Title: HOCHUEKKITO IMPROVES SYSTEMIC INFLAMMATION AND NUTRITIONAL STATUS IN ELDERLY PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Abstract: To the Editor: Chronic obstructive pulmonary disease (COPD) has significant systemic effects, such as weight loss and nutritional abnormalities.1 Although not much is known regarding the underlying mechanisms of systemic effects, any new therapeutic strategy would be required to improve this chronic inflammatory process. The traditional herbal medicine Hochuekkito (Bu-Zhong-Yi-Qi-Tang) could improve the quality of life and immunological status of elderly patients and be useful in protecting infection.2,3 The effects of Hochuekkito on systemic inflammation and nutritional status in elderly patients with COPD were investigated. It has been reported that Hochuekkito inhibits rhinovirus infection, one of the major causes of common colds, and modulates airway inflammation by reducing cytokine production.4 In the present study, the effects of Hochuekkito on systemic inflammation and nutritional status was investigated in 71 elderly patients with moderate to severe COPD. COPD was diagnosed based on past history, physical examination, and spirometric data.5 Patients with COPD frequently experience common colds6 and exacerbations7 in winter season in Japan. This study was started in September to December 2004 and 2005, so that it would cover the winter for 6 months of the study period, and subjects would have more chances to acquire common colds and experience exacerbations. Health-related quality of life was evaluated according to the Symptoms score of the St. George's Respiratory Questionnaire (SGRQ). This report is based on the results of a prospective, multicenter (n=20), parallel-group, randomized study. The results from Chiba University have been reported previously.8 The study group (n=34) was given 7.5 g of Hochuekkito extract daily in addition to inhaled bronchodilators, inhaled glucocorticosteroids, or both, whereas the control group (n=37) continued the previous prescription of inhaled bronchodilators, inhaled glucocorticosteroids, or both. The daily dose of Hochuekkito extract was divided into three doses of 2.5 g each taken orally 30 minutes before each meal for 6 months. There were no significant differences between the two groups regarding age, sex, body mass index, pulmonary function, previous prescriptions, body weight, or Symptoms score of the SGRQ at the start of the study. Body weight increased from baseline (50.9±2.0 kg) to the end of the trial (52.2±1.9 kg) in the study group (P<.05), and remained unchanged in the control group. The Symptoms score decreased with treatment with Hochuekkito in the study group (from 59.8±4.1 to 45.6±3.3; P<.05), but did not in the control group, indicating that Hochuekkito improved patient quality of life. The mean number of common colds for 6 months was significantly lower in the study group (2.04±0.46) than in the control group (3.42±0.49) (P<.05). The number of exacerbations over 6 months was also significantly lower in the study group (0.12±0.06) than in the control group (0.52±0.13) (P<.05). Serum inflammatory (C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6) and nutritional (prealbumin) markers were examined before and 6 months after the treatments. CRP, TNF-α, and IL-6 were not significantly different between the groups in the baseline period. Blood levels of CRP, TNF-α, and IL-6 correlated negatively with percentage predicted forced expiratory volume in 1 minute in the baseline period. CRP, TNF-α, and IL-6 decreased after Hochuekkito treatment but remained unchanged in the control group. Serum prealbumin correlated positively with body mass index and was not significantly different between groups in the baseline period. In the study group, serum prealbumin level increased and was unchanged in the control group (Figure 1). Any apparent adverse effect due to Hochuekkito therapy was not observed during the study period. (left panel) Serum pre-albumin values and body mass index were positively correlated at the start of the study. (right panel) Serum pre-albumin values did not differ significantly between the two groups before treatment. In the Hochuekkito-treated group, the mean value±standard error of serum pre-albumin increased significantly from 23.7±0.7 to 26.0±0.8 mg/dL (P<.01). In the control group, serum pre-albumin remained unchanged from 22.9±0.9 to 22.2±0.9 mg/dL during the study period (P=.09). These data indicate that Hochuekkito treatment improves systemic inflammation and nutritional status and decreases the chances of the common cold and exacerbations, suggesting that Hochuekkito may have a biodefensive effect against viruses or bacteria. The biodefensive effects of Hochuekkito may be linked to the decreased systemic inflammatory responses. These effects may result in the increase in body weight and improvement of patients' quality of life in elderly patients with COPD. Whatever the mechanisms, lower CRP levels may be associated with better outcomes.9 This study suggests an interrelationship between systemic inflammation and nutritional status in patients with COPD, because Hochuekkito improved the inflammatory and metabolic responses simultaneously, although long-term, large-scale studies are needed to determine whether Hochuekkito can modify all-cause morbidity and mortality from COPD. The COPD Herbal Medicine Research Group consisted of the following investigators: Koichiro Tatsumi and Nariyuki Shinozuka, Department of Respirology, Graduate School of Medicine, Chiba University; Nobuyasu Sekiya, Department of Frontier Japanese-Oriental Medicine, Graduate School of Medicine, Chiba University; Katustoshi Nakayama, Department of Geriatrics and Gerontology, Tohoku University School of Medicine; Michiaki Mishima, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University; Masakazu Ichinose, Third Department of Internal Medicine, Wakayama Medical University; Hisamichi Aizawa, Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine; Atsushi Nagai, First Department of Medicine, Tokyo Women's Medical University; Yukihiko Sugiyama, Division of Pulmonary Medicine, Department of Medicine, Jichi Medical School; Kuniaki Seyama, Department of Respiratory Medicine, Juntendo University School of Medicine; Jun Ueki, School of Health Care and Nursing, Juntendo University; and Yoshinosuke Fukuchi, Department of Respiratory Medicine, Juntendo University School of Medicine. Conflict of Interest: Koichiro Tatsumi, Katsutoshi Nakayama, and Yoshinosuke Fukuchi were supported by a grant to the COPD Herbal Medicine Research Group (17120801) from the Ministry of Health, Labor and Welfare, Japan. In addition, Koichiro Tatsumi and Takayuki Kuriyama were supported by a grant to Respiratory Failure Research Group from the Ministry of Health, Labor and Welfare, Japan. Author Contributions: Koichiro Tatsumi and Nariyuki Shinozuka had equally full access to all of the data in the study and take responsibility for the integrity of the data analysis. Katsutoshi Nakayama and Nobuyasu Sekiya were the main clinical investigators. Takayuki Kuriyama and Yoshinosuke Fukuchi contributed to study supervision and the study design. Sponsor's Role: None.