Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes

Abstract

ABSTRACT:The relationship between smoking, lung cancer and airflow obstruction is recognised but it is unclear whether the presence of minimal lung function damage constitutes an independent risk factor for the development of lung cancer.In order to identify those individuals at higher risk of lung cancer on the basis of functional impairment, we evaluated baseline pulmonary function tests of 3,806 heavy smokers undergoing annual chest computed tomography screening, and compared the forced expiratory volume in 1 s (FEV1) % predicted of 57 lung cancer cases and that of 3,749 subjects without cancer.We obtained odds ratios (ORs) of lung cancer and the corresponding 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age, sex, study and smoking variables. Compared with subjects with FEV1 o90% pred, the OR of lung cancer was 2.45 (95% CI 1.39-4.33) for subjects with FEV1 ,90% pred and 2.90 (95% CI 1.34-6.27) for subjects with FEV1 ,70% pred.These data show that even a relatively small reduction in FEV1 % pred is a significant predictor of increased lung cancer risk. Test screening for lung cancer using airflow obstruction with FEV1 ,90% is a strategy worth future consideration.

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial–American College of Radiology Imaging Network Cohort

“…In a second analysis (Figure 2), we found that this linear relationship extended to smokers meeting GOLD U and restrictive spirometry (4, 23) with a magnitude comparable to those with airflow limitation of GOLD 1-2 severity. This study also shows that, not only is a reduced expiratory flow rate an important risk variable for developing lung cancer among heavy smokers, it is also one of the most important risk variables relative to those of age and pack-years (Tables 1 and 2, Table E3) (1,2,5,8,24). This suggests that airflow limitation represents a global barometer of susceptibility to the key smoking-related lung diseases, including lung cancer (25).…”

“…Over the past 30 years, both cross-sectional and prospective studies have consistently shown that the presence of chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow limitation and reduced expiratory flow rates, confers a greater risk of lung cancer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). This association is independent of smoking history and, strongest when COPD is defined by spirometry with the control group confirmed to have normal lung function (1,4,5).…”

“…When the lung cancer risk conferred by FEV 1 was examined, an inverse dose-response relationship was found where even a small decrease in percent predicted FEV 1 (,90%) was associated with an increased risk of lung cancer (8).…”

“…With the recent interest in CT screening for lung cancer, the relationship between airflow limitation and lung cancer can be more robustly examined (6)(7)(8). Using data from the American College of Radiology, Imaging Network (ACRIN) cohort of the National Lung Screening Trial (NLST), a large, prospective study in 18,714 subjects, we re-examined the relationship between GOLD-based airflow limitation and the development of lung cancer.…”

Mitochondrial-Related Gene Expression and Macrophage Signatures in Non-Small Cell Lung Cancer, Including Patients with Emphysema as Co-Morbidity

“…The high proportion of patients with COPD developing lung cancer is not solely related to the common risk factor of cigarette smoking. COPD patients are at increased risk of developing lung cancer, irrespective of their smoking history [6][7][8]. Smokers with airflow obstruction have a five-fold increased risk of lung cancer compared to those with normal lung function [4].…”