A Novel Device for Pulmonary Expansion Under Simulated Healthy and Neuromuscular Conditions: A Bench Simulation Study

Abstract

Background

Amyotrophic Lateral Sclerosis (ALS) leads to a progressive decline in respiratory function, requiring volumetric expansion techniques to prevent hypoventilation. However, the mechanical performance of devices used for this purpose requires evaluation under controlled conditions in bench simulation studies. Devices, such as the manual resuscitator, are commonly used, but present limitations, including high pressures, variable flow, among others. A novel respiratory muscle training device designed to provide controlled flow and pressure (ILLIFE-T) was developed.

Objective

To evaluate the behavior of the variables pressure, volume, and flow during the volumetric expansion technique, comparing the new device with the manual resuscitator and the manual resuscitator + Positive Expiratory Pressure (PEP), using simulated models of healthy and ALS affected lungs.

Methods

This bench simulation study used the ASL 5000 simulator, configured with predefined respiratory profiles representing healthy and ALS respiratory conditions. Four repetitions of the volumetric expansion maneuver were performed for each device and simulated respiratory condition, with five insufflations per repetition. One recording was randomly selected from each repetition for analysis, resulting in four observations per device and simulated respiratory condition.

Results

In the simulation with healthy respiratory conditions, the new device generated higher pressure (23.38±3.81 cmH₂O), volume (1991.25 ±174.10 mL), and lower flow variability (–1.47±11.43 L/min) compared with the manual resuscitator (12.25±11.73 cmH₂O; 1113.64±131.75 mL; 18.84±61.31 L/min) and the manual resuscitator with PEP valve (16.89±0.64 cmH₂O; 1817.25±86.77 mL; –49.49±9.96 L/min), respectively. In ALS simulated models, the new device also achieved higher pressure (23.69±3.29 cmH₂O) and volume (2235.28±264.74 mL) compared with the manual resuscitator (8.33±8.34 cmH₂O; 563.45±212.03 mL, respectively) and the manual resuscitator with PEP valve (14.89±7.60 cmH₂O; 1449.86±153.09 mL, respectively). Flow values were similar among devices: 15.10 ± 18.00 L/min for the new device, 19.28±56.03 L/min for the manual resuscitator, and 0.18±51.67 L/min for the manual resuscitator with PEP valve.

Conclusion

Pressure and volume were higher with the new device in both simulated models. Flow did not differ significantly among devices, although lower variability was descriptively observed with the new device.

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Introduction

Amyotrophic Lateral Sclerosis (ALS) is a degenerative and idiopathic disease of the human motor system. Survival depends on factors such as clinical presentation (phenotype), rate of disease progression, early onset of respiratory failure, and nutritional status.1 Among the clinical phenotypes, bulbar can be mentioned, characterized by early impairment of the muscles responsible for speech, swallowing, and breathing, and associated with faster disease progression and a higher risk of respiratory complications.2,3 A decline in lung volumes, including Tidal Volume (TV) and Vital Capacity (VC) represents a major ventilatory limitation, leading to alveolar hypoventilation, progressive hypercapnia and eventual respiratory failure. These symptoms require alveolar recruitment techniques and mechanical ventilation for proper management.4

In individuals with ALS, maximal expiratory pressure (MEP) shows a marked decline compared with other pulmonary function variables, indicating deterioration of expiratory muscle strength, which leads to hypoventilation and inadequate gas exchange,5 which is the main cause of mortality in this population,6 as well as an increased risk of pneumonia and other respiratory infections due to impaired cough reflex and ineffective airway secretion clearance.7 MEP is therefore considered a sensitive measure for monitoring respiratory muscle strength in this population.5

Resistance exercises provide functional benefits measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS), such as improved muscle strength, reduced fatigue, and functional independence,8 as well as quality of life.9 However, they are not capable of increasing forced vital capacity (FVC).10,11

Bello-Haas et al10 applied resistance exercises to the upper and lower limbs with moderate load, observing functional benefits without ventilatory impact. Similarly, Su et al11 analyzed protocols combining 1RM-based resistance and aerobic exercises in a systematic review, showing maintenance of pulmonary function but no increase in FVC. Lyall et al12 reported that resistance exercise combined with phrenic nerve stimulation had no clear effect on respiratory strength, particularly in individuals with bulbar dysfunction.

