normal and transplanted dog lungs. J Appl Physiol 23:359, Miller JM, Ali K, Howe CD: Clinical determination of regional pulmonary function during normal breathing using Xenon 133. Am Rev Respir Dis 11:218, Fowler WS, Cornish ER, Kety SS: Lung function studies: V. Analysis of alveolar ventilation by pulmonary Nz clearance curves. J Clin nvest 31:4, Zar JH: Biostatistical Analysis. Englewood Cliffs, NJ, Prentice-Hall, 1974, pp Gelb AF, Gold WM, Nadel JA: Mechanisms limiting airflow in bullous lung disease. Am Rev Respir Dis 17571, Ting EY, Klopstock R, Lyons HA: Mechanical properties of pulmonary cysts and bullae. Am Rev Respir Dis 87538, 1963