Pub Date : 2025-10-01Epub Date: 2025-07-03DOI: 10.1016/j.resp.2025.104470
Islam Ahmed Abdelmawgood , Mohamed A. Kotb , Hassan Samy Hassan Eltras , Noha A. Mahana , Lamiaa Goda , Ahmed M. Rochdi , Nader Hassan Sayed , Reem H. Elsafoury , Amal M. Saber , Mahmoud Nabil Youssef , Nancy George Waheeb , Hamid Ashry , Bassam W. Ebeed , Mohamed W.A. Al-Rifai , Abeer Mahmoud Badr , Hadeer Hesham Abdelfattah
Background
Asthma is a chronic airway disease characterized by immunological dysregulation that causes sustained inflammation, leading to aberrant airway narrowing and mucus production. Isopimpinellin (IP) is a naturally occurring furanocoumarin, generated by an association of coumarin and a furan ring, possessing antifungal, antibacterial, and antioxidant properties; however, its potential in asthma treatment has not been investigated. This study sought to evaluate the anti-inflammatory and antioxidant effects of IP in an ovalbumin (OVA)-induced murine model of asthma.
Methods
Mice were grouped into four groups (n = 8 per group): control, OVA, and IP-treated (35 and 70 mg/kg). At the end of the experiment, lung oxidative stress, inflammation, and histopathological changes were evaluated.
Results
IP treatment significantly ameliorated airway oxidative stress by decreasing the concentration of malondialdehyde (MDA) and increasing the levels of antioxidants, including glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx); reduced inflammatory cell infiltration; mitigated histological changes; and decreased levels of IL-4, IL-13, and IgE. Additionally, IP prevented NF-κB phosphorylation. This study is the first examination of the anti-asthmatic properties of IP in allergic asthma in murine models.
Conclusion
Our data indicate that IP may function as an anti-asthmatic medication via regulating oxidative stress and inflammation.
{"title":"Protective effect of isopimpinellin on ovalbumin-induced airway inflammation and oxidative stress in mouse model of asthma","authors":"Islam Ahmed Abdelmawgood , Mohamed A. Kotb , Hassan Samy Hassan Eltras , Noha A. Mahana , Lamiaa Goda , Ahmed M. Rochdi , Nader Hassan Sayed , Reem H. Elsafoury , Amal M. Saber , Mahmoud Nabil Youssef , Nancy George Waheeb , Hamid Ashry , Bassam W. Ebeed , Mohamed W.A. Al-Rifai , Abeer Mahmoud Badr , Hadeer Hesham Abdelfattah","doi":"10.1016/j.resp.2025.104470","DOIUrl":"10.1016/j.resp.2025.104470","url":null,"abstract":"<div><h3>Background</h3><div>Asthma is a chronic airway disease characterized by immunological dysregulation that causes sustained inflammation, leading to aberrant airway narrowing and mucus production. Isopimpinellin (IP) is a naturally occurring furanocoumarin, generated by an association of coumarin and a furan ring, possessing antifungal, antibacterial, and antioxidant properties; however, its potential in asthma treatment has not been investigated. This study sought to evaluate the anti-inflammatory and antioxidant effects of IP in an ovalbumin (OVA)-induced murine model of asthma.</div></div><div><h3>Methods</h3><div>Mice were grouped into four groups (n = 8 per group): control, OVA, and IP-treated (35 and 70 mg/kg). At the end of the experiment, lung oxidative stress, inflammation, and histopathological changes were evaluated.</div></div><div><h3>Results</h3><div>IP treatment significantly ameliorated airway oxidative stress by decreasing the concentration of malondialdehyde (MDA) and increasing the levels of antioxidants, including glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx); reduced inflammatory cell infiltration; mitigated histological changes; and decreased levels of IL-4, IL-13, and IgE. Additionally, IP prevented NF-κB phosphorylation. This study is the first examination of the anti-asthmatic properties of IP in allergic asthma in murine models.</div></div><div><h3>Conclusion</h3><div>Our data indicate that IP may function as an anti-asthmatic medication via regulating oxidative stress and inflammation.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104470"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-06-25DOI: 10.1016/j.resp.2025.104461
Obada Alfarawati, Bill T. Ameredes
Acrolein exposure in the lung was studied to determine the effect of acrolein on airway responsiveness and pulmonary mechanics, as measured by the forced oscillation technique (FOT), under conditions of airway activation by methacholine (MCh), as well as with no activation, using the negative pressure-driven forced expiratory (NPFE) maneuvers to assess quasi-static lung compliance. Direct intratracheal acrolein was applied to C57BL/6 J male mice in dosages of 0 (saline vehicle-only) or 4 mg/kg, with FOT and NPFE assessments made 48 hr post-acrolein administration. Our results suggest that lipid peroxidation may be a primary factor in the observed attenuated response of resistance of the respiratory system (Rrs) to MCh (25 % decrease), potentially due to the alteration of the lipid bilayer that contains the transmembrane muscarinic receptors that respond to MCh. Furthermore, static lung compliance was significantly reduced in mice receiving acrolein. The product of lipid peroxidation, malondialdehyde (MDA), was confirmed in the bronchoalveolar lavage fluid (BALF) of the acrolein group to be significantly higher than the control groups (35 % increase). The nitrite concentration measured in the acrolein group BALF was consistent with elevated levels of nitric oxide (NO) (∼50 % increase), and perhaps peroxynitrite, which could be additional nitrosative stress factors promoting lipid peroxidation in our acute model of acrolein toxicity. Furthermore, the decrease in glutathione peroxidase (GPx) (52 % decrease) that we observed suggested a significant reduction in endogenous antioxidant capacity, with the oxidative stress associated with increased lipid peroxidation resultant from acrolein exposure. We conclude that the lipid peroxidation and decline in redox capacity due to nitrosative stress induced by acrolein could be an important factor in modulation of pulmonary mechanics, airway remodeling, and bronchial responsiveness.
