Inhalation Patterns Research Articles

The role of home polygraphy sleep studies in the diagnosis of catathrenia.

Catathrenia is an uncommon sleep disorder. Having been originally classified as a parasomnia it is now considered a sleep related breathing disorder. Polysomnography (PSG) is the gold standard for diagnosing catathrenia which demonstrates a classic pattern of a deep inhalation followed by a protracted exhalation, accompanied by groaning sounds. Home polygraphy sleep studies are widely used to assess for sleep disordered breathing and have previously been demonstrated to yield sufficient evidence to warrant a suspicion of catathrenia, later confirmed by PSG. We present sleep studies from five patients presenting with fragmented sleep and daytime somnolence. Two were clinically suspicious for a diagnosis of catathrenia with the remaining patients suspected as having obstructive sleep apnea. Analysis of their sleep studies identified changes in flow and effort consistent with those found on PSG in catathrenia. Analysis of concomitant sound recordings revealed groaning and moaning sounds different to any recorded snoring. Our findings demonstrate that polygraphy sleep studies demonstrating an initial positive inflection in flow, immediately followed by a fall in flow and a slow attenuation in both thoracic and abdominal effort signals are suggestive of a catathrenia diagnosis. Careful analysis of traces is required to prevent misdiagnosis of central events.

Rapid deposition analysis of inhaled aerosols in human airways

A rapid data-driven method for determining regional deposition of inhaled medication aerosols in human airways is presented, which is patient specific. Inhalation patterns, device characteristics, and aerodynamic particle size distribution of medications are considered. The method is developed using dimensional analysis and Buckingham Pi theorem, and provides total, regional, and lobar distributions of aerosol deposition. 34 dimensionless quantities are selected, of which 22 encode features of the airway trees and segmented lobes, 14 pertain to the device and the drug formulation, and 13 the inhalation profile of the subject. The dimensionless correlations are obtained using a large database of computational fluid dynamics results on patient specific airways. The intraclass correlation coefficient between the current method and its training dataset is 0.92. The difference between the predicted average lobar deposition in the six asthma patients and the in-vivo data is 1.3%. The model has the potential to offer insights into the effectiveness of personalized drug delivery in clinical settings and can aid in drug development cycles.

Real-Time Particle Emission Monitoring for the Non-Invasive Prediction of Lung Deposition via a Dry Powder Inhaler

Although inhalation therapy represents a promising drug delivery route for the treatment of respiratory diseases, the real-time evaluation of lung drug deposition remains an area yet to be fully explored. To evaluate the utility of the photo reflection method (PRM) as a real-time non-invasive monitoring of pulmonary drug delivery, the relationship between particle emission signals measured by the PRM and in vitro inhalation performance was evaluated in this study. Symbicort® Turbuhaler® was used as a model dry powder inhaler. In vitro aerodynamic particle deposition was evaluated using a twin-stage liquid impinger (TSLI). Four different inhalation patterns were defined based on the slope of increased flow rate (4.9–9.8 L/s2) and peak flow rate (30 L/min and 60 L/min). The inhalation flow rate and particle emission profile were measured using an inhalation flow meter and a PRM drug release detector, respectively. The inhalation performance was characterized by output efficiency (OE, %) and stage 2 deposition of TSLI (an index of the deagglomerating efficiency, St2, %). The OE × St2 is defined as the amount delivered to the lungs. The particle emissions generated by four different inhalation patterns were completed within 0.4 s after the start of inhalation, and were observed as a sharper and larger peak under conditions of a higher flow increase rate. These were significantly correlated between the OE or OE × St2 and the photo reflection signal (p < 0.001). The particle emission signal by PRM could be a useful non-invasive real-time monitoring tool for dry powder inhalers.Graphical

An Automated "Hands-Off" Method for Sampling Mainstream Smoke from Cannabis Cigarettes.

A simple-to-use, portable, and relatively inexpensive system for characterizing the chemical components of mainstream smoke from cannabis cigarettes was developed and tested by using commercial hemp cigarettes. The system is described, and its performance for reproducing actual user puff topographies is shown along with extensive chemical analysis data, including PAHs, carbonyls, and organic and elemental carbon, for a small set of initial samples. By using a solid-state flow meter and fast-response mass flow controller, the prototype can reproduce measured puff topography with excellent fidelity, which will allow users to accurately reproduce the actual inhalation patterns for various types of smoking products and consumers, and to collect samples of mainstream smoke without the need to bring test subjects or controlled substances into a laboratory.

