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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
<issn pub-type="epub">2296-858X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2025.1538280</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Medicine</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Effects of different exhalation valves on CO<sub>2</sub> rebreathing and ventilator performance during noninvasive ventilation</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Li</surname> <given-names>Xinyu</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Dai</surname> <given-names>Bing</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Zhou</surname> <given-names>Chengguang</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Hou</surname> <given-names>Haijia</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Wang</surname> <given-names>Shengchen</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Li</surname> <given-names>Xiangrui</given-names></name>
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<contrib contrib-type="author">
<name><surname>Zhao</surname> <given-names>Hongwen</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Wang</surname> <given-names>Wei</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Tan</surname> <given-names>Wei</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of China Medical University</institution>, <addr-line>Shenyang</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Shenyang RMS Medical Tech Co., Ltd.</institution>, <addr-line>Shenyang</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001">
<p>Edited by: Manoj Biniwale, University of Southern California, United States</p>
</fn>
<fn fn-type="edited-by" id="fn0002">
<p>Reviewed by: Meng Dai, Fourth Military Medical University, China</p>
<p>Ahmet Cemal Pazarl&#x0131;, Gaziosmanpa&#x015F;a University, T&#x00FC;rkiye</p>
</fn>
<corresp id="c001">&#x002A;Correspondence: Wei Tan, <email>canhetingyu987@yeah.net</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>23</day>
<month>07</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>12</volume>
<elocation-id>1538280</elocation-id>
<history>
<date date-type="received">
<day>02</day>
<month>12</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>07</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Li, Dai, Zhou, Hou, Wang, Li, Zhao, Wang and Tan.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Li, Dai, Zhou, Hou, Wang, Li, Zhao, Wang and Tan</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Background</title>
<p>Noninvasive ventilation (NIV) is widely used to improve oxygenation and reduce carbon dioxide (CO<sub>2</sub>) retention in patients with respiratory failure. However, it remains unclear whether different types of exhalation valves affect CO<sub>2</sub> rebreathing and ventilator performance during NIV.</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>Three noninvasive ventilators (V60, Flexo, and Stellar150) with single-limb circuits and four different exhalation valves (single-arch, whisper swivel, plateau exhalation, and vented mask valves) were separately connected in series to a lung simulator. CO<sub>2</sub> gas was injected from the simulated lung outlet, maintaining the end-expiratory CO<sub>2</sub> (PetCO<sub>2</sub>) at 80&#x202F;mmHg. Both the CO<sub>2</sub> rebreathing volume (CO<sub>2REB</sub>) and the parameters displayed on the lung simulator and ventilator were recorded under each condition.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>The mean CO<sub>2REB</sub> values of the four aforementioned valves were 18.51&#x202F;&#x00B1;&#x202F;2.87, 18.25&#x202F;&#x00B1;&#x202F;2.73, 17.78&#x202F;&#x00B1;&#x202F;2.98, and 14.26&#x202F;&#x00B1;&#x202F;0.92&#x202F;mL/breath, respectively, with no significant differences among the first three types but all significantly higher than that of the mask valve (all <italic>p</italic>&#x202F;&#x003C;&#x202F;0.0001, rate of difference &#x003E; 10%). Except with the V60 ventilator, some ventilator performance parameters (triggering and control performance) were significantly lower for the plateau valve than for the others, the rate of difference in tidal volume (V<sub>T</sub>) between the ventilator and the simulated lung exceeded 10% for all exhalation valves (all <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01).</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>Mask valves showed significantly lower CO<sub>2</sub> rebreathing than circuit-located valves (single-arch, whisper swivel, and plateau exhalation) in this NIV bench study. The different valves influenced ventilator performance differently, particularly the plateau valve. These findings necessitate further clinical validation <italic>in vivo</italic>.</p>
</sec>
</abstract>
<kwd-group>
<kwd>noninvasive ventilation</kwd>
<kwd>exhalation valves</kwd>
<kwd>CO<sub>2</sub> rebreathing</kwd>
<kwd>ventilator performance</kwd>
<kwd>plateau exhalation</kwd>
</kwd-group>
<counts>
<fig-count count="4"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="20"/>
<page-count count="8"/>
