Bullectomy for giant bullae in emphysema

J

THORAC CARDIOVASC SURG

91:63-70, 1986

Bullectomy for giant bullae in emphysema The results of changes in dyspnea and pulmonary function are reported in 27 emphysemato~ patients

followed up for about 10 years after removal of giant bullae, which occupied at least 50% of a hemithorax. In 10 patients bilateral bullectomy was done. The spirographic improvement depends on the typeof bulla. Resection of bullaeat opencommunication withthe bronchial tree resulted predominantly in improvement of forced expiratory volume as a percentage of vital capacity, whereas after closed bullae were resected, the increase in vital capacity was most apparent. Dyspnealessened in all patients. Seven older patients died of ventilatory insufficiency. Preoperatively they were clinically and functionally severely disabled. They improved markedly after bullectomy, and their mean survival time was more than 7 years. In 1lll 27 patients improvement of dyspnea and pulmonary function lasted several years and only gradually returnedto preoperative values and beyond. No giant bullaerecurred in the observation period; neither was there an accelerated progression of the emphysemato~ process. Our present selection criteria, based on previ~ experience, are as follows: giant bullae occupying at least 50 % of a hemithorax, defmite displacement of adjacent lung tissue, excl~ion of the presence of vallishing lung syndrome, and absence of chronic purulent bronchitis.

C. D. Laros, M.D., H. J. Gelissen, M.D., P. G. M. Bergstein, J. M. M. Van Den Bosch, M.D., R. G. J. R. A. Vanderschueren, M.D., C. J. J. Westermann, M.D., and P. J. Knaepen, Nieuwegein, The Netherlands

Since the introduction of elective bullectomy in the

early 19508 to reduce breathlessness in patients with bullous degeneration of diffuse emphysema, several reports havestressed the importance of careful preoperative selection of patients.1-6 When an elective operation for bullousemphysemais considered, the differentiation between simple giant bullae and vanishing lobes or segmentsis important.I, 2, 7, 8 When simple bullaeappear to be present,surgery should not beconsidered if the bullaeoccupyonethird or lessof a hemithorax, because in such cases operation hardly improves pulmonaryfunction and validity. 2,6,9-11 This article describes the long-term clinical course and function changes in 27 patients with resection of giant bullae occupying 50% or more of a hemithorax.

From the Departments of Pulmonology (Drs. Laros, Bergstein, Van Den Bosch, Vanderschueren, and Westermann) and Thoracic Surgery (Drs. Gelissen and Knaepen), St. Antonius Hospital, Nieuwegein, The Netherlands. Received for publication Sept. 20, 1984. Accepted for publication March 12, 1985. Address for reprints: C. D. Laros, M.D, St. Antonius Ziekenhuis, Postbus 2500, 3430 EM Nieuwegein, The Netherlands.

Patients and methods In our hospital bullectomy was considered in 142 patients with bullous degeneration of diffuse emphysema during the period 1958 through 1977. After extensive clinical, roentgenologic, and functional analysis, 65 patients, underwent operation. In six patients resection of vanishing lobes was performed, and in three other patients the thorax was closed without any intervention because the presence of a vanishing lung necessitated extensive resection. In these patients a definite loss in pulmonary function was found postoperatively. The bullae occupied one third or less of a hemithorax in 29 patients. In these patients no improvement or only a small, temporary improvement in pulmonary function could be demonstrated during a follow-up period of 9 years. Bullae occupying 50% or more of a hemithorax were removed in 27 patients. All patients were men, with an average age at operation of 52 years (range 35 to 64 years). All were smokers of cigarettes, with an average of 29 pack-years, (range 13 to 59 pack-years). The commondenominatorof the populationwas generalized emphysema with a flaccid lung. The commoncomplaint was dyspnea. Alpha-l-antitrypsin levels were normal in all patients; in 16 of them the protease inhibitor 63

64

The Journal of Thoracic and Cardiovascular Surgery

Laros et al.

