Mok L Clara, Garcia-Uceda Antonio, Cooper Matthew N, Kemner-Van De Corput Mariette, De Bruijne Marleen, Feyaerts Nathalie, Rosenow Tim, De Boeck Kris, Stick Stephen, Tiddens Harm A W M
Faculty of Medicine and Health Sciences, The University of Western Australia, Perth, WA, Australia.
Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia.
Front Pharmacol. 2023 Apr 11;14:1147348. doi: 10.3389/fphar.2023.1147348. eCollection 2023.
Newly developed quantitative chest computed tomography (CT) outcomes designed specifically to assess structural abnormalities related to cystic fibrosis (CF) lung disease are now available. CFTR modulators potentially can reduce some structural lung abnormalities. We aimed to investigate the effect of CFTR modulators on structural lung disease progression using different quantitative CT analysis methods specific for people with CF (PwCF). PwCF with a gating mutation (Ivacaftor) or two Phe508del alleles (lumacaftor-ivacaftor) provided clinical data and underwent chest CT scans. Chest CTs were performed before and after initiation of CFTR modulator treatment. Structural lung abnormalities on CT were assessed using the Perth Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), airway-artery dimensions (AA), and CF-CT methods. Lung disease progression (0-3 years) in exposed and matched unexposed subjects was compared using analysis of covariance. To investigate the effect of treatment in early lung disease, subgroup analyses were performed on data of children and adolescents aged <18 years. We included 16 modulator exposed PwCF and 25 unexposed PwCF. Median (range) age at the baseline visit was 12.55 (4.25-36.49) years and 8.34 (3.47-38.29) years, respectively. The change in PRAGMA-CF %Airway disease (-2.88 (-4.46, -1.30), = 0.001) and %Bronchiectasis extent (-2.07 (-3.13, -1.02), < 0.001) improved in exposed PwCF compared to unexposed. Subgroup analysis of paediatric data showed that only PRAGMA-CF %Bronchiectasis (-0.88 (-1.70, -0.07), = 0.035) improved in exposed PwCF compared to unexposed. In this preliminary real-life retrospective study CFTR modulators improve several quantitative CT outcomes. A follow-up study with a large cohort and standardization of CT scanning is needed to confirm our findings.
新开发的专门用于评估与囊性纤维化（CF）肺病相关结构异常的定量胸部计算机断层扫描（CT）结果现已可用。CFTR调节剂有可能减少一些肺部结构异常。我们旨在使用针对CF患者（PwCF）的不同定量CT分析方法，研究CFTR调节剂对肺部结构疾病进展的影响。携带门控突变（依伐卡托）或两个Phe508del等位基因（鲁马卡托-依伐卡托）的PwCF提供了临床数据并接受了胸部CT扫描。在开始CFTR调节剂治疗之前和之后进行胸部CT扫描。使用针对CF的珀斯鹿特丹注释网格形态计量分析（PRAGMA-CF）、气道-动脉尺寸（AA）和CF-CT方法评估CT上的肺部结构异常。使用协方差分析比较暴露组和匹配的未暴露组受试者的肺病进展情况（0至3年）。为了研究治疗在早期肺病中的效果，对年龄小于18岁的儿童和青少年的数据进行了亚组分析。我们纳入了16名接受调节剂治疗的PwCF和25名未接受治疗的PwCF。基线访视时的中位（范围）年龄分别为12.55（4.25 - 36.49）岁和8.34（3.47 - 38.29）岁。与未暴露组相比，暴露组的PRAGMA-CF气道疾病百分比（-2.88（-4.46，-1.30），P = 0.001）和支气管扩张程度百分比（-2.07（-3.13，-1.02），P < 0.001）有所改善。儿科数据的亚组分析表明，与未暴露组相比，暴露组仅PRAGMA-CF支气管扩张百分比（-0.88（-1.70，-0.07），P = 0.035）有所改善。在这项初步的真实生活回顾性研究中，CFTR调节剂改善了多项定量CT结果。需要进行一项有大量队列且CT扫描标准化的随访研究来证实我们的发现。
