**Prediction of Postoperative Lung Function**

## Seung Hun Jang

*Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Republic of Korea* 

#### **1. Introduction**

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Lung cancer is the leading cause of cancer death in many counties. Despite significant improvement in chemotherapy and radiotherapy, surgery is still the cornerstone of nonsmall cell lung cancer treatment. The lung cancer is categorized into non-small cell lung cancer or small cell lung cancer according to the histology. The patients with stage IA-IIB non-small cell lung cancer and stage I small cell lung cancer are good candidates for lung resection which can offer the best chance for cure. In a series of 407 individuals with resectable cancer, the 346 who went to thoracotomy had a median survival of 30.9 months compared with 15.6 months in the 57 who did not go to surgery (Loewen, et al. 2007). A part of individuals with stage IIIA non-small cell stage may also be the surgical candidates if they are adequately treated with chemotherapy and/or radiotherapy before and/or after surgery. The long term goals of lung cancer surgery include cancer control improving survival and quality of life of the patients.

Smoking is the important risk factor not only for lung cancer but also for other comorbid diseases such as chronic obstructive pulmonary disease (COPD) and coronary heart disease. The patients with lung cancer and COPD have reduced ability to tolerate further losses in lung function. Because of relatively high incidence of postoperative complications, the hospital mortality, as well as disappointing long-term survival after surgical resection of lung cancer, the appropriate selection of patients for pulmonary resection is a continuing challenge. It was reported that only about 30% of individuals with lung cancer were determined to be candidates for lung resection because of the advanced stage (Damhuis & Schutte 1996). In addition, a report showed that 37% of individuals who present with anatomically resectable disease deemed not to be surgical candidates based on poor lung function alone (Baser, et al. 2006). If a patient is deemed a candidate for surgery, it must be realized that pulmonary function will be affected by the resection. The decline in lung function varies with the extent of the resection. Accordingly, it is important to be informed about the risk factors and how they affect postoperative morbidity, mortality, and long-term survival.

Pulmonary function measures such as the forced expiratory volume in one second (FEV1) and the diffusing capacity for carbon monoxide (DLco) are useful predictors of postoperative outcome (Bousamra, et al. 1996; Ferguson, et al. 1988; Markos, et al. 1989). Postoperative value of FEV1 is certainly the most widely used parameter for preoperative risk stratification. It has been shown to be an independent predictor of complications including mortality (Kearney, et al. 1994; Mitsudomi, et al. 1996; Ribas, et al. 1998). The

Prediction of Postoperative Lung Function 253

Algorithmic approaches for the candidate selection have been developed in an effort to improve decision making (Colice, et al. 2007; Wyser, et al. 1999). Wyser et al. showed that algorithmic decision reduced the complications in half compared with the author's prior series. In summary, individuals with VO2max < 10 mL/kg/min, or < 15 mL/kg/min with both ppoFEV1 and ppoDLco < 40% predicted, are at high risk for perioperative death and complications. Both preoperative FEV1 and DLco ≥ 80% predicted normal or VO2max ≥ 20

If cardiopulmonary exercise test were not available, another simple exercise test could replace the test. Stair climbing has been investigated, and it was proven to correlate with FEV1 and VO2max very well (Bolton, et al. 1987; Pollock, et al. 1993). It is generally accepted that patient who can climb five flights of stairs has VO2max > 20 mL/kg/min, and conversely, patient who cannot climb one flight of stairs has VO2max < 10 mL/kg/min (Beckles, et al. 2003). The data about the shuttle walking or 6-minute walking test are

The results of arterial blood gas analysis reflect the cardiopulmonary functional status. Historically, hypercapnea (PaCO2 > 45 mmHg) has been regarded as an exclusion criterion for lung resection (Celli 1993). However, a few clinical studies suggested that hypercapnea did not increase perioperative complications (Harpole, et al. 1996; Kearney, et al. 1994). Hypercapnea is not an independent risk factor for increased perioperative complications,

The surgical procedure depends on the stage of lung cancer and on the cardiopulmonary reserve of the patients. A prospective randomized trial comparing limited resection to lobectomy in patients with peripheral stage I lung cancers reported that the patients treated with limited resection had a three-fold increase in local recurrence, a 75% increase in combined local and distant recurrence, and a 50% increase in death with cancer (Ginsberg & Rubinstein 1995). Therefore, anatomic resection such as lobectomy or pneumonectomy should be done if physiologically feasible. Lung sparing anatomic resection like sleeve lobectomy is preferred over pneumonectomy, if anatomically appropriate and if marginnegative resection can be achieved. A study compared clinical outcomes of the elderly patients undergoing sleeve lobectomy or pneumonectomy due to non-small-cell lung cancer (Bolukbas, et al. 2011). The loss of FEV1 was 12.0% vs. 27.3% (p = 0.001), and 5 year survival rate was 59% vs. 0% favoring sleeve lobectomy although there was no statistical difference in postoperative mortality (6.5% in sleeve lobectomy vs. 10.3% in pneumonectomy). Sublobar resection, either segmentectomy (preferred) or wedge resection, is appropriate in selected patients if margin-negative resection can be achieved. The limited resection is appropriate especially for the patients with poor pulmonary reserve or other major co-

