Simulated Breathing Research Articles

Are the Reference Values for the Provocative Concentration of Methacholine Appropriate for Children?

Background: Preliminary data in a randomly selected pediatric cohort study in 8-year-olds suggested a rate of positivity to a methacholine challenge test that was unexpectedly high, roughly 30%. The current recommendation for a negative methacholine test is a 20% decrease in the forced expiratory volume in one second at a dose greater than 400 μg. This was derived from studies in adults using the obsolete English Wright nebulizer. One explanation for the high incidence of positivity in the study in 8-year-olds could be that children deposit more methacholine on a μg/kg basis than adults, due to differences in their breathing patterns. The purpose of this study was to determine if pediatric breathing patterns could result in a higher dose of methacholine depositing in the lungs of children based on μg/kg body weight compared with adults. Methods: An AeroEclipse Breath Actuated nebulizer delivered methacholine aerosol, generated from a 16 mg/mL solution, for one minute, using age-appropriate breathing patterns for a 70 kg adult and a 30 and 50 kg child produced by a breathing simulator. Predicted lung deposition was calculated from the collected dose of methacholine on a filter placed at the nebulizer outport, multiplied by the fraction of the aerosol mass contained in particles ≤5 μm. The dose of methacholine on the inspiratory filter was assayed by high performance liquid chromatography (HPLC). Particle size was measured using laser diffraction technology. Results: The mean (95% confidence intervals) predicted pulmonary dose of methacholine was 46.1 (45.4, 46.8), 48.6 (45.3, 51.9), and 36.1 (34.2, 37.9) μg/kg body weight for the 30 kg child, 50 kg child, and 70 kg adult, respectively. Conclusions: On a μg/kg body weight, the predicted pulmonary dose of methacholine was greater with the pediatric breathing patterns than with the adult pattern.

An Enhanced YSZ Gas Sensor through Optimizing Electrode Thickness for ppb-level H2S Detection

Nowadays, there is uncertainty regarding the impact of sensing electrode thickness on the gas sensing performance of mixed potential gas sensors due to simultaneous competitive heterogeneous catalytic reaction and electrochemical reaction. In this study, yttrium oxide doped zirconia gas sensors with varying thickness of NiFe2O4 sensing electrode have been fabricated for H2S gas detection. The operating temperature of yttrium oxide doped zirconia gas sensors have been firstly optimized, followed by a systematic study of the effects of NiFe2O4 sensing electrode thickness on H2S sensing performance. The best sensing performance have been achieved for the yttrium oxide doped zirconia gas sensor with a 10 μm-thick sensing electrode (S-10 sensor). Sensitivities of −8.7 and −44.6 mV/decade have been attained for 10–100 ppb and 100–10000 ppb, respectively, with a lower limit of detection as low as 10 ppb at 510 °C for the S-10 sensor. Furthermore, the potential application of the S-10 sensor in halitosis detection was further evaluated using simulated exhaled breath from patient with halitosis and healthy volunteers. The significant change in human exhaled gas response values detect by the S-10 sensor at different times provide additional support for the prospect of diagnosing halitosis.

Co3O4/CQDs composite for selective ammonia detection in exhaled human breath analysis

Co3O4 was synthesized using electrospinning method and different amounts of carbon quantum dots (CQDs) were subsequently doped into the Co3O4 matrix via grinding, resulting in Co3O4/CQDs composite materials with various ratios. Gas sensing tests revealed that the resulting composite Co3O4/CQDs sensors exhibited excellent performance at a low temperature of 50°C, with outstanding selectivity towards ammonia gas and rapid response and recovery characteristics. Specifically, response and recovery time for 50 ppm ammonia gas were 14 s and 164 s, respectively. The outcomes of the exhalation simulation test utilizing sensors composed of this material demonstrate that the sensor's response to simulated chronic kidney disease breath closely approximates that of pure biological samples (1.08), exceeding the average response value of healthy exhaled breath samples (1.0). This demonstrates the sensor's capability to differentiate between healthy individuals and chronic kidney disease patients despite significant water vapor and carbon dioxide interference. This study provides valuable insights for the development of more efficient ammonia sensors and their role in the early detection of chronic kidney disease.