{"title":"Acrolein-induced oxidative and nitrosative stress and its impact on respiratory mechanics in mice assessed using the forced oscillation technique","authors":"Obada Alfarawati, Bill T. Ameredes","doi":"10.1016/j.resp.2025.104461","DOIUrl":"10.1016/j.resp.2025.104461","url":null,"abstract":"<div><div>Acrolein exposure in the lung was studied to determine the effect of acrolein on airway responsiveness and pulmonary mechanics, as measured by the forced oscillation technique (FOT), under conditions of airway activation by methacholine (MCh), as well as with no activation, using the negative pressure-driven forced expiratory (NPFE) maneuvers to assess quasi-static lung compliance. Direct intratracheal acrolein was applied to C57BL/6 J male mice in dosages of 0 (saline vehicle-only) or 4 mg/kg, with FOT and NPFE assessments made 48 hr post-acrolein administration. Our results suggest that lipid peroxidation may be a primary factor in the observed attenuated response of resistance of the respiratory system (Rrs) to MCh (25 % decrease), potentially due to the alteration of the lipid bilayer that contains the transmembrane muscarinic receptors that respond to MCh. Furthermore, static lung compliance was significantly reduced in mice receiving acrolein. The product of lipid peroxidation, malondialdehyde (MDA), was confirmed in the bronchoalveolar lavage fluid (BALF) of the acrolein group to be significantly higher than the control groups (35 % increase). The nitrite concentration measured in the acrolein group BALF was consistent with elevated levels of nitric oxide (NO) (∼50 % increase), and perhaps peroxynitrite, which could be additional nitrosative stress factors promoting lipid peroxidation in our acute model of acrolein toxicity. Furthermore, the decrease in glutathione peroxidase (GPx) (52 % decrease) that we observed suggested a significant reduction in endogenous antioxidant capacity, with the oxidative stress associated with increased lipid peroxidation resultant from acrolein exposure. We conclude that the lipid peroxidation and decline in redox capacity due to nitrosative stress induced by acrolein could be an important factor in modulation of pulmonary mechanics, airway remodeling, and bronchial responsiveness.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104461"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-08-11DOI: 10.1016/j.resp.2025.104473
Edward Bliss , Dean E. Mills
We investigated the cerebrovascular and executive function responses to increased inspiratory muscle work. Eight healthy men (33 ± 6 years) performed two separate 10 min bouts of inspiratory pressure threshold loading (ITL) targeting 70 % of maximal inspiratory mouth pressure (PImax) (ITL-Load) and two separate 10 min bouts of ITL targeting 2 % of PImax (ITL-Control). The order in which each participant undertook ITL-Load and ITL-Control conditions was randomized. Transcranial Doppler ultrasonography was used to measure middle cerebral artery blood velocity (MCAV) and executive function was measured using the trail making task (TMT) Parts A and B during the 4–6th min of ITL-Load and ITL-Control. The cerebrovascular conductance index (CVCi) and cerebrovascular resistance index (CVRi) were calculated. There were time x condition interactions (P < 0.01) for MCAV, CVCi and CVRi. This demonstrated during ITL-Load a small time-dependent increase (P < 0.01) in MCAV and CVCi, and a small time-dependent decrease (P < 0.01) in CVRi. Part A (P = 0.007) and Part B (P = 0.013) times for the TMT were slower for ITL-Load compared to ITL-Control. There were significant correlations between the change in MCAV from rest to the end of ITL and TMT times for Part A (r = 0.81, P = 0.009) and Part B (r = 0.67, P = 0.048). This is the first study to demonstrate that high-intensity ITL results in an increase in MCAV, and a decreased executive function measured by the TMT, and these two measures were related in that the increase in MCAV resulted in slower TMT times.
