Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Effect of Inspiratory Muscle Training on Aerosol Deposition and Pulmonary Perfusion in Post-COVID-19 Syndrome: A Gamma Scintigraphy Study.","authors":"Jose Carlos Nóbrega Júnior, Simone Soares Brandão, James B Fink, Daiara Xavier, Roberta Torres, Arzu Ari, Cyda Reinaux, Shirley Campos, Daniella Brandão, Armèle Dornelas de Andrade","doi":"10.1177/19412711261418482","DOIUrl":"10.1177/19412711261418482","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary dysfunction in individuals with post-coronavirus disease-2019 (COVID-19) syndrome may impair aerosol deposition and pulmonary perfusion, compromising respiratory efficiency. Inspiratory muscle training (IMT) has been proposed as a strategy to improve respiratory mechanics and lung function.</p><p><strong>Objective: </strong>To compare aerosol deposition and pulmonary perfusion in individuals with post-COVID-19 syndrome before and after 8 weeks of IMT.</p><p><strong>Methods: </strong>This was a randomized controlled clinical trial involving 19 participants, divided into an IMT group (<i>n</i> = 10) and a control group (<i>n</i> = 9). The IMT group performed training with a load adjusted to 50% of maximal inspiratory pressure, while the control group used a device without resistance. Aerosol deposition and pulmonary perfusion were evaluated by gamma scintigraphy using the radioisotopes technetium-labeled diethylene-triamine-pentaacetic acid and technetium99-labeled macroaggregated human serum albumin, respectively. Total radiopharmaceutical activity in both lungs, as well as in the right and left lungs separately, was quantified pre- and post-intervention.</p><p><strong>Results: </strong>After 8 weeks, the IMT group showed a significant increase in total lung activity for both aerosol deposition (<i>p</i> = 0.028) and perfusion (<i>p</i> = 0.013). In the right lung, activity increased significantly for aerosol deposition (<i>p</i> = 0.005) and perfusion (<i>p</i> = 0.005). In the left lung, significant increases were also observed for perfusion (<i>p</i> = 0.007). No significant increases were observed in the control group. In the between-group analysis, the IMT group showed higher activity in both lungs combined and separately, compared with controls, for aerosol deposition (all <i>p</i> < 0.05) and in the right lung for perfusion (<i>p</i> = 0.010).</p><p><strong>Conclusion: </strong>IMT improved total aerosol deposition and perfusion in individuals with post-COVID-19 syndrome. These findings support the use of IMT as a rehabilitation strategy to enhance pulmonary deposition of inhaled agents and increase pulmonary perfusion in this population.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"198-206"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112806","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":"Pharmacokinetic Analysis of Compounds Instilled into the Mouse Lung: Study with <i>In Vivo</i> Electron Spin Resonance Spectroscopy and Nitroxyl Spin Probes as Model Drugs.","authors":"Jin-Yi Han, Keizo Takeshita, Shoko Okazaki, Hideo Utsumi","doi":"10.1177/19412711251379678","DOIUrl":"10.1177/19412711251379678","url":null,"abstract":"<p><strong>Introduction: </strong>Detailed understanding of the absorption mechanisms of compounds in the lungs is important for developing effective systems for the pulmonary administration of drugs. This study analyzed the pharmacokinetics of model compounds instilled into the mouse lungs using <i>in vivo</i> electron spin resonance (ESR) spectroscopy.</p><p><strong>Methods: </strong>An aqueous solution of a nitroxyl probe with cationic, anionic, or neutral groups was instilled into the lungs of healthy mice at high concentrations as model drugs, and the behavior of the probes was assessed using concentration-dependent changes in the linewidths of ESR signals obtained in live mice.</p><p><strong>Results: </strong>When solutions of nitroxyl probes at high concentrations, which produce broad ESR signals, were instilled into the mouse lungs, sharp ESR signals originating from diluted probes were superimposed onto broad signals. Broad signals decreased at various rates for all probes depending on their lipophilicity. Sharp signals for neutral probe and anionic probe immediately increased after instillation and then decreased. Sharp signals for cationic probe with a quaternary ammonium group continued to increase after instillation. Pharmacokinetic analysis of the blood concentrations of these probes suggests that the probes are distributed to lung tissues in addition to the blood. The concentration dependence of the initial velocity of broad signal decay suggests the possibility that the transfer of charged probes from the alveolar space to the bloodstream may be mediated by transporters, whereas a neutral probe may be transferred via passive diffusion.