The Traditional Herbal Medicine Hochuekkito Improves Systemic Inflammation in Patients With Chronic Obstructive Pulmonary Disease

To the Editor: Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability throughout the world. The risk of airflow limitation is significantly greater with older age.1 The chronic pulmonary inflammatory process in patients with COPD has systemic repercussions. The effect of the systemic manifestations of COPD on the prediction of mortality using a multidimensional index has recently been reported.2 We investigated the effects of the traditional herbal medicine Hochuekkito (Bu-Zhong-Yi-Qi-Tang) on systemic inflammation in older patients with COPD whose forced expiratory volume in 1 second (FEV1)/forced vital capacity was less than 70%. One randomized, controlled trial of Hochuekkito showed that the quality of life and immunological status of elderly patients improved during treatment.3 Thirty-five consecutive and clinically stable patients with COPD (mean age±standard error 73±1) were prospectively and randomly divided into two groups. One group (n=17) was given 7.5 g of Hochuekkito extract daily in addition to inhaled bronchodilators, whereas the control group (n=18) continued to use previously prescribed bronchodilators. The daily dose of Hochuekkito extract was divided into three doses of 2.5 g each to be taken orally 30 minutes before each meal for 6 months. A controller determined whether Hochuekkito was given to patients. There were no significant differences between the two groups regarding age, sex, body mass index (19.3±0.7 vs 20.7±0.8 kg/m2), or the results of pulmonary function tests (FEV1%predicted 40.7±5.0% vs 45.4±2.3%). Serum inflammatory markers were examined before and after the treatment period. Previous studies have demonstrated that serum C-reactive protein (CRP) is higher in patients with COPD without clinically relevant ischemic heart disease independent of smoking, whereas it is lower in patients with COPD receiving inhaled corticosteroid therapy.4-6 Serum CRP correlated negatively with FEV1%predicted, a marker of COPD severity, before treatment (r=−0.43, P<.001). Serum CRP did not differ significantly between the two groups before treatment (P=.08). In the Hochuekkito-treated group, serum CRP decreased significantly, from 3,230±450 to 2,060±330 ng/mL (P<.01), whereas it was unchanged in the control group (Figure 1). Serum C-reactive protein (CRP) values before and at the end of the study period. Serum CRP did not differ significantly between the two groups before treatment (P=.08). In the Hochuekkito-treated group, the mean value±standard error of serum CRP decreased significantly from 3,230±450 ng/mL to 2,060±330 ng/mL (P<.01). In the control group, serum CRP remained unchanged from 2,380±380 ng/mL to 2,380±360 ng/mL during the study period. NS=not significant. Regarding markers of systemic inflammation in COPD, serum tumor necrosis factor alpha (TNF-α; r=−0.42, P<.001) and interleukin (IL)-6 (r=−0.21, P<.001) also correlated negatively with FEV1% predicted at baseline. The pretreatment value of serum TNF-α was significantly higher (P=.02) in the Hochuekkito-treated group and decreased significantly from 3.6±0.6 pg/mL to 2.1±0.4pg/mL after treatment, whereas it was unchanged in the control group (2.2±0.3 pg/mL before and after treatment). Serum IL-6 remained unchanged in both groups. In the Hochuekkito-treated group, serum prealbumin level, a marker of nutritional status, increased from 23.6±1.1 mg/dL to 26.6±1.2 mg/dL, whereas it was unchanged in the control group. These data suggest that Hochuekkito improves systemic inflammation and nutritional status in older patients with moderate to severe COPD, although the mechanisms of Hochuekkito have not been defined. Systemic inflammation, in addition to nutritional status, is a determinant of quality of life and prognosis in COPD patients.2, 7 Further larger studies on its effects and mechanisms of action will be needed, although Hochuekkito has a long history of use in patients with COPD and weakness, and its safety has been clinically established. This study was supported by a grant to the COPD Herbal Medicine Research Group and a grant to Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan. Financial Disclosure: Koichiro Tatsumi was supported by grants to the COPD Herbal Medicine Research Group and the Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan. Takayuki Kuriyama was supported by a grant to the Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan. Author Contributions: Nariyuki Shinozuka, Akira Nakamura, and Jiro Terada: acquisition of subjects, data analysis, and interpretation of data. Koichiro Tatsumi: acquisition of subjects, data analysis, interpretation of data, and preparation of manuscript. Takayuki Kuriyama: interpretation of data. Sponsor's Role: None.