Characterization of tracheobronchomalacia in infants with hypophosphatasia

Orphanet Journal of Rare Diseases 15, Article number: 204 (2020) Cite this article

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Abstract

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.