Among the available strategies for respiratory improvement, manual hyperinflation (MH) using a manual resuscitator (MR) has been shown to improve lung mechanics,13 gas exchange,13,14 static and dynamic compliance,15 chest X-ray findings, lung volume,14 secretion clearance,16 muscle strength, and infection rates.17 This technique consists of delivering a series of tidal volumes greater than normal, combined with an inspiratory pause and a rapid release of the MR and reservoir.13,16 Despite the reported benefits of using the MR for MH, there are controversies regarding its use. An increase in cardiac output and significant variations in peak inspiratory pressure percentage was observed during the technique, due to a reduction in left ventricular afterload detected in a six-week HM protocol.18 Concerns have been raised about the effects of the MH technique using a MR, both in healthy lungs and in those that are severely injured. This technique may produce high inspiratory pressures, excessive VT, impairing the pulmonary barrier and leading to the translocation of pro-inflammatory substances into the systemic circulation, exacerbating injury and pulmonary inflammation,19 as well as repetitive alveolar opening and closing cycles during mechanical ventilation. This can be caused by increased pulmonary hyperinflation of compliant units, diverting airflow from well-ventilated areas to non-ventilated regions,13 exacerbating alveolar hypoventilation,20 and worsening ventilatory control due to reduced airway defense.21

Mechanical insufflation-exsufflation (MI-E) is commonly used to help with coughing in patients with ALS, but it can provoke adverse laryngeal responses, potentially leading to treatment failure.22 In particular, patients with bulbar ALS exhibit extreme fluctuations in airflow during forced expiration, indicating increased laryngeal resistance. Moreover, the presence of sawtooth-like airflow patterns suggests that laryngeal dysfunction may impair effective cough mechanisms, resulting in inadequate airway clearance.23

To overcome these limitations, a new device was developed based on a previous device,24 for respiratory muscle training, enabling lung volume expansion therapy combined with increased pressure in the upper airways and expiratory training after achieving maximum lung volume. It allows for controlled passive air release through a spring-based mechanism, using counter-resistance to train the respiratory muscles and improving their response in individuals with severely limited lung capacity. This includes a calibrated flow and volume generation system for optimized alveolar opening, a non-return valve coupled to a manometer for precise control of inspiratory pressure, and a graduated air outlet mechanism that allows the recruited lung volume to be maintained. This device was designed to maximize alveolar opening through controlled flow and volume, maintain recruitment throughout the entire respiratory cycle, and optimize ventilation distribution in collapsed lung areas.

Previous comparative bench studies have primarily evaluated different manual resuscitation circuits and techniques.25,26 However, these approaches may provide less predictable control of pressure, flow, and delivered volume during lung volume expansion, while evidence on devices specifically designed to provide controlled pressure and flow during this maneuver remains limited. Given the above, this experimental study aims to evaluate and compare the behavior of lung variables (pressure, flow, and volume) in an experimental model simulating a healthy adult and an adult with ALS during a volumetric expansion technique using the new device, compared with a MR and a MR combined with an adjustable Positive Expiratory Pressure (PEP) valve (MR+PEP).

Methods

Mechanical characteristics of a healthy adult and an adult with ALS were simulated in a bench study.

