Department of Paediatric Endocrinology, Royal Manchester Children's Hospital and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
McMaster University, Hamilton, ON, Canada.
Orphanet J Rare Dis. 2020 Aug 6;15(1):204. doi: 10.1186/s13023-020-01483-9.
Perinatal and infantile hypophosphatasia (HPP) are associated with respiratory failure and respiratory complications. Effective management of such complications is of key clinical importance. In some infants with HPP, severe tracheobronchomalacia (TBM) contributes to respiratory difficulties. The objective of this study is to characterize the clinical features, investigations and management in these patients.
We report a case series of five infants with perinatal HPP, with confirmed TBM, who were treated with asfotase alfa and observed for 3-7 years. Additionally, we reviewed respiratory function data in a subgroup of patients with perinatal and infantile HPP included in the clinical trials of asfotase alfa, who required high-pressure respiratory support (positive end-expiratory pressure [PEEP] ≥6 cm HO and/or peak inspiratory pressure ≥18 cm HO) during the studies.
The case series showed that TBM contributed significantly to respiratory morbidity, and prolonged respiratory support with high PEEP was required. However, TBM improved over time, allowing weaning of all patients from ventilator use. The review of clinical trial data included 20 patients and found a high degree of heterogeneity in PEEP requirements across the cohort; median PEEP was 8 cm HO at any time and some patients presented with high PEEP (≥8 cm HO) over periods of more than 6 months.
In infants with HPP presenting with persistent respiratory complications, it is important to screen for TBM and initiate appropriate respiratory support and treatment with asfotase alfa at an early stage.
ClinicalTrials.gov numbers: NCT00744042 , registered 27 August 2008; NCT01205152 , registered 17 September 2010; NCT01176266 , registered 29 July 2010.
围产期和婴儿期低磷酸酯酶症（HPP）与呼吸衰竭和呼吸并发症有关。有效管理这些并发症具有重要的临床意义。在一些 HPP 婴儿中，严重的气管支气管软化症（TBM）导致呼吸困难。本研究的目的是描述这些患者的临床特征、检查和治疗方法。
我们报告了五例围产期 HPP 伴确诊 TBM 的婴儿病例系列，他们接受了阿法特酶治疗，并观察了 3-7 年。此外，我们回顾了阿法特酶临床试验中包括的围产期和婴儿期 HPP 患者亚组的呼吸功能数据，这些患者在研究期间需要高压呼吸支持（呼气末正压[PEEP]≥6cm H2O 和/或吸气峰压≥18cm H2O）。
病例系列表明，TBM 对呼吸发病率有重要影响，需要长时间的高 PEEP 呼吸支持。然而，随着时间的推移，TBM 有所改善，所有患者均成功脱离呼吸机。对临床试验数据的回顾包括 20 名患者，发现该队列中 PEEP 需求存在高度异质性；任何时候的中位 PEEP 为 8cm H2O，一些患者的 PEEP 较高（≥8cm H2O）超过 6 个月。
在出现持续性呼吸并发症的 HPP 婴儿中，重要的是要筛查 TBM，并在早期阶段启动适当的呼吸支持和阿法特酶治疗。
ClinicalTrials.gov 编号：NCT00744042，于 2008 年 8 月 27 日注册；NCT01205152，于 2010 年 9 月 17 日注册；NCT01176266，于 2010 年 7 月 29 日注册。