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.

Flexible, Breathable and Hydrophobic SnO2–SnS2–SiO2/SiO2 All‐Inorganic Self‐Supporting Nanofiber Membrane for Ultralow‐Concentration NO2 Sensing Under High Humidity

AbstractInorganic semiconductor gas sensors, being widely utilized in gas‐sensing applications, face significant challenges in attaining mechanical flexibility and humidity resistance in wearable sensing fields. Herein, a highly flexible, breathable, and hydrophobic all‐inorganic self‐supporting nanofiber (NF) gas sensor is developed using electrospinning combined with thermal sulfidation approach. This innovative sensor features a bilayer configuration, with an amorphous SiO2 nanofiber substrate layer and an interwoven SiO2 and SnO2–SnS2 nanofiber active layer. The relatively low elastic modulus of the amorphous SiO2 nanofibers, combined with the three‐dimensional network interwoven structure, endow the SnO2–SnS2–SiO2/SiO2 sensor with superior mechanical flexibility. The sensor exhibits excellent sensitivity, selectivity, moisture resistance, and cycling stability (&gt;10 000 cycles at 140° bending) to both high and low concentration NO2. Notably, an excellent flexible detecting capability of the sensor to NO2, an asthma‐related biomarker, is demonstrated at ultralow concentrations (≈25 ppb) in simulated exhaled breath environments. The enhanced moisture resistance is attributed to the effective inhibition of hydrogen bond formation from H2O molecules by the Sn─S bonds formed through sulfidation of SnO2 nanofibers. This work represents a substantial advancement in the universal fabrication of flexible, breathable and moisture‐resistant inorganic semiconductor sensors for wearable breath sensing applications.

Assemble and validation of a simulated device of human exhaled breath aerosols for screening of illicit drug abuse by HPLC-TQ-MS/MS detection

Collecting exhaled breath aerosols (EBA) as a sample has a great potential to monitoring illicit drug abuse due to advantages of simple, non-invasiveness and unrestricted sampling. However, scarcity of positive samples has cramped development of more efficient techniques for monitoring illicit drug abuse in EBA. In this work, a simulated human exhaled breath aerosol (SHEBA) generating device based on Venturi jet principle was constructed by integrating nebulizing unit and collection unit to prepare positive EBAs. By means of ultra high-performance hyphenated with triple quadrupole tandem mass spectrometry (HPLC-TQ-MS/MS), using caffeine as a target drug, the device parameters were investigated by studying the effects of flow rates of nebulizing and auxiliary gases, drug concentration and etc., the performance was further validated by commonly abused drugs such as amphetamines (AMP, MAMP, MDA and MDMA). Electret material as adsorbent was used to collect SHEBAs generated by the device, achieving HPLC-TQ-MS/MS detection of the captured drugs at 40.0–2000.0 pg/filter. By this way, caffeine content in EBAs from six volunteers was successfully detected in the range of 51.6 ± 6.8–708 ± 51 pg/filter after drinking the caffeinated beverage. These validation experiments proved that SHEBA generating device could not only meet to the requirement of EBA analysis for illicit drug abuse at trace levels, but also provide the correction factors to calibrate the lower detection value caused by incomplete material adsorption.

Functionalized N95 Face Mask with a Chemical-Free Paper-Based Collector for Exhaled Breath Analysis: SARS-CoV-2 Detection with a Printed Immunosensor as a Case Study.

