Which Smokers Get Lung Cancer?

Abstract & commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips reports no financial relationship to this field of study.

Synopsis: The presence of emphysema by CT scan or of airflow obstruction by spirometry predicts an increased risk of lung cancer.

Source: Wilson DO, et al. Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med 2008;178:738-744.

This report comes from the Pittsburgh Lung Screening Study, an ongoing study of individuals at high risk for development of cancer. At baseline, recruited individuals underwent low-dose CT scanning and spirometry, and completed an extensive questionnaire. In addition to questions about occupation, smoking, and general medical history, the questionnaire asked participants to report if they had been told by a physician that they had chronic bronchitis, emphysema, or asthma. They were also asked if they ever had hemoptysis, a dry or productive cough, wheezing, or shortness of breath. CT scanning was repeated at approximately 1 year, and a subset of participants also had a third CT at about 3 years after baseline. Subjects were followed annually for about 3.5 years, and investigators obtained medical records and pathology reports, if applicable.

The final cohort was 3538 people (49% women, 7% minority). About 60% were still smoking at enrollment. One-fourth of them had a history of bronchitis, emphysema, or bronchitis, and two-thirds had symptoms of cough, sputum, or wheezing. Pulmonary function testing demonstrated mild airflow obstruction in 13.6%, moderate obstruction in 22.8%, and severe obstruction in 6.4% of the participants. Nearly half (42%) of the cohort had CT evidence for emphysema; CT scan revealed trace emphysema in 18.8%, mild emphysema in 14.6%, and moderate-to-severe emphysema in 9.1%. Risk factors for emphysema were age, years and numbers of cigarettes smoked, a prior diagnosis of emphysema, bronchitis, or asthma, and pulmonary symptoms. Airflow obstruction on spirometry correlated well with evidence of emphysema on CT.

Over an average follow-up period of 3.5 years, there were 99 incident lung cancers (86 non-small cell and 13 small cell). Risk factors for lung cancer were age, years and numbers of cigarettes smoked, and respiratory symptoms. Gender, race, current smoking status, or history of emphysema, bronchitis, or asthma did not predict incident lung cancer. Both airflow obstruction by spirometry and emphysema by CT were strong determinants of development of lung cancer; lung cancer was diagnosed most frequently among people who had both emphysema and moderate-to-severe airflow obstruction.

Commentary

We have known for a long time that airflow obstruction (by spirometry) predicts an increased risk of lung cancer.1-4 What is new about this study is that emphysema detected by CT scanning also strongly predicted an increased risk of lung cancer, and the highest frequency of lung cancer was observed in subjects with both emphysema and moderate-to-severe airflow obstruction. This is important new information, since people who are at risk for lung cancer are increasingly seeking low-dose screening CT scans in attempts to pick up cancer "early." The authors note: "Using low-dose helical CT scanning to screen for lung cancer and emphysema at the same time can be efficient because the screened population is at risk for both diseases."

The accompanying editorial notes that the visual semiquantitative assessment score of emphysema severity used in this study likely provides a more accurate and reproducible assessment of emphysema.5 The editorial also notes that, while there were no sex differences in lung cancer risk in this study, there appears to be a sex-based differential phenotype of COPD, with men showing more CT evidence of emphysema at all spirometric stages than women do.

This paper also amplifies what we know about symptoms, clinical diagnoses, and cancer risk. In this study, having been told by a physician that you had emphysema, bronchitis, or asthma did not predict increased lung cancer risk, but respiratory symptom of cough, sputum, or wheeze did.

What practical use can we make of these new data? If one of your high-risk patients plans to have a "screening CT" for lung cancer (not currently recommended or covered by insurance, but frequently done nevertheless), suggest that a semiquantitative emphysema score also be included. You can also take the "low-tech" approach, and point out that symptoms alone (cough, sputum, or wheeze) predict an increased cancer risk.

References

1. Skillrud DM, et al. Higher risk of lung cancer in chronic obstructive pulmonary disease. A prospective, matched, controlled study. Ann Intern Med 1986;105:503-507.

2. Tockman MS, et al. Airways obstruction and the risk for lung cancer. Ann Intern Med 1987;106:512-518.

3. Wasswa-Kintu S, et al. Relationship between reduced forced expiratory volume in one second and the risk of lung cancer: A systematic review and meta-analysis. Thorax 2005;60:570-575.

4. Petty TL. Are COPD and lung cancer two manifestations of the same disease? Chest 2005;128:1895-1897.

5. Dubinett SM, et al. The partners—airflow obstruction, emphysema, and lung cancer. Am J Respir Crit Care Med 2008;178:665-666.