Breathing Profiles Research Articles

Towards smart and secure batteries: Linking pressure and temperature profiles with electrochemical behavior through hybrid optical fiber sensors

A hybrid sensing configuration combining fiber Bragg grating (FBG) with a Fabry-Perot interferometer is proposed for highly sensitive detection of pressure and temperature inside a commercial lithium-ion battery (LiB). The battery is also instrumented externally with FBGs to monitor its surface temperature variations. The LiB is operated under several cycling tests at different C-rates and environmental temperatures. High pressure and temperature resolutions of ±0.4 mbar and ±0.5 °C, respectively, are attained for the developed hybrid sensor, along with a minimum response time of 1.7 s. When the LiB is subjected to higher environmental temperatures, reduced thermal variations and higher pressure variations are registered by the optical sensor. Overall, during the cycling tests, the external temperature sensors closely follows the internal sensors behavior. Incremental capacity analysis derivative curves were systematically applied throughout the battery cycling experiments to unveil relevant insights into the interplay between pressure and temperature variations and the LiB electrochemical behavior. It was found that the pressure fluctuations present a “breathing profile” directly linked with the volume electrode lithiation and delithiation processes.

Inhaled corticosteroid delivery is markedly affected by breathing pattern and valved holding chamber model.

There is a scarcity of high-quality research on the efficient delivery of inhaled corticosteroids using valved holding chambers (VHCs) in children. The delivered dose (DD) of fluticasone from a metered dose inhaler (pMDI) was tested using four VHCs: AeroChamber plus Flow-Vu (AC), Babyhaler (BH), EasyChamber (EC), and Optichamber Diamond (OD). The in vitro setup included an anatomical child throat model, Next Generation Impactor, and a breathing simulator to generate tidal breathing of a four and a 6-year-old child, and adult type single inhalation. OD showed the lowest proportion of fluticasone trapped in the throat with all breathing patterns. AC showed similar fine particle dose (FPD) in the respirable range (1-5 µm) irrespective of the breathing pattern. For BH, the median FPD 1-5 µm was highest during adult breathing. OD and EC showed higher overall DD and higher doses in the 1-5 µm range with paediatric breathing profiles compared to adult inhalation. The median DD and FPD 1-5 µm were significantly lower with BH compared to any other VHCs during tidal breathing. Compared to EC, the FPD of the other VHCs were skewed towards <2 µm particles. Fluticasone delivery is markedly affected by breathing pattern and VHC model. The observed differences in throat deposition and FPD delivered may have significant clinical implications for side effects and controlling airway inflammation. All VHCs intended for paediatric use should undergo testing using internationally recognised standardised methods incorporating clinically relevant paediatric breathing patterns.

Nebulization and In Vitro Upper Airway Deposition of Liposomal Carrier Systems.

Liposomal carrier systems have emerged as a promising technology for pulmonary drug delivery. This study focuses on two selected liposomal systems, namely, dipalmitoylphosphatidylcholine stabilized by phosphatidic acid and cholesterol (DPPC-PA-Chol) and dipalmitoylphosphatidylcholine stabilized by polyethylene glycol and cholesterol (DPPC-PEG-Chol). First, the research investigates the stability of these liposomal systems during the atomization process using different kinds of nebulizers (air-jet, vibrating mesh, and ultrasonic). The study further explores the aerodynamic particle size distribution of the aerosol generated by the nebulizers. The nebulizer that demonstrated optimal stability and particle size was selected for more detailed investigation, including Andersen cascade impactor measurements, an assessment of the influence of flow rate and breathing profiles on aerosol particle size, and an in vitro deposition study on a realistic replica of the upper airways. The most suitable combination of a nebulizer and liposomal system was DPPC-PA-Chol nebulized by a Pari LC Sprint Star in terms of stability and particle size. The influence of the inspiration flow rate on the particle size was not very strong but was not negligible either (decrease of Dv50 by 1.34 μm with the flow rate increase from 8 to 60 L/min). A similar effect was observed for realistic transient inhalation. According to the in vitro deposition measurement, approximately 90% and 70% of the aerosol penetrated downstream of the trachea using the stationary flow rate and the realistic breathing profile, respectively. These data provide an image of the potential applicability of liposomal carrier systems for nebulizer therapy. Regional lung drug deposition is patient-specific; therefore, deposition results might vary for different airway geometries. However, deposition measurement with realistic boundary conditions (airway geometry, breathing profile) brings a more realistic image of the drug delivery by the selected technology. Our results show how much data from cascade impactor testing or estimates from the fine fraction concept differ from those of a more realistic case.

