JMIR Publications

ABSTRACT

Background:

Pulmonary arterial hypertension (PAH) restricts the ability of patients to perform routine physical activities. Iloprost, an inhaled PAH therapy, can be administered via the Breelib nebulizer which tracks inhalation behavior. PAH treatment is guided by intermittent clinical measurements such as 6-minute walk distance (6MWD) taken during regular physician visits. Continuous digital monitoring of physical activity may provide a more complete assessment of the impact of PAH on daily life. Physical activity tracking with a wearable has not been assessed with simultaneous tracking of PAH medication intake.

Objective:

We aimed to track daily physical activity, heart rate, and iloprost inhalation behavior digitally in patients with PAH starting treatment with iloprost using the Breelib nebulizer. The primary objective was to investigate correlations between changes in digital physical activity measures and changes in traditional clinical measures and health-related quality of life (HRQoL) over 3 months. Secondary objectives included evaluating changes in digital and traditional measures, HRQoL, and sleep quality after initiation of inhaled iloprost, and adverse events.

Methods:

VENTASTEP was a prospective, multicenter observational study of adults with PAH (functional class III) adding inhaled iloprost to existing PAH therapy (pre-iloprost baseline: ≤2 weeks; observation period with iloprost: 3 months±2 weeks). Digital measures (distance walked, step count, number of standing-up events, and digital 6MWD [based on step count and a stride length algorithm trained on healthy volunteer data])were obtained using smartwatches (Apple Watch Series 2) and smartphones (iPhone 6S) with 6MWD and study-specific apps. Traditional measures were 6MWD, Borg dyspnea, functional class, and brain natriuretic peptide (BNP) or N-terminal proBNP levels. HRQoL and sleep quality were assessed using the Euroqol-5D questionnaire and Pittsburgh Sleep Quality Index, respectively.

Results:

18 of 31 enrolled patients were eligible for full analysis (median [IQR] observation period: 91.5 [88.0, 92.0] days). During the last 14 days of observation, 13/18 patients (72%) wore the smartwatch every day (16/18 [89%] wore the smartwatch ≥6 h/day). Changes from baseline in traditional and digital 6MWD were moderately correlated (r=0.57). Digital daily physical activity measures and traditional clinical measures both improved from baseline to the end of observation (eg, median [IQR] daily distance walked, +0.4 [−0.2, +1.9] km; daily step count, +591 [−509, +2413]; traditional 6MWD, +26 [0, +40] m). The Euroqol-5D weighted index showed little change (+0.02 [0.00, +0.08]), total sleep score improved (−1.0 [−2.0, 0.0]), and resting heart rate decreased slightly (−1.3 [−8.0, +3.5] beats/min). Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified (safety analysis set, n=30).

Conclusions:

Although the sample size limits generalizability, our results suggest that parallel digital tracking of physical activity, heart rate, and iloprost inhalation is feasible in PAH and may support traditional measures to guide treatment. Clinical Trial: ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407