Exhaled breath electrochemical sensing is a promising biomedical technology owing to its portability, painlessness, cost-effectiveness, and user-friendliness. Here, we present a novel approach for target analysis in exhaled breath by integrating a comfortable paper-based collector into an N95 face mask, providing a universal solution for analyzing several biomarkers. As a model analyte, we detected SARS-CoV-2 spike protein from the exhaled breath by sampling the target analyte into the collector, followed by its detection out of the N95 face mask using a magnetic bead-based electrochemical immunosensor. This approach was designed to avoid any contact between humans and the chemicals. To simulate human exhaled breath, untreated saliva samples were nebulized on the paper collector, revealing a detection limit of 1 ng/mL and a wide linear range of 3.7-10,000 ng/mL. Additionally, the developed immunosensor exhibited high selectivity toward the SARS-CoV-2 spike protein, compared to other airborne microorganisms, and the SARS-CoV-2 nucleocapsid protein. Accuracy assessments were conducted by analyzing the simulated breath samples spiked with varying concentrations of SARS-CoV-2 spike protein, resulting in satisfactory recovery values (ranging from 97 ± 4 to 118 ± 1%). Finally, the paper-based hybrid immunosensor was successfully applied for the detection of SARS-CoV-2 in real human exhaled breath samples. The position of the collector in the N95 mask was evaluated as well as the ability of this paper-based analytical tool to identify the positive patient.

Novel High-tech, Low-cost Ventilation for Military Use, Mass Casualty Incidents, Stockpiling, and Underserved Communities.

Despite the significant need for mechanical ventilation in- and out-of-hospital, mechanical ventilators remain inaccessible in many instances because of cost or size constraints. Mechanical ventilation is especially critical in trauma scenarios, but the impractical size and weight of standard mechanical ventilators restrict first responders from carrying them in medical aid bags, leading to reliance on imprecise manual bag-mask ventilation. This is particularly important in combat-related injury, where airway compromise and respiratory failure are leading causes of preventable death, but medics are left without necessary mechanical ventilation. To address the serious gaps in mechanical ventilation accessibility, we are developing an Autonomous, Modular, and Portable Ventilation platform (AMP-Vent) suitable for austere environments, prolonged critical care, surgical applications, mass casualty incidents, and stockpiling. The core system is remarkably compact, weighing <2.3 kg, and can fit inside a shoebox (23.4 cm × 17.8 cm × 10.7 cm). Notably, this device is 65% lighter than standard transport ventilators and astoundingly 96% lighter than typical intensive care unit ventilators. Beyond its exceptional portability, AMP-Vent can be manufactured at less than one-tenth the cost of conventional ventilators. Despite its reduced size and cost, the system's functionality is uncompromised. The core system is equipped with closed-loop sensors and advanced modes of ventilation (pressure-control, volume-control, and synchronized intermittent mandatory ventilation), enabling quality care in a portable form factor. The current prototype has undergone preliminary preclinical testing and optimization through trials using a breathing simulator (ASL 5000) and in a large animal model (swine). This report aims to introduce a novel ventilation system and substantiate its promising performance through evidence gathered from preclinical studies. Lung simulator testing was performed using the ASL 5000, in accordance with table201.105 "pressure-control inflation-type testing" from ISO 80601-2-12:2020. Following simulations, AMP-Vent was tested in healthy 10-kg female domestic piglets. The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee approved all animal procedures. Swine received 4-min blocks of alternating ventilation, where AMP-Vent and a conventional anesthesia ventilator (GE AISYS CS2) were used to titrate to varied end-tidal carbon dioxide (EtCO2) goals with the initial ventilator switching for each ascending target (35, 40, 45, 50, 55 mmHg). During ASL 5000 simulations, AMP-Vent exhibited consistent performance under varied conditions, maintaining a coefficient of variation of 2% or less within each test. In a large animal study, AMP-Vent maintained EtCO2 and SpO2 targets with comparable performance to a conventional anesthesia ventilator (GE AISYS CS2). Furthermore, the comparison of minute ventilation (Ve) distributions between the conventional anesthesia ventilator and AMP-Vent at several EtCO2 goals (35, 40, 45, 50, and 55 mmHg) revealed no statistically significant differences (p = 0.46 using the Kruskal-Wallis rank sum test). Preclinical results from this study highlight AMP-Vent's core functionality and consistent performance across varied scenarios. AMP-Vent sets a benchmark for portability with its remarkably compact design, positioning it to revolutionize trauma care in previously inaccessible medical scenarios.

