GENERAL THORACIC

Minimal Alteration of Pulmonary Function After Lobectomy in Lung Cancer Patients With Chronic Obstructive Pulmonary Disease Yasuo Sekine, MD, Takekazu Iwata, MD, Masako Chiyo, MD, Kazuhiro Yasufuku, MD, Shinichiro Motohashi, MD, Shigetoshi Yoshida, MD, Makoto Suzuki, MD, Toshihiko Iizasa, MD, Yukio Saitoh, MD, and Takehiko Fujisawa, MD Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

Background. The aim of this study was to evaluate the influence of chronic obstructive pulmonary diseases (COPD) on postoperative pulmonary function and to elucidate the factors for decreasing the reduction of pulmonary function after lobectomy. Methods. We conducted a retrospective chart review of 521 patients who had undergone lobectomy for lung cancer at Chiba University Hospital between 1990 and 2000. Forty-eight patients were categorized as COPD, defined as percentage of predicted forced expiratory volume at 1 second (FEV1) less than or equal to 70% and percentage of FEV1 to forced vital capacity less than or equal to 70%. The remaining 473 patients were categorized as non-COPD. Results. Although all preoperative pulmonary function test data and arterial oxygen tension were significantly lower in the COPD group, postoperative arterial oxygen tension and FEV1 were equivalent between the two

groups, and the ratio of actual postoperative to predicted postoperative FEV1 was significantly better in the COPD group (p < 0.001). With multivariable analysis, COPD and pulmonary resection of the lower portion of the lung (lower or middle-lower lobectomies) were identified as independent factors for the minimal deterioration of FEV1. Actual postoperative FEV1 was 15% lower and higher than predicted, respectively, in the non-COPD patients with upper portion lobectomy and the COPD patients with lower portion lobectomy. Finally, we created a new equation for predicting postoperative FEV1, and it produced a higher coefficient of determination (R2) than the conventional one. Conclusions. The postoperative ventilatory function in patients with COPD who had lower or middle-lower lobectomies was better preserved than predicted. (Ann Thorac Surg 2003;76:356 – 62) © 2003 by The Society of Thoracic Surgeons

L

was the absolute risk factor for both postoperative refractory supraventricular arrhythmia and various types of pulmonary complications and poor long-term survival [7, 8]. However, sometimes these patients with moderate emphysema had better postoperative pulmonary function than expected. Because we frequently encounter such lung cancer patients with moderate emphysema, we need to know not only the operative risks but also accurate postoperative residual lung function. Based on the above results, we hypothesized that even in patients with moderate emphysema, lobectomy for lung cancer also has some beneficial effects to suppress functional deterioration of the residual lung similar to effects of volume reduction operation. To evaluate the functional resectability for lung cancer, the preoperative pulmonary function test (PFT) is still the gold standard, and ppoFEV1 is the most reliable predictor for mortality and morbidity [2, 9]. Although several approaches, such as inhalation perfusion (single-photon emission computed tomography) imaging [10], perfusion lung scintigraphy [11], and quantitative computed tomography [12] have been proposed for predicting precise postoperative FEV1, none of these methods has been proven to be more accurate than the simple calculation based on the number of the bronchopulmonary segments removed.

ung cancer and chronic obstructive pulmonary disease (COPD) are common fatal diseases, and lung cancer is far more common in patients with COPD than in those with normal airflow obstruction [1]. It is well known that patients with severe emphysema have a higher risk of postoperative complications than patients without emphysema [2]. However, it has been reported that pulmonary function improved after lobectomy in some severely emphysematous patients [3–5]. Edwards and colleagues [6] have shown that although patients with severe emphysema who fulfilled predicted postoperative forced expiratory volume in 1 second (ppoFEV1) less than 40% of predicted had a significant risk of mortality after lobectomy, actual postoperative FEV1 was not different between patients with ppoFEV1 less than 40% and those with ppoFEV1 more than 40%. We recently reported that even moderate COPD, which was defined as an FEV1 at or below 70% of predicted and an FEV1:forced vital capacity (FVC) ratio at or below 70%,

Accepted for publication March 4, 2003. Address reprint requests to Dr Fujisawa, Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; e-mail: [email protected].

