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Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study

Abstract

Background

The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years.

Methods

This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable.

Results

During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01).

Conclusions

In patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Background

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by persistent respiratory symptoms and airflow limitation [1]. Comorbidities are common in patients with COPD and can contribute to symptom severity and disease progression [2]. Lung cancer is one of the most frequent and burdensome comorbidities and the leading cause of death in patients with COPD [3]. Cigarette smoking is a well-known common risk factor for both COPD and lung cancer, and it further increases the risk of lung cancer in patients with COPD [4]. Indeed, a large national cohort study showed that smokers with COPD and never smokers with COPD had approximately 6.2 and 2.6 times the incidence of lung cancer, respectively, compared with never smokers without COPD [4]. Accordingly, the attainment of complete smoking cessation is the most effective way to reduce the risk of lung cancer [5, 6]. Regarding smoking reduction, although the prospective cohort study for cardiovascular disease (from mid-1970s to 2003) found no difference in lung cancer related mortality between sustainers and > 50% reducers [7], accumulated general population studies showed that there is a dose-dependent effect of the amount of smoking reduction [5, 6, 8] and the duration of smoking cessation [9] on the risk of lung cancer.

In patients with COPD, few studies have investigated the effect of changes in smoking habits on lung cancer-related outcomes. The Lung Health Study reported the impact of changes in smoking habits on lung cancer mortality in patients with COPD [10]. However, based on smoking history, the patients in that study were categorized as sustainers, quitters, and intermittent quitters, and the dose-dependent association between smoking habit change and lung cancer mortality could not be measured [10]. A single-center retrospective study in China found a reduction in all-cause mortality in patients with COPD who quit smoking compared with those who continued smoking; however, there was no significant difference in lung cancer mortality between the two groups, which might be explained by the small sample size (n = 204) and number of lung cancer mortality cases (n = 15) [11]. No study has investigated the dose-dependent effects of smoking reduction on the incidence of lung cancer in patients with COPD.

Landmark studies have shown that lung cancer mortality was reduced by lung cancer screening using chest computed tomography in a high-risk population with a minimum of 15 to 30 pack-years of smoking history [12, 13]. In contrast, those with less smoking exposure have not received enough attention despite growing evidence showing that smokers with less than 30 pack-years of exposure also have a considerable risk of developing lung cancer [14, 15]. Although the recent guideline from the United States on lung cancer screening have expanded the selection criteria [16], still there is a scarcity of data regarding the lung cancer development in individuals with less smoking exposure. Furthermore, given that the COPD itself is regarded as a risk factor in selecting the candidate for lung cancer screening [17, 18], it would be of interest to estimate the degree of lung cancer risk reduction in patients with COPD by the amount of smoking reduction. In this context, this nationwide cohort study aimed to evaluate the impact of smoking reduction on the incidence of lung cancer after a COPD diagnosis in smokers using less than 30 pack-years, by categorizing them as quitters, reducers, or sustainers.

Methods

Data source

This retrospective cohort study used data from the Korean National Health Insurance System (K-NHIS) database. The K-NHIS database represents the entire South Korean population. The K-NHIS claims database contains information on patient demographics, medical treatments, procedures, prescription drugs, diagnostic codes, and hospital use. Diagnoses in the K-NHIS database were based on the International Classification of Diseases, 10th revision (ICD-10). The K-NHIS regularly audits ICD-10 codes, procedure records, and prescription records to avoid unnecessary medical expenses. Additionally, the K-NHIS claims database includes data from the National Health Screening Examination, a standardized health screening program provided to all insured persons every 2 years [19]. The participation rate of the target population in the National Health Screening Examination is approximately 76% [19]. The Health Screening Examination data includes a self-administered questionnaire on medical history, lifestyle habits, anthropometric measurements, and laboratory tests [19]. Health examination facilities are designated and overseen for quality control according to relevant national laws and regulations. Further details regarding the NHIS database and health examinations are described elsewhere [19, 20].