Simulator, Lung Model, and Devices for the Volumetric Expansion Technique

An experimental study was carried out using an ASL 5000 simulator (IngMar Medical, Pittsburgh, PA, USA), operated using predefined respiratory simulation profiles, with respiratory characteristics determined by the device according to the selected respiratory condition. Static compliance and airway resistance were predetermined by the device and incorporated in a standardized manner without manual adjustment. For the simulated healthy adult lung, the system applied a compliance of 80 mL/cmH₂O and resistance of 6 cmH₂O/L/s. For the simulated lung of an individual with ALS, compliance was defined as 100 mL/cmH₂O and resistance as 8 cmH₂O/L/s. This procedure ensured reproducibility and accuracy of the experimental conditions. The volumetric expansion technique was performed using three devices: a respiratory muscle training device (ILLIFE-T) (Lumiar Healthcare Ltda, São Caetano do Sul, SP Brazil), MR (Lumiar Healthcare Ltda, São Caetano do Sul, SP Brazil), and PEP valve (Besmed Health Business Corp., Taipei, Taiwan). The simulator was connected to an analog manometer to monitor the downstream pressure generated by each device. All maneuvers were performed by the same operator using the air stacking technique. In all three devices evaluated, insufflation was performed using a MR, whose bag was compressed with both hands. Five consecutive insufflations were performed to progressively stack air into the simulated lung. During the maneuver, pressure was continuously monitored using the manometer and was not allowed to exceed 30 cmH₂O. After the fifth insufflation, the bag was allowed to return to its initial position before the next sequence of five insufflations was initiated. Regarding PEP, in the device without an adjustable valve, PEP was determined by the ventilator. In the MR with an adjustable valve, the valve was set at 15 cmH₂O. In the new device, the counter-resistance valve was adjusted to 15 cmH₂O for the healthy lung simulation and to 8 cmH₂O for the ALS lung simulation. The PEP values established in this study were based on physiological evidence indicating that levels between 8 and 15 cmH₂O are recommended to promote an increase in functional residual capacity (FRC) during spontaneous breathing. At these levels, PEP does not act directly to reopen already-collapsed alveoli, as its application occurs predominantly during the expiratory phase. A benefit is the sustained increase in FRC, which allows the subsequent tidal volume to reach values above the alveolar opening volume. This mechanism helps prevent atelectasis and maintain previously unstable airways open, an effect already demonstrated in populations such as postoperative patients.27 The new device is protected by Brazilian patent application BR1020220255300 and is commercially available from Lumiar Health Builders Equipamentos Hospitalares Ltda, São Caetano do Sul, SP Brazil (Figures 1 and 2). The device is currently regulated in Brazil as a Class II medical device under ANVISA notification No. 80488299016. Its commercialization is subject to the applicable Brazilian regulatory requirements for medical devices, including requirements related to safety, performance, quality, and good manufacturing practices.

Figure 1.

Schematic representation of the respiratory muscle training device and airflow pathways. 1: Air inlet from the Manual Resuscitator. 2: Air passage through the retention valves. 3: Air flow directed to the patient. 4: Air outlet through the safety valve in case of high pressure. 5: Return airflow from the patient. 6: Endurance valve opening 7: Air outlet to the environment. Source: Adir Schoier (Victum Design).

Figure 2.

Final version of the new device shown in different views. Source: Adir Schoier (Victum Design).

An adult MR was connected directly to the ASL 5000 simulator and to an analog manometer. Insufflations were performed using the MR at its maximum capacity. Subsequently, an adjustable PEP valve was attached to the MR and the manometer (MR+PEP). Finally, the new device was connected between the simulator and MR. All three devices were evaluated using the same air-input system and under the same simulator configuration for each respiratory condition.

For each device and simulated respiratory condition, four repetitions of the volumetric expansion maneuver were performed, with five insufflations in each repetition, totaling 20 insufflations per device per condition. All maneuvers were performed by the same operator using the air stacking technique. For each repetition, one recording was randomly selected from the five insufflations, from which pressure, volume, and flow values were obtained from the ASL 5000. Thus, each repetition provided one observation for each variable, resulting in four observations per device per simulated respiratory condition for statistical analysis. Accordingly, the repetition was considered the experimental unit, and the individual insufflations within each repetition were not treated as independent observations. Pressure, volume, and flow signals were recorded by the ASL 5000 throughout the insufflations.