{"title":"The cerebrovascular and executive function responses to increased inspiratory muscle work","authors":"Edward Bliss , Dean E. Mills","doi":"10.1016/j.resp.2025.104473","DOIUrl":"10.1016/j.resp.2025.104473","url":null,"abstract":"<div><div>We investigated the cerebrovascular and executive function responses to increased inspiratory muscle work. Eight healthy men (33 ± 6 years) performed two separate 10 min bouts of inspiratory pressure threshold loading (ITL) targeting 70 % of maximal inspiratory mouth pressure (P<sub>Imax</sub>) (ITL-Load) and two separate 10 min bouts of ITL targeting 2 % of P<sub>Imax</sub> (ITL-Control). The order in which each participant undertook ITL-Load and ITL-Control conditions was randomized. Transcranial Doppler ultrasonography was used to measure middle cerebral artery blood velocity (MCA<sub>V</sub>) and executive function was measured using the trail making task (TMT) Parts A and B during the 4–6th min of ITL-Load and ITL-Control. The cerebrovascular conductance index (CVCi) and cerebrovascular resistance index (CVRi) were calculated. There were time x condition interactions (<em>P</em> < 0.01) for MCA<sub>V</sub>, CVCi and CVRi. This demonstrated during ITL-Load a small time-dependent increase (<em>P</em> < 0.01) in MCA<sub>V</sub> and CVCi, and a small time-dependent decrease (<em>P</em> < 0.01) in CVRi. Part A (<em>P</em> = 0.007) and Part B (<em>P</em> = 0.013) times for the TMT were slower for ITL-Load compared to ITL-Control. There were significant correlations between the change in MCA<sub>V</sub> from rest to the end of ITL and TMT times for Part A (<em>r</em> = 0.81, <em>P</em> = 0.009) and Part B (<em>r</em> = 0.67, <em>P</em> = 0.048). This is the first study to demonstrate that high-intensity ITL results in an increase in MCA<sub>V</sub>, and a decreased executive function measured by the TMT, and these two measures were related in that the increase in MCA<sub>V</sub> resulted in slower TMT times.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104473"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-07-22DOI: 10.1016/j.resp.2025.104471
A.S. Hind , R.A. Mitchell , J.R. Dunsford , O.N. Ferguson , M. Flynn , S.S. Dhillon , K. Badra , M.S. Koehle , K.M. Milne , J.A. Guenette
Background
Expiratory flow limitation (EFL) during exercise in highly trained individuals is thought to result from increased ventilatory demands that exceed the capacity of the respiratory system, which does not fully adapt to exercise training. Reduced forced expiratory flow between 25 % and 75 % of forced vital capacity (FEF25–75 %), a marker of small airway function, may contribute to EFL by limiting the maximum expiratory flows available during the hyperpnea of exercise. This study investigated whether FEF25–75 %, peak minute ventilation (V̇E), and breathing patterns differ between highly trained endurance athletes with and without EFL.
Methods
Forty highly trained endurance athletes (20 males and 20 females; V̇O2max: 59.6 ± 9.2 mL∙kg−1∙min−1) completed spirometry and a maximal incremental cardiopulmonary treadmill exercise test. EFL was assessed by superimposing tidal flow-volume loops within the maximum flow-volume loop according to end-expiratory lung volume.
Results
During maximal exercise, 40 % of participants (n = 16: 7 males, 9 females) developed EFL, with no significant sex differences (P > 0.05). Athletes with EFL had significantly lower FEF25–75 % (3.45 ± 0.78 vs. 4.16 ± 0.98 L·s−1, P = 0.020, d = 0.802) and a higher ventilatory demand-to-capacity ratio (V̇E/V̇Ecap) (0.86 ± 0.14 vs. 0.66 ± 0.11, P = 0.002, d = 1.589) compared to those without EFL. There were no significant differences in absolute tidal volume, breathing frequency or V̇E between groups (P > 0.05).
Conclusion
In a homogeneous cohort of highly trained endurance athletes, EFL during maximal treadmill exercise appears to be primarily driven by a reduced capacity to generate expiratory flow, as evidenced by lower FEF25–75 %, rather than differences in ventilatory demand.