Study population

Our database included all patients with COPD aged ≥ 40 years between January 1, 2014 and December 31, 2019. COPD was defined as the presence of the J43-J44 code (except J43.0) (ICD-10) and the prescription of COPD medication at least twice within 1 year. Medications for COPD include long-acting muscarinic antagonists (LAMAs), long-acting beta-2 agonists (LABAs), inhaled corticosteroids (ICSs) plus LABAs, short-acting muscarinic antagonists (SAMAs), short-acting beta-2 agonists (SABAs), methylxanthines, systemic beta agonists, and phosphodiesterase-4 (PDE-4) inhibitor [4, 21, 22].

As the purpose of this study was to evaluate the effects of smoking reduction and cessation after COPD diagnosis on lung cancer development, we included only patients who were smoking before the diagnosis of COPD (Exam 1, N = 45,271). Among them, 38,077 patients had health examination data within 3 years of the date of COPD diagnosis (Exam 2). We excluded 2,816 participants who had cancer before the Exam 2. Furthermore, to minimize potential reverse causality, we further excluded 1,232 participants who developed any cancer or died within the first 6 months of follow-up from the Exam 2 index date. To focus on low-dose smokers, 16, 832 participants who had smoked less than 30 pack-years were selected. A period of 3 years was chosen a priori based on previous literature as well as the anticipated sample size and follow-up duration [23, 24]. A brief summary of the study process is shown in Fig. 1.

Fig. 1
figure 1

Study flow process

The Institutional Review Board of Samsung Medical Center approved the study (approval no.2022-09-022) and waived the requirement for informed consent because the K-NHIS data were de-identified.

Assessment of smoking habit

Smoking status was assessed using a self-reported questionnaire during each of the last examinations within 2 years before COPD diagnosis (Exam 1) and within 3 years after COPD diagnosis (Exam 2). Current smokers were questioned about their duration of smoking and the mean number of cigarettes smoked per day. According to the smoking intensity in Exam 1, smokers were defined as light (< 10 cigarettes per day), moderate (10–19 cigarettes per day), and heavy (≥ 20 cigarettes per day) smokers [5].

In this study, changes in cigarette smoking intensity were identified based on relative changes in the number of cigarettes smoked per day. Participants were categorized into three groups based on the relative change in smoking intensity between Exam 1 and Exam 2: quitters, reducers, and sustainers, based on the definitions used in previous studies [25]. Quitters were defined as those who had completely stopped smoking (i.e., current smokers in Exam 1 who became former smokers in Exam 2). The reducer group included those who decreased their number of cigarettes consumed per day by 20% or more. Additionally, the reducer group was divided into subcategories to evaluate the possible dose responsiveness of smoking reduction: >50% reducers were defined as those who decreased the number of cigarettes per day by 50% or more, while 20–50% reducers were defined as those who decreased the number of cigarettes per day by 20–50%. Sustainers were defined as those who maintained (increased or decreased by less than 20%) the number of cigarettes they consumed per day.

Covariables

Residential areas and income levels were obtained from insurance eligibility. The residential areas were categorized as metropolitan cities (Seoul, Busan, Daegu, Daejeon, Gwangju, Incheon, and Ulsan) and others. Income levels were categorized as Medical Aid, ≤ 30th, 30–70th, or > 70th percentile. Data on alcohol consumption, physical activity, and body mass index (BMI) were collected during Exam 2.

Severe COPD exacerbation was defined as hospitalization or emergency room visit with one of the following ICD-10 codes as the principal or secondary diagnosis: COPD (J43.X [except J43.0] or J44.X), COPD-related disease (pneumonia [J12.X–J17.X], pulmonary thromboembolism [I26, I26.0, or I26.9], dyspnea [R06.0], or acute respiratory distress syndrome [J80]), and a prescription for systemic steroids or antibiotics at the same visit [26]. Comorbidities during the year prior to Exam 2 were obtained from claims data defined using ICD-10 codes and summarized using the Charlson comorbidity index (CCI) [27]. In addition to CCI, we included pulmonary tuberculosis (ICD-10: A15, A16, and B90.9), interstitial lung disease (ICD-10: J84), bronchiectasis (ICD-10: J47), and pneumonia (ICD-10: J11 ~ J18, J69) using insurance claims data during a 1-year look-back period from Exam 2.

