Department of Paediatrics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
Department of Histology and Embryology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Am J Physiol Lung Cell Mol Physiol. 2023 Aug 1;325(2):L125-L134. doi: 10.1152/ajplung.00058.2023. Epub 2023 Jun 6.
Reticular basement membrane (RBM) thickening may occur in children with allergic bronchial asthma (BA), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD). Its functional consequences remain unknown. We investigated the relationship between baseline RBM thickness and subsequent spirometry. In our cohort follow-up study, patients aged 3-18 yr with BA, CF, and PCD and controls underwent baseline lung clearance index (LCI) measurement, spirometry, and endobronchial biopsy sampling. Total RBM and collagen IV-positive layer thickness were measured. Trends in forced vital capacity (FVC), forced expired volume in 1 s (FEV), and FEV/FVC were analyzed during follow-up, and their relationship to baseline characteristics was studied using univariate analysis and multiple regression models. Complete baseline data were available in 19 patients with BA, 30 patients with CF, 25 patients with PCD, and 19 controls. The RBM was thicker in patients with BA (6.33 ± 1.22 μm), CF (5.60 ± 1.39 μm), and PCD (6.50 ± 1.87 μm) than in controls (3.29 ± 0.55 μm) (all < 0.001). The LCI was higher in patients with CF (15.32 ± 4.58, < 0.001) and PCD (10.97 ± 2.46, = 0.002) than in controls (7.44 ± 0.43). The median follow-up times were 3.6, 4.8, 5.7, and 1.9 years in patients with BA, CF, PCD, and controls, respectively. The scores of FEV and FEV/FVC deteriorated significantly in all groups except in controls. In patients with CF and PCD, trends in FEV scores correlated with baseline LCI and RBM; in BA, it correlated with collagen IV. In multiple regression models, RBM morphology and ventilation inhomogeneity could predict up to 84.4% of variability in spirometry trends. In conclusion, baseline LCI value and RBM morphology may predict trends in subsequent spirometry. This paper deals with the relationship between reticular basement membrane (RBM) morphology at baseline and follow-up spirometry in children with asthma, cystic fibrosis, and primary ciliary dyskinesia. For the first time, to our knowledge, the possibility to predict subsequent lung function development using selected baseline characteristics (reticular basement membrane morphology from endobronchial biopsy and ventilation inhomogeneity from nitrogen multiple breath washout test) is proposed. Corresponding predictive models are presented.
基底膜网状层（RBM）增厚可能发生在过敏性支气管哮喘（BA）、囊性纤维化（CF）和原发性纤毛运动障碍（PCD）的儿童中。其功能后果仍不清楚。我们研究了基线 RBM 厚度与随后的肺活量测定之间的关系。在我们的队列随访研究中，3-18 岁的 BA、CF 和 PCD 患者和对照者接受了基线肺清除指数（LCI）测量、肺活量测定和支气管内活检采样。测量了总 RBM 和胶原 IV 阳性层的厚度。在随访期间分析了用力肺活量（FVC）、1 秒用力呼气量（FEV）和 FEV/FVC 的趋势，并使用单变量分析和多元回归模型研究了它们与基线特征的关系。19 例 BA 患者、30 例 CF 患者、25 例 PCD 患者和 19 例对照者有完整的基线数据。BA（6.33±1.22μm）、CF（5.60±1.39μm）和 PCD（6.50±1.87μm）患者的 RBM 比对照组（3.29±0.55μm）厚（均<0.001）。CF（15.32±4.58，<0.001）和 PCD（10.97±2.46，=0.002）患者的 LCI 高于对照组（7.44±0.43）。BA、CF、PCD 和对照组患者的中位随访时间分别为 3.6、4.8、5.7 和 1.9 年。除对照组外，所有组的 FEV 和 FEV/FVC 评分均显著恶化。在 CF 和 PCD 患者中，FEV 评分的趋势与基线 LCI 和 RBM 相关；在 BA 中，与胶原 IV 相关。在多元回归模型中，RBM 形态和通气不均匀性可预测高达 84.4%的肺活量测定趋势的变异性。总之，基线 LCI 值和 RBM 形态可能预测随后的肺活量测定趋势。本文研究了哮喘、囊性纤维化和原发性纤毛运动障碍儿童基线时 LCI 值和 RBM 形态与随访时肺活量测定的关系。据我们所知，这是首次提出使用选定的基线特征（支气管内活检的网状基底膜形态和氮多次呼吸冲洗试验的通气不均匀性）来预测随后的肺功能发育的可能性。提出了相应的预测模型。