© 2003 by The Society of Thoracic Surgeons Published by Elsevier Inc

0003-4975/03/$30.00 PII S0003-4975(03)00489-2

However, recent studies have shown that underestimation of the actual postoperative FEV1 may occur due to heterogeneous distribution of ventilation and perfusion [13]. The purpose of this study was to evaluate the influence of COPD on the change in pulmonary function after lobectomy in lung cancer patients and to elucidate the characteristics of patients with less diminished postoperative pulmonary function in order to establish a more accurate formula for predicting postoperative FEV1.

Patients and Methods We retrospectively reviewed the medical records of 950 patients with non-small cell lung cancer who underwent thoracotomy and pulmonary resection between January 1990 and March 2000 at Chiba University Hospital. Of those, 816 lobectomies, 63 pneumonectomies, 20 segmentectomies, 40 partial lung resections, and 11 combined resections with lungs and major organs were performed. We focused on the 816 lobectomy cases because the anatomic and physiologic changes of residual lungs on the operative side were thought to be most influential to postoperative pulmonary function. Furthermore, to exclude cases with bronchial stenosis or atelectasis, 147 central type lung cancers or cases accompanied by subsegmental or wider atelectasis and 103 cases with tumor diameter exceeding 5 cm were all excluded. These cases were excluded because the predicted postoperative pulmonary function was expected to differ greatly from the actual function because of the nonfunctioning lung. Of the remaining 566 cases, postoperative pulmonary function data were not available in 45 cases because of severe postoperative pulmonary complications; therefore, they were excluded from the analysis. Finally, 521 cases with PFT data for pulmonary function tests and blood gas analyses preoperatively and 1 month postoperatively were entered into this study. Preoperative evaluation for all patients otherwise included a detailed history and physical examination, complete blood cell count, serum electrolytes and renal profile, spirometry, and a 12-lead electrocardiogram. Spirometry was repeated three times, and the highest value was adopted. All current smokers were instructed to cease smoking at the first visit to our hospital, and PFT was repeated immediately before the operation. After discharge from the hospital, we confirmed continuous smoking cessation in all patients postoperatively at least for 3 months by questioning the patients and their families at every visit to the outpatient clinic. Airway obstruction was defined as percentage of predicted forced expiratory volume in 1 second (percent predicted FEV1) at or below 70% and FEV1:FVC at or below 70% [7, 14]. FEV1 and FEV1:FVC were independent predictors of all cause or respiratory disease mortality [15]. These two variables were used to grade the severity of obstructive abnormalities. In the American Thoracic Society statement [16], when FEV1:FVC is below the normal range (less than 70% to 80% of predicted), percent predicted FEV1 less than 70% was recognized as moder-

