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The present study investigated the maintenance/repeatability of expiratory flow limitation (EFL) between normoxia and hypoxia. Fifty-one healthy active individuals (27 men and 24 women) performed a lung function test and a maximal incremental cycling test in both normoxia and hypoxia (inspired oxygen fraction = 0.14) on two separate visits. During exercise in normoxia, 28 participants exhibited EFL (55 %). In hypoxia, another cohort of 28 participants exhibited EFL. The two groups only partly overlapped. Individuals with EFL only in normoxia reported lower maximal ventilation values in hypoxia than in normoxia (n=5; -13.5 ± 7.8 %) compared to their counterparts with EFL only in hypoxia (n=5; +6.7 ± 6.3 %) or without EFL (n=18; +5.1 ± 10.3 %) (p=0.004 and p<0.001, respectively). EFL development may be induced by different mechanisms in hypoxia vs. normoxia since the individuals who exhibited flow limitation were not the same between the two environmental conditions. This change seems influenced by the magnitude of the maximal ventilation change.

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Chronic hypoxia (CH) during postnatal development attenuates the hypoxic ventilatory response (HVR) in mammals, but there are conflicting reports on whether this plasticity is permanent or reversible. This study tested the hypothesis that CH-induced respiratory plasticity is reversible in neonatal rats and investigated whether the initial plasticity or recovery differs between sexes. Rat pups were exposed to 3 d of normobaric CH (12 % O2) beginning shortly after birth. Ventilation and metabolic CO2 production were then measured in normoxia and during an acute hypoxic challenge (12 % O2) immediately following CH and after 1, 4-5, and 7 d in room air. CH pups hyperventilated when returned to normoxia immediately following CH, but normoxic ventilation was similar to age-matched control rats within 7 d after return to room air. The early phase of the HVR (minute 1) was only blunted immediately following the CH exposure, while the late phase of the HVR (minute 15) remained blunted after 1 and 4-5 d in room air; recovery appeared complete by 7 d. However, when normalized to CO2 production, the late phase of the hypoxic response recovered within only 1 d. The initial blunting of the HVR and subsequent recovery were similar in female and male rats. Carotid body responses to hypoxia (in vitro) were also normal in CH pups after approximately one week in room air. Collectively, these data indicate that ventilatory and metabolic responses to hypoxia recover rapidly in both female and male neonatal rats once normoxia is restored following CH.

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Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components. Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems. PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns. Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

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Unsteady respiratory airflow characteristics play a crucial role in understanding the deposition of toxic particles and inhaled aerosol drugs in the human respiratory tract. Considering the variations in respiratory flow rate and glottis motion under different respiratory frequencies, these respiratory airflow characteristics are studied by large-eddy simulations, including pressure field, power loss, modal spatial patterns, and vortex structures. Firstly, the results reveal that varying respiratory frequencies significantly affect airflow unsteadiness, turbulent evolution, and vortex structure dissipation, as they increase the complexity and butterfly effect introduced by the turbulent disturbance. Secondly, the pressure drops and flow rate at the glottis also conform to a power-law relationship considering the respiratory physiological characteristics, especially under low respiratory frequencies. Glottis motion plays different roles in energy consumption during inspiration and expiration, and its magnitude can be predicted using a polynomial function based on glottis area and respiratory flowrate under different respiratory frequencies. Finally, modal decomposition can be effectively applied to the study of respiratory flow characteristics, but we recommend separately studying the inspiration and expiration. The spatial distribution of the dominant mode characterizes the majority of respiratory flow characteristics and are influenced by respiratory frequency. Spectral entropy results indicate that glottis motion and slow breathing both delay the transitions in the upper respiratory tract during inspiration and expiration. These results confirm that the respiratory physiology characteristics under different respiratory frequencies have a significant impact on the unsteady respiratory airflow characteristics and warrant further study.