Outcomes

The primary endpoint was lung cancer incidence. Lung cancer was defined as the presence of a cancer-specific insurance claims code (V193) with a C33 or C34 code, which is the ICD-10 code for lung cancer. In Korea, once a person receives a cancer diagnosis, he/she is registered with the National Cancer Registry with a specific code that indicates to the system that the person has been diagnosed with cancer and is receiving special insurance benefits.

Statistical analysis

The incidence rates were calculated as the number of events per 100 person-years of follow-up. We used the Kaplan-Meier curve to evaluate the cumulative incidence of lung cancer by group. In the figure, age was used as a timescale. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of the outcomes for each group were calculated using Cox proportional hazards models. The proportionality of the hazards was confirmed by visual inspection of the log-minus-log plots and Schoenfeld residuals.

The models were adjusted for age, sex, BMI, residential area, income, regular physical activity, smoking pack-years (Exam 1), ICS prescription within 1 year of Exam 2, history of severe exacerbation within 1 year of Exam 2, and comorbidities within 1 year of Exam 2. Covariables were selected a priori based on their possible association with smoking habits and lung cancer development.

To further investigate the influence of smoking reduction, we modelled the amount of change in smoking as a continuous variable using restricted cubic splines. If the patients had − 100%, it meant that they quit smoking. Four knots were selected based on a model comparison using the Akaike Information Criterion. We performed cubic splines for the change in smoking with knots at the 5th, 35th, 65th, and 95th percentiles of our sample distributions based on Harrell’s suggested knot locations. We then calculated the linearity of the association between the amount of change in smoking and the incidence of lung cancer by testing whether the coefficients associated with the nonlinear components were equal to zero.

Additionally, we used the Fine and Gray method to calculate the sub-distribution hazard ratios (subHRs) for the incidence of lung cancer to account for competing risks due to mortality [28].

All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Of the 16,832 patients with COPD (median age, 64 years; 87.3% men), 7,859 (46.7%) continued smoking, 2,823 (16.8%) reduced smoking, and 6,150 (36.5%) quit smoking after their respective COPD diagnoses. Among the reducers, 1,498 and 1,325 reduced daily smoking amounts by 20–50% and > 50%, respectively. Compared with sustainers, reducers and quitters were more likely to be older, have more comorbidities, and have a severe exacerbation history, but they were less frequent drinkers, had higher physical activity levels, and had a lower smoking pack-years at Exam 1 (Table 1).

Table 1 Characteristics of study participants (N = 16,832)

During a median follow-up of 3.94 years, a total of 469 new lung cancer diagnoses were made. The cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters (Fig. 2). The multivariable-adjusted HRs (95% CIs) for lung cancer were 0.74 (0.56, 0.98), and 0.78 (0.64, 0.96) in reducers and quitters, respectively. The results were similar when competing risk analysis was performed (Table 2).

Fig. 2
figure 2

Kaplan Meier curve for incidence of lung cancer. Age as time scale

Table 2 Hazard ratio (HR) with 95% confidence interval (CI) for incident lung cancer associated with change of smoking status

When the effect of smoking reduction was analyzed in subcategories by the amount of reduction, the multivariable-adjusted HRs (95% CIs) for lung cancer were 0.84 (0.60, 1.18), and 0.64 (0.64, 0.95) in 20–50% reducers and >50% reducers, respectively, compared with those who continued smoking (Table 2). These findings remained consistent after conducting a competing risk analysis. In the restricted cubic spline model, the incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01, Fig. 3).