Investigating factors in indoor transmission of respiratory disease through agent‐based modeling

AbstractThe transmission of respiratory diseases such as COVID‐19 is exacerbated in densely populated urban areas and crowded indoor settings. Despite the majority of transmissions occurring in such settings, controlling viral spread through individual‐level contacts indoors remains challenging. Experimental studies have investigated the transmission patterns of respiratory behaviors such as coughing or sneezing in controlled spatial environments. However, the effects of dynamic movement and spatial structures have been ignored, making it difficult to apply findings to urban policy and planning. To address this gap, we developed agent‐based simulations to investigate individual virus inhalation patterns across multiple scenarios in a symmetrical and formulaic indoor space. We conducted sensitivity analysis using regression emulator models to identify significant factors for viral transmission. Our results indicate positive associations with viral transmission in descending order of: (1) stay time; (2) encounter frequency; and (3) initial infected population; while negative associations are: (4) mask wearing; (5) distance to infected people; (6) nearest infected people's mask wearing; and (7) distance to entrance. We also found that narrow passages between obstacles increase virus transmission from breathing. Furthermore, we conducted a case study to investigate the potential of reducing the amount of individually inhaled virus by controlling behaviors and spatial environments. Our findings suggest that mask wearing and reduced stay time can substantially reduce transmission risk, while a large number of contacts and high grouping time result in the growth of the infected population at a certain threshold. These results provide guidance for decision makers to formulate guidelines for curbing the spread of respiratory diseases in indoor spaces.

Exposure Assessment of Air Pollution in Lungs

In this article, a comprehensive literature survey on air pollution and its effects on the human respiratory system is carried out. Based on the knowledge gaps, a computational assessment is proposed to find the impact of air quality on respiratory suspended particulate matter (RSPM) deposition in the human airways. A realistic 3D geometric model of the human airway was constructed to study the airflow characteristics and RSPM (PM2.5 and PM10) transport and deposition in it for normal and moderate inhalation patterns (corresponding to natural breathing) of air having an unhealthy air quality index (AQI). The results identify inertial impact as the primary mechanism of particle deposition in the human airways. They also reveals the significant differences in the deposition patterns of PM2.5 and PM10 in the right and left bronchial airways.

CHARACTERISTICS OF BUDEFORU® FOR BUDESONIDE AND FORMOTEROL MIXTURE

Recently, BudeForu® (BF), a generic of Symbicort Turbuhaler® (SMB), is widely used in Japan. Although appearance of BF resembles to SMB, several differences in length, weight, and side-hole sizes are seen with precise inspection. As particle releases from the inhalation device is strongly influenced by its mechanical characteristics, we compared their particle release patterns. An inhalation simulator generated either ramp-up or triangular (time to reach peak inhaling flow (PIF) = 0.42 s) inhalation pattern. Time trajectories of inhaled flow and released particles from either device were depicted with a photo-reflection method. Internal resistances of them were also measured. Particle release patterns of both dry powder inhalers resembled each other. Immediately after release from the inhaler, they reached the peak value and then completed in 0.5 s. In either ramp-up or triangular inspiration pattern, a single burst developed at early inhalation. There were linear relationships between PIFs and emitted doses. The regression lines using ramp-up patters were: Y = 0.00241 X - 0.039, r2 = 0.700, p ＜ 0.0001 (BF), Y = 0.00210 X - 0.038, r2 = 0.654, p ＜ 0.0001 (SMB), and those using triangular patterns were: Y = 0.00223X － 0.0015, r2 = 0.445, p ＜ 0.0001 (BF), and Y = 0.00229X － 0.0023, r2 = 0.687, p ＜ 0.0001 (SMB). Internal resistances of the BF and SMB were 0.105±0.004 and 0.119±0.105 cmH2O0.5/L/min respectively. Present experimental study suggested that aerodynamic characteristics of BF were quite similar to those of SMB.

