LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Both lung cancer and chronic obstructive pulmonary disease (COPD) are closely related to smoking. Lung cancer is now the most common fatal malignancy of both men and women, with an approximate 13% to 15% survival rate at 5 years when all cases are considered. This dismal status has remained unchanged during the past 30 years. In 1996, the American Cancer Society estimates the occurrence of 177,000 new lung cancers, with 158,700 deaths using conventional approaches to diagnosis and treatment. 019 COPD is now the fourth most common cause of death in the United States today. It has been known for a long time that COPD and lung cancer are linked by the common denominator of smoking. 006,007 More recent studies have shown that lung cancer is far more common in patients who have COPD than in those who have normal airflow obstruction, with everything else such as smoking, family, and occupational histories being equal. 015,017,018 The reason for this association is not well known, but the author believes that a common pathogenetic mechanism related to toxic oxidant species or elastase-mediated injury is responsible for both lesions. Both can be caused by smoking. Interestingly, lung cancer is most prevalent in the upper half of the lungs. 005 Centrilobular emphysema also predominates in the upper half of the lungs. It is also interesting that the residual volume exists in the upper lobes, and thus a reasonable hypothesis to explain the association might be the failure of emptying of the lungs resulting in the retention of carcinogens and the common pathogens for both lung cancer and COPD. Skillrud and associates 017 at the Mayo Clinic were one of the first to show the significant difference in the prevalence of lung cancer in patients with abnormal airflow (i.e., forced expiratory volume in 1 second [FEV 1 ]). They used 70% of the FEV 1 predicted normal value as evidence of airflow obstruction compared with patients matched by age, sex, occupation, and smoking history who had an FEV 1 of more than 85% of predicted as evidence of normal airflow. All patients were men. Over a 10-year follow-up, nine men with airflow obstruction developed lung cancer, compared with only two with normal airflow. The 10-year survival in the patients with airflow obstruction, including death from all causes, was 74%, compared with 91.1% in those with normal airflow. 017 Tockman and colleagues 018 compared data from the National Heart, Lung, and Blood Institute (IPPB Trial) in which 667 men between the ages of 30 and 74 were enrolled with an FEV 1 of less than 60% of predicted or an FEV 1 % forced vital capacity (FVC) of less than 60%. All were smokers. They compared the prevalence of lung cancer from these 667 patients, all with airflow obstruction, with data from the Johns Hopkins Lung Cancer Project, in which 3728 white men had spirometric testing, annual chest films, and annual sputum examinations as part of the National Cancer Institute three-center study of screening for lung cancer. Patients in the Johns Hopkins study could have had either normal or abnormal pulmonary function on entry, whereas all patients in the IPPB trial by definition had airflow obstruction. Table 1 compares the background factors between the IPPB patients and those in the Johns Hopkins lung project. Because many of the Johns Hopkins patients had normal airflow, the FEV 1 percent of predicted was higher than in the IPPB study group. Other factors, such as age of starting smoking and pack-years smoked, were similar, as indicated in Table 1. The results of these comparisons were striking. In patients with abnormal airflow obstruction in the IPPB group, there were 11 deaths per 1000 person-years. In the Johns Hopkins lung project, when airflow was abnormal, there was an almost identical death rate per 1000 person-year follow-up of 11.4. In patients with normal airflow, deaths per 100,000 person-years were only 3.5. 018 Thus, the study strongly indicates that the presence of airflow obstruction is associated with a higher death rate from lung cancer than when airflow is normal. Because lung cancer and pack-years smoked are related, it is interesting to look at the exposure to cigarettes in those with impaired lung function and lung cancer compared with persons with normal lung function who also developed lung cancer. These data are presented in Table 2. Thus, an increased prevalence of lung cancer occurs at all smoking levels but is highest in those with the most pack-years consumed. Lung cancer is also related to age. Table 3 shows the relationship between age and the prevalence of lung cancer in patients with abnormal airflow compared with normal airflow. Again, lung cancer is more common across all age groups when airflow obstruction is present compared with persons with normal airflow. Perhaps one of the most powerful associations between airflow obstruction and lung cancer comes from the Lung Health Study. 001 The Lung Health Study enrolled 5887 patients in 10 centers to evaluate the effectiveness of smoking cessation and the possibility of improvement in airflow using an anticholinergic bronchodilator in patients with only mild airways disease and a smoking history of at least 10 cigarettes in the 30 days just preceding the first screening. In all, 5887 current smokers were enrolled between the ages of 35 and not yet 60 (mean 48.5 ± 6.8 years). The group constituted 63% men and 37% women. The major objective of the Lung Health Study was to evaluate the rate of change of ventilatory function over time as judged by FEV 1 in those persons who were successful in stopping smoking, either by special intervention or by usual care, compared with those who continued smoking. In this study, the use of an inhaled anticholinergic bronchodilator consistently caused improved airflow, but it had no effect on baseline lung function. There were striking differences in the rate of decline of ventilatory function in those who stopped smoking compared with those who continued. Those who were successful in stopping smoking had an FEV 1 that initially elevated slightly from 2.8 to 2.9 L/second at 1-year follow-up. At the end of 5 years, FEV 1 was 2.8 L, showing no losses during the 5-year follow-up. By contrast, those patients who continued to smoke began with a slightly lower FEV 1 of approximately 2.75 L/second. At the end of 5 years, their ventilatory function was nearly down to 2.4 L/second but still not in the symptomatic range. One of the most striking, unexpected findings of the Lung Health Study is the cause of death. Table 4 shows that there were 20 more lung cancer deaths than from cardiovascular disease or stroke, and, in fact, lung cancer deaths exceeded all other deaths. Unfortunately, chest films were not done at time of entry into this study, so the number of patients who had diagnosable lung cancer compared with roentgenographically occult lung cancer at time of entry is not known. One year after the initial reporting of the results of the Lung Health Study, the total cases of lung cancer, including those who still survived had increased to 93 (Miller RD: personal communication, May 1995). Fortunately a further follow-up is planned to identify the huge risk of developing lung cancer even in patients with mild airflow obstruction.