BACKGROUND Cachexia is an important extra-pulmonary manifestation of chronic obstructive pulmonary disease (COPD) presenting as unintentional weight loss and altered body composition. Previous studies have focused on the relative importance of body composition compared with body mass rather than the relative importance of dynamic compared with static measures. We aimed to determine the prevalence of cachexia and pre-cachexia phenotypes in COPD and examine the associations between cachexia and its component features with all-cause mortality. METHODS We enrolled 1755 consecutive outpatients with stable COPD from two London centres between 2012 and 2017, stratified according to European Respiratory Society Task Force defined cachexia [unintentional weight loss >5% and low fat-free mass index (FFMI)], pre-cachexia (weight loss >5% but preserved FFMI), or no cachexia. The primary outcome was all-cause mortality. We calculated hazard ratios (HRs) using Cox proportional hazards regression for cachexia classifications (cachexia, pre-cachexia, and no cachexia) and component features (weight loss and FFMI) and mortality, adjusting for age, sex, body mass index, and disease-specific prognostic markers. RESULTS The prevalence of cachexia was 4.6% [95% confidence interval (CI): 3.6-5.6] and pre-cachexia 1.6% (95% CI: 1.0-2.2). Prevalence was similar across sexes but increased with worsening Global Initiative for Chronic Obstructive Pulmonary Disease spirometric stage and Medical Research Council dyspnoea score (all P < 0.001). There were 313 (17.8%) deaths over a median (interquartile range) follow-up duration 1089 (547-1704) days. Both cachexia [HR 1.98 (95% CI: 1.31-2.99), P = 0.002] and pre-cachexia [HR 2.79 (95% CI: 1.48-5.29), P = 0.001] were associated with increased mortality. In multivariable analysis, the unintentional weight loss feature of cachexia was independently associated with mortality [HR 2.16 (95% CI: 1.31-3.08), P < 0.001], whereas low FFMI was not [HR 0.88 (95% CI: 0.64-1.20), P = 0.402]. Sensitivity analyses using body mass index-specific, age-specific, and gender-specific low FFMI values found consistent findings. CONCLUSIONS Despite the low prevalence of cachexia and pre-cachexia, both confer increased mortality risk in COPD, driven by the unintentional weight loss component. Our data suggest that low FFMI without concurrent weight loss may not confer the poor prognosis as previously reported for this group. Weight loss should be regularly monitored in practice and may represent an important target in COPD management. We propose the incorporation of weight monitoring into national and international COPD guidance.

中文翻译：

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体重减轻对慢性阻塞性肺疾病相关恶病质的预后意义：一项前瞻性队列研究。


背景技术恶病质是慢性阻塞性肺病(COPD)的重要肺外表现，表现为无意的体重减轻和身体成分改变。先前的研究重点关注身体成分与体重相比的相对重要性，而不是动态与静态测量相比的相对重要性。我们的目的是确定 COPD 中恶病质和恶病质前期表型的患病率，并检查恶病质及其组成特征与全因死亡率之间的关联。方法 我们在 2012 年至 2017 年间连续招募了来自两个伦敦中心的 1755 名稳定期慢性阻塞性肺病 (COPD) 门诊患者，根据欧洲呼吸学会工作组定义的恶病质 [无意体重减轻 >5% 和低无脂质量指数 (FFMI)]、恶病质前期进行分层（体重减轻>5%，但保留 FFMI），或无恶病质。主要结局是全因死亡率。我们使用 Cox 比例风险回归计算恶病质分类（恶病质、恶病质前期和无恶病质）和组成特征（体重减轻和 FFMI）和死亡率的风险比 (HR)，并根据年龄、性别、体重指数和疾病进行调整-特异性预后标志物。结果 恶病质患病率为 4.6% [95% 置信区间 (CI)：3.6-5.6]，恶病质前期患病率为 1.6%（95% CI：1.0-2.2）。不同性别的患病率相似，但随着全球慢性阻塞性肺疾病倡议肺量计分期和医学研究委员会呼吸困难评分的恶化而增加（所有 P < 0.001）。在中位（四分位距）随访持续时间 1089（547-1704）天内，有 313 例（17.8%）死亡。恶病质[HR 1.98（95% CI：1.31-2.99），P = 0.002]和恶病质前期[HR 2.79（95% CI：1.48-5.29），P = 0。001]与死亡率增加相关。在多变量分析中，恶病质的无意体重减轻特征与死亡率独立相关[HR 2.16 (95% CI: 1.31-3.08)，P < 0.001]，而低 FFMI 则与死亡率无关[HR 0.88 (95% CI: 0.64- 1.20），P = 0.402]。使用特定体重指数、特定年龄和特定性别的低 FFMI 值进行的敏感性分析发现了一致的结果。结论 尽管恶病质和恶病质前期的患病率较低，但由于无意的体重减轻，两者都会增加 COPD 的死亡风险。我们的数据表明，低 FFMI 且同时体重减轻可能不会导致先前报道的该组的不良预后。在实践中应定期监测体重减轻，这可能是慢性阻塞性肺病管理的一个重要目标。我们建议将体重监测纳入国家和国际慢性阻塞性肺病指南。