Pub Date : 2024-11-21DOI: 10.1016/j.resp.2024.104366
Laszlo Markasz , Hamid Mobini-Far , Richard Sindelar
Collagen type VI (COL6) is an important component of the extracellular matrix (EM) and may have a major role in lung development and disease. Studies on COL6 expression during lung development are mainly based on animal models. The aim of the study was to define COL6 expression pattern in lung parenchyma in infants with different lung maturational stages.
COL6 expression in 115 lung samples from deceased newborn infants (21–41 weeks’ gestational age; 0–228 days’ postnatal age) was studied by immunohistochemistry combined with digital image analysis.
The distribution of COL6 expression was generally heterogeneous in the lung parenchyma of preterm and term infants. The size of the high-density and low-density areas appeared with logarithmic correlation and COL6 defined the basement membrane (BM) with a prominent expression around the air spaces in the canalicular stage during the first postnatal week. Infants at the alveolar stage showed linear correlation and a fine filamentous appearance during the first week of postnatal life, similarly to adults.
COL6 is condensed to areas corresponding to the BM during the first postnatal week of the canalicular stage of lung development. After the first postnatal week COL6 expression changes to a microfibrillar appearance in the ECM, similar to the pattern that characterizes the later alveolar stage and adults. The localization of COL6 during the canalicular and saccular stages might have a higher impact on lung development than the amount of COL6.
{"title":"Early and late postnatal lung distribution of collagen type VI in preterm and term infants","authors":"Laszlo Markasz , Hamid Mobini-Far , Richard Sindelar","doi":"10.1016/j.resp.2024.104366","DOIUrl":"10.1016/j.resp.2024.104366","url":null,"abstract":"<div><div>Collagen type VI (COL6) is an important component of the extracellular matrix (EM) and may have a major role in lung development and disease. Studies on COL6 expression during lung development are mainly based on animal models. The aim of the study was to define COL6 expression pattern in lung parenchyma in infants with different lung maturational stages.</div><div>COL6 expression in 115 lung samples from deceased newborn infants (21–41 weeks’ gestational age; 0–228 days’ postnatal age) was studied by immunohistochemistry combined with digital image analysis.</div><div>The distribution of COL6 expression was generally heterogeneous in the lung parenchyma of preterm and term infants. The size of the high-density and low-density areas appeared with logarithmic correlation and COL6 defined the basement membrane (BM) with a prominent expression around the air spaces in the canalicular stage during the first postnatal week. Infants at the alveolar stage showed linear correlation and a fine filamentous appearance during the first week of postnatal life, similarly to adults.</div><div>COL6 is condensed to areas corresponding to the BM during the first postnatal week of the canalicular stage of lung development. After the first postnatal week COL6 expression changes to a microfibrillar appearance in the ECM, similar to the pattern that characterizes the later alveolar stage and adults. The localization of COL6 during the canalicular and saccular stages might have a higher impact on lung development than the amount of COL6.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104366"},"PeriodicalIF":1.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692460","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 : 2024-11-19DOI: 10.1016/j.resp.2024.104372
Yan-Jhih Shen , Ping-Hsun Ou , Yan-Cheng Shen , Ching Jung Lai
Obstructive sleep apnea, characterized by airway exposure to intermittent hypoxia (IH), is associated with laryngeal airway hyperreactivity (LAH) and laryngeal inflammation. The sensitization of capsaicin-sensitive superior laryngeal afferents (CSSLAs) by inflammatory mediators has been implicated in the pathogenesis of LAH. Nerve growth factor (NGF) is an inflammatory mediator that acts on tropomyosin receptor kinase A (TrkA) and the p75 neurotrophin receptor (p75NTR) to induce lower airway hyperresponsiveness. In this study, we investigated the role of NGF in the development of LAH and laryngeal inflammation induced by IH in anesthetized rats. Compared with rats subjected to room air exposure for 14 days, rats with 14-day IH exposure exhibited augmented reflex apneic responses to the laryngeal provocation of three different chemical stimulants of CSSLAs, resulting in LAH. The apneic responses to laryngeal stimulants were abolished by either perineural capsaicin treatment (a procedure that selectively blocks the conduction of CSSLAs) or denervation of the superior laryngeal nerves, suggesting that the reflex was mediated through CSSLAs. The IH-induced LAH was significantly attenuated by daily treatment with anti-NGF antibody, but was unaffected by daily treatment with immunoglobulin G. IH exposure also induced laryngeal inflammation as evidenced by increases in laryngeal levels of NGF, lipid peroxidation, tumor necrosis factor-α, interleukin-1β, TrkA, and p75NTR. Similarly, IH-induced laryngeal inflammation was significantly reduced by daily treatment with anti-NGF antibody. We concluded that NGF contributes to the development of LAH and laryngeal inflammation induced by IH in rats. The LAH may result from the sensitizing effect of NGF on CSSLAs.
