Holgersen Mathias G, Marthin June K, Raidt Johanna, Qvist Tavs, Johansen Helle K, Omran Heymut, Nielsen Kim G
Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine.
Department of General Paediatrics, University Children's Hospital Muenster, Muenster, Germany.
Ann Am Thorac Soc. 2025 Feb;22(2):216-225. doi: 10.1513/AnnalsATS.202404-340OC.
Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by progressive lung disease. is a major pathogen in this disease and is known to impact lung function. Previous genotype-phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. We aimed to explore long-term lung function in PCD grouped by genotypes and ultrastructural defects, considering the influence of . In this retrospective observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated forced expiratory volume in 1 second -score trends and compared them at ages 10, 25, and 50 years, whereas generalized estimating equations were used to assess prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of on lung function. We included 127 genotyped patients, 6,691 spirometry measurements, and 10,082 microbiology samples. and variants showed early-onset and sustained decline in lung function, whereas and variants demonstrated relative stability. Lung function in the proximity of positive cultures was on average 0.06 -score lower. Despite this, differences between groups remained largely unaffected by . Long-term lung function in PCD follows discrete genotype-specific profiles and appears independent of infection. We confirm and extend previous findings of and as variants associated with early-onset severe lung function impairment persisting in the long term.
原发性纤毛运动障碍（PCD）是一种罕见的遗传性疾病，其特征为进行性肺部疾病。[病原体名称]是该疾病的主要病原体，已知会影响肺功能。以往的基因型-表型研究受到横断面设计、孤立的成人或儿童群体、样本量小或随访时间短的限制。我们旨在探讨按基因型和超微结构缺陷分组的PCD患者的长期肺功能，并考虑[病原体名称]的影响。在这项回顾性观察研究中，我们分析了43年的肺活量测定数据和20年的微生物学数据。使用线性混合效应模型，我们估计了1秒用力呼气量评分趋势，并在10岁、25岁和50岁时进行比较，而广义估计方程用于评估组间[病原体名称]的患病率。在二次分析中，我们对肺活量测定和微生物学样本进行匹配，以评估[病原体名称]对肺功能的影响。我们纳入了127例进行基因分型的患者、6691次肺活量测定结果和10082份微生物学样本。[基因名称1]和[基因名称2]变异显示肺功能早期发病并持续下降，而[基因名称3]和[基因名称4]变异表现出相对稳定性。阳性[病原体名称]培养物附近的肺功能平均低0.06评分。尽管如此，组间差异在很大程度上不受[病原体名称]的影响。PCD患者的长期肺功能遵循离散的基因型特异性模式，且似乎独立于[病原体名称]感染。我们证实并扩展了先前关于[基因名称1]和[基因名称2]作为与早期发病的严重肺功能损害长期持续相关的变异的研究结果。
