Simulated Breathing Patterns Research Articles

Real-time respiration monitoring using the radiotherapy treatment beam and four-dimensional computed tomography (4DCT)—a conceptual study

Real-time knowledge of intra-fraction motion, such as respiration, is essential for four-dimensional (4D) radiotherapy. Surrogate-based and internal-fiducial-based methods may suffer from one or many drawbacks such as false correlation, being invasive, delivering extra patient radiation, and requiring complicated hardware and software development and implementation. In this paper we develop a simple non-surrogate, non-invasive method to monitor respiratory motion during radiotherapy treatments in real time. This method directly utilizes the treatment beam and thus imposes no additional radiation to the patient. The method requires a pre-treatment 4DCT and a real-time detector system. The method combines off-line processes with on-line processes. The off-line processes include 4DCT imaging and pre-calculating detector signals at each phase of the 4DCT based on the planned fluence map and the detector response function. The on-line processes include measuring detector signal from the treatment beam, and correlating the measured detector signal with the pre-calculated signals. The respiration phase is determined as the position of peak correlation. We tested our method with extensive simulations based on a TomoTherapy machine and a 4DCT of a lung cancer patient. Three types of simulations were implemented to mimic the clinical situations. Each type of simulation used three different TomoTherapy delivery sinograms, each with 800 to 1000 projections, as input fluences. Three arbitrary breathing patterns were simulated and two dose levels, 2 Gy/fraction and 2 cGy/fraction, were used for simulations to study the robustness of this method against detector quantum noise. The algorithm was used to determine the breathing phases and this result was compared with the simulated breathing patterns. For the 2 Gy/fraction simulations, the respiration phases were accurately determined within one phase error in real time for most projections of the treatment, except for a few projections at the start and end of the treatment in which beam intensities were extremely low. At 2 cGy/fraction dose level, the method can still determine the respiration phase very well with less than 10% of projections having more than two phases (∼1 s) error. This technique can also be applied in other delivery systems such as orthogonal x-ray systems, although in those cases it would entail the delivery of additional non-treatment radiation.

In VitroDetermination of the Optimal Particle Size for Nebulized Aerosol Delivery to Infants

We investigated the in vitro influence of breathing patterns on lung dose (LD) and particle size distribution in an infant upper airway cast model in order to determine the optimal particle size for nebulized aerosol delivery to infants. Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200 mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm, respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8-30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p < 0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4 microm) through the upper airway cast showed a negative correlation with increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available as LD for all simulated breathing pattern showed a particle size distribution with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From our in vitro study, we conclude that the optimal particle size for nebulized aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.

Modeling Age-Related Particle Deposition in Humans

Inhalation of airborne material poses a potential health risk to various subpopulations one of which is children. Little is known about the fate of particles in the respiratory tracts of children. Modeling efforts have been limited due largely to the lack of adequate information on lung geometry during growth. Lung morphometry measurements in children and adults between 3 months and 21 years of age were used to create 5-lobe lung geometries. Each lobe had a dichotomous, symmetric branching structure and was structurally different from the other lobes. The lung geometries were used in a multiple-path particle deposition model to calculate particle deposition fractions in different regions, lobes and airway generations of the lungs. Simulated breathing patterns were representative of resting breathing. Age-dependent, semi-empirical expressions of particles losses in the nasal airways, which were based on fits to the available experimental measurements, showed larger nasal deposition in adults than in children. Predicted tracheobronchial deposition patterns were similar among different ages for a given particle size. In the alveolar region, the predicted deposition fraction varied with age such that a clear trend could not be identified. Deposition fraction in a lobe was proportional to the volume of air going to that lobe. Deposition fractions in the lower left and right lobes were similar but higher than those in the other lobes for a given particle diameter. Lobar deposition fraction adjusted for lobar lung volume or lung deposition fraction adjusted for lung volume was found to be a unique property for an individual and presented a means for age-dependent deposition comparisons. The adjusted tracheobronchial and pulmonary deposition fractions were greatest for infants and decreased with age. A similar trend was also observed for deposition fraction per unit area as a function of airway generation. The distribution of particle deposition fraction per unit surface area varied with particle size for an individual, with ultrafine particles being more uniformly distributed throughout the lungs and coarse particles depositing primarily in the first few tracheobronchial airways. The trend of particle deposition with age indicates that children, particularly infants, may be at a greater health risk from exposure to airborne particulate matter and noxious materials all other conditions being equal. The age-dependent predicted deposition fraction pattern per unit area of different size particles has implications in the calculation of inhaled reference concentrations as well as site-specific delivery of drugs and other therapeutic compounds to the lungs of patients.

Predicting in vivo aerosol delivery using simulated breathing patterns

Predicting in vivo aerosol delivery using simulated breathing patterns

Breathing patterns and aerosol delivery: impact of regular human patterns, and sine and square waveforms on rate of delivery.