A Pediatric Bench Model of Continuous Albuterol Delivery Using Heliox.

The optimal setup for continuously administering albuterol with heliox remains unclear, especially for pediatric patients. This study aimed to evaluate the efficiency of continuous albuterol delivery with heliox using different nebulizer setups in a pediatric model. A pediatric manikin with simulated spontaneous breathing was used to receive continuous albuterol (20 mg/h) with heliox (80/20) in 3 setups: (1) The MiniHEART nebulizer, driven by oxygen at 3 L/min, was attached to a Y-piece, linking to a non-rebreather mask and a valved reservoir with 11 L/min heliox; (2) a vibrating mesh nebulizer (VMN) placed at the humidifier inlet of high-flow nasal cannula (HFNC) with 11 L/min heliox and the manikin's mouth sealed; and (3) a VMN placed between a valved reservoir with 11 L/min heliox and a non-rebreather mask. Both tight-fitting and loose-fitting mask configurations were tested in the setup with vibrating mesh nebulizer and mask. Heliox of 70/30 was tested with a VMN and a loose-fitting mask. Albuterol was delivered continuously to the nebulizer via an infusion pump at 8 mL (20 mg)/h for each 20-min run and each experiment was repeated five times. A collecting filter placed between the manikin's trachea and lung model was removed after each run, and the drug was eluted and assayed via ultraviolet spectrophotometry (276 nm). During continuous albuterol nebulization using heliox, the VMN either in line with HFNC or with a tight-fitting mask achieved the highest and similar inhaled dose (8.5 ± 0.4 vs 8.8 ± 0.7%, P = .35), while the MiniHEART nebulizer yielded the lowest aerosol deposition (1.5 ± 0.2%). The inhaled dose was lower with the loose-fitting mask than with the tight-fitting mask (5.9 ± 0.9 vs 8.8 ± 0.7%, P=.009), and heliox of 80/20 delivered a higher inhaled dose than heliox of 70/30 (5.9 ± 0.9 vs 3.9 ± 0.4%, P=.009). When administering continuous albuterol with heliox in a pediatric model, utilizing a VMN in line with HFNC during closed-mouth breathing yielded a higher inhaled dose compared to both the MiniHEART nebulizer and VMN with a loose-fitting mask.

Gas Phase Aldehydes Detection in Exhaled Breath in Screening of Barrett's Esophagus

Aldehydes, e.g., acetaldehyde, have been classified as toxic and carcinogenic volatile organic compounds (VOCs) and are recognized as one determinant of upper aerodigestive tract cancer like Barrett's esophagus. Measuring aldehyde levels in breath provides information about the aldehydes released by abnormal cells, the level of aldehyde dehydrogenase (ALDH2) activity, and risks and diseases associated with high levels of acetaldehyde, which include liver disease and lung and upper digestive cancers. Devices currently available for breath analysis are state-of-the-art, high-resolution mass spectrometry instruments. These instruments have some drawbacks such as size, initial cost, and operational expense. Electrochemical sensors are capable of miniaturization and are available as portable and handheld breathalyzers. The non-invasive nature of breath analysis and its easy sampling makes smaller devices a more attractive alternative, particularly for continuous monitoring and point-of-care (POC) testing.1 However, the lack of an exchangeable/disposable sensing element, the resulting memory effect, and the need for frequent recalibration is the main drawback of currently available electrochemical breathalyzers.Herein we examine the feasibility of a POC testing device for aldehyde in exhaled breath to assess the medical application of such a device in noninvasive diagnostic testing for Barrett’s esophagus. To improve the selectivity of the method we harness the unique catalytic activity of the aminoxyl radical/oxoammonium redox couple toward aldehyde oxidation. The highly selective/sensitive device offers the capability for use in the detection of Barrett's esophagus, ideally at early stages, without the need for a high-cost screening test. Our functional sensing element consists of a screen-printed electrode (SPE) in which the graphene oxide-based is the working electrode. Exposing this electrode to simulated breath that contains aldehyde, while applying the required potential for oxidation of the aminoxyl radical (4-acetamido-TEMPO known as ACT), generates an electrocatalytic current proportional to the aldehyde concentration in the breath. These simple, sensitive, durable, and inexpensive electrodes may contribute to the development of a single-use reliable aldehyde sensor for personal or law enforcement applications.1. M. Mayer, M. Rafiee, Electrocatalytic Detection of Ethanol and Acetaldehyde by Aminoxyl Radicals: Utilizing Molecular Catalysis for Breath Analysis. Analyst 147, 2022, 3420 – 3423.

