慢性阻塞性肺疾病患者持续性系统性炎症的前瞻性研究

Prospective research on persistent systemic inflammation of COPD patients

目的分析本地区慢性阻塞性肺疾病(简称慢阻肺)患者是否存在持续性系统性炎症(PSI),找出影响PSI的危险因素。方法选取150例慢阻肺稳定期患者和70例无吸烟史健康体检者。检测受试者血清中炎症因子白细胞介素-6(IL-6)、IL-18和激活素A的浓度,同时对受试者进行肺功能检测和一般资料的收集,并对受试者于第6个月、第12个月和第24个月进行为期2年的随访。将健康非吸烟者血清中炎症因子浓度的第95百分位数值定义为临界值,即正常上限值,大于该值即为异常。慢阻肺患者每次血清中如都有2个及2个以上的炎症因子的浓度升高(超过临界值)则说明存在PSI。在慢阻肺患者中按有0个、1个、2个及2个以上的炎症因子浓度升高分成3个组。在基线(初次招募时)、第6个月、第12个月和第24个月4个时间点上,持续为2个及2个以上炎症因子浓度升高的慢阻肺患者定义为PSI亚组,持续为0个炎症因子浓度升高的慢阻肺患者定义为非系统性炎症亚组。结果经过2年的随访,22例慢阻肺患者(14.7%)存在PSI,60例慢阻肺患者(40.0%)没有表现出有任何一个炎症因子浓度升高。PSI亚组的体重指数(BMI)更高,吸烟指数更高,纳入前1年的急性加重次数更多,随访2年期间存在持续急性加重高风险的人数更多,圣乔治医院呼吸问题调查问卷评分总分更高,第1秒用力呼气容积占预计值百分比降低,第1秒用力呼气容积与用力肺活量比值降低(均P<0.05)。较高的BMI和存在持续急性加重高风险为影响PSI的危险因素(OR值分别为0.1486、28.960,均P<0.05),而后者是最主要的危险因素。结论本地区部分慢阻肺患者存在PSI,这部分患者可能构成一种新的慢阻肺表型——全身炎症表型。较高的BMI和存在持续急性加重高风险为影响PSI的危险因素,针对这类患者进行个体化治疗预防急性加重以及适当的体重控制可能是更好的干预措施。

Objective To investigate the existence of persistent systemic inflammation(PSI)among patients with chronic obstructive pulmonary disease(COPD)in local areas,and identify the risk factors of PSI.Methods A total of 150 patients with stable COPD and 70 non-smoking healthy individuals were enrolled in our study.The levels of interleukin-6(IL-6),IL-18 and activin A in serum were detected.Pulmonary function was tested,and basic information of the candidates was acquired at the same time.All of the patients were followed-up at 6 months,12 months and 24 months for two years.The value at the 95th percentile of the concentration of inflammation markers of non-smoking healthy samples was defined as the threshold value,also known as normal ceiling limit value.Existence of PSI was defined as the condition that two or more kinds of inflammation markers exceed the threshold at each follow-up visit.The COPD patients were categorized into three classes,in which there were respectively none,one and two or more kinds of inflammation markers with over-threshold values.Based on a 2-year followup,patients with two or more kinds of inflammation markers exceeding threshold values were classified as PSI subgroup,and patients without inflammation markers exceeding threshold values as never inflamed subgroup.Results There were 22 patients(14.7%)had persistent systemic inflammation,whereas 60 patients(40.0%)did not show evidence of systemic inflammation.Single factor analysis of two subgroups showed that the patients in PSI subgroup had higher body mass index(BMI),higher smoking index,higher prior frequency of time to exacerbation,higher proportion of patients at high risk for recurrent acute exacerbation during 2-year followup,higher SGRQ total score,lower FEV1%pred and lower FEV1/FVC ratio significantly(all P<0.05).Higher BMI and higher risk of recurrent acute exacerbation were independent risk factors leading to PSI,of which the higher risk of recurrent acute exacerbation had a more important effect on PSI.Conclusions Some COPD patients have PSI in this region,which may constitute a novel COPD phenotype(called systemic inflammatory phenotype).Higher BMI and higher risk of recurrent acute exacerbation are independent risk factors leading to PSI.Individualized treatment to prevent acute exacerbation and appropriate weight control may be a better intervention for these patients.