Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington.
Seattle Children's Research Institute, Seattle, Washington.
Ann Am Thorac Soc. 2024 Dec;21(12):1723-1732. doi: 10.1513/AnnalsATS.202311-1008OC.
Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder than CF in childhood, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD; pathogenic variants in and , causing inner dynein arm/microtubular defects (IDA/MTD), are associated with more severe disease. To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency). Children with PCD enrolled in a prospective, multicenter, observational study were matched with patients with CF from the Cystic Fibrosis Foundation Patient Registry by birth cohort, age, sex, race/ethnicity, and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD vs. all other defects and CF-minimal vs. residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models. Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean forced expiratory volume in 1 second percent predicted compared with CF (e.g., at age 10, -5.4% predicted lower; 95% confidence interval [CI], -7.7, -3.1). Compared with the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar body mass index; estimated mean forced expiratory volume in 1 second percent predicted was significantly lower by age 10 (mean difference, -10.6%; 95% CI, -14.7, -6.4), increasing at age 14 (mean difference, -15.7%; 95% CI, -20.3, -11.2). The CF cohort had increased prevalence of cultured on one or more occasions compared with children with PCD (67% vs. 27%; < 0.001); there was no difference in the prevalence of between children with PCD-IDA/MTD and PCD-other. In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.
原发性纤毛运动障碍（PCD）和囊性纤维化（CF）都是影响黏液纤毛清除功能的遗传性疾病，它们都可导致早发性进行性肺部疾病。基于有限的证据，PCD 通常被认为在儿童期比 CF 更轻微。与 CF 一样，PCD 也存在基因型-表型相关性；导致内动力臂/微管缺陷（IDA/MTD）的 和 种系变异与更严重的疾病相关。本研究旨在比较匹配的 PCD 和 CF 儿童的纵向结局。我们假设，与具有最小功能基因型（即与胰腺功能不全相关）的匹配 CF 儿童相比，具有 IDA/MTD 缺陷的 PCD 儿童的肺功能较低，但营养指数较好。在一项前瞻性、多中心、观察性研究中，PCD 患儿按照出生队列、年龄、性别、种族/民族和研究就诊年份与囊性纤维化基金会患者登记处的 CF 患者进行匹配。使用三次样条混合效应模型评估疾病组（PCD-IDA/MTD 与所有其他缺陷和 CF-最小与残余功能）与 17 岁以下纵向结局的相关性。
研究纳入了 136 名 PCD 患儿（40 名 IDA/MTD，96 名其他缺陷）和 476 名 CF 患儿（446 名最小功能，30 名残余功能）。在 14 岁以下，PCD 组的预计 1 秒用力呼气量百分比预测值与 CF 组相似或更低（例如，在 10 岁时，低 5.4%预测值；95%置信区间[CI]，-7.7，-3.1）。与 CF-最小功能（胰腺功能不全）组相比，PCD-IDA/MTD 组的体重指数相似；10 岁时，预计 1 秒用力呼气量百分比预测值显著较低（平均差异，-10.6%；95%CI，-14.7，-6.4），14 岁时增加（平均差异，-15.7%；95%CI，-20.3，-11.2）。与 PCD 患儿相比，CF 组在一次或多次培养中 的检出率更高（67%比 27%；<0.001）；PCD-IDA/MTD 患儿与 PCD-其他患儿的 检出率无差异。在儿童时期，PCD 的平均肺功能异常并不比 CF 更轻微，特别是对于那些存在 IDA/MTD 纤毛缺陷的患儿。迫切需要新的指南和治疗方法来改善 PCD 的结局。