In-vitro measurement of aerosol generated by Respimat SMI penetrating through upper airways

Respimat soft mist inhaler (SMI) is an inhaler producing a soft mist with low velocity. The liquid drug solution is emitted by the mechanical energy of compressed spring, so the device is propellant-free. This paper describes the measurement of particle fraction penetrating through the model of the upper respiratory tract (mouth cavity, pharynx, larynx trachea). The solution inside the cartridge was marked by fluorescein in order to evaluate the regional particle deposition in the model. After the exposition, segments of the model, as well as the filter, were washed out and the deposited fluorescein was extracted into water. The analysis showed that the fraction of particles penetrating through the upper respiratory tract was 64.7±6.7 %. However, the real inhalation pattern was not simulated and measurement was provided with continual “inhalation” without “exhalation”.

Effect of inner physical properties on powder adhesion in inhalation capsules in case of a high resistance device.

The inhalation performance of a dry powder inhaler (DPI) depends on the inhalation patterns of patients, inhalation particle characteristics and inhalation devices. In capsule-based DPIs, the capsule plays an important role in the dispersion of inhalation particles. The present study investigated the effects of inner physical properties of capsules on drug release from capsules-based DPIs with high resistance device. Atomic force microscopy (AFM) was used to evaluate the capsule physical properties, such as the capsule inner structure and surface potential, of three capsules with different compositions (G-Cap, PEG/G-Cap, and HPMC-Cap). As a model dry powder for capsule-based DPIs, the dry powder in Spiriva® Inhalation Capsules containing tiotropium bromide was used. Inhalation performance was evaluated using a twin-stage liquid impinge and Handihaler® (flow rate 30 l/min). The results indicated that the capsule inner surface presented with numerous valleys and mountains, regardless of the capsule type. Furthermore, the valley and mountain areas on the capsule inner surface showed a significantly higher or lower surface potential. Following inhalation of capsule-based DPIs, the drug remained in the valleys on the capsule inner surface; however, no significant difference was observed in the drug release from capsule and lung drug delivery. Therefore, inhalation performance in capsule-based DPIs when a high resistance device, such as Handihaler®, is used at an appropriately flow rate is not markedly affected by the physical properties of the capsule inner surface due to capsule composition.

Effect of swirling flow and particle-release pattern on drug delivery to human tracheobronchial airways

The present study aims to investigate the effect of swirling flow on particle deposition in a realistic human airway. A computational fluid dynamic (CFD) model was utilized for the simulation of oral inhalation and particle transport patterns, considering the k-ω turbulence model. Lagrangian particle tracking was used to track the particles' trajectories. A normal breathing condition (30 L/min) was applied, and two-micron particles were injected into the mouth, considering swirling flow to the oral inhalation airflow. Different cases were considered for releasing the particles, which evaluated the impacts of various parameters on the deposition efficiency (DE), including the swirl intensity, injection location and pattern of the particle. The work's novelty is applying several injection locations and diameters simultaneously. The results show that the swirling flow enhances the particle deposition efficiency (20-40%) versus no-swirl flow, especially in the mouth. However, releasing particles inside the mouth, or injecting them randomly with a smaller injection diameter (dinj) reduced DE in swirling flow condition, about 50 to 80%. Injecting particles inside the mouth can decrease DE by about 20%, and releasing particles with smaller dinj leads to 50% less DE in swirling flow. In conclusion, it is indicated that the airflow condition is an important parameter for a reliable drug delivery, and it is more beneficial to keep the inflow uniform and avoid swirling flow.

Cognitive and hormonal regulation of appetite for food presented in the olfactory and visual modalities

The ability to regulate appetite is essential to avoid food over-consumption. The desire for a particular food can be triggered by its odor before it is even seen. Using fMRI, we identify the neural systems modulated by cognitive regulation when experiencing appetizing food stimuli presented in both olfactory and visual modalities, while being hungry. Regulatory instruction modulated bids for food items and inhalation patterns. Distinct brain regions were observed for up and down appetite-regulation, respectively the dorsomedial prefrontal cortex (dmPFC) and dorsolateral PFC. Food valuation engaged the ventromedial PFC and bilateral striatum. Furthermore, we identified a neurobiological marker for successful appetite upregulation. Individuals with higher blood levels of ghrelin were better at exercising up-regulation, and engaged the dmPFC more. These findings characterize the neural circuitry regulating food consumption within the healthy population and highlight how cognitive regulation modulates olfactomotor measures of olfaction.

