Pub Date : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub 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":"2026-02-01","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}
Pub Date : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub 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":"10.1016/j.resp.2025.104524","url":null,"abstract":"","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"340 ","pages":"Article 104524"},"PeriodicalIF":1.6,"publicationDate":"2026-02-01","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}
Pub Date : 2026-01-01Epub Date: 2025-09-18DOI: 10.1016/j.resp.2025.104490
Camila Melo Coelho Loureiro , Eloara V.M. Ferreira , Rudolf K.F. Oliveira , Andrei Augusto Assis de Campos Cordeiro , Elaine Brito Vieira , Meliane de Oliveira Daud , Ivan Teruaki Ivanaga , Luiz Eduardo Nery , Jaquelina Sonoe Ota-Arakaki , Roberta Pulcheri Ramos
Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is mainly caused by mechanical obstruction by thrombi associated with pulmonary vascular remodeling. Bronchial collateral circulation has been studied as a protective mechanism or implicated in the pathogenesis of microvascular disease, also contributing to changes in gas exchange at rest and during exercise. In this study, we sought to characterize the gas exchange abnormalities in patients with CTEPH with particular attention to bronchopulmonary shunt.
Methods
Prospective, cross-sectional study with diagnostic intervention. After undergoing right heart catheterization, subjects performed a 50 % maximal workload steady-state exercise at room air and receiving 100 % oxygen with a face mask from a Douglas bag. Arterial and mixed venous blood samples were obtained for gas analysis and calculation of shunt.
Results
Data from 14 subjects (7 women, 49 ± 15 years) with CTEPH were analyzed. All participants showed an increased shunt volume/fraction detected by 100 % oxygen breathing at rest that decreased during exercise (17.0 ± 3.6 % versus 9.8 ± 3.0 %; P < 0.001). Shunt fraction was negatively correlated with hemodynamic severity at rest, degree of pulmonary vascular obstruction and dilation of the pulmonary artery trunk. A drop in PaO₂ was observed in 71 % of patients with RVP > 750 dynes.s.cm5, compared to 14 % among those with less severe hemodynamic profile. Multiple linear regression analysis revealed that both PVR and the Qanadli score were independently associated with bronchopulmonary shunt fraction during exercise.
Conclusion
Bronchopulmonary shunt seems to be an adaptive mechanism in CTEPH at rest and during exercise.
背景:慢性血栓栓塞性肺动脉高压(CTEPH)主要由与肺血管重构相关的血栓机械性阻塞引起。支气管侧枝循环作为一种保护机制或参与微血管疾病的发病机制,也有助于休息和运动时气体交换的变化。在这项研究中,我们试图描述CTEPH患者的气体交换异常,特别关注支气管肺分流。方法:前瞻性、横断面研究和诊断干预。在接受右心导管插管后,受试者在室内空气中进行50%最大负荷稳态运动,并在道格拉斯袋面罩下接受100%氧气。取动脉血和混合性静脉血进行气体分析和分流计算。结果:分析了14例CTEPH患者(7例女性,49±15岁)的数据。所有参与者在休息时100%氧气呼吸检测到的分流体积/分数增加,在运动期间下降(17.0±3.6% vs 9.8±3.0%;P 750 dydys)。而在血流动力学不太严重的患者中,这一比例为14%。多元线性回归分析显示PVR和Qanadli评分与运动时支气管肺分流分数独立相关。结论:支气管肺分流可能是静止和运动时CTEPH的一种适应性机制。
{"title":"Gas exchange dynamics and responses to exercise in chronic thromboembolic pulmonary hypertension","authors":"Camila Melo Coelho Loureiro , Eloara V.M. Ferreira , Rudolf K.F. Oliveira , Andrei Augusto Assis de Campos Cordeiro , Elaine Brito Vieira , Meliane de Oliveira Daud , Ivan Teruaki Ivanaga , Luiz Eduardo Nery , Jaquelina Sonoe Ota-Arakaki , Roberta Pulcheri Ramos","doi":"10.1016/j.resp.2025.104490","DOIUrl":"10.1016/j.resp.2025.104490","url":null,"abstract":"<div><h3>Background</h3><div>Chronic thromboembolic pulmonary hypertension (CTEPH) is mainly caused by mechanical obstruction by thrombi associated with pulmonary vascular remodeling. Bronchial collateral circulation has been studied as a protective mechanism or implicated in the pathogenesis of microvascular disease, also contributing to changes in gas exchange at rest and during exercise. In this study, we sought to characterize the gas exchange abnormalities in patients with CTEPH with particular attention to bronchopulmonary shunt.