Comparisons between In-Check DIAL® and PF810® in evaluation and training inspiratory capacity for using dry powder inhalers

BackgroundDry powder inhalers (DPIs) rely on both internal resistance and patients’ inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity.MethodsThe accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland–Altman graphical analysis.ResultsPF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland–Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients.ConclusionsIn-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.

Determining the optimum high-flow nasal cannula flow rate to achieve the desired fraction of inspired oxygen: A bench study

BackgroundPurpose: High-flow nasal cannula (HFNC) has many benefits in various clinical conditions. The original hypothesis suggests that the high and constant fraction of inspired oxygen (FiO2) is one of the main physiological effects. However, increasing evidence shows that there is a gap between the actual FiO2 and administered FiO2. We aimed to determine the actual FiO2 under different respiratory conditions and develop a regression model using a spontaneous breathing lung model. MethodsA spontaneous breathing simulation model was built using an airway manikin and a model lung. The FiO2 was measured under different respiratory conditions with varying tidal volumes and respiratory and HFNC flow rates. The relationships between the respiratory parameters and actual FiO2 were determined and used to build the predictive model. ResultsThe actual FiO2 was negatively correlated with respiratory rate and tidal volume and positively correlated with HFNC flow. The regression model could not be developed using simple respiratory parameters. Therefore, we introduced a new variable, defined as flow ratio, which equaled the HFNC flow divided by inspiratory flow. Our equation demonstrated that the actual FiO2 was mainly determined by the flow ratio in a non-linear relationship. Accordingly, a flow ratio greater than 1 did not ensure a constant high FiO2, whereas a flow ratio >1.435 could produce FiO2 >0.9. ConclusionThe FiO2 during HFNC was not constant even at sufficiently high oxygen flow compared with inspiratory flow. The predictive model showed that the actual FiO2 was mainly determined by the flow ratio.

Do ceiling fans in rooms help to reduce or disperse the transmission of breathing aerosols?

The main focus of this study is the transmission of SARS-CoV-2 through virus-laden aerosols in enclosed spaces that utilize ceiling fans. The impact of an air circulation of ceiling fans on virus transmission is not clear. Computational modeling is employed to investigate aerosol transmission within an enclosed space that features ceiling fans. The aerosol concentration is modeled using a transport equation, and the probability of infection distribution across individuals’ breathing zones is assessed. The particle removal efficiency for two ceiling fan speeds of 10 and 35 rad/s is calculated to evaluate the effect of the ceiling fan’s shear flows on the spread of breathing aerosols. The simulated breathing aerosol considers various environmental situations, including thermal gradients, thermally active surface interaction, and deformability. The results indicate that increasing the ceiling fan speed within an enclosed space causes the aerosol cloud to circulate within the room rather than exiting it. Therefore, ceiling fans may not effectively suppress breathing aerosols and could increase transmissibility. Understanding aerosol behavior is essential in reducing the risk of SARS-CoV-2 transmission in enclosed spaces.