{"title":"Expiratory flow limitation in highly trained endurance athletes: The role of FEF25–75% and ventilatory capacity during treadmill running","authors":"A.S. Hind , R.A. Mitchell , J.R. Dunsford , O.N. Ferguson , M. Flynn , S.S. Dhillon , K. Badra , M.S. Koehle , K.M. Milne , J.A. Guenette","doi":"10.1016/j.resp.2025.104471","DOIUrl":"10.1016/j.resp.2025.104471","url":null,"abstract":"<div><h3>Background</h3><div>Expiratory flow limitation (EFL) during exercise in highly trained individuals is thought to result from increased ventilatory demands that exceed the capacity of the respiratory system, which does not fully adapt to exercise training. Reduced forced expiratory flow between 25 % and 75 % of forced vital capacity (FEF<sub>25–75 %</sub>), a marker of small airway function, may contribute to EFL by limiting the maximum expiratory flows available during the hyperpnea of exercise. This study investigated whether FEF<sub>25–75 %</sub>, peak minute ventilation (V̇<sub>E</sub>), and breathing patterns differ between highly trained endurance athletes with and without EFL.</div></div><div><h3>Methods</h3><div>Forty highly trained endurance athletes (20 males and 20 females; V̇O<sub>2</sub>max: 59.6 ± 9.2 mL∙kg<sup>−1</sup>∙min<sup>−1</sup>) completed spirometry and a maximal incremental cardiopulmonary treadmill exercise test. EFL was assessed by superimposing tidal flow-volume loops within the maximum flow-volume loop according to end-expiratory lung volume.</div></div><div><h3>Results</h3><div>During maximal exercise, 40 % of participants (<em>n</em> = 16: 7 males, 9 females) developed EFL, with no significant sex differences (<em>P</em> > 0.05). Athletes with EFL had significantly lower FEF<sub>25–75 %</sub> (3.45 ± 0.78 vs. 4.16 ± 0.98 L·s<sup>−1</sup>, <em>P</em> = 0.020, <em>d</em> = 0.802) and a higher ventilatory demand-to-capacity ratio (V̇<sub>E</sub>/V̇<sub>Ecap</sub>) (0.86 ± 0.14 vs. 0.66 ± 0.11, <em>P</em> = 0.002, <em>d</em> = 1.589) compared to those without EFL. There were no significant differences in absolute tidal volume, breathing frequency or V̇<sub>E</sub> between groups (<em>P</em> > 0.05).</div></div><div><h3>Conclusion</h3><div>In a homogeneous cohort of highly trained endurance athletes, EFL during maximal treadmill exercise appears to be primarily driven by a reduced capacity to generate expiratory flow, as evidenced by lower FEF<sub>25–75 %,</sub> rather than differences in ventilatory demand.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104471"},"PeriodicalIF":1.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-06-30DOI: 10.1016/j.resp.2025.104468
Catherine A. Rattley , Paul Ansdell , Louise Burgess , Malika Felton , Susan Dewhurst , Matthew Armstrong , Rebecca Neal
<div><h3>Background</h3><div>Minute ventilation (V̇E) may vary across the menstrual cycle due to cyclical changes in sex hormones, potentially exerting an exercise intensity dependent effect.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aimed to quantify differences in V̇E, respiratory frequency (RF), and tidal volume (VT) between the follicular and luteal phases at rest, during submaximal exercise (≤90 %V̇O<sub>2max</sub>), and at incremental maximum (100 %V̇O<sub>2max</sub>).</div></div><div><h3>Methods</h3><div>The systematic review adhered to PRISMA guidelines for conducting and reporting systematic reviews. Studies included healthy eumenorrheic females (≥18 years) not using hormonal contraceptives. Studies that reported V̇E in the follicular and luteal phases were included. RF and VT were extracted as secondary outcome measures. Searches were conducted in Cochrane, PubMed, and EBSCO databases in January 2025. Study quality was assessed using the modified Downs and Black checklist for menstrual cycle research. Data were extracted and analysed using maximum likelihood random-effect meta-analyses followed with meta-regressions with intensity and duration as a moderator in submaximal exercise. Publication bias was assessed using Egger’s test. Meta-regressions were also conducted for resting and submaximal datasets using change in progesterone as a moderator.</div></div><div><h3>Results</h3><div>A total of 35 studies inclusive of 743 participants and 64 paired datasets were included. V̇E was lower in the follicular phase than the luteal phase at rest (ES = −0.64, <em>p</em> < 0.001, I<sup>2</sup> = 75.74 %) and during submaximal exercise (ES = −0.89, <em>p</em> < 0.001, I<sup>2</sup> = 76.58 %), with no effect of study quality. Meta-regression revealed that duration and intensity did not influence menstrual cycle effect on V̇E in submaximal exercise. At incremental maximum, a small but significant effect was observed towards higher V̇E in the luteal phase than the follicular phase (ES = −0.33, <em>p</em> = 0.03, I<sup>2</sup> = 61.5 %) however this effect was no longer observed after removal of low-quality studies. All analyses were coupled with significant heterogeneity. Meta-regression demonstrated that change in progesterone significantly predicted V̇E changes during submaximal exercise (<em>p</em> = 0.02), but not at rest (<em>p</em> = 0.07). RF and VT analyses suggested minimal menstrual cycle effect, with only VT reductions at rest contributing to V̇E differences, this was likely related to the low number of studies included.</div></div><div><h3>Conclusions</h3><div>The menstrual cycle significantly influences V̇E, with lower values in the follicular phase at rest and during submaximal exercise. Changes in progesterone partially explain the differences in V̇E between menstrual phases during exercise but not at rest. At maximal intensities, hormonal influence on V̇E is minimal which corroborates the h