</div></div><div><h3>Methods</h3><div>Prospective, cross-sectional study with diagnostic intervention. After undergoing right heart catheterization, subjects performed a 50 % maximal workload steady-state exercise at room air and receiving 100 % oxygen with a face mask from a Douglas bag. Arterial and mixed venous blood samples were obtained for gas analysis and calculation of shunt.</div></div><div><h3>Results</h3><div>Data from 14 subjects (7 women, 49 ± 15 years) with CTEPH were analyzed. All participants showed an increased shunt volume/fraction detected by 100 % oxygen breathing at rest that decreased during exercise (17.0 ± 3.6 % versus 9.8 ± 3.0 %; <em>P</em> < 0.001). Shunt fraction was negatively correlated with hemodynamic severity at rest, degree of pulmonary vascular obstruction and dilation of the pulmonary artery trunk<strong>.</strong> A drop in PaO₂ was observed in 71 % of patients with RVP > 750 dynes.s.cm<sup>5</sup>, compared to 14 % among those with less severe hemodynamic profile. Multiple linear regression analysis revealed that both PVR and the Qanadli score were independently associated with bronchopulmonary shunt fraction during exercise.</div></div><div><h3>Conclusion</h3><div>Bronchopulmonary shunt seems to be an adaptive mechanism in CTEPH at rest and during exercise.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"339 ","pages":"Article 104490"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102752","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 : 2026-01-01Epub Date: 2025-09-27DOI: 10.1016/j.resp.2025.104498
Apostolos A. Menis , Vasiliki Tsolaki , Maria E. Papadonta , Vasileios Vazgiourakis , Konstantinos Mantzarlis , Epaminondas Zakynthinos , Demosthenes Makris
Introduction
The effect of MIP on extravascular lung water generation (EVLW) is not known. Our aim was to compare a resistive breathing trial (RBT) to MIP in terms of EVLW generation and in predicting the weaning outcome.
Methods
In patients undergoing a spontaneous breathing trial (SBT) for the first time we compared the EVLW generated, using lung ultrasound (B-lines), during MIP to SBT and RBT; MIP, airway pressure swings during RBT (ΔPawRBT) and its ratio to rapid shallow breathing index during RBT (ΔPaw/RSBI)RBT were assessed as indices of weaning prediction. Additionally, we assessed the relationship of MIP, ΔPawRBT and (ΔPaw/RSBI)RBT to esophageal (Pes) and transdiaphragmatic pressure (Pdi) and the pressure-time product of the Pes (PTPes). Weaning failure was defined as SBT failure or need for reintubation at 48 h.
Measurement and main results
Thirty-three patients were enrolled. B-lines, heart rate and blood pressure were higher during MIP compared to RBT (p < 0.001). ΔPawRBT, (ΔPaw/RSBI)RBT and MIP were higher in patients succeeding weaning compared to those who failed [19.53 cmH2O (±11.91) vs 10.77 cmH2O (±8.94), p = 0.027], [0.16 cmH₂O·L·min⁻¹ (0.16) vs 0.05 cmH₂O·L·min⁻¹ (0.03), p < 0.001)], [41.39 cmH2O (14.59) vs 16.34 cmH2O (20.3), p = 0.002]. ROC analysis showed no difference between MIP and ΔPawRBT or (ΔPaw/RSBI)RBT in predicting weaning outcome; ΔPawRBT and (ΔPaw/RSBI)RBT correlated with Pes, Pdi and PTPes (p < 0.05).
Conclusions
(ΔPaw/RSBI)RBT predicted weaning outcome with similar accuracy to MIP and was associated with less B-lines, HR and BP alterations; RBT-derived airway pressures are a promising novel method for weaning outcome prediction and respiratory muscle strength assessment.
