Wucherpfennig Lena, Wuennemann Felix, Eichinger Monika, Seitz Angelika, Baumann Ingo, Stahl Mirjam, Graeber Simon Y, Zhao Shengkai, Chung Jaehi, Schenk Jens-Peter, Alrajab Abdulsattar, Kauczor Hans-Ulrich, Mall Marcus A, Sommerburg Olaf, Wielpütz Mark O
Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Front Pharmacol. 2023 Apr 10;14:1161891. doi: 10.3389/fphar.2023.1161891. eCollection 2023.
Chronic rhinosinusitis (CRS) usually presents with nasal congestion, rhinorrhea and anosmia impacts quality of life in cystic fibrosis (CF). Especially mucopyoceles pathognomonic for CRS in CF may cause complications such as spread of infection. Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of CRS from infancy to school age in patients with CF, and mid-term improvements of CRS in preschool and school-age children with CF treated with lumacaftor/ivacaftor for at least 2 months. However, long-term data on treatment effects on paranasal sinus abnomalities in preschool and school-age children with CF are lacking. 39 children with CF homozygous for F508del (mean age at baseline MRI 5.9 ± 3.0 years, range 1-12 years) underwent MRI before (MRI1) and about 7 months after starting lumacaftor/ivacaftor and then annually (median 3 follow-up MRI, range 1-4) (MRI2-4). MRI were evaluated using the previously evaluated CRS-MRI score with excellent inter-reader agreement. For intraindividual analysis ANOVA mixed-effects analysis including Geisser-Greenhouse correction and Fisher's exact test, and for interindividual group analysis Mann-Whitney test were used. The CRS-MRI sum score at baseline was similar in children starting lumacaftor/ivacaftor in school age and children starting therapy at preschool age (34.6 ± 5.2 vs.32.9 ± 7.8, = 0.847). Mucopyoceles were the dominant abnormality in both, especially in maxillary sinus (65% and 55%, respectively). In children starting therapy in school age the CRS-MRI sum score decreased longitudinally from MRI1 to MRI2 (-2.1 ± 3.5, < 0.05), MRI3 (-3.0 ± 3.7, < 0.01) and MRI4 (-3.6 ± 4.7, < 0.01), mainly due to a decrease in the mucopyoceles subscore (-1.0 ± 1.5, = 0.059; -1.2 ± 2.0, < 0.05; -1.6 ± 1.8, < 0.01; and -2.6 ± 2.8, = 0.417, respectively). In children starting lumacaftor/ivacaftor in preschool age, the CRS-MRI sum score remained stable under therapy over all three follow-up MRI (0.6 ± 3.3, = 0.520; 2.4 ± 7.6, = 0.994; 2.1 ± 10.5, > 0.999 and -0.5 ± 0.5, = 0.740; respectively). Longitudinal paranasal sinus MRI shows improvements in paranasal sinus abnormalities in children with CF starting lumacaftor/ivacaftor therapy at school age. Further, MRI detects a prevention of an increase in paranasal sinus abnormalities in children with CF starting lumacaftor/ivacaftor therapy at preschool age. Our data support the role of MRI for comprehensive non-invasive therapy and disease monitoring of paranasal sinus abnormalities in children with CF.
慢性鼻-鼻窦炎（CRS）通常表现为鼻塞、流涕和嗅觉减退，影响囊性纤维化（CF）患者的生活质量。尤其是CF中CRS的特征性黏液囊肿可能会引起感染扩散等并发症。以往使用磁共振成像（MRI）的研究表明，CF患者从婴儿期到学龄期CRS发病早且病情进展，而接受鲁马卡托/依伐卡托治疗至少2个月的学龄前和学龄期CF儿童的CRS有中期改善。然而，缺乏关于CF学龄前和学龄期儿童鼻窦异常治疗效果的长期数据。39名F508del纯合子CF儿童（基线MRI时的平均年龄为5.9±3.0岁，范围为1 - 12岁）在开始鲁马卡托/依伐卡托治疗前（MRI1）、开始治疗约7个月后以及之后每年（中位数为3次随访MRI，范围为1 - 4次）（MRI2 - 4）接受MRI检查。使用先前评估的CRS - MRI评分对MRI进行评估，阅片者间一致性良好。个体内分析采用包括Geisser - Greenhouse校正的方差分析混合效应分析和Fisher精确检验，个体间组分析采用Mann - Whitney检验。开始在学龄期接受鲁马卡托/依伐卡托治疗的儿童与开始在学龄前接受治疗的儿童在基线时的CRS - MRI总分相似（34.6±5.2对32.9±7.8, P = 0.847）。黏液囊肿在两者中都是主要异常，尤其是在上颌窦（分别为65%和55%）。在学龄期开始治疗的儿童中，CRS - MRI总分从MRI1到MRI2（-2.1±3.5, P < 0.05）、MRI3（-3.0±3.7, P < 0.01）和MRI4（-3.6±4.7, P < 0.01）纵向下降，主要是由于黏液囊肿子评分下降（分别为-1.0±1.5, P = 0.059；-1.2±2.0, P < 0.05；-1.6±1.8, P < 0.01；以及-2.6±2.8, P = 0.417）。在学龄前开始鲁马卡托/依伐卡托治疗的儿童中，在所有三次随访MRI期间治疗下CRS - MRI总分保持稳定（分别为0.6±3.3, P = 0.520；2.4±7.6, P = 0.994；2.±10.5, P > 0.999以及-0.5±0.5, P = 0.740）。纵向鼻窦MRI显示，在学龄期开始鲁马卡托/依伐卡托治疗的CF儿童鼻窦异常有改善。此外，MRI检测到在学龄前开始鲁马卡托/依伐卡托治疗的CF儿童鼻窦异常没有增加。我们的数据支持MRI在CF儿童鼻窦异常的综合无创治疗和疾病监测中的作用。