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ate COPD and less than 50% as severe. Therefore, the criterion of this study was defined as moderate. No bronchodilator was used at PFT. Forty-eight patients fulfilled this criterion (COPD group), and the other 473 were categorized as non-COPD. Only 7 patients had less than 50% of preoperative predicted FEV1, and 1 patient had critically severe emphysema with 0.76 L (27.6% of predicted) of preoperative FEV1. Incentive spirometry was used routinely for enhancing lung expansion 2 weeks before and after the operation. Preoperative pulmonary rehabilitation for COPD patients was done from the time of admission to operation (approximately 2 weeks). If PFT data fulfilled the COPD criterion, preoperative PFT was repeated after the respiratory rehabilitation for the final classification. We estimated ppoFEV1 by using the following equation: ppoFEV1 ⫽ preoperative FEV1 ⫻ (1 – S ⫻ 0.0526), where S ⫽ number of resected bronchopulmonary segments [17]. After actual postoperative FEV1 (apoFEV1) was obtained, the ratio of apoFEV1 to ppoFEV1 (apo/ppo FEV1) was calculated. Then, the minimal deterioration of postoperative FEV1 was determined when apo/ppo FEV1 was 1.15 or more, which was the highest 10% in this study population. This cut-off point was determined based on the distribution of apo/ppo FEV1. We created a histogram where the apo/ppo FEV1 was divided every 0.05. The parametric method was not appropriate for analysis because the distribution had two peaks (n ⫽ 69 at 1.00 to 1.05 and n ⫽ 21 at 1.15 to 1.20). Therefore, the cut-off point was set to the trough (apo/ppo FEV1 ⫽ 1.15) between the two peaks. The clinical record of each patient was reviewed for the following information: age, gender, body mass index, smoking history, concomitant diseases, and postoperative complications. Positive smoking history included any former smokers as well as current smokers. Descriptions of operations were studied for method of thoracotomy and portion of lobectomy. We divided the portion of lobectomy into two groups, upper portion (upper, middle or upper-middle lobectomies) and lower portion (lower or middle-lower lobectomies). Pathologic staging was determined according to the TNM (tumor, node, and metastasis) classification by Mountain [18]. To evaluate the radiologic severity of emphysema, chest conventional or high-resolution computed tomography was reviewed utilizing the semiquantitative method reported by Goddard and colleagues [19]. A total of three slices were obtained from the lung apex to the lung base at the following levels: upper margin of the aortic arch, origin of the middle lobe bronchus, and right lower pulmonary vein. Right and left lungs were evaluated separately. Then each of the six views was classified into five grades as follows: grade 0 ⫽ no emphysema, 1 ⫽ emphysematous lesions less than 25%, 2 ⫽ emphysematous lesions between 25% and 50%, 3 ⫽ emphysematous lesions between 51% and 75%, and 4 ⫽ emphysematous lesions over 75%. Areas of low attenuation, indicating less than ⫺950 HU (the lowest level of the mean computed tomographic value of normal lung), and vascular disruption were considered to be suggestive of emphy-

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sema [19]. The evaluation was performed by three thoracic specialists independently in a blinded fashion, and the final score was calculated as the mean of scores assigned by the three readers. Finally, we classified all patients into four subgroups according to the results of multivariable analysis, created the new equation for predicted postoperative FEV1, and validated the usefulness of this formula in 142 lung cancer patients who matched the criteria of this study and had lobectomy at our hospital between April 2000 and March 2002.

Statistical Analysis Data were analyzed using the Stat View Version 5.0 (Statistical Analysis Systems; Cary, NC, USA) by a statistician. To compare the differences between the COPD and non-COPD groups, a Mann-Whitney U test was utilized to analyze continuous variables, and the ␹2 test or Fisher exact test to analyze for categorical variables. The correlation between ppoFEV1 and apoFEV1 was calculated by simple linear regression analysis. The TukeyKramer multiple comparison was applied for comparing variables among four subgroups. All preoperative and intraoperative variables including gender, age, body mass index, pathologic type and stage, existence of COPD, portion of lobectomy, type of thoracotomy, operative time, and blood loss were entered into a logistic regression model to identify variables that were independently predictive of less deteriorated postoperative FEV1 (apo/ppo FEV1 ⱖ 1.15). A p value less than 0.05 was considered statistically significant.

Ann Thorac Surg 2003;76:356 – 62

Table 1. Patient Characteristics Characteristic Gender (male/female) Age (years)a BMI (kg/m2)a Smoking history Other medical problems Hypertension Cardiac disease Histologic diagnoses Squamous cell carcinoma Adenocarcinoma Others Pathologic staging I II III IV Unknown Methods of thoracotomy Standard Muscle sparing Others Type of lobectomy Upper Middle Upper ⫹ middle Lower Middle ⫹ lower

Non-COPD (n ⫽ 473)