OPEN COMMUNICATION

BALL VALVE ACTION

BULLAE

COLLAPSED \IT> \10 2

COMPRESSED \IT ""~02

Fig. 1. Schematic drawings of the effect of giant bullae on the adjacent lung tissue. In communicating, open bullae, the lung tissue is deprived of its natural expanding counterpressure and collapses. In the closed bullae the adjacent lung tissue is compressed. PB, Barometric pressure. VT, Tidal ventilation.

phenotypes were also determined and no homozygous or heterozygous deficiencies were found. After bullectomy all patients were followed up in the Outpatient Department of the S1. Antonius Hospital for 5 to 25 yeats (mean 10.4 years). The mean number of follow-up examinations was 19 (range 9 to 54). Dyspnea index. Breathlessness was assessed clinically according to a scale of symptoms: 0 = no dyspnea on exertion; I = dyspnea while running or climbing two flights of stairs; II = dyspnea while walking or bicycling against wind; III = unable to walk or cycle more than 1,000 meters; IV = unable to walk more than 100 meters; and V = dyspnea on walking in the house, dressing, and washing. Radiology. In all patients plain posteroanterior and lateral chest radiographs were made at maximal inspiration and expiration. Compression or collapse of adjacent parenchyma was also judged by tomography, by angiography, and sometimes by bronchography (Fig. 1).12 The differentiation between bullae and vanishing lung was also based on the results of these techniques.':" i3 Respiratory function tests. In all patients ventilatory function was measured before operation and at regular intervals in the follow-up period, with water-sealed spirometers. Lung volumes were measured by the closed circuit helium method, with 33% initial helium concentration. All volumes are given in BTPS conditions. Bronchospirometry with determination of residual

volume (CR.V) and helium washout studies were done in 25 of the patients before operation. Xenon ventilationperfusion studies were done in two patients preoperatively and in 16 patients several years after bullectomy. Blood gases were measured in all patients with the useof whole blood, preoperatively and at regular intervals in the follow-up period. In 25 of the 27 patients, breathing mechanics and lung elasticity were measured with the esophageal balloon method before operation. 14 The lung elasticity is expressed as volumic compliance: Cv = CL/FRC (normal range 0.5 to 0.8 kPa- l ) in which CL represents lung compliance and FRC is the functional residual capacity. Selection criteria for operation for open and closed bullae. Only patients with giant bullae occupying 50% or more of one hemithorax and with demonstrated displacement of the adjacent parenchyma are subjects of this report. The size of the bullae was estimated from the anteroposterior arid lateral chest films at maximal inspiration. Based on radiologic and functional studies a differentiation was made between "open," communicating, and "closed," noncommunicating bullae.': 3, 8, 9 In closed bullae a relatively small inspiratory vital capacity (VC) is present because the bullae do not contribute to volume change. The loss is located on the affected side, which also has only a moderately elevated residual volume with bronchospirometry. No helium peaks appear on this side with deep expiration at the end of unilateral helium washout. Roentgenologically the bulla size does not change at maximal expiration. In the open bullae a nearly normal VC is found with spirometry and also the VC of the affected side is normal with bronchospirometry. The RV on this side is high and a typical helium peak appears at maximal expiration (Fig. 2). Both open and closed bullae were considered suitable for operation. Surgical policy. The giant bullae were either excised or sutured, whereas coexisting smaller bullae were obliterated by coagulation. Since 1975 large bullae were stapled before excision. No lung tissue was resected, regardless of its quality. In 10 patients bilateral bullectomy was done, but in only one was this done in the same instance. Meticulous postoperative care, including underwater seal drainage or suction with a slight negative pressure and sometimes intrapleural instillation of blood in case of persisting air leak, were successful in all but two patients. Site of the bullae. The site of the operated bullae was as follows: in 14 of the 17 patients having a unilateral

Volume 91 Number 1 January, 1986

Bullectomy for giant bullae

65

Fig. 2. Example of the maximal expiratory maneuver at the end of the helium washout procedure during bronchospirometry, in a patient with bilateral open bullae. A typical bulla peak small arrow occurs in both the right and left curve, at the moment that the alveolar space is almost completely washed out.

Table I. Preoperative grade of dyspnea in 27 emphysema patients with giant bullae. in relation to spirographic data Grade of dyspnea* (preop.)