<word-count count="4936"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Intensive Care Medicine and Anesthesiology</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<title>Introduction</title>
<p>Noninvasive ventilation (NIV) is extensively used among patients with acute and chronic respiratory failure, reducing the intubation rate, the risk of respiratory failure after extubation, hospital length of stay, and mortality (<xref ref-type="bibr" rid="ref1 ref2 ref3 ref4 ref5">1&#x2013;5</xref>). In certain patient populations, such as those experiencing an exacerbation of chronic obstructive pulmonary disease (COPD), NIV is considered first-line therapy and the standard of care (<xref ref-type="bibr" rid="ref1 ref2 ref3">1&#x2013;3</xref>).</p>
<p>NIV is delivered via a noninvasive ventilator with a single limb, utilizing an exhalation port that directs exhaled gasses from the breathing circuit to the atmosphere. Currently, four types of exhalation valve are available for clinical practice: the single-arch, plateau, whisper swivel, and vented mask (integrated leak port within the mask) valves (<xref ref-type="bibr" rid="ref6">6</xref>). The characteristics of such valves including design features that allow controlled amounts of air to escape as &#x201C;intentional leaks&#x201D; vary greatly (<xref ref-type="bibr" rid="ref7">7</xref>), influencing rebreathing risk and carbon dioxide retention, particularly in hypercapnic respiratory failure. Recent clinical data (<xref ref-type="bibr" rid="ref8">8</xref>) suggested that insufficient CO<sub>2</sub> clearance may be associated with worse medium-term outcomes, highlighting the importance of CO<sub>2</sub> washout during inpatient NIV use. Besides, the characteristics of exhalation valves affecting the ability of a ventilator to generate pressure and thus its performance; this is particularly true of plateau exhalation valves (<xref ref-type="bibr" rid="ref7">7</xref>). However, it remains unclear whether commercial exhalation valves differ in their effects on CO<sub>2</sub> rebreathing and ventilator performance when used with different ventilators, and the optimal standards for exhalation valve selection have yet to be identified. We therefore employed bench methodologies to systematically quantify valve performance mechanisms, establishing a mechanistic basis for subsequent clinical validation.</p>
<p>In the present bench study, we applied the simulated lung model to comprehensively compare CO<sub>2</sub> rebreathing among the four types of valve in combination with three noninvasive ventilators. We also evaluated the impact of valve type on ventilator performance, including triggering, control, and monitoring parameters.</p>
</sec>
<sec sec-type="materials|methods" id="sec6">
<title>Materials and methods</title>
<sec id="sec7">
<title>Bench model setup</title>
<p>The Active Servo Lung simulation system (ASL5000, Ingmar, Pittsburgh, PA) is a precise breathing simulator containing a piston that moves inside a cylinder, capable of simulating breathing patterns of patients with COPD. The following parameters adopted from previous literature were applied to the simulated COPD lung model: compliance of 60&#x202F;mL/cmH<sub>2</sub>O, inspiratory resistance of 10 cmH<sub>2</sub>O/L/s, expiratory resistance of 15 cmH<sub>2</sub>O/L/s, and maximum inspiratory pressure drop of &#x2212;8 cmH<sub>2</sub>O. To simulate the profile of the negative pressure produced by respiratory muscles, 5% of the respiratory cycle time was set to active inspiration, 3% to an end-inspiratory hold, and 15% to return pressure to baseline (<xref ref-type="bibr" rid="ref9 ref10 ref11 ref12 ref13">9&#x2013;13</xref>). Breathing frequency was set at 10, 15, and 25 breaths/min, respectively.</p>
<p>Three noninvasive ventilators were used: the V60 (Philips, Carlsbad, United States), Flexo (Curative Medical, Jiangsu, China), and Stellar150 (ResMed, Saint Priest, France) ventilators. Both the Flexo and Stellar150 ventilators were used in S (Spontaneous) mode with an inspiratory pressure airway pressure (IPAP) and expiratory positive airway pressure (EPAP) of 12/4 and 16/4 cmH<sub>2</sub>O, respectively. The other settings were as follows: inspiratory trigger sensitivity (Isens) of 2, expiratory trigger sensitivity (Esens) of 2, and inspiratory slope (Islop) of 2 for the Flexo ventilator; and a trigger of high, switch of high, rise of 150, and decline of 10 for the Stellar150. The V60 ventilator was used in S/T (Spontaneous/Timed) mode with the lowest respiratory rate (4 breaths/min), as there is no S mode. The pressure settings were the same as above, with the following additional settings: inspiratory time (Ti) of 0.9, rise time of 1, and trigger of automatic. If miss-triggering occurred, the trigger parameter was readjusted to avoid this.</p>