COPD (n ⫽ 48)

p Value

273/200 62.3 ⫾ 9.6 22.6 ⫾ 2.9 274 (57.9%)

46/2 66 ⫾ 6.6 22.1 ⫾ 3.8 46 (95.8%)

⬍ 0.001 0.009 0.27 ⬍ 0.001

126 (26.6) 44 (9.3)

10 (20.8) 5 (10.4)

79 (16.7) 350 (74) 44 (9.3)

21 (43.8) 25 (52) 2 (4.2)

249 (52.6) 50 (10.6) 153 (32.3) 19 (4) 2 (0.4)

25 (52.1) 7 (14.6) 14 (29.2) 2 (4.2) 0 (0)

388 (82) 73 (15.5) 12 (2.5)

42 (87.5) 2 (4.2) 4 (8.3)

269 (56.9) 29 (6.1) 10 (2.1) 156 (33) 9 (1.9)

30 (62.5) 2 (4.2) 2 (4.2) 13 (27.1) 1 (2.1)

0.59

0.013

0.77

Results

Data are presented as mean ⫾ standard deviation; (%).

Preoperative Patient Characteristics

BMI ⫽ body mass index; disease.

a

Patient characteristics are summarized in Table 1. There were more men in the COPD group (95.8%) compared with the non-COPD group (57.7%, p ⬍ 0.001). Smoking was significantly more prevalent in the COPD group (p ⬍ 0.001). The distribution of age and body mass index were similar between the two groups. There were no statistically significant differences between the groups with respect to preoperative hypertension and cardiac diseases. Although the distribution of pathologic non-small cell lung cancer stage and type of lobectomy were similar between the two groups, distribution of squamous cell carcinoma (p ⬍ 0.001) and standard thoracotomy in the methods of thoracotomy (p ⫽ 0.013) were more predominant in the COPD group.

Arterial Blood Gas Analyses and Pulmonary Function Tests Comparing preoperative arterial blood gas analyses and PFT between the two groups, COPD patients had significantly diminished arterial oxygen tension (Pao2) (nonCOPD 89 ⫾ 9 mm Hg, COPD 85 ⫾ 11 mm Hg, p ⬍ 0.01), FEV1 (non-COPD 2.3 ⫾ 0.6 L, COPD 1.8 ⫾ 0.3 L, p ⬍ 0.01), and percent predicted FVC (non-COPD 103% ⫾ 50%, COPD 87% ⫾ 11%, p ⫽ 0.02) than patients in the nonCOPD group as well as percent predicted FEV1 and

0.49 0.79

all other data are n

COPD ⫽ chronic obstructive pulmonary

FEV1:FVC. Conversely, postoperatively, only percent predicted FVC (non-COPD 70% ⫾ 16%, COPD 65% ⫾ 9%, p ⫽ 0.018), percent predicted FEV1 (non-COPD 75% ⫾ 17%, COPD 50% ⫾ 10%, p ⬍ 0.01), and FEV1:FVC (non-COPD 81% ⫾ 9%, COPD 71% ⫾ 9%, p ⬍ 0.01) were lower in the COPD group than those in the non-COPD group. Postoperative PaO2 and FEV1 were equivalent between the two groups. The ratio of apo/ppo FEV1 was higher in the COPD group than that in the non-COPD group (p ⬍ 0.001, Fig 1). The changing ratios of PaO2, arterial carbon dioxide tension, FVC, FEV1, and FEV1:FVC, which represent percent change ⫽ (postoperative value – preoperative value)/preoperative value ⫻ 100, were calculated from arterial blood gas and PFT data. PaO2, FVC and FEV1 were less diminished in the COPD group than those in the non-COPD group. The FEV1:FVC ratio was improved in the COPD group and significantly better than that in the non-COPD group (Table 2).