阻塞性睡眠呼吸暂停的特点是气道暴露于间歇性缺氧（IH），与喉气道高反应性（LAH）和喉部炎症有关。炎症介质对辣椒素敏感的喉上传入（CSSLA）的致敏作用与 LAH 的发病机制有关。神经生长因子（NGF）是一种炎症介质，可作用于肌球蛋白受体激酶 A（TrkA）和 p75 神经营养素受体（p75NTR），诱导下呼吸道高反应性。在本研究中，我们研究了 NGF 在麻醉大鼠 IH 诱导的 LAH 和喉部炎症发展中的作用。与暴露于室内空气中 14 天的大鼠相比，暴露于 IH 14 天的大鼠对三种不同的 CSSLAs 化学刺激物的喉刺激表现出更强的反射性呼吸暂停反应，从而导致 LAH。对喉部刺激物的呼吸暂停反应可通过硬膜外辣椒素治疗（一种选择性阻断 CSSLAs 传导的方法）或去神经支配喉上神经而消失，这表明反射是通过 CSSLAs 介导的。IH诱导的LAH在每天使用抗NGF抗体治疗后明显减弱，但在每天使用免疫球蛋白G治疗后则不受影响。IH暴露还诱导喉部炎症，表现为喉部NGF、脂质过氧化物、肿瘤坏死因子-α、白细胞介素-1β、TrkA和p75NTR水平的升高。同样，每天使用抗 NGF 抗体治疗可显著减轻 IH 引起的喉部炎症。我们的结论是，NGF有助于IH诱导的大鼠LAH和喉部炎症的发展。LAH可能是NGF对CSSLAs的增敏作用所致。
{"title":"Role of endogenous nerve growth factor in laryngeal airway hyperreactivity and laryngeal inflammation induced by intermittent hypoxia in rats","authors":"Yan-Jhih Shen , Ping-Hsun Ou , Yan-Cheng Shen , Ching Jung Lai","doi":"10.1016/j.resp.2024.104372","DOIUrl":"10.1016/j.resp.2024.104372","url":null,"abstract":"<div><div>Obstructive sleep apnea, characterized by airway exposure to intermittent hypoxia (IH), is associated with laryngeal airway hyperreactivity (LAH) and laryngeal inflammation. The sensitization of capsaicin-sensitive superior laryngeal afferents (CSSLAs) by inflammatory mediators has been implicated in the pathogenesis of LAH. Nerve growth factor (NGF) is an inflammatory mediator that acts on tropomyosin receptor kinase A (TrkA) and the p75 neurotrophin receptor (p75<sup>NTR</sup>) to induce lower airway hyperresponsiveness. In this study, we investigated the role of NGF in the development of LAH and laryngeal inflammation induced by IH in anesthetized rats. Compared with rats subjected to room air exposure for 14 days, rats with 14-day IH exposure exhibited augmented reflex apneic responses to the laryngeal provocation of three different chemical stimulants of CSSLAs, resulting in LAH. The apneic responses to laryngeal stimulants were abolished by either perineural capsaicin treatment (a procedure that selectively blocks the conduction of CSSLAs) or denervation of the superior laryngeal nerves, suggesting that the reflex was mediated through CSSLAs. The IH-induced LAH was significantly attenuated by daily treatment with anti-NGF antibody, but was unaffected by daily treatment with immunoglobulin G. IH exposure also induced laryngeal inflammation as evidenced by increases in laryngeal levels of NGF, lipid peroxidation, tumor necrosis factor-α, interleukin-1β, TrkA, and p75<sup>NTR</sup>. Similarly, IH-induced laryngeal inflammation was significantly reduced by daily treatment with anti-NGF antibody. We concluded that NGF contributes to the development of LAH and laryngeal inflammation induced by IH in rats. The LAH may result from the sensitizing effect of NGF on CSSLAs.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104372"},"PeriodicalIF":1.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681521","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 : 2024-11-14DOI: 10.1016/j.resp.2024.104371
J.C. Brown, R. Boat, N.C. Williams, M.A. Johnson, G.R. Sharpe
Introduction
Dyspnoea perception is influenced by a complex interplay of physiological, psychological, and environmental factors. Recently, we showed that males with high trait self-control experience less dyspnoea and persist for longer in a carbon dioxide (CO2) rebreathing challenge than males with low trait self-control. As self-control can also vary within individuals (state self-control), the primary aim of the present study was to investigate whether prior self-control exertion influenced perceptions of dyspnoea and tolerance of a CO2 rebreathing challenge in healthy young males. We also used functional near-infrared spectroscopy (fNIRS) to assess haemodynamic activity of the pre-frontal cortex (PFC) which is a region of interest (ROI) in dyspnoea research, and the primary brain region associated with exertion of self-control.
Methods
In a within-subjects design, fifteen healthy young males completed an easy (congruent) Stroop task (control condition) and a difficult (incongruent) Stroop task (prior self-control exertion, experimental condition) followed by a CO2 rebreathing challenge until the limit of tolerance. Changes in oxyhaemoglobin (ΔO2Hb) and deoxyhaemoglobin (ΔHHb) were assessed continuously in the Stroop task and CO2 rebreathing challenge. During the CO2 rebreathing challenge, dyspnoea intensity and unpleasantness were rated every 30 s.