<p>Two oronasal masks (first- and second-generation), with identical inner volumes and shape, were used from the same manufacturer (Bestfit&#x2122; I/II; Curative, Santa Clara, California). The first-generation mask, without an exhalation valve, was separately connected to a single-arch valve, whisper swivel valve, and plateau exhalation valve (all from Respironics, Andover, MA). The second-generation mask has an exhalation port integrated into the mask itself, located above the nose bridge. To measure leak of the exhalation valve (<xref ref-type="fig" rid="fig1">Figure 1A</xref>), the VT Plus airflow analyzer (Fluke Biomedical, Everett, WA) was connected in series in the single-limb breathing circuit. The mask was fixed to the face of an adult-sized model head equipped with a mouth port and a headband. To avoid unintentional leaks, plasticine was used to seal any spaces around the interface between the interface and the head model. The leakage of each valve was measured at continuous positive airway pressures (CPAPs) of 4, 12, and 20 cmH<sub>2</sub>O.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Illustration of the experiment. <bold>(A)</bold> Measuring the intentional leak of the exhalation valves, <bold>(B)</bold> schematic diagram of experimental setup, <bold>(C)</bold> time curve of flow and CO<sub>2</sub> concentration and the equation, <bold>(D)</bold> graphic explanation of the ventilator parameters.</p>
</caption>
<graphic xlink:href="fmed-12-1538280-g001.tif">
<alt-text content-type="machine-generated">Diagram showing noninvasive ventilation setups with labeled components. Panel A illustrates a ventilator connected to a head model via a mask with a valve box. Panel B includes additional elements like a vital sign monitor, gas analyzer, and CO2 cylinder. Symbols for different mask valves are shown in both panels. Panel C displays a graph of flow and CO2 percentages against time, with a mathematical equation. Panel D presents a pressure-time graph, indicating points for PEEP, trigger pressure, and TPmin.</alt-text>
</graphic>
</fig>
<p>The bench model is diagrammed in <xref ref-type="fig" rid="fig1">Figure 1B</xref>. The noninvasive ventilator was connected to the simulated lung through a single-limb breathing circuit behind the model head, which was connected one of the four valves. A micro gas flow controller (YJ-700CF, kongxin instrument company, Guangxi, China) was connected to a compressed CO<sub>2</sub> cylinder (0.3 kpa), and CO<sub>2</sub> was injected from the simulated lung outlet. The partial pressure of end-tidal carbon dioxide (PetCO<sub>2</sub>) was monitored using a vital sign monitor (NTID, newtech medical, Shenzheng, China), which was situated behind the model head to maintain PetCO<sub>2</sub> at 80&#x202F;mmHg. A self-made gas analyzer, integrating flow rate and CO<sub>2</sub> sensors, was located between the model and the lung simulator.</p>
</sec>
<sec id="sec8">
<title>Data acquisition</title>
<p>Inspiratory flow was continuously monitored with a flow sensor (OOM109/OOM109-LF2, EnviteC, Wismar/Honeywell, Morristown, NJ) at a sampling frequency of 30&#x202F;ms. The inspiratory phase was identified according to the flow waveform. We designed software that multiplied the CO<sub>2</sub> concentration by the inspiratory flow at each sampling point during the inspiratory phase. The delivered CO<sub>2</sub> volume was calculated using the equation shown in <xref ref-type="fig" rid="fig1">Figure 1C</xref>.</p>
<p>When the noninvasive ventilator and CO<sub>2</sub> ran stable for more than 5&#x202F;min, ventilator parameters were recorded for 10 consecutive respiratory cycles (<xref ref-type="fig" rid="fig1">Figure 1D</xref>). The parameters included triggering performance, including time to trigger (Ttrig, in milliseconds [ms]), time from the beginning of the lung simulator&#x2019;s inspiratory effort to the lowest airway pressure needed to trigger the ventilator (TPmin), and the magnitude of airway pressure drop needed to trigger (Ptrig); control performance, dividing into time to achieve 90% of the inspiratory target during inspiration (T90%, in ms), inspiratory time (Ti), peak inspiratory pressure (PIP), peak inspiratory flow (PIF), mean inspiratory flow (MIF), and positive end expiratory pressure (PEEP); and tidal volume (V<sub>T</sub>) parameters including actual V<sub>T</sub> (V<sub>T-L</sub>, that displayed on the simulated lung) and monitored V<sub>T</sub> (V<sub>T-V</sub>, that displayed on the ventilator).</p>
</sec>
<sec id="sec9">
<title>Statistical analysis</title>
<p>All statistical analyses were performed using GraphPad Prism (GraphPad Software, San Diego, CA). Data are expressed as means &#x00B1; standard deviations. Differences between parameters displayed on the ventilator and lung simulator were calculated as follows: rate of difference&#x202F;=&#x202F;(the parameters displayed on the ventilator &#x2013; those on the lung simulator) / the parameters displayed on the lung simulator. A paired <italic>t</italic>-test was used to assess these differences. One-way analysis of variance (ANOVA) was used to compare the influence of different exhalation valves on CO<sub>2</sub> rebreathing and ventilator performance under the same condition. Changes were considered clinically significant only when the rate of difference exceeded 10% and the differences were statistically significant at <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05 (<xref ref-type="bibr" rid="ref9 ref10 ref11 ref12 ref13">9&#x2013;13</xref>).</p>