Multivariate Analysis of Factors for the Minimal Deterioration of Postoperative FEV1 Next, we focused on why COPD patients had less loss of pulmonary function, especially FEV1, than the non-

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Table 3. Multivariable Analysis of Preoperative and Operative Factors for Minimal Deterioration of Postoperative FEV1 (apo/ppo FEV1 ⱖ 1.15) Variable

Fig 1. The ratio of actual postoperative forced expiratory volume in 1 second to predicted postoperative forced expiratory volume in 1 second (apo/ppo FEV1) was higher in the chronic obstructive pulmonary disease (COPD) group than that in the non-COPD group (p ⬍ 0.01). (Dotted line ⫽ apo/ppoFEV1 ⫽ 1.0.)

COPD patients. To clarify this question, we made a criterion of the minimal deterioration of postoperative FEV1 as apo/ppo FEV1 at least 1.15, which was the highest 10% rank of apo/ppo FEV1 (51 patients, 35 non-COPD and 16 COPD) as mentioned in the Methods section. With a multivariable logistic regression model, COPD and pulmonary resection of lower portion (lower or middle-lower lobectomies) were identified as independent factors for the minimal deterioration of postoperative FEV1 (Table 3).

Semiquantitative Evaluation of the Grade of Emphysema on Preoperative Chest Computed Tomography From the results of the multivariable analysis above, we divided all patients into four subgroups; group 1 ⫽ non-COPD with lobectomy of upper portion (n ⫽ 308), group 2 ⫽ non-COPD with lobectomy of lower portion (n ⫽ 165), group 3 ⫽ COPD with lobectomy of upper portion (n ⫽ 34), and group 4 ⫽ COPD with lobectomy of lower portion (n ⫽ 14) (Table 4). Apo/ppo FEV1 in groups 1 and 2 was significantly lower than those in groups 3 and 4. In particular, group 4 had the highest apo/ppo FEV1. To clarify the radiologic characteristics in each group, chest computed tomograms were randomly selected, and Table 2. Percent Changes in Arterial Blood Gas and Pulmonary Function From Preoperative to Postoperative Measurements

Pao2 (%) Paco2 (%) FVC (%) FEV1 (%) FEV1:FVC (%)

COPD (COPD vs. nonCOPD) Portion of resection (lower vs. upper portion) Method of thoracotomy (standard vs. muscle spare and others) Histologic type (Squamous vs. others) Age (ⱖ 70 vs. ⬍ 70 years) Gender (male vs. female) BMI (ⱖ 25 vs. ⬍ 25 kg/m2)

Odds Ratio

95% CI

p Value

6.871

3.033–15.569

⬍ 0.0001

5.415

2.743–10.69

⬍ 0.0001

0.396

0.113–1.387

0.148

1.148

0.551–2.390

0.713

1.036 1.695 0.807

0.507–2.118 0.788 –3.645 0.345–1.888

0.923 0.177 0.620

BMI ⫽ body mass index; CI ⫽ confidence interval; chronic obstructive pulmonary disease

COPD ⫽

the grade of emphysema was evaluated. Computed tomographic values in the COPD groups (groups 3 and 4) were higher than those in the non-COPD groups. However, most COPD patients had radiologically homogeneous emphysema, and there were no significant differences among three evaluation levels in each group (data not shown). From the data of apo/ppo FEV1 (Table 4), we found that apoFEV1 was approximately 15% lower and higher than ppo FEV1 in groups 1 and 4, respectively, and equivalent to ppo FEV1 in groups 2 and 3. Therefore, we multiplied a specific coefficient to ppoFEV1 in each group in order to improve predictive accuracy, ie, 0.85 in group 1, 1.0 in groups 2 and 3, and 1.15 in group 4. For example, the new formula of ppoFEV1 in the group 1 ⫽ 0.85 ⫻ preoperative FEV1 ⫻ (1 – S ⫻ 0.0526), where S ⫽ number of resected bronchopulmonary segments. The correlation between the ppoFEV1 and the apoFEV1 was improved from R2 ⫽ 0.367 to R2 ⫽ 0.634 by this modified formula. We validated the new equation by applying it to the 142 lung cancer patients who underwent lobectomy between April 2000 and March 2002. The criteria for patient selection were the same as those mentioned in the Methods section. The number of patients was 80 in group 1, 42 in group 2, 12 in group 3, and 8 in group 4. Modified ppoFEV1 was significantly correlated with apoFEV1 (R2 ⫽ 0.619, Fig 2) compared with the conventional model (R2 ⫽ 0.421) similar to that in the study population.

