Pub Date : 2025-12-17DOI: 10.1016/j.resp.2025.104529
Michael L Frazure, Emily G Flanigan, Ralph F Fregosi
We tested the hypothesis that developmental nicotine exposure (DNE) disrupts the cardiorespiratory response to brief, severe hypoxia by measuring ventilatory and heart rate during a 15s epoch of N2 breathing in one-to-six-day-old Sprague Dawley rat pups. Data were analyzed with a 3-way ANOVA, with inspired O2 concentration, treatment group and sex the main factors. As expected, N2 breathing significantly increased the inspired pulmonary ventilation rate (V̇)in control pups of both sexes, driven by an increase of tidal volume. In contrast, neither male nor female DNE pups increased V̇during the N2 challenge. There was no effect of hypoxia on heart rate in any group. These findings reveal a selective vulnerability: DNE specifically compromises the respiratory system's ability to increase ventilation in response to brief severe hypoxia. This dissociation between ventilatory and heart rate responses to severe hypoxia provides fresh insight into the impact of DNE on cardiorespiratory function during a critical developmental stage.
{"title":"Developmental nicotine exposure eliminates the ventilatory response to a brief episode of severe hypoxia, independently of sex.","authors":"Michael L Frazure, Emily G Flanigan, Ralph F Fregosi","doi":"10.1016/j.resp.2025.104529","DOIUrl":"https://doi.org/10.1016/j.resp.2025.104529","url":null,"abstract":"<p><p>We tested the hypothesis that developmental nicotine exposure (DNE) disrupts the cardiorespiratory response to brief, severe hypoxia by measuring ventilatory and heart rate during a 15s epoch of N<sub>2</sub> breathing in one-to-six-day-old Sprague Dawley rat pups. Data were analyzed with a 3-way ANOVA, with inspired O<sub>2</sub> concentration, treatment group and sex the main factors. As expected, N<sub>2</sub> breathing significantly increased the inspired pulmonary ventilation rate (V̇)in control pups of both sexes, driven by an increase of tidal volume. In contrast, neither male nor female DNE pups increased V̇during the N<sub>2</sub> challenge. There was no effect of hypoxia on heart rate in any group. These findings reveal a selective vulnerability: DNE specifically compromises the respiratory system's ability to increase ventilation in response to brief severe hypoxia. This dissociation between ventilatory and heart rate responses to severe hypoxia provides fresh insight into the impact of DNE on cardiorespiratory function during a critical developmental stage.</p>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104529"},"PeriodicalIF":1.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794640","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}
Posturo-respiratory coupling (PRC) reflects the interaction between breathing and postural control, and its accurate assessment is essential for understanding breathing-related balance disorders. This study investigates whether the use of a fixed-point spirometer to assess breathing profile biases PRC evaluation compared to a contactless method—optoelectronic plethysmography (OEP). Thirty healthy participants underwent two conditions in a random order: natural breathing and breathing through a spirometer. Segmental oscillations and center of pressure (CoP) displacements were recorded using contactless motion capture and force platform. Respiratory emergence (REm) and Time Lock Averaging (TLA) were used to assess the effect of breathing on the multi-segmental balance. Breathing through a spirometer significantly reduced the amplitude and velocity of segmental oscillations and CoP displacement compared to natural breathing, while breathing frequency remained unchanged. The spirometer condition induced higher incidence of neck flexion during inspiration (TLA), and altered the REm, particularly by increasing REm at the shoulder level. These findings suggest that using a fixed-point, in-contact spirometer introduces a significant bias in PRC measurements. Two mechanisms of PRC alteration are suggested: (1) due to the physical constraints associated with subject’s connection with the device; (2) of cortical origin in response to mouth breathing. In conclusion, although spirometry remains a gold standard for breathing assessment, it is unsuitable for PRC evaluation due to its disruptive influence on natural postural-respiratory dynamics. OEP, by preserving natural breathing and posture, offers a more reliable alternative for studying PRC, especially in ecological or clinical contexts such as respiratory rehabilitation or musical performance.