</p><p><strong>Conclusion: </strong>The differences in pharmacokinetic behavior in lungs could be examined <i>in vivo</i> among model compounds with different charge states. <i>In vivo</i> ESR spectroscopy is a powerful tool for the <i>in vivo</i> analysis of pulmonary pharmacokinetics, in combination with nitroxyl probes as model drugs.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"177-184"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199547","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":"Safety and Pharmacokinetic Data for Inhaled Administration of Nintedanib Dry Powder Inhalation for Treatment of Pulmonary Fibrotic Diseases.","authors":"Wassim H Fares, Michael Castagna","doi":"10.1177/19412711251414386","DOIUrl":"10.1177/19412711251414386","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is an incurable disease marked by irreversible fibrosis and declining respiratory function. Nintedanib inhalation powder is a novel dry powder inhalation formulation of nintedanib consisting of Technosphere® particles that deliver active drug directly to the lungs, aiming to reduce systemic effects associated with oral treatment. The objective of the present work was to assess whether nintedanib dry powder inhalation (DPI) has the potential to provide improved safety and thus effectiveness compared with that of currently available therapeutic options for IPF.</p><p><strong>Methods: </strong>Three preclinical studies evaluated pharmacokinetic and toxicity outcomes associated with nintedanib inhalation powder. Two 28-day repeat-dose studies (one in rats and one in dogs), and a 6-month toxicity study in dogs assessed pulmonary and histological changes after inhaled nintedanib therapy. A phase 1, first-in-human, randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of nintedanib DPI versus placebo in healthy adults.</p><p><strong>Results: </strong>In the 28-day repeat-dose studies and the 6-month study, animals survived to scheduled necropsy without significant adverse findings, including no gastrointestinal adverse findings, and most achieved target pulmonary-deposited nintedanib concentrations. The phase 1 study demonstrated dose-proportional increases in nintedanib plasma concentrations after single doses and rapid absorption of nintedanib, with maximum concentrations within a few minutes of first dose at levels consistent with deep lung deposition. Nintedanib inhalation powder was considered safe and well tolerated throughout the study duration.</p><p><strong>Conclusion: </strong>Inhaled administration of nintedanib via DPI may offer advantages over oral therapies in patients with IPF, potentially reducing adverse effects associated with systemic exposure. Results of the preclinical and phase 1 studies support continued assessment of this formulation in patients with IPF and other pulmonary fibrotic diseases.</p><p><strong>Clinical trial registration number: </strong>NCT06532942.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"39 4","pages":"185-197"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351898","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":"<i>Letter:</i> Impact of Suboptimal Peak Inspiratory Flow on Exacerbations in Chronic Obstructive Pulmonary Disease Patients Using Dry Powder Inhalers.","authors":"Ji-Yong Moon, Sang Hyuk Kim, Youlim Kim, Hyun Lee, Chin Kook Rhee, Seung Won Ra, Chang Youl Lee, Joo Hun Park, Yong Bum Park, Kwang Ha Yoo","doi":"10.1177/19412711261470936","DOIUrl":"https://doi.org/10.1177/19412711261470936","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261470936"},"PeriodicalIF":2.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562106","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":"Toward Next-Generation Propellants: Assessing Lung Deposition of Beclometasone Dipropionate, Formoterol, and Glycopyrrolate Formulated with HFA-152a Using Functional Respiratory Imaging.","authors":"Angelo Matturro, Navid Monshi Tousi, Hosein Sadafi, Erika Cuoghi, Sara Panigone, Diego González-Segura, Gianluigi Poli, Federica Sandri","doi":"10.1177/19412711261464842","DOIUrl":"https://doi.org/10.1177/19412711261464842","url":null,"abstract":"<p><strong>Background: </strong>Pressurized metered-dose inhalers (pMDIs) rely on hydrofluoroalkane (HFA) propellants that have a high global warming potential (GWP). Reformulation with next-generation, low-GWP propellants, such as HFA-152a, offers a strategy to reduce climate impact; however, changes in propellant composition can affect aerosol characteristics and potentially alter lung deposition, requiring robust demonstration of therapeutic equivalence.