</sec>
</sec>
<sec sec-type="results" id="sec10">
<title>Results</title>
<sec id="sec11">
<title>Leakage</title>
<p>The leakages of different exhalation valves are shown in <xref ref-type="fig" rid="fig2">Figure 2</xref>. Those of the single-arch, whisper swivel, and mask valves increased linearly with increasing CPAP. With CPAP as the independent variable and leakage as the dependent variable, the general linear equations for the valves were y&#x202F;=&#x202F;1.08x&#x202F;+&#x202F;8.54 (<italic>R</italic><sup>2</sup>&#x202F;=&#x202F;0.99, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01) y&#x202F;=&#x202F;1.64x&#x202F;+&#x202F;12.93 (<italic>R</italic><sup>2</sup>&#x202F;=&#x202F;0.99, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01), and y&#x202F;=&#x202F;2.28x&#x202F;+&#x202F;10.40 (<italic>R</italic><sup>2</sup>&#x202F;=&#x202F;0.99, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01), respectively. In contrast, the plateau exhalation valve exhibited a relatively constant leakage at different CPAP levels (24.44&#x202F;&#x00B1;&#x202F;0.9&#x202F;L/min) (<xref ref-type="fig" rid="fig2">Figure 2</xref>).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>The leakage of different exhalation valves.</p>
</caption>
<graphic xlink:href="fmed-12-1538280-g002.tif">
<alt-text content-type="machine-generated">Line graph showing leak rates in liters per minute against pressure in centimeters of water for different valves and a vented mask. Single-arch valve (brown triangles) shows minimal increase from 20 to 25. Whisper swivel valve (black circles) rises from 20 to 40. Plateau exhalation valve (gray diamonds) increases slightly from 20 to 28. Vented mask (blue squares) increases significantly from 25 to 55.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec12">
<title>CO<sub>2</sub> rebreathing</title>
<p>The mean CO<sub>2REB</sub> values under different ventilator settings for the single-arch, whisper swivel, plateau, and mask valves were 18.51&#x202F;&#x00B1;&#x202F;2.87, 18.25&#x202F;&#x00B1;&#x202F;2.73, 17.78&#x202F;&#x00B1;&#x202F;2.98, and 14.26&#x202F;&#x00B1;&#x202F;0.92&#x202F;mL/breath, respectively. There were no significant differences among the first three valve types, all of which were significantly higher than that of the mask valve (all <italic>p</italic>&#x202F;&#x003C;&#x202F;0.0001, rate of difference &#x003E; 10%). Similar results were observed at different pressure settings (IPAP/EPAP&#x202F;=&#x202F;12/4 and 16/4 cmH<sub>2</sub>O) (<xref ref-type="fig" rid="fig3">Figure 3A</xref>) and breathing frequencies (10 and 15, but not at 25, breaths/min) (<xref ref-type="fig" rid="fig3">Figure 3B</xref>), and for different types of ventilator (V60, Flexo, and Stellar150) (<xref ref-type="fig" rid="fig3">Figure 3C</xref>).</p>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>The CO<sub>2REB</sub> of different exhalation valves under different conditions. <bold>(A)</bold> Comparison under different pressure settings (IPAP/EPAP = 12/4 and 16/4 cmH2O); <bold>(B)</bold> Comparison at different breathing frequencies (10, 15, and 25 breaths/min); <bold>(C)</bold> Comparison across different ventilator types (V60, Flexo, and Stellar150). &#x002A; Significantly higher than IPAP&#x202F;=&#x202F;12cmH<sub>2</sub>O (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01), # significantly lower than other exhalation valves (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01), &#x0026; significantly lower than <italic>f</italic>&#x202F;=&#x202F;10/15 breaths/min (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01).</p>
</caption>
<graphic xlink:href="fmed-12-1538280-g003.tif">
<alt-text content-type="machine-generated">Bar graphs labeled A, B, and C compare CO2 levels (ml/breath) under various conditions using a V60 ventilator. Graph A shows results with two different IPAP/EPAP settings, Graph B varies the breathing rate, and Graph C compares different ventilator models. Each graph uses different valve and mask types, indicated by distinct patterns. Graphs highlight significant differences with symbols such as asterisks and hashtags.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec13">
<title>Ventilator performance</title>
<p>The effects of each valve on ventilator performance varied greatly, particularly for the plateau valve. In regard to triggering performance (Ttrig, Tpmin, Ptrig), values were significantly lower for the plateau valve versus all others (all <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01, rate of difference &#x003E; 10%), except for the V60 ventilator (<xref ref-type="fig" rid="fig4">Figure 4A</xref>). Regarding control performance, T90% and Ti were the lowest when using the plateau valve with the Flexo and Stellar150 ventilators (all <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01, rate of difference &#x003E; 10%); there were no significant differences in PIP, PIF, MIF, or PEEP among the valves (<xref ref-type="fig" rid="fig4">Figure 4B</xref>). Finally, in terms of V<sub>T-L</sub>, the value was significantly lower when using the plateau valve with the Stellar150 ventilator than any other combination (all <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01, rate of difference &#x003E; 10%) (<xref ref-type="fig" rid="fig4">Figure 4C</xref>).</p>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>Effects of different exhalation valves on ventilator performance. <bold>(A)</bold> Triggering parameters (Ttrig, Tpmin and Ptrig); <bold>(B)</bold> control parameters (T90%, Ti, PIP, PIF, MIF and PEEP); <bold>(C)</bold> tidal volume displayed on the lung simulator (V<sub>T-L</sub>). # significantly lower than other exhalation valves (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01).</p>