In vitro tests are commonly employed to assess nebulizer performance. Whether the square or sine waveforms employed during in vitro tests could alter the nebulizer performance compared to that observed when a patient breathes through the nebulizer is debatable. Accordingly, the aim of this in vitro study was to compare the rates of delivery from nebulizers with simulated human breathing patterns to those obtained with matching sine and square waveforms. Regular human breathing patterns with tidal volumes (VT) of approximately 40, approximately 200, approximately 500, and approximately 800 mL were selected. Sine and square waveforms that matched the VT, peak inspiratory flow rate (PIF), breathing frequency (f), and inspiratory duty cycle (t(i)/t(tot)) of the human breathing patterns were created with a breathing simulator. The rate of delivery of nebulized technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTC-DTPA) from two different jet nebulizer brands was determined. The rate of delivery was defined as the amount of the 99mTC-DTPA deposited during 30 sec of nebulization on a filter placed between the nebulizer and the breathing simulator. The rate of delivery of 99mTC-DTPA with the human breathing pattern was similar to that measured with the matching sine or square waveforms for either nebulizer. The configuration of the breath (PIF, VT, f, t(i)/t(tot)) did, however, influence the rate of delivery. In conclusion, the shape of the waveform, in other words, one resulting from a human breathing pattern, or a matching sine or square waveform, did not influence the rate of 99mTC-DTPA delivery from a nebulizer in vitro.

In Vitro Comparison of Beclomethasone and Salbutamol Metered-Dose Inhaler Aerosols Inhaled During Pediatric Tidal Breathing From Four Valved Holding Chambers

To determine the amount of salbutamol or beclomethasone delivered from metered-dose inhalers (MDIs) in particle sizes appropriate for inhalational treatment with four common holding chambers (AeroChamber, OptiChamber, Space Chamber, E-Z Spacer) when used under simulated pediatric tidal breathing conditions. Five devices of each type were tested with salbutamol (100 microg, Glaxo-Wellcome) and beclomethasone (50 microg, Glaxo-Wellcome) MDIs. Each device was connected to face replicas representative of 7-month-old (infant), 2-year-old (toddler), and 4-year-old (child) children and aerosol inhaled into a cascade impactor (Anderson) using a valve system and simulated tidal breathing patterns representative of children of these ages. Amounts of drug inhaled in fine particles varied significantly between devices and ages (p < 0.01), eg, for beclomethasone, from 4 microg (infant, Space Chamber) to 8 microg (toddler, OptiChamber), and for salbutamol, from 18 to 36 microg. The AeroChamber and OptiChamber behaved quite similarly, delivering more drug in the fine particles than the other two devices, and having insignificant variations in these amounts with age (p > 0.05). Amounts of drug inhaled in fine particles during pediatric tidal breathing from valved holding chambers are dependent on the holding chamber model, the drug used, and the breathing pattern, although dependence on the breathing pattern is relatively small for some of the devices tested.

A Review of Issues Relating to Nebulizer Standards

The standardization of in vitro bench-top assessment of nebulizer performance could prove to be extremely beneficial in the advancement of aerosol delivered by nebulizers. At the present time, there is considerable confusion as to how different nebulizer systems perform. Clinical in vivo tests are often compromised, as high patient variability requires large study numbers before differences become significant. In vitro tests should offer less variability and much lower costs, but the test criteria must be standardized and be clinically representative. Standard methods to assess nebulizer performance should therefore be designed to reflect the clinical situation as far as practicable. This would incorporate test methods involving: 1. simulated breathing patterns to estimate the amount of aerosol released and inhaled 2. use of solute tracers to measure aerosol release of salts or drugs themselves 3. use of aerosol sizing instruments such as low-flow cascade impactors that would reflect in vivo deposition. Standards must be written to accommodate the variety of existing devices currently on the market. Because standards take a significant time (typically 1-3 years) to prepare and are intended to operate for a further 10 or more years, they should also aim to accommodate possible advancements in device technology. The potential for such developments should not be overlooked in preparing a standard for in vitro testing of nebulization devices.

Drug Nebuliser Design and Performance: Breath Enhanced Jet Vs. Constant Output Jet Vs. Ultrasonic