</p><p><strong>Methods: </strong>Functional respiratory imaging, combining high-resolution computed tomography and computational fluid dynamics, was used to compare the lung deposition of a fixed triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) delivered via a pMDI formulated with either HFA-134a (Reference) or HFA-152a (Test). Ten patients with chronic obstructive pulmonary disease (GOLD stages 2-4) were retrospectively selected. Patient-specific airway geometries, a standardized inhalation profile, and formulation-specific particle size distributions and plume characteristics were applied. Deposition was quantified in the intrathoracic, central + distal, and peripheral lung regions, and the (central + distal)/peripheral ([C + D]/P) deposition ratio was evaluated.</p><p><strong>Results: </strong>Mean intrathoracic deposition was comparable between the Reference and Test formulations, ranging from 45.95% to 46.88% of the delivered dose (DD). Deposition in the central + distal airways accounted for 12% of DD for both formulations, whereas peripheral deposition predominated, with 33.7% of DD for the Test formulation and 34.5% of DD for the Reference formulation. The (C + D)/P ratios were similar across all active components (0.35-0.37), indicating consistent preferential deposition in the peripheral/small airways. Although inter-patient variability was observed, intra-subject comparisons showed close agreement between propellants.</p><p><strong>Conclusion: </strong>Reformulation of the BDP/FF/GB pMDI with the low-GWP propellant HFA-152a preserved total and regional lung deposition characteristics relative to the current HFA-134a formulation. These findings support the maintenance of deposition performance while enabling a substantial reduction in environmental impact, reinforcing the potential of HFA-152a as a next-generation propellant for carbon minimal pMDI therapies.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261464842"},"PeriodicalIF":2.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470820","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":"Mucociliary Clearance Following a Next-Generation Propellant Versus Hydrofluoroalkane-134a via Pressurized Metered-Dose Inhaler: A Randomized, Double-Blind, Two-Way Crossover Study in Healthy Adults.","authors":"Scott H Donaldson, Kirby L Zeman, Alan Bell, Mandeep Jassal, Hitesh Pandya, Jennifer L Bell, Margareta Puu, Magnus Aurivillius, Mehul Patel, William Bennett","doi":"10.1177/19412711261470884","DOIUrl":"https://doi.org/10.1177/19412711261470884","url":null,"abstract":"<p><strong>Background: </strong>Pressurized metered-dose inhalers (pMDIs) are commonly used for respiratory disease treatment but contain propellants, such as hydrofluoroalkane-134a (HFA-134a), with global warming potential (GWP) that contribute to the climate emergency. To safeguard essential medicine access, it is crucial to transition to lower-GWP propellants, such as hydrofluoroolefin-1234ze (HFO-1234ze), which has 99% lower GWP than HFA-134a. In accordance with global regulatory requirements, this study was conducted to support the registration of pMDIs with HFO-1234ze.</p><p><strong>Methods: </strong>This randomized, double-blind, multicenter, two-way crossover study assessed the effects of HFO-1234ze versus HFA-134a on mucociliary clearance (MCC) in healthy participants aged 18-60 years. Participants received six inhalations twice daily of HFO-1234ze and HFA-134a in two 7-day (+3) intervention periods separated by a 7- to 14-day washout. The primary and secondary endpoints were change from period-specific baseline in average whole lung MCC (%) through 60 minutes (MCC60) and at 3 hours (MCC3h), respectively, measured via inhalation of ^99mTc-labeled colloid and gamma camera imaging. Given significant baseline variability, a <i>post hoc</i> analysis of the primary endpoint assessed change from average baseline instead of period-specific baseline MCC60. Additional safety and tolerability measures were assessed.</p><p><strong>Results: </strong>Forty-five participants were screened; the Primary Analysis Set included 34 participants who completed both intervention periods. For the primary endpoint, change from period-specific baseline in MCC60 was negligible, with an estimated change (95% confidence interval [CI]) of -0.6% (-3.2%, 1.9%) for HFO-1234ze and 0.8% (-1.7%, 3.3%) for HFA-134a. The estimated least-squares mean difference (95% CI) between HFO-1234ze and HFA-134a was -1.4% (-5.8%, 2.9%). For the secondary endpoint, the estimated least-squares mean difference for change from period-specific baseline in MCC3h between HFO-1234ze and HFA-134a was -5.7% (-10.9%, -0.5%). There were no unexpected safety findings.</p><p><strong>Conclusion: </strong>There was no clinically relevant impact of HFO-1234ze versus HFA-134a on MCC in healthy participants.</p><p><strong>Clinical trial registration number: </strong>NCT05755932.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261470884"},"PeriodicalIF":2.