The effect of lung emptying before the inhalation of aerosol drugs on drug deposition in the respiratory system

The amount of drug depositing in the airways depends, among others, on the inhalation manoeuvre and breathing parameters. The objective of this study was to quantify the effect of lung emptying before the inhalation of drugs on the lung doses. Thirty healthy adults were recruited. Their breathing profiles were recorded while inhaling through six different emptied DPI devices without breathe-out and after comfortable or forced exhalation. The corresponding emitted doses and aerosol size distributions were derived from the literature. The Stochastic Lung Model was used to estimate the deposited doses. In general, forceful exhalation caused increased flow rate and inhaled air volume. Increased flow rate led to the increase of the average lung dose for drugs with positive lung dose-flow rate correlation (e.g. Symbicort®: relative increase of 6.7%, Bufomix®: relative increase of 9.2%). For drugs with negative correlation of lung dose with flow rate (all the studied drugs except the above two) lung emptying caused increased (Foster® by 2.7%), almost unchanged (Seebri®, Relvar®, Bretaris®) and also decreased (Onbrez® by 6.6%) average lung dose. It is worth noting that there were significant inter-individual differences, and lung dose of each drug could be increased by a number of subjects. In conclusion, the change of lung dose depends on the degree of lung emptying, but it is also inhaler and drug specific. Forceful exhalation can help in increasing the lung dose only if the above specificities are taken into account.

A multimodal AI-based non-invasive COVID-19 grading framework powered by deep learning, manta ray, and fuzzy inference system from multimedia vital signs

The COVID-19 pandemic has presented unprecedented challenges to healthcare systems worldwide. One of the key challenges in controlling and managing the pandemic is accurate and rapid diagnosis of COVID-19 cases. Traditional diagnostic methods such as RT-PCR tests are time-consuming and require specialized equipment and trained personnel. Computer-aided diagnosis systems and artificial intelligence (AI) have emerged as promising tools for developing cost-effective and accurate diagnostic approaches. Most studies in this area have focused on diagnosing COVID-19 based on a single modality, such as chest X-rays or cough sounds. However, relying on a single modality may not accurately detect the virus, especially in its early stages. In this research, we propose a non-invasive diagnostic framework consisting of four cascaded layers that work together to accurately detect COVID-19 in patients. The first layer of the framework performs basic diagnostics such as patient temperature, blood oxygen level, and breathing profile, providing initial insights into the patient's condition. The second layer analyzes the coughing profile, while the third layer evaluates chest imaging data such as X-ray and CT scans. Finally, the fourth layer utilizes a fuzzy logic inference system based on the previous three layers to generate a reliable and accurate diagnosis. To evaluate the effectiveness of the proposed framework, we used two datasets: the Cough Dataset and the COVID-19 Radiography Database. The experimental results demonstrate that the proposed framework is effective and trustworthy in terms of accuracy, precision, sensitivity, specificity, F1-score, and balanced accuracy. The audio-based classification achieved an accuracy of 96.55%, while the CXR-based classification achieved an accuracy of 98.55%. The proposed framework has the potential to significantly improve the accuracy and speed of COVID-19 diagnosis, allowing for more effective control and management of the pandemic. Furthermore, the framework's non-invasive nature makes it a more attractive option for patients, reducing the risk of infection and discomfort associated with traditional diagnostic methods.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Effect of transient breathing cycle on the deposition of micro and nanoparticles on respiratory walls

