The Effects of Allopurinol on Glutathione Sulfhydryl (GSH) Serum Level, %FEV1, Six Minute Walking Test, and CAT Score of Chronis Obstructive Pulmonary Disease Patients

Introduction: Stress oxidative in chronic obstructive pulmonary disease (COPD) impaired striated muscle thus worsening COPD clinical symptoms. Allopurinol as antioxidant reduces stress oxidative in COPD so it can improve exercise capacity and clinical symptoms of COPD patients. The aims of this study were to analyze the effect of allopurinol on glutathione sulfhydryl (GSH) serum level, %FEV1 , six-minute walking test (6MWT), and COPD assessment test (CAT) score of COPD group C and D patients. Methods: This was a pre and post test group clinical trials held in pulmonology outpatient clinic in Dr. Moewardi general hospital, Surakarta from January to February 2018 using purposive sampling. The COPD group C and D patients were categorized as intervention group which received allopurinol 300 mg/day for four weeks and a control group which did not receive allopurinol. Glutathione sulfhydryl serum level, %FEV1, 6MWT, and CAT score were measured at baseline and after four weeks in both groups. Results: A total of 37 stable COPD group C and D patients were included in this study. The intervention group showed decreased of GSH level (52.58 ± 38.39) µg/ml and CAT score (10.37 ± 4.46) which were statistically significant compared to control group (p<0,05) while decreased of %FEV1 in intervention group (6.91 ± 10.60) and control group (8.43 ± 11.26) were not significant statistically (p=0.94). The intervention group also showed a significant increase of 6MWT (p=0.005) while the control group showed no significant increase (p=0.109); however, the 6MWT differences in both groups were not significant with p=0.057. Conclusion: Allopurinol decreased GSH serum level, did not influence %FEV1 , increased 6MWT, and decreased CAT score of stable COPD group C and D patients. Keywords: COPD, allopurinol, GSH, %FEV1, 6MWT, CA

Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction

Abnormal lung inflammation and oxidant burden are associated with a significant reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid resistance in attenuating lung inflammatory response, which may be due to oxidant/antioxidant imbalance. Loss of antioxidant transcription factor Nrf2 resulted in decreased HDAC2 in lung, and increased inflammatory lung response which was not reversed by steroid. Thus, steroid resistance or inability of steroids to control lung inflammatory response is dependent on Nrf2-HDAC2 axis. These findings have implications in steroid resistance, particularly during the conditions of oxidative stress when the lungs are more susceptible to inflammatory response, which is seen in patients with chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, and inflammatory bowel disease

A pilot study of the multiherb Kampo medicine bakumondoto for cough in patients with chronic obstructive pulmonary disease

Objectives: To evaluate the effect of bakumondoto. Kampo medicine, on cough in patients with chronic obstructive pulmonary disease (COPD). Design: A 16-week, randomized, open-labeled, cross-over design. Setting: Outpatient clinics at one university hospital and two general hospitals in Japan from May 2007 to March 2009. Participants: Twenty-four elderly patients (14 men and 9 women aged over 65) with COPD. Intervention: Treatment with or without bakumondoto for 8 weeks in a cross-over design. Measurements: The primary outcome measurements were the frequency and intensity of cough assessed by a visual analogue scale (VAS) and a daily cough diary. Secondary outcome measurements were quality of life (QOL) assessed using St. George's Respiratory Questionnaire (SGRQ) and lung functions measured using spirometry. Results: Treatment with bakumondoto significantly improved cough severity during the first treatment period (week 0 vs. week 8, p = 0.004) and showed a trend to decrease during the second treatment period (week 8 vs. week16, p=0.129) assessed by the VAS. Neither QOL nor lung function was affected by the treatment with bakumondoto. Conclusion: Bakumondoto may be effective in suppressing cough in elderly patients with COPD. To further confirm the efficacy, a larger and placebo-controlled study with objective cough assessment is necessary