I II

111 IV V Mean

No. of patients

2 3 12 4 6 27

Preop. spirographic data VC%VCn

124 124 97 78 66

I

FEV,VC

56 53 48 32 29 42

92

I

FlV,VC

84 81 80 81 82 82

I

RV%TLC

31 35 37 45 47 40

Legend: VC, Vital capacity. VCn, Calculated normal vital capacity. FEY" Forced expiratory volume in I second. FIY h Forced inspiratory volume in 1 second. RY, Residual volume. TLC, Total lung capacity. ·For details see text.

operation, the bullae were located in the upper lobes (nine right, five left), and in three patients in the lower lobes (two right, one left). In eight of these patients small bullae also were present in the contralateral lung, as judged from roentgenologic studies. In six of the 10 patients having bilateral operations the bullae were found in the upper lobes, and in two of these six patients bullae were also present in the right middlelobe. In two other patients the bullae were located in the apical segments of both lower lobes, and in another patient also in the middle lobe. In one patient the right lower lobe and the left lower lobe were involved. Postoperative complications. Severe subcutaneous emphysema complicated the postoperative course of 12 patients; 10 of these patients had dyspnea Grades IV

and V prior to operation. Air leakage persisted for more than 2 weeks in 12 patients, and eight of those had severe subcutaneous emphysema. In two patients a repeat thoracotomy had to be done for air leak and was successful. Results The preoperative clinical grades of dyspnea in relation to spirographic data are given in Table I. The differences in ventilatory function between Grades I and II are small. The VC in these patients is large compared with calculated normal values (i.e., 124%); the RV as a percentage of totallung capacity (RV%TLC) is only slightly increased; and the forced expiratory volume as a percentage of VC (FEV1%VC) is moderately reduced.

The Journal of Thoracic and Cardiovascular Surgery

6 6 Laros et al.

Table II. Preoperative versus postoperative grade of dyspnea in 27 patients No. of patients having bu/lectomy

Grade of dyspnea* Total

[preop.]

I

I

Unilateral

0 I II III IV V

2 3 12 4 6

2 3 6 2 4

Total

27

17

Bilateral

Grade of dyspnea

12 yr postop.)

I

Bilateral

Unilateral

2

2 3 5 2 2 3

10

17

6 2

6 3 I 10

• For details see text.

Table ill. Duration of improvement of dyspnea after bullectomy related to grade of dyspnea Improvement of symptoms after bu/lectomy {yr] Grade of dyspnea * I II III IV V

2

I

2

3

I

4

I

I 2 I

5

7

I

I

I

9 I

I 4 I

It 5 I 2

Deaths

10

9 I

It I 6

• For details see text. tPalient died of disseminated bronchial' carcinoma.

Table IV. Spirographic data of patients with open and closed bullae at three different times Spirographic data

Open bullae VC%VCn RV%TLC FEV,%VC FIV,%VC Closed bullae VC%VCn RV%TLC FEV,%VC FIV,%VC

No. of patients

VCn* ImIBTPs)

10

4450

17

Preop.

I

2 yr postop.

I

Last checkup

108 41 31 82

118 32 44 90

99 44 38 84

84 40 48 82

118 36 51 88

88 44 39 80

4100

'YCn, Calculated normal value of vital capacity according to Baldwin, Cournand, and Richards" corrected by factor of 1.21 for Our own population.

With increasing grades decrease in VC and increase in RV%TLC, volume (FIV,%VC)

of dyspnea there is a progressive FEV,%VC, and a progressive whereas the forced inspiratory was normal in all patients

(~80%VC).

The combination of a severely disturbed FEVt%VC and a normal FIV,%VC is characteristic of loss in lung elasticity-a flaccid lung. This is also shown by the large compliance in relation to the functional residual capacity (Fig. 3). In all patients there was a high volurnic compliance, with a mean value of 1.72 kPa- 1 (SD 0.27).

There was no correlation between the grades of dyspnea and volurnic compliance. The postoperative results are given in Tables II through V. Table II shows the clinical grades of dyspnea before and 2 years after bullectomy. After an initial improvement in the first postoperative years dyspnea gradually increased within a period of about 5 years (Table III). Patients with bilateral bullectomy improved most. In Table IV the overall results of spirography are given, for open and closed bullae, before and 2 years after bullectomy and at the latest check-up. In Table V

