Chen Ya-Hong, Yao Wan-Zhen, Ding Yan-Ling, Geng Bin, Lu Ming, Tang Chao-Shu
Respiratory Department, Peking University, Third Hospital, Beijing 100083, China.
Pulm Pharmacol Ther. 2008;21(1):40-6. doi: 10.1016/j.pupt.2006.11.002. Epub 2006 Nov 21.
Airway inflammation plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Endogenous hydrogen sulfide (H2S) is involved in the physiological and pathophysiological process in systemic inflammation and may be involved in the pathogenesis of airway inflammation and airflow obstruction in COPD. The non-selective phosphodiesterase inhibitor theophylline has bronchodilator/anti-inflammatory properties and is widely used in the treatment of airways diseases. It is not fully understood whether endogenous H2S mediates the mechanism of theophylline anti-inflammatory effect.
The effect of short-term theophylline treatment on airway inflammation and endogenous H2S production was prospectively studied in thirty-seven patients with stable COPD. Patients were randomly divided into theophylline-treatment group (nineteen patients, orally given sustained theophylline tablets for 1 month, 0.2g, q 12h) and control group (eighteen patients, not given any theophylline). Symptom score, lung function, total and differential cell counts in sputum, serum H2S and nitric oxide (NOx) levels, sputum and serum IL-8 levels were measured at baseline and 1 month later.
No significant difference was found in symptom scores, lung function and other investigated experimental parameters at baseline between treatment and control groups, and between baseline and a month follow-up in control patients. Symptom scores were significantly lowered only in the treated patients after treatment, compared with those before (P<0.01). The proportion of neutrophils in sputum was significantly decreased (P<0.05) while that of macrophages was markedly increased (P<0.01) in the treated patients after treatment, compared with that before. No significant change was found in serum H2S and NOx levels, serum and sputum IL-8 levels before and after experiment in treatment group. Serum H2S level correlated positively with percentage of predicted FEV1 (r=0.465, P=0.005), and with proportion of sputum macrophages (r=0.349, P=0.05), but negatively with proportion of sputum neutrophils (r=-0.351, P=0.049) in all patients at baseline.
Short-term theophylline treatment improved symptoms and decreased sputum neutrophils in COPD, while serum H2S levels were not affected in our study population. Large samples will be needed to illustrate the effect of long-term theophylline treatment on inflammatory mediators and H2S generation in COPD.
气道炎症在慢性阻塞性肺疾病（COPD）的发病机制中起作用。内源性硫化氢（H₂S）参与全身炎症的生理和病理生理过程，可能参与COPD气道炎症和气流阻塞的发病机制。非选择性磷酸二酯酶抑制剂茶碱具有支气管扩张/抗炎特性，广泛用于气道疾病的治疗。内源性H₂S是否介导茶碱抗炎作用的机制尚不完全清楚。
前瞻性研究了37例稳定期COPD患者短期茶碱治疗对气道炎症和内源性H₂S产生的影响。患者随机分为茶碱治疗组（19例，口服缓释茶碱片1个月，0.2g，每12小时1次）和对照组（18例，未给予任何茶碱）。在基线和1个月后测量症状评分、肺功能、痰液中的总细胞数和分类细胞数、血清H₂S和一氧化氮（NOx）水平、痰液和血清白细胞介素-8（IL-8）水平。
治疗组和对照组在基线时以及对照组患者基线和随访1个月之间，症状评分、肺功能和其他研究的实验参数均无显著差异。治疗后仅治疗组患者的症状评分较治疗前显著降低（P<0.01）。治疗后治疗组患者痰液中中性粒细胞比例显著降低（P<0.05），而巨噬细胞比例显著增加（P<0.01）。治疗组实验前后血清H₂S和NOx水平、血清和痰液IL-8水平均无显著变化。在所有患者基线时，血清H₂S水平与预计第一秒用力呼气容积（FEV₁）百分比呈正相关（r=0.465，P=0.005），与痰液巨噬细胞比例呈正相关（r=0.349，P=0.05），但与痰液中性粒细胞比例呈负相关（r=-0.351，P=0.049）。
短期茶碱治疗可改善COPD患者的症状并减少痰液中的中性粒细胞，而在我们的研究人群中血清H₂S水平未受影响。需要大样本研究来说明长期茶碱治疗对COPD炎症介质和H₂S产生的影响。
