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Ann Thorac Surg 2007;83:1134-1139
© 2007 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Predicted Versus Observed FEV₁ and DLCO After Major Lung Resection: A Prospective Evaluation at Different Postoperative Periods

Division of Thoracic Surgery, "Umberto I" Regional Hospital, Ancona, Italy

Accepted for publication November 20, 2006.

^_* Address correspondence to Dr Brunelli, Via S. Margherita 23, Ancona 60129, Italy (Email: alexit_2000{at}yahoo.com).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
Background: The objective of this study was to prospectively assess the agreement between predicted and observed postoperative values of forced expiratory volume in 1 second (FEV₁) and carbon monoxide lung diffusion capacity (DLCO) after major lung resection.

Methods: Two hundred consecutive patients undergoing lobectomy or pneumonectomy for lung cancer in a single center were prospectively evaluated with complete preoperative and repeated postoperative measurements of FEV₁ and DLCO. Predicted postoperative (ppo) values were compared with the observed postoperative values. The precision of ppoFEV₁ and ppoDLCO at 3 months was subsequently evaluated by plotting the cumulative predicted postoperative values against the observed ones.

Results: After lobectomy, observed values were 11% lower at discharge (p < 0.0001), and 6% higher at 3 months (p < 0.0001), compared with ppoFEV₁. No differences were noted at 1 month. Observed DLCO values were 12% lower than predicted at discharge (p < 0.0001) and 10% higher than predicted at 3 months (p < 0.0001), without differences noted at 1 month. After pneumonectomy, no differences were noted between predicted and observed values of FEV₁ at every evaluation time, and of DLCO at discharge and 1 month. However, the observed DLCO value was 17% higher than predicted at 3 months (p = 0.002). Plots of predicted and observed postoperative values at 3 months showed that ppoFEV₁ predicted worse at lower levels of ppoFEV₁, and ppoDLCO was constantly lower than the observed values at every ppoDLCO levels.

Conclusions: Given the imprecision of the prediction of postoperative function, particularly of gas exchange determinants and after pneumonectomy, and at low ppoFEV₁ levels, the use of ppoFEV₁ and ppoDLCO for risk stratification needs to be reconsidered.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
Predicted postoperative respiratory measures for forced expiratory volume in 1 second (FEV₁) and carbon monoxide lung diffusion capacity (DLCO [ppoFEV₁ and ppoDLCO]) are considered the mainstays for patient selection before major lung resection [1, 2]. Several studies have shown that the predicted values correlate fairly well with the observed ones 3 to 6 months after operation [3–7]. The traditional equations used to predict postoperative FEV₁ and DLCO and widely applied in current clinical practice, however, have been validated in series with small numbers of patients, operated on, in most of the cases, more than a decade ago through a posterolateral thoracotomy.

Therefore, the main objectives of the present analysis were twofold: (1) to assess the agreement between predicted and observed values of FEV₁ and DLCO in a large prospective series of more than 200 consecutive patients undergoing to major lung resection for lung cancer and evaluated at different postoperative times in a single center; and (2) to elaborate plots of predicted against observed FEV₁ and DLCO values, which could be used to improve the accuracy of the postoperative prediction.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Two hundred and fifty-three patients underwent major lung resections (lobectomy or pneumonectomy) for nonsmall-cell lung cancer at our unit from June 2003 through December 2005 and were prospectively enrolled in this study. The study was approved by the local Institutional Review Board of the hospital, and all patients gave their informed consent to participate. The postoperative early mortality rate was 4% (10 cases). Patients were evaluated by pulmonary function test before the operation (usually 2 to 3 days before surgery), at discharge (median, 8 days; range, 4 to 14), and at 1 and 3 months postoperatively. Five patients who underwent chest wall or diaphragm resection were not included. Twenty patients did not perform the repeat examination at discharge for the occurrence of postoperative complications that contraindicated pulmonary function testing (prolonged air leak with chest tube in place, atrial fibrillation, myocardial ischemia), but were reexamined at 1 month. That left a total of 218 patients with pulmonary function assessment at discharge (193 lobectomies, 25 pneumonectomies) and 238 at 1 month (212 lobectomies, 26 pneumonectomies). At 3 months, 38 patients dropped out for several reasons (lung cancer recurrence, current chemotherapy, refusal), leaving 200 patients (180 lobectomies, 20 pneumonectomies) with complete FEV₁ and DLCO assessment.

Patients were operated on by qualified thoracic surgeons and were managed in a dedicated thoracic surgery unit. Criteria for inoperability or lesser resections (whenever feasible) were predicted postoperative FEV₁ and predicted postoperative DLCO less than 30% of predicted in association with insufficient exercise tolerance (height at preoperative stair climbing test less than 12 m or maximum volume oxygen consumption (VO₂max) measured at cycle ergometry less than 10 mL · kg^–1 · min^–1). As a rule, lung resections were performed through a muscle-sparing lateral thoracotomy. Postoperative management included chest physiotherapy, early as possible mobilization, antibiotic and antithrombotic prophylaxis, thoracotomy chest pain control by continuous intravenous infusion of ketorolac and tramadol to keep the Visual Analogue Scale score below 3 to 4 in the first 72 hours (on a scale from 0 to 10, assessed twice daily). No formal preadmission or postdischarge physiotherapy programs were administered.