Evaluation of phrenic nerve stimulation trigger lag and synchronization in different modes of ventilation.

Phrenic nerve stimulation is currently being investigated for the prevention of diaphragm atrophy in patients with mechanically supported breathing. Patients receiving breathing support from mechanical ventilation are at risk of mismatches between respiratory demand and ventilator support. Our objectives were to determine if a novel phrenic nerve stimulation device provided stimulation during inspiration as intended and did not exacerbate any potential discordances. A benchtop electromechanical simulation model was developed to validate phrenic nerve stimulation with simulated breathing. The phrenic nerve stimulation device was evaluated with a mechanical ventilator attached to a breathing simulator. The trigger ratio and time lag between phrenic nerve stimulation and mechanical ventilation was measured for multiple disease and ventilator parameters. For the 1:1 breath trigger ratio test, 99.79% of intended stimulation breaths received stimulation at the correct time. For the 1:4 breath trigger ratio test, 99.72% of intended stimulation breaths received stimulation at the correct time. For trigger lag times for the inspiratory and expiratory phases, the mean inspiratory lag was 36.10 ± 10.50ms and 16.61 ± 3.61ms, respectively. The following discordance scenarios were evaluated in conjunction with simulated phrenic nerve stimulation: asynchrony-false trigger, dyssynchrony-early trigger, dyssynchrony-late trigger, dyssynchrony-early cycling, dyssynchrony-late cycling. Testing demonstrated none of these discordances were exacerbated by the simulated phrenic nerve stimulation. The novel phrenic nerve stimulation device delivered electrical stimulation therapy as intended and did not exacerbate any simulated discordances.

InGaN/GaN multi-quantum well nanowires: Enhanced trace-level NO2 detection for environmental and breath analysis

The World Health Organization highlights nitrogen dioxide (NO2) as a key atmospheric pollutant impacting air quality and human health. To date, several sensors have been proposed for NO2 detection and disease monitoring, but their effectiveness is limited because of low sensitivity and high operational temperatures. Herein, we propose a selective and sensitive NO2 sensor based on indium gallium nitride/gallium nitride multiple quantum wells (InGaN/GaN-MQWs). We explored different InGaN/GaN-MQWs configurations (InGaN/GaN-MQW1, InGaN/GaN-MQW2, InGaN/GaN-MQW3), developed through metal–organic chemical vapor deposition (MOCVD), to analyze their impact on gas sensing performance. Our findings reveal that the InGaN/GaN-MQW2 sensor at 150 °C exhibits a response 4.0, 3.1, and 1.65 times greater than GaN-NWs, InGaN/GaN-MQW1, and InGaN/GaN-MQW3 sensors, respectively. The limit of detection (LOD) for the InGaN/GaN-MQW2 sensor is 3 parts per billion (ppb), significantly lower than the NO2 threshold value of 53 ppb. Under ultraviolet (UV) light, the response of InGaN/GaN-MQW2 is 5.51-fold, 4.18-fold, and 1.82-fold higher than that of the GaN-NWs, InGaN/GaN-MQW1, and InGaN/GaN-MQW2 sensors, respectively. Importantly, our hybrid nanocomposite-based electronic nose (e-nose) sensor arrays could distinguish between healthy and simulated unhealthy breaths with high accuracy, promising a new era of efficient, non-invasive disease detection through breath analysis.

