To evaluate the safety, efficacy and tolerability of inhaled treprostinil in children, we retrospectively reviewed the data from all Group 1 PAH patients treated with inhaled treprostinil for at ≥6weeks, at 2 large pediatric pulmonary hypertension Centers, (Columbia University Medical Center and Children's Hospital CO). Indications for initiation of inhaled treprostinil therapy included symptomatic PAH on background therapy, or as a strategy to transition select patients off parenteral prostanoids. Before the initiation of inhaled treprostinil, all children were trained on proper nebulizer technique with the OPTINEB device, (a hand-held ultrasonic, single-breath nebulizer Opti-Neb, Metropolitan Medical, Inc., Winchester, Virginia), and therapy was started at 3 breaths (6 mcg/breath) four times daily. Specialty home nursing was utilized to train the subjects on the technique and monitor therapy. In general, the dose was up-titrated weekly as tolerated as determined by weekly phone call, to a maximum of 9 breaths (54 micrograms/treatment) four times daily (). Some younger patients were intentionally held at 4- 6 breaths/treatment. Some patients with cough or known asthma were treated with a bronchodilator before treatment. Baseline data collected before initiation of inhaled treprostinil included: demographics, functional class, serum BNP levels, echocardiographic parameters, 6 minute walk (6MWD), cardiopulmonary exercise testing (CPET) and cardiac catheterization with vaso-reactivity testing. Pulmonary function testing (PFT) data included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, mid-volume forced expiratory flow (FEF 25-75).
Administration of inhaled treprostinil (dosage and frequency at initiation, 6 months and 1 year follow-up)
Echocardiographic parameters included baseline diagnostic study, tricuspid regurgitation (TR) gradient to estimate right ventricular systolic pressure (mmHg), pulmonary regurgitation (PR) gradient (mmHg) and RV function. Hemodynamic parameters recorded at cardiac catheterization on room air, 100% oxygen and iNO (40-80PPM) included mean right atrial pressures (mRAP), mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), mean arterial pressure (MAP). Oxymetry included mixed venous, pulmonary artery, pulmonary vein (when available) and systemic arterial saturations (SaO2). Parameters calculated were systemic and pulmonary blood flows (Qs and Qp L/min), and indexed resistances (Rs and Rp in wood units*m2). The 6MWD test was performed in children ≥ 6 years old. Borg dyspnea scores were recorded. Heart rate and SaO2 were measured at rest and at 6 minutes and the distance walked was recorded in meters. WHO functional class obtained from the history was included for analysis. BNP (pg/ml) was recorded when available. CPET measurements included peak workload (watts), peak oxygen consumption (pVO2) ml/kg/min, VE/VCO2 and ETCO2.
Patients were followed at 3-6 month intervals and data collected included functional class, echocardiogram, BNP levels, 6MWD, CPET, PFTs, and hemodynamics when available. Adverse events and need to stop or alter the inhaled treprostinil dose were documented.
We compared the 6MWD, WHO class, BNP, CPET and hemodynamics at baseline and follow-up. Because this was a retrospective descriptive analysis, the study was not powered to detect a specific effect. Summary statistics were prepared for numeric results. All values are given as either median with range or mean ± SD. Paired 2-tailed Student t tests were used to compare key variables at baseline and on latest follow-up; p < 0.05 was considered statistically significant.