Background and objectiveFrom various perspectives (e.g. inhalation exposure and drug delivery), it is important to provide insights into the behavior of inhaled particles in the human respiratory system. Although most of the experimental and numerical studies have relied on an assumption of steady inhalation, the transient breathing profile is a key factor in particle deposition in the respiratory tract. In this study, particle transportation and deposition were predicted in a realistic human airway model during a breathing cycle and the effects of steady-state and transient flows on the deposition fraction were observed using computational fluid dynamics. MethodsTwo transient breathing cycles with different respiratory durations were considered to evaluate the effects of respiration duration on particle transport and deposition characteristics. Two types of steady breathing conditions with corresponding steady-state respiratory volumes were reproduced. The Lagrangian discrete phase model approach was used to investigate particle transportation and deposition under transient breathing conditions. Additionally, the Eulerian approach was used to analyze the transport of nanoparticles in the gas phase. A total of >50,000 monodispersed particles with aerodynamic diameters ranging between 2 nm and 10 μm were selected for comprehensive deposition predictions for particle sizes ranging from the nano- to microscale. ResultsThe predicted results were compared with the experimental data. The particle deposition fraction in the nasal cavity and tracheal regions showed differences between the steady and transient simulations. In addition, particle analysis under steady inhalation conditions cannot accurately predict particle transportation and deposition in the lower airway. Furthermore, the breathing cycle had a significant effect on the deposition fraction of the particles and the behavior of the inhaled particles. ConclusionsTransient simulation mimicking the breathing cycle was observed to be an important factor in accurately predicting the transportation and deposition of particles in the respiratory tract.

Computational analysis of human upper airway aerodynamics.

There is a considerable interest in understanding transient human upper airway aerodynamics, especially in view of assessing the effects of various ventilation therapies. Experimental analyses in a patient-specific manner pose challenges as the upper airway consists of a narrow confined region with complex anatomy. Pressure measurements are feasible, but, for example, PIV experiments require special measures to accommodate for the light refraction by the model. Computational fluid dynamics can bridge the gap between limited experimental data and detailed flow features. This work aims to validate the use of combined lattice Boltzmann method and a large eddy scale model for simulating respiration, and to identify clinical features of the flow and show the clinical potential of the method. Airflow was computationally analyzed during a realistic, transient, breathing profile in an upper airway geometry ranging from nose to trachea, and the resulting pressure calculations were compared against in vitro experiments. Simulations were conducted on meshes containing about 1 billion cells to ensure accuracy and to capture intrinsic flow features. Airway pressures obtained from simulations and in vitro experiments are in good agreement both during inhalation and exhalation. High velocity pharyngeal and laryngeal jets and recirculation in the region of the olfactory cleft are observed. Graphical Abstract The Lattice-Boltzmann Method combined with Large Eddy Simulations was used to compute the aerodynamics in a human upper airway geometry. The left side of this graphical abstract shows the velocity and vorticity (middle figure in bottom row, and right figure of the right bottom figure) profiles at peak exhalation. The simulations were validated against experiments on a 3D-print of the geometry (shown in the top figures on the right hand side). The pressure drop (right bottom corner) shows a good agreement between experiments and simulations.

Surface tension effects on flow dynamics and alveolar mechanics in the acinar region of human lung

BackgroundComputational fluid dynamics (CFD) simulations, in-vitro setups, and experimental ex-vivo approaches have been applied to numerous alveolar geometries over the past years. They aimed to study and examine airflow patterns, particle transport, particle propagation depth, particle residence times, and particle-alveolar wall deposition fractions. These studies are imperative to both pharmaceutical and toxicological studies, especially nowadays with the escalation of the menacing COVID-19 virus. However, most of these studies ignored the surfactant layer that covers the alveoli and the effect of the air-surfactant surface tension on flow dynamics and air-alveolar surface mechanics. MethodsThe present study employs a realistic human breathing profile of 4.75s for one complete breathing cycle to emphasize the importance of the surfactant layer by numerically comparing airflow phenomena between a surfactant-enriched and surfactant-deficient model. The acinar model exhibits physiologically accurate alveolar and duct dimensions extending from lung generations 18 to 23. Airflow patterns in the surfactant-enriched model support previous findings that the recirculation of the flow is affected by its propagation depth. Proximal lung generations experience dominant recirculating flow while farther generations in the distal alveolar region exhibit dominant radial flows. In the surfactant-enriched model, surface tension values alternate during inhalation and exhalation, with values increasing to 25 mN/m at the inhalation and decreasing to 1 mN/m at the end of the exhalation. In the surfactant-deficient model, only water coats the alveolar walls with a high surface tension value of 70 mN/m. ResultsResults showed that surfactant deficiency in the alveoli adversely alters airflow behavior and generates unsteady chaotic breathing through the production of vorticities, accompanied by higher vorticity magnitudes (100% increase at the end of exhalation) and higher velocity magnitudes (8.69% increase during inhalation and 11.9% increase during exhalation). In addition, high air-water surface tension in the surfactant-deficient case was found to induce higher shear stress values (by around a factor of 10) on the alveolar walls than that of the surfactant-enriched case. ConclusionOverall, it was concluded that the presence of the surfactant improves respiratory mechanics and allows for smooth breathing and normal respiration.