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Preterm birth elicits long-lasting physiological effects in various organ systems, potentially modulating exercise and environmental stress responses. To establish whether prematurely-born adults respond uniquely during early high-altitude acclimatization at rest and during exercise, 17 healthy adults born preterm (gestational age < 32 wk) and 17 term-born, age- and aerobic-capacity-matched, control participants completed a three-day high-altitude sojourn (3,375 m). Oxygen uptake, pulmonary ventilation, and hemodynamic responses, as well as pulse oxygen saturation, brain tissue saturation index (TSI), and skeletal muscle TSI, were measured daily at rest and during moderate-intensity steady-state exercise bouts. In general, the prematurely-born group displayed comparable acclimatization responses at rest, with similar ventilation and cardiac output observed between groups throughout. Resting brain TSI was, however, higher in the preterm group upon arrival at high altitude (72 ± 7% vs. 68 ± 3%; d = 1.20). Absolute exercising oxygen uptake was lower in the preterm participants (P = 0.047), with this group displaying lower exercising cardiac output underpinned by reduced stroke volume (both P = 0.035). Nevertheless, exercising minute ventilation (V̇e) did not differ between groups (P = 0.237) while brain TSI (70 ± 6% vs. 66 ± 3%; d = 1.35) and pulse oxygen saturation (85 ± 3% vs. 82 ± 5%; d = 1.52) were higher with prematurity upon arrival to high altitude. These findings suggest that healthy prematurely-born adults exhibit comparable early acclimatization patterns to their term-born counterparts and better maintain cerebral oxygenation at rest. Together, these data suggest that prematurely-born adults should not be discouraged from high-altitude sojourns involving physical activity.NEW & NOTEWORTHY The acclimatization pattern across three days at 3,375 m, at rest and during moderate-intensity exercise, was similar between healthy adults born prematurely and their term-born counterparts. Preterm adults free from respiratory complications were found to better maintain brain tissue and capillary oxygen saturation at high altitudes, whereas the term-born group experienced larger altitude-induced reductions. Despite apparent cardiac limitations, preterm individuals tolerated exercise similarly to their term-born peers. These findings underscore the notion that preterm birth per se does not predispose healthy adults to decreased altitude tolerance during exercise.

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Obstructive sleep apnea (OSA) is an airway disease caused by periodic collapse of the airway during sleep. Imaging-based subject-specific computational fluid dynamics (CFD) simulations allow non-invasive assessment of clinically relevant metrics such as total pressure loss (TPL) in patients with OSA. However, most of such studies use static airway geometries, which neglect physiological airway motion. This study aims to quantify how much the airway moves during the respiratory cycle, and to determine how much this motion affects CFD pressure loss predictions. Motion of the airway wall was quantified using cine MRI data captured over a single respiratory cycle in three subjects with OSA. Synchronously-measured respiratory airflow was used as the flow boundary condition for all simulations. Simulations were performed for full respiratory cycles with 5 different wall boundary conditions: (1) a moving airway wall, and static airway walls at (2) peak inhalation, (3) end inhalation, (4) peak exhalation, and (5) end exhalation. Geometric analysis exposed significant local airway cross-sectional area (CSA) variability, with local CSA varying as much as 300%. The comparative CFD simulations revealed the discrepancies between dynamic and static wall simulations are subject-specific, with TPL differing by up to 400% between static and dynamic simulations. There is no consistent pattern to which static wall CFD simulations overestimate or underestimate the airway TPL. This variability underscores the complexity of accurately modeling airway physiology and the importance of considering dynamic anatomical factors to predict realistic respiratory airflow dynamics in patients with OSA.

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BACKGROUND: The Phase III slope from a single breath nitrogen washout test provides information about ventilation heterogeneity (VH) in the lungs. PURPOSE: To determine if the Phase III slope from the exhaled tracer gas concentration during a standard, single breath DLCO test using rapid gas analysis provides similar information about VH. BASIC PROCEDURES: Retrospective analysis of clinical pulmonary function laboratory data including spirometry, lung volumes, and DLCO. The normalized Phase III slope from the exhaled CH4 concentration (SnCH4) was compared among different patterns of physiologic abnormality and with VA/TLC as an indicator of VH. MAIN FINDINGS: SnCH4 was the steepest in the group with "Obstruction and Low DLCO", with significant differences between this group and the "Normal", "Obstruction with Normal DLCO", "Mixed Obstruction and Restriction" and "Isolated Low DLCO" groups. SnCH4 was steeper in current and former smokers compared to non-smokers. Among the entire study sample, SnCH4 correlated with VA/TLC (Spearman rho = -0.56, p < 0.01) and remained a significant determinant of VA/TLC by regression modeling. PRINCIPAL CONCLUSIONS: The SnCH4 derived from a standard, single breath DLCO test using rapid gas analysis varied among distinct patterns of physiologic abnormalities and was associated with VA/TLC as a measure of VH.