Non-COPD

COPD

p Value

Comment

⫺2.5 ⫾ 12.4 ⫺0.6 ⫾ 18.0 ⫺30.9 ⫾ 12.0 ⫺29.2 ⫾ 11.6 3.2 ⫾ 11.8

2.2 ⫾ 15.7 ⫺2.0 ⫾ 9.9 ⫺25.7 ⫾ 11.7 ⫺13.1 ⫾ 18.0 17.3 ⫾ 18.4

0.019 0.608 0.004 ⬍ 0.001 ⬍ 0.001

The frequent coexistence of COPD increases the risk of operation because of impaired postoperative ventilatory function [7, 20]. Despite great advances in anesthesia, minimally invasive surgical technique, preoperative and postoperative patient management, including radical physiotherapy, bronchodilator inhalation, and incentive spirometry, COPD patients frequently have cardiopulmonary complications. Conversely, lung volume reduction improves pulmonary function in patients with severe

All data are presented as mean ⫾ standard deviation. FEV1 ⫽ forced expiratory volume in 1 second; FVC ⫽ forced vital capacity; Paco2 ⫽ arterial carbon dioxide tension; Pao2 ⫽ arterial oxygen tension.

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Table 4. Semiquantitative Evaluation of Low Attenuation Area on Preoperative Chest Computed Tomography Group

COPD status Resected portion n apo/ppo FEV1a CT value (n) Operative sideb Nonoperative sidec

1

2

3

4

non-COPD Upper 308 0.86 ⫾ 0.14 50 2.04 ⫾ 1.53 1.98 ⫾ 1.4

non-COPD Lower 165 0.98 ⫾ 0.16 36 2.34 ⫾ 1.37 2.28 ⫾ 1.21

COPD Upper 34 1.08 ⫾ 0.22 27 4.56 ⫾ 2.21 4.52 ⫾ 2.54

COPD Lower 14 1.15 ⫾ 0.1 14 3.59 ⫾ 1.86 3.24 ⫾ 1.73

p ⬍ 0.01 group 1 vs. groups 2, 3, 4; group 2 vs. groups 3, 4. vs. groups 1, 2.

a

b

p ⬍ 0.01 group 3 vs. groups 1, 2; p ⬍ 0.05 group 4 vs. group 1.

apo ⫽ actual postoperative; COPD ⫽ chronic obstructive pulmonary disease; in 1 second; ppo ⫽ predicted postoperative.

COPD. This phenomenon suggested to us that resection of emphysematous lung might be beneficial for preserving lung function even in patients with moderate COPD. In this study, we clarified that in COPD patients, defined by pulmonary function tests, arterial blood gas data were undiminished and pulmonary function was less diminished when compared to the data from patients with normal airflow obstruction. In particular, FEV1:FVC improved after lobectomy in COPD patients. This phenomenon occurred not only in patients with heterogeneous emphysema but also in those with homogeneous emphysema confirmed by chest computed tomographic evaluation. Furthermore, by multivariable analysis, lobectomy of lower portion (lower lobectomy or middlelower lobectomies) was an independent factor for inducing the minimal deterioration of postoperative FEV1. Finally, we established a modified formula for predicting postoperative FEV1 based on the bronchopulmonary segments according to the existence of COPD and the portion of lobectomy. The effects of lung volume reduction are thought to be related to restoration of the elastic recoil of pulmonary

Fig 2. The correlation between actual postoperative forced expiratory volume in 1 second (apoFEV1) and modified predicted postoperative forced expiratory volume in 1 second calculated by the new equation. Modified predicted postoperative forced expiratory volume in 1 second (ppoFEV1) was significantly correlated with apoFEV1 (R2 ⫽ 0.619, p ⬍ 0.001). (Black diamonds ⫽ the value of the modified ppoFEV1 plotted against the apoFEV1 values.)

