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Protocol and Guidelines for Point-of-Care Lung Ultrasound in Diagnosing Neonatal Pulmonary Diseases Based on International Expert Consensus
Published on: March 6, 2019
Characterization of tracheobronchomalacia in infants with hypophosphatasia
Raja Padidela1, Robert Yates2, Dan Benscoter3
1Department of Paediatric Endocrinology, Royal Manchester Children's Hospital and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Raja.Padidela@mft.nhs.uk.
Insights
Infants with hypophosphatasia (HPP) and tracheobronchomalacia (TBM) require significant respiratory support. Early treatment with asfotase alfa and respiratory management can lead to improvement and ventilator weaning.
Area of Science:
- Pediatric Pulmonology
- Rare Diseases
- Metabolic Bone Disorders
Background:
- Perinatal and infantile hypophosphatasia (HPP) often present with severe respiratory complications.
- Tracheobronchomalacia (TBM) is a significant contributor to respiratory distress in some infants with HPP.
- Effective management strategies for these respiratory complications are crucial.
Purpose of the Study:
- To characterize the clinical features, investigations, and management of infants with HPP and TBM.
- To evaluate the impact of asfotase alfa treatment on respiratory outcomes in this patient group.
Main Methods:
- A case series of five infants with perinatal HPP and TBM treated with asfotase alfa over 3-7 years.
- Review of respiratory function data from clinical trials of asfotase alfa in patients requiring high-pressure respiratory support (PEEP ≥6 cm H2O or PIP ≥18 cm H2O).
Main Results:
- TBM significantly contributed to respiratory morbidity, necessitating prolonged high PEEP support.
- All patients in the case series eventually weaned from ventilator support as TBM improved over time.
- Analysis of clinical trial data (n=20) showed heterogeneous PEEP requirements, with a median of 8 cm H2O and some patients needing high PEEP for over 6 months.
Conclusions:
- Early screening for TBM in infants with HPP and persistent respiratory issues is essential.
- Prompt initiation of appropriate respiratory support and asfotase alfa treatment is recommended.
- TBM can improve over time, allowing for eventual discontinuation of ventilatory support.
Background:
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.
Methods:
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 H2O and/or peak inspiratory pressure ≥18 cm H2O) during the studies.
Results:
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 H2O at any time and some patients presented with high PEEP (≥8 cm H2O) over periods of more than 6 months.
Conclusion:
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.
Trial Registration:
ClinicalTrials.gov numbers: NCT00744042 , registered 27 August 2008; NCT01205152 , registered 17 September 2010; NCT01176266 , registered 29 July 2010.
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