Volume 91 Number 1

Bullectomy for giant bullae

67

January, 1986

9

CL

l/kPa

2.5

1.5

1.25

8

1.33

1.0

2.18

BIlFORI B1lLLIlCTC»IY

'l'IiO YIAIlS APTI!R

BILArIlRAL B1lLLIlCTOMY

Fig. 4. Example of a xenon 133 study in a patient with

:. . - -

-----~--_:_--7_-~-FRC in 1 BTPS

Fig. 3. Comparison of the quasistatic lung compliance (CL) and the actual functional residual capacity (FRC) measured under body conditions (BTPS). The numbers refer to the individual patients as given in Table V, (A, B, C). Isovolumic compliance lines are drawn. The normal range is given as the shaded area between 0.5 and 0.8 kPa-l •

these data are given in more detail for the patients who diedbecauseof ventilatory insufficiency (Group A), and for the survivors with open (Group B) and with closed bullae (Group C). Mortality data (Table V). Seven patients died of progressive ventilatory insufficiency. All had dyspnea Grades IV or V. Three of them were operated on bilaterally. This group is characterized by a small VC and an extremely small FEV1%VC before operation. Two years after bullectomy a marked increase in VC is found, whereas the FEV1%VC hardly changes and the FIV1%VC remains normal. The decrease of RV%TLC after bullectomy is mainly due to the increase in VC. The last available spirographic data taken at a mean of 7 years after operation show a loss in VC and a further deterioration of FEV1%VC. The arterial oxygen pressure (Po 2) at rest was subnormal prior to bullectomy, 8.5 kPa (SD 1.5). Two years after operation it was normal, 10.4 kPa (SD 1.0), and subsequently it deteriorated gradually. The last available mean value was 7.1 kPa (SD 1.5). A slight hypoventilation occurred in the [mal stage in only two patients; the other five remained normocapnic. One patient who died is not included in Group A, because he died of disseminated bronchial carcinoma and not of ventilatory insufficiency (Group C).

bilateral giantbullae before and 2 years after bullectomy. The regional alveolar ventilation in L/min/L is given before and after surgery. Regional alveolar ventilation isderived from the equation: N, = N_ (l - e-kt) by calculating the value of k which, with certain limitations, represents alveolar ventilation eVA) divided by alveolar volume (VA), according to Kety." Bullae were removed from right upper lobe, apex of right lower lobe, leftupper lobe, and apex of leftlower lobe. Before bullectomy a good alveolar ventilation was found only in the right lower lobe; 2 years after operation alveolar ventilation was markedly improved in all lung regions.

Open bullae (Table V). Eight ofthe 10 patients with open bullae are still alive; two were operated on bilaterally. The data of the survivors show a relatively small increase in VC 2 years after bullectomy, because prior to operation the bullae contributed to the VC as was demonstrated bronchospirometrically. After 2 years there is a defmite improvement in FEV1%VC; the FIV1%VC remained normal. The decrease in RV%TLC is due to the removal of the ventilated bullae. Subsequently, there is a gradual deterioration with an annual loss in VC of 110 rnl (SD 50), and in FEV 1of 130 rnl (SD 35). Bloodgases at rest showed no significant changes and stayed within normal limits during follow-up. Closed bullae (Table V). Five of the 17 patients with closed bullae died of ventilatory insufficiency. The data of the 12 survivors are shown; one of those died of disseminated bronchial carcinoma. Five were operated on bilaterally. The increase in VC in the first postoperative years is marked, with a concomitant decrease in RV%TLC. The improvement in FEVj%VC is small, and FIV1%VC remained normal. In this group after the first 2 years a gradual deterioration also occurs and after a mean follow-up period of 13 years pulmonary function, particularly FEV1%VC, is poorer than before bullectomy. The

The Journal of Thoracic and Cardiovascular Surgery

6 8 Laros et al.

Table V. Preoperative spirographic data compared with data 2 years postoperatively and at last check-up for three patient groups

Groups Group A Died of ventilatory insufficiency (1-7)* VC%VCn RV%TLC FEV,%VC FIV,%VC Group B Open bullae (8-15)* VC%VCn RV%TLC FEV,%VC FIV,%VC Group C Closed bullae (16-27)* VC%VCn RV%TLC FEV,%VC FIV,%VC

Bullectomy

No. of patients

Age (yr) at bullectomy

Unilateral

7t

56 ± 5

4

8

12

46 ± 9

49 ± 6

6

I Bilateral 3

2

5

Observation period (yr)

VCn (ml)

7.7 ± 4

3970 ± 370

10.5 ± 4

13.0 ± 5

Spirographic data Preop.

12 yr

postop.

