Background TBX4 variants are a recognised cause of paediatric pulmonary hypertension (PH), often associated with interstitial lung disease (ILD). Evidence for ILD-directed therapy in this group is lacking.

Methods We conducted a retrospective study of children (≤18 years) with TBX4-associated PH at a national centre (2001–2025). ILD was defined using ChILD-EU criteria. Patients treated with pulsed intravenous methylprednisolone were assessed for response using ChILD-EU categories. Secondary outcomes included respiratory severity score (RSS), functional class (FC), echocardiographic measures, and NT-proBNP.

Results Of 21 children, 11 (52%) had ILD; 9 received corticosteroids. Median age at treatment was 0.8 years. A clear or best response occurred in 7/9 (78%). RSS improved in 6/9 (p=0.02), with all children on respiratory support showing partial or complete weaning. Functional class improved in all with FC III/IV at baseline (p=0.02). Right ventricular function improved (TAPSE z-score +1.65, p=0.04), and elevated NT-proBNP normalised. Key clinical milestones included ECMO weaning, transplant delisting, and discontinuation of prostacyclin therapy. No significant adverse effects were observed. Untreated children showed no early improvement.

Conclusions Corticosteroids were associated with meaningful improvements in respiratory and PH outcomes in TBX4-associated PH with ILD. Prospective evaluation is warranted.

Shahin Moledina has acted as a consultant for Janssen-Cilag ltd and GSK.

This study did not receive any funding

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by London - South East Research Ethics Committee (17/LO/0008) allowing individual consent to be waived.

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Funding: No funding was secured for this study.

“At a Glance”: Children with TBX4-associated pulmonary hypertension and interstitial lung disease showed meaningful improvements in respiratory status and pulmonary vascular disease following pulsed intravenous corticosteroids, supporting further prospective evaluation.

All data produced in the present work are contained in the manuscript