Statistical Analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), version 26.0 (IBM Corporation, Armonk, NY, USA). Means and standard deviations were calculated for continuous variables to describe the data. One-way ANOVA was used to compare parameters between the three different devices within each respiratory condition. When ANOVA indicated statistically significant differences, Tukey’s post hoc test was applied to identify pairwise comparisons with significant differences. The comparison of pressure, volume, and flow parameters between devices based on the group (simulated healthy individuals and simulated individuals with ALS) was performed using a factorial analysis of variance (ANOVA), considering two independent factors: group and type of device, as well as the interaction between these factors (group*device). The assumptions underlying the ANOVA models were assessed using the Shapiro–Wilk test for normality of residuals and Levene’s test for homogeneity of variances. No significant violations were identified (all p > 0.05). Effect sizes for the factorial ANOVA were reported as partial eta squared (η²p), calculated from the F statistics and corresponding degrees of freedom. Ninety-five percent confidence intervals (95% CIs) for η²p were calculated using the noncentral F distribution. All tests were two-sided, with a significance level of α = 0.05.

The statistical power calculation was conducted post hoc, based on the effect sizes observed in the factorial analyses, using the statsmodels package (Python, version 0.14). For the ANOVA with the dependent variable “volume,” the power was approximately 99.8%, indicating adequate capability to detect differences between groups. For “pressure,” the power was 83.3%, also considered satisfactory. However, for “flow,” the estimated power was only 69.8%, suggesting a limited ability to detect true effects, possibly due to an insufficient sample size for this specific variable. The calculations followed Cohen’s recommendations,28 considering a 5% significance level and six groups formed by the combinations of the “group” and “device” factors.

Results

This is a bench study that compared the behavior of respiratory variables using three different devices in simulated models of healthy individuals and those with ALS during the volumetric expansion technique. Table 1 presents the means and standard deviations of pressure, volume, and flow in simulated models of healthy individuals and those with ALS, evaluated using the new device, MR, and MR+PEP valve in a simulator. In simulated individuals with ALS, the new device, compared with the MR and the MR+PEP, showed higher values for pressure (23.69 ± 3.29 cmH₂O vs 8.33 ± 8.34 cmH₂O vs 14.89 ± 7.60 cmH₂O, p = 0.032, respectively) and volume (2235.28 ± 264.74 mL vs 563.45 ± 212.03 mL vs 1449.86 ± 153.09 mL, p < 0.001, respectively) (Figures 3 and 4). However, flow indicated high variability, showing similar values between the MR and the new device (19.28 ± 56.03 L/min vs 15.10 ± 18.00 L/min, respectively) (Figure 5). The MR+PEP valve showed a mean flow of 0.18 ± 51.67 L/min. Simple comparisons revealed significant differences in pressure and volume between the devices. Post hoc analysis indicated that pressure was significantly higher with the new device compared to the MR. Regarding volume, significant differences were observed between the MR and the MR+PEP valve, between the MR and the new device, and between the MR+PEP valve and the new device (Table 1).

Table 1.

Descriptive Statistics of Pressure, Volume, and Flow Generated by the Devices in a Bench Model Simulating Healthy and Amyotrophic Lateral Sclerosis Respiratory Mechanics

	New Device	MR	MR + PEP	p*
Healthy model
Pressure	23.38±3.81	12.25±11.73	16.89±0.64	0.14
Volume	1991.25±174.10†	1113.64 ±131.75	1817.25±86.77†	<0.001
Flow	−1.47±11.43	18.84±61.31	−49.49±9.96	0.067
ALS model
Pressure	23.69±3.29†	8.33±8.34	14.89±7.60	0.032
Volume	2235.28±264.74†	563.45±212.03	1449.86±153.09†	<0.001
Flow	15.10±18.00	19.28±56.03	0.18±51.67	0.82

Notes: Values are presented as mean ± standard deviation. *One-way ANOVA; ^† Post Hoc Tukey’s test.

Abbreviations: ALS, Amyotrophic Lateral Sclerosis; MR, manual resuscitator; MR+PEP, manual resuscitator with an adjustable PEP valve.

Figure 3.

Comparison of pressure (cmH₂O) among the Manual Resuscitator (MR), Manual Resuscitator with an adjustable PEP valve (MR+PEP), and New Device in simulated healthy and ALS respiratory conditions. Boxplots show the distribution of pressure measurements for each device and simulated respiratory condition. Boxes represent the median and interquartile range, and open circles represent individual measurements (n = 4 per device in each group; N = 24). Main effect of group, p = 0.519; main effect of device, p = 0.005; group × device interaction, p = 0.833.