Results
Prior self-control exertion did not affect perceptions of dyspnoea or tolerance time in the CO2 rebreathing challenge (all P > 0.05). ΔO2Hb from baseline was higher in the left (+38 %) and right (+44 %) pre-frontal cortices during the difficult Stroop task than the easy Stroop task (both P < 0.05). During the subsequent CO2 rebreathing challenge, ΔO2Hb was attenuated following prior self-control exertion in the left PFC.
Conclusions
Although prior self-control exertion decreased pre-frontal cortex oxygenation during a subsequent CO2 rebreathing challenge, there was no change in tolerance time or perceptions of dyspnoea.
{"title":"Prior self-control exertion decreases pre-frontal cortex oxygenation during a CO2 rebreathing challenge but does not affect perceptions of dyspnoea or tolerance time","authors":"J.C. Brown, R. Boat, N.C. Williams, M.A. Johnson, G.R. Sharpe","doi":"10.1016/j.resp.2024.104371","DOIUrl":"10.1016/j.resp.2024.104371","url":null,"abstract":"<div><h3>Introduction</h3><div>Dyspnoea perception is influenced by a complex interplay of physiological, psychological, and environmental factors. Recently, we showed that males with high trait self-control experience less dyspnoea and persist for longer in a carbon dioxide (CO<sub>2</sub>) rebreathing challenge than males with low trait self-control. As self-control can also vary within individuals (state self-control), the primary aim of the present study was to investigate whether prior self-control exertion influenced perceptions of dyspnoea and tolerance of a CO<sub>2</sub> rebreathing challenge in healthy young males. We also used functional near-infrared spectroscopy (fNIRS) to assess haemodynamic activity of the pre-frontal cortex (PFC) which is a region of interest (ROI) in dyspnoea research, and the primary brain region associated with exertion of self-control.</div></div><div><h3>Methods</h3><div>In a within-subjects design, fifteen healthy young males completed an easy (congruent) Stroop task (control condition) and a difficult (incongruent) Stroop task (prior self-control exertion, experimental condition) followed by a CO<sub>2</sub> rebreathing challenge until the limit of tolerance. Changes in oxyhaemoglobin (ΔO<sub>2</sub>Hb) and deoxyhaemoglobin (ΔHHb) were assessed continuously in the Stroop task and CO<sub>2</sub> rebreathing challenge. During the CO<sub>2</sub> rebreathing challenge, dyspnoea intensity and unpleasantness were rated every 30 s.</div></div><div><h3>Results</h3><div>Prior self-control exertion did not affect perceptions of dyspnoea or tolerance time in the CO<sub>2</sub> rebreathing challenge (all <em>P</em> > 0.05). ΔO<sub>2</sub>Hb from baseline was higher in the left (+38 %) and right (+44 %) pre-frontal cortices during the difficult Stroop task than the easy Stroop task (both <em>P</em> < 0.05). During the subsequent CO<sub>2</sub> rebreathing challenge, ΔO<sub>2</sub>Hb was attenuated following prior self-control exertion in the left PFC.</div></div><div><h3>Conclusions</h3><div>Although prior self-control exertion decreased pre-frontal cortex oxygenation during a subsequent CO<sub>2</sub> rebreathing challenge, there was no change in tolerance time or perceptions of dyspnoea.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104371"},"PeriodicalIF":1.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644674","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 : 2024-11-13DOI: 10.1016/j.resp.2024.104370
Athena Rivera, Sarah N. Framnes-DeBoer, Deanna M. Arble