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The master circadian clock, located in the suprachiasmatic nuclei (SCN), organizes the daily rhythm in minute ventilation (V̇e). However, the extent that the daily rhythm in V̇e is secondary to SCN-imposed O2 and CO2 cycles (i.e., metabolic rate) or driven by other clock mechanisms remains unknown. Here, we experimentally shifted metabolic rate using time-restricted feeding (without affecting light-induced synchronization of the SCN) to determine the influence of metabolic rate in orchestrating the daily V̇e rhythm. Mice eating predominantly at night exhibited robust daily rhythms in O2 consumption (V̇o2), CO2 production (V̇co2), and V̇e with similar peak times (approximately ZT18) that were consistent with SCN organization. However, feeding mice exclusively during the day separated the relative timing of metabolic and ventilatory rhythms, resulting in an approximately 8.5-h advance in V̇co2 and a disruption of the V̇e rhythm, suggesting opposing circadian and metabolic influences on V̇e. To determine if the molecular clock of cells involved in the neural control of breathing contributes to the daily V̇e rhythm, we examined V̇e in mice lacking BMAL1 in Phox2b-expressing respiratory cells (i.e., BKOP mice). The ventilatory and metabolic rhythms of predominantly night-fed BKOP mice did not differ from wild-type mice. However, in contrast to wild-type mice, exclusive day feeding of BKOP mice led to an unfettered daily V̇e rhythm with a peak time aligning closely with the daily V̇co2 rhythm. Taken together, these results indicate that both daily V̇co2 changes and intrinsic circadian time-keeping within Phox2b respiratory cells are predominant orchestrators of the daily rhythm in ventilation.NEW & NOTEWORTHY The master circadian clock organizes the daily rhythm in ventilation; however, the extent that this rhythm is driven by SCN regulation of metabolic rate versus other clock mechanisms remains unknown. We report that metabolic rate alone is insufficient to explain the daily oscillation in ventilation and that neural respiratory clocks within Phox2b-expressing cells additionally optimize breathing. Collectively, these findings advance our mechanistic understanding of the circadian rhythm in ventilatory control.

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Objective.In the future, thoracic electrical impedance tomography (EIT) monitoring may include continuous and simultaneous tracking of both breathing and heart activity. However, an effective way to decompose an EIT image stream into physiological processes as ventilation-related and cardiac-related signals is missing.Approach.This study analyses the potential ofMulti-dimensional Ensemble Empirical Mode Decompositionby application of theComplete Ensemble Empirical Mode Decomposition with Adaptive Noiseand a novel frequency-based combination criterion for detrending, denoising and source separation of EIT image streams, collected from nine healthy male test subjects with similar age and constitution.Main results.In this paper, a novel approach to estimate the lung, the heart and the perfused regions of an EIT image is proposed, which is based on theRoot Mean Square Errorbetween the index of maximal respiratory and cardiac variation to their surroundings. The summation of the indexes of the respective regions reveals physiologically meaningful time signals, separated into the physiological bandwidths of ventilation and heart activity at rest. Moreover, the respective regions were compared with the relative thorax movement and photoplethysmogram (PPG) signal. In linear regression analysis and in the Bland-Altman plot, the beat-to-beat time course of both the ventilation-related signal and the cardiac-related signal showed a high similarity with the respective reference signal.Significance.Analysis of the data reveals a fair separation of ventilatory and cardiac activity realizing the aimed source separation, with optional detrending and denoising. For all performed analyses, a feasible correlation of 0.587 to 0.905 was found between the cardiac-related signal and the PPG signal.