{"title":"Ventilation differences in the menstrual cycle: A systematic review and meta-analysis","authors":"Catherine A. Rattley , Paul Ansdell , Louise Burgess , Malika Felton , Susan Dewhurst , Matthew Armstrong , Rebecca Neal","doi":"10.1016/j.resp.2025.104468","DOIUrl":"10.1016/j.resp.2025.104468","url":null,"abstract":"<div><h3>Background</h3><div>Minute ventilation (V̇E) may vary across the menstrual cycle due to cyclical changes in sex hormones, potentially exerting an exercise intensity dependent effect.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aimed to quantify differences in V̇E, respiratory frequency (RF), and tidal volume (VT) between the follicular and luteal phases at rest, during submaximal exercise (≤90 %V̇O<sub>2max</sub>), and at incremental maximum (100 %V̇O<sub>2max</sub>).</div></div><div><h3>Methods</h3><div>The systematic review adhered to PRISMA guidelines for conducting and reporting systematic reviews. Studies included healthy eumenorrheic females (≥18 years) not using hormonal contraceptives. Studies that reported V̇E in the follicular and luteal phases were included. RF and VT were extracted as secondary outcome measures. Searches were conducted in Cochrane, PubMed, and EBSCO databases in January 2025. Study quality was assessed using the modified Downs and Black checklist for menstrual cycle research. Data were extracted and analysed using maximum likelihood random-effect meta-analyses followed with meta-regressions with intensity and duration as a moderator in submaximal exercise. Publication bias was assessed using Egger’s test. Meta-regressions were also conducted for resting and submaximal datasets using change in progesterone as a moderator.</div></div><div><h3>Results</h3><div>A total of 35 studies inclusive of 743 participants and 64 paired datasets were included. V̇E was lower in the follicular phase than the luteal phase at rest (ES = −0.64, <em>p</em> < 0.001, I<sup>2</sup> = 75.74 %) and during submaximal exercise (ES = −0.89, <em>p</em> < 0.001, I<sup>2</sup> = 76.58 %), with no effect of study quality. Meta-regression revealed that duration and intensity did not influence menstrual cycle effect on V̇E in submaximal exercise. At incremental maximum, a small but significant effect was observed towards higher V̇E in the luteal phase than the follicular phase (ES = −0.33, <em>p</em> = 0.03, I<sup>2</sup> = 61.5 %) however this effect was no longer observed after removal of low-quality studies. All analyses were coupled with significant heterogeneity. Meta-regression demonstrated that change in progesterone significantly predicted V̇E changes during submaximal exercise (<em>p</em> = 0.02), but not at rest (<em>p</em> = 0.07). RF and VT analyses suggested minimal menstrual cycle effect, with only VT reductions at rest contributing to V̇E differences, this was likely related to the low number of studies included.</div></div><div><h3>Conclusions</h3><div>The menstrual cycle significantly influences V̇E, with lower values in the follicular phase at rest and during submaximal exercise. Changes in progesterone partially explain the differences in V̇E between menstrual phases during exercise but not at rest. At maximal intensities, hormonal influence on V̇E is minimal which corroborates the h","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104468"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-06-21DOI: 10.1016/j.resp.2025.104458
Anshuman Vikram, Tanmay Pal
Effective mechanical ventilation depends on precise control of multiple parameters, including respiratory frequency. This study explores the influence of respiratory frequency on ventilation through a comparative analysis of four mathematical models. Understanding optimal frequency selection is paramount for ventilator design and control algorithms. Furthermore, the relationship between frequency, minute ventilation, lung resistance, and elastance can aid in managing respiratory diseases. With this approach, the respiratory frequency can be optimized during assisted ventilation, contributing to a better understanding and control of various respiratory therapies. The models were evaluated by varying key physiological parameters such as resistance, elastance, and alveolar ventilation. The effects of parameter variations on predicted respiratory frequencies were illustrated graphically, accompanied by a sensitivity analysis to quantify how changes in parameters influence frequency. To further evaluate model performance, a comparison with published datasets was conducted. This comprehensive assessment ultimately identified a specific model that exhibited the least mean percentage error and closely resembled published data, highlighting its potential for future research and clinical applications.
{"title":"A comparative analysis of computational models for respiratory frequency","authors":"Anshuman Vikram, Tanmay Pal","doi":"10.1016/j.resp.2025.104458","DOIUrl":"10.1016/j.resp.2025.104458","url":null,"abstract":"<div><div>Effective mechanical ventilation depends on precise control of multiple parameters, including respiratory frequency. This study explores the influence of respiratory frequency on ventilation through a comparative analysis of four mathematical models. Understanding optimal frequency selection is paramount for ventilator design and control algorithms. Furthermore, the relationship between frequency, minute ventilation, lung resistance, and elastance can aid in managing respiratory diseases. With this approach, the respiratory frequency can be optimized during assisted ventilation, contributing to a better understanding and control of various respiratory therapies. The models were evaluated by varying key physiological parameters such as resistance, elastance, and alveolar ventilation. The effects of parameter variations on predicted respiratory frequencies were illustrated graphically, accompanied by a sensitivity analysis to quantify how changes in parameters influence frequency. To further evaluate model performance, a comparison with published datasets was conducted. This comprehensive assessment ultimately identified a specific model that exhibited the least mean percentage error and closely resembled published data, highlighting its potential for future research and clinical applications.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104458"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-07-03DOI: 10.1016/j.resp.2025.104469
Heba A.A. Abdeen , Hady Atef , Nesreen G. Elnahas , Omnia A. Khalaf , Youssef M.A. Soliman , Reem I.M. Elkorashy , Samah Mowad , Noemi Moreno-Segura , Juan Jose Carrasco , Elena Marques-Sule
Background
Prolonged mechanical ventilation in chronic obstructive pulmonary disease is associated with severe complications, and then earlier weaning is desirable. Then, strategies such as inspiratory muscle training (IMT) have been studied. This study aimed to compare the effects of IMT via Threshold device versus trigger sensitivity adjustment of the mechanical ventilator versus conventional therapy on respiratory parameters on chronic obstructive pulmonary disease weaning patients.