Abbreviations: ALS, Amyotrophic Lateral Sclerosis; MR, Manual Resuscitator; MR+PEP, Manual Resuscitator with an adjustable PEP valve.

Figure 4.

Comparison of volume (mL) among the Manual Resuscitator (MR), Manual Resuscitator with an adjustable PEP valve (MR+PEP), and New Device in simulated healthy and ALS respiratory conditions. Boxplots show the distribution of volume measurements for each device and simulated respiratory condition. Boxes represent the median and interquartile range, and open circles represent individual measurements (n = 4 per device in each group; N = 24). ***p < 0.001.

Abbreviations: ALS: Amyotrophic Lateral Sclerosis. MR: Manual Resuscitator. MR+PEP: Manual Resuscitator with an adjustable PEP valve.

Figure 5.

Comparison of flow (L/min) among the Manual Resuscitator (MR), Manual Resuscitator with an adjustable PEP valve (MR+PEP), and New Device in simulated healthy and ALS respiratory conditions. Boxplots show the distribution of flow measurements for each device and simulated respiratory condition. Boxes represent the median and interquartile range, and open circles represent individual measurements (n = 4 per device in each group; N = 24). Main effect of group, p = 0.202; main effect of device, p = 0.118; group × device interaction, p = 0.488.

Abbreviations: ALS, Amyotrophic Lateral Sclerosis; MR, Manual Resuscitator; MR+PEP, Manual Resuscitator with an adjustable PEP valve.

In simulated healthy individuals, pressure was also higher using the new device compared with the MR and the MR+PEP (23.38 ± 3.81 cmH₂O vs 12.25 ± 11.73 cmH₂O vs 16.89 ± 0.64 cmH₂O, p = 0.14, respectively), as was volume (1991.25 ± 174.10 mL vs 1113.64 ± 131.75 mL vs 1817.25 ± 86.77 mL, p < 0.001, respectively) (Figures 3 and 4). Flow varied widely and was negative using the MR+PEP valve (–49.49 ± 9.96 L/min) and the new device (–1.47 ± 11.43 L/min), whereas the MR alone showed positive values (18.84 ± 61.31 L/min) (Figure 5). The comparison of the analyzed variables in simulated healthy individuals showed a significant difference only for volume, with post hoc analysis revealing differences between the MR and the MR+PEP, as well as between the MR and the new device. No significant differences were found for flow in either group (Table 1 and Figure 3).

Factorial ANOVA revealed significant effects of the devices on pressure (p = 0.005) and volume (p < 0.001), as well as a significant interaction effect between the group and device concerning volume (p = 0.001). Flow did not show significant differences in the factorial ANOVA for devices, groups, or the device*group interaction (Table 2), and was therefore omitted from the post hoc analysis. Tukey post hoc analysis indicated that pressure was significantly higher using the new device compared with the MR (p = 0.004). For volume, significant differences were observed between the MR and the MR+PEP (p < 0.001), between the MR and the new device (p < 0.001), and between the MR+PEP and the new device (p < 0.001). To interpret the factorial ANOVA results, the trends observed in the means and standard deviations in Table 1 were considered, indicating higher pressure and volume with the new device, while flow remained highly variable with no statistically significant differences (Figure 6). Figure 6 shows the estimated marginal means and the effects of respiratory condition, device, and their interaction. Pressure showed an interaction effect between devices (Figure 6A). Volume exhibited a significant interaction between groups, between devices, and between groups and devices (Figure 6B). Flow did not show significant interaction (Figure 6C).

Table 2.

Comparison of Pressure, Volume, and Flow Between Groups Based on the Devices

Comparisons	Pressure	Volume	Flow
Groups	0.519 η2p = 0.023 (95% CI: 0.000–0.275)	0.007 η2p = 0.342 (95% CI: 0.036–0.603)	0.202 η2p = 0.089 (95% CI: 0.000–0.379)
Devices	0.005 η2p = 0.448 (95% CI: 0.074–0.667)	<0.001 η2p = 0.919 (95% CI: 0.825–0.954)	0.118 η2p = 0.211 (95% CI: 0.000–0.482)
Device*Group	0.833 η2p = 0.020 (95% CI: 0.000–0.189)	<0.001 η2p =0.544 (95% CI: 0.172–0.730)	0.488 η2p = 0.077 (95% CI: 0.000–0.324)

Notes: Bold values indicate statistically significant results (p < 0.05). Factorial ANOVA.

