Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center, Houston, TX.
Blood Adv. 2024 Oct 8;8(19):5156-5165. doi: 10.1182/bloodadvances.2024013748.
Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative computed tomography (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using pulmonary function tests (PFTs) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from 2 large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFTs were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CITs), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients, 66 with BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with forced expiratory volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS; P < .0001). CITs distinguished 94% of participants with BOS vs non-BOS, 85% of early BOS vs non-BOS, 92% of early BOS vs NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.74-0.94) and early BOS with AUC of 0.84 (95% CI, 0.69-0.97). qCT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.
骨髓移植(HCT)后闭塞性细支气管炎综合征(BOS)与较高的发病率和死亡率相关。定量计算机断层扫描(qCT)可有助于诊断符合美国国立卫生研究院(NIH)标准的晚期 BOS(NIH-BOS),但尚未用于诊断早期无症状 BOS(早期 BOS),从而限制了早期干预和改善预后的可能性。我们使用肺功能检查(PFT)来定义 2 家大型癌症中心患者中的 NIH-BOS、早期 BOS 和混合 BOS(具有限制性肺病的 NIH-BOS),并用 qCT 来识别早期 BOS 并区分 BOS 类型。同时纳入有短暂性肺功能损害或健康肺的患者进行比较。PFT 于 0、6 和 12 个月时进行。采用关联统计学、主成分分析、条件推断树(CIT)和机器学习(ML)分类器模型进行分析。我们的队列包括 84 例异基因 HCT 受者,其中 66 例患有 BOS(NIH 定义的早期或混合性),18 例无 BOS。所有 qCT 指标与 1 秒用力呼气量均有中度相关性,且每个 qCT 指标均能将 BOS 与非 BOS 区分开(P<0.0001)。CIT 可区分 94%的 BOS 与非 BOS 患者、85%的早期 BOS 与非 BOS 患者、92%的早期 BOS 与 NIH-BOS 患者。ML 模型诊断 BOS 的曲线下面积(AUC)为 0.84(95%置信区间 [CI],0.74-0.94),诊断早期 BOS 的 AUC 为 0.84(95%CI,0.69-0.97)。qCT 指标可识别出有早期 BOS 的个体,为该脆弱人群的密切监测和早期治疗铺平了道路。