Obesity increases the risk of respiratory diseases that reduce respiratory chemosensitivity, such as Obesity Hypoventilation Syndrome and sleep apnea. Recent evidence suggests that obesity-related changes in the brain, including alterations in melanocortin signaling via the melanocortin-4 receptor (MC4R), may underly altered chemosensitivity. Setmelanotide, an MC4R agonist, causes weight loss in both humans and animal models. However, it is unknown the extent to which setmelanotide affects respiratory chemosensitivity independent of body weight loss. The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR). We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR. In a separate group of animals, we find that we can emulate setmelanotide’s effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide. These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide. We conclude that acute treatment with setmelanotide is as effective as weight loss at improving respiratory hypercapnic chemosensitivity.
{"title":"The MC4R agonist, setmelanotide, is associated with an improvement in hypercapnic chemosensitivity and weight loss in male mice","authors":"Athena Rivera, Sarah N. Framnes-DeBoer, Deanna M. Arble","doi":"10.1016/j.resp.2024.104370","DOIUrl":"10.1016/j.resp.2024.104370","url":null,"abstract":"<div><div>Obesity increases the risk of respiratory diseases that reduce respiratory chemosensitivity, such as Obesity Hypoventilation Syndrome and sleep apnea. Recent evidence suggests that obesity-related changes in the brain, including alterations in melanocortin signaling via the melanocortin-4 receptor (MC4R), may underly altered chemosensitivity. Setmelanotide, an MC4R agonist, causes weight loss in both humans and animal models. However, it is unknown the extent to which setmelanotide affects respiratory chemosensitivity independent of body weight loss. The present study uses diet-induced obese, male C57bl/6 J mice to determine the extent to which acute setmelanotide treatment affects the hypercapnic ventilatory response (HCVR). We find that ten days of daily setmelanotide treatment at 1 mg/kg, but not 0.2 mg/kg, is sufficient to cause weight loss and increase HCVR. In a separate group of animals, we find that we can emulate setmelanotide’s effect on weight loss by restricting daily calories to match the hypophagia triggered by setmelanotide. These pair-fed animals exhibit improvements in HCVR similar to those who receive setmelanotide. We conclude that acute treatment with setmelanotide is as effective as weight loss at improving respiratory hypercapnic chemosensitivity.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104370"},"PeriodicalIF":1.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627115","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 : 2024-11-12DOI: 10.1016/j.resp.2024.104369
Aaron A. Jones , Jose R. Oberto , Marissa C. Ciesla , Yasin B. Seven , Latoya L. Allen , Elisa J. Gonzalez-Rothi, Gordon S. Mitchell
Acute intermittent hypoxia (AIH) elicits spinal neuroplasticity and is emerging as a potential therapeutic modality to improve respiratory and non-respiratory motor function in people with chronic incomplete spinal cord injury (SCI). Brain-derived neurotrophic factor (BDNF) is necessary and sufficient for moderate AIH-induced phrenic long-term facilitation, a well-studied form of respiratory motor plasticity. Repetitive daily AIH (dAIH) enhances BDNF expression within the phrenic motor neurons of normal rats, but its effects on BDNF after chronic cervical spinal cord injury (cSCI) are unknown. In contrast to AIH, chronic intermittent hypoxia (CIH), simulating that experienced during sleep apnea, elicits neuropathology and undermines plasticity. Here, we tested the hypothesis that daily AIH vs CIH differentially regulate phrenic motor neuron BDNF expression in spinally intact and injured rats. Rats with and without C2 hemisection (C2Hx; 8 weeks post-injury) were exposed to 28 days of: 1) sham normoxia (Nx, 21 % O2); 2) daily AIH (dAIH: 10, 5 min episodes of 10.5 % O2 per day; 5 min normoxic intervals); 3) mild CIH (CIH5/5: 5 min of 10.5 % O2, 5 min intervals, 8 hrs/day); or 4) moderate CIH (CIH2/2: 2 min of 10.5 % O2, 2 min intervals, 8 hrs/day). After 28 days of daily exposure (i.e., 12 weeks post-injury), BDNF immunoreactivity was assessed within phrenic motor neurons identified via retrograde cholera toxin B fragment labeling. In intact rats, daily AIH increased BDNF protein levels in phrenic motor neurons (∼31 %) but not in rats with C2Hx. CIH had no effects on phrenic motor neuron BDNF levels in intact rats, although there was a trend towards increased phrenic motor neuron BDNF after C2Hx, suggesting the need for further study. Since dAIH effects on phrenic motor neuron BDNF are not observed in rats with chronic cervical SCI, the potential of dAIH to enhance BDNF-dependent phrenic motor plasticity may be suppressed by conditions prevailing with chronic cSCI.