Abbreviation: η²p, partial eta squared; CI, confidence interval.

Figure 6.

Comparison of estimated marginal means for pressure, volume, and flow between simulated healthy and ALS respiratory conditions according to device type. (A) pressure (cmH₂O); (B) volume (mL); (C) flow (L/min). Error bars represent 95% confidence intervals (n = 4 per device × group; N = 24). P-values for the effects of respiratory condition (Groups), device, and the Group × Device interaction are shown in each panel. The codes displayed in each panel refer to the ANOVA effects: ns, not significant; **p < 0.01; ***p < 0.001. (A), group p = 0.519 (ns), device p = 0.005 (**), group × device p = 0.833 (ns). (B), group p = 0.007 (**), device p < 0.001 (***), group × device p < 0.001 (***). (C), group p = 0.202 (ns), device p = 0.118 (ns), group × device p = 0.488 (ns).

Abbreviations: ALS, Amyotrophic Lateral Sclerosis; MR, Manual Resuscitator; MR+PEP, Manual Resuscitator with an adjustable PEP valve.

Discussion

The present study evaluated the pressure, volume, and flow variable behaviors using different devices in simulated models of healthy and ALS-affected lungs. To the best of our knowledge, this is the first study to document these evaluations using different devices in simulated models with these conditions. In the pressure analysis, the new device generated numerically higher pressure than the other devices in both simulated conditions, however, this difference was statistically significant only in the ALS model. The increase in volume with the new device compared with the other devices was more pronounced in simulated individuals with ALS than in the simulation of healthy individuals, suggesting that the impact of the device on volume is modulated by clinical condition. Although the New Device showed lower variability in flow than the other devices, this difference was not statistically significant, and the flow measurements showed substantial variability across devices. Therefore, the lower flow variability should be considered a descriptive finding rather than a demonstrated advantage, and conclusions regarding flow performance should be interpreted with caution.

The average change in pressure, flow, and volume during the volumetric expansion technique in patients with ALS has been investigated, paying special attention to its effects on respiratory function. Evidence indicates that volumetric expansion techniques using pressures of up to 50 cmH₂O can increase the maximum insufflation capacity (MIC) in individuals with ALS,29,30 although the overall impact on pressure and flow metrics remains poorly defined. Healthy individuals may require inspiratory pressures around 40 cmH₂O to fully re-expand collapsed alveoli.31 One study30 reported a significant increase in MIC of 0.13 L after three months of intervention, especially evident during the first month, suggesting that volumetric expansion can increase lung volume, but does not necessarily lead to relevant improvements in respiratory mechanics or flow rates.

Maintaining inspiratory pressure for a few seconds allows greater redistribution of air to alveolar units with longer time constants, leading to more homogeneous ventilation. When air enters quickly and is exhaled shortly after, it tends to ventilate primarily areas with lower resistance and higher compliance.32,33 In clinical settings, sustained pressures of 20 to 30 cmH₂O for up to 10 seconds are considered safe for expansion maneuvers, as long as the individual’s physiological limits are respected.34,35

Lung compliance is influenced by the elastic properties of lung tissue and surface tension, which can be altered by the presence of secretions.33 The mucus viscosity and volume can increase airway resistance, thereby reducing lung compliance, as higher mucus viscosity impedes airflow and limits lung expansion.36 Patients with neuromuscular diseases (NMD) often face significant challenges related to respiratory secretions due to muscle weakness, which affects cough efficiency and hinders their ability to clear secretions effectively.37 The combination of muscle weakness and increased secretions resulting from infections can therefore lead to serious complications, including atelectasis and pneumonia.38 Techniques such as air stacking and mechanically assisted cough are essential in improving secretion clearance in these individuals.37,39