For the prediction of postoperative remnant lung function, the anatomy of the lung should be understood. The right lung consists of three lobes; upper, middle and lower lobe. The right upper lobe consists of 3 segments, the right middle lobe 2 segments, and

mL/kg/min allow lobectomy or pneumonectomy without any further evaluation.

limited, but they can also surrogate cardiopulmonary exercise test.

and the operability should be decided after further physiologic testing.

**3. The methods for prediction of postoperative lung function** 

**2.2 Stair climbing and walking test** 

**2.3 Arterial blood gas analysis** 

morbidity that contraindicates lobectomy.

assessment of regional lung function to predict postoperative function is integral to preoperative evaluation of pulmonary resection candidates who have impaired lung function. There are four validated ways to predict postoperative FEV1. However, all of them tend to underestimate the predicted value compared with the actual postoperative lung function. Although predicted postoperative FEV1 (ppoFEV1) somewhat exactly correlates with actual postoperative FEV1 (apoFEV1), the correlation can be affected by several clinical factors. If actual postoperative lung function quite differs from predicted value, it may be a cause of serious clinical outcome especially in the patients with marginal postoperative lung function; someone may undergo life-threatening lung resection, and someone may lose the opportunity to be cured by surgery. Therefore, we need to know clinical factors as many as possible which can affect the discrepancy between apoFEV1 and ppoFEV1. The aim of the chapter is to review the accuracy of the prediction methods for postoperative lung function, especially FEV1, and the clinical factors affecting the prediction accuracy. This will confer the ideas about the appropriate selection of patients for pulmonary resection and perioperative management for risk reduction.

#### **2. The physiologic evaluation for the decision about operability**

#### **2.1 Lung function test**

Among lung function measures, FEV1 and DLco are the most useful predictors of postoperative outcomes. Both absolute values and percent predicted normal values have been studied and proved as a predictors of postoperative complications including mortality (Licker, et al. 2006). The generally accepted lung function for minimal postoperative mortality is preoperative FEV1 > 1.5 L for a lobectomy, and > 2L for a pneumonectomy. Those who have lung function above this level can undergo surgery without further evaluation. There is little evidence that one cutoff absolute value of FEV1 should be used to permit resection of varying extent. Although the absolute value for ppoFEV1 that would allow resection has not been found, the previous studies suggested the values greater than 0.8-1 L for acceptable postoperative mortality (Boysen, et al. 1981; Wernly, et al. 1980). The values of pulmonary function expressed as percentage of normal are more convenient and useful because they are affected by individual's age, sex, height, and race. In terms of percentage of normal, ppoFEV1 less than 30% predicted would be very highly risky for perioperative death and ppoFEV1 greater than 40% has been suggested for tolerable resection up to calculated extent of resection (Beckles, et al. 2003; Colice, et al. 2007; Markos, et al. 1989). If ppoFEV1 is between 30% and 40%, the decision had better to incorporate the result of maximal oxygen consumptions (VO2max).

Cardiopulmonary exercise testing has been used as a means to access a patient's fitness for lung resection. Several studies have identified exercise capacity (VO2max) as a predictor of postoperative complications as well as of postoperative long term mortality (Bolliger, et al. 1995; Brutsche, et al. 2000). Risk for perioperative complications can generally be stratified by VO2max. Several studies demonstrated that preoperative VO2max > 20 mL/kg/min was not associated with increased risk of complications or death (Bolliger, et al. 1994; Richter Larsen, et al. 1997). Patients with VO2max of 15 to 20 mL/kg/min can undergo curative lung cancer surgery with an acceptably low mortality rate (Richter Larsen, et al. 1997; Win, et al. 2005). On the contrary, the risk of perioperative death sharply increases below the level of VO2max < 15 mL/kg/min (Bolliger, et al. 1995; Win, et al. 2005). VO2max < 10 mL/kg/min has been reported as a very high risk of postoperative death (Holden, et al. 1992; Olsen, et al. 1989).