I Last check-up

82 42 29 82

± ± ± ±

18 5 8 3

120 38 30 85

± ± ± ±

14 4 8 4

85 47 23 78

± ± ± ±

17 5 7 4

109 40 34 82

± ± ± ±

14 4 18 4

120 31 50 90

± ± ± ±

13 3 21 5

99 44 43 84

± ± ± ±

21 7 14 4

89 39 54 82

± ± ± ±

19 7 8 4

115 34 59 88

± ± ± ±

16 5 8 4

92 42 45 83

± 16 ± 6 ± 14 ± 5

4480 ± 290

4210 ± 195

Legend: Values expressed as mean ± I standard deviation.

'Numbers refer to patients in Fig. 3. tTwo patients had open and five had closed bullae. :j:One patient died of disseminated bronchial carcinoma.

decline in VC and FEV I was 110 ml/yr (SO 80) and 115 ml/yr (SO 80), respectively, with a wide interindividual variation. Blood gases stayed within normal limits during the observation period. Reappearance of bullae. In all patients with very poor pulmonary function before operation (Group A), bullous degeneration progressed gradually, but no giant bullae reappeared. In two of the eight patients with open bullae a vanishing destruction of both lower lobes developed, and small bullae recurred in one. In the 12 patients with closed bullae small bullae appeared in four patients. During the observation period, no recurrence of giant bullae occurred in any patients in these two groups. Discussion Surgical removal of giant bullae in generalized pulmonary emphysema is a well-known procedure. The vanishing type of bullous disease is, in our experience and that of others, not a good indication for elective operation. I, 2, 7 In the early years several patients with vanishing lung syndrome have been operated on in our clinic, and either a resection had to be done or the thorax

was closed without intervention. Soon after the operation the preoperative situation reappeared in the remaining emphysematous parenchyma with a marked loss in pulmonary function. A vanishing lobe is a lobe destroyed by bullae. There is no displacement of the adjacent tissue. The destroyed lobe has a buffer function and prevents the remaining lung tissue from overstretch. During the preoperative work-up vanishing lobes were recognized by angiography and tomography. Characteristically these lobes showed pruned vessels and septae within the bullous zone. The introduction of digital subtraction angiography and the computed tomographic scan has certainly improved our means of differentiating vanishing lung syndrome from simple bullae with noninvasive techniques. Both open and closed bullae constitute a proper indication for elective operation in generalized emphysema, provided that the bullae occupy at least 50% of a hemithorax and displace adjacent lung tissue. The postoperative improvement depends on the size and the type of the bullae removed. Open bullae have a free connection with the bronchial tree and contribute to VC as well as to RV. The slow space ventilation of these

Volume 91

Bullectomy for giant bullae

Number 1 January, 1986

bullae can well be demonstrated by separate helium washout procedures: At the end of the washout a characteristic helium peak appears at maximal expiration (Fig. 2). The adjacent parenchyma is collapsed rather than compressed (Fig. 1). After resection there is little change in VC, but FEV l improves because of expansion of the previously collapsed parenchyma. R V is reduced because of the obliteration of the bullous residue. Closed bullae do not contribute to VC and RV. They have a space-occupying effect and compress the remaining parenchyma. VC and RV are low on the affected side and both increase after bullectomy, resulting in little change in RV%TLC. FEVI improves in proportion to the increase in VC and therefore, FEV\%VC is hardly altered by removal of the bullae. Our 27 patients with giant bullae all had generalized emphysema and a flaccid lung. Preoperatively, the majority was severely disabled and had a poor pulmonary function, mean FEVI%VC = 42 (for the total group). After bullectomy all patients experienced subjectiveimprovement, which was most pronounced in the most seriously ill patients, even if the absolute improvement of pulmonary function was small. With time dyspnea increased again, but in many patients the amelioration of symptoms lasted several years (Table III). As expected, the postoperative improvement of pulmonary function concerned particularly FEVI%VC and RV%TLC in the patients with open bullae and VC in the patients with closed bullae (Table IV). In both types ofpatients xenon studies showed a great improvement in alveolar ventilation in the area that was previously occupied in bullae (Fig. 4),15,16 In patients with a very poor pulmonary function (Table V, Group A) the preoperative arterial P02 was too low, improved in the first 2 years postoperatively, and gradually deteriorated. In the other patients the arterial P02 levels remained normal during the observation period. The improvement shown by the spirographic data persisted for several years and then gradually returned to preoperative values and beyond. These fmdings are compatible with the results in the literature.s 5, 6, II Seven patients died of ventilatory insufficiency with a mean postoperative survival of 7.7 years. These patients had very poor pulmonary function prior to operation (FEV! below 940 mI). After bullectomy FEV I increased to 1,430 mI. Although the patients ultimately died, we think that bullectomy in these patients Certainly lengthened survival and improved quality of life. 7, 8 The annual decline of VC and FEV after bullectomy in our patients is comparable with the deterioration of pulmonary function in populations with emphysema. II We therefore