Fig. 3
figure 3

Multivariable-adjusted hazard ratios (95% CI) for incidence of lung cancer according to amount of smoking change. The curves represent the adjusted odds ratios (solid lines) and their 95% confidence intervals (dashed lines) for the incidence of lung cancer based on restricted cubic splines for the amount of smoking change with knots at the 5th, 35th, 65th, and 95th percentiles of their sample distributions. The reference value (diamond dots) was set to zero, which did not change. Quitter group was categorized in -100%

An association between smoking reduction or cessation and the risk of lung cancer was observed in all analysed subgroups. In particular, the protective effect was stronger in males than in females (P for interaction = 0.02) (Table 3).

Table 3 Subgroup analysis

Discussion

In this nationwide population-based cohort with comprehensive data on health status and medical service utilization of the entire Korean population, smoking reduction and smoking cessation were independently associated with a lower risk of lung cancer development in patients with COPD who smoked less than 30 pack-years, after adjusting for major confounders, including cumulative smoking amount and sociodemographic factors. This association was consistent across all the subgroups, with a less pronounced effect observed in females than in males. In particular, we found a decreasing trend of lung cancer risk with a decreasing amount of smoking. Our results underscore that smoking cessation should remain the most effective way to reduce the risk of lung cancer development, but smoking reduction may be used as an adjusted strategy to reduce the risk of lung cancer in patients with COPD, particularly in those who have smoked less than 30 pack-years and are unable to quit smoking immediately.

Importantly, our study found that the risk of lung cancer development in patients with COPD decreased when they merely reduced their smoking amount, which is in line with a previous reports based on population-based samples [5, 6, 29, 30]. A previous large population-based Danish study (n = 19,714) demonstrated a decrease in the lung cancer risk with smoking reduction by 27% compared to the persistent heavy smokers for up to 31 years of follow-up [8]. In our study, the benefit of smoking reduction and cessation in lowering lung cancer risk was clear with a relatively short follow-up period (median, 4 years). This result encourages patients with COPD who are current smokers but are unable to stop smoking immediately in real-world practice to gradually reduce their smoking amount. Gradual smoking reduction could serve as an intermediate step towards achieving complete smoking cessation. Although abrupt smoking cessation is more likely to result in lasting abstinence than a gradual decrease [31], various real-world barriers, such as social and environmental factors, could make it impractical or challenging for certain groups of smokers to quit smoking abruptly [32]. Moreover, smokers who reduce their smoking before quitting are more likely to quit smoking successfully than those who do not [33]. In particular, a greater reduction in cigarettes smoked per day increased the likelihood of future cessation [34]. Therefore, for patients with COPD who are unable to quit smoking immediately, a gradual reduction in the amount of smoking might have a positive impact on lowering the risk of developing lung cancer. However, it should be acknowledged that smoking cessation is the cornerstone of preventing smoking-related cancer development as well as mitigating the progression of COPD, which will inevitably progress with accelerated lung function decline and increased exacerbation with continuous smoking [10, 35].

Several factors are thought to play a role in this observation that smoking reduction and cessation confers a decreased risk of lung cancer in patients with COPD. Possible biological mechanisms have also been suggested. Smoking reduction and cessation could lower exposure to carcinogenic substances, reduce oxidative stress, and have the potential to mitigate or reverse epigenetic alterations resulting from tobacco use [36,37,38]. Changes in smoking habits may also contribute to the restoration of immune function [39]. Genes responsible for the antitumor response are hypermethylated in patients with COPD who smoke, suggesting reduced infiltration of immune cells against tumor [40]. Moreover, patients with COPD who changed their behavior to smoking reduction or cessation were more likely to be concerned about their health status. In our exploratory analysis, quitters exhibited the lowest alcohol consumption and highest engagement in regular physical activity. In addition, a higher rate of severe exacerbation in the previous year and a higher disease burden in quitters could have motivated them to quit smoking. Although further research is needed to establish the causality and significance of these factors in the context of smoking reduction and lung cancer risk in patients with COPD, it is important to provide information that motivates behavioral changes to quit or reduce smoking.

