Liver Injury by the Traditional Chinese Medicine Hanshirento, Zenshikunshito, and Ninjin'yoeito in a Patient with Lung Cancer: Probable Causality Assessed by the Updated Roussel Uclaf Causality Assessment Method.

INTRODUCTION: Traditional Chinese medicine (TCM) is a traditional treatment based on herbal medicines and holistic healing. It has resulted in both favorable and unfavorable patient outcomes when used to treat cancer. Cancer patients frequently depend on second opinions and folk remedies. In this case, we report the case of TCM inducing repeated moderate liver injury and delay for chemotherapy. CASE PRESENTATION: A 59-year-old woman was diagnosed with lung cancer and conducted surgery a month ago. She went to a TCM specialty clinic expecting a complete cure for the lung cancer, to improve her physical condition, and to enhance her immunity. She received the TCM formulas hanshirento, zenshikunshito, and ninjin'yoeito. After starting these medicines, she felt severe fatigue but continued them for approximately 2 weeks, After discontinuing the medicine, her fatigue was improved. She was admitted to our hospital for adjuvant chemotherapy. On admission, laboratory tests revealed moderate liver injury (AST: 705 U/L, ALT: 1091 U/L). In view of her medication history, the laboratory tests, and her lifestyle history, we thought that moderate liver injury was caused by TCM, employing the Roussel Uclaf Causality Assessment Method (RUCAM). DISCUSSION: TCM are known to be metabolized by the resident bacteria in the small intestine, but the specific metabolic processes are not well understood. Cancer patients sometimes try TCM from their own research to stay healthy. However, as with our case, TCM rarely induces liver injury, which is not well known to TCM users. Medical staffs need to be vigilant with their drug histories, including TCM, if patients have liver injuries.

The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma.

INTRODUCTION: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. OBJECTIVE: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. RESULTS: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-ß in the lung. This result indicates that the production of TGF-ß is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. CONCLUSIONS: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.