Add-on Chinese medicine for hospitalized chronic obstructive pulmonary disease (CHOP): A cohort study of hospital registry

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The effect of Chinese medicine (CM) on mortality during acute exacerbation of COPD is unclear. We evaluated the real-world effectiveness of add-on personalized CM in hospitalized COPD patients with acute exacerbation. Methods: This is a retrospective cohort study with new-user design. All electronic medical records of hospitalized adult COPD patients (n = 4781) between July 2011 and November 2019 were extracted. Personalized CM exposure was defined as receiving CM that were prescribed, and not in a fixed form and dose at baseline. A 1:1 matching control cohort was generated from the same source and matched by propensity score. Primary endpoint was mortality. Multivariable Cox regression models were used to estimate the hazard ratio (HR) adjusting the same set of covariates (most prevalent with significant inter-group difference) used in propensity score calculation. Secondary endpoints included the change in hematology and biochemistry, and the association between the use of difference CMs and treatment effect. The prescription pattern was also assessed and the putative targets of the CMs on COPD was analyzed with network pharmacology approach. Results: 4325 (90.5%) patients were included in the analysis. The mean total hospital stay was 16.7 +/- 11.8 days. In the matched cohort, the absolute risk reduction by add-on personalized CM was 5.2% (3.9% vs 9.1%). The adjusted HR of mortality was 0.13 (95% CI: 0.03 to 0.60, p = 0.008). The result remained robust in the sensitivity analyses. The change in hematology and biochemistry were comparable between groups. Among the top 10 most used CMs, Poria (Fu-ling), Citri Reticulatae Pericarpium (Chen-pi) and Glycyrrhizae Radix Et Rhizoma (Gan-cao) were associated with significant hazard reduction in mortality. The putative targets of the CM used in this cohort on COPD were related to Jak-STAT, Toll-like receptor, and TNF signaling pathway which shares similar mechanism with a range of immunological disorders and infectious diseases. Conclusion: Our results suggest that add-on personalized Chinese medicine was associated with significant mortality reduction in hospitalized COPD patients with acute exacerbation in real-world setting with minimal adverse effect on liver and renal function. Further randomized trials are warranted.