Tunable laser spectroscopy for carbon dioxide capnography and water vapor sensing inside a breathing mask: application to pilot life support

Tunable laser spectroscopy (TLS) near 2683 nm was used to measure carbon dioxide and water vapor inside a pilot mask during jet fighter flights. Measurement frequency was 100 Hz in order to capture breathing profiles and other gas flow dynamics. Analysis of the full inhalation and exhalation breathing cycle allowed precise monitoring of breathing performance and interaction of the pilot with the life-support system. Measurements revealed dynamic phenomena pertaining to mechanical gas flow and pilot respiration that may be used to understand gas delivery stresses imposed upon the pilot and pilot physiology during flight. Typically, such measurements are made with non-dispersive infrared instrumentation for only carbon dioxide with intrinsic challenges regarding time and optical resolution. The TLS approach is a major advance because the sensor is placed directly into the mask improving its time response and enabling use of water vapor measurements that are less impacted from memory effects. This article presents the implementation of TLS and shows highly time-resolved pilot breathing data for high-performance aircraft tests.

A Wire-Free and Fiber-Based Smart T-Shirt for Real-Time Breathing Rate Monitoring

A new wearable smart T-Shirt design for breathing rate monitoring using Received Signal Strength Indicator (RSSI) is proposed. This new design features three principal functions: a wireless sensor to monitor the breathing rate, a wireless power transfer system, and a user interface to analyze the collected breathing data. First, the breathing curves obtained from a breathing sensor incorporated in a smart T-shirt were presented. Then, the data analysis methods are applied for extracting the important parameters for medical diagnosis. To observe multiple breathing profiles, additional results are presented for different tests on male and female subjects using another design of a smart T-shirt system consisting of an array of six sensors.

Effect of breathing profiles on nebuliser drug delivery targeting the paranasal sinuses in a post-operative nasal cavity

Chronic rhinosinusitis (CRS) is a common sinonasal condition that debilitates quality of life. Nasal sprays are inefficient for targeting the sinuses because of the highly inertial atomised droplets. This study evaluated sinus drug delivery via a nebuliser in a human nasal cavity using Computational Fluid Dynamics (CFD) simulations of different breathing conditions. The nebuliser was quantified through high-speed imaging of the spray plume and average velocity, while laser diffraction was used for droplet size distributions. A CT scan was acquired of a 75-year-old male with a confirmed diagnosis of CRS, and airway segmentation was performed to extract the nasal cavity and sinuses. Virtual surgery was then performed on the computational model. Two nozzle designs for the nebuliser under normal breathing, slow exhalation, and breath hold were investigated. The results demonstrated that drug delivery with a fully blocked nostril with a breath hold notably improved deposition targeting the maxillary sinuses and ethmoid sinuses, while using a nozzle that allowed co-flow of air was recommended for targeting the frontal and sphenoid sinuses.