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BACKGROUND: Long COVID is defined as persistency of symptoms, such as exertional dyspnea, twelve weeks after recovery from SARS-CoV-2 infection. OBJECTIVES: To investigate ventilatory efficiency by the use of cardiopulmonary exercise testing (CPET) in patients with exertional dyspnea despite normal basal spirometry after 18 (T18) and 36 months (T36) from COVID-19 pneumonia. METHODS: One hundred patients with moderate-critical COVID-19 were prospectively enrolled in our Long COVID program. Medical history, physical examination and lung high-resolution computed tomography (HRCT) were obtained at hospitalization (T0), 3 (T3) and 15 months (T15). All HRCTs were revised using a semi-quantitative CT severity score (CSS). Pulmonary function tests were obtained at T3 and T15. CPET was performed in a subset of patients with residual dyspnea (mMRC ≥ 1), at T18 and at T36. RESULTS: Remarkably, at CPET, ventilatory efficiency was reduced both at T18 (V'E/V'CO2 slope = 31.4±3.9 SD) and T36 (V'E/V'CO2 slope = 31.28±3.70 SD). Furthermore, we identified positive correlations between V'E/V'CO2 slope at T18 and T36 and both percentage of involvement and CSS at HRCT at T0, T3 and T15. Also, negative linear correlations were found between V'E/V'CO2 slope at T18 and T36 and DLCO at T3 and T15. CONCLUSIONS: At eighteen months from COVID-19 pneumonia, 20 % of subjects still complains of exertional dyspnea. At CPET this may be explained by persistently reduced ventilatory efficiency, possibly related to the degree of lung parenchymal involvement in the acute phase of infection, likely reflecting a damage in the pulmonary circulation.

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INTRODUCTION: Cardiopulmonary exercise testing (CPET) is nowadays used to study the exercise response in healthy subjects and in disease. Ventilatory efficiency is one of the main determinants in exercise tolerance, and its main variables are a useful tool to guide pathophysiologists toward specific diagnostic pathways, providing prognostic information and improving disease management, treatment, and outcomes. AREAS COVERED: This review will be based on today's available scientific evidence, describing the main physiological determinants of ventilatory efficiency at rest and during exercise, and focusing also on how CPET variables are modified in specific diseases, leading to the possibility of early diagnosis and management. EXPERT OPINION: Growing knowledge on CPET interpretation and a wider use of this clinical tool is expected in order to offer more precise diagnostic and prognostic information to patients and clinicians, helping in the management of therapeutic decisions. Future research could be able to identify new and more simple markers of ventilatory efficiency, and to individuate new interventions for the improvement of symptoms, such as exertional dyspnea.

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This study assesses the impact of three volumetric gas flow measurement methods-turbine (fT); pneumotachograph (fP), and Venturi (fV)-on predictive accuracy and precision of expired gas analysis indirect calorimetry (EGAIC) across varying exercise intensities. Six males (Age: 38 ± 8 year; Height: 178.8 ± 4.2 cm; V ̇ O 2 peak $$ \dot{V}{\mathrm{O}}_2\mathrm{peak} $$ : 42 ± 2.8 mL O2 kg-1 min-1) and 14 females (Age = 44.6 ± 9.6 year; Height = 164.6 ± 6.9 cm; V ̇ O 2 peak $$ \dot{V}{\mathrm{O}}_2\mathrm{peak} $$ = 45 ± 8.6 mL O2 kg-1 min-1) were recruited. Participants completed physical exertion on a stationary cycle ergometer for simultaneous pulmonary minute ventilation ( V ̇ $$ \dot{V} $$ ) measurements and EGAIC computations. Exercise protocols and subsequent conditions involved a 5-min cycling warm-up at 25 W min-1, incremental exercise to exhaustion ( V ̇ O 2 $$ \dot{V}{\mathrm{O}}_2 $$ ramp test), then a steady-state exercise bout induced by a constant Watt load equivalent to 80% ventilatory threshold (80% VT). A linear mixed model revealed that exercise intensity significantly affected V ̇ O 2 $$ \dot{V}{\mathrm{O}}_2 $$ measurements (p < 0.0001), whereas airflow sensor method (p = 0.97) and its interaction with exercise intensity (p = 0.91) did not. Group analysis of precision yielded a V ̇ O 2 $$ \dot{V}{\mathrm{O}}_2 $$ CV % = 21%; SEM = 5 mL O2 kg-1 min-1. Intra- and interindividual analysis of precision via Bland-Altman revealed a 95% confidence interval (CI) precision benchmark of 3-5 mL kg-1 min-1. Agreement among methods decreased at power outputs eliciting V ̇ $$ \dot{V} $$ up to 150 L min-1, indicating a decrease in precision and highlighting potential challenges in interpreting biological variability, training response heterogeneity, and test-retest comparisons. These findings suggest careful consideration of airflow sensor method variance across metabolic cart configurations.