The new device, which was evaluated in this simulated study of healthy individuals and those with ALS, demonstrated greater delivered volume during the simulated volumetric expansion maneuver, which may warrant investigation of its potential effects on maximum insufflation capacity in clinical studies. These mechanical characteristics may warrant further investigation regarding their potential role in secretion mobilization, as secretion clearance was not directly assessed in the present study. This performance may be related to its controlled resistance system and ability to sustain continuous flow for a longer duration. The higher pressure generated by the new device may have implications for lung volume expansion, although alveolar recruitment was not directly assessed in the study. The greater volume observed may indicate a greater capacity for air delivery under the simulated conditions. Although the new device generated higher pressure, all measured pressures remained below the predefined experimental limit of 30 cmH₂O, as recommended in the literature.32,35 The device’s adjustable resistance feature may allow load adaptation. However, its effects on clinical safety and the risk of barotrauma require evaluation in clinical studies.

MH is a technique aimed at restoring lung volumes and is crucial for maintaining respiratory function in individuals with NMD. This procedure involves the insufflation of large volumes of air into the lungs, which helps counteract the restrictive lung disease commonly associated with these conditions. Lung volume recovery is particularly important for patients with reduced VC and maximum insufflation capacity.30 In our study, we observed a significant increase in volume during the MH technique, generating volume expansion using the new device. This effect may be explained by the functioning of the device, which operates based on eccentric contraction. This contraction is induced by the counter-resistance force within the pharyngeal air column, facilitated by the increase in total lung volume, thus promoting the active lengthening of the muscle under external load. A study40 involving children’s congenital muscular dystrophy using MH with a CoughAssist machine observed a volume increase at 4 and 8 months in the intervention group, as well as an improvement in the quality of life reported by the caregiver, compared to the control group, which required increased maximum insufflation pressure to achieve high volumes. This study provided important contributions to understanding the effects of the intervention on lung compliance, respiratory volumes, and the prevention of respiratory complications in this population.

Individuals with ALS have a low cough capacity, which causes difficulty clearing airway secretion and is a frequent cause of hospitalizations. Increases in lung volume may contribute to the generation of expiratory flow required for effective cough;17 however, cough effectiveness was not directly assessed in the present study. The increase in volume observed with the new device may have potential implications for cough effectiveness; however, cough effectiveness was not directly assessed in the present study. Other devices on the market also aim to address this issue, including mechanical insufflation/exsufflation systems and expiratory flow acceleration technologies. In the study by Nicoli et al41 no significant increases in cough were observed in individuals using the devices mentioned earlier. Future research using the new device should be conducted to evaluate its potential effect on cough effectiveness and the maintenance of respiratory variables in the long term.

In addition to the pressure and volume outcomes, the new device demonstrated a noteworthy functional characteristic: the ability to maintain a flow with low variation over time, leading to a more linear and predictable pattern during the inspiratory phase. This feature is particularly relevant when considering the laryngeal response to abrupt changes in airflow.

Studies42,43 show that when applying MI-E in individuals with ALS, the high airflow velocity can trigger undesirable upper airway responses, such as laryngeal adduction during insufflation. This phenomenon was particularly associated with upper motor neuron and pseudobulbar dysfunction, which hinders the free flow of air into the lungs and consequently impairs the effectiveness of the maneuver. Additionally, the authors highlight that these alterations may be linked to fluid-structure interaction mechanisms, where increased airflow velocity leads to undesired laryngeal deformation through finely tuned motor reflexes.42 Despite its well-established use, the specific dynamics of pressure transmission in the upper airways during MI-E remain unclear. Moreover, the precise relationships between anatomical structures, applied pressure, and the resulting airflow during MI-E are not yet fully understood.43 When triggered, these responses result in dynamic constriction of the upper airways, increased resistance, and potential laryngeal collapse.42

