Study design and patients

Data for this study were obtained as part of a multicenter, cross-sectional study conducted at six facilities in four prefectures in Japan between November 2017 and May 2020 that comprehensively evaluated patients with COPD and their families’ smoking status, satisfaction, and understanding of the disease. The participants were outpatients, and questionnaires were randomly distributed at the discretion of the outpatient doctor. Among the patients who had previously smoked, those who answered that they had quit smoking and had not smoked at all for longer than one month were defined as past smokers, while those who answered that they were currently smoking were defined as current smokers¹⁸. We also confirmed on the questionnaire whether the patient was using HTP. The diagnosis of COPD was made based on the Global Initiative for Chronic Obstructive Lung Disease criteria: a post-bronchodilator ratio⁴ of forced expiratory volume in one second to forced vital capacity <0.7 and a clinical diagnosis of COPD made by a respiratory physician. The inclusion criteria were: age ≥40 years and a smoking history. The exclusion criteria were: acute exacerbation of COPD within 4 weeks, concomitant respiratory diseases other than COPD, concurrent active malignancy, and an inability to read or understand questionnaires. A total of 108 patients were excluded due to the following reasons: the questionnaire could not be collected for various reasons (n=59), there was a discrepancy in the answers to the questions regarding tobacco (n=43), and there was a large discrepancy in the answers regarding clinical items other than tobacco (n=6). Although we have data on the number of questionnaires distributed and collected by physicians, the exact number of patients with COPD who were treated by physicians at outpatient clinics was unclear; therefore, the actual total number of patients with COPD visiting our study facilities was unknown. Finally, this study included 411 outpatients with COPD. All participants provided written informed consent. This study was conducted in accordance with the Declaration of Helsinki guidelines and was approved by the ethics committee of the relevant institution as well as an independent ethics committee.

Questionnaire contents and investigated clinical factors

The participants in this study received a questionnaire, which was returned to the outpatient physician upon completion. The duration of smoking and the number of cigarettes smoked per day were confirmed. For current smokers including HTP users, a survey was conducted on smoking behavior, reasons for not quitting smoking, and the content of guidance on smoking cessation that was provided by an outpatient doctor. For past smokers, the reason for quitting smoking and whether they regretted smoking were confirmed using the questionnaire. One family member, identified by the patient as their closest, was evaluated and classified as either a current smoker, past smoker, or a never smoker.

Data on the education level of patients were collected and the level classified as lower than high school, high school, vocational school, or university. The patients’ most recent respiratory function test results and body mass index (BMI: kg/m²) measurements were extracted from the clinical records. Patient health status was assessed using the COPD Assessment Test (CAT)¹⁹, dyspnea was evaluated using the modified Medical Research Council (mMRC) dyspnea scale²⁰, appetite was measured using the Simplified Nutritional Appetite Questionnaire (SNAQ)²¹, and mood disorders using the Hospital Anxiety and Depression Scale -Anxiety (HADS-A) and HADS-Depression (HADS-D)²². A higher score for CAT, mMRC, HADS-A, and HADS-D indicated that the patient had more severe symptoms. A high SNAQ score was indicative of an increased appetite.

Statistical analysis

Continuous variables that were normally distributed in the histogram were expressed as mean ± standard deviation, while the non-normally distributed variables were expressed as median and interquartile range. Student’s t-test or the Mann-Whitney U test was used for continuous variables. The χ² and Fisher’s exact test were used for categorical variables.

Logistic regression analysis was performed to identify the clinical factors associated with current smokers and patients who switched to HTP. Age, sex, and clinical variables were selected as covariates for multivariable analysis. In performing multivariable analysis, education level was divided into two groups: lower than school and high school, and vocational school and university. Multivariable analysis was conducted for factors with a p≤0.2 in the univariate analysis. In the multivariable analysis including more factors whose p-value in the univariate analysis was >0.2, the duration of smoking and number of cigarettes smoked per day were analyzed separately from the smoking pack-years. All statistical tests were two-tailed, and p<0.05 was considered to indicate statistical significance. All statistical analyses were performed using JMP Pro for Macintosh version 14 (SAS Institute, Cary, NC).

Patient background and clinical features of current smokers

Table 1 shows the patient background data. A total of 411 patients with COPD and a mean age of 73.8±8.4 years were enrolled in this study. The number of current smokers was 82 (20.0%), the average duration of smoking was 39.5±12.2 years, and the average number of cigarettes smoked per day was 25.9±13.0. The median CAT score, and mean mMRC score and predicted %FEV₁ were 14 (8–20), 1.4±1.1, and 64.5±23.4%, respectively. The proportion of current smokers in the families of participating patients with COPD was 11%.