CT ⫽ computed tomographic;

c

p ⬍ 0.01 group 3

FEV1 ⫽ forced expiratory volume

parenchyma and improvement of thoracic motion [21, 22]. However, the mechanism of change of pulmonary function in the COPD patients of this study seemed to be different. First, the subjects of this study were not patients with severe emphysema who needed volume reduction operations. Second, both FVC and FEV1 did not increase in the COPD patients. This may be due to removal of functioning lung tissues. Third, lobectomy of the lower portion resulted in better residual lung function compared with upper portion lobectomy. In general, emphysema is more predominant in the upper lobe than in the lower lobe; therefore, the target of lung volume reduction is frequently the apex of the upper lobe. No patient had alpha 1 anti-trypsin deficiency, and there was no emphysema predominant in the lower lobe. We sometimes find occasional anatomic repositioning after upper lobectomy, which causes narrowing of the orifice of lower or middle lobe bronchus [23]. Conversely, lower lobectomy usually has no effect on the remaining upper and middle bronchus. These anatomic differences may have influenced the synchronization of lung and chest wall motion. After lobectomy, residual lungs overinflate, the diaphragm elevates, the mediastinum shifts to the operative side, and the intercostal space is reduced in order to fill the space of the resected lung. We speculate that the movement and elevation of the diaphragm may be different between postlower lobectomy and postupper lobectomy [24]. To answer this question, we are now conducting a prospective study to determine the cause of good postoperative FEV1 after lobectomy of the lower portion in COPD patients. This retrospective study has certain limitations. First, preoperative optimization of respiratory reserve in the COPD patients on medications (including antibiotics, bronchodilators, and steroids) and physical rehabilitation are all confounding variables. Because the study was not controlled, these factors were not incorporated into our statistical analysis. Second, the recovery of ventilatory function takes at least 3 to 6 months [25, 26]. In this study, postoperative PFT was measured 1 month after operation, which is earlier than that of other studies [3, 4]. The postoperative lung function might not have been fully recovered at this point. The main cause of loss of forced

respiratory maneuvers is restricted thoracic wall motion influenced by wound pain [27]. The severity of postoperative pain depends on the method of thoracotomy and affects pulmonary gas exchange immediately after thoracic operation [28]. However, we found that the method of thoracotomy was not an independent factor influencing the outcome of less diminished FEV1. We speculate that wound pain might not have strongly affected the PFT data in this study. Giordano and associates [11] reported that perfusion lung scintigraphy could predict postlobectomy residual lung function 1 month after operation. Because pulmonary function recovers in a timedependent manner [25], the postoperative PFT data 1 month after operation may be consistent with the longterm pulmonary function. Finally, we established a modified equation for predicting postoperative FEV1. If a patient has marginal pulmonary function, such as 800 mL of ppoFEV1, and lower lobectomy is planned, the patient’s modified ppoFEV1 would become 920 mL, which is acceptable for operation. This new equation has a potency of expanding the functional indication of standard operation for lung cancer patients with COPD. In conclusion, although COPD patients have a higher risk of postoperative complications, the preservation of ventilatory function may be better than predicted. In particular, lobectomy of the lower portion induced minimal deterioration of postoperative FEV1. Therefore, we propose a new equation for predicting individual postoperative FEV1 according to the patient’s pulmonary function and the portion of the lung lobe resected.

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9.

10.

11. 12. 13. 14. 15. 16. 17.

18. 19. 20.

We thank Eri Sekine, BS, MPH (Data Management and Biostatistics, Wyeth Lederle Japan, Ltd, Tokyo, Japan), for statistical assistance. 21.

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