</caption>
<graphic xlink:href="fmed-12-1538280-g004.tif">
<alt-text content-type="machine-generated">Graphs titled "IPAP/EPAP=16/4 cmH&#x2082;O, f=15 breaths/min" compare ventilatory parameters across devices V60, Flexo, and Stellar150 using different valve types. Charts A and B show parameters like Ttrig, Tpmin, Ptrig, T90%, TI, PIP, PIF, MIF, and PEEP in milliseconds or centimeters of water. Chart C shows VTe-L in milliliters. Bar patterns denote single-hole valves, whisper swivel valves, plateau exhalation valves, and vented masks.</alt-text>
</graphic>
</fig>
<p>Except for the V60 ventilator, the rate of difference in V<sub>T</sub> between the ventilator and the simulated lung exceeded 10% for all exhalation valve types. The rate of difference in PIP remained below 10% under all conditions (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>The difference rate of tidal volume (Vt, mL) and peak inspiratory pressure (PIP, cmH&#x2082;O) between the ventilator and simulated lung with various exhalation valve types.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th rowspan="2"/>
<th align="center" valign="top" colspan="3">V60</th>
<th align="center" valign="top" colspan="3">Flexo</th>
<th align="center" valign="top" colspan="3">Stellar150</th>
</tr>
<tr>
<th align="center" valign="top">V<sub>t -L</sub></th>
<th align="center" valign="top">V<sub>t -V</sub></th>
<th align="center" valign="top">the difference rate,%</th>
<th align="center" valign="top">V<sub>t -L</sub></th>
<th align="center" valign="top">V<sub>t -V</sub></th>
<th align="center" valign="top">the difference rate,%</th>
<th align="center" valign="top">V<sub>t -L</sub></th>
<th align="center" valign="top">V<sub>t -V</sub></th>
<th align="center" valign="top">the difference rate,%</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="4">The difference rate of Vt (mL) between ventilator and simulated lung</td>
<td align="center" valign="top">553.53&#x00B1;4.34</td>
<td align="center" valign="top">595.40&#x00B1;2.84</td>
<td align="center" valign="top">7.57&#x00B1;0.79</td>
<td align="center" valign="top">549.70&#x00B1;4.43</td>
<td align="center" valign="top">819.0&#x00B1;14.86</td>
<td align="center" valign="top">49.0&#x00B1;2.87</td>
<td align="center" valign="top">548.58&#x00B1;4.01</td>
<td align="center" valign="top">611.15&#x00B1;5.35</td>
<td align="center" valign="top">11.41&#x00B1;0.44</td>
</tr>
<tr>
<td align="center" valign="top">547.76&#x00B1;6.99</td>
<td align="center" valign="top">592.90&#x00B1;3.03</td>
<td align="center" valign="top">8.25&#x00B1;1.34</td>
<td align="center" valign="top">553.09&#x00B1;4.85</td>
<td align="center" valign="top">826.7&#x00B1;6.25</td>
<td align="center" valign="top">49.48&#x00B1;1.67</td>
<td align="center" valign="top">577.02&#x00B1;2.61</td>
<td align="center" valign="top">631.4&#x00B1;3.72</td>
<td align="center" valign="top">24.59&#x00B1;0.91</td>
</tr>
<tr>
<td align="center" valign="top">550.40&#x00B1;3.40</td>
<td align="center" valign="top">599.10&#x00B1;2.73</td>
<td align="center" valign="top">8.85&#x00B1;0.86</td>
<td align="center" valign="top">535.27&#x00B1;5.18</td>
<td align="center" valign="top">829.1&#x00B1;10.51</td>
<td align="center" valign="top">54.91&#x00B1;2.47</td>
<td align="center" valign="top">492.14&#x00B1;3.45</td>
<td align="center" valign="top">394.63&#x00B1;103.5</td>
<td align="center" valign="top">-19.7&#x00B1;0.81</td>
</tr>
<tr>
<td align="center" valign="top">558.56&#x00B1;6.49</td>
<td align="center" valign="top">600.50&#x00B1;4.06</td>
<td align="center" valign="top">7.52&#x00B1;1.36</td>
<td align="center" valign="top">546.06&#x00B1;4.83</td>
<td align="center" valign="top">932.9&#x00B1;4.04</td>
<td align="center" valign="top">70.86&#x00B1;1.70</td>
<td align="center" valign="top">573 56&#x00B1;2 66</td>
<td align="center" valign="top">702.29&#x00B1;0.8</td>
<td align="center" valign="top">22.44&#x00B1;0.5</td>
</tr>
<tr>
<td rowspan="2"/>
<td align="center" valign="top" colspan="3">V60</td>
<td align="center" valign="top" colspan="3">Flexo</td>
<td align="center" valign="top" colspan="3">Stellar150</td>
</tr>
<tr>
<td align="center" valign="top">PIP <sub>-L</sub></td>
<td align="center" valign="top">PIP<sub>-V</sub></td>
<td align="center" valign="top">the difference rate,%</td>
<td align="center" valign="top">PIP <sub>-L</sub></td>
<td align="center" valign="top">PIP<sub>-V</sub></td>
