Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

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There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19. 新冠肺炎患者雾化治疗期间存在传播风险。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-10-01 Epub Date: 2023-08-22 DOI: 10.1089/jamp.2023.0010
Christophe Thibon, Laurent Vecellio, Leila Belkhir, Jean-Christophe Dubus, Annie Robert, Benoît Kabamba, Gregory Reychler
{"title":"There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19.","authors":"Christophe Thibon,&nbsp;Laurent Vecellio,&nbsp;Leila Belkhir,&nbsp;Jean-Christophe Dubus,&nbsp;Annie Robert,&nbsp;Benoît Kabamba,&nbsp;Gregory Reychler","doi":"10.1089/jamp.2023.0010","DOIUrl":"10.1089/jamp.2023.0010","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. <b><i>Methods:</i></b> In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler<sup>®</sup> and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. <b><i>Results:</i></b> Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5 × 10<sup>6</sup> copies/mL. Two out of the 10 samples from the fugitive aerosol collected were positive to SARS-CoV-2. <b><i>Conclusion:</i></b> The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"268-274"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433927","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}
引用次数: 0
The Pharmacokinetics of Inhaled Drugs. 吸入药物的药代动力学。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-10-01 DOI: 10.1089/jamp.2023.29091.gt
Glyn Taylor
{"title":"The Pharmacokinetics of Inhaled Drugs.","authors":"Glyn Taylor","doi":"10.1089/jamp.2023.29091.gt","DOIUrl":"10.1089/jamp.2023.29091.gt","url":null,"abstract":"<p><p>The pharmacokinetic (PK) profile of a drug after inhalation may differ quite markedly from that seen after dosing by other routes of administration. Drugs may be administered to the lung to elicit a local action or as a portal for systemic delivery of the drug to its site of action elsewhere in the body. Some knowledge of PK is important for both locally- and systemically-acting drugs. For a systemically-acting drug, the plasma concentration-time profile shares some similarities with drug given by the oral or intravenous routes, since the plasma concentrations (after the distribution phase) will be in equilibrium with concentrations at the site of action. For a locally-acting drug, however, the plasma concentrations reflect its fate after it has been absorbed and removed from the airways, and not what is available to its site of action in the lung. Consequently, those typical PK parameters which are determined from plasma concentration measurements, e.g., area under the curve (AUC), C<sub>max</sub>, t<sub>max</sub> and post-peak t1/2 may provide information on the deposition and absorption of drugs from the lung; however, the information from these parameters becomes more complicated to decipher for those drugs which are locally-acting in the lung. Additionally, the plasma concentration profile for both locally- and systemically-acting drugs will not only reflect drug absorbed from the lung but also that absorbed from the gastrointestinal (GI) tract from the portion of the dose which is swallowed. This absorption from the GI tract adds a further complication to the interpretation of plasma concentrations, particularly for locally-acting drugs. The influence of physiological and pathological factors needs to be considered in the absorption of some inhaled drugs. The absorption of some hydrophilic drugs is influenced by the inspiratory maneuver used during initial inhalation of the drug, and at later times after deposition. Similarly, the effects of smoking have been shown to increase lung permeability and increase the absorption of certain hydrophilic drugs. The effects of different disease states of the lung have less defined influences on absorption into the systemic circulation.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 5","pages":"281-288"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677698","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}
引用次数: 0
Aerosol Delivery of a Novel Recombinant Modified Superoxide Dismutase Protein Reduces Oxidant Injury and Attenuates Escherichia coli Induced Lung Injury in Rats. 气溶胶递送一种新型重组修饰的超氧化物歧化酶蛋白可减少氧化损伤并减轻大肠杆菌诱导的大鼠肺损伤。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-10-01 Epub Date: 2023-08-28 DOI: 10.1089/jamp.2022.0069
Sean D McCarthy, Maura A Tilbury, Claire H Masterson, Ronan MacLoughlin, Héctor E González, John G Laffey, J Gerard Wall, Daniel O'Toole