The subgroup analysis revealed that the benefits of smoking reduction and cessation on lung cancer risk were less evident in females than in males. Several studies have shown an increased susceptibility to cigarette smoke in female smokers compared with male smokers, including a higher risk of airflow obstruction development and hospitalization for COPD with accelerated lung function decline in females [41,42,43]. However, there are conflicting data regarding sex differences in smoking and the incidence of lung cancer. Several case-control and cohort studies have shown that female smokers have a higher risk of lung cancer than male smokers with the same smoking quantity [44,45,46,47], whereas other cohort studies have shown a similar incidence of lung cancer with comparable smoking histories [48, 49]. Few studies have investigated whether the impact of smoking reduction and cessation on lung cancer risk differs between females and males, especially in smokers using less than 30 pack-years [50]. Given the variations in smoking patterns as well as biological differences between males and females could contribute to the differences in lung cancer risk reduction, this discrepancy observed in the subgroup analysis requires validation in further studies.

To the best of our knowledge, this study is the first to show the immediate impact of smoking reduction and cessation on lowering lung cancer risk in patients with COPD with a smoking history of less than 30 pack-years. We also demonstrated a decreasing trend of lung cancer risk with a decreasing amount of smoking among reducer and sustainer group, although risk in reducers were not statistically different compared to that in complete quitters. Estimates derived from national insurance data may guarantee the representativeness of the entire COPD population in South Korea. However, this study also has several limitations. First, data of spirometric measurements are not available in K-NHIS data. Thus, the COPD diagnosis was based on administrative data rather than clinical diagnosis using spirometry, which may have resulted in misclassification bias. Nevertheless, several previous studies based on claims data have adopted this operational definition of COPD [3, 4, 21, 22]. Second, smoking habits were self-reported through questionnaires rather than confirmed through biochemical methods, such as urine cotinine levels, which may lead to recall, misclassification, and measurement errors. Third, we lacked information on the histologic types of lung cancer. Additional efforts are necessary to fully elucidate the effect of smoking reduction and cessation on the development of lung cancer in patients with COPD across several lung cancer subtypes [9]. Fourth, the median 4-year follow-up period in this study was relatively short, and the long-term protective effect of smoking reduction (i.e., continued smoking, albeit in a reduced amount) cannot be guaranteed. Further longitudinal studies are necessary to validate our findings. Therefore, healthcare providers must encourage patients with COPD to stop smoking in every clinic visit. Fifth, our study population may not represent the entire COPD population, as we focused COPD patients who utilized health care services including the prescription of COPD medication and who participated the national health screening examinations. The participation rate for the health screening exam is 74% despite its being free-of-charge. Lastly, the majority of study participants (87.3%) were males, which raises concerns regarding the generalizability of our findings to female patients.

Conclusions

Our study highlights the importance of smoking reduction and smoking cessation in lowering the risk of lung cancer development in patients with COPD who smoked less than 30 pack-years. Reducing the smoking amount might be a starting point for individuals who struggle to quit abruptly with active encouragement of smoking cessation in every clinic, as smoking cessation is the single most effective way not only to reduce lung cancer development and mortality in patients with COPD, but also to ameliorate the natural course of COPD.

Data availability

The data are available from the Korean National Health Insurance Sharing Service (NHISS; https://nhiss.nhis.or.kr/) database, which is open to researchers on request with approval by the Institutional Review Board.

References

  1. Venkatesan P. GOLD COPD report: 2023 update. Lancet Respir Med. 2023;11:18.

    Article  PubMed  Google Scholar 

  2. Raherison C, Ouaalaya EH, Bernady A, Casteigt J, Nocent-Eijnani C, Falque L, Le Guillou F, Nguyen L, Ozier A, Molimard M. Comorbidities and COPD severity in a clinic-based cohort. BMC Pulm Med. 2018;18:117.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Park HY, Kang D, Lee H, Shin SH, Kang M, Kong S, Rhee CK, Cho J, Yoo KH. Impact of chronic obstructive pulmonary disease on mortality: a large national cohort study. Respirology. 2020;25:726–34.

