Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Magnetic Resonance Imaging of Aerosol Deposition.","authors":"Richard B Thompson,&nbsp;Chantal Darquenne","doi":"10.1089/jamp.2023.29087.rbt","DOIUrl":"https://doi.org/10.1089/jamp.2023.29087.rbt","url":null,"abstract":"<p><p>Nuclear magnetic resonance imaging (MRI) uses non-ionizing radiation and offers a host of contrast mechanisms with the potential to quantify aerosol deposition. This chapter introduces the physics of MRI, its use in lung imaging, and more specifically, the methods that are used for the detection of regional distributions of inhaled particles. The most common implementation of MRI is based on imaging of hydrogen atoms (¹H) in water. The regional deposition of aerosol particles can be measured by the perturbation of the acquired ¹H signals via labeling of the aerosol with contrast agents. Existing <i>in vitro</i> human and <i>in vivo</i> animal model measurements of regional aerosol deposition in the respiratory tract are described, demonstrating the capability of MRI to assess aerosol deposition in the lung.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"228-234"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Inhaled Drug Dose Generated by Mesh Nebulizers.","authors":"Yu-Chung Hsu,&nbsp;Hsin-Hsien Li,&nbsp;Li-Chung Chiu,&nbsp;Wen-Chieh Chiang,&nbsp;Tien-Pei Fang,&nbsp;Hui-Ling Lin","doi":"10.1089/jamp.2022.0055","DOIUrl":"https://doi.org/10.1089/jamp.2022.0055","url":null,"abstract":"<p><p><b><i>Background:</i></b> The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. <b><i>Methods:</i></b> An <i>in vitro</i> model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns (<i>n</i> = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the <i>ex vivo</i> study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. <b><i>Results:</i></b> The <i>in vitro</i> model showed that the inspiratory time to total respiratory cycle time (<i>T_i</i>/<i>T</i>_total; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The <i>ex vivo</i> model showed that <i>T_i</i>/<i>T</i>_total was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the <i>ex vivo</i> model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. <b><i>Conclusions:</i></b> The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"162-170"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring Anatomical Distributions of Ventilation and Aerosol Deposition with PET-CT.","authors":"Jose G Venegas","doi":"10.1089/jamp.2023.29086.jgv","DOIUrl":"10.1089/jamp.2023.29086.jgv","url":null,"abstract":"<p><p>In disease, lung function and structure are heterogeneous, and aerosol transport and local deposition vary significantly among parts of the lung. Understanding such heterogeneity is relevant to aerosol medicine and for quantifying mucociliary clearance from different parts of the lung. In this chapter, we describe positron emission tomography (PET) imaging methods to quantitatively assess the deposition of aerosol and ventilation distribution within the lung. The anatomical information from computed tomography (CT) combined with the PET-deposition data allows estimates of airway surface concentration and peripheral tissue dosing in bronchoconstricted asthmatic subjects. A theoretical framework is formulated to quantify the effects of heterogeneous ventilation, uneven aerosol ventilation distribution in bifurcations, and varying escape from individual airways along a path of the airway tree. The framework is applied to imaging data from bronchoconstricted asthmatics to assess the contributions of these factors to the unevenness in lobar deposition. Results from this analysis show that the heterogeneity of ventilation contributes on average to more than one-third of the variability in interlobar deposition. Actual contribution of ventilation in individual lungs was variable and dependent on the breathing rate used by the subject during aerosol inhalation; the highest contribution was in patients breathing slowly. In subjects breathing faster, contribution of ventilation was reduced, with more expanded lobes showing lower deposition per unit ventilation than less expanded ones in these subjects. The lobar change in expansion measured from two static CT scans, which is commonly used as a surrogate for ventilation, did not correlate with aerosol deposition or with PET-measured ventilation. This suggests that dynamic information is needed to provide proper estimates of ventilation for asthmatic subjects. We hope that the enhanced understanding of the causes of heterogeneity in airway and tissue dosing using the tools presented here will help to optimize therapeutic effectiveness of inhalation therapy while minimizing toxicity.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"210-227"},"PeriodicalIF":2.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vitro</i> Effect of Combined Hypertonic Saline and Salbutamol on Ciliary Beating Frequency and Mucociliary Transport in Human Nasal Epithelial Cells of Healthy Volunteers and Patients with Cystic Fibrosis.","authors":"Anaïs Escher,&nbsp;Elisabeth Kieninger,&nbsp;Susan De Groof,&nbsp;Sibel T Savas,&nbsp;Martin Schneiter,&nbsp;Stefan A Tschanz,&nbsp;Martin Frenz,&nbsp;Philipp Latzin,&nbsp;Carmen Casaulta,&nbsp;Loretta Müller","doi":"10.1089/jamp.2022.0026","DOIUrl":"https://doi.org/10.1089/jamp.2022.0026","url":null,"abstract":"<p><p><b><i>Background:</i></b> Inhalation of hypertonic saline (HS) is standard of care in patients with cystic fibrosis (CF). However, it is unclear if adding salbutamol has-besides bronchodilation-further benefits, for example, on the mucociliary clearance. We assessed this <i>in vitro</i> by measuring the ciliary beating frequency (CBF) and the mucociliary transport rate (MCT) in nasal epithelial cells (NECs) of healthy volunteers and patients with CF. <b><i>Aims:</i></b> To investigate the effect of HS, salbutamol, and its combination on (muco)ciliary activity of NECs <i>in vitro</i>, and to assess potential differences between healthy controls and patients with CF. <b><i>Methods:</i></b> NECs obtained from 10 healthy volunteers and 5 patients with CF were differentiated at the air-liquid interface and aerosolized with 0.9% isotonic saline ([IS] control), 6% HS, 0.06% salbutamol, or combined HS and salbutamol. CBF and MCT were monitored over 48-72 hours. <b><i>Results:</i></b> In NECs of healthy controls, the absolute CBF increase was comparable for all substances, but CBF dynamics were different: HS increased CBF slowly and its effect lasted for an extended period, salbutamol and IS increased CBF rapidly and the effect subsided similarly fast, and HS and salbutamol resulted in a rapid and long-lasting CBF increase. Results for CF cells were comparable, but less pronounced. Similar to CBF, MCT increased after the application of all the tested substances. <b><i>Conclusion:</i></b> CBF and MCT of NECs of healthy participants and CBF of patients with CF increased upon treatment with aerosolized IS, HS, salbutamol, or HS and salbutamol, showing a relevant effect for all tested substances. The difference in the CBF dynamics can be explained by the fact that the properties of the mucus are changed differently by different saline concentrations.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"171-180"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Long-Acting Antimuscarinic Agents in the Treatment of Asthma.","authors":"Bahar Arslan,&nbsp;Gülden Paçacı Çetin,&nbsp;İnsu Yilmaz","doi":"10.1089/jamp.2022.0059","DOIUrl":"https://doi.org/10.1089/jamp.2022.0059","url":null,"abstract":"<p><p>The journey of using anticholinergics in the treatment of asthma started with anticholinergic-containing plants such as Datura stramonium and Atropa belladonna, followed by ipratropium bromide and continued with tiotropium, glycopyrronium, and umeclidinium. Although antimuscarinics were used in the maintenance treatment of asthma over a century ago, after a long time (since 2014), it has been recommended to be used as an add-on long-acting antimuscarinic agent (LAMA) therapy in the maintenance treatment of asthma. The airway tone controlled by the vagus nerve is increased in asthma. Allergens, toxins, or viruses cause airway inflammation and inflammation-related epithelial damage, increased sensory nerve stimulation, ganglionic and postganglionic acetylcholine (ACh) release by inflammatory mediators, intensification of ACh signaling at M1 and M3 muscarinic ACh receptors (mAChRs), and dysfunction of M2 mAChR. Optimal anticholinergic drug for asthma should effectively block M3 and M1 receptors, but have minimal effect on M2 receptors. Tiotropium, umeclidinium, and glycopyrronium are anticholinergic agents with this feature. Tiotropium has been used in a separate inhaler as an add-on treatment to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), and glycopyrronium and umeclidinium have been used in a single inhaler as a combination of ICS/LABA/LAMA in asthma in recent years. Guidelines recommend this regimen as an optimization step for patients with severe asthma before initiating any biologic or systemic corticosteroid therapy. In this review, the history of antimuscarinic agents, their effectiveness and safety in line with randomized controlled trials, and real-life studies in asthma treatment will be discussed according to the current data.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"189-209"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for <i>Journal of Aerosol Medicine and Pulmonary Drug Delivery</i>.","authors":"Rachel K Redmann","doi":"10.1089/jamp.2023.29096.rfs2022","DOIUrl":"https://doi.org/10.1089/jamp.2023.29096.rfs2022","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"153"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Analysis of Aerosol Release from a Pressurized Metered Dose Inhaler Combined with a Valved Holding Chamber Using Simplified Laser Photometry.","authors":"Tetsuri Kondo,&nbsp;Toshimori Tanigaki,&nbsp;Makoto Hibino,&nbsp;Sakurako Tajiri,&nbsp;Shigeto Horiuchi,&nbsp;Kazunari Maeda,&nbsp;Shunichi Tobe,&nbsp;Riko Kamada","doi":"10.1089/jamp.2022.0060","DOIUrl":"10.1089/jamp.2022.0060","url":null,"abstract":"<p><p><b><i>Background:</i></b> A pressurized metered dose inhaler combined with a valved holding chamber (pMDI+VHC) is used to prevent upper airway complications and improve the efficiency of inhaled drug delivery; however, the aerodynamic behavior of the released particles has not been well investigated. This study aimed at clarifying the particle release profiles of a VHC using simplified laser photometry. <b><i>Methods:</i></b> An inhalation simulator comprised a computer-controlled pump and a valve system that withdrew aerosol from a pMDI+VHC using a jump-up flow profile. A red laser illuminated the particles leaving VHC and evaluated the intensity of the light reflected by the released particles. <b><i>Results:</i></b> The data suggested that the output (OPT) from the laser reflection system represented particle concentration rather than particle mass, and the latter was calculated as OPT × instantaneous withdrawn flow (WF). Summation of OPT hyperbolically decreased with flow increment, whereas summation of OPT × instantaneous flow was not influenced by WF strength. Particle release trajectories consisted of three phases, namely increment with a parabolic curve, flat, and decrement with exponential decay phases. The flat phase appeared exclusively at low-flow withdrawal. These particle release profiles suggest the importance of early phase inhalation. The hyperbolic relationship between WF and particle release time revealed the minimal required withdrawal time at an individual withdrawal strength. <b><i>Conclusions:</i></b> The particle release mass was calculated as laser photometric output × instantaneous flow. Simulation of the released particles suggested the importance of early phase inhalation and predicted the minimally required withdrawal time from a pMDI+VHC.