{"title":"Comparison of maximal inspiratory pressure to resistive breathing for weaning prediction","authors":"Apostolos A. Menis , Vasiliki Tsolaki , Maria E. Papadonta , Vasileios Vazgiourakis , Konstantinos Mantzarlis , Epaminondas Zakynthinos , Demosthenes Makris","doi":"10.1016/j.resp.2025.104498","DOIUrl":"10.1016/j.resp.2025.104498","url":null,"abstract":"<div><h3>Introduction</h3><div>The effect of MIP on extravascular lung water generation (EVLW) is not known. Our aim was to compare a resistive breathing trial (RBT) to MIP in terms of EVLW generation and in predicting the weaning outcome.</div></div><div><h3>Methods</h3><div>In patients undergoing a spontaneous breathing trial (SBT) for the first time we compared the EVLW generated, using lung ultrasound (B-lines), during MIP to SBT and RBT; MIP, airway pressure swings during RBT (ΔPaw<sub>RBT</sub>) and its ratio to rapid shallow breathing index during RBT (ΔPaw/RSBI)<sub>RBT</sub> were assessed as indices of weaning prediction. Additionally, we assessed the relationship of MIP, ΔPaw<sub>RBT</sub> and (ΔPaw/RSBI)<sub>RBT</sub> to esophageal (Pes) and transdiaphragmatic pressure (Pdi) and the pressure-time product of the Pes (PTPes). Weaning failure was defined as SBT failure or need for reintubation at 48 h.</div></div><div><h3>Measurement and main results</h3><div>Thirty-three patients were enrolled. B-lines, heart rate and blood pressure were higher during MIP compared to RBT (p < 0.001). ΔPaw<sub>RBT</sub>, (ΔPaw/RSBI)<sub>RBT</sub> and MIP were higher in patients succeeding weaning compared to those who failed [19.53 cmH<sub>2</sub>O (±11.91) vs 10.77 cmH<sub>2</sub>O (±8.94), p = 0.027], [0.16 cmH₂O·L·min⁻¹ (0.16) vs 0.05 cmH₂O·L·min⁻¹ (0.03), p < 0.001)], [41.39 cmH<sub>2</sub>O (14.59) vs 16.34 cmH<sub>2</sub>O (20.3), p = 0.002]. ROC analysis showed no difference between MIP and ΔPaw<sub>RBT</sub> or (ΔPaw/RSBI)<sub>RBT</sub> in predicting weaning outcome; ΔPaw<sub>RBT</sub> and (ΔPaw/RSBI)<sub>RBT</sub> correlated with Pes, Pdi and PTPes (p < 0.05).</div></div><div><h3>Conclusions</h3><div>(ΔPaw/RSBI)<sub>RBT</sub> predicted weaning outcome with similar accuracy to MIP and was associated with less B-lines, HR and BP alterations; RBT-derived airway pressures are a promising novel method for weaning outcome prediction and respiratory muscle strength assessment.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"339 ","pages":"Article 104498"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192744","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 : 2026-01-01Epub Date: 2025-10-27DOI: 10.1016/j.resp.2025.104509
Anatoly S. Borovik , Roman Yu. Zhedyaev , Vladimir O. Negulyaev , Kirill A. Bogotskoy , Viktoriia A. Iashina , Elena S. Tomilovskaya , Olga S. Tarasova , Olga L. Vinogradova
Purpose
We studied the synchronization of mean arterial pressure (MAP) and heart rate (HR) high frequency (HF) respiratory oscillations in young men in the supine position and during head-up tilt (HUT), and then analyzed the effect of blood redistribution on these parameters in the lower body negative pressure (LBNP) test, sit-to-stand test and HUT test performed after a 7-day dry immersion (DI, on-ground model of microgravity).
Methods
75 young male volunteers participated in the study. Blood pressure and ECG were continuously recorded, to obtain mean arterial pressure (MAP), heart rate (HR) and wavelet spectra of these parameters. Phases of the oscillations were calculated using Morse analytical wavelets. The synchronization between oscillations was estimated using phase synchronization index (PSI) calculated from Shannon entropy for phase difference distribution histogram.
Results
HUT increased the amplitude of HF MAP waves, but decreased the amplitude of HF waves of HR. The phase shift between HF MAP and HR waves decreased, but the degree of their synchronization increased, as reflected by an increase in the HF peak in PSI spectrum. Similar changes, except for an increase in PSI, were recorded upon exposure to LBNP and in the sit-to-stand test. After 7-day exposure to DI conditions, phase shift between HF MAP and HR oscillations decreased in supine position and then did not change during orthostasis.
Conclusion
The changes in body position, LBNP and dry immersion exposure, which are associated with a decrease in vagal activity, affect the phase relationship between respiratory MAP and HR waves.