<td align="center" valign="top">the difference rate,%</td>
<td align="center" valign="top">PIP<sub>-L</sub></td>
<td align="center" valign="top">PIP<sub>-V</sub></td>
<td align="center" valign="top">the difference rate,%</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="4">The difference rate of PIP (cmH<sub>2</sub>O) between ventilator and simulated lung</td>
<td align="center" valign="top">15.78&#x00B1;0.02</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">1.38&#x00B1;0.12</td>
<td align="center" valign="top">15.77&#x00B1;0.02</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">1.58&#x00B1;0.13</td>
<td align="center" valign="top">15.10&#x00B1;0.04</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">6.11&#x00B1;0.32</td>
</tr>
<tr>
<td align="center" valign="top">15.73&#x00B1;0.03</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">1.69&#x00B1;0.22</td>
<td align="center" valign="top">15.82&#x00B1;0.02</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">1.30&#x00B1;0.14</td>
<td align="center" valign="top">15.39&#x00B1;0.06</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">4.00&#x00B1;0.40</td>
</tr>
<tr>
<td align="center" valign="top">15.79&#x00B1;0.02</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">1.36&#x00B1;0.13</td>
<td align="center" valign="top">15.60&#x00B1;0.02</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">2.31&#x00B1;0.16</td>
<td align="center" valign="top">14.39&#x00B1;0.10</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">6.23&#x00B1;0.74</td>
</tr>
<tr>
<td align="center" valign="top">15.88&#x00B1;0.04</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">0.73&#x00B1;0.29</td>
<td align="center" valign="top">15.96&#x00B1;0.02</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">0.21&#x00B1;0.15</td>
<td align="center" valign="top">15.50&#x00B1;0.03</td>
<td align="center" valign="top">16.0</td>
<td align="center" valign="top">3.20&#x00B1;0.20</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec sec-type="discussion" id="sec14">
<title>Discussion</title>
<p>We comprehensively assessed the effects of four types of exhalation valve on CO<sub>2</sub> rebreathing and ventilator performance under different NIV settings and ventilators. Although no significant differences in CO<sub>2</sub> rebreathing were observed among the single-arch, whisper swivel, and plateau valves, all showed significantly higher rebreathing volumes than the mask valve. Additionally, except for the V60 ventilator, some ventilator performance parameters were significantly lower for the plateau valve than for the others, and the rate of difference in V<sub>T</sub> between the ventilator and the simulated lung with all exhalation valves exceeded 10%.</p>
<p>NIV can be delivered via a single-limb circuit, requiring a valve to enable exhalation. Clinically, four types of such valve are commonly used, depending on preference and equipment availability. However, their structural and functional characteristics differ. Previous study has indicated that leakage from the single-arch, whisper swivel, and mask valves increases with pressure, whereas the plateau valve maintains relatively constant leakage across different pressure levels due to its unique silicon diaphragm structure (<xref ref-type="bibr" rid="ref7">7</xref>). Our study corroborates these findings, and further comprehensively analyzed their impact on CO<sub>2</sub> rebreathing and ventilator performance.</p>
<p>Both bench and clinical studies (<xref ref-type="bibr" rid="ref14 ref15 ref16 ref17 ref18">14&#x2013;18</xref>) have demonstrated that CO<sub>2</sub> may not be adequately cleared during NIV, for an additional rebreathing process occurred and exhaled gasses constituted a fraction of the delivered tidal volume. Various factors&#x2014;including patient-associated characteristics (e.g., baseline CO<sub>2</sub> levels, spontaneous breathing patterns), ventilator settings (e.g., IPAP, EPAP), and interface-related elements (e.g., exhalation valve type and position)&#x2014;have been reported to affect CO<sub>2</sub> rebreathing during NIV (<xref ref-type="bibr" rid="ref15 ref16 ref17 ref18">15&#x2013;18</xref>). The simulated COPD lung model, which replicates key pathophysiological features of hypercapnic COPD such as increased dead space, has been widely used in previous bench studies (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref11">11</xref>) to evaluate CO<sub>2</sub> clearance efficacy. Similarly, maintaining a simulated PetCO<sub>2</sub> of 80&#x202F;mmHg&#x2014;consistent with our previous approach (<xref ref-type="bibr" rid="ref9">9</xref>)&#x2014;provides a standardized hypercapnic condition for assessing the impact of different exhalation valves on rebreathing. As in prior methodology (<xref ref-type="bibr" rid="ref15">15</xref>), the calculated CO<sub>2</sub> rebreathing represented the total rebreathing volume from the ventilator circuit, mask, and upper airway dead space of the mannequin, and not solely the CO<sub>2</sub> rebreathed from the circuit. Besides, previous studies also suggested that CO<sub>2</sub> rebreathing can be minimized by using an EPAP of up to 8 cmH<sub>2</sub>O or an IPAP of up to 20 cmH<sub>2</sub>O (<xref ref-type="bibr" rid="ref16">16</xref>). Therefore, to eliminate ventilator parameter influences while accounting for clinical constraints (specifically, the 4 cmH<sub>2</sub>O minimum EPAP setting on most devices), we applied IPAP levels of 12 or 16 cmH<sub>2</sub>O with a fixed EPAP of 4 cmH<sub>2</sub>O in this bench study. This design enables isolated investigation of exhalation valve effects on CO<sub>2</sub> rebreathing within an <italic>in vitro</italic> COPD model.</p>