    Article  PubMed  Google Scholar 

  4. Park HY, Kang D, Shin SH, Yoo KH, Rhee CK, Suh GY, Kim H, Shim YM, Guallar E, Cho J, Kwon OJ. Chronic obstructive pulmonary disease and lung cancer incidence in never smokers: a cohort study. Thorax. 2020;75:506–9.

    Article  PubMed  Google Scholar 

  5. Song YM, Sung J, Cho HJ. Reduction and cessation of cigarette smoking and risk of cancer: a cohort study of Korean men. J Clin Oncol. 2008;26:5101–6.

    Article  PubMed  Google Scholar 

  6. Yoo JE, Han K, Shin DW, Jung W, Kim D, Lee CM, Kwon H, Jung KW, Song YM. Effect of smoking reduction, cessation, and resumption on cancer risk: a nationwide cohort study. Cancer. 2022;128:2126–37.

    Article  PubMed  Google Scholar 

  7. Tverdal A, Bjartveit K. Health consequences of reduced daily cigarette consumption. Tob Control. 2006;15:472–80.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Godtfredsen NS, Prescott E, Osler M. Effect of smoking reduction on lung cancer risk. JAMA. 2005;294:1505–10.

    Article  CAS  PubMed  Google Scholar 

  9. Vlaanderen J, Portengen L, Schüz J, Olsson A, Pesch B, Kendzia B, Stücker I, Guida F, Brüske I, Wichmann HE, et al. Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY study. Am J Epidemiol. 2014;179:290–8.

    Article  PubMed  Google Scholar 

  10. Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005;142:233–9.

    Article  PubMed  Google Scholar 

  11. Bai JW, Chen XX, Liu S, Yu L, Xu JF. Smoking cessation affects the natural history of COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:3323–8.

    Article  PubMed  PubMed Central  Google Scholar 

  12. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409.

  13. de Koning HJ, van der Aalst CM, de Jong PA, Scholten ET, Nackaerts K, Heuvelmans MA, Lammers JJ, Weenink C, Yousaf-Khan U, Horeweg N, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382:503–13.

  14. Pinsky PF, Kramer BS. Lung cancer risk and demographic characteristics of current 20–29 pack-year smokers: implications for screening. J Natl Cancer Inst 2015; 107(11).

  15. Pasquinelli MM, Tammemägi MC, Kovitz KL, Durham ML, Deliu Z, Rygalski K, Liu L, Koshy M, Finn P, Feldman LE. Risk prediction model versus United States Preventive Services Task Force lung cancer screening eligibility criteria: reducing race disparities. J Thorac Oncol. 2020;15:1738–47.

  16. Krist AH, Davidson KW, Mangione CM, Barry MJ, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Kubik M, et al. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962–70.

  17. de-Torres JP, Wilson DO, Sanchez-Salcedo P, Weissfeld JL, Berto J, Campo A, Alcaide AB, García-Granero M, Celli BR, Zulueta JJ. Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening score. Am J Respir Crit Care Med. 2015;191:285–91.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tammemägi MC, Katki HA, Hocking WG, Church TR, Caporaso N, Kvale PA, Chaturvedi AK, Silvestri GA, Riley TL, Commins J, Berg CD. Selection criteria for lung-cancer screening. N Engl J Med. 2013;368:728–36.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Cheol Seong S, Kim YY, Khang YH, Heon Park J, Kang HJ, Lee H, Do CH, Song JS, Hyon Bang J, Ha S, et al. Data resource profile: the National Health Information Database of the National Health Insurance Service in South Korea. Int J Epidemiol. 2017;46:799–800.