{"title":"Fixed-point spirometry biases the evaluation of posturo-respiratory coupling: A comparison with optoelectronic plethysmography","authors":"Rémi Valentin , Benoit Fabre , Delphine Chadefaux , Nathan Ouvrai , Thomas Similowski , Baptiste Sandoz , Valérie Attali","doi":"10.1016/j.resp.2025.104528","DOIUrl":"10.1016/j.resp.2025.104528","url":null,"abstract":"<div><div>Posturo-respiratory coupling (PRC) reflects the interaction between breathing and postural control, and its accurate assessment is essential for understanding breathing-related balance disorders. This study investigates whether the use of a fixed-point spirometer to assess breathing profile biases PRC evaluation compared to a contactless method—optoelectronic plethysmography (OEP). Thirty healthy participants underwent two conditions in a random order: natural breathing and breathing through a spirometer. Segmental oscillations and center of pressure (CoP) displacements were recorded using contactless motion capture and force platform. Respiratory emergence (REm) and Time Lock Averaging (TLA) were used to assess the effect of breathing on the multi-segmental balance. Breathing through a spirometer significantly reduced the amplitude and velocity of segmental oscillations and CoP displacement compared to natural breathing, while breathing frequency remained unchanged. The spirometer condition induced higher incidence of neck flexion during inspiration (TLA), and altered the REm, particularly by increasing REm at the shoulder level. These findings suggest that using a fixed-point, in-contact spirometer introduces a significant bias in PRC measurements. Two mechanisms of PRC alteration are suggested: (1) due to the physical constraints associated with subject’s connection with the device; (2) of cortical origin in response to mouth breathing. In conclusion, although spirometry remains a gold standard for breathing assessment, it is unsuitable for PRC evaluation due to its disruptive influence on natural postural-respiratory dynamics. OEP, by preserving natural breathing and posture, offers a more reliable alternative for studying PRC, especially in ecological or clinical contexts such as respiratory rehabilitation or musical performance.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104528"},"PeriodicalIF":1.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737158","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 : 2025-12-11DOI: 10.1016/j.resp.2025.104526
Caroline O. Ribeiro , Cíntia M.S. Sousa , Manuela G. Torres , Raphael F.J. Oliveira , Agnaldo J. Lopes , Pedro L. Melo
Respiratory oscillometry can help understand pathophysiological changes and detect early abnormalities. However, little is known about oscillometry in adult individuals with cystic fibrosis (CF). This research examines the emerging role of respiratory oscillometry in the context of groups of adult CF patients associated with greater severity. The contributions to our understanding of the respiratory abnormalities along the course of increasing severity and the diagnostic use of this method were also evaluated.
This cross-sectional study was conducted in 15 individuals with no history of smoking or pulmonary diseases (control group), and 52 individuals with diagnoses of CF were studied, being classified into 10 normal to the spirometric exam, 14 mild, 16 moderate, and 12 severe cases. The mean age of the patients was 25.2 years.
Airway obstruction resulted in increased values of resistance at 4 Hz (R4, Kruskal-Wallis, p = 0.0002), 12 Hz (R12, p = 0.0032), and resistance dependence (R4-R20, p < 0.0001). Similar analysis revealed reductions in dynamic compliance (Cdyn, p < 0.0001) and ventilation homogeneity, as assessed by resonance frequency (fr, p < 0.0001) and reactance area (Ax, p < 0.0001). Respiratory work, as measured by the impedance modulus, also showed increased values (Z4, p < 0.0001). Oscillometric indexes showed moderate to good correlations with spirometric and plethysmographic parameters. The early abnormalities in mild airway obstruction were detected by fr and Ax with adequate accuracy (AUC>0.70). At the same time, R4-R20, fr, and Ax achieved high diagnostic accuracy (AUC>0.95) in diagnosing late-stage respiratory changes. We conclude that 1) airflow obstruction in adults with CF introduces significant changes in the resistive and reactive properties of the respiratory system compared with healthy subjects; 2) these changes are proportional to airway obstruction; and 3) oscillometry provides novel information suitable to facilitate the diagnosis of respiratory abnormalities in adults with CF.
