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COPD failed to provide independent risk factor for lung cancer
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Previous correlations between chronic obstructive pulmonary disease and lung cancer were due largely to smoking and ascertainment bias; therefore, chronic obstructive pulmonary disease did not represent an independent risk factor for lung cancer, according to results of a matched case-control study.
In previous studies of the relationship between lung cancer and prior lung diseases, chronic obstructive pulmonary disease (COPD) was found to be associated with an increase in risk for lung cancer. However, a few studies — including one that involved never-smokers — showed reduced risks.
“When patients with lung cancer first present to a clinician, their symptoms may be consistent with a new diagnosis of COPD and are recorded as such, before the lung cancer diagnosis is made,” Helen A. Powell, BMBS, and colleagues from the University Of Nottingham, United Kingdom, wrote. “Patients referred to secondary care for suspected lung cancer may consequently be investigated for, and diagnosed with, COPD. For this reason, in studies of COPD and lung cancer, there is likely to be strong ascertainment bias.”
To assess the association between COPD and lung cancer in the U.K. population while controlling for smoking and the effect of timing of diagnoses, Powell and colleagues used The Health Improvement Network — a general U.K. practice database — to identify 11,888 incident cases of lung cancer and controls matched on age, sex and practice.
Using conditional logistic regression, the researchers assessed the effects of timing of first diagnoses of COPD, pneumonia and asthma on the odds of lung cancer while adjusting for smoking habit.
Controls for this study were selected at random from the general population in The Health Improvement Network, with up to four controls matched to each case based on sex, year of birth and the general practice with which they were registered. The 37,605 controls were required to exhibit no evidence of lung cancer in the 12 months before their index date, defined as the date of lung cancer diagnosis in their matched case.
According to study results, 23% of the incident cases of lung cancer exhibited a prior diagnosis of COPD vs. 6% of the controls. The odds of lung cancer in patients who had COPD diagnosed within 6 months of their cancer diagnosis were 11 times those of patients without COPD (OR=11.47; 95% CI, 9.38-14.02).
However, when restricted to earlier COPD diagnoses, with adjustment for smoking, the effect distinctly diminished for COPD diagnoses of more than 10 years before lung cancer diagnosis (OR=2.18; 95% CI, 1.87-2.54). The pattern was similar for pneumonia. The effect of COPD on lung cancer remained after excluding patients who had a co-diagnosis of asthma, according to the study data.
“Our data suggest that the association between COPD and lung cancer is largely because of confounding by smoking and ascertainment bias, and do not support COPD as an independent risk factor for lung cancer,” Powell and colleagues wrote. “There is, however, an extremely strong unadjusted relationship between both COPD and pneumonia and lung cancer in the 6 months immediately before lung cancer diagnosis.”
The researchers added: “This is useful in a clinical context, highlighting the need to consider a diagnosis of lung cancer when making new diagnoses of COPD or pneumonia, and supporting the current recommendations of the American Thoracic Society and the U.K. National Institute for Health Research, that all patients should have a chest radiograph looking for evidence of lung cancer at the time of COPD diagnosis.”
Disclosure: The researchers reported employment relationships and partial funding from GlaxoSmithKline and the National Institute of Health Research.
Perspective
Back to TopPeter Mazzone, MD, MPH, FCCP
Several epidemiologic and some mechanistic studies have suggested an association between the presence of COPD and the risk of developing lung cancer, independent of smoking history. The potential for biases and residual confounding to influence this association was evaluated in the current study. The authors evaluated whether the possibility that COPD is diagnosed frequently when undergoing an evaluation for lung cancer (an ascertainment bias) could account for the majority of the reported association. They found that the association between COPD and lung cancer risk was minimized when removing those diagnosed with COPD near the time of their lung cancer diagnosis. They also felt that confounding by smoking could explain some of the association. Finally, they found the same bias influenced other associations, such as a link between pneumonia and the risk of lung cancer. They conclude that COPD is unlikely to be an independent risk factor for lung cancer development. I believe this is too broad a conclusion, as the association remained significant even after eliminating those with COPD diagnoses within 10 years of lung cancer presentation. However, the results do strongly suggest that the link is weaker than previously suggested.
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