{"title":"Enhanced phrenic motor neuron BDNF expression elicited by daily acute intermittent hypoxia is undermined in rats with chronic cervical spinal cord injury","authors":"Aaron A. Jones , Jose R. Oberto , Marissa C. Ciesla , Yasin B. Seven , Latoya L. Allen , Elisa J. Gonzalez-Rothi, Gordon S. Mitchell","doi":"10.1016/j.resp.2024.104369","DOIUrl":"10.1016/j.resp.2024.104369","url":null,"abstract":"<div><div>Acute intermittent hypoxia (AIH) elicits spinal neuroplasticity and is emerging as a potential therapeutic modality to improve respiratory and non-respiratory motor function in people with chronic incomplete spinal cord injury (SCI). Brain-derived neurotrophic factor (BDNF) is necessary and sufficient for moderate AIH-induced phrenic long-term facilitation, a well-studied form of respiratory motor plasticity. Repetitive daily AIH (dAIH) enhances BDNF expression within the phrenic motor neurons of normal rats, but its effects on BDNF after chronic cervical spinal cord injury (cSCI) are unknown. In contrast to AIH, chronic intermittent hypoxia (CIH), simulating that experienced during sleep apnea, elicits neuropathology and undermines plasticity. Here, we tested the hypothesis that daily AIH <em>vs</em> CIH differentially regulate phrenic motor neuron BDNF expression in spinally intact and injured rats. Rats with and without C2 hemisection (C2Hx; 8 weeks post-injury) were exposed to 28 days of: 1) sham normoxia (Nx, 21 % O<sub>2</sub>); 2) daily AIH (dAIH: 10, 5 min episodes of 10.5 % O<sub>2</sub> per day; 5 min normoxic intervals); 3) mild CIH (CIH5/5: 5 min of 10.5 % O<sub>2</sub>, 5 min intervals, 8 hrs/day); or 4) moderate CIH (CIH2/2: 2 min of 10.5 % O<sub>2</sub>, 2 min intervals, 8 hrs/day). After 28 days of daily exposure (<em>i.e</em>., 12 weeks post-injury), BDNF immunoreactivity was assessed within phrenic motor neurons identified <em>via</em> retrograde cholera toxin B fragment labeling. In intact rats, daily AIH increased BDNF protein levels in phrenic motor neurons (∼31 %) but not in rats with C2Hx. CIH had no effects on phrenic motor neuron BDNF levels in intact rats, although there was a trend towards increased phrenic motor neuron BDNF after C2Hx, suggesting the need for further study. Since dAIH effects on phrenic motor neuron BDNF are not observed in rats with chronic cervical SCI, the potential of dAIH to enhance BDNF-dependent phrenic motor plasticity may be suppressed by conditions prevailing with chronic cSCI.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104369"},"PeriodicalIF":1.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627114","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 : 2024-11-12DOI: 10.1016/j.resp.2024.104368
Yilun Liu , Jiana Li , Rongchang Chen , Fei Shi , Yi Xiong
Asthma is a common chronic inflammatory airway disease, imposing a substantial health and economic burden on society and individuals. Current treatments primarily focus on symptom relief and lung function improvement, often failing to address the underlying pathology. Thus, exploring new therapeutic approaches is crucial. Airway smooth muscle cells (ASMCs) play a key role in regulating airway tone and airflow, while abnormal ASMCs proliferation contributes to airway remodeling in asthma. Airway epithelial cells (AECs), serving as the first barrier against pathogens and allergens, also have critical immune functions.
