A total of 44 COPD patients were considered for the study at baseline, but complete datasets were available for analyses from 38 COPD patients (31 male, 7 female) by the end of the study. Three COPD patients in the HTP user group discontinued the use of their device during follow-up (two resulting in relapse to cigarette smoking, one stopping the use of tobacco products completely) and were excluded. Datasets from three COPD patients of the control group were not available for analysis (one moved to a different city area, and two transferred to stroke clinics). The baseline demographics, parameters assessed, and COPD GOLD staging are outlined in Table 1. There were no statistical differences between the two study groups for any of the parameters. Most patients had mild-to-severe airflow limitation as per the COPD GOLD guidelines and were managed accordingly with various combinations of inhaled therapies (corticosteroids, β2 agonists and long-acting anti-cholinergics, individually or in combination).
Cigarette consumption and HTP use
In the COPD HTP users, a significant reduction in conventional cigarette use was noted with a mean (± SD) cigarettes/day of 20.5 (± 3.4) at baseline falling to 1.5 (± 2), 1.2 (± 1.8) and 1.2 (± 1.8) at F/up1, F/up 2, and F/up 3, respectively (p < 0.001 for all 3 visits) (Tables 2, 3; Fig. 1). There were no remarkable differences over the course of the study in the number of cigarettes smoked per day in the COPD controls. Among COPD HTP users, 11/19 (57.9%) completely abstained from smoking conventional cigarettes (exclusive HTP users/single users) at F/up 3 (Table 4). In those continuing to smoke (dual users), there was a considerable decline in daily cigarette consumption, the mean (± SD) cigarettes/day at baseline decreasing from 21 (± 4.6) to 3.6 (± 1.1), 3.3 (± 1.3) and to 3.7 (± 1) at F/up1, F/up2 and F/up3, respectively (p < 0.001 for all three visits) (Table 4). Of note, all dual users consistently reduced their daily smoking by at least 70% of their baseline consumption throughout the whole duration of the study. Overall, there was a marked reduction in daily cigarettes smoked between the two study groups over the 36-month observation period (p < 0.001).
At F/up1, all HTP users were on IQOS. Three IQOS users were found to have switched to glo at F/up2. At F/up3, 17 HTP users were on IQOS and two on glo. No detail on tobacco stick consumption was recorded.
COPD HTP users had a significant decline in COPD exacerbations; with the mean (± SD) annual exacerbation rate decreasing from 2.2 (± 1.1) at baseline to 1.4 (± 0.8) (p = 0.012), 1.2 (± 0.8) (p = 0.002) and 1.3 (± 0.8) (p = 0.004) at F/up1, F/up2 and F/up3, respectively (Tables 2, 3). No significant changes in the annual COPD exacerbation rates were observed in the control group. There was an overall significant (p = 0.024) between group decrease in annual COPD exacerbations over the observation period (Tables 2, 3; Fig. 2). In the exclusive (single) HTP users, significant reductions in annual COPD exacerbations from baseline were noted at all three F/up visits (Table 4). Of note, a steady decline in annual COPD exacerbations was also observed in dual users with the mean (± SD) yearly exacerbation rate of 2.1 (± 0.6) at baseline declining to 1.6 (± 0.5) (p = 0.108) at F/up1, 1.1 (± 0.7) (p = 0.077) at F/up 2 and 1.2 (± 0.4) at F/up3 (p = 0.021) (Table 4).
Lung function assessments and COPD staging
There was no significant post-baseline improvement in post-bronchodilator FEV1 and FVC at any of the follow-up visits in the COPD HTP users (Tables 2, 3). Likewise, no significant change in spirometric indices was observed in the control group throughout the study (Tables 2, 3). Overall, there were no significant differences between the two groups in the spirometric assessments (Tables 2, 3).
GOLD COPD staging changes throughout the study are illustrated in Table 4 and Fig. 3. By the end of the study, three COPD patients in the HTP user group down-staged (i.e. improved) from GOLD COPD Stages 4 and 3 to Stages 2 and 1; in contrast, COPD GOLD stage classification was relatively stable in patients belonging to the control group throughout the whole duration of the study.
CAT scores and 6MWD test
Subjective COPD assessment using CAT scores significantly improved in the COPD HTP user group at all three follow-up visits compared to baseline (p < 0.01 at all follow-up visits) (Tables 2, 3). Both dual and single users experienced significant reductions (improvements) in CAT scores from baseline (Tables 2, 3). In contrast, there were no significant or clinically relevant improvements noted at any of the follow-up visits from baseline in the control group. Over the 3-year study period, we observed an overall significant improvement in CAT scores between COPD HTP users and COPD smokers (p = 0.008) (Tables 2, 3; Fig. 4).
Results of 6MWD at all four follow-up visits were available only for 22 patients (11 from each study group). In the HTP user group, the 6MWD significantly improved from baseline at all follow-up visits (p < 0.01), whereas no remarkable improvements in 6MWD were observed in the control group (Tables 2, 3); at F/up3, we observed a median increment in 6MWD of 69 m (p = 0.005) in the COPD HTP user group, whereas there was a small but not significant increase in median 6MWD of 20 m (p = 0.155) in the COPD control group (Tables 2, 3). Overall, there was a significant improvement (p = 0.001) in 6MWD noted between the two study groups over the entire follow-up period (Tables 2, 3).