Pulmonary function tests were performed according to the American Thoracic Society criteria. The DLCO was measured by the single-breath method. Results of spirometry and DLCO were collected after bronchodilator administration and were expressed as percentage of predicted for age, sex, and height according to the European Community for Steel and Coal prediction equations [8]. Thoracotomy chest pain at the time of repeat pulmonary function testing was assessed and, if any, controlled by administration of oral analgesics. In all cases, the Visual Analogue Scale scores before the pulmonary function tests and repeat exercise tests were kept below 2 (on a scale from 0 to 10).

Predicted postoperative FEV₁ and DLCO were calculated based on the number of functioning/unobstructed segments to be removed during operation in keeping with the British Thoracic Society recommendation [1]. In all candidates for pneumonectomy and in all patients with a preoperative FEV₁ less than 70%, a quantitative lung perfusion scan was also performed and used to estimate the predicted postoperative function. A total of 45 patients evaluated a 3 months had preoperative lung perfusion scan. In these patients, the correlation coefficients between predicted and observed postoperative FEV₁ and DLCO were similar using the anatomical and scintigraphic methods (FEV₁, 0.6 versus 0.61; DLCO, 0.62 versus 0.65).

The percentage of functioning/unobstructed parenchyma removed during operation was estimated by means of computed tomography scan (to check for the presence of segmental or lobar atelectasis), bronchoscopy (to check for obstructed segments or subsegments), and when performed, quantitative perfusion lung scan (for all pneumonectomy candidates and for patients with preoperative FEV₁ < 70%). Chronic obstructive pulmonary disease (COPD) was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV₁ < 80% and FEV/forced vital capacity [FVC] < 0.7).

Statistical Analysis
Predicted postoperative values of FEV₁ and DLCO (ppoFEV₁ and ppoDLCO) and repeat observed postoperative (discharge, 1 month, 3 months) values of FEV₁ and DLCO were compared by means of the paired t test or the Wilcoxon signed rank test, as appropriate. The Bonferroni correction for multiple comparison was used.

The precision of the ppoFEV₁ and ppoDLCO at 3 months was evaluated by plotting the cumulative predicted postoperative values against the observed values of FEV₁ and DLCO, respectively, with the patients ordered by groups of increasing ppoFEV₁ or ppoDLCO.

The changes in the actual postoperative values of FEV₁ and DLCO over time have been analyzed by the repeated measures analysis of variance with correction for multiple measurements.

All the statistical tests were two-tailed with a significant level of p equals 0.05, and were performed on the statistical software Stata 8.2 (Stata Corp, College Station, Texas).

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Table 1 shows the characteristics of the patients enrolled in the study. The analysis of variance in the patients with complete data at each evaluation time (200 patients) showed a significant impact of time on the observed values of postoperative FEV₁ and DLCO, either after lobectomy (F = 13.6, p < 0.01, and F = 10, p < 0.01, respectively) and pneumonectomy (F = 12.2, p < 0.01, and F = 10.3, p < 0.01, respectively).

View larger version (31K): [in this window] [in a new window]   Fig 1. (A) The actual and predicted postoperative (apo/ppo) forced expiratory volume in 1 second (FEV1) ratio at each postoperative evaluation time (discharge, 1 month, and 3 months) of patients with chronic obstructive pulmonary disease (COPD [48 cases]) and without COPD (132 cases) undergoing lobectomy (COPD defined as FEV1 < 80% and FEV1/forced vital capacity [FVC] ratio < 0.7). Only lobectomy patients with complete evaluations at discharge, 1, and 3 months were displayed (180 cases). (0 = non-COPD; 1 = COPD.) (Line = FEV1 ratio; vertical lines = 95% confidence limits.) (B) The apo/ppo carbon monoxide lung diffusion capacity (DLCO) ratio at each postoperative evaluation time (discharge, 1 month, and 3 months) in patients with COPD (48 cases) and without COPD (132 cases) undergoing lobectomy (COPD defined as FEV1 80% and FEV1/FVC ratio < 0.7). Only lobectomy patients with complete evaluations at discharge, 1 month, and 3 months were displayed (180 cases). (0 = non-COPD; 1 = COPD.) (Line = DLCO ratio; vertical lines = 95% confidence limits.)

View larger version (16K): [in this window] [in a new window]   Fig 2. Plot of the cumulative predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) values (dashed line) against the observed ones (solid line) at 3 months, stratified by groups of patients with increasing ppoFEV1 (observed and predicted postoperative FEV1 expressed as percentage of predicted for age, sex, and height).

View larger version (18K): [in this window] [in a new window]   Fig 3. Plot of the cumulative predicted postoperative (ppo) carbon monoxide lung diffusion capacity (DLCO) values (dashed line) against the observed ones (solid line) at 3 months stratified by groups of patients with increasing ppoDLCO (observed and predicted postoperative DLCO expressed as percentage of predicted for age, sex, and height).