69

found no evidence for acceleration of the underlying emphysematous process. Also there was no tendency for giant bullae to recur in the observation period. In agreement with the literature, the bullae in our population were not confmed to the upper lobes. 5, 6, II. 17 In nine patients giant bullae were located in the middle and lower lobes. In 10 patients bilateral giant bullae were present and these were operated on bilaterally. They did comparatively well. Only one patient had bilateral operations in the same session. Since 1979 similar patients are operated on simultaneously on both sides by a midsternal approach, if the bullae can be reached by the anterior route. The surgical risk of unilateral and bilateral bullectomy is acceptable even in seriously ill patients. There were no surgical and postoperative deaths in our 27 patients with giant bullae. A repeat thoracotomy had to be done in two patients because of persisting air leak. In our opinion high-pressure ventilation during anesthesia and strongly negative pressures during postoperative suction drainage of the pleural cavity should be avoided. The presence of chronic purulent bronchitis forms a contraindication for bullectomy in our department. REFERENCES Billig DM: Surgery for bullous emphysema. Chest 70:572573, 1976 2 FitzGerald MX, Keelan PJ, Cugell DW, Gaensler EA:

Long-term results of surgery for bullous emphysema. J THORAC CARDIOVASC SURG 68:566-588, 1974 3 Gunstensen J, McCormack RJM: The surgical management of bullous emphysema. J THORAC CARDIOVASC SURG 65:920-925, 1973 4 Knudson RJ, Gaensler EA: Surgery for emphysema. Ann Thorac Surg 1:332-362, 1965

5 Pride NB, Hugh-Jones P, O'Brien EN, Smith NA: Changes in lung function following the surgical treatment of bullous emphysema. Q J Moo 39:49-69, 1970 6 Wesley JR, Macleod WM, Mullard SM: Evaluation and surgery of bullous emphysema. J THORAC CARDIOVASC SURG 63:945-955, 1972 7 Potgieter BD, Benatar SR, Hewitson RF, Ferguson AD: Surgical treatment of bullous lung disease. Thorax 36:885-890, 1981

8 Boushy SF, Kohen R, Billig DM, Heiman MJ: Bullous emphysema. Clinical, roentgenologic and physiologic study of 49 patients. Chest 54:327-334, 1968 9 Boushy SF, Billig DM, Kohen R: Changes in pulmonary function after bullectomy. Am J Moo 47:916-922, 1969 10 Foreman S, Weill H, Duke R, George R, Ziskind M: Bullous disease of the lung. Physiologic improvement after surgery. Ann Intern Moo 69:757-767, 1968 11 Pearson MG, Ogilvie C: Surgical treatment of emphysematous bullae. Late outcome. Thorax 38:134-137, 1983

7 0 Laros et al.

12 Laros CD: Preoperative function analysis-possibilities and limits. Pneumonology 147:83-96, 1972 13 Fain WR, Conn JH, Campbeli GD, Chavez CM, Gee HL, Hardy JD: Excisionof giant pulmonary emphysematous cysts. Report of 20 cases without deaths. Surgery 62:552-559, 1967 14 Douma JH, Laros CD: A device for plotting volume pressure curves of esophageal ballons in situ in a clinical set up. Bull Physiopathol Respir 7:215-225, 1971 15 Baldwin EF, Coumand A, Richards DW: Pulmonary

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insufficiency, physiological classification of clinical methods of analysis, standard values in normal subjects. Medi-

cine 27:243-265, 1948 16 Kety SS: Theory and application of the exchange of inert gas at the lungs and tissues. Pharmacol Rev 3:1-41, 1951 17 Lopez-Majano V, Kieffer RF, Marine DN, Garcia DA, Wagner HN Jr: Pulmonary resection for bullous disease. Am Rev Respir Dis 99:554-564, 1969

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