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"181-188"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of Inhaled Nanopharmaceuticals.","authors":"Sarah Barthold,&nbsp;Nicole Kunschke,&nbsp;Xabier Murgia,&nbsp;Brigitta Loretz,&nbsp;Cristiane de Souza Carvalho-Wodarz,&nbsp;Claus-Michael Lehr","doi":"10.1089/jamp.2023.29089.sb","DOIUrl":"https://doi.org/10.1089/jamp.2023.29089.sb","url":null,"abstract":"<p><p>Nanopharmaceuticals represent a group of nanoparticles engineered for medical purposes. Nowadays, nanotechnology offers several possibilities to improve the safety and efficacy of medicines by designing advanced carrier systems which have been found to offer particular advantages when formulated in the nanoscale. Some of the initially marketed nano-formulations already demonstrate advantages over conventional formulations. Innovative delivery systems offer the possibility to not only control drug release but also to overcome biological barriers. For the translation of new drug products from bench to bedside, however, it is pivotal to test and prove their safety. This is of course also true for nanopharmaceuticals, where in particular the biocompatibility and also the clearance/biodegradation of the carrier material after drug delivery has to be demonstrated. The pulmonary route offers some great opportunities for noninvasive drug delivery but also implicates peculiar challenges. Advanced aerosol formulations with innovative drug carriers have already contributed to the significant progress of inhalation therapy. However, in spite of the large alveolar epithelial surface area, the respiratory tract still features diverse efficient biological barriers, primarily designed by nature to protect the human body against inhaled pollutants and pathogens. Only a thorough understanding of particle-lung interactions will allow the rational design of novel nanopharmaceuticals capable of overcoming these barriers, while of course always keeping in mind the strict demands for their safety. While the recent resurrection of inhaled insulin has already confirmed the potential of the pulmonary route for systemic delivery of biopharmaceuticals, inhaled nanopharmaceuticals, currently under investigation, promise to improve also local therapies like anti-infectives.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"144-151"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Age and Head Position on Total and Regional Aerosol Deposition in Three-Dimensional Models of Human Intranasal Airways Using a Mucosal Atomization Device.","authors":"Jana S Kesavan,&nbsp;Kristina Kuypers,&nbsp;Douglas R Sommerville,&nbsp;Keith Sedberry,&nbsp;Beth L Laube","doi":"10.1089/jamp.2022.0056","DOIUrl":"https://doi.org/10.1089/jamp.2022.0056","url":null,"abstract":"<p><p><b><i>Background:</i></b> This study examined the effect of age and head position on total and regional deposition of aerosol delivered by a mucosal atomization device (MAD™) in three-dimensional (3D) models of the intranasal airways of an 18-, 5-, and 2-year-old human. Models consisted of four pieces: anterior nose and nasal cavity that was divided horizontally into upper, middle, and lower thirds. <b><i>Methods:</i></b> Models were tested six times at supine, supine with head backward at 45° (supine45), and sitting with head backward at 45° (sitting45). The MAD delivered saline/fluorescein aerosol into model nostrils, during static airflow. Model pieces were tested for fluorescence using a fluorometer, and deposition calculated as percent fluorescence per piece relative to its reference. Total deposition (four pieces combined) and regional deposition (four pieces separately) were calculated. <b><i>Results:</i></b> Age and head position had little effect on total deposition. In contrast, deposition in the upper and middle third supine45 and in the lower third sitting45 was significantly different in the 2-year-old model, compared with the two older models. In addition, some head positions significantly increased deposition in the upper, middle, and lower thirds within each model, compared with other positions. Upper deposition was significantly greater at supine45, compared with sitting45 (18-year-old) and supine45, compared with supine and sitting45 (5-year-old). Middle deposition was significantly greater at supine and supine45, compared with sitting45 (2-year-old). Lower deposition was significantly greater at sitting45, compared with supine45 (18-year-old); supine and sitting45, compared with supine45 (5-year-old); and sitting45, compared with supine45 and supine (2-year-old). <b><i>Conclusions:</i></b> Age and head position significantly affected regional deposition of aerosol delivered by the MAD in these 3D models. Such models might be used to study other methods for targeting intranasal regions with aerosolized medications in children and adults.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"89-100"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9985662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.","authors":"","doi":"10.1089/jamp.2023.ab01.abstracts","DOIUrl":"https://doi.org/10.1089/jamp.2023.ab01.abstracts","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"A1-A39"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}