A review of nebulized drug delivery in COPD.
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ABSTRACT:
SUBMITTER: Tashkin DP
PROVIDER: S-EPMC5076803 | biostudies-other | 2016
REPOSITORIES: biostudies-other
Publications
A review of nebulized drug delivery in COPD.
International journal of chronic obstructive pulmonary disease 20161018
Current guidelines recommend inhaled pharmacologic therapy as the preferred route of administration for treating COPD. Bronchodilators (β<sub>2</sub>-agonists and antimuscarinics) are the mainstay of pharmacologic therapy in patients with COPD, with long-acting agents recommended for patients with moderate to severe symptoms or those who are at a higher risk for COPD exacerbations. Dry powder inhalers and pressurized metered dose inhalers are the most commonly used drug delivery devices, but the ...[more]
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Project description:Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to the lungs efficiently following nebulization. We have developed a high-affinity angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD-62) that can be used as a medication to inhibit infection with SARS-CoV-2 and its variants. In this study, we established a nebulization protocol for drug delivery by inhalation using two commercial vibrating mesh (VM) nebulizers (Aerogen Solo and PARI eFlow) that generate similar mist size distribution in a size range that allows efficient deposition in the small respiratory airway. In a series of experiments, we show the high activity of RBD-62, interferon-α2 (IFN-α2), and other proteins following nebulization. The addition of gelatin significantly stabilizes the proteins and enhances the fractions of active proteins after nebulization, minimizing the medication dosage. Furthermore, hamster inhalation experiments verified the feasibility of the protocol in pulmonary drug delivery. In short, the gelatin-modified RBD-62 formulation in coordination with VM nebulizer can be used as a therapy to cure SARS-CoV-2.
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Project description:Arformoterol is the (R,R)-enantiomer of formoterol. Preclinical studies suggest that it is a stronger bronchodilator than the racemic (R,R/S,S)-formoterol; however, its potential clinical advantages have not been demonstrated. This study compared the length of stay (LOS), 30-day readmission rates, and doses of rescue medication administered in hospitalized patients with COPD who were treated with nebulized arformoterol or nebulized formoterol.This retrospective analysis utilized data from Premier, Inc. (Charlotte, NC, USA), the largest nationwide hospital-based administrative database. COPD patients ≥40 years of age were included if they were hospitalized between January 2011 and July 2014, had no asthma diagnoses, and were treated with nebulized arformoterol or nebulized formoterol. LOS was measured from the day the patients initiated the study medication (index day). Rescue medications were defined as short-acting bronchodilators used from the index day onward. Multivariate statistical models included a random effect for hospital and controlled for patient demographics, hospital characteristics, admission characteristics, prior hospitalizations, comorbidities, pre-index service use, and pre-index medication use.A total of 7,876 patients received arformoterol, and 3,612 patients received nebulized formoterol. There was no significant difference in 30-day all-cause (arformoterol =11.9%, formoterol =12.1%, odds ratio [OR] =0.981, P=0.82) or COPD-related hospital readmission rates (arformoterol =8.0%, formoterol =8.0%, OR =1.002, P=0.98) after adjusting for covariates. The adjusted mean LOS was significantly shorter for arformoterol-treated vs formoterol-treated patients (4.6 vs 4.9 days, P=0.039), and arformoterol-treated patients used significantly fewer doses of rescue medications vs formoterol-treated patients (5.9 vs 6.6 doses, P=0.006).During inpatient stays, treating with arformoterol instead of nebulized formoterol may lead to shorter LOS and lower rescue medication use.
