COPD患者急性加重的频率：对COPD亚人群中期结果分析（SPIROMICS）的队列研究
2017/08/08
摘要
背景：当前的治疗策略对COPD患者急性加重的危险分层主要基于过去一年是否出现不少于两次的急性加重。
目的：本研究旨在了解COPD急性加重的频率的类型及与加重相关的因素。
方法：我们分析了40-80岁之间的、具备3年的前瞻数据（数据可以通过不同的途径获取，包括医疗服务中心、口述、现有的病历档案）的COPD患者。研究对象在2010年11月12日至2015年7月31日之间入组。根据观察的3年间病情急性加重的频率将病人分为3类：第一类：3年均无急性加重，第二类：每年均有急性加重，第三类：不规律出现加重（指3年间某些年份出现急性加重、某些不出现）。病人按照GOLD指南中肺功能分级的标准进行分组（指吸入支气管舒张剂后FEV1的水平）。通过逻辑回归法比较第一类和第二类人群的相关因素。同时通过数学建模分析COPD急性加重的预测指标.基线症状程度通过COPD调查问卷评估。
结果：1843名患者中，1105名患者有完整的随访信息。其中538名（49%）患者在3年中至少出现1次病情加重，567 名(51%)未出现病情加重。82名 (7%)患者每年至少出现1次病情加重，只有23名 (2%)患者每年均出现不少于2次病情加重。不规律出现病情加重（指3年间某些年份出现急性加重、某些不出现）的患者较常见，(456名 [41%])， GOLD分级3和4级的患者较多见（456名不规律出现急性加重的患者中共有256名，占56%）。与未出现急性加重的患者相比，持续加重（3年内每年均出现不少于1次急性加重）与基线症状、既往加重情况、CT下小气道异常、较低的白介素15浓度及较高的白介素8 浓度相关。
结论：尽管COPD急性加重很常见，大多数个体年与年之间急性加重的程度有较大不同。在观察的3年中至少出现1次急性加重的患者中，极少部分每年均出现不少于2次的加重。除了在进入观察前1年患者的急性加重症状及病史以外，我们发现许多其他的与持续加重相关的因素，包括CT下小气道异常、白介素15及白介素8 的水平。
Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.
MeiLan K Han, Pedro M Quibrera, Elizabeth E Carretta, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Christopher B Cooper, Alejandro Comellas, David J Couper, Jeffrey L Curtis, Gerard Criner, Mark T Dransfield, Nadia N Hansel, Eric A Hoffman, Richard E Kanner,Jerry A Krishnan, Carlos H Martinez, Cheryl B Pirozzi, Wanda K O’Neal, Stephen Rennard, Donald P Tashkin, Jadwiga A Wedzicha,Prescott Woodruff, Robert Paine III*, Fernando J Martinez*, for the SPIROMICS investigators†.
Abstract
BACKGROUND:Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year.
OBJECTIVE:The aim of this study was to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time
METHODS:In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40–80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1–4) on the basis of post-bronchodilator FEV 1 . Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe.Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test.
RESULTS:2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations.
CONCLUSIONS:Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations.
背景：当前的治疗策略对COPD患者急性加重的危险分层主要基于过去一年是否出现不少于两次的急性加重。
目的：本研究旨在了解COPD急性加重的频率的类型及与加重相关的因素。
方法：我们分析了40-80岁之间的、具备3年的前瞻数据（数据可以通过不同的途径获取，包括医疗服务中心、口述、现有的病历档案）的COPD患者。研究对象在2010年11月12日至2015年7月31日之间入组。根据观察的3年间病情急性加重的频率将病人分为3类：第一类：3年均无急性加重，第二类：每年均有急性加重，第三类：不规律出现加重（指3年间某些年份出现急性加重、某些不出现）。病人按照GOLD指南中肺功能分级的标准进行分组（指吸入支气管舒张剂后FEV1的水平）。通过逻辑回归法比较第一类和第二类人群的相关因素。同时通过数学建模分析COPD急性加重的预测指标.基线症状程度通过COPD调查问卷评估。
结果：1843名患者中，1105名患者有完整的随访信息。其中538名（49%）患者在3年中至少出现1次病情加重，567 名(51%)未出现病情加重。82名 (7%)患者每年至少出现1次病情加重，只有23名 (2%)患者每年均出现不少于2次病情加重。不规律出现病情加重（指3年间某些年份出现急性加重、某些不出现）的患者较常见，(456名 [41%])， GOLD分级3和4级的患者较多见（456名不规律出现急性加重的患者中共有256名，占56%）。与未出现急性加重的患者相比，持续加重（3年内每年均出现不少于1次急性加重）与基线症状、既往加重情况、CT下小气道异常、较低的白介素15浓度及较高的白介素8 浓度相关。
结论：尽管COPD急性加重很常见，大多数个体年与年之间急性加重的程度有较大不同。在观察的3年中至少出现1次急性加重的患者中，极少部分每年均出现不少于2次的加重。除了在进入观察前1年患者的急性加重症状及病史以外，我们发现许多其他的与持续加重相关的因素，包括CT下小气道异常、白介素15及白介素8 的水平。
(中日友好医院呼吸与危重症医学科 张科文摘译 林江涛审校)
（Lancet Respir Med 2017 Published Online June 28, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30207-2）
（Lancet Respir Med 2017 Published Online June 28, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30207-2）
Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.
MeiLan K Han, Pedro M Quibrera, Elizabeth E Carretta, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Christopher B Cooper, Alejandro Comellas, David J Couper, Jeffrey L Curtis, Gerard Criner, Mark T Dransfield, Nadia N Hansel, Eric A Hoffman, Richard E Kanner,Jerry A Krishnan, Carlos H Martinez, Cheryl B Pirozzi, Wanda K O’Neal, Stephen Rennard, Donald P Tashkin, Jadwiga A Wedzicha,Prescott Woodruff, Robert Paine III*, Fernando J Martinez*, for the SPIROMICS investigators†.
Abstract
BACKGROUND:Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year.
OBJECTIVE:The aim of this study was to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time
METHODS:In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40–80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1–4) on the basis of post-bronchodilator FEV 1 . Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe.Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test.
RESULTS:2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations.
CONCLUSIONS:Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations.
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