<p>We found that CO<sub>2</sub> rebreathing with the mask valve was significantly lower than with the single-arch, whisper swivel, and plateau valves. This aligns with Schettino et al. (<xref ref-type="bibr" rid="ref15">15</xref>), who demonstrated that exhalation port position influences CO<sub>2</sub> rebreathing. Compared to circuit-located leak ports, the mask-integrated exhalation port (as in the Facial-MEP design) enhances residual gas washout by fresh airflow, reducing dead space ventilation and rebreathing volume. Meanwhile, our previous work confirms substantial design-dependent variation in CO<sub>2</sub> rebreathing among oronasal masks with integrated ports, with mean values ranging 11.01&#x2013;16.78&#x202F;mL (<xref ref-type="bibr" rid="ref9">9</xref>). Notably, all integrated-port masks exhibited lower rebreathing volumes than single-arch, whisper swivel, and plateau valves in this study.</p>
<p>Among the circuit-located exhalation ports, the plateau valve is generally believed to facilitate lower CO<sub>2</sub> rebreathing due to its unique controlled leakage mechanism (<xref ref-type="bibr" rid="ref16">16</xref>). However, no significant differences in CO<sub>2</sub> rebreathing were observed among the single-arch, plateau, and whisper swivel valves in our study. This aligns with Hill et al.&#x2019;s <italic>in vivo</italic> findings (<xref ref-type="bibr" rid="ref19">19</xref>), where plateau valves showed no clinical advantage over whisper swivel valves in long-term NIV patients. This null effect likely relates to leakage characteristics. Except the minimum EPAP (4 cmH<sub>2</sub>O), plateau valves demonstrated equivalent leakage to whisper swivel and single-arch valves at both 12 and 20 cmH<sub>2</sub>O (<xref ref-type="fig" rid="fig2">Figure 2</xref>). Consequently, at our tested IPAP levels (12/16 cmH<sub>2</sub>O) with fixed EPAP (4 cmH<sub>2</sub>O), plateau valves conferred no additional rebreathing reduction. Notably, Ferguson and Gilmartin (<xref ref-type="bibr" rid="ref16">16</xref>) observed superior performance of plateau valves at EPAP&#x202F;=&#x202F;0 cmH<sub>2</sub>O, with valve differences disappearing at higher EPAP levels. Thus, at clinically relevant pressures (&#x003E;4 cmH<sub>2</sub>O EPAP), rebreathing differences among these circuit-located valves become negligible. Further integrated bench-to-bedside studies are warranted to define valve selection criteria across therapeutic pressure ranges.</p>
<p>In terms of ventilator performance, we found that the plateau valve differed from the others. Triggering parameters (Ttrig, Tpmin, Ptrig) and control parameters (T90%, Ti) were significantly lower than for the others across the tested ventilators, except for the V60 ventilator. This may be due to the constant leakage of the plateau valve, and there is a greater leakage during the expiratory phase when EPAP is relatively low. This greater leakage may cause the ventilator to mistakenly perceive that the patient starting to inhale, thereby prematurely triggering the ventilator to deliver gas to the patient, resulting in a decrease in triggering parameters. Additionally, the relatively low leakage with the plateau valve at higher IPAP settings (16 cmH<sub>2</sub>O) may cause the ventilator to switch to expiration earlier, resulting in shorter inspiratory times and reduced tidal volumes. Therefore, when selecting exhalation valves in clinical practice, it is crucial to consider their impact on triggering and control performance during NIV.</p>
<p>Furthermore, we found that the rate of difference in V<sub>T</sub> between the ventilator and the simulated lung exceeded 10% for all exhalation valve types when using the Flexo and Stellar150 ventilators but not the V60 ventilator. During NIV, the monitored tidal volume displayed on the ventilator is an estimated value. Luj&#x00E1;n et al. (<xref ref-type="bibr" rid="ref20">20</xref>) reported that different valve types have different leakage, which can affect the accuracy of ventilator parameter monitoring during NIV. To be able to display accurate tidal and minute volumes, the ventilator must know the intentional leak characteristics of the specific mask/patient interface and exhalation port. With V60 ventilator, select the desired exhalation port type or/and run an exhalation port test is needed before the ventilator starts working. We previously found that tidal volume monitoring was more accurate after leak tests when using certain industrial masks (<xref ref-type="bibr" rid="ref13">13</xref>). These findings suggest that exhalation valves may not be interchangeable among ventilators with single-limb circuits. If interchangeable, leak tests of the valves from different manufacturers may be required.</p>