{"title":"The change in phase shift between respiratory oscillations of mean arterial pressure and heart rate in head-up tilt test: The effect of simulated microgravity","authors":"Anatoly S. Borovik , Roman Yu. Zhedyaev , Vladimir O. Negulyaev , Kirill A. Bogotskoy , Viktoriia A. Iashina , Elena S. Tomilovskaya , Olga S. Tarasova , Olga L. Vinogradova","doi":"10.1016/j.resp.2025.104509","DOIUrl":"10.1016/j.resp.2025.104509","url":null,"abstract":"<div><h3>Purpose</h3><div>We studied the synchronization of mean arterial pressure (MAP) and heart rate (HR) high frequency (HF) respiratory oscillations in young men in the supine position and during head-up tilt (HUT), and then analyzed the effect of blood redistribution on these parameters in the lower body negative pressure (LBNP) test, sit-to-stand test and HUT test performed after a 7-day <em>dry immersion</em> (<em>DI</em>, on-ground model of microgravity).</div></div><div><h3>Methods</h3><div>75 young male volunteers participated in the study. Blood pressure and ECG were continuously recorded, to obtain mean arterial pressure (MAP), heart rate (HR) and wavelet spectra of these parameters. Phases of the oscillations were calculated using Morse analytical wavelets. The synchronization between oscillations was estimated using phase synchronization index (PSI) calculated from Shannon entropy for phase difference distribution histogram.</div></div><div><h3>Results</h3><div>HUT increased the amplitude of HF MAP waves, but decreased the amplitude of HF waves of HR. The phase shift between HF MAP and HR waves decreased, but the degree of their synchronization increased, as reflected by an increase in the HF peak in PSI spectrum. Similar changes, except for an increase in PSI, were recorded upon exposure to LBNP and in the sit-to-stand test. After 7-day exposure to <em>DI</em> conditions, phase shift between HF MAP and HR oscillations decreased in supine position and then did not change during orthostasis.</div></div><div><h3>Conclusion</h3><div>The changes in body position, LBNP and <em>dry immersion</em> exposure, which are associated with a decrease in vagal activity, affect the phase relationship between respiratory MAP and HR waves.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"339 ","pages":"Article 104509"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401803","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 : 2026-01-01Epub Date: 2025-10-08DOI: 10.1016/j.resp.2025.104502
Bernard Korzeniewski
The hyperbolic-like decrease with time in power output during all-out exercise (AOE) correlates well with changes in “fatigue-related” metabolites: Pi, H2PO4- (Pi-) and H+. A simple mechanism of muscle fatigue during AOE, named “Pipeak-Pi-distance” mechanism, is proposed and incorporated into a dynamic computer model of the skeletal muscle bioenergetic system. It involves the dependence of the current power output (PO) on the difference between peak Pi (Pipeak), at which exercise is terminated because of fatigue in constant-power exercise (CPE), and current Pi. This mechanism can account for several dynamic properties of the skeletal muscle bioenergetic system during AOE, including PO decrease over time, (almost) identical V̇O2max in AOE and CPE, much faster on-kinetics of V̇O2 and metabolites than PO in AOE, much faster V̇O2 on-kinetics in AOE than CPE, much lower V̇O2 slow component (and higher primary phase II) at the same V̇O2max in AOE than CPE, different rates of approaching a steady-state by PO in different experiments, the V̇O2 decrease during AOE after reaching a maximum observed in some experiments and others. The mechanism is also able to explain mechanistically a broad spectrum of system behaviors, including the above-mentioned phenomena. The Pipeak-Pi-distance mechanism for AOE can be unified with the Pi-double-threshold mechanism proposed previously for CPE (and ramp-incremental exercise, RIE) into the “PiPipeak” mechanism of muscle fatigue. Generally, this unified mechanism, with Pi and Pipeak as central elements, allows to explain the similarities and differences in fatigue generation in various exercise types.
{"title":"Pi-based mechanism of muscle fatigue during all-out exercise in humans","authors":"Bernard Korzeniewski","doi":"10.1016/j.resp.2025.104502","DOIUrl":"10.1016/j.resp.2025.104502","url":null,"abstract":"<div><div>The hyperbolic-like decrease with time in power output during all-out exercise (AOE) correlates well with changes in “fatigue-related” metabolites: P<sub>i</sub>, H<sub>2</sub>PO<sub>4</sub><sup>-</sup> (P<sub>i</sub><sup>-</sup>) and H<sup>+</sup>. A simple mechanism of muscle fatigue during AOE, named “Pi<sub>peak</sub>-P<sub>i</sub>-distance” mechanism, is proposed and incorporated into a dynamic computer model of the skeletal muscle bioenergetic system. It involves the dependence of the current power output (PO) on the difference between peak P<sub>i</sub> (Pi<sub>peak</sub>), at which exercise is terminated because of fatigue in constant-power exercise (CPE), and current P<sub>i</sub>. This mechanism can account for several dynamic properties of the skeletal muscle bioenergetic system during AOE, including PO decrease over time, (almost) identical