This study focuses on the interaction between AECs and ASMCs, as AECs are more accessible for drug delivery due to their location at the airway surface. Investigating this relationship could facilitate novel interventions targeting AECs to inhibit pathological ASMCs activity. In our experiment, we isolated ASMCs and AECs from healthy mice and found that AECs significantly promoted ASMCs proliferation in co-culture. RNA sequencing revealed that this process might be linked to the activation of the canonical Wnt signaling pathway in ASMCs. By using Wnt pathway inhibitors (endo-IWR1) and siRNA to disrupt Wnt receptors, we reversed this phenotype. This finding suggests that AECs may promote ASMCs proliferation by activating the Wnt pathway in ASMCs. The Wnt/β-catenin pathway appears to play an important role in ASMCs proliferation, indicating that future pathological studies should consider the potential involvement of the Wnt pathway in airway remodeling.
{"title":"Airway epithelial cells promote in vitro airway smooth muscle cell proliferation by activating the Wnt/β-catenin pathway","authors":"Yilun Liu , Jiana Li , Rongchang Chen , Fei Shi , Yi Xiong","doi":"10.1016/j.resp.2024.104368","DOIUrl":"10.1016/j.resp.2024.104368","url":null,"abstract":"<div><div>Asthma is a common chronic inflammatory airway disease, imposing a substantial health and economic burden on society and individuals. Current treatments primarily focus on symptom relief and lung function improvement, often failing to address the underlying pathology. Thus, exploring new therapeutic approaches is crucial. Airway smooth muscle cells (ASMCs) play a key role in regulating airway tone and airflow, while abnormal ASMCs proliferation contributes to airway remodeling in asthma. Airway epithelial cells (AECs), serving as the first barrier against pathogens and allergens, also have critical immune functions.</div><div>This study focuses on the interaction between AECs and ASMCs, as AECs are more accessible for drug delivery due to their location at the airway surface. Investigating this relationship could facilitate novel interventions targeting AECs to inhibit pathological ASMCs activity. In our experiment, we isolated ASMCs and AECs from healthy mice and found that AECs significantly promoted ASMCs proliferation in co-culture. RNA sequencing revealed that this process might be linked to the activation of the canonical Wnt signaling pathway in ASMCs. By using Wnt pathway inhibitors (endo-IWR1) and siRNA to disrupt Wnt receptors, we reversed this phenotype. This finding suggests that AECs may promote ASMCs proliferation by activating the Wnt pathway in ASMCs. The Wnt/β-catenin pathway appears to play an important role in ASMCs proliferation, indicating that future pathological studies should consider the potential involvement of the Wnt pathway in airway remodeling.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104368"},"PeriodicalIF":1.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627112","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 : 2024-11-10DOI: 10.1016/j.resp.2024.104367
Marcel Veternik , Michal Simera , Lukas Martvon , Lucia Cibulkova , Zuzana Kotmanova , Ivan Poliacek
The relationship between the level (rate) of stimulus and the characteristics of the cough response was studied on 15 spontaneously breathing anesthetized cats. Three modes of stimulation were used to elicit cough. ‘High’ vs. ‘low’ level of stimulation was accomplished: 1st mode by 1 vs. 4 penetrations of the soft catheter through the trachea (approximately 10 cm), 2nd mode by 2 penetrations with the soft catheter equipped with 4 fine cross nylon fibers vs. 4 penetrations by the stimulator with 8 fibers, and 3rd mode by a similar stimulator with 4 cross fibers probing 4 cm of the trachea either right below the larynx or deeper under the upper part of the sternum (data were pooled) vs. stimulating both areas at the same time. ‘High’ stimulation rate in each stimulation mode resulted in a higher number of coughs, increased cough efforts, and shortened several temporal cough features. Mechanical stimulation resulting in higher cough afferent drive induces more vigorous coughing with shorter temporal cough characteristics. Modulation of cough afferent input affects both spatial and temporal components of the cough motor pattern, representing a crucial point in cough management.