Methods
Ninety patients (aged 50–70) with acute respiratory failure on mechanical ventilation selected from the Intensive Care Unit were randomly assigned into: IMT via Threshold and conventional physical therapy group; trigger sensitivity adjustment of the mechanical ventilator and conventional physical therapy group; and conventional physical therapy alone group. Negative inspiratory force (NIF), respiratory rate (RR), tidal volume (VT), rapid shallow breathing index (RSBI), pH, and oxygenation parameters (PaO2, PaCO2, and P/F ratio) were measured pre and post-treatment.
Results
Threshold group showed higher improvements in NIF than the trigger sensitivity adjustment group (p = 0.002; ES: 0.91). Threshold group showed better results in all measures than conventional physical therapy group except for pH and PaCO2. Trigger sensitivity adjustment and conventional physical therapy groups showed significant improvements in all measurements (p < 0.005 for NIF (2.30), RR (1.69), VT (0.80); RSBI (2.09), PaO2 (1.20), P/F ratio (1.22) except for VT, pH, and PaCO2 with preference to trigger sensitivity adjustment group. No significant differences were found in the percentage of weaning between groups, but Threshold group showed significantly lower weaning days than conventional physical therapy group (p = 0.004, ES:1.01).
Conclusion
The respiratory training with the IMT device has significantly higher improvements than the other techniques and reduces the weaning duration.
{"title":"Effects of threshold inspiratory muscle trainer versus trigger sensitivity adjustment versus conventional therapy on respiratory function in mechanically ventilated patients: a randomized controlled trial.","authors":"Heba A.A. Abdeen , Hady Atef , Nesreen G. Elnahas , Omnia A. Khalaf , Youssef M.A. Soliman , Reem I.M. Elkorashy , Samah Mowad , Noemi Moreno-Segura , Juan Jose Carrasco , Elena Marques-Sule","doi":"10.1016/j.resp.2025.104469","DOIUrl":"10.1016/j.resp.2025.104469","url":null,"abstract":"<div><h3>Background</h3><div>Prolonged mechanical ventilation in chronic obstructive pulmonary disease is associated with severe complications, and then earlier weaning is desirable. Then, strategies such as inspiratory muscle training (IMT) have been studied. This study aimed to compare the effects of IMT via Threshold device versus trigger sensitivity adjustment of the mechanical ventilator versus conventional therapy on respiratory parameters on chronic obstructive pulmonary disease weaning patients.</div></div><div><h3>Methods</h3><div>Ninety patients (aged 50–70) with acute respiratory failure on mechanical ventilation selected from the Intensive Care Unit were randomly assigned into: IMT via Threshold and conventional physical therapy group; trigger sensitivity adjustment of the mechanical ventilator and conventional physical therapy group; and conventional physical therapy alone group. Negative inspiratory force (NIF), respiratory rate (RR), tidal volume (VT), rapid shallow breathing index (RSBI), pH, and oxygenation parameters (PaO<sub>2</sub>, PaCO<sub>2,</sub> and P/F ratio) were measured pre and post-treatment.</div></div><div><h3>Results</h3><div>Threshold group showed higher improvements in NIF than the trigger sensitivity adjustment group (p = 0.002; ES: 0.91). Threshold group showed better results in all measures than conventional physical therapy group except for pH and PaCO<sub>2</sub>. Trigger sensitivity adjustment and conventional physical therapy groups showed significant improvements in all measurements (p < 0.005 for NIF (2.30), RR (1.69), VT (0.80); RSBI (2.09), PaO<sub>2</sub> (1.20), P/F ratio (1.22) except for VT, pH, and PaCO<sub>2</sub> with preference to trigger sensitivity adjustment group. No significant differences were found in the percentage of weaning between groups, but Threshold group showed significantly lower weaning days than conventional physical therapy group (p = 0.004, ES:1.01).</div></div><div><h3>Conclusion</h3><div>The respiratory training with the IMT device has significantly higher improvements than the other techniques and reduces the weaning duration.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"337 ","pages":"Article 104469"},"PeriodicalIF":1.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-11DOI: 10.1016/j.resp.2025.104456
Olivia N. Ferguson , Dennis Jensen , Jordan A. Guenette , Hayley Lewthwaite
Dyspnea, or breathlessness, is a complex, multidimensional symptom of breathing discomfort, which significantly impacts quality of life and clinical prognosis. While traditional assessments have primarily focused on breathlessness sensory intensity, this approach does not consider affective and/or qualitative dimensions. Growing evidence highlights the need for multidimensional assessment approaches that provide a more comprehensive understanding of breathlessness, particularly in the context of exercise. Cardiopulmonary exercise testing (CPET) provides a standardized physiological stimulus to assess breathlessness responses in real-time, offering valuable insights into its underlying mechanisms and response to therapeutic intervention. Normative reference equations can help identify abnormally high breathlessness intensity during CPET. This review examines current methodologies for multidimensional breathlessness assessment during exercise, including single-item rating scales, multidimensional tools, descriptor lists, and locus of symptom limitation. We also discuss best practices for linking breathlessness with physiological responses during CPET to enhance mechanistic understanding, inform targeted interventions, and evaluate interventional efficacy. Standardizing assessment approaches and ensuring transparent reporting are critical steps toward improving the clinical and research utility of exertional breathlessness assessments.