{"title":"Aerosol Delivery of a Novel Recombinant Modified Superoxide Dismutase Protein Reduces Oxidant Injury and Attenuates <i>Escherichia coli</i> Induced Lung Injury in Rats.","authors":"Sean D McCarthy,&nbsp;Maura A Tilbury,&nbsp;Claire H Masterson,&nbsp;Ronan MacLoughlin,&nbsp;Héctor E González,&nbsp;John G Laffey,&nbsp;J Gerard Wall,&nbsp;Daniel O'Toole","doi":"10.1089/jamp.2022.0069","DOIUrl":"10.1089/jamp.2022.0069","url":null,"abstract":"<p><p><b><i>Background:</i></b> Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. <b><i>Objectives:</i></b> To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat <i>Escherichia coli</i> induced ARDS. <b><i>Methods:</i></b> Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in <i>E. coli</i>. Purified proteins were evaluated in <i>in vitro</i> assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an <i>E. coli</i>-induced ARDS rat model. <b><i>Results:</i></b> SOD proteins exhibited high SOD activity <i>in vitro</i> and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an <i>E. coli</i>-induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. <b><i>Conclusions:</i></b> Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates <i>E. coli</i> induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"246-256"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10084999","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}
引用次数: 0
Aerosol Particle Size Influences the Infectious Dose and Disease Severity in a Golden Syrian Hamster Model of Inhalational COVID-19. 在金叙利亚仓鼠吸入性新冠肺炎模型中,气溶胶颗粒大小影响感染剂量和疾病严重程度。
IF 2 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-10-01 Epub Date: 2023-06-01 DOI: 10.1089/jamp.2022.0072
Jeremy A Boydston, Jennifer Biryukov, John J Yeager, Heather A Zimmerman, Gregory Williams, Brian Green, Amy L Reese, Katie Beck, Jordan K Bohannon, David Miller, Denise Freeburger, Amanda Graham, Victoria Wahl, Michael C Hevey, Paul A Dabisch
{"title":"Aerosol Particle Size Influences the Infectious Dose and Disease Severity in a Golden Syrian Hamster Model of Inhalational COVID-19.","authors":"Jeremy A Boydston, Jennifer Biryukov, John J Yeager, Heather A Zimmerman, Gregory Williams, Brian Green, Amy L Reese, Katie Beck, Jordan K Bohannon, David Miller, Denise Freeburger, Amanda Graham, Victoria Wahl, Michael C Hevey, Paul A Dabisch","doi":"10.1089/jamp.2022.0072","DOIUrl":"10.1089/jamp.2022.0072","url":null,"abstract":"<p><p><b><i>Background:</i></b> Significant evidence suggests that SARS-CoV-2 can be transmitted via respiratory aerosols, which are known to vary as a function of respiratory activity. Most animal models examine disease presentation following inhalation of small-particle aerosols similar to those generated during quiet breathing or speaking. However, despite evidence that particle size can influence dose-infectivity relationships and disease presentation for other microorganisms, no studies have examined the infectivity of SARS-CoV-2 contained in larger particle aerosols similar to those produced during coughing, singing, or talking. Therefore, the aim of the present study was to assess the influence of aerodynamic diameter on the infectivity and virulence of aerosols containing SARS-CoV-2 in a hamster model of inhalational COVID-19. <b><i>Methods:</i></b> Dose-response relationships were assessed for two different aerosol particle size distributions, with mass median aerodynamic diameters (MMADs) of 1.3 and 5.2 μm in groups of Syrian hamsters exposed to aerosols containing SARS-CoV-2. <b><i>Results:</i></b> Disease was characterized by viral shedding in oropharyngeal swabs, increased respiratory rate, decreased activity, and decreased weight gain. Aerosol particle size significantly influenced the median doses to induce seroconversion and viral shedding, with both increasing ∼30-fold when the MMAD was increased. In addition, disease presentation was dose-dependent, with seroconversion and viral shedding occurring at lower doses than symptomatic disease characterized by increased respiratory rate and decreased activity. <b><i>Conclusions:</i></b> These results suggest that aerosol particle size may be an important factor influencing the risk of COVID-19 transmission and needs to be considered when developing animal models of disease. This result agrees with numerous previous studies with other microorganisms and animal species, suggesting that it would be generally translatable across different species. However, it should be noted that the absolute magnitude of the observed shifts in the median doses obtained with the specific particle sizes utilized herein may not be directly applicable to other species.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"235-245"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192713","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}