V̇O<sub>2max</sub> in AOE and CPE, much faster on-kinetics of V̇O<sub>2</sub> and metabolites than PO in AOE, much faster V̇O<sub>2</sub> on-kinetics in AOE than CPE, much lower V̇O<sub>2</sub> slow component (and higher primary phase II) at the same V̇O<sub>2max</sub> in AOE than CPE, different rates of approaching a steady-state by PO in different experiments, the V̇O<sub>2</sub> decrease during AOE after reaching a maximum observed in some experiments and others. The mechanism is also able to explain mechanistically a broad spectrum of system behaviors, including the above-mentioned phenomena. The Pi<sub>peak</sub>-P<sub>i</sub>-distance mechanism for AOE can be unified with the P<sub>i</sub>-double-threshold mechanism proposed previously for CPE (and ramp-incremental exercise, RIE) into the “PiPipeak” mechanism of muscle fatigue. Generally, this unified mechanism, with P<sub>i</sub> and Pi<sub>peak</sub> as central elements, allows to explain the similarities and differences in fatigue generation in various exercise types.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"339 ","pages":"Article 104502"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270033","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 : 2026-01-01Epub Date: 2025-10-13DOI: 10.1016/j.resp.2025.104505
Alexandros Sotiridis , Charalambos Dardamanis-Aidonas , Anastasios Makris , Ioannis Loukas , Nickos Geladas , Maria Koskolou
Tobacco smoking involves the inhalation of carbon monoxide (CO), a gas that binds to hemoglobin molecules to form carboxyhemoglobin (COHb), and thus acutely reduces arterial oxygen content. Whether regular tobacco smoking elicits a compensatory increase in hemoglobin mass (HbM) and concomitant gains in intravascular volumes of even relatively trained individuals was examined in the present study. Thirty young males were split in independent groups based on smoking status (CS; chronic smokers and NS; non-smokers) and aerobic fitness level (MF; more fit and LF; less fit) (CS-MF, CS-LF, NS-MF and NS-LF; n = 8 for all but the first group). CS had been smoking > 10 cigarettes·day−1 at least for the last three years. Assessed using an incremental running exercise test to exhaustion, the age-adjusted VO2peak was selected as the criterion for the inclusion in the MF and LF groups, respectively. The CO-rebreathing technique was applied to assess HbM and intravascular blood volumes. A two-way ANOVA was performed to detect differences in means of hematological and endurance performance parameters. VO2peak was found higher in MF groups (p < 0.001) but was similar between groups of similar fitness level (p = 0.57). Accordingly, peak aerobic speed was lower in CS (p < 0.001) and LF groups (p = 0.004). HbM (p = 0.013), total blood (p = 0.001) and red cell (p < 0.001) volumes were higher in CS groups. Despite the underlying expansion in HbM and total blood volume in smokers of varying fitness levels, endurance performance seems to be impaired. Future research could develop insight into the regulation of hematocrit in smokers.
{"title":"Tobacco smoking: A stimulus for blood volume expansion","authors":"Alexandros Sotiridis , Charalambos Dardamanis-Aidonas , Anastasios Makris , Ioannis Loukas , Nickos Geladas , Maria Koskolou","doi":"10.1016/j.resp.2025.104505","DOIUrl":"10.1016/j.resp.2025.104505","url":null,"abstract":"<div><div>Tobacco smoking involves the inhalation of carbon monoxide (CO), a gas that binds to hemoglobin molecules to form carboxyhemoglobin (COHb), and thus acutely reduces arterial oxygen content. Whether regular tobacco smoking elicits a compensatory increase in hemoglobin mass (HbM) and concomitant gains in intravascular volumes of even relatively trained individuals was examined in the present study. Thirty young males were split in independent groups based on smoking status (CS; chronic smokers and NS; non-smokers) and aerobic fitness level (MF; more fit and LF; less fit) (CS-MF, CS-LF, NS-MF and NS-LF; n = 8 for all but the first group). CS had been smoking > 10 cigarettes·day<sup>−1</sup> at least for the last three years. Assessed using an incremental running exercise test to exhaustion, the age-adjusted VO<sub>2peak</sub> was selected as the criterion for the inclusion in the MF and LF groups, respectively. The CO-rebreathing technique was applied to assess HbM and intravascular blood volumes. A two-way ANOVA was performed to detect differences in means of hematological and endurance performance parameters. VO<sub>2peak</sub> was found higher in MF groups (p < 0.001) but was similar between groups of similar fitness level (p = 0.57). Accordingly, peak aerobic speed was lower in CS (p < 0.001) and LF groups (p = 0.004). HbM (p = 0.013), total blood (p = 0.001) and red cell (p < 0.001) volumes were higher in CS groups. Despite the underlying expansion in HbM and total blood volume in smokers of varying fitness levels, endurance performance seems to be impaired. Future research could develop insight into the regulation of hematocrit in smokers.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"339 ","pages":"Article 104505"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302935","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}