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      lloprost delivered via the BREELIB TM nebulizer: a review of the clinical evidence for efficacy and safety

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          Abstract

          Inhaled iloprost is a well-established medication to treat pulmonary arterial hypertension (PAH), a serious and potentially fatal disease of the pulmonary resistance vessels. The therapeutic administration of iloprost requires six to nine inhalations per day, due to the short biological half-life of this prostacyclin analogue. The I-Neb TM AAD TM, introduced in 2006, is the most commonly used nebulizer for delivering iloprost, requiring at least 6.5 min for an inhaled dose of 5 µg. In order to reduce inhalation time, a portable nebulizer based on modern-device technology was developed. The acute safety and tolerability of rapid iloprost inhalation via the BREELIB TM nebulizer was assessed in a four-part clinical trial. In this review, I describe the rationale and features of the new nebulizer, with particular emphasis on the safety and tolerability profile of iloprost inhalation via BREELIB TM observed in the first clinical studies. Meanwhile, the BREELIB TM nebulizer is approved and available for inhaled iloprost therapy combining significantly reduced inhalation time with good tolerability. This new approach will certainly improve patient convenience and compliance, possibly resulting in broader acceptance and improved efficacy of iloprost aerosol therapy in PAH.

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          Most cited references53

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          A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.

          Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.
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            Selexipag for the Treatment of Pulmonary Arterial Hypertension.

            In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension.
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              An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry.

              The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) was established to characterize the clinical course, treatment, and predictors of outcomes in patients with pulmonary arterial hypertension (PAH) in the United States. To date, estimated survival based on time of patient enrollment has been established and reported. To determine whether the survival of patients with PAH has improved over recent decades, we assessed survival from time of diagnosis for the REVEAL Registry cohort and compared these results to the estimated survival using the National Institutes of Health (NIH) prognostic equation. Newly or previously diagnosed patients (aged ≥ 3 months at diagnosis) with PAH enrolled from March 2006 to December 2009 at 55 US centers were included in the current analysis. A total of 2,635 patients qualified for this analysis. One-, 3-, 5-, and 7-year survival rates from time of diagnostic right-sided heart catheterization were 85%, 68%, 57%, and 49%, respectively. For patients with idiopathic/familial PAH, survival rates were 91% ± 2%, 74% ± 2%, 65% ± 3%, and 59% ± 3% compared with estimated survival rates of 68%, 47%, 36%, and 32%, respectively, using the NIH equation. Comprehensive analysis of survival from time of diagnosis in a large cohort of patients with PAH suggests considerable improvements in survival in the past 2 decades since the establishment of the NIH registry, the effects of which most likely reflect a combination of changes in treatments, improved patient support strategies, and possibly a PAH population at variance with other cohorts
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                Author and article information

                Journal
                Ther Adv Respir Dis
                Ther Adv Respir Dis
                TAR
                sptar
                Therapeutic Advances in Respiratory Disease
                SAGE Publications (Sage UK: London, England )
                1753-4658
                1753-4666
                15 March 2019
                Jan-Dec 2019
                : 13
                : 1753466619835497
                Affiliations
                [1-1753466619835497]Universities of Giessen and Marburg Lung Centre (UGMLC), German Centre for Lung Research (DZL), Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstraße 33, D-35392 Giessen, Germany
                Author notes
                Author information
                https://orcid.org/0000-0003-2946-1102
                Article
                10.1177_1753466619835497
                10.1177/1753466619835497
                6421612
                30874487
                308a17ec-cfd2-4d04-a432-fd6f887b8979
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 7 November 2018
                : 13 January 2019
                Categories
                Review
                Custom metadata
                January-December 2019

                breelibtm,inhaled iloprost,i-nebtm aadtm,nebulizer,pulmonary arterial hypertension,safety of rapid inhalation

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