Supplementary Material for: Sputum Eicosanoid Profiling in Exacerbations of Chronic Obstructive Pulmonary Disease

<b><i>Background:</i></b> Eicosanoids are small lipid molecules with diverse biological functions in the airways. <b><i>Objectives:</i></b> The aim of this study was to investigate changes in leukotriene B₄ (LTB₄), 8-isoprostane, prostaglandin E₂ (PGE₂) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery. <b><i>Methods:</i></b> Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay. <b><i>Results:</i></b> Sputum PGE₂ [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p &lt; 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p &lt; 0.01] and LTB₄ [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p &lt; 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE₂ levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p &lt; 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE₂ and sputum neutrophil and lymphocyte cell counts in patients with exacerbation. <b><i>Conclusions:</i></b> Our results suggest that 8-isoprostane, LTB₄ and PGE₂ but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE₂ for use as a biomarker of recovery from an exacerbation requires further studies.

<b><i>背景：</i></b> 类二十烷酸（Eicosanoids）是一类小分子脂质分子，在气道中发挥多种生物学功能。<b><i>目的：</i></b> 本研究旨在探讨慢性阻塞性肺疾病（COPD）患者在严重急性加重发作时及康复过程中，痰液中白三烯B4（LTB4）、8-异前列腺素、前列腺素E2（PGE2）及半胱氨酰白三烯（cys-LT）水平的变化情况。<b><i>方法：</i></b> 本研究纳入37例出现急性加重发作的既往吸烟COPD患者。分别于（i）入院时及（ii）常规治疗后采集痰液样本。另纳入25例病情稳定的既往吸烟COPD患者作为对照。采用酶免疫测定法检测类二十烷酸水平。<b><i>结果：</i></b> 与病情稳定的受试者相比，急性加重患者的痰液中PGE2[39.8(13.3~103.3) vs. 5.05(2.3~12.1) pg/ml，P<0.001]、8-异前列腺素[89.5(36.9~184.7) vs. 29.7(13.8~68.8) pg/ml，P<0.01]及LTB4[587.7(252.9~774.8) vs. 276.1(105.4~594.7) pg/ml，P<0.05]水平均升高。常规治疗后，仅PGE2水平显著降低[出院时：19.6(4.6~52.5) pg/ml，P<0.01]，其余类二十烷酸水平仍维持升高状态（P=无统计学意义）。病情稳定患者与急性加重患者的痰液cys-LT水平无明显差异，且治疗对cys-LT水平亦无影响。在急性加重患者中，痰液PGE2水平与中性粒细胞及淋巴细胞计数存在显著相关性。<b><i>结论：</i></b> 本研究结果表明，8-异前列腺素、LTB4及PGE2而非cys-LTs可能参与了COPD患者气道内与急性加重相关的炎症过程。将PGE2作为急性加重后康复的生物标志物进行验证，仍需开展进一步研究。