Reduction in exacerbation of COPD in patients of advanced age using the Japanese Kampo medicine Dai-kenchu-to: a retrospective cohort study

Abstract

Purpose

Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD.

Patients and methods

We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy.

Results

Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67–0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference.

Conclusion

Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD.

Keywords:

• TU-100
• herbal medicine
• muscarinic receptor antagonists
• propensity score
• survival analysis

Supplementary materials

Table S1 List of drugs used to treat COPD and drugs used to define COPD exacerbation in outpatient settings

Table S2 ICD-10 codes used to identify comorbidities

Acknowledgments

This work was supported by grants from the Ministry of Health, Labor and Welfare, Japan (H30-Policy-Designated-001, H30-Policy-Designated-004, and H29-ICT-Genral-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141). The funding bodies had no role in the design of the study; collection, analysis, or interpretation of the data; or writing of the manuscript.

Disclosure

TJ (corresponding author), NM, and HY have received financial contributions from Tsumura & Company (Tokyo, Japan) because they have academic affiliations with the Department of Health Services Research, Graduate School of Medicine, The University of Tokyo supported by Tsumura & Company. Tsumura & Company played no role in this study. The corresponding author also receives research funding from Tsumura & Company for research not related to this study. The authors report no other conflicts of interest in this work.

Author contributions

TJ: study design, data analysis, data interpretation, and manuscript preparation. NM: data analysis, data interpretation, and manuscript preparation. HY: data analysis, data interpretation, and manuscript preparation. YS: data analysis and data interpretation. HM: data collection, data analysis, and data interpretation. HU: study design and data interpretation. AM: study design and data interpretation. YY: study design and data interpretation. KF: data collection and data interpretation. HY: study design and data interpretation. YH: study design, data interpretation, and manuscript preparation. All authors contributed to data analysis, draft or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.