<p>Our <italic>in vitro</italic> findings yield some clinical and research implications. Consistent with prior studies, mask-integrated valve demonstrated significantly lower CO<sub>2</sub> rebreathing than circuit-located valves (single-arch, whisper swivel, plateau) during NIV, aligning with our previous work confirming superior CO<sub>2</sub> clearance across oronasal mask valves. Crucially, the plateau valve&#x2014;despite its controlled-leak mechanism&#x2014;showed no rebreathing reduction at clinically relevant settings, this provides actionable guidance for optimizing NIV trial protocols and clinical implementation. Furthermore, valve-dependent performance variations revealed some imperatives: rigorous monitoring of ventilator parameters (trigger sensitivity, control, and ventilation monitoring) during exhalation valves selection; development of ventilators with real-time intentional leak monitoring to optimize ventilator performance; and future studies also need to validate these findings across different patient populations (e.g., restrictive lung diseases) through bench-to-bedside investigations.</p>
<p>Several methodological limitations warrant consideration. This <italic>in vitro</italic> analysis employed a simulated COPD model with fixed hypercapnia (PetCO<sub>2</sub> 80&#x202F;mmHg) and restricted ventilator pressure settings, thereby failing to capture physiological variations in respiratory patterns, metabolic CO<sub>2</sub> fluctuations, or compensatory mechanisms in chronic respiratory failure. The restriction to 12/4 and 16/4 cmH<sub>2</sub>O pressure settings&#x2014;while clinically relevant&#x2014;precludes evaluation across the full therapeutic spectrum, and the absence of human variables (e.g., airway humidity, spontaneous breathing variability) limits clinical extrapolation. Though providing rigorously controlled conditions for quantifying CO<sub>2</sub> rebreathing dynamics, these constraints necessitate: (1) expanded pathophysiological models (e.g., restrictive disease); (2) systematic valve evaluation across incremental pressures (e.g., IPAP 8&#x2013;25 cmH&#x2082;O; EPAP 4&#x2013;12 cmH<sub>2</sub>O); and (3) prioritized clinical validation measuring ventilator performance parameters, and gas exchange efficacy in target populations.</p>
</sec>
<sec sec-type="conclusions" id="sec15">
<title>Conclusion</title>
<p>Our bench study demonstrated that different exhalation valves significantly affect CO<sub>2</sub> rebreathing and ventilator performance during NIV. CO<sub>2</sub> rebreathing was significantly lower with the mask valve than with the single-arch, whisper swivel, and plateau valves during NIV. Except for the V60 ventilator, ventilator performance parameters of the plateau valve differed from those of the other valves; additionally, the rate of difference in V<sub>T</sub> between the ventilator and the simulated lung exceeded 10% for all exhalation valves. Further clinical studies are needed to validate these results <italic>in vivo</italic>, taking into account patient variability in respiratory mechanics, ventilator settings, and CO<sub>2</sub> production.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec16">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec sec-type="author-contributions" id="sec17">
<title>Author contributions</title>
<p>XinL: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Writing &#x2013; original draft. BD: Software, Supervision, Writing &#x2013; review &#x0026; editing. CZ: Investigation, Methodology, Writing &#x2013; original draft. HH: Data curation, Formal analysis, Writing &#x2013; original draft. SW: Software, Validation, Writing &#x2013; original draft. XiaL: Validation, Visualization, Writing &#x2013; original draft. HZ: Methodology, Supervision, Writing &#x2013; review &#x0026; editing. WW: Supervision, Validation, Writing &#x2013; review &#x0026; editing. WT: Formal analysis, Funding acquisition, Project administration, Software, Supervision, Visualization, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec sec-type="funding-information" id="sec18">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. This research was funded by the China Postdoctoral Science Foundation (Certificate number: 2023M733905).</p>
</sec>
<ack>
<p>The laboratory of respiratory medicine of the first affiliated hospital of China medical university gave the necessary support.</p>
</ack>
<sec sec-type="COI-statement" id="sec19">
<title>Conflict of interest</title>
<p>CZ was employed by Shenyang RMS Medical Tech Co., Ltd.</p>
<p>The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec20">
<title>Generative AI statement</title>
<p>The authors declare that no Gen AI was used in the creation of this manuscript.</p>
</sec>
<sec sec-type="disclaimer" id="sec21">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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