Regional Deposition: Targeting.

Patterns of regional aerosol deposition within the lungs are known to vary in a predictable manner with a number of factors, most notably aerodynamic particle size and inhalation pattern. Targeting deposition involves the intentional manipulation of one or more of these factors to promote aerosol deposition in certain locations within the respiratory tract. This section will begin by exploring existing evidence supporting the need to target regional deposition. Thereafter, various approaches to targeting will be introduced. In addition to control of aerodynamic particle size and inhalation pattern, a collection of approaches are available through which to passively target deposition to more central or peripheral lung regions. These include the delivery of short aerosol boluses at prescribed time points in inhalation, control of transient hygroscopic aerosol size changes during transport through the respiratory tract, and use of alternative carrier gas mixtures such as helium/oxygen mixtures. Comparatively, targeting aerosol deposition locally to very precise, spatially-defined lung regions is in its infancy. Early, exploratory techniques used for local targeting will be described. The continued evolution of deposition targeting towards ever more specific locations within the lungs is required to explore fundamental research questions in aerosol medicine: namely, how precise does targeting need to be before additional refinement fails to produce appreciably different therapeutic effects, and which nascent applications of aerosols in medicine might benefit from more selective regional targeting?

Multispecies aerosol evolution and deposition in a human respiratory tract cast model

Accurate predictions of aerosol transport, evolution, and deposition in the human airways are crucial for inhalation dosimetry investigations. Inhaled aerosol transported through the airways undergoes thermodynamic changes due to changes in temperature and humidity. Aerosol evolution processes are particularly important for liquid multispecies aerosols. These aerosols are sensitive to condensation and/or evaporation dynamics, which can modify gas/liquid partitioning of each species and particle size distribution. In this manuscript, we present computational fluid dynamics simulations of complex aerosol mixtures in a realistic geometry of the human respiratory tract cast model. We used a publicly available computational framework, AeroSolved, developed for simulation of evolving multispecies aerosol mixtures. We evaluated the dynamics of liquid particles in physiologically relevant conditions of 100% relative humidity at the temperature of 37°C. We studied two separate inhalation flow scenarios: in the first case, a warm aerosol at 50°C was inhaled and subsequently cooled down while flowing in the airways. In the second case, an aerosol at room temperature was inhaled and heated up to the temperature of 37°C. Our results demonstrated that aerosol evolution mainly occurs in the upper segments of the airways (throat and trachea) at the very short timescales. Apart from showing the significant influence of temperature and humidity conditions on aerosol dynamics and evolution, we also measured aerosol deposition fluxes investigating the dependence of the delivered aerosol mass on evolution mechanisms. We showed that the delivered regional mass of each species depends on the physico-chemical properties of the mixture, and it is also significantly influenced by the airways’ humidity and thermal conditions. It was also shown that the species-specific properties of the liquid mixture (e.g., activity coefficient) play an important role in gas/liquid partitioning of the species. With AeroSolved such dependencies can be further investigated with greater attention towards specific needs and physiologically important conditions (e.g., transient flow inhalation patterns, aerosol mixture composition and its properties).

Correcting Photo Reflection Method Output and Its Application in the Dynamic Analysis of Particle Release from Dry Powder Inhalers.

Background: The photo reflection method (PRM) is used to measure light reflected from particles released from dry powder inhalers (DPIs). This simple method depicts time trajectories of released drugs; however, it underestimates the number of particles at high peak inhalation flow rates (PIFs). In this study, we aimed to correct this underestimation and clarify whether long inhalation is necessary for capsule-type DPIs, using this unique method. Methods: To establish quantitative measurements using the PRM, several types of DPIs were inhaled with square-wave inhalations at different PIFs using an inhalation simulator, and the total emitted dose (TED) and the release time of the TED (TTED) were measured. Next, capsule-type DPIs were inhaled using inhalation patterns of patients with chronic obstructive pulmonary disease (COPD), and particle release time trajectories were recorded. Results: For all DPIs, except for Turbuhaler® (TBH), both TED and TTED were hyperbolically decreased with an increase in the PIF of square-wave inhalations. TED correction using the TTED showed flat TED changes at high PIF ranges. The patient inhalation analysis showed that the corrected TEDs of seven COPD inhalation patterns were not significantly different. The PRM further revealed that the inhaled flow rate and release time of all seven patterns were sufficient to release particles in the capsule. Conclusions: The inhaled flow rate and TTED that exceeded specific conditions enabled complete particle release from the DPIs except for TBH. Therefore, an extremely long inhalation is not required for capsule-type DPIs. Our corrected time trajectory analysis using the PRM provides a new strategy for the particle release analysis of DPIs.