Excipient-Free Inhalable Microparticles of Azithromycin Produced by Electrospray: A Novel Approach to Direct Pulmonary Delivery of Antibiotics

Inhalation therapy offers several advantages in respiratory disease treatment. Azithromycin is a macrolide antibiotic with poor solubility and bioavailability but with a high potential to be used to fight lung infections. The main objective of this study was to generate a new inhalable dry powder azithromycin formulation. To this end, an electrospray was used, yielding a particle size around 2.5 µm, which is considered suitable to achieve total deposition in the respiratory system. The physicochemical properties and morphology of the obtained microparticles were analysed with a battery of characterization techniques. In vitro deposition assays were evaluated after aerosolization of the powder at constant flow rate (100 L/min) and the consideration of the simulation of two different realistic breathing profiles (healthy and chronic obstructive pulmonary disease (COPD) patients) into a next generation impactor (NGI). The formulation was effective in vitro against two types of bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the particles were biocompatible, as evidenced by tests on the alveolar cell line (A549) and bronchial cell line (Calu-3).

A robotic system for real-time analysis of inhaled submicron and microparticles

SummaryVitamin E acetate (VEA) has been strongly linked to outbreak of electronic cigarette (EC) or vaping product use-associated lung injury. How VEA leads to such an unexpected morbidity and mortality is currently unknown. To understand whether VEA impacts the disposition profile of inhaled particles, we created a biologically inspired robotic system that quantitatively analyzes submicron and microparticles generated from ECs in real-time while mimicking clinically relevant breathing and vaping topography exactly as happens in humans. We observed addition of even small quantities of VEA was sufficient to alter size distribution and significantly enhance total particles inhaled from ECs. Moreover, we demonstrated utility of our biomimetic robot for studying influence of nicotine and breathing profiles from obstructive and restrictive lung disorders. We anticipate our system will serve as a novel preclinical scientific research, decision-support tool when insight into toxicological impact of modifications in electronic nicotine delivery systems is desired.

Speech breathing: variable but individual over time and according to limb movements.

Breathing is variable but also highly individual. Since the 1980s, evidence of a ventilatory personality has been observed in different physiological studies. This original term refers to within-speaker consistency in breathing characteristics across days or even years. Speech breathing is a specific way to control ventilation while supporting speech planning and phonation constraints. It is highly variable between speakers but also for the same speaker, depending on utterance properties, bodily actions, and the context of an interaction. Can we yet still observe consistency over time in speakers' breathing profiles despite these variations? We addressed this question by analyzing the breathing profiles of 25 native speakers of German performing a narrative task on 2 days under different limb movement conditions. The individuality of breathing profiles over conditions and days was assessed by adopting methods used in physiological studies that investigated a ventilatory personality. Our results suggest that speaker-specific breathing profiles in a narrative task are maintained over days and that they stay consistent despite light physical activity. These results are discussed with a focus on better understanding what speech breathing individuality is, how it can be assessed, and the types of research perspectives that this concept opens up.

Large variations of oxygen delivery in self-inflating resuscitation bags used for preoxygenation - a mechanical simulation

BackgroundSelf-Inflating Resuscitation Bags (SIRB) are common and essential tools in airway management and ventilation. They are often used in resuscitation and emergency anaesthesia outside the operating theatre. There is a common notion that all SIRBs applied with a tight sealed mask will deliver close to 100 % oxygen during spontaneous breathing. The aim of the study was to measure the oxygen delivery of six commonly used SIRBs in a mechanical spontaneous breathing adult in vitro model.MethodsThree SIRBs of each of the six models were evaluated for oxygen delivery during simulated breathing with an adult mechanical lung. The test was repeated three times per device (54 tests in total). The breathing profile was fixed to a minute volume of 10 L/min, a tidal volume of 500 mL and the SIRBs supplied with an oxygen fresh gas flow of 15 L/min. The fraction of delivered oxygen (FDO2) was measured over a three-minute period. Average FDO2 was calculated and compared at 30, 60 and 90 s.ResultsAt 90 s all models had reached a stable FDO2. Average FDO2 at 90 s; Ambu Oval Plus 99,5 %; Ambu Spur II 99,8 %; Intersurgical BVM Resuscitator 76,7 %; Laerdal Silicone 97,3 %; Laerdal The Bag II 94,5 % and the O-Two Smart Bag 39,0 %. All differences in FDO2 were significant apart from the two Ambu models.Conclusions In simulated spontaneous breathing, four out of six (by Ambu and Laerdal) Self-Inflating Resuscitation Bags delivered a high fraction of oxygen while two (Intersurgical and O-two) underperformed in oxygen delivery. These large variations confirm results reported in other studies. It is our opinion that underperforming Self-Inflating Resuscitation Bags might pose a serious threat to patients’ health if used in resuscitation and anaesthesia. Manufacturers of Self-Inflating Resuscitation Bags rarely provide information on performance for spontaneous breathing. This poses a challenge to all organizations that need their devices to deliver adequate oxygen during spontaneous breathing.