  20. Seong SC, Kim YY, Park SK, Khang YH, Kim HC, Park JH, Kang HJ, Do CH, Song JS, Lee EJ, et al. Cohort profile: the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) in Korea. BMJ Open. 2017;7:e016640.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Park HY, Kang D, Shin SH, Choi H, Jang SH, Lee CH, Kim H, Kwon OJ, Rhee CK, Cho J. Pulmonary tuberculosis and the incidence of lung cancer among patients with chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2022;19:640–8.

  22. Kim T, Kim H, Kong S, Shin SH, Cho J, Kang D, Park HY. Association between regular moderate-to-vigorous physical activity initiation after COPD diagnosis and mortality: an emulated target trial using nationwide cohort data. Chest. 2024;165(1):84–94.

  23. Tarasenko YN, Linder DF, Miller EA. Muscle-strengthening and aerobic activities and mortality among 3 + year cancer survivors in the U.S. Cancer Causes Control. 2018;29:475–84.

    Article  PubMed  Google Scholar 

  24. Irwin ML, Smith AW, McTiernan A, Ballard-Barbash R, Cronin K, Gilliland FD, Baumgartner RN, Baumgartner KB, Bernstein L. Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol. 2008;26:3958–64.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Godtfredsen NS, Osler M, Vestbo J, Andersen I, Prescott E. Smoking reduction, smoking cessation, and incidence of fatal and non-fatal myocardial infarction in Denmark 1976–1998: a pooled cohort study. J Epidemiol Community Health. 2003;57:412–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kim J, Rhee CK, Yoo KH, Kim YS, Lee SW, Park YB, Lee JH, Oh Y, Lee SD, Kim Y, et al. The health care burden of high grade chronic obstructive pulmonary disease in Korea: analysis of the Korean Health Insurance Review and Assessment Service data. Int J Chron Obstruct Pulmon Dis. 2013;8:561–8.

    PubMed  PubMed Central  Google Scholar 

  27. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173:676–82.

    Article  PubMed  Google Scholar 

  28. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Article  MathSciNet  Google Scholar 

  29. Choi S, Chang J, Kim K, Park SM, Lee K. Effect of smoking cessation and reduction on the risk of cancer in Korean men: a population based study. Cancer Res Treat. 2018;50:1114–20.

  30. Chang JT, Anic GM, Rostron BL, Tanwar M, Chang CM. Cigarette smoking reduction and health risks: a systematic review and meta-analysis. Nicotine Tob Res. 2021;23:635–42.

  31. Lindson-Hawley N, Banting M, West R, Michie S, Shinkins B, Aveyard P. Gradual versus abrupt smoking cessation: a randomized, controlled noninferiority trial. Ann Intern Med. 2016;164:585–92.

  32. Twyman L, Bonevski B, Paul C, Bryant J. Perceived barriers to smoking cessation in selected vulnerable groups: a systematic review of the qualitative and quantitative literature. BMJ Open. 2014;4:e006414.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hyland A, Levy DT, Rezaishiraz H, Hughes JR, Bauer JE, Giovino GA, Cummings KM. Reduction in amount smoked predicts future cessation. Psychol Addict Behav. 2005;19:221–5.

    Article  PubMed  Google Scholar 

  34. Klemperer EM, Hughes JR. Does the magnitude of reduction in cigarettes per day predict smoking cessation? A qualitative review. Nicotine Tob Res. 2016;18:88–92.

  35. Scanlon PD, Connett JE, Waller LA, Altose MD, Bailey WC, Buist AS, Tashkin DP. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease. The Lung Health Study. Am J Respir Crit Care Med. 2000;161:381–90.

    Article  CAS  PubMed  Google Scholar 

  36. Chen LS, Baker T, Hung RJ, Horton A, Culverhouse R, Hartz S, Saccone N, Cheng I, Deng B, Han Y, et al. Genetic risk can be decreased: quitting smoking decreases and delays lung cancer for smokers with high and low CHRNA5 risk genotypes - a meta-analysis. EBioMedicine. 2016;11:219–26.

