Division of Pulmonary, Allergy and Critical Care Medicine.
UAB Lung Imaging Core, and.
J Clin Invest. 2018 Dec 3;128(12):5374-5382. doi: 10.1172/JCI120693. Epub 2018 Oct 29.
Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling. Characterization of airway changes on computed tomography has been challenging due to the complexity of the recurring branching patterns, and this can be better measured using fractal dimensions.
We analyzed segmented airway trees of 8,135 participants enrolled in the COPDGene cohort. The fractal complexity of the segmented airway tree was measured by the Airway Fractal Dimension (AFD) using the Minkowski-Bougliand box-counting dimension. We examined associations between AFD and lung function and respiratory morbidity using multivariable regression analyses. We further estimated the extent of peribronchial emphysema (%) within 5 mm of the airway tree, as this is likely to affect AFD. We classified participants into 4 groups based on median AFD, percentage of peribronchial emphysema, and estimated survival.
AFD was significantly associated with forced expiratory volume in one second (FEV1; P < 0.001) and FEV1/forced vital capacity (FEV1/FVC; P < 0.001) after adjusting for age, race, sex, smoking status, pack-years of smoking, BMI, CT emphysema, air trapping, airway thickness, and CT scanner type. On multivariable analysis, AFD was also associated with respiratory quality of life and 6-minute walk distance, as well as exacerbations, lung function decline, and mortality on longitudinal follow-up. We identified a subset of participants with AFD below the median and peribronchial emphysema above the median who had worse survival compared with participants with high AFD and low peribronchial emphysema (adjusted hazards ratio [HR]: 2.72; 95% CI: 2.20-3.35; P < 0.001), a substantial number of whom were not identified by traditional spirometry severity grades.
Airway fractal dimension as a measure of airway branching complexity and remodeling in smokers is associated with respiratory morbidity and lung function change, offers prognostic information additional to traditional CT measures of airway wall thickness, and can be used to estimate mortality risk.
ClinicalTrials.gov identifier: NCT00608764.
This study was supported by NIH K23 HL133438 (SPB) and the COPDGene study (NIH Grant Numbers R01 HL089897 and R01 HL089856). The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, Sunovion and GlaxoSmithKline.
慢性阻塞性肺疾病（COPD）的特征是气道重塑。由于反复分支模式的复杂性，对 CT 上气道变化的特征描述具有挑战性，而使用分形维数可以更好地进行测量。
我们分析了 COPDGene 队列中 8135 名参与者的分段气道树。使用气道分形维数（AFD）通过 Minkowski-Bougliand 盒计数维数来测量分段气道树的分形复杂性。我们使用多变量回归分析研究了 AFD 与肺功能和呼吸发病率之间的关联。我们进一步估计了气道树 5mm 范围内的支气管周围肺气肿（%），因为这可能会影响 AFD。我们根据中位数 AFD、支气管周围肺气肿百分比和估计的生存率将参与者分为 4 组。
在调整年龄、种族、性别、吸烟状况、吸烟包年数、BMI、CT 肺气肿、空气潴留、气道厚度和 CT 扫描仪类型后，AFD 与一秒用力呼气量（FEV1；P<0.001）和 FEV1/用力肺活量（FEV1/FVC；P<0.001）显著相关。在多变量分析中，AFD 也与呼吸质量和 6 分钟步行距离以及纵向随访中的恶化、肺功能下降和死亡率相关。我们确定了一组 AFD 低于中位数且支气管周围肺气肿高于中位数的参与者，与 AFD 高且支气管周围肺气肿低的参与者相比，生存率较差（调整后的危害比[HR]：2.72；95%CI：2.20-3.35；P<0.001），其中相当一部分人未被传统的肺活量计严重程度分级识别。
作为气道分支复杂性和重塑的测量指标，气道分形维数与吸烟者的呼吸发病率和肺功能变化相关，提供了比传统 CT 气道壁厚度测量更有价值的预后信息，并且可以用于估计死亡率风险。
ClinicalTrials.gov 标识符：NCT00608764。
这项研究得到了 NIH K23 HL133438（SPB）和 COPDGene 研究（NIH 拨款号 R01 HL089897 和 R01 HL089856）的支持。COPDGene 项目还得到了 COPD 基金会的支持，该基金会通过向由阿斯利康、勃林格殷格翰、诺华、辉瑞、西门子、山德士和葛兰素史克组成的行业顾问委员会做出贡献来提供支持。