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470804","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":"Selecting the Optimal Inhaler in Asthma: Respiratory and Peripheral Muscle Strength as Predictors of DPI and MDI Response.","authors":"Buğra Kerget, Alperen Aksakal, Sırma Merve Çetin, Elif Yılmazel Uçar","doi":"10.1177/19412711261464825","DOIUrl":"10.1177/19412711261464825","url":null,"abstract":"<p><strong>Background: </strong>Asthma is characterized by variable airway obstruction, and proper inhaler choice and use are critical for effective treatment. This study aimed to identify factors influencing treatment response in newly diagnosed patients started on dry powder inhalers (DPIs) or metered-dose inhalers (MDIs).</p><p><strong>Methods: </strong>Between March and September 2025, 177 newly diagnosed asthma patients were screened. Eighty patients with at least high-school education, correct inhaler use, and good adherence were included (40 DPI, 40 MDI). Pulmonary function, respiratory muscle strength, Asthma Control Test (ACT), and handgrip strength (HGS) were assessed at baseline and after one month.</p><p><strong>Results: </strong>After one month, improvements in forced expiratory volume in 1 second (FEV₁) (% predicted), maximum inspiratory pressure (MIP) and MIP (%), and maximum expiratory pressure (MEP) (%) were significantly greater in the DPI group compared with the MDI group (<i>p</i> = 0.03, 0.04, 0.02 respectively). In multivariate regression, among MDI users, MIP (kPa) (<i>B</i> = -11.305, <i>p</i> = 0.001), MIP (%) (<i>B</i> = -0.902, <i>p</i> = 0.003), ACT (<i>B</i> = 1.277, <i>p</i> = 0.014), and HGS (<i>B</i> = 0.103, <i>p</i> = 0.039) were independent predictors of ΔFEV₁ (%). Among DPI users, MIP (kPa) (<i>B</i> = 11.987, <i>p</i> = 0.015), MIP (%) (<i>B</i> = 1.041, <i>p</i> = 0.009), MEP (kPa) (<i>B</i> = -6.554, <i>p</i> = 0.014), MEP (%) (<i>B</i> = -0.816, <i>p</i> < 0.001), and HGS (<i>B</i> = 0.201, <i>p</i> = 0.005) were significant determinants of ΔFEV₁.</p><p><strong>Conclusion: </strong>DPIs may be preferable for patients with higher inspiratory muscle strength, whereas MDIs may be better for those with lower MIP. HGS appears to be an important factor for both inhaler control and treatment efficacy.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261464825"},"PeriodicalIF":2.2,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345469","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":"Usability of Levodopa Cyclops^® Compared to INBRIJA^® During an off Episode in Parkinson's Disease Patients.","authors":"Valesca Wangsawirana, Lara de Jong, Annebet van der Meulen, Paul Hagedoorn, Marianne Luinstra, Henderik Willem Frijlink","doi":"10.1177/19412711261456530","DOIUrl":"https://doi.org/10.1177/19412711261456530","url":null,"abstract":"<p><strong>Background: </strong>This study compares the usability of two levodopa dry powder inhalers. The Inbrija^® inhaler involves several preparatory steps, including blister opening and capsule insertion. The Cyclops^® inhaler is preloaded and disposable, designed for immediate use. Ease of use is critical, as cognitive and motor impairments may hinder the patients' ability to operate an inhaler.</p><p><strong>Methods: </strong>Sixteen patients with Parkinson's disease experiencing predictable and recognizable off episodes were enrolled. After receiving inhalation instructions, patients performed the inhalation maneuver during their off-episode to assess the correct execution. They completed a questionnaire evaluating the ease of use for both devices. Each patient used both the Cyclops^® and Inbrija^® inhalers in a randomized sequence and completed the questionnaire.</p><p><strong>Results: </strong>All 16 patients correctly performed the Cyclops^® inhaler steps during an off episode, while only 10 patients successfully completed the steps with the Inbrija^® inhaler. Twelve of the sixteen patients (75%) expressed a preference for the Cyclops^®, rating it higher in terms of ease of use and hygiene. However, concerns were raised regarding the environmental sustainability of its single-use design. For the Inbrija^®, patients reported difficulties with opening the peel-off blister packaging, assembling the mouthpiece, and puncturing the capsules.</p><p><strong>Conclusion: </strong>The Cyclops^® inhaler was more user-friendly during off episodes due to its ease of use and simpler handling. Since the Cyclops^® is preloaded, it requires fewer and simpler steps. The preparation steps of Inbrija^® posed usability challenges, particularly with opening the peel-off blister packaging of the capsule and assembling the mouthpiece and handle.