  37. Zong D, Liu X, Li J, Ouyang R, Chen P. The role of cigarette smoke-induced epigenetic alterations in inflammation. Epigenetics Chromatin. 2019;12:65.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Trivedi A, Bade G, Madan K, Ahmed Bhat M, Guleria R, Talwar A. Effect of smoking and its cessation on the transcript profile of peripheral monocytes in COPD patients. Int J Chron Obstruct Pulmon Dis. 2022;17:65–77.

  39. Piaggeschi G, Rolla S, Rossi N, Brusa D, Naccarati A, Couvreur S, Spector TD, Roederer M, Mangino M, Cordero F, et al. Immune trait shifts in association with tobacco smoking: a study in healthy women. Front Immunol. 2021;12:637974.

  40. Wauters E, Janssens W, Vansteenkiste J, Decaluwé H, Heulens N, Thienpont B, Zhao H, Smeets D, Sagaert X, Coolen J, et al. DNA methylation profiling of non-small cell lung cancer reveals a COPD-driven immune-related signature. Thorax. 2015;70:1113–22.

    Article  PubMed  Google Scholar 

  41. Amaral AFS, Strachan DP, Burney PGJ, Jarvis DL. Female smokers are at greater risk of airflow obstruction than male smokers. UK Biobank. Am J Respir Crit Care Med. 2017;195:1226–35.

  42. Sørheim IC, Johannessen A, Gulsvik A, Bakke PS, Silverman EK, DeMeo DL. Gender differences in COPD: are women more susceptible to smoking effects than men? Thorax. 2010;65:480–5.

    Article  PubMed  Google Scholar 

  43. Prescott E, Bjerg AM, Andersen PK, Lange P, Vestbo J. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J. 1997;10:822–7.

    Article  CAS  PubMed  Google Scholar 

  44. Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type. Am J Epidemiol. 1993;138:281–93.

    Article  CAS  PubMed  Google Scholar 

  45. Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst. 1996;88:183–92.

    Article  CAS  PubMed  Google Scholar 

  46. Powell HA, Iyen-Omofoman B, Hubbard RB, Baldwin DR, Tata LJ. The association between smoking quantity and lung cancer in men and women. Chest. 2013;143:123–9.

    Article  PubMed  Google Scholar 

  47. Henschke CI, Yip R, Miettinen OS. Women’s susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. JAMA. 2006;296:180–4.

    Article  PubMed  Google Scholar 

  48. Bain C, Feskanich D, Speizer FE, Thun M, Hertzmark E, Rosner BA, Colditz GA. Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst. 2004;96:826–34.

    Article  PubMed  Google Scholar 

  49. Freedman ND, Leitzmann MF, Hollenbeck AR, Schatzkin A, Abnet CC. Cigarette smoking and subsequent risk of lung cancer in men and women: analysis of a prospective cohort study. Lancet Oncol. 2008;9:649–56.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Park B, Kim Y, Lee J, Lee N, Jang SH. Sex difference and smoking effect of lung cancer incidence in Asian population. Cancers (Basel). 2020;13.

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Acknowledgements

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Funding

This work was supported by the National Research Foundation of Korea grants funded by the Korean government (Ministry of Science and ICT) [NRF-2021R1A2C2093987].

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SHS & TK: Writing the original draft. HK & JC: Methodology, formal analysis, and investigation. HYP: Writing, review, editing, supervision, and project administration. DK: Methodology, formal analysis, investigation, writing, review, and editing. All the authors discussed the results and approved the final version of the manuscript.

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Correspondence to Danbee Kang or Hye Yun Park.

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The Institutional Review Board of the Samsung Medical Center approved the study (approval no:2022-09-022) and waived the requirement for informed consent because the K-NHIS data were deidentified.

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The authors declare no competing interests.

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Shin, S.H., Kim, T., Kim, H. et al. Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study. Respir Res 25, 133 (2024). https://doi.org/10.1186/s12931-024-02741-1

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