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

As all our patients were operated on for lung cancer, we chose the 3-month period as the latest evaluation time with the main intent to limit the drop-out rate. Indeed, at 3 months, 16% of patients evaluated at 1 month had dropped out for several reasons (recurrence, adjuvant chemotherapy, refusal to show at follow-up). Concerns about drop-out rates have been reported in other studies [9, 10], which reported drop-out rates as high as 50% at 6 to 12 months after operation. Patients who fail to present at follow-up should presumably be considered the ones in the worse conditions, and prolonging the last evaluation time (ie, 6 or 12 months) could affect the results for a selection bias.

We found that the prediction of postoperative values was almost perfect at 1 month after lobectomy either for FEV₁ and DLCO. However, at 3 months the apo/ppo ratios of FEV₁ and DLCO were 1.06 and 1.10, respectively. After pneumonectomy, the prediction of FEV₁ was excellent at every postoperative time, as the postoperative FEV₁ value did not change much from discharge to 3 months (apo/ppo FEV₁ ratio at 3 months was 0.98). Conversely, at 3 months, the apo/ppo DLCO ratio was 1.17. Apparently, gas exchange recovered better than FEV₁ after major lung resection, particularly after pneumonectomy, presumably owing to hemodynamic and pulmonary vascular compensatory mechanisms. This finding has never been reported in detail before, and we believe it may have important clinical implications. In fact, allowance should be made for this better than expected recovery of DLCO if this factor is used for patient selection.

These findings were further highlighted by plotting the cumulative predicted postoperative DLCO value against the observed value at 3 months. These curves showed that the observed DLCO was constantly above the predicted one at every level of ppoDLCO, warranting the future development of some form of correction factor or a new equation to improve the accuracy of the prediction of postoperative DLCO.

The plot of the cumulative predicted and observed postoperative FEV₁ values showed that the accuracy of the prediction of ppoFEV₁ was lower at lower levels of ppoFEV₁, levels at which the observed values were higher than the predicted ones.

We are currently using these plots in clinical practice to correct the calculated ppoFEV₁ and ppoDLCO and derive more precise estimates of the residual postoperative FEV₁ and DLCO at 3 months after operation. Given the large sample size of this study, we confidently believe that these plots may be tested in and possibly generalized to other units.

We further analyzed the relationship between observed and predicted postoperative FEV₁ and DLCO values in patients with and without COPD after lobectomy. The apo/ppo ratios were higher in COPD patients compared with non-COPD patients both at 1 and 3 months. This finding was consistent with previous investigations into the minimal loss or even improvement of FEV₁ after lobar resection in COPD patients, and showed that even postoperative DLCO was positively affected by the lung resection in these patients, presumably for an improvement in ventilation-perfusion relationship [11–13].

The better than predicted FEV₁ and DLCO at 1 and 3 months supports the concept of a lung volume reduction effect benefiting patients with lung cancer and COPD who undergo lobectomy. The reliability of predicted postoperative values for risk-stratification in these patients should be carefully reconsidered.

This study has potential limitations. The first limitation is one common to most of the follow-up analyses and concerns the dropped-out patients. As these patients could have been those with the worst functional status, their inclusion in the analysis could have perhaps changed the results, and that should be taken into account when interpreting the results.

Second, a certain proportion of our patients had adjuvant chemotherapy. Because chemotherapy has been proved to impair the gas exchange [14], the inclusion of these patients could have influenced the results. As most of our patients started chemotherapy 4 to 6 weeks after operation, the problem refers mainly to the last evaluation time (3 months). However, only 20 of the 200 patients studied at 3 months underwent adjuvant chemotherapy. Another 21 patients, who performed the 1-month evaluation test, dropped out for concomitant chemotherapy at 3 months. We decided to include the 20 patients under chemotherapy after a preliminary analysis did not show differences in PFTs at 3 months compared with the other patients.

Finally, the calculation we used to estimate ppoFEV₁ and ppoDLCO was the one recommended by the British Thoracic Society guidelines [1], which takes into account the degree of obstruction and function of the segments removed during operation. Furthermore, all pneumonectomy candidates and all those lobectomy patients with a FEV₁ less than 70% performed a quantitative lung perfusion scan, the results of which were used to estimate the percentage of functioning tissue removed. Although we are aware that these methods are not universally used in clinical practice, recent studies have shown the substantial equivalency of different methods of prediction of residual postoperative function [15, 16], warranting a certain degree of generalization of our results.

In conclusion, we showed that the prediction of postoperative FEV₁ and DLCO was fairly accurate at 1 month after major lung resection but underestimated the actual values at 3 months, particularly for DLCO and after pneumonectomy. Curves plotting the cumulative predicted and observed postoperative values of FEV₁ and DLCO were generated and could be used to correct the predicted values at 3 months. Future studies are warranted to develop new equations to refine the prediction of postoperative respiratory function. Given the imprecision of the prediction of postoperative function, particularly of gas exchange determinants and after pneumonectomy, the use of ppoFEV₁ and ppoDLCO (as they are currently estimated) for patient selection needs to be reconsidered.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

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