COPD in nonsmokers: inc risk of lung cancer

A recent article confirmed the high incidence of lung cancer in patients with COPD who were never smokers (see copd nonsmoker inc lung ca thorax2020 in dropbox, or doi:10.1136/thoraxjnl-2019-213732)

 

Details:

-- South Korean study of 338,548 subjects aged 40-84 with no history of lung cancer at baseline who were in their National Health Insurance Service National Sample Cohort (a population-based retrospective cohort study based on a representative sample of Korean citizens, from 2002-2014)

-- followed 7.0 years (2,355,005 person-years of follow-up)

-- those who had COPD were older (62 vs 53yo), more likely to be male (52% vs 43%), current smokers (26% vs 22%), and have lower income (26% vs 21% had <30^th percentile of income) and more comorbidities (Charlson comorbidity index skewed: 16% vs 10% were at least 2)

-- 1834 developed lung cancer: 290 in participants with COPD and 1544 in those without COPD

  

Results:

-- as compared to never smokers without COPD, the hazard ratio (adjusted for sex, BMI, and Charlson comorbidity index):

    -- never smokers with COPD, aHR 2.67 (2.09-3.40)

    -- ever smokers without COPD, aHR 1.97( 1.75-2.21)

    -- ever smokers with COPD, aHR 6.19 (5.04-7.61)

-- a review of their graphs show a significant and increasing difference beginning at around 65 years old

-- sensitivity analyses in propensity score matched groups found similar results

-- only 2% of never smokers over time changed to being smokers

  

Commentary:

-- 39% of COPD patients in a Chinese study were never smokers; US studies are more on the order of 23% (eg see Lamprecht B. Chest 2011; 139(4):752)

-- but, the relationship between COPD in non-smokers and lung cancer has not been adequately studied

-- interesting in this Korean study that the cumulative risk of lung cancer is higher in non-smokers with COPD vs smokers without COPD. This raises a few issues:

    -- COPD does seem to be an independent risk factor for lung cancer. There have been a few studies in smokers in the past showing that those who smoke and have COPD had about 3x the risk of lung cancer as those who smoked similar amounts but did not have COPD (which is almost exactly what was found in this study). And this makes lots of sense: COPD reflects significant lung damage (which may be from smoking, perhaps in combination with air pollution, or other environmental/occupational exposures). And cancer is likely more often to occur in those with underlying chronic tissue damage, likely associated with fundamental changes in cell function/genetics/etc, and likely to predispose them to cancerous changes (the multiple-hit hypothesis)

    -- in lung cancer risk calculators, COPD is considered an independent variable, beyond smoking

    -- and, there have been many many critiques of the USPSTF and Medicare recommendations to do low-dose lung CT (LDCT) screening in smokers:

        -- for a summary of several of the concerns, see http://gmodestmedblogs.blogspot.com/2020/02/lung-cancer-screening-in-smokers.html

            -- one of the major ones is that people who smoke are more likely to die from cardiovascular disease than lung cancer, and focusing on LDCT screening potentially distorts people’s perceptions of the predominant risks of smoking. There are well-documented examples of smokers having a normal LDCT and feeling reassured that it was okay to continue smoking

            -- a few blogs have reviewed studies showing that smoking even <1 cigarette a day is associated with increased mortality and increased cardiovascular disease: eg see http://gmodestmedblogs.blogspot.com/2020/06/smoking-less-than-1-cigaretted-assoc.html

        -- for an article and blog finding that some people not qualifying for low-dose lung CT screening by USPSTF (they used a smoking history of at least 30 pack-yrs) are really high risk and some qualifying are at low risk, see http://gmodestmedblogs.blogspot.com/2016/07/lung-cancer-screening-for-smokers.html

        -- and another another blog advocating risk-based LDCT screening beyond just smoking: http://gmodestmedblogs.blogspot.com/2018/01/risk-based-low-dose-ct-screening-in.html

 

Limitations of study:

-- COPD severity was unknown, either clinically or by spirometry

-- there was no information about environmental or occupational exposures, and studies suggest a significant role for these exposures in leading to lung cancer, which may be amplified in smokers

-- they did not present quantitative data showing changes in smoking behavior over time: for example the cumulative amount people smoked at different points in time over the baseline assessment and whether that influenced the final outcomes

 

So, this study really supports a broader conception of lung cancer risk, noting that the incidence seems to be even a bit higher in nonsmokers with COPD than smokers without COPD. and, this study reinforces the need for a much more nuanced approach to lung cancer screening. One issue, for example, is that those with severe COPD have poorer outcomes from surgical interventions, suggesting that earlier pick-up and intervention for concerning lung nodules may be safer and even more beneficial in those with COPD, even if they never smoked or only smoked less than the cutpoint for current screening recommendations.

geoff

 

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