Chronic Obstructive Pulmonary Disease Outcomes Among Individuals in Japan Who Switched to Heated Tobacco Products Compared to Those Who Continued Smoking or Formerly Smoked Combustible Cigarettes: Protocol for a Real-World Retrospective Study.

Background: Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease that is highly associated with smoking. Despite widespread knowledge of the health risks of smoking, many patients with COPD continue to smoke. Growing evidence suggests that alternatives to combustible cigarettes (CIG), such as heated tobacco products (HTP), may be less harmful.

Objective: To evaluate the impact of switching from CIG to HTP on the time to subsequent COPD exacerbations in patients who have had a COPD-related hospitalization.

Methods: This retrospective cohort study will be conducted in Japan using electronic health data and tobacco exposure data from questionnaires and consumer databases. The study will invite approximately 30,000 patients who had a COPD-related hospitalization between May 2016 and December 2022. The first of these hospitalizations will be considered a patient's study Index Event. The primary outcome is the time from Index Event to subsequent COPD exacerbation (a composite outcome of subsequent COPD-related hospitalization and all-cause mortality); patients will be observed until March 2025. The primary exposure groups are HTP use and CIG use, respectively, pre- and post-index. We will use weighted Cox proportional hazard models, with propensity score weighting to balance potential confounders, to compare the primary outcome between the primary exposure groups. We will also compare the primary outcome between exclusive HTP users and ancillary exposure groups of dual users of CIG and HTP and former CIG smokers. Secondary outcomes include all-cause mortality, pneumonia-related hospitalization, COPD-related hospitalizations, and all-cause hospitalizations and will be assessed in primary and ancillary exposure groups.

Results: The study described in this protocol intends to assess whether there is a longer time to subsequent COPD hospitalizations and all-cause mortality for HTP users compared to CIG smokers.

Conclusions: This protocol describes the first large-scale study that will identify patients with COPD from a nationally representative healthcare database and evaluate the history of tobacco product usage from multiple sources. Additionally, this study protocol is the first in the tobacco medical literature that embraces real-world data providing information on HTP use from various tobacco product exposure sources. This will also be the first study to assess the relationship between HTP use and mortality in this patient population. Given the limited evidence on the health effects of HTP in COPD, the results of this study will provide real-world insights into the effects of switching to HTP use compared to continued CIG smoking in patients with COPD.

Clinicaltrial: Not applicable.