Acute response to rapid iloprost inhalation using the Breelib™ nebulizer in pulmonary arterial hypertension: the Breelib™ acute study.
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ABSTRACT:
SUBMITTER: Richter MJ
PROVIDER: S-EPMC6740066 | biostudies-literature | 2019 Jul-Sep
REPOSITORIES: biostudies-literature
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Acute response to rapid iloprost inhalation using the Breelib™ nebulizer in pulmonary arterial hypertension: the Breelib™ acute study.
Richter Manuel J MJ Wan Jun J Ghofrani Hossein A HA Seeger Werner W Gall Henning H Rieth Andreas A Tello Khodr K
Pulmonary circulation 20190701 3
The Breelib™ nebulizer was designed to reduce iloprost inhalation times for patients with pulmonary arterial hypertension (PAH). In 30 patients with PAH, rapid inhalation of iloprost 2.5 µg using Breelib™ caused significant improvements in invasively measured afterload and cardiac index but not echocardiographic right ventricular strain during 30 min post-inhalation. ...[more]
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Project description:BackgroundInhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy.AimsIn this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6-9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed.ResultsMost patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (-74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001).ConclusionsPulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status.
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Project description:BackgroundPulmonary arterial hypertension restricts the ability of patients to perform routine physical activities. As part of pulmonary arterial hypertension treatment, inhaled iloprost can be administered via a nebulizer that tracks inhalation behavior. Pulmonary arterial hypertension treatment is guided by intermittent clinical measurements, such as 6-minute walk distance, assessed during regular physician visits. Continuous digital monitoring of physical activity may facilitate more complete assessment of the impact of pulmonary arterial hypertension on daily life. Physical activity tracking with a wearable has not yet been assessed with simultaneous tracking of pulmonary arterial hypertension medication intake.ObjectiveWe aimed to digitally track the physical parameters of patients with pulmonary arterial hypertension who were starting treatment with iloprost using a 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 over 3 months. Secondary objectives were to evaluate inhalation behavior, adverse events, and changes in heart rate and sleep quality.MethodsWe conducted a prospective, multicenter observational study of adults with pulmonary arterial hypertension in World Health Organization functional class III who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy. Daily distance walked, step count, number of standing-up events, heart rate, and 6-minute walk distance were digitally captured using smartwatch (Apple Watch Series 2) and smartphone (iPhone 6S) apps during a 3-month observation period (which began when iloprost treatment began). Before and at the end of the observation period (within 2 weeks), we also evaluated 6-minute walk distance, Borg dyspnea, functional class, B-type natriuretic peptide (or N-terminal pro-B-type natriuretic peptide) levels, health-related quality of life (EQ-5D questionnaire), and sleep quality (Pittsburgh Sleep Quality Index).ResultsOf 31 patients, 18 were included in the full analysis (observation period: median 91.5 days, IQR 88.0 to 92.0). Changes from baseline in traditional and digital 6-minute walk distance were moderately correlated (r=0.57). Physical activity (daily distance walked: median 0.4 km, IQR -0.2 to 1.9; daily step count: median 591, IQR -509 to 2413) and clinical measures (traditional 6-minute walk distance: median 26 m, IQR 0 to 40) changed concordantly from baseline to the end of the observation period. Health-related quality of life showed little change. Total sleep score and resting heart rate slightly decreased. Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified (safety analysis set: n=30).ConclusionsOur results suggest that despite challenges, parallel monitoring of physical activity, heart rate, and iloprost inhalation is feasible in patients with pulmonary arterial hypertension and may complement traditional measures in guiding treatment; however, the sample size of this study limits generalizability.Trial registrationClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407.International registered report identifier (irrid)RR2-10.2196/12144.
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Project description:Microarray analysis of peripheral blood mononuclear (PBMC) cells in pulmonary arterial hypertension. Keywords = mononuclear cells Keywords = gene microarray Keywords = pulmonary arterial hypertension Keywords = Herpesvirus Keywords = biomarker Keywords: other
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