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PURPOSE: Ventilatory constraints are common during exercise in children, but the effects of obesity and sex are unclear. The purpose of this study was to investigate the effects of obesity and sex on ventilatory constraints (i.e., expiratory flow limitation (EFL) and dynamic hyperinflation) during a maximal exercise test in children. METHODS: Thirty-four 8- to 12-yr-old children without obesity (18 females) and 54 with obesity (23 females) completed pulmonary function testing and maximal cardiopulmonary exercise tests. EFL was calculated as the overlap between tidal flow-volume loops during exercise and maximal expiratory flow-volume loops. Dynamic hyperinflation was calculated as the change in inspiratory capacity from rest to exercise. RESULTS: Maximal minute ventilation was not different between children with and without obesity. Average end-inspiratory lung volumes (EILV) and end-expiratory lung volumes (EELV) were significantly lower during exercise in children with obesity (EILV: 68.8% ± 0.7% TLC; EELV: 41.2% ± 0.5% TLC) compared with children without obesity (EILV: 73.7% ± 0.8% TLC; EELV: 44.8% ± 0.6% TLC; P < 0.001). Throughout exercise, children with obesity experienced more EFL and dynamic hyperinflation compared with those without obesity ( P < 0.001). Also, males experienced more EFL and dynamic hyperinflation throughout exercise compared with females ( P < 0.001). At maximal exercise, the prevalence of EFL was similar in males with and without obesity; however, the prevalence of EFL in females was significantly different, with 57% of females with obesity experiencing EFL compared with 17% of females without obesity ( P < 0.05). At maximal exercise, 44% of children with obesity experienced dynamic hyperinflation compared with 12% of children without obesity ( P = 0.002). CONCLUSIONS: Obesity in children increases the risk of developing mechanical ventilatory constraints such as dynamic hyperinflation and EFL. Sex differences were apparent with males experiencing more ventilatory constraints compared with females.

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Regional lung ventilation assessment is a critical tool for the early detection of lung diseases and postoperative evaluation. Biosensor-based impedance measurements, known for their non-invasive nature, among other benefits, have garnered significant attention compared to traditional detection methods that utilize pressure sensors. However, solely utilizing overall thoracic impedance fails to accurately capture changes in regional lung air volume. This study introduces an assessment method for lung ventilation that utilizes impedance data from the five lobes, develops a nonlinear model correlating regional impedance with lung air volume, and formulates an approach to identify regional ventilation obstructions based on impedance variations in affected areas. The electrode configuration for the five lung lobes was established through numerical simulations, revealing a power-function nonlinear relationship between regional impedance and air volume changes. An analysis of 389 pulmonary function tests refined the equations for calculating pulmonary function parameters, taking into account individual differences. Validation tests on 30 cases indicated maximum relative errors of 0.82% for FVC and 0.98% for FEV1, all within the 95% confidence intervals. The index for assessing regional ventilation impairment was corroborated by CT scans in 50 critical care cases, with 10 validation trials showing agreement with CT lesion localization results.

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Background: Occupational health is closely related to harmful factors in the workplace. Dust is the primary contributing factor causing impaired lung ventilation function among employees with dust exposure, and their lung ventilation function may also be influenced by other factors. We aimed at assessing the status and influencing factors of lung ventilation function among employees exposed to dust in the enterprises of the Eighth Division located in the Xinjiang Production and Construction Corps (XPCC), China. Methods: Employees exposed to dust in enterprises of the Eighth Division located in the XPCC in 2023 were selected as the subjects of this cross-sectional study. Their lung ventilation function indicators were extracted from health examination records, and an on-site electronic questionnaire survey was conducted among them. Binary logistic regression analyses were conducted to evaluate the factors influencing lung ventilation function. Results: According to the fixed value criteria, the abnormal rates of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were 31.6, 1.4, and 0.4%, respectively. The lower limit of normal (LLN) criteria could overestimate the rate of abnormal lung ventilation function. Several factors were related to impaired lung ventilation function, including gender, age, education level, marital status, body mass index (BMI), smoking status, physical activity, the type of dust, industry, enterprise scale, occupation, length of service, working shift, monthly income, and respiratory protection. Conclusions: A relatively low abnormal rate of lung ventilation function was observed among employees exposed to dust in enterprises of the Eighth Division, XPCC, and their lung ventilation function was associated with various factors. Effective measures should be taken urgently to reduce the effects of adverse factors on lung ventilation function, thereby further protecting the health of the occupational population.