| S-EPMC5490469 | biostudies-other
Project description:Current guidelines recommend inhalation therapy as the preferred route of drug administration for treating patients with chronic obstructive pulmonary disease (COPD). Inhalation devices consist of nebulizers and handheld inhalers, such as dry-powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), and soft mist inhalers (SMIs). Although pMDIs, DPIs and SMIs may be appropriate for most patients with COPD, certain patient populations may have challenges with these devices. Patients who have cognitive, neuromuscular, or ventilatory impairments (and receive limited assistance from caregivers), as well as those with suboptimal peak inspiratory flow may not derive the full benefit from handheld inhalers. A considerable number of patients are not capable of producing a peak inspiratory flow rate to overcome the internal resistance of DPIs. Furthermore, patients may have difficulty coordinating inhalation with device actuation, which is required for pMDIs and SMIs. However, inhalation devices such as spacers and valved holding chambers can be used with pMDIs to increase the efficiency of aerosol delivery. Nebulized treatment provides patients with COPD an alternative administration route that avoids the need for inspiratory flow, manual dexterity, or complex hand-breath coordination. The recent approval of two nebulized long-acting muscarinic antagonists has added to the extensive range of nebulized therapies in COPD. Furthermore, with the availability of quieter and more portable nebulizer devices, nebulization may be a useful treatment option in the management of certain patient populations with COPD. The aim of this narrative review was to highlight recent updates and the treatment landscape in nebulized therapy and COPD. We first discuss the pathophysiology of patients with COPD and inhalation device considerations. Second, we review the updates on recently approved and newly marketed nebulized treatments, nebulized treatments currently in development, and technological advances in nebulizer devices. Finally, we discuss the current applications of nebulized therapy in patients with COPD.
| S-EPMC7367939 | biostudies-literature
Project description:IntroductionLung hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with activity limitation, impaired cardiac output, and mortality. Several studies have demonstrated that long-acting muscarinic antagonists (LAMAs) delivered by dry powder inhalers can promote lung deflation; however, the potential of nebulized LAMAs on improving hyperinflation in COPD is currently unknown.MethodsThis single-center, randomized, double-blind, two-way crossover study (NCT04155047) evaluated the efficacy of a single dose of nebulized LAMA [glycopyrrolate (GLY) 25 µg] versus placebo in patients with COPD and lung hyperinflation. Patients with moderate-to-severe COPD and a residual volume (RV) ≥ 130% of predicted normal were included. The primary endpoint was changed from baseline in RV at 6 h post-treatment. Other endpoints included changes from baseline in spirometric and plethysmographic measures up to 6 h post-treatment.ResultsA total of 22 patients (mean pre-bronchodilator RV, 153.7% of predicted normal) were included. The primary objective of the study was not met; the placebo-adjusted least squares (LS) mean [95% confidence interval (CI) change from baseline in RV with GLY at 6 h post-treatment was - 0.323 l (- 0.711 to 0.066); p = 0.0987]. A post hoc evaluation of the primary analysis was conducted after excluding a single statistical outlier; substantial improvements in RV with GLY compared with placebo was observed after exclusion of this outlier [placebo-adjusted LS mean change from baseline (95% CI) in RV was - 0.446 l (- 0.741 to - 0.150)]. Improvements from baseline were also observed with GLY compared with placebo in spirometric and plethysmographic measures up to 6 h post-treatment. GLY was generally safe, and no new safety signals were detected.ConclusionsThis is the first study to evaluate the effect of nebulized GLY on lung deflation. Nebulized GLY resulted in marked improvements in RV up to 6 h post-treatment, compared with placebo. Improvements were also observed with GLY in spirometric and plethysmographic parameters of lung function.Trial registrationClinicalTrials.gov identifier, NCT04155047.
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Project description:Bronchodilation with muscarinic antagonists, β2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using "duration and lung selectivity-by-design." This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.
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Project description:IntroductionConvection-enhanced delivery (CED) is a method of targeted, local drug delivery to the central nervous system (CNS) that bypasses the blood-brain barrier (BBB) and permits the delivery of high-dose therapeutics to large volumes of interest while limiting associated systemic toxicities. Since its inception, CED has undergone considerable preclinical and clinical study as a safe method for treating glioblastoma (GBM). However, the heterogeneity of both, the surgical procedure and the mechanisms of action of the agents studied-combined with the additional costs of performing a trial evaluating CED-has limited the field's ability to adequately assess the durability of any potential anti-tumor responses. As a result, the long-term efficacy of the agents studied to date remains difficult to assess.Materials and methodsWe searched PubMed using the phrase "convection-enhanced delivery and glioblastoma". The references of significant systematic reviews were also reviewed for additional sources. Articles focusing on physiological and physical mechanisms of CED were included as well as technological CED advances.ResultsWe review the history and principles of CED, procedural advancements and characteristics, and outcomes from key clinical trials, as well as discuss the potential future of this promising technique for the treatment of GBM.ConclusionWhile the long-term efficacy of the agents studied to date remains difficult to assess, CED remains a promising technique for the treatment of GBM.
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