Time-resolved magnetic resonance fingerprinting for radiotherapy motion management.

This study aims to develop a novel time-resolved magnetic resonance fingerprinting (TR-MRF) technique for respiratory motion imaging applications. The TR-MRF technique consists of repeated MRF acquisitions using an unbalanced steady-state free precession sequence with spiral-in-spiral-out trajectory. Time-resolved magnetic resonance fingerprinting was first tested via computer simulation using a four-dimensional (4D) extended cardiac-torso (XCAT) phantom for both regular and irregular breathing profiles, and was tested in three healthy volunteers. Parametric TR-MRF maps at different respiratory phases were subsequently estimated using our TR-MRF sorting and reconstruction techniques. The resulting TR-MRF maps were evaluated using a set of metrices related to radiotherapy applications, including absolute difference in motion amplitude, error in the amplitude of diaphragm motion (ADM), tumor volume error (TVE), signal-to-noise ratio (SNR), and tumor contrast. TR-MRF maps with regular and irregular breathing were successfully generated in XCAT phantom. Numerical simulations showed that the TVE were 1.6±2.7% and 1.3±2.2%, the average absolute differences in tumor motion amplitude were 0.3±0.7mm and 0.3±0.6mm, and the ADM were 4.1±0.9% and 3.5±0.9% for irregular and regular breathing, respectively. The SNR of the T1 and T2 maps of the liver and the tumor were generally higher for regular breathing compared to irregular breathing, whereas tumor-to-liver contrast is similar between the two breathing patterns. The proposed technique was successfully implemented on the healthy volunteers. We have successfully demonstrated in both digital phantom and healthy subjects a novel TR-MRF technique capable of imaging respiratory motions with simultaneous quantification of MR multiparametric maps.

Dynamics of aerosol generation and release – Dry powder inhaler performance considerations

The main objective of the work was to investigate how the dynamics of inhalation affect aerosol release process in real-time, with an unsteady airflow through passive dry powder inhalers (DPIs) of comparable airflow resistance, but different principle of powder release. It consists of two complementary studies, concerning dynamics of controlled aerosol release (emission kinetics) and dynamics of aerosol generation (aerosol size characteristics in time series).Aerosol behavior of the powder was studied experimentally at the outlet of the inhalers: RS01 inhaler (Plastiape Spa, Osnago LC, Lombardy, Italy) and Turbospin (Ph&T, Milano, Lombardy, Italy). Two breathing profiles were analyzed throughout the study. Timing of aerosol emission was done by light scattering. Aerosol characterization was done by laser diffraction. It resulted in time evolution of volume concentration and volumetric particle size distribution.Both the design of the passive DPI inhaler and the dynamics of the inhalation (along with its intensification) influence the course of the aerosol generation and emission. The process of aerosol emission occurs only in the initial part of the inhalation process, before the peak inspiratory flow rate is established. This part is strongly responsible for the quality of the aerosol emitted from the device and consequently will potentially influence the drug delivery.

