Supplementary Material for: GOLD-grade specific disease characterization and phenotyping of COPD using quantitative computed tomography in the nationwide COSYCONET multicenter trial in Germany

Abstract
Introduction: To apply quantitative computed tomography (QCT) for GOLD-grade specific disease characterization and phenotyping of air-trapping, emphysema, and airway abnormalities in patients with chronic obstructive pulmonary disease (COPD) from a nationwide cohort study.
Methods: As part of the COSYCONET multicenter study, standardized CT in ex- and inspiration, lung function assessment (FEV1/FVC) and clinical scores (BODE index) were prospectively acquired in 525 patients (192women, 327men, aged 65.7±8.5y) at risk for COPD and at GOLD1-4. QCT parameters total lung volume (TLV), emphysema index (EI), parametric response mapping (PRM) for emphysema (PRMEmph) and functional small airway disease (PRMfSAD), total airway volume (TAV), wall percentage (WP) and total diameter (TD) were computed using automated software.
Results: TLV, EI, PRMfSAD and PRMEmph increased incrementally with each GOLD grade (p<0.001). Aggregated WP5-10 of subsegmental airways was higher from GOLD1 to GOLD3 and lower again at GOLD4 (p<0.001), whereas TD5-10 was significantly dilated only in GOLD4 (p<0.001). 58 patients were phenotyped as 'non-airway non-emphysema type', 202 as 'airway type', 96 as 'emphysema type' and 169 as 'mixed type'. FEV1/FVC was best in 'non-airway non-emphysema type' compared to other phenotypes, while 'mixed type' had worst FEV1/FVC (p<0.001). BODE index was 0.56±0.72 in the 'non-airway non-emphysema type' and highest with 2.55±1.77 in 'mixed type' (p<0.001).
Conclusion: QCT demonstrates increasing hyperinflation and emphysema dependent on GOLD grade, while airway wall thickening increases until GOLD 3 and airway dilatation occurs in GOLD4. QCT identifies four disease phenotypes with implications for lung function and prognosis.

摘要
引言：本研究依托一项全国性队列研究，旨在应用定量计算机断层扫描（quantitative computed tomography, QCT）对慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）患者开展基于GOLD分级的疾病特征表征与表型分型，覆盖空气潴留、肺气肿及气道异常三类病理改变。
方法：作为多中心研究COSYCONET的组成部分，本研究前瞻性纳入525例存在COPD患病风险且GOLD分级为1~4级的患者（其中女性192例，男性327例，年龄65.7±8.5岁），采集呼气相与吸气相标准化CT图像、行肺功能评估[第1秒用力呼气容积/用力肺活量（FEV1/FVC）]及临床评分[BODE指数（BODE index）]。采用自动化软件计算定量CT参数：肺总体积（total lung volume, TLV）、肺气肿指数（emphysema index, EI）、肺气肿参数响应图（parametric response mapping for emphysema, PRMEmph）、功能性小气道病变参数响应图（functional small airway disease, PRMfSAD）、气道总体积（total airway volume, TAV）、管壁占比（wall percentage, WP）及气道总直径（total diameter, TD）。
结果：TLV、EI、PRMfSAD及PRMEmph随GOLD分级升高呈渐进性升高（均P<0.001）。亚段气道的WP5-10汇总值从GOLD1级至GOLD3级逐渐升高，至GOLD4级时再次降低（P<0.001）；而TD5-10仅在GOLD4级时出现显著扩张（P<0.001）。本研究共完成525例患者的表型分型：58例为「非气道非肺气肿型」，202例为「气道型」，96例为「肺气肿型」，169例为「混合型」。与其余表型相比，「非气道非肺气肿型」患者的FEV1/FVC水平最优，而「混合型」患者的FEV1/FVC水平最差（P<0.001）。「非气道非肺气肿型」患者的BODE指数为0.56±0.72，「混合型」患者的BODE指数最高，达2.55±1.77（P<0.001）。
结论：定量计算机断层扫描（QCT）可反映随GOLD分级升高而加重的肺过度充气与肺气肿病变；气道壁增厚程度随分级升高至GOLD3级达到峰值，而气道扩张仅见于GOLD4级。QCT可识别出四种疾病表型，其与患者肺功能及预后密切相关。