1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling.

(1) Background: Inhalant abuse and misuse are still widespread problems. 1,1-Difluoroethane abuse is reported to be potentially fatal and to cause acute and chronic adverse health effects. Lab testing for difluoroethane is seldom done, partly because the maximum detection time (MDT) is unknown. We sought to reliably estimate the MDT of difluoroethane in blood after inhalation abuse; (2) Methods: MDT were estimated for the adult male American population using a physiologically based pharmacokinetic (PBPK) model and abuse patterns detailed by two individuals. Based on sensitivity analyses, variability in huffing pattern and body mass index was introduced in the model by Monte Carlo simulation; (3) Results: With a detection limit of 0.14 mg/L, the median MDT was estimated to be 10.5 h (5th–95th percentile 7.8–12.8 h) after the 2-h abuse scenario and 13.5 h (10.5–15.8 h) after the 6-h scenario. The ranges reflect variability in body mass index and hence amount of body fat; (4) Conclusions: Our simulations suggest that the MDT of difluoroethane in blood after abuse ranges from 7.8 to 15.8 h. Although shorter compared to many other drugs, these MDT are sufficient to allow for testing several hours after suspected intoxication in a patient.

The effect of mode of inhaled salbutamol delivery on measures of small airways obstruction in asthma: a comparison of treatment delivered via spacer and nebuliser

Background Conventional clinical respiratory tests tell us little about the small airways of the lung (less than 2 mm in internal diameter). Patients with asthma affecting the small airways may respond differently to inhaled bronchodilator treatment (salbutamol) depending on the method of administration. Aims In this study, we aimed to assess if there was a difference in the effect of salbutamol treatment via metered-dose inhaler (MDI) and spacer compared to via nebuliser on measures of small airways function. It was hypothesised that the nebulised salbutamol would have a greater effect on the outcome measures due to the particle size being more appropriate for penetrating the smaller airways. Methods Two visits were completed by 14 participants with stable asthma. At both visits, lung function tests were completed both before and after administration of 1 mg salbutamol to measure airway obstruction (spirometry), mechanical load to ventilation (impulse oscillometry), and ventilation heterogeneity (multiple breath nitrogen washout). At visit one, seven participants were randomized to take salbutamol via MDI and spacer, and seven via nebuliser. At visit two, all participants took salbutamol via whichever method they had not been given at visit one. Results Results indicated that participants given salbutamol via MDI and spacer (compared to via nebuliser) showed a greater improvement, which was statistically significant, between the pre- and post-salbutamol values for most lung function tests. Discussion This result was unexpected and may have been due to greater wastage of drug via nebuliser than via MDI and spacer, and differing inhalation patterns. Tidal breathing during nebulised administration, and deep inhalation during use of MDI and spacer, could have affected the delivery of the drug. Conclusion This study implies that taking salbutamol via MDI and spacer would be beneficial if higher doses (e.g. 1 mg) were taken.

Investigation of inhalation and exhalation flow pattern in a realistic human upper airway model by PIV experiments and CFD simulations.