Respiration and Cough in Pompe Disease: Results from a neuromechanical computational model of the respiratory control system

Late Onset Pompe Disease (LOPD) is an incurable, rare progressive genetic disease. It is characterized by glycogen build-up, due to mutations in the gene encoding the lysosomal enzyme acid alpha glucosidase, throughout muscle and neural regions. This accumulation is associated with cell death and muscle fiber swelling, eventually leading to respiratory insuffciency and airway clearance (i.e. cough) deficiency. Impairments in effective airway clearance result from the inability to clear normal pulmonary volume. Emerging evidence indicates significant respiratory neuron dysfunction, altering pulmonary function in humans and animal models. It has been suggested that respiratory and airway clearance insuffciency observed in LOPD may be attributed to medullary motoneurons potentially associated with the respiratory and cough pattern generators (Fuller et al., 2013; DeRuisseau et al., 2009). However, the precise neural mechanisms that suppress breathing and cough are not fully understood. One possible target for LOPD respiratory insuffciencies may be reduced medullary inspiratory neuron activity within this network, which could result in decreased phrenic motoneuron output. Using a stochastic neural network simulator that consisted of discrete “integrate and fire” populations, we simulated a systematic decrease in three medullary inspiratory neuron populations: inspiratory driver (I-Driver), inspiratory decrementing (I-Dec), or inspiratory augmenting (I-Aug) neurons. We simulated breathing and three cough trials. By targeting these populations, we expected global decreased neural bursts, suppressed inspiratory motor drive, and/or suppressed expiratory motoneuron output. Simulations indicated that when the I-Dec motoneuron population decreased by 25%, it resulted in apnea and abolished cough. Reducing the I-Aug motoneuron population by 20% resulted in longer inspiratory phase durations (TI) and a decreased respiratory rate. During cough, there was a decrease in the duration and amplitudes of the expiratory motoneuronal activity associated with decreased cough receptor and pulmonary stretch receptor afferent feedback. When the I-Driver motoneuron population was reduced by 25%, TI decreased and I amplitude increased during respiration. During cough, lumbar and phrenic motoneuron discharge duration and amplitude decreased. These results are consistent with previously reported in vivo data. Overall, our simulation data support the plausibility of glycogen storage dysfunction impairing medullary neuronal and premotoneuronal excitability within the inspiratory network. Our results also suggest that some neurons may be more sensitive to glycogen storage than others within the brainstem inspiratory network. Supported by NHLBI L30HL165496, NIH T32 HL 134621 and 3OT2OD023854. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Optimizing Oxygen Delivery by Low-Flow Nasal Cannula to Small Infants: A Bench Study.

In infants treated with a low-flow nasal cannula (LFNC), the oxygen concentration delivered to the lungs (i.e., the effective FiO2) is difficult to estimate. The existing mathematical formulas rely on important assumptions regarding the values of respiratory parameters and, thus, may be inaccurate. We aimed to assess oxygen delivery by LFNC to small infants using realistic simulations on a mechanical breathing model. A mechanical breathing simulator (infant upper-airway replica, single-space breathing compartment, electric motor, microcontroller) was developed. Breathing simulations (n = 1200) were performed at various tidal volume (VT), inspiratory time (Ti), and respiratory rate (RR) combinations and different cannula flows. Minute ventilation (MV) was the most significant predictor of effective FiO2. FiO2 was higher at lower VT and higher Ti values. Benaron and Benitz's formula underestimated the effective FiO2 at lower MV values, while Finer's formula significantly overestimated it. A set of predictive FiO2 charts was developed based on cannula flow, infant body weight, and RR. The effective FiO2 delivered by LFNC to small infants critically depends on VT, Ti, and RR. However, since VT and Ti values are not available in clinical practice, the existing mathematical formulas may be inaccurate. Our novel predictive FiO2 charts could assist in optimizing oxygen delivery by LFNC using easy-to-obtain parameters, such as infant body weight and RR.

Performance Characterisation of the Airvo2TM Nebuliser Adapter in Combination with the Aerogen SoloTM Vibrating Mesh Nebuliser for in Line Aerosol Therapy during High Flow Nasal Oxygen Therapy.