{"title":"Multidimensional assessment of breathlessness during exercise: current methods and recommendations","authors":"Olivia N. Ferguson , Dennis Jensen , Jordan A. Guenette , Hayley Lewthwaite","doi":"10.1016/j.resp.2025.104456","DOIUrl":"10.1016/j.resp.2025.104456","url":null,"abstract":"<div><div>Dyspnea, or breathlessness, is a complex, multidimensional symptom of breathing discomfort, which significantly impacts quality of life and clinical prognosis. While traditional assessments have primarily focused on breathlessness sensory intensity, this approach does not consider affective and/or qualitative dimensions. Growing evidence highlights the need for multidimensional assessment approaches that provide a more comprehensive understanding of breathlessness, particularly in the context of exercise. Cardiopulmonary exercise testing (CPET) provides a standardized physiological stimulus to assess breathlessness responses in real-time, offering valuable insights into its underlying mechanisms and response to therapeutic intervention. Normative reference equations can help identify abnormally high breathlessness intensity during CPET. This review examines current methodologies for multidimensional breathlessness assessment during exercise, including single-item rating scales, multidimensional tools, descriptor lists, and locus of symptom limitation. We also discuss best practices for linking breathlessness with physiological responses during CPET to enhance mechanistic understanding, inform targeted interventions, and evaluate interventional efficacy. Standardizing assessment approaches and ensuring transparent reporting are critical steps toward improving the clinical and research utility of exertional breathlessness assessments.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104456"},"PeriodicalIF":1.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our study aimed to investigate swallowing coordination by analyzing ventilatory patterns during of solids and liquids food intakes. Twenty-one patients with severe to very severe stable COPD (GOLD III and IV) underwent ventilation and swallowing recordings while performing standardized swallowing tasks. The results revealed that the expiratory-expiratory (EE) swallowing pattern was predominant, accounting for 80 % of swallows, with no significant differences between solid and liquid swallows. Non-EE patterns occurred in an average of 20.68 % of swallows per patient. Our results demonstrated an increased inspiratory time (IT) during liquid swallows compared to rest (1.05 ± 0.28 s vs 1.29 ± 0.22 s; p < 0.0125), as well as prolonged expiratory time (ET: 2.09 ± 0.78 s vs 3.42 ± 1.16 s; p < 0.001) and total respiratory cycle time (TT: 3.14 ± 1.03 s vs 4.70 ± 1.21 s; p < 0.01) during both solid and liquid swallows compared to rest. These changes resulted in a decreased IT/TT ratio during swallowing. Our findings confirm that the EE swallowing pattern remains predominant in stable COPD patients, consistent with observations in healthy individuals. Additionally, the study highlights significant alterations in ventilatory patterns during swallowing. These results contribute to a better understanding of the interplay between swallowing and ventilation in COPD and its potential implications for airways protection.
我们的研究旨在通过分析固体和液体食物摄入时的通气模式来研究吞咽协调。21例重度至极重度稳定期COPD (GOLD III和IV)患者在执行标准化吞咽任务时进行通气和吞咽记录。结果显示,以呼气-呼气(EE)吞咽方式为主,占吞咽方式的80%,固体吞咽与液体吞咽无显著差异。每位患者平均有20.68%的燕子出现非ee模式。我们的研究结果表明,与休息时相比,液体吞咽时吸气时间(IT)增加(1.05±0.28s vs. 1.29±0.22s;p < 0.0125),以及呼气时间延长(ET: 2.09±0.78s vs. 3.42±1.16s;p < 0.001)和总呼吸周期时间(TT: 3.14±1.03s∶4.70±1.21s;P < 0.01)。这些变化导致吞咽时IT/TT比值降低。我们的研究结果证实,在稳定型COPD患者中,EE吞咽模式仍然占主导地位,这与健康个体的观察结果一致。此外,该研究还强调了吞咽过程中通气模式的显著改变。这些结果有助于更好地理解COPD患者吞咽和通气之间的相互作用及其对气道保护的潜在影响。
{"title":"Swallowing and ventilation patterns in stable COPD patients: An observational study","authors":"Virgil Rolland , Armand Bonne , Rimeh Ayari , Grégoire Prum , Eric Verin","doi":"10.1016/j.resp.2025.104419","DOIUrl":"10.1016/j.resp.2025.104419","url":null,"abstract":"<div><div>Our study aimed to investigate swallowing coordination by analyzing ventilatory patterns during of solids and liquids food intakes. Twenty-one patients with severe to very severe stable COPD (GOLD III and IV) underwent ventilation and swallowing recordings while performing standardized swallowing tasks. The results revealed that the expiratory-expiratory (EE) swallowing pattern was predominant, accounting for 80 % of swallows, with no significant differences between solid and liquid swallows. Non-EE patterns occurred in an average of 20.68 % of swallows per patient. Our results demonstrated an increased inspiratory time (IT) during liquid swallows compared to rest (1.05 ± 0.28 s vs 1.29 ± 0.22 s; <em>p</em> < 0.0125), as well as prolonged expiratory time (ET: 2.09 ± 0.78 s vs 3.42 ± 1.16 s; <em>p</em> < 0.001) and total respiratory cycle time (TT: 3.14 ± 1.03 s vs 4.70 ± 1.21 s; <em>p</em> < 0.01) during both solid and liquid swallows compared to rest. These changes resulted in a decreased IT/TT ratio during swallowing. Our findings confirm that the EE swallowing pattern remains predominant in stable COPD patients, consistent with observations in healthy individuals. Additionally, the study highlights significant alterations in ventilatory patterns during swallowing. These results contribute to a better understanding of the interplay between swallowing and ventilation in COPD and its potential implications for airways protection.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104419"},"PeriodicalIF":1.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-03-24DOI: 10.1016/j.resp.2025.104418