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Objective.Impedance pneumography (IP) has provided static assessments of subjects' breathing patterns in previous studies. Evaluating the feasibility and limitation of ambulatory IP based respiratory monitoring needs further investigation on clinically relevant exercise designs. The aim of this study was to evaluate the capacity of an advanced IP in ambulatory respiratory monitoring, and its predictive value in independent ventilatory capacity quantification during cardiopulmonary exercise testing (CPET).Approach.35 volunteers were examined with the same calibration methodology and CPET exercise protocol comprising phases of rest, unloaded, incremental load, maximum load, recovery and further-recovery. In 3 or 4 deep breaths of calibration stage, thoracic impedance and criterion spirometric volume were simultaneously recorded to produce phase-specific prior calibration coefficients (CCs). The IP measurement during exercise protocol was converted by prior CCs to volume estimation curve and thus calculate minute ventilation (VE) independent from the spirometry approach.Main results.Across all measurements, the relative error of IP-derived VE (VER) and flowrate-derived VE (VEf) was less than 13.8%. In Bland-Altman plots, the aggregate VE estimation bias was statistically insignificant for all 3 phases with pedaling exercise and the discrepancy between VERand VEffell within the 95% limits of agreement (95% LoA) for 34 or all subjects in each of all CPET phases.Significance.This work reinforces the independent use of IP as an accurate and robust alternative to flowmeter for applications in cycle ergometry CPET, which could significantly encourage the clinical use of IP and improve the convenience and comfort of CPET.

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BACKGROUND: The Incentive Spirometer (IS) increases lung volume and improves gas exchange by visually stimulating patients to take slow, deep breaths. It prevents respiratory complications and treats postoperative atelectasis in patients undergoing abdominal, thoracic, and neurosurgical procedures. Its effectiveness has been validated in studies that support improved lung capacities and volumes in individuals with respiratory complications, postoperative thoracic surgery, upper abdominal surgery, and bariatric surgery. The modified Pachón incentive spirometer (MPIS) is a cost-effective alternative to branded IS. It is crucial to validate whether the MPIS distributes ventilation as effectively as commercial devices do. Ventilation distribution will be measured using electrical impedance tomography. OBJECTIVE: The aim is to compare the distribution of pulmonary ventilation between the MPIS and another commercial IS in healthy adults using electrical impedance tomography. METHODS: A crossover clinical trial is proposed to evaluate the measurement of pulmonary ventilation distribution using EIT in a sample of healthy adults. All participants will use a commercial flow IS and the MPIS, with the order of assignment randomized. This research will use electrical impedance tomography to validate the operation of the MPIS. CONCLUSIONS: This study protocol will compare two incentive spirometers' impact on pulmonary ventilation, potentially endorsing the adoption of a cost-effective device to enhance accessibility for targeted populations. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NTC05532748).

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High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self-administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide-free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. HIGHLIGHTS: What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide-free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

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The movement of air into and out of the lungs is facilitated by changes in pressure within the thoracic cavity relative to atmospheric pressure, as well as the resistance encountered by airways. In this process, the movement of air into and out of the lungs is driven by pressure gradients established by changes in lung volume and intra-alveolar pressure. However, pressure never sucks! The concept that pressure never sucks, pressure only pushes encapsulates a fundamental principle in the behavior of gases. This concept challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we explore the essence of this concept and its applications in pulmonary ventilation. Pressure is one of the most important concepts in physics and physiology. Atmospheric pressure at sea level is equal to 1 atmosphere or around 101,325 Pascal [Pa (1 Pa = 1 N/m2)]. This huge pressure is pushing down on everything all the time. However, this pressure is difficult to understand because we do not often observe the power of this incredible force. We used five readily available, simple, and inexpensive demonstrations to introduce the physics and power of pressure. This extraordinarily complex physics concept was approached in a straightforward and inexpensive manner while still providing an understanding of the fundamental concepts. These simple demonstrations introduced basic concepts and addressed common misconceptions about pressure.NEW & NOTEWORTHY The concept that pressure never sucks, pressure only pushes challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we will explore the essence of this concept and its applications in pulmonary ventilation. Specifically, we used five readily available, simple, inexpensive demonstrations to introduce the physics and power of pressure.

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