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Effectiveness and Safety of Inhaled Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Children

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The introduction of prostanoid therapy has revolutionized the treatment of pulmonary arterial hypertension (PAH). However, continuous intravenous prostacyclin infusion poses significant risks and challenges, particularly in children. Inhaled treprostinil has been shown to be safe and efficacious in adults. This study describes the safety and efficacy of inhaled treprostinil in children with PAH. A retrospective analysis of 29 children treated with inhaled treprostinil for ≥6 weeks was performed. Effects of inhaled treprostinil on exercise capacity, functional class, and echocardiographic and hemodynamic data were evaluated. Adverse events were documented. Patients received 3 to 9 breaths (6 μg/breath) of inhaled treprostinil 4 times/day. All were receiving background PAH therapy; 12 had previously received parenteral prostanoid. Inhaled treprostinil was discontinued in 4 patients because of symptoms including cough and bronchospasm (n = 3) and progression of PAH (n = 1). Mild side effects including cough (n = 9) and sore throat (n = 6) did not require discontinuation of therapy. World Health Organization functional class improved in 19 and was unchanged in 10; exercise capacity significantly improved with the 6-minute walk distance, improving on follow-up from 455.7 ± 71.5 to 498 ± 70 m (p = 0.01) and peak oxygen consumption increasing from 25.5 ± 10.2 to 27.4 ± 10 (p = 0.04). In conclusion, inhaled treprostinil was associated with improvement in exercise capacity and World Health Organization functional class when added to background targeted PAH therapy in children and had an acceptable safety profile. Based on these early data, further study of inhaled treprostinil appears warranted in pediatric patients with PAH.

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Methods

To evaluate the safety, efficacy, and tolerability of inhaled treprostinil in children, we retrospectively reviewed the data from all patients with group 1 PAH treated with inhaled treprostinil for ≥6 weeks at 2 large pediatric pulmonary hypertension centers (Columbia University Medical Center and Children's Hospital Colorado). Indications for initiation of inhaled treprostinil therapy included symptomatic PAH on background therapy or as a strategy to transition select patients off parenteral

Results

Twenty-nine consecutive pediatric patients with Group 1 PAH who received inhaled treprostinil for ≥6 weeks were included. Baseline demographic data are listed in Table 2. There were 14 male and 15 female subjects (mean age 11.3 ± 4.5 years, median 12, range 3.2 to 19) with idiopathic PAH (n = 19) or associated PAH (n = 10). Average treatment duration was 15.7 ± 8.2 months (median 17, range 1.5 to 27.5). All patients were on background therapy. Four patients were on calcium channel blockers, 26

Discussion

Inhaled iloprost was initially studied in children with PAH in 22 pediatric patients and was found to have acceptable safety and tolerability.20 Iloprost therapy requires treatments every 2 to 4 hours, with each treatment taking 5 to 20 minutes. Delivery of inhaled iloprost can be difficult for young children because of the need for actuated breaths with the Opti-Neb device. Availability of a longer-acting inhaled prostanoid, inhaled treprostinil, has enabled patients to transition from

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  • Cited by (0)

    This study was funded by Specialized Centers of Clinically Oriented Research Grant HL-084923-02 from the National Institutes of Health, Bethesda, Maryland, Grant UL1RR025780 from the National Institutes of Health/National Center for Research Resources Colorado CTSI, Denver, Colorado, the Jayden DeLuca Foundation, and the Leah Bult PH Research Fund, Denver, Colorado. Columbia University and University of Colorado receive consultant fees from Actelion, Gilead, Pfizer, and United Therapeutics.

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