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"19412711261456530"},"PeriodicalIF":2.2,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301832","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":"Lung Deposition of Tanimilast, an Inhaled Phosphodiesterase-4 Inhibitor, in Patients with Asthma or COPD, Evaluated Using Functional Respiratory Imaging.","authors":"Navid Monshi Tousi, Romina Osello, Debora Santoro, Laura Campochiaro, Jason H T Bates, Dmitry Galkin, Jan De Backer, Hosein Sadafi, Gwen Skloot","doi":"10.1177/19412711251396759","DOIUrl":"10.1177/19412711251396759","url":null,"abstract":"<p><strong>Background: </strong>Tanimilast is a novel phosphodiesterase-4 inhibitor under clinical development for the maintenance therapy of asthma and chronic obstructive pulmonary disease (COPD). Since tanimilast is inhaled, it is important to evaluate lung deposition as part of its clinical development. The current study, therefore, used functional respiratory imaging, a validated, noninvasive quantification imaging methodology, to evaluate the lung deposition of tanimilast in patients with asthma or COPD.</p><p><strong>Methods: </strong>This retrospective study used data from 12 patients with asthma and 12 patients with COPD, primarily selected based on disease severity. Patients with COPD had chronic bronchitis, with minimal high-resolution computerized tomography evidence of emphysema. Total intrathoracic, central, distal, peripheral, and extrathoracic deposition of tanimilast 400 µg and 800 µg was evaluated using three inhalation profiles-inhalation durations of 1, 2, and 3 seconds, with associated peak flows of 100, 60, and 45 L/min, respectively.</p><p><strong>Results: </strong>Intrathoracic deposition as a percentage of the delivered dose was similar in asthma and COPD, with mean ± SD varying between 34.6 ± 8.5% and 44.9 ± 5.9%, increasing slightly with increasing inhalation duration (i.e., from 1 to 3 seconds), whereas extrathoracic deposition decreased progressively. Central deposition was low (<5%) regardless of inhalation duration (2.7 ± 0.9% to 4.4 ± 1.6%). Distal deposition was similar with the two tanimilast doses and although not impacted by inhalation duration was slightly higher in COPD than asthma. Peripheral deposition increased with increasing inhalation duration (e.g., in asthma for tanimilast 400 µg, from 14.1 ± 3.6% for a duration of 1 second to 19.9 ± 4.0% for a duration of 3 seconds) and was higher in asthma than in COPD.</p><p><strong>Conclusions: </strong>Tanimilast effectively reached all levels of the airway in patients with asthma or COPD. Peripheral deposition was enhanced by lower inspiratory flows (i.e., longer inhalation durations), suggesting that specific inhalation strategies may have the potential to improve therapeutic outcomes in obstructive lung diseases.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"133-140"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564012","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":"Design of Dry Powder Inhalers: 2. The Impact of Suboptimal Peak Inspiratory Flow Rates on Bronchodilation in Patients with Obstructive Lung Diseases.","authors":"Jeffry G Weers, Thomas E Tarara, Danforth P Miller","doi":"10.1177/19412711251415063","DOIUrl":"10.1177/19412711251415063","url":null,"abstract":"<p><strong>Background: </strong>Suboptimal peak inspiratory flow rate (sPIFR) has been proposed as a biomarker of disease progression in people with chronic obstructive pulmonary disease (COPD). Furthermore, sPIFR has been claimed to result in poor drug delivery, which in turn leads to poor clinical outcomes with passive dry powder inhalers (DPIs).</p><p><strong>Results: </strong>Breathing studies suggest that most patients with COPD-including those with severe disease or experiencing an acute pulmonary exacerbation-can generate a pressure drop of at least 1.0 kPa. Across the 1.0-6.0 kPa range, variations in mean total lung dose of inhaled bronchodilators delivered with passive DPIs are modest: typically, no > 3-fold, and only 1.1 to 1.4-fold for most lactose blend-based products. Due to their large therapeutic indices, inhaled bronchodilators are formulated on the plateau of the dose-response curve, where comparable bronchodilation is typically achieved across a 2- to 4-fold dose range. Head-to-head comparisons of active delivery devices with passive DPIs show no differences in bronchodilation for the same drug, even in patients with sPIFR.</p><p><strong>Conclusions: </strong>There is no compelling evidence to support the assertion that sPIFR with inhaled bronchodilators in asthma and COPD patients leads to inadequate drug delivery that results in marked decreases in lung function. On the contrary, the variations in PIFR typically observed with inhaled bronchodilators lead to consistent bronchodilation across a range of PIFR. Reductions in forced expiratory volume in one second with disease progression reflect reduced responsiveness to bronchodilators, not impaired drug delivery due to sPIFR. Options exist to dramatically improve lung targeting and dose consistency with inhaled medicines. These options are particularly valuable for treatments where the drug has a narrow therapeutic index or a high cost of goods.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"39 3","pages":"155-167"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199052","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}