assessment of regional lung function to predict postoperative function is integral to preoperative evaluation of pulmonary resection candidates who have impaired lung function. There are four validated ways to predict postoperative FEV1. However, all of them tend to underestimate the predicted value compared with the actual postoperative lung function. Although predicted postoperative FEV1 (ppoFEV1) somewhat exactly correlates with actual postoperative FEV1 (apoFEV1), the correlation can be affected by several clinical factors. If actual postoperative lung function quite differs from predicted value, it may be a cause of serious clinical outcome especially in the patients with marginal postoperative lung function; someone may undergo life-threatening lung resection, and someone may lose the opportunity to be cured by surgery. Therefore, we need to know clinical factors as many as possible which can affect the discrepancy between apoFEV1 and ppoFEV1. The aim of the chapter is to review the accuracy of the prediction methods for postoperative lung function, especially FEV1, and the clinical factors affecting the prediction accuracy. This will confer the ideas about the appropriate selection of patients for pulmonary resection and

perioperative management for risk reduction.

result of maximal oxygen consumptions (VO2max).

**2.1 Lung function test** 

1992; Olsen, et al. 1989).

**2. The physiologic evaluation for the decision about operability** 

Among lung function measures, FEV1 and DLco are the most useful predictors of postoperative outcomes. Both absolute values and percent predicted normal values have been studied and proved as a predictors of postoperative complications including mortality (Licker, et al. 2006). The generally accepted lung function for minimal postoperative mortality is preoperative FEV1 > 1.5 L for a lobectomy, and > 2L for a pneumonectomy. Those who have lung function above this level can undergo surgery without further evaluation. There is little evidence that one cutoff absolute value of FEV1 should be used to permit resection of varying extent. Although the absolute value for ppoFEV1 that would allow resection has not been found, the previous studies suggested the values greater than 0.8-1 L for acceptable postoperative mortality (Boysen, et al. 1981; Wernly, et al. 1980). The values of pulmonary function expressed as percentage of normal are more convenient and useful because they are affected by individual's age, sex, height, and race. In terms of percentage of normal, ppoFEV1 less than 30% predicted would be very highly risky for perioperative death and ppoFEV1 greater than 40% has been suggested for tolerable resection up to calculated extent of resection (Beckles, et al. 2003; Colice, et al. 2007; Markos, et al. 1989). If ppoFEV1 is between 30% and 40%, the decision had better to incorporate the

Cardiopulmonary exercise testing has been used as a means to access a patient's fitness for lung resection. Several studies have identified exercise capacity (VO2max) as a predictor of postoperative complications as well as of postoperative long term mortality (Bolliger, et al. 1995; Brutsche, et al. 2000). Risk for perioperative complications can generally be stratified by VO2max. Several studies demonstrated that preoperative VO2max > 20 mL/kg/min was not associated with increased risk of complications or death (Bolliger, et al. 1994; Richter Larsen, et al. 1997). Patients with VO2max of 15 to 20 mL/kg/min can undergo curative lung cancer surgery with an acceptably low mortality rate (Richter Larsen, et al. 1997; Win, et al. 2005). On the contrary, the risk of perioperative death sharply increases below the level of VO2max < 15 mL/kg/min (Bolliger, et al. 1995; Win, et al. 2005). VO2max < 10 mL/kg/min has been reported as a very high risk of postoperative death (Holden, et al. Algorithmic approaches for the candidate selection have been developed in an effort to improve decision making (Colice, et al. 2007; Wyser, et al. 1999). Wyser et al. showed that algorithmic decision reduced the complications in half compared with the author's prior series. In summary, individuals with VO2max < 10 mL/kg/min, or < 15 mL/kg/min with both ppoFEV1 and ppoDLco < 40% predicted, are at high risk for perioperative death and complications. Both preoperative FEV1 and DLco ≥ 80% predicted normal or VO2max ≥ 20 mL/kg/min allow lobectomy or pneumonectomy without any further evaluation.

#### **2.2 Stair climbing and walking test**

If cardiopulmonary exercise test were not available, another simple exercise test could replace the test. Stair climbing has been investigated, and it was proven to correlate with FEV1 and VO2max very well (Bolton, et al. 1987; Pollock, et al. 1993). It is generally accepted that patient who can climb five flights of stairs has VO2max > 20 mL/kg/min, and conversely, patient who cannot climb one flight of stairs has VO2max < 10 mL/kg/min (Beckles, et al. 2003). The data about the shuttle walking or 6-minute walking test are limited, but they can also surrogate cardiopulmonary exercise test.

#### **2.3 Arterial blood gas analysis**

The results of arterial blood gas analysis reflect the cardiopulmonary functional status. Historically, hypercapnea (PaCO2 > 45 mmHg) has been regarded as an exclusion criterion for lung resection (Celli 1993). However, a few clinical studies suggested that hypercapnea did not increase perioperative complications (Harpole, et al. 1996; Kearney, et al. 1994). Hypercapnea is not an independent risk factor for increased perioperative complications, and the operability should be decided after further physiologic testing.
