COPD 首次短期临床显著恶化后的长期结局。

Long-term outcomes following first short-term clinically important deterioration in COPD.

机构信息

Respiratory Medicine, GSK, Brentford, Middlesex, UK.

Precise Approach Ltd, Contingent worker on assignment at GSK, Uxbridge, Middlesex, UK.

出版信息

Respir Res. 2018 Nov 20;19(1):222. doi: 10.1186/s12931-018-0928-3.

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline. Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed. We evaluated post hoc the link between early CID and long-term adverse outcomes.

METHODS

CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV), ≥4-unit increase in St George's Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies. Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE). Association between presence (+) or absence (-) of CID and long-term deterioration in FEV, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.

RESULTS

In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+. At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001). Similar risks post-CID were observed in ECLIPSE.

CONCLUSIONS

A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV and health status amongst survivors.

TRIAL REGISTRATION

NCT00268216 ; NCT00292552 .

背景

慢性阻塞性肺疾病（COPD）的特征是下降轨迹各不相同。需要了解预防肺功能、健康状况或首次中度/重度加重的短期临床重要恶化（CID）作为恶化的复合终点的预后价值。我们事后评估了早期 CID 与长期不良结局之间的联系。

方法

CID 定义为用力呼气量在 1 秒内下降≥100mL（FEV），圣乔治呼吸问卷（SGRQ）评分从基线增加≥4 单位，或在两项为期 3 年的研究入组期间发生中度/重度加重。在主要分析（TORCH）中，在 6 个月时评估 CID 的存在（TORCH），在确认分析（ECLIPSE）中在 12 个月时评估 CID 的存在。评估 CID 存在（+）或不存在（-）与 FEV、SGRQ 未来恶化、加重风险和全因死亡率之间的关系。

结果

共有 2870 名（54%；TORCH）和 1442 名（73%；ECLIPSE）患者 CID+。在 36 个月时，在 TORCH 中，CID+患者（vs CID-）的 FEV 持续出现有临床意义的恶化（-117mL；95%置信区间[CI]：-134，-100mL；P<0.001）和 SGRQ 评分（+6.42 单位；95%CI：5.40，7.45；P<0.001），并且加重风险更高（危险比[HR]：1.61[95%CI：1.50，1.72]；P<0.001）和全因死亡率（HR：1.41[95%CI：1.15，1.72]；P<0.001）。在 ECLIPSE 中也观察到 CID 后存在类似的风险。