Table 2 shows the clinical characteristics of the patients with COPD who were current and past smokers. Current smokers have been smoking for longer (45.5±11.2 vs 38.0±12.0 years, p<0.01) and smoked fewer cigarettes per day (20.3±11.4 vs 27.3±13.0, p<0.01) than past smokers. Current smokers had milder symptoms of shortness of breath (mMRC: 1.2±0.9 vs 1.5±1.1, p=0.04), had less of an appetite (SNAQ: 14^13-15 vs 15^14-16, p<0.01), were more usually living alone (34.2% vs 20.4%, p<0.01), and had more current smokers in their family (26.7% vs 7.9%, p<0.01) than past smokers. There was no difference between the two groups regarding age, sex, CAT score, HADS-A score, HADS-D score, respiratory function, or education level.

Logistic regression analysis was performed to evaluate the clinical factors associated with current smoking (Supplementary file Table S1). A younger age, longer duration of smoking, fewer number of cigarettes smoked per day, lower mMRC score, and lower SNAQ score were characteristics of current smokers after multivariable analysis: age (OR=0.94; 95% CI: 0.91–0.98, p<0.01); duration of smoking (OR=1.07; 95% CI: 1.04–1.11, p<0.01); number of cigarettes per day (OR=0.94; 95% CI: 0.91–0.97, p<0.01); mMRC (OR=0.68; 95% CI: 0.50–0.92, p=0.01); and SNAQ (OR=0.83; 95% CI: 0.71–0.97, p=0.02; Supplementary file Table S1). Living alone was not found to be significant after multivariable analysis but tended to be associated with current smoking (OR=1.71; 95% CI: 0.94– 3.14, p=0.08).

Smoking behavior, reasons for continuing smoking, guidance on smoking cessation, and characteristics of HTP users in current smokers

Current smokers were surveyed on smoking behaviors that applied to them: 61 (74.4%) answered ‘I reduced smoking’, 40 (48.8%) answered ‘I switched to a light cigarette’, and 16 (19.5%) answered ‘I switched to HTP’ (Supplementary file Table S2). The most common reason for not quitting smoking was ‘I want to quit smoking but I have a desire to smoke’ (n=55; 67.1%), the second most common reason was ‘I reduced smoking or switched to HTP’ (n=23; 28.0%), and the third most common reason was ‘I don't think smoking cessation will be effective anymore’ (n=15; 18.3%) (Supplementary file Table S2). Table 3 shows the characteristics of the patients whose reason for continuing smoking was to reduce their amount of smoking or having switched to HTP. These patients were young (p<0.01) and had a poor HADS-A score (p=0.01). The guidance on smoking cessation that current smokers received from outpatient doctors was: 25 (30.5%) answered ‘instructed to quit smoking every time’, 32 (39.0%) answered ‘instructed to quit smoking occasionally’, and 18 (22.0%) answered ‘almost no smoking cessation guidance given or smoking status not confirmed’ (Supplementary file Table S2).

Table 4 shows the clinical characteristics of the 16 patients who were using HTP and the 66 patients who were not. HTP users were younger (p<0.01) and more highly educated (p=0.01), although no significant differences were found for other clinical factors. Three logistic regression analysis models were constructed to evaluate the clinical factors associated with patients using HTP (Table 5). Even after performing multivariable analysis, a younger age was associated with HTP users, while a higher education level tended to be associated with HTP users (Table 5).

Reasons for quitting smoking and views on past smoking by past smokers

The reasons for quitting smoking by past smokers were: 122 (37.1%) answered ‘because I was diagnosed with a respiratory disease’, 79 (24.0%) answered ‘because I had difficulty breathing’, 72 (21.9%) answered ‘because I was instructed by a doctor’, 50 (15.2%) answered ‘because my family told me to quit’, and 6 (1.8%) answered ‘because the price of cigarettes went up’ (Supplementary file Table S3).

In response to the question ‘what would you like to do if you knew you had a lung disease and could go back to the past before you started smoking?’, the participants provided the following answers: 117 (35.5%) answered ‘if I could go back in time, I wouldn't have smoked a single cigarette’, and 145 (44.1%) answered ‘if I could go back in time, I would have stopped when I was young’ (Supplementary file Table S3).

Limitations

This study has several limitations. First, carbon monoxide levels in exhaled breath were not measured and the smoking status was based on self-report. Second, the primary medical institution was not included and the total number of patients with COPD who were treated at the institutions participating in our study was unclear; therefore, there is a possibility that selection bias may have occurred. Third, the section of the questionnaire on smoking that was used in this study has not been previously validated. Based on the above limitations, a larger longitudinal study among patients with COPD is required in the future.