Zihlif Nadwa, Paraskakis Emmanouil, Tripoli Candida, Lex Christiane, Bush Andrew
Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK.
Pediatr Pulmonol. 2006 Jun;41(6):509-14. doi: 10.1002/ppul.20344.
Macroscopically, the airways in primary ciliary dyskinesia (PCD) are inflamed and infected, and the eventual result is bronchiectasis. The measurement of noninvasive markers of inflammation in PCD may allow determination of mechanisms of tissue damage, and even allow monitoring of therapy. The aim of this study was to measure in exhaled breath condensate (EBC) of children with PCD the concentrations of the neutrophil chemoattractants leukotriene (LT) B4 and interleukin (IL)-8 and the marker of oxidative stress 8-isoprostane (8-IP), and to try determining whether these markers can be used to assess mechanisms of airway inflammation in these patients. Concentrations of LTB4, IL-8, and 8-IP in the EBC of 23 PCD and 11 age-matched healthy children were measured using an enzyme immunoassay (EIA). The children also performed spirometry and underwent sputum induction, the latter for differential cell count. The concentrations of 8-IP in EBC of children with stable PCD were significantly increased compared to normal controls (median, 7.8 pg/ml vs. 3.1 pg/ml; P = 0.004). There was no difference in the median concentrations of EBC LTB4 between PCD subjects and healthy controls (28 pg/ml vs. 28 pg/ml; P = 0.5). IL-8 levels were below the detection limit of the assay, and were not analyzed further. There was no correlation between concentrations of either 8-IP or LTB(4) in EBC and forced expired volume in 1 sec in PCD children. Sputum induction was successful in 83% of the subjects; the median induced sputum neutrophil count was 69% (interquartile range, 59.3-73.6). No significant correlation was found between sputum neutrophils and either EBC 8-IP or LTB4 concentrations in PCD children. This study showed that oxidative stress, as reflected by increased exhaled 8-IP concentration, is increased in PCD children. The mechanism of airway neutrophilia is unclear, but is unlikely to be related to increased production of LTB4, at least in stable PCD patients.
从宏观上看，原发性纤毛运动障碍（PCD）患者的气道存在炎症和感染，最终结果是支气管扩张。对PCD患者炎症的非侵入性标志物进行检测，可能有助于确定组织损伤机制，甚至可用于监测治疗效果。本研究的目的是测量PCD患儿呼出气体冷凝液（EBC）中中性粒细胞趋化因子白三烯（LT）B4和白细胞介素（IL）-8的浓度以及氧化应激标志物8-异前列腺素（8-IP），并尝试确定这些标志物是否可用于评估这些患者气道炎症的机制。采用酶免疫测定法（EIA）测量了23例PCD患儿和11例年龄匹配的健康儿童EBC中LTB4、IL-8和8-IP的浓度。这些儿童还进行了肺活量测定，并接受了痰液诱导检查，后者用于进行细胞分类计数。与正常对照组相比，病情稳定的PCD患儿EBC中8-IP的浓度显著升高（中位数，7.8 pg/ml对3.1 pg/ml；P = 0.004）。PCD患者与健康对照者EBC中LTB4的中位数浓度无差异（28 pg/ml对28 pg/ml；P = 0.5）。IL-8水平低于该检测方法的检测限，未作进一步分析。PCD患儿EBC中8-IP或LTB4的浓度与1秒用力呼气量之间无相关性。83%的受试者痰液诱导成功；诱导痰液中中性粒细胞计数的中位数为69%（四分位间距，59.3 - 73.6）。PCD患儿痰液中的中性粒细胞与EBC中8-IP或LTB4的浓度之间未发现显著相关性。本研究表明，呼出的8-IP浓度升高所反映的氧化应激在PCD患儿中有所增加。气道中性粒细胞增多的机制尚不清楚，但至少在病情稳定的PCD患者中，不太可能与LTB4产生增加有关。
