Inhaled Aerosol Distribution in Human Airways: A Scintigraphy-Guided Study in a 3D Printed Model

Verbanck, Sylvia; Ghorbaniasl, Ghader; Biddiscombe, Martyn; Dragojlovic, Dusica; Ricks, Nathan; Lacor, Christian; Ilsen, Bart; Mey, Johan De; Schuermans, Daniël; Underwood, S. Richard; Barnes, Peter J.; Vincken, Walter; Usmani, Omar

doi:10.1089/jamp.2016.1291

Cited by 30 publications

(38 citation statements)

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“…Therefore, the human data reported here support the cast data as well as the computational fluid dynamics (CFD) simulations presented in Ref. (40) For scales smaller than the lobar level (segmental level), Verbanck et al reported a higher variability in the cast's ventilation-to-deposition ratio. The limited lung coverage and co-registration across modalities (limitations given next) limit our ability to produce reliable data at the scale of lung segments and sub-segments.…”

Section: Figsupporting

confidence: 89%

“…In a recent paper using a three-dimensional printed, realistic airway cast (mouth to generation 5), Verbanck et al (40) reported for 3 and 6 lm particles, at higher flows than the flow imposed here (30 and 60 L/min, compared with 15 L/ min), direct proportionality between lobar-level ventilation and aerosol distribution. The quartile lung regions used in our analysis samples ventilation and deposition across neighboring lobes.…”

Section: Figmentioning

confidence: 50%

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Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing

Sá

Zeman

Bennett

et al. 2017

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Section: Figsupporting

confidence: 89%

Section: Figmentioning

confidence: 50%

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing

Sá

Zeman

Bennett

et al. 2017

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…Such altered flow patterns and aerosol deposition have been demonstrated using computational fluid dynamics in lung models. 39,40 Methods to reduce airway closure, such as application of positive expiratory pressure, may thus have benefit for improving inhaled drug deposition. 41 Our data reveal a median closing index of 0.67 among a large, diverse group of patients with asthma.…”

Section: Discussionmentioning

confidence: 99%

Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma

et al. 2019

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Background and objective: The reduction of forced expiratory volume in 1 s (FEV 1 ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV 1 /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC). Methods: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV 1 , and calculated as %ΔFVC/%ΔFEV 1 . Results: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control. Conclusion: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.Airway closure during methacholine challenge contributes importantly to airway hyperresponsiveness in asthma and is associated with older age and obesity.provocative concentration of methacholine causing a 20% decrease in FEV 1 ; SARA, Study of Acid Reflux and Asthma; SARCA, Study of Acid Reflux in Childhood Asthma; STAN, Study of Asthma and Nasal Steroids.

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“…As most asthma therapy is topically acting, the inhaler is of little use if it can only deliver a dose to the healthy part of the lungs while the diseased part goes untreated. 13 Therefore, the physical characteristics of the discharged aerosol dose are as vital for a successful outcome as the pharmacodynamics of the drug itself. Particle size is the most important physical property of the aerosol cloud and is an important determinate of how far into the airways a dose can be delivered.…”

Section: Desirable Inhaler Characteristics For Treating Asthmamentioning

confidence: 99%

Inhaler Characteristics in Asthma

Biddiscombe¹

2017

European Respiratory &Amp; Pulmonary Diseases

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The history of inhaled therapy goes back a surprisingly long way. More than 4,000 years ago, in India, the vapour of plants from the nightshade family placed on hot bricks was inhaled to alleviate breathing difficulties. The bronchodilators, derived from these plants, and compounds related to them, have played a significant part in therapeutic aerosol delivery over the years and remain important in the treatment of lung diseases today. The development of inhaled therapy has accelerated over the past 60 years with the arrival of the first truly portable inhaler in 1956 to relieve the symptoms of asthma. Initially, only bronchodilators were delivered from these devices, but as the true nature of asthma was revealed, inhaled corticosteroids were introduced to treat the underlying inflammation that is a major component of asthma. Further advances have led to long-acting bronchodilators becoming available, and combination therapies containing both longacting bronchodilators and corticosteroids in one inhaler. Asthma therapy has come a long way in a comparatively short time with over 230 device and drug combinations available for treating the disease. However, despite enormous investment asthma remains a huge healthcare problem. The number of people with asthma continues to grow with over 300 million people affected worldwide and 250,000 annual deaths attributed to the disease. It affects people of all ages and has a varying degree of severity. In this article, we look at the ideal characteristics for asthma inhalers and highlight some of the most important reasons for the failure of current asthma treatments.

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Inhaled Aerosol Distribution in Human Airways: A Scintigraphy-Guided Study in a 3D Printed Model

Cited by 30 publications

References 30 publications

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing

Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma

Inhaler Characteristics in Asthma

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