Numerical simulation of the effect of inhalation parameters, gender, age and disease severity on the lung deposition of dry powder aerosol drugs emitted by Turbuhaler®, Breezhaler® and Genuair® in COPD patients

The effect of breathing parameters on the airway deposition of the inhaled aerosols with known size was intensively studied in the literature. However, in the case of dry powder aerosol drugs both the quantity and quality of the particles emitted by the inhaler and inhaled by the patients is a complex function of the patient's breathing parameters, which in turn depend also on the disease severity and current status of the patient. The aim of this study was to evaluate the impact of breathing parameters, gender, age, symptoms and exacerbation history related disease severity (GOLD groups) of chronic obstructive pulmonary disease (COPD) patients on the lung dose of four different drugs emitted by three DPIs (dry powder inhalers). Breathing profiles of 47 COPD patients were recorded while they inhaled through Turbuhaler®, Breezhaler® and Genuair® inhalers. Patient specific emitted doses and particle size distributions were determined for Symbicort® Turbuhaler®, Onbrez® Breezhaler®, Seebri® Breezhaler® and Bretaris® Genuair® aerosol drugs. Airway deposition was quantified by a validated whole respiratory tract particle deposition model. Correlation analysis of the lung doses with breathing parameters through the devices and with standard spirometric parameters was performed. The effects of gender, age and degree of disease severity (GOLD groups) on the lung doses were also studied by statistical analysis. Mean values and distributions of the deposited lung doses proved to be both drug and device specific, yielding 24.2 (±7.8), 22.6 (±3.6), 34.2 (±4.8) and 23.9 (±5.4) % values for Symbicort®, Onbrez®, Seebri® and Bretaris®, respectively. Drugs with flow rate sensitive emitted dose and emitted particle size distribution exhibited higher intersubject variability of the lung doses. The degree of correlation of lung doses with breathing parameters through the devices was also drug specific. Correlation with flow rate was the strongest for Symbicort® Turbuhaler®. Longer breath-hold increased the lung dose of all the studied drugs. Correlations of lung dose with standard spirometric parameters was generally weaker than its correlation with the parameters measured when inhaling through the devices. Men had higher lung deposition than women, younger patients had higher deposition than older ones and patients with less severe disease higher doses than those with more severe COPD, but the differences were statistically significant only upon gender and only in case of Symbicort® and Seebri®. Patients with better inhalation parameters are likely to have higher lung deposition when inhaling a drug with emitted dose and particle size distribution sensitive to the inhalation flow rate. At the same time, patients with lower lung capacity show better deposition results when inhaling from inhalers emitting a more constant amount of drug and particles with more stable aerodynamic characteristics. A more powerful inhalation significantly increases the lung dose for the drug emitted by Turbuhaler®, while long breath-hold is likely to yield significantly higher deposition for drugs emitted by Breezhaler® and Genuair®. Lung doses of two different drugs dispensed in the same inhaler can be significantly different.

Decreased respiratory-related postural perturbations at the cervical level under cognitive load.

In healthy humans, postural and respiratory dynamics are intimately linked and a breathing-related postural perturbation is evident in joint kinematics. A cognitive dual-task paradigm that is known to induce both postural and ventilatory disturbances can be used to modulate this multijoint posturo-ventilatory (PV) interaction, particularly in the cervical spine, which supports the head. The objective of this study was to assess this modulation. With the use of optoelectronic sensors, the breathing profile, articular joint motions of the cervical spine, hip, knees and ankles, and centre of pressure (CoP) displacement were measured in 20 healthy subjects (37years old [29; 49], 10 females) during natural breathing (NB), a cognitive dual task (COG), and eyes-closed and increased-tidal-volume conditions. The PV interaction in the CoP and joint motions were evaluated by calculating the respiratory emergence (REm). Only the COG condition induced a decrease in the cervical REm (NB: 17.2% [7.8; 37.2]; COG: 4.2% [1.8; 10.0] p = 0.0020) concurrent with no changes in the cervical motion. The CoP REm (NB: 6.2% [3.8; 10.3]; COG: 12.9% [5.8; 20.7] p = 0.0696) and breathing frequency (NB: 16.6min-1 [13.3; 18.7]; COG: 18.6min-1 [16.3; 19.4] p = 0.0731) tended to increase, while the CoP (p = 0.0072) and lower joint motion displacements (p < 0.05) increased. This study shows stable cervical spine motion during a cognitive dual task, as well as increased postural perturbations globally and in other joints. The concurrent reduction in the PV interaction at the cervical spine suggests that this "stabilization strategy" is centrally controlled and is achieved by a reduction in the breathing-related postural perturbations at this level. Whether this strategy is a goal for maintaining balance remains to be studied.