Journal of Aerosol MedicineVol. 8, No. 3 Drug Nebuliser Design and Performance: Breath Enhanced Jet Vs. Constant Output Jet Vs. UltrasonicJ.H. DENNISJ.H. DENNISSearch for more papers by this authorPublished Online:4 Feb 2009https://doi.org/10.1089/jam.1995.8.277AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byNovel Test Bench for Inhaler Characterization Including Real-Time Determination of Output, Output Rate, and Liquid Water Content of Delivered Aerosols Felix C. Wiegandt, Ulrich P. Froriep, Theodor Doll, Andreas Dietzel, and Gerhard Pohlmann3 February 2021 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 34, No. 1A current update on advanced drug delivery devices for nasal and pulmonary administrationInsight into pulmonary drug delivery: Mechanism of drug deposition to device characterization and regulatory requirementsPulmonary Pharmacology & Therapeutics, Vol. 54Nebulized Medications for the Treatment of Dyspnea: A Literature Review Jackelyn Y. Boyden, Stephen R. Connor, Lily Otolorin, Steven D. Nathan, Perry G. Fine, Malene S. Davis, and J. Cameron Muir4 February 2015 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 28, No. 1Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy29 April 2014 | Human Gene Therapy Clinical Development, Vol. 2Aerosol Delivery of DNA/Liposomes to the Lung for Cystic Fibrosis Gene Therapy Lee A. Davies, Graciela A. Nunez-Alonso, Gerry McLachlan, Stephen C. Hyde, and Deborah R. Gill28 April 2014 | Human Gene Therapy Clinical Development, Vol. 25, No. 2Aerosol Delivery to the Lung Is More Efficient Using an Extension with a Standard Jet Nebulizer than an Open-Vent Jet Nebulizer L. Pitance, G. Reychler, T. Leal, H. Reychler, G. Liistro, J. Montharu, Tech Lab, P. Diot, and L. Vecellio26 July 2013 | Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol. 26, No. 4Darreichungsformen, Formulierungen und Depositionscharakteristika24 August 2011 | Pharmazie in unserer Zeit, Vol. 40, No. 5Pulmonary Drug Delivery System for inhalation therapy in mechanically ventilated patients9 January 2014 | Expert Review of Medical Devices, Vol. 5, No. 1Evaluation of an in vitro in vivo correlation for nebulizer delivery using artificial neural networksJournal of Pharmaceutical Sciences, Vol. 96, No. 12Optimizing Aerosol Gene Delivery and Expression in the Ovine LungMolecular Therapy, Vol. 15, No. 2Nebulized Drug Admixtures: Effect on Aerosol Characteristics and Albuterol Output Ariel Berlinski and J. Clifford Waldrep29 December 2006 | Journal of Aerosol Medicine, Vol. 19, No. 4Aerosolised antibiotics: a critical appraisal of their use22 December 2005 | Expert Opinion on Drug Delivery, Vol. 3, No. 1In Vitro Estimations of In Vivo Jet Nebulizer Efficiency Using Actual and Simulated Tidal Breathing Patterns Andrew P. Bosco, Rod G. Rhem, and Myrna B. Dolovich27 December 2005 | Journal of Aerosol Medicine, Vol. 18, No. 4Electrohydrodynamic Comminution: A Novel Technique for the Aerosolisation of Plasmid DNA3 August 2005 | Pharmaceutical Research, Vol. 22, No. 8The Effect of Breathing Pattern on Nebulizer Drug Delivery A. P. Roth, C. F. Lange, and W. H. Finlay7 July 2004 | Journal of Aerosol Medicine, Vol. 16, No. 3A Widely Available Method for the Assessment of Aerosol Delivery in Cystic FibrosisPulmonary Pharmacology & Therapeutics, Vol. 15, No. 6An Investigation of In Vitro/In Vivo Correlations for Salbutamol Nebulized by Eight Systems V.L. Silkstone, J.H. Dennis, C.A. Pieron, and H. Chrystyn7 July 2004 | Journal of Aerosol Medicine, Vol. 15, No. 3New Nebulizer Technology23 August 2013Aerosol Characterization of Nebulized Intranasal Glucocorticoid Formulations Ariel Berlinski and J. Clifford Waldrep7 July 2004 | Journal of Aerosol Medicine, Vol. 14, No. 2Bench Testing of Nebulizers: A Comparison of Three Methods THOMAS G. O'RIORDAN, MICHAEL D. WEINSTEIN, and YONGMING MAO30 January 2009 | Journal of Aerosol Medicine, Vol. 12, No. 2Drug administration by jet nebulizationPediatric Pulmonology, Vol. 26, No. 6Symposium Session Summaries: Sessions 19.1 to 21.4Pediatric Pulmonology, Vol. 26, No. S17A Review of Issues Relating to Nebulizer Standards JOHN H. DENNIS25 March 2010 | Journal of Aerosol Medicine, Vol. 11, No. s1Variations in Predicted Regional Lung Deposition of Salbutamol Sulphate Between 19 Nebulizer Types W.H. FINLAY, K.W. STAPLETON, and P. ZUBERBUHLER30 January 2009 | Journal of Aerosol Medicine, Vol. 11, No. 2Aerosol deposition in equine lungs following ultrasonic nebulisation versus jet aerosol delivery systemEquine Veterinary Journal, Vol. 29, No. 5Workshop Definitions and Standards30 January 2009 | Journal of Aerosol Medicine, Vol. 10, No. 3Effect of Aerosol Delivery System and Formulation on Nebulized Budesonide Output ARIEL BERLINSKI and J. CLIFFORD WALDREP30 January 2009 | Journal of Aerosol Medicine, Vol. 10, No. 4Fifth Symposium on Aerosols and the Lung19 March 2009 | Journal of Aerosol Medicine, Vol. 9, No. 4 Volume 8Issue 3Jan 1995 To cite this article:J.H. DENNIS.Drug Nebuliser Design and Performance: Breath Enhanced Jet Vs. Constant Output Jet Vs. Ultrasonic.Journal of Aerosol Medicine.Jan 1995.277-280.http://doi.org/10.1089/jam.1995.8.277Published in Volume: 8 Issue 3: February 4, 2009PDF download