{"title":"Effect of various modes of tracheal mechanical stimulation on the cough motor pattern","authors":"Marcel Veternik , Michal Simera , Lukas Martvon , Lucia Cibulkova , Zuzana Kotmanova , Ivan Poliacek","doi":"10.1016/j.resp.2024.104367","DOIUrl":"10.1016/j.resp.2024.104367","url":null,"abstract":"<div><div>The relationship between the level (rate) of stimulus and the characteristics of the cough response was studied on 15 spontaneously breathing anesthetized cats. Three modes of stimulation were used to elicit cough. ‘High’ vs. ‘low’ level of stimulation was accomplished: 1st mode by 1 vs. 4 penetrations of the soft catheter through the trachea (approximately 10 cm), 2nd mode by 2 penetrations with the soft catheter equipped with 4 fine cross nylon fibers vs. 4 penetrations by the stimulator with 8 fibers, and 3rd mode by a similar stimulator with 4 cross fibers probing 4 cm of the trachea either right below the larynx or deeper under the upper part of the sternum (data were pooled) vs. stimulating both areas at the same time. ‘High’ stimulation rate in each stimulation mode resulted in a higher number of coughs, increased cough efforts, and shortened several temporal cough features. Mechanical stimulation resulting in higher cough afferent drive induces more vigorous coughing with shorter temporal cough characteristics. Modulation of cough afferent input affects both spatial and temporal components of the cough motor pattern, representing a crucial point in cough management.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104367"},"PeriodicalIF":1.9,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627113","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 : 2024-11-06DOI: 10.1016/j.resp.2024.104363
Diana Andrea Arias Fernández , Héctor Alfonso Romero Diaz , Alan David Figueroa Garnica , Pablo Iturri-Soliz , Christian Arias-Reyes , Edith Mariane Schneider Gasser , Jorge Soliz
In addition to its hematopoietic function, erythropoietin (EPO) has demonstrated neuroprotective properties in preclinical studies, particularly in cases of reduced oxygenation or ischemia in the neonatal brain. While these findings have sparked optimism for its potential clinical application, the efficacy of EPO remains contentious in translational assays. Notably, while repeated administration of low doses of EPO has correlated with a decrease in adverse outcomes, the use of high EPO doses has shown either negligible or potentially detrimental effects on the incidence of brain injury. In this pilot study, we explored the effects of low and sustained doses of EPO (400 IU/kg) on the incidence of intraventricular hemorrhage (IVH) in premature infants. EPO was administered intravenously three times a week until the infants reached 32 weeks corrected gestational age. Our results indicate a significant decrease in the incidence of IVH with EPO treatment. Although, this study does not provide conclusive evidence on EPO's ability to reverse established IVH, these results strongly support the need for larger-scale clinical trials to further assess EPO's therapeutic potential.