The more continuous and controlled airflow observed with the new device may warrant further investigation regarding its potential effects on upper-airway responses. This controlled flow profile may have potential implications for airway tolerance and safety. However, patient safety and comfort were not directly assessed in the present bench study and require evaluation in future clinical studies. According to Bernoulli’s principle,24 in a flowing fluid, static pressure is inversely proportional to flow velocity: the higher the airspeed, the lower the pressure exerted on the airway walls. Thus, variations in airflow directly influence intraluminal pressures. However, smaller fluctuations in flow lead to less significant pressure changes, which implies a reduced risk of airway wall collapse or suction. This occurs because Bernoulli’s equation demonstrates an exponential relationship between fluid velocity and pressure drop (P + ½ρv² + ρgh = constant). Consequently, significant increases in air velocity (ie, large flow variations) result in more substantial reductions in static pressure.27 This means that the more abrupt the acceleration of air within the airway, for example, during forced inspiration or partial obstruction with increased resistance, the more significant the Bernoulli effect will be, and therefore, the greater the risk of dynamic collapse in more compliant segments such as the oropharynx. Conversely, small flow variations, such as those occurring during quiet breathing, tend to preserve a more homogeneous pressure distribution, reducing the risk of soft airway structures collapsing.

From a practical perspective, the mechanical profile observed with the new device may be relevant to lung volume expansion strategies in individuals with neuromuscular diseases, particularly when controlled delivery of pressure and volume is desired. The higher pressure and lung volume observed in both simulated respiratory conditions suggest that the device may provide a more consistent mechanical response than the MR-based approaches evaluated in this study. These characteristics may support its further investigation as a tool for respiratory physiotherapy and lung volume recruitment. However, the present findings represent mechanical performance under controlled bench conditions and do not establish clinical effectiveness or superiority. Clinical studies are therefore required to determine whether these mechanical characteristics translate into meaningful physiological or functional benefits in patients.

Our study is preclinical, conducted using simulations of healthy individuals and those with ALS. Furthermore, the study did not include analyses involving real patients, such as the MIC. Our results cannot be extrapolated to outcomes such as improved survival, cough effectiveness, or reduced hospitalizations. In addition, we did not assess how oxygenation would behave with the different devices, nor did we collect spirometry data that could have provided a more comprehensive view of pulmonary function. Another limitation is the lower statistical power observed for the flow outcome, which may have limited the ability to detect true differences between devices and simulated respiratory conditions. Therefore, the flow findings should be interpreted with caution and confirmed in studies with larger sample sizes. Nevertheless, as a first laboratory-based study, our observations open up new perspectives for future investigations involving real participants.

Conclusion

The results of this experimental study demonstrate that the new device generated higher pressure and volume than MR based approaches under the simulated respiratory conditions. Additionally, the new device showed lower flow variability, although this difference was not statistically significant. These findings indicate a distinct mechanical performance profile of the new device under controlled experimental conditions and support further clinical validation to determine whether these mechanical characteristics translate into clinically meaningful physiological or functional benefits in individuals with neuromuscular diseases.

Funding Statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Previous Presentation

Poster: Comparative analysis among pressure resistance valve and ambu therapy on flow rate, pressure, and volume during volume recruitment in healthy individuals. JIVD-ERCA, Lyon, March, 2025. Authors: Alessandra Carneiro Dorça, Aline Leal Silva, Raiene Campos Caminha, Letícia de Araújo Morais. Presenter: Alessandra Carneiro Dorça.

Abbreviations

ALS, Amyotrophic Lateral Sclerosis; PEP, Positive Expiratory Pressure; TV, Tidal Volume; VC, Vital Capacity; MEP, Maximal Expiratory Pressure; ALSFRS, Amyotrophic Lateral Sclerosis Functional Rating Scale; FVC, Forced Vital Capacity; MH, Manual Hyperinflation; MI-E, Mechanical insufflation-exsufflation; FRC, Functional Residual Capacity; SPSS, Statistical Package for the Social Sciences; ANOVA, Factorial Analysis of Variance; NMD, Neuromuscular Diseases; MIC, Maximum Insufflation Capacity.

Data Sharing Statement

The datasets generated and/or analyzed during the current study are available from the authors upon reasonable request.

Ethics Approval and Consent to Participate

This was deemed not applicable.

Consent for Publication

This was deemed not applicable.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

ACD is the patent holder of the ILLIFE-T device and has a commercial interest in its development and commercialization. LAM declares no conflicts of interest.