引用次数: 0
Multidrug Aerosol Delivery During Mechanical Ventilation. 机械通气时多药气雾剂给药。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-08-01 DOI: 10.1089/jamp.2022.0057
Ann D Cuccia, Michael McPeck, Janice A Lee, Gerald C Smaldone
{"title":"Multidrug Aerosol Delivery During Mechanical Ventilation.","authors":"Ann D Cuccia,&nbsp;Michael McPeck,&nbsp;Janice A Lee,&nbsp;Gerald C Smaldone","doi":"10.1089/jamp.2022.0057","DOIUrl":"https://doi.org/10.1089/jamp.2022.0057","url":null,"abstract":"<p><p><b><i>Background:</i></b> In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as bronchodilators or antibiotics are needed, vasodilator therapy may be interrupted. This study assesses aerosol systems designed for simultaneous delivery of two aerosols using continuous nebulization and bolus injection without interruption or circuit disconnection. <b><i>Methods:</i></b> One i<i>-AIRE</i> dual-port breath-enhanced jet nebulizer (BEJN) or two Aerogen<sup>®</sup> Solo vibrating mesh nebulizers (VMNs) were installed on the dry side of the humidifier. VMN were stacked; one for infusion and the second for bolus drug delivery. The BEJN was powered by air at 3.5 L/min, 50 psig. Radiolabeled saline was infused at 5 and 10 mL/h with radiolabeled 3 and 6 mL bolus injections at 30 and 120 minutes, respectively. Two adult breathing patterns (duty cycle 0.13 and 0.34) were tested with an infusion time of 4 hours. Inhaled mass (IM) expressed as % of initial syringe activity (IM%/min) was monitored in real time with a ratemeter. All delivered radioaerosol was collected on a filter at the airway opening. Transients in aerosol delivery were measured by calibrated ratemeter. <b><i>Results:</i></b> IM%/h during continuous infusion was linear and predictable, mean ± standard deviation (SD): 2.12 ± 1.45%/h, 2.47 ± 0.863%/h for BEJN and VMN, respectively. BEJN functioned without incident. VMN continuous aerosol delivery stopped spontaneously in 3 of 8 runs (38%); bolus delivery stopped spontaneously in 3 of 16 runs (19%). Tapping restarted VMN function during continuous and bolus delivery runs. Bolus delivery IM% (mean ± SD): 20.90% ± 7.01%, 30.40% ± 11.10% for BEJN and VMN, respectively. <b><i>Conclusion:</i></b> Simultaneous continuous and bolus nebulization without circuit disconnection is possible for both jet and mesh technology. Monitoring of VMN devices may be necessary in case of spontaneous interruption of nebulization.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 4","pages":"154-161"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154301","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}
引用次数: 0
Magnetic Resonance Imaging of Aerosol Deposition. 气溶胶沉积的磁共振成像。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-08-01 DOI: 10.1089/jamp.2023.29087.rbt
Richard B Thompson, Chantal Darquenne
{"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 (<sup>1</sup>H) in water. The regional deposition of aerosol particles can be measured by the perturbation of the acquired <sup>1</sup>H 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}
引用次数: 0
Predicting Inhaled Drug Dose Generated by Mesh Nebulizers. 网状雾化器吸入药物剂量预测。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-08-01 DOI: 10.1089/jamp.2022.0055
Yu-Chung Hsu, Hsin-Hsien Li, Li-Chung Chiu, Wen-Chieh Chiang, Tien-Pei Fang, Hui-Ling Lin
{"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<sub>i</sub></i>/<i>T</i><sub>total</sub>; %) 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<sub>i</sub></i>/<i>T</i><sub>total</sub> 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}
引用次数: 0
Measuring Anatomical Distributions of Ventilation and Aerosol Deposition with PET-CT. 用PET-CT测量通风和气溶胶沉积的解剖学分布。
IF 2 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-08-01 DOI: 10.1089/jamp.2023.29086.jgv
Jose G Venegas
{"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}
引用次数: 0
In Vitro 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. 高渗盐水联合沙丁胺醇对健康志愿者和囊性纤维化患者鼻上皮细胞纤毛跳动频率和粘膜纤毛运输的体外影响
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-08-01 DOI: 10.1089/jamp.2022.0026
Anaïs Escher, Elisabeth Kieninger, Susan De Groof, Sibel T Savas, Martin Schneiter, Stefan A Tschanz, Martin Frenz, Philipp Latzin, Carmen Casaulta, Loretta Müller
{"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}
引用次数: 0
The Role of Long-Acting Antimuscarinic Agents in the Treatment of Asthma. 长效抗毒蕈碱类药物在哮喘治疗中的作用。
IF 3.4 4区 医学
Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2023-08-01 DOI: 10.1089/jamp.2022.0059
Bahar Arslan, Gülden Paçacı Çetin, İnsu Yilmaz
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