High flow oxygen (HFO) therapy is a well-established treatment in respiratory disease. Concurrent aerosol delivery can greatly expediate their recovery. The aim of this work was to complete a comprehensive characterisation of one such HFO therapy system, the Airvo2TM, used in combination with the Aerogen SoloTM vibrating mesh nebuliser. Representative adult, infant, and paediatric head models were connected to a breathing simulator via a collection filter placed at the level of the trachea. A tracheostomy interface and nasal cannulas were used to deliver the aerosol. Cannula size and gas flow rate were varied across the full operating range recommended by the manufacturer. The tracheal and emitted doses were quantified via UV-spectrophotometry. The aerosol droplet diameter at the exit of the nares and tracheal interface was measured via cascade impaction. High gas flow rates resulted in low emitted and tracheal doses (%). Nasal cannula size had no significant effect on the tracheal dose (%) available in infant and paediatric models. Higher gas flow rates resulted in smaller aerosol droplets at the exit of the nares and tracheostomy interface. Gas flow rate was found to be the primary parameter affecting aerosol delivery. Thus, gas flow rates should be kept low and where possible, delivered using larger nasal cannulas to maximise aerosol delivery.

Enhanced selectivity of novel sea urchin-like h-/m-WO3 hetero nanoflowers for highly sensitive detection of ammonia by double filtration method

Real-time monitoring of toxic gases and breath markers can be performed by metal oxide semiconductor-based chemo-resistive gas sensors due to their simple structures, low cost, and faster and better recovery and response. Due to the effective electron-hole separation, tuning the development of phase junctions of the metal oxide is an efficient method for improving their gas sensing properties. In this study, two distinct hydrothermal methods were used to synthesize h-/m-WO3 hetero-nanoflowers. In the first method, L-Cysteine was used to facilitate the formation of phase junctions between h-WO3 and m-WO3 nanostructures, whereas Thiourea was used in the second. Various characterisation approaches validated the hexagonal-monoclinic phase junction development in the nanoflowers. The sensing material fabricated using Thiourea with a concentration of 0.01M performed better than other sensors. At 350°C, the selected sample displayed outstanding ammonia sensing capacity with the experimental detection limit of 1 ppm (response=3.33). The theoretical detection limit is determined to be 27 ppb. The selectivity of the sensor towards NH3 over H2S and acetone is increased by combining the devices with a double filtration setup. The effectiveness of the selected h-/m-WO3 sensor for diagnosing kidney dysfunction was evaluated by analyzing simulated breath samples.

Wearable sensor for real-time monitoring of oxidative stress in simulated exhaled breath

High concentrations of H2O2, indicative of increased oxidative stress in the lung, are observed in the exhaled breath of individuals affected by different respiratory diseases. Therefore, measuring H2O2 in exhaled breath represents a promising and non-invasive approach for monitoring the onset and progression of these diseases. Herein, we have developed an innovative, inexpensive, and easy-to-use device for the measurement of H2O2 in exhaled breath. The device is based on a silver layer covered with an electrodeposited thin film of chitosan, that ensures the wettability of the sensor in a humid atmosphere. The s-ensor was calibrated in the aerosol phase using both phosphate buffer solution and cell culture medium. In the buffer, a sensitivity of 0.110 ± 0.0042 μA μM−1 cm−2 (RSD: 4%) and a limit of detection of 30 μM were calculated, while in the cell culture medium, a sensitivity of 0.098 ± 0.0022 μA μM−1 cm−2 (RSD 2%) and a limit of detection of 40 μM were obtained. High selectivity to different interfering species was also verified. The sensor was further tested versus an aerosol phase obtained by nebulizing the culture medium derived from human bronchial epithelial cells that had been exposed to pro-oxidant and antioxidant treatments. The results were comparable with those obtained using the conventional cytofluorimetric method. Finally, sensor was tested in real exhaled breath samples and even after undergoing physical deformations. Data herein presented support that in future applications this device can be integrated into face masks allowing for easy breath monitoring.