In this study, flow field characteristics in the trachea region in a realistic human upper airway model were firstly measured by particle image velocimetry (PIV) in the air under three constant inhalation and exhalation conditions: 36L/min, 64L/min and 90L/min, representing flow rates of 18L/min, 32L/min and 45L/min in real human airway (the model was twice the size of a human airway). Computational fluid dynamics (CFD) analyses were performed on four turbulence models, with boundary conditions corresponding to the PIV experiments. The effects of flow rates and breathing modes on the airflow patterns were investigated. The CFD prediction results were compared with the PIV measurements and showed relatively good agreement in all cases. During inhalation, the higher the flow rates, the less significant the "glottal jet" phenomenon, and the smaller the area of the separation zone. The air in the nasal inhalation condition accelerated more dramatically after glottis. The SST-Transition model was the best choice for predicting inhalation velocity profiles. For exhalation condition, the maximum velocity was much smaller than that during inhalation due to the more uniform flow field. The exhalation flow rates and breathing modes had little effect on the flow characteristics in the trachea region. The RNG k - ε model and SST k - ω model were recommended to simulate the flow field in the respiratory tract during exhalation.

Foreign Body Inhalation: A shift in Clinical Pattern

Background: Foreign body inhalation is a common presentation in thoracic surgery and it is well known to present mainly in toddlers, commonly due to sun flower seeds or water melon seeds. Objectives: To determine the changes in clinical pattern of foreign body inhalation regarding the age, sex, and type of foreign body. Methods: This is a case series study of patients with foreign body inhalation admitted to Al-Jumhori teaching hospital in Mosul. The parameters used in this study are sex, age group and type of foreign body. Results: The main age group affected was adolescents, and the commonest foreign body inhaled was the veil pin. Conclusion: The bad habit of holding pins in mouth while doing other things with your hand has led to this change in clinical pattern of foreign body inhalation.

Is "Slow Inhalation" Always Suitable for Pressurized Metered Dose Inhaler?

To achieve adequate inhalation therapy, a proper inhalation technique is needed in clinical practice. However, there is limited information on proper inhalation flow patterns of commercial inhalers. Here, we quantitatively estimated airway deposition of two commercial pressurized metered dose inhalers (pMDIs) to determine their optimal inhalation patterns. Sultanol® inhaler (drug particles suspended in a propellant, suspension-pMDI) and QVAR™ (drug dissolved in a propellant with ethanol, solution-pMDI) were used as model pMDIs. Aerodynamic properties of the two pMDIs were determined using an Andersen cascade impactor with human inhalation flow simulator developed by our laboratory. As indices of peripheral-airway drug deposition, fine particle fractions (FPFPA) at different inhalation flow rates were calculated. The time-dependent particle diameters of sprayed drug particles were determined by laser diffraction. On aerodynamic testing, FPFPA of suspension-pMDI significantly decreased depending on the increasing inhalation flow rate, while solution-pMDI achieved higher and constant FPFPA in the range of the tested inhalation flow rates. The particle diameter of solution-pMDI markedly decreased from 5 to 3μm in a time-dependent manner. Conversely, that of suspension-pMDI remained at 4μm during the spraying time. Although "slow inhalation" is recommended for pMDIs, airway drug deposition via solution-pMDI (extra-fine particles) is independent of patients' inhalation flow pattern. Clinical studies should be performed to validate instruction for use of pMDIs for each inhaler for the optimization of inhalation therapy.

Effect of Particle–Wall Interaction and Particle Shape on Particle Deposition Behavior in Human Respiratory System

Dry powder inhalation (DPI) has attracted much attention as a treatment for respiratory diseases owing to the large effective absorption area in a human respiratory system. Understanding the drug particle motion in the respiratory system and the deposition behavior is necessary to improve the efficiency of DPI. We conducted computer simulations using a model coupling a discrete element method and a computational fluid dynamics method (DEM-CFD) to evaluate the particle deposition in human respiratory system. A simple artificial respiratory model was developed, which numerically investigated the effect of particle properties and inhalation patterns on the particle deposition behavior. The DEM-CFD simulations demonstrated that the smaller- and lower-density particles showed higher reachability into the simple respiratory model, and the particle arrival ratio to the deep region strongly depended on the aerodynamic diameter. The particle arrival ratio can be described as an exponential function of the aerodynamic diameter. Furthermore, the exponential relationship between the particle reachability into the depth of the simple respiratory model and the aerodynamic diameter predicted the particle aerodynamic diameter based on the required reachability. The particle shape also had an impact on the particle deposition behavior. The rod-like particles with a larger aspect ratio indicated higher reachability into the depth of the simple respiratory model. This was attributed to the high velocity motion of the particles whose long axis was in the direction of the deep region.