Valentina Jelinčić , Pei-Ying S. Chan , Paul W. Davenport , Andreas von Leupoldt
Context
Dyspnea – the subjective experience of breathing discomfort – is a prevalent and debilitating symptom in various chronic conditions, featuring a complex interplay of sensory, cognitive, and emotional factors contributing to its perception. In recent years, growing evidence emerged for the importance of neural processing in shaping symptom experiences such as dyspnea.
Objective
This frontiers review focuses on the neural gating of respiratory sensations (NGRS), as a potential neural mechanism underlying dyspnea perception. NGRS is measured by the repetition suppression of respiratory-related evoked potentials (RREP) elicited by paired inspiratory occlusions. NGRS may reflect the brain’s capacity to filter redundant respiratory input, and reduced NGRS may constitute a biomarker for aversive dyspnea experience.
Review
We summarize the current state-of-the-art on the relationships between NGRS and dyspnea, noting the inconsistent findings in healthy individuals along with promising evidence from clinical populations, such as chronic obstructive pulmonary disease (COPD). The inconsistent findings may be attributed to methodological limitations, including the significant variability in experimental designs and analytical choices hampering NGRS reliability, and the influence of top-down attention and expectations. In the final part of the review, we suggest future directions for the investigation of the NGRS-dyspnea relationship, including mechanistic research using advanced EEG analysis, mobile neuroimaging, and brain stimulation techniques to delineate the contributions of top-down and bottom-up mechanisms to NGRS.
Conclusions
By addressing the current knowledge gaps, this review forms a part of the concentrated effort to promote brain-based interventions for alleviating the distressing experience of chronic dyspnea.
{"title":"Neural gating of respiratory sensations as a potential mechanism of dyspnea perception: State-of-the-art and future directions","authors":"Valentina Jelinčić , Pei-Ying S. Chan , Paul W. Davenport , Andreas von Leupoldt","doi":"10.1016/j.resp.2025.104418","DOIUrl":"10.1016/j.resp.2025.104418","url":null,"abstract":"<div><h3>Context</h3><div>Dyspnea – the subjective experience of breathing discomfort – is a prevalent and debilitating symptom in various chronic conditions, featuring a complex interplay of sensory, cognitive, and emotional factors contributing to its perception. In recent years, growing evidence emerged for the importance of neural processing in shaping symptom experiences such as dyspnea.</div></div><div><h3>Objective</h3><div>This frontiers review focuses on the neural gating of respiratory sensations (NGRS), as a potential neural mechanism underlying dyspnea perception. NGRS is measured by the repetition suppression of respiratory-related evoked potentials (RREP) elicited by paired inspiratory occlusions. NGRS may reflect the brain’s capacity to filter redundant respiratory input, and reduced NGRS may constitute a biomarker for aversive dyspnea experience.</div></div><div><h3>Review</h3><div>We summarize the current state-of-the-art on the relationships between NGRS and dyspnea, noting the inconsistent findings in healthy individuals along with promising evidence from clinical populations, such as chronic obstructive pulmonary disease (COPD). The inconsistent findings may be attributed to methodological limitations, including the significant variability in experimental designs and analytical choices hampering NGRS reliability, and the influence of top-down attention and expectations. In the final part of the review, we suggest future directions for the investigation of the NGRS-dyspnea relationship, including mechanistic research using advanced EEG analysis, mobile neuroimaging, and brain stimulation techniques to delineate the contributions of top-down and bottom-up mechanisms to NGRS.</div></div><div><h3>Conclusions</h3><div>By addressing the current knowledge gaps, this review forms a part of the concentrated effort to promote brain-based interventions for alleviating the distressing experience of chronic dyspnea.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104418"},"PeriodicalIF":1.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}