呼吸振荡测量可以帮助了解病理生理变化和发现早期异常。然而，对囊性纤维化（CF）成人个体的振荡测量知之甚少。本研究探讨了呼吸振荡测量法在与严重程度相关的成年CF患者组中的新作用。对我们对呼吸异常随着严重程度的增加而增加的认识以及该方法的诊断应用的贡献也进行了评估。本横断面研究选取了15例无吸烟史或肺部疾病的个体（对照组），52例诊断为CF的个体进行研究，肺活量检查分为正常至正常10例，轻度14例，中度16例，重度12例。患者平均年龄25.2岁。气道阻塞导致4 Hz （R4, Kruskal-Wallis, p = 0.0002）、12 Hz （R12, p = 0.0032）和阻力依赖性（R4- r20, p <； 0.0001）的阻力值升高。类似的分析显示，通过共振频率（fr, p <； 0.0001）和电抗面积（Ax, p <； 0.0001）评估，动态顺应性（Cdyn, p <； 0.0001）和通风均匀性降低。通过阻抗模量测量的呼吸功也显示出增加的值（Z4, p <； 0.0001）。振荡指标与肺活量测定和容积描记参数表现出中度至良好的相关性。fr和Ax检测轻度气道阻塞的早期异常具有足够的准确性（AUC>0.70）。同时，R4-R20、fr、Ax在诊断晚期呼吸变化方面具有较高的诊断准确率（AUC>0.95）。我们得出结论：1)与健康受试者相比，CF成人气流阻塞导致呼吸系统的阻力和反应特性发生显著变化；2)这些变化与气道阻塞成正比；3)振荡测量法提供了适合于诊断成人CF呼吸异常的新信息。
{"title":"Oscillation mechanics in adults with cystic fibrosis: Effect of airway obstruction and detection of early dysfunction","authors":"Caroline O. Ribeiro , Cíntia M.S. Sousa , Manuela G. Torres , Raphael F.J. Oliveira , Agnaldo J. Lopes , Pedro L. Melo","doi":"10.1016/j.resp.2025.104526","DOIUrl":"10.1016/j.resp.2025.104526","url":null,"abstract":"<div><div>Respiratory oscillometry can help understand pathophysiological changes and detect early abnormalities. However, little is known about oscillometry in adult individuals with cystic fibrosis (CF). This research examines the emerging role of respiratory oscillometry in the context of groups of adult CF patients associated with greater severity. The contributions to our understanding of the respiratory abnormalities along the course of increasing severity and the diagnostic use of this method were also evaluated.</div><div>This cross-sectional study was conducted in 15 individuals with no history of smoking or pulmonary diseases (control group), and 52 individuals with diagnoses of CF were studied, being classified into 10 normal to the spirometric exam, 14 mild, 16 moderate, and 12 severe cases. The mean age of the patients was 25.2 years.</div><div>Airway obstruction resulted in increased values of resistance at 4 Hz (R4, Kruskal-Wallis, p = 0.0002), 12 Hz (R12, p = 0.0032), and resistance dependence (R4-R20, p < 0.0001). Similar analysis revealed reductions in dynamic compliance (Cdyn, p < 0.0001) and ventilation homogeneity, as assessed by resonance frequency (fr, p < 0.0001) and reactance area (Ax, p < 0.0001). Respiratory work, as measured by the impedance modulus, also showed increased values (Z4, p < 0.0001). Oscillometric indexes showed moderate to good correlations with spirometric and plethysmographic parameters. The early abnormalities in mild airway obstruction were detected by fr and Ax with adequate accuracy (AUC>0.70). At the same time, R4-R20, fr, and Ax achieved high diagnostic accuracy (AUC>0.95) in diagnosing late-stage respiratory changes. We conclude that 1) airflow obstruction in adults with CF introduces significant changes in the resistive and reactive properties of the respiratory system compared with healthy subjects; 2) these changes are proportional to airway obstruction; and 3) oscillometry provides novel information suitable to facilitate the diagnosis of respiratory abnormalities in adults with CF.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104526"},"PeriodicalIF":1.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737159","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 : 2025-12-10DOI: 10.1016/j.resp.2025.104527
T.J. Pereira , H. Edgell
The mechanoreflex mediates the initial cardiorespiratory response during dynamic exercise, via input from the mechanical deformation of the exercising muscle. In response to passive movement (PM), engaging a greater number of limbs elicits a higher heart rate response. Additionally, males have larger pressor responses to arm PM; however, no sex differences exist in the pressor response to leg PM. Considering that the legs are a larger muscle mass and the pressor response to leg PM was not different between sexes, this may suggest inherent limb-dependant differences. This study aimed to determine sex differences and the role of limb volume and muscle strength on the cardiorespiratory responses to arm and leg PM. Females were smaller (i.e., stature, limb volume), less fit and had weaker handgrip strength compared