{"title":"Low and sustained doses of erythropoietin prevent preterm infants from intraventricular hemorrhage","authors":"Diana Andrea Arias Fernández , Héctor Alfonso Romero Diaz , Alan David Figueroa Garnica , Pablo Iturri-Soliz , Christian Arias-Reyes , Edith Mariane Schneider Gasser , Jorge Soliz","doi":"10.1016/j.resp.2024.104363","DOIUrl":"10.1016/j.resp.2024.104363","url":null,"abstract":"<div><div>In addition to its hematopoietic function, erythropoietin (EPO) has demonstrated neuroprotective properties in preclinical studies, particularly in cases of reduced oxygenation or ischemia in the neonatal brain. While these findings have sparked optimism for its potential clinical application, the efficacy of EPO remains contentious in translational assays. Notably, while repeated administration of low doses of EPO has correlated with a decrease in adverse outcomes, the use of high EPO doses has shown either negligible or potentially detrimental effects on the incidence of brain injury. In this pilot study, we explored the effects of low and sustained doses of EPO (400 IU/kg) on the incidence of intraventricular hemorrhage (IVH) in premature infants. EPO was administered intravenously three times a week until the infants reached 32 weeks corrected gestational age. Our results indicate a significant decrease in the incidence of IVH with EPO treatment. Although, this study does not provide conclusive evidence on EPO's ability to reverse established IVH, these results strongly support the need for larger-scale clinical trials to further assess EPO's therapeutic potential.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104363"},"PeriodicalIF":1.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606152","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 : 2024-11-01DOI: 10.1016/j.resp.2024.104365
Fang Liu , Alice Y.M. Jones , Raymond C.C. Tsang , Timothy T.T. Yam , William W.N. Tsang
Background
Inspiratory muscle training (IMT) is often employed to enhance improvement in inspiratory muscle strength. However, the relationship between inspiratory muscle recruitment patterns and increasing inspiratory load remains unclear. Furthermore, the effect of breathing instructions on diaphragm activity at various inspiratory loads is unknown.
Objective
To investigate the recruitment activity of the diaphragm and sternocleidomastoid (SCM) muscle under increased inspiratory pressure loading, with and without diaphragmatic breathing instructions, in healthy young adults.
Methods
Participants were invited to breathe, in random order, 6 sets of 10 breaths at inspiratory loads of 30 % to 80 % maximal inspiratory pressure (MIP), in 10 % increments. The measurement process was repeated with a specific focus of diaphragmatic descent during inspiration. During each targeted breath, recordings of surface electromyography of the right SCM muscle and thickness of the right hemi-diaphragm measured by ultrasonography were undertaken concurrently.
Results
Sixty-two adults (31 males, age: 23±3 years) participated in the study. Irrespective of breathing instructions, computed diaphragm thickening fraction (DTf) increased with increasing inspiratory load but peaked at 50 % MIP and declined with increasing load to 80 % MIP. SCM recruitment increased with increasing inspiratory load to 80 % MIP. Forced inspiration with diaphragmatic breathing was associated with a higher DTf and lower SCM muscle activity. The above pattern was similar for both male and female participants. Female participants produced higher SCM activity compared with males but only at inspiration loads below 50 % MIP.
Conclusions
In a cohort of young healthy adults, magnitude of diaphragmatic effort was greatest at 50 % MIP but declined with increasing inspiratory load to 80 % MIP. Forced inspiration combined with focused diaphragmatic breathing accentuated diaphragm contraction and reduced SCM muscle contribution. Our findings show that diaphragmatic muscle recruitment is non-linear and that the generic clinical prescription of an IMT program may need to be reconfigured.
{"title":"Recruitment of the diaphragm and sternocleidomastoid muscle during increasing inspiratory pressure loads in healthy young adults","authors":"Fang Liu , Alice Y.M. Jones , Raymond C.C. Tsang , Timothy T.T. Yam , William W.N. Tsang","doi":"10.1016/j.resp.2024.104365","DOIUrl":"10.1016/j.resp.2024.104365","url":null,"abstract":"<div><h3>Background</h3><div>Inspiratory muscle training (IMT) is often employed to enhance improvement in inspiratory muscle strength. However, the relationship between inