RATIONALE Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice. OBJECTIVE To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality. METHODS In CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality. MEASUREMENTS AND RESULTS Higher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28). CONCLUSIONS A proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.

中文翻译：

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呼吸易感性增加的蛋白质组学风险评分：一项多队列研究。


基本原理 肺功能加速下降与慢性阻塞性肺病、住院和死亡有关。然而，在临床实践中，通过纵向肺活量测定法测量确定这一轨迹是具有挑战性的。目的 确定以肺功能加速下降为训练的蛋白质组学风险评分是否可以评估未来呼吸系统疾病和死亡的风险。方法 在 CARDIA 中，一个从青年期开始的基于人群的队列，使用预测的 FEV1% 的纵向测量值（30 年内最多六个时间点）来确定加速和正常的下降轨迹。与加速下降轨迹相关的蛋白质适配体通过多变量 logistic 回归和 LASSO 回归确定。蛋白质组学呼吸敏感性评分基于这些循环蛋白得出，并应用于英国生物样本库和 COPDGene 研究，以检查与未来呼吸发病率和死亡率的关联。测量和结果 较高的易感性评分与全因死亡率独立相关 （UKBB： HR 1.56,95%CI 1.50-1.61;COPDGene：HR 1.75,95% CI 1.63-1.88），呼吸系统死亡率（UKBB：HR 2.39,95% CI 2.16-2.64;COPDGene：HR 1.83,95%CI 1.33-2.51）、事件 COPD （UKBB：HR 1.84,95%CI 1.71-1.98）、事件呼吸恶化（COPDGene：OR 1.11,95%CI 1.03-1.20）和需要住院治疗的事件恶化（COPDGene：OR 1.18,95% CI 1.08-1.28）。结论 呼吸易感性增加的蛋白质组学特征可识别有呼吸系统死亡、新发 COPD 和呼吸恶化风险的人群。 该药敏评分由与肺部健康具有众所周知和新颖关联的蛋白质组成，有望及早发现肺部疾病，而无需多年的肺活量测定测量。