Clinical and Inflammatory Phenotypes During Exacerbations Predict In-Hospital Adverse Outcomes in Asthma-COPD Overlap.

IF 7.2 2区医学 Q1 RESPIRATORY SYSTEM

Respirology Pub Date : 2026-09-01 Epub Date: 2026-06-23 DOI:10.1002/resp.70275

Lishan Yuan, Lei Wang, Yulai Yuan, Yilai Li, Li Zhang, Ying Liu, Lei Liu, Lingyun Lu, Min Feng, Gang Wang, Shuwen Zhang, Chongyang Zhao, Qin Wang, Deying Kang, Xin Zhang

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引用次数: 0

Abstract

Background and objectives: Exacerbations of asthma-chronic obstructive pulmonary disease overlap (EACO) are associated with high mortality, yet the acute-phase heterogeneity remains poorly characterized. This study aimed to identify distinct inflammatory phenotypes of EACO during hospitalization and evaluate their associations with clinical outcomes.

Methods: A prospective two-centre cohort study enrolled 2444 EACO patients (training and validation cohort). Baseline inflammatory markers and clinical data were collected. Unsupervised k-means clustering identified inflammatory phenotypes, with sensitivity analysis excluding demographic variables. In-hospital clinical outcomes (ICU admission, invasive ventilation, in-hospital mortality) were assessed. Logistic regression and causal mediation analysis evaluated phenotype-outcome associations. A nomogram was developed and validated using receiver operating characteristic curves (AUC).

Results: Three distinct phenotypes were identified: Cluster T1 (neutrophil-to-lymphocyte ratio [NLR]-elevated hypoeosinophilic systemic inflammatory), Cluster T2 (eosinophilic), and Cluster T3 (eosinophil-neutrophil balanced). Cluster T1 exhibited systemic hyperinflammation (elevated white blood cell count, neutrophils, NLR, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)), and the highest composite adverse outcome rate (24.2%; p < 0.001). Logistic regression revealed absolute neutrophil count (β = 0.38, p < 0.001), D-dimer (β = 0.25, p < 0.001), and absolute lymphocyte count (β = -0.41, p < 0.001) as key outcome predictors, confirmed by causal mediation analysis. The nomogram showed robust predictive performance (AUC training = 0.775; validation = 0.766).

Conclusion: Inflammatory phenotypes during EACO predict differential in-hospital outcomes, with neutrophil-dominant phenotypes conferring the highest risk. Early phenotype-based risk stratification using simple blood biomarkers may guide individualized EACO management.

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急性发作期间的临床和炎症表型可预测哮喘-慢性阻塞性肺病重叠患者的住院不良结局。

背景和目的：哮喘-慢性阻塞性肺疾病重叠（EACO）加重与高死亡率相关，但急性期异质性仍然缺乏特征。本研究旨在确定住院期间EACO的不同炎症表型，并评估其与临床结果的关系。方法：前瞻性双中心队列研究纳入2444例EACO患者（训练和验证队列）。收集基线炎症标志物和临床数据。无监督k-均值聚类识别炎症表型，敏感性分析排除人口统计学变量。评估院内临床结果（ICU入院、有创通气、院内死亡率）。逻辑回归和因果中介分析评估了表型与结果的关联。利用受者工作特征曲线（AUC）建立并验证了nomogram。结果：鉴定出三种不同的表型：集群T1（中性粒细胞与淋巴细胞比例[NLR]-嗜酸性粒细胞升高的系统性炎症），集群T2（嗜酸性粒细胞）和集群T3（嗜酸性粒细胞与中性粒细胞平衡）。集群T1表现出全体性高炎症（白细胞计数、中性粒细胞、NLR、c反应蛋白（CRP）、降钙素原（PCT）和白细胞介素-6 （IL-6）升高），综合不良转归率最高（24.2%）；p结论：EACO期间的炎症表型预测不同的住院结果，中性粒细胞显性表型具有最高的风险。使用简单的血液生物标志物进行早期表型风险分层可以指导个体化EACO管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respirology 医学-呼吸系统

CiteScore

10.60

自引率

5.80%

发文量

225

审稿时长

1 months

期刊介绍： Respirology is a journal of international standing, publishing peer-reviewed articles of scientific excellence in clinical and clinically-relevant experimental respiratory biology and disease. Fields of research include immunology, intensive and critical care, epidemiology, cell and molecular biology, pathology, pharmacology, physiology, paediatric respiratory medicine, clinical trials, interventional pulmonology and thoracic surgery. The Journal aims to encourage the international exchange of results and publishes papers in the following categories: Original Articles, Editorials, Reviews, and Correspondences. Respirology is the preferred journal of the Thoracic Society of Australia and New Zealand, has been adopted as the preferred English journal of the Japanese Respiratory Society and the Taiwan Society of Pulmonary and Critical Care Medicine and is an official journal of the World Association for Bronchology and Interventional Pulmonology.