to males (all p < 0.05); although, both sexes had similar plantarflexion strength (p = 0.3). During arm PM, only males experienced an increased MAP response to arm PM (p < 0.001), compared to females (p < 0.05); however, this sex difference was eliminated when accounting for disparities in forearm volume. Males and females had similar cardiorespiratory responses to leg PM (all p > 0.05). Further, greater plantarflexion strength enhanced the ventilatory response to leg PM in both sexes (p = 0.024). Based on covariate analysis, differences in limb volume and muscle strength contributed almost half of the variability in the cardiorespiratory responses to arm or leg PM. Contrary to our hypotheses, the results of the current study suggest that the previously observed sex and limb-dependant differences were influenced by disparities in limb characteristics (i.e., volume or strength).
{"title":"Sex differences in the cardiovascular and ventilatory responses to arm or leg mechanoreflex activation","authors":"T.J. Pereira , H. Edgell","doi":"10.1016/j.resp.2025.104527","DOIUrl":"10.1016/j.resp.2025.104527","url":null,"abstract":"<div><div>The mechanoreflex mediates the initial cardiorespiratory response during dynamic exercise, via input from the mechanical deformation of the exercising muscle. In response to passive movement (PM), engaging a greater number of limbs elicits a higher heart rate response. Additionally, males have larger pressor responses to arm PM; however, no sex differences exist in the pressor response to leg PM. Considering that the legs are a larger muscle mass and the pressor response to leg PM was not different between sexes, this may suggest inherent limb-dependant differences. This study aimed to determine sex differences and the role of limb volume and muscle strength on the cardiorespiratory responses to arm and leg PM. Females were smaller (i.e., stature, limb volume), less fit and had weaker handgrip strength compared to males (all p < 0.05); although, both sexes had similar plantarflexion strength (p = 0.3). During arm PM, only males experienced an increased MAP response to arm PM (p < 0.001), compared to females (p < 0.05); however, this sex difference was eliminated when accounting for disparities in forearm volume. Males and females had similar cardiorespiratory responses to leg PM (all p > 0.05). Further, greater plantarflexion strength enhanced the ventilatory response to leg PM in both sexes (p = 0.024). Based on covariate analysis, differences in limb volume and muscle strength contributed almost half of the variability in the cardiorespiratory responses to arm or leg PM. Contrary to our hypotheses, the results of the current study suggest that the previously observed sex and limb-dependant differences were influenced by disparities in limb characteristics (i.e., volume or strength).</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104527"},"PeriodicalIF":1.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744149","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 : 2025-12-08DOI: 10.1016/j.resp.2025.104525
Lucía Vaamonde , Miguel Martell , Patricia Vollono , Tatiana Gagliardi , Cecilia Fernández , Fernando E. Silvera , M. Fernanda Blasina
Hypoxic-ischemic encephalopathy (HIE) in newborns treated with therapeutic hypothermia(TH) represents a challenge, especially during cooling phase which could be less controlled. This study explored the hemodynamic effects of the cooling phase of TH in a piglet model of perinatal asphyxia with lung injury. Cardiovascular parameters, including systemic arterial pressure (SAP), pulmonary artery pressure (PAP), heart rate (HR), and cardiac output (CO) were monitored from 38.5 to 39.5°C -physiological- to 31.0°C. The piglets were divided into TH without (H, n = 12) and TH with lung injury (Hi, n = 7). Both groups showed decreases in SAP, HR, and CO, more pronounced in Hi. PAP was consistently higher in Hi, though it decreased significantly below 33.5°C (40 % less at 31°C, compared to baseline). Myocardial contractility decreased along the cooling, particularly in Hi group, explaining CO reduction (40 % and 35 % in Hi and H group, respectively). No significant changes were observed in brain monitoring, oxygen extraction ratio, or acid-base status. We concluded that in HIE model, close hemodynamic monitoring during the induction phase of TH as well as monitoring of tissue oxygenation warrants detection of changes, a special challenge when lung injury is developed. Although hemodynamic changes were observed with TH in this model, it was not contraindicated since brain oxygenation was unchanged. These data suggest that TH may be a viable option for human neonates with similar conditions, but further research is essential to evaluate its safety and efficacy in this vulnerable population.
{"title":"Key hemodynamic parameters during induced hypothermia cooling phase in healthy and injured piglets","authors":"Lucía Vaamonde , Miguel Martell , Patricia Vollono , Tatiana Gagliardi , Cecilia Fernández , Fernando E. Silvera , M. Fernanda Blasina","doi":"10.1016/j.resp.2025.104525","DOIUrl":"10.1016/j.resp.2025.104525","url":null,"abstract":"<div><div>Hypoxic-ischemic encephalopathy (HIE) in newborns treated with therapeutic hypothermia(TH) represents a challenge, especially during cooling phase which could be less controlled. This study explored the hemodynamic effects of the cooling phase of TH in a piglet model of perinatal asphyxia with lung injury. Cardiovascular parameters, including systemic arterial pressure (SAP), pulmonary artery pressure (PAP), heart rate (HR), and cardiac output (CO) were monitored from 38.5 to 39.5°C -physiological- to 31.0°C. The piglets were divided into TH without (H, n = 12) and TH with lung injury (Hi, n = 7). Both groups showed decreases in SAP, HR, and CO, more pronounced in Hi. PAP was consistently higher in Hi, though it decreased significantly below 33.5°C (40 % less at 31°C, compared to baseline). Myocardial contractility decreased along the cooling, particularly in Hi group, explaining CO reduction (40 % and 35 % in Hi and H group, respectively). No significant changes were observed in brain monitoring, oxygen extraction ratio, or acid-base status. We concluded that in HIE model, close hemodynamic monitoring during the induction phase of TH as well as monitoring of tissue oxygenation warrants detection of changes, a special challenge when lung injury is developed. Although hemodynamic changes were observed with TH in this model, it was not contraindicated since brain oxygenation was unchanged. These data suggest that TH may be a viable option for human neonates with similar conditions, but further research is essential to evaluate its safety and efficacy in this vulnerable population.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104525"},"PeriodicalIF":1.6,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725571","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 : 2025-11-25DOI: 10.1016/j.resp.2025.104524
K Michael Spyer, Julian F R Paton
{"title":"Diethelm Richter (1943-2025); a life in Respiratory Neurobiology.","authors":"K Michael Spyer, Julian F R Paton","doi":"10.1016/j.resp.2025.104524","DOIUrl":"https://doi.org/10.1016/j.resp.2025.104524","url":null,"abstract":"","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104524"},"PeriodicalIF":1.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638050","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 : 2025-11-25DOI: 10.1016/j.resp.2025.104524
K Michael Spyer, Julian F R Paton
{"title":"Diethelm Richter (1943-2025): A life in respiratory neurobiology.","authors":"K Michael Spyer, Julian F R Paton","doi":"10.1016/j.resp.2025.104524","DOIUrl":"https://doi.org/10.1016/j.resp.2025.104524","url":null,"abstract":"","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":" ","pages":"104524"},"PeriodicalIF":1.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757471","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}
Respiratory dysfunction in people with multiple sclerosis (PwMS) is often attributed to respiratory pump failure, yet central respiratory drive and automatic breathing control remain underexplored. We assessed the prevalence of breathing automatic-voluntary dissociation (AVD) in PwMS.
Methods
We analyzed prospectively collected data from a tertiary care rehabilitation center observational cohort. All adult PwMS, who underwent pulmonary function testing, including a CO₂ ventilatory response test, while relapse-free for ≥ 3 months, between January 2018 and December 2024 were screened. AVD was defined by maximal tidal volume (VTmax) during CO₂ response test higher than vital capacity (VC)(VTmax/VC>1), reflecting discordance between voluntary and automatic respiratory response. Univariate analysis and multivariate logistic regression were performed to identify variables associated with AVD.
Results
Fifty-five PwMS were included (age 59 ±7 years, disease duration 23 ± 11 years, women 64 %, median EDSS 8[7,5;8,5]). Restrictive ventilatory pattern was observed in 65 %, 32 % being severely impaired, and with cough impairment in 64 %. Eighteen (33 %) presented AVD. It was associated with significantly lower VC, inspiratory capacity, peak cough flow (p < 0.001), higher EDSS scores and greater use of respiratory support devices (CPAP/NIV, p = 0.002; mechanical in-exsufflation, p = 0.002).
Conclusion
Breathing AVD is frequent in PwMs with severe disease, underscoring the relevance of thorough respiratory assessment to individualize respiratory care.
{"title":"Description of automatic-voluntary dissociation of breathing in multiple sclerosis","authors":"Alicia Garcia Alvarez , Djamel Bensmail , Caroline Hélie , Manon Tamiatto , Isabelle Bossard , Jonathan Levy , Hélène Prigent","doi":"10.1016/j.resp.2025.104523","DOIUrl":"10.1016/j.resp.2025.104523","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory dysfunction in people with multiple sclerosis (PwMS) is often attributed to respiratory pump failure, yet central respiratory drive and automatic breathing control remain underexplored. We assessed the prevalence of breathing automatic-voluntary dissociation (AVD) in PwMS.</div></div><div><h3>Methods</h3><div>We analyzed prospectively collected data from a tertiary care rehabilitation center observational cohort. All adult PwMS, who underwent pulmonary function testing, including a CO₂ ventilatory response test, while relapse-free for ≥ 3 months, between January 2018 and December 2024 were screened. AVD was defined by maximal tidal volume (VTmax) during CO₂ response test higher than vital capacity (VC)(VTmax/VC>1), reflecting discordance between voluntary and automatic respiratory response. Univariate analysis and multivariate logistic regression were performed to identify variables associated with AVD.</div></div><div><h3>Results</h3><div>Fifty-five PwMS were included (age 59 ±7 years, disease duration 23 ± 11 years, women 64 %, median EDSS 8[7,5;8,5]). Restrictive ventilatory pattern was observed in 65 %, 32 % being severely impaired, and with cough impairment in 64 %. Eighteen (33 %) presented AVD. It was associated with significantly lower VC, inspiratory capacity, peak cough flow (p < 0.001), higher EDSS scores and greater use of respiratory support devices (CPAP/NIV, p = 0.002; mechanical in-exsufflation, p = 0.002).</div></div><div><h3>Conclusion</h3><div>Breathing AVD is frequent in PwMs with severe disease, underscoring the relevance of thorough respiratory assessment to individualize respiratory care.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104523"},"PeriodicalIF":1.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582312","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 : 2025-11-14DOI: 10.1016/j.resp.2025.104513
Debolina D. Biswas , Nicolas H. Han , Marán Y. Hernández Rodríguez, Jane Lee, Sarra M. Abdelbarr, Evelyn R. Scarrow, Mai K. ElMallah
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by a deficiency of dystrophin. Dystrophin deficiency leads to progressive muscle weakness, including involvement of the respiratory muscles, ultimately resulting in respiratory failure. Adeno-associated virus (AAV)-mediated gene therapy carrying a microdystrophin (µDys) transgene was recently approved by the Food and Drug Administration (FDA); however, its effects on the respiratory system remain unclear. Further, effective transduction of all muscle groups requires high systemic AAV doses, which are associated with dose-dependent toxicities. In this study, we investigated whether respiratory-directed gene therapy can 1) specifically target respiratory muscles and (2) reduce the total AAV-µDys dose required for therapeutic benefit. We compared the efficiency of AAV9-µDys delivery using different administration routes and dosages in D2.mdx mice, a mouse model of DMD. AAV9-µDys was administered either systemically at a high dose, locally at intermediate doses via intralingual and intrathoracic injections, or through a combination of systemic and respiratory-directed intermediate dosing. All treatments resulted in improved respiratory muscle dystrophin expression and decreased pathology; however, the intermediate and combination dosing led to lower liver vector genome expression. In conclusion, respiratory-targeted gene therapy can improve respiratory muscle pathology while reducing the need for high systemic AAV doses associated with liver toxicity.
{"title":"AAV9 gene therapy to target respiratory insufficiency in the D2.mdx mouse model of duchenne muscular dystrophy","authors":"Debolina D. Biswas , Nicolas H. Han , Marán Y. Hernández Rodríguez, Jane Lee, Sarra M. Abdelbarr, Evelyn R. Scarrow, Mai K. ElMallah","doi":"10.1016/j.resp.2025.104513","DOIUrl":"10.1016/j.resp.2025.104513","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by a deficiency of dystrophin. Dystrophin deficiency leads to progressive muscle weakness, including involvement of the respiratory muscles, ultimately resulting in respiratory failure. Adeno-associated virus (AAV)-mediated gene therapy carrying a microdystrophin (µDys) transgene was recently approved by the Food and Drug Administration (FDA); however, its effects on the respiratory system remain unclear. Further, effective transduction of all muscle groups requires high systemic AAV doses, which are associated with dose-dependent toxicities. In this study, we investigated whether respiratory-directed gene therapy can 1) specifically target respiratory muscles and (2) reduce the total AAV-µDys dose required for therapeutic benefit. We compared the efficiency of AAV9-µDys delivery using different administration routes and dosages in D2.mdx mice, a mouse model of DMD. AAV9-µDys was administered either systemically at a high dose, locally at intermediate doses via intralingual and intrathoracic injections, or through a combination of systemic and respiratory-directed intermediate dosing. All treatments resulted in improved respiratory muscle dystrophin expression and decreased pathology; however, the intermediate and combination dosing led to lower liver vector genome expression. In conclusion, respiratory-targeted gene therapy can improve respiratory muscle pathology while reducing the need for high systemic AAV doses associated with liver toxicity.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104513"},"PeriodicalIF":1.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534762","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 : 2025-11-14DOI: 10.1016/j.resp.2025.104512
D. van Scheppingen , M. de Haan , M. Gerrits , STJ van der Landen , GM Lötgerink , R. De Jongh , R. Bezemer
The aim of this study was to better understand the ventilatory response to controlled progressive hypoxia in healthy individuals and identify factors influencing the development of periodic breathing under hypoxic conditions. The study was conducted in a hypoxia room at the Complementary Medical Centre in Genk, Belgium. Eighteen healthy participants were subjected to controlled progressive hypoxia, with oxygen levels ranging from 0.21 to 0.10. Oxygen saturation (SpO2) was measured using a Nellcor® PM10N pulse oximeter, and carbon dioxide levels, including end-tidal carbon dioxide (EtCO2), were monitored using a Philips LoFlo® sidestream device. Recorded data of SpO2 sensor and capnography were analyzed whether sex, age, and Body Mass Index (BMI) were factors influencing the participants’ ventilatory response to hypoxic conditions.
Results
showed that 22 % of the study participants developed periodic breathing, all of whom were men, particularly older individuals, with an average age of 40.0 ± 16.2 years (p = 0.026). There was a notable sex-specific response, with 100 % of periodic breathing cases being male (p = 0.078). Significant correlations were found within the periodic breathing group: BMI correlated with the SpO2 value at the start of PB (R2=0.987, p = 0.013), the pulse rate at the start of periodic breathing (R2=-0.992, p = 0.008), and the EtCO2 at the end of the first breath after the apneic phase (R2=0.908, p = 0.092). These findings indicate that sex, age, and BMI are critical factors in determining an individual's ventilatory response to hypoxic conditions. Periodic breathing developed exclusively in men, and the physiological state at the onset of periodic breathing, measured by the SpO2 and pulse rate, was significantly correlated with BMI.
{"title":"Development of periodic breathing in awake healthy individuals under controlled progressive hypoxia","authors":"D. van Scheppingen , M. de Haan , M. Gerrits , STJ van der Landen , GM Lötgerink , R. De Jongh , R. Bezemer","doi":"10.1016/j.resp.2025.104512","DOIUrl":"10.1016/j.resp.2025.104512","url":null,"abstract":"<div><div>The aim of this study was to better understand the ventilatory response to controlled progressive hypoxia in healthy individuals and identify factors influencing the development of periodic breathing under hypoxic conditions. The study was conducted in a hypoxia room at the Complementary Medical Centre in Genk, Belgium. Eighteen healthy participants were subjected to controlled progressive hypoxia, with oxygen levels ranging from 0.21 to 0.10. Oxygen saturation (SpO<sub>2</sub>) was measured using a Nellcor® PM10N pulse oximeter, and carbon dioxide levels, including end-tidal carbon dioxide (EtCO<sub>2</sub>), were monitored using a Philips LoFlo® sidestream device. Recorded data of SpO<sub>2</sub> sensor and capnography were analyzed whether sex, age, and Body Mass Index (BMI) were factors influencing the participants’ ventilatory response to hypoxic conditions.</div></div><div><h3>Results</h3><div>showed that 22 % of the study participants developed periodic breathing, all of whom were men, particularly older individuals, with an average age of 40.0 ± 16.2 years (p = 0.026). There was a notable sex-specific response, with 100 % of periodic breathing cases being male (p = 0.078). Significant correlations were found within the periodic breathing group: BMI correlated with the SpO<sub>2</sub> value at the start of PB (R<sup>2</sup>=0.987, p = 0.013), the pulse rate at the start of periodic breathing (R<sup>2</sup>=-0.992, p = 0.008), and the EtCO<sub>2</sub> at the end of the first breath after the apneic phase (R<sup>2</sup>=0.908, p = 0.092). These findings indicate that sex, age, and BMI are critical factors in determining an individual's ventilatory response to hypoxic conditions. Periodic breathing developed exclusively in men, and the physiological state at the onset of periodic breathing, measured by the SpO<sub>2</sub> and pulse rate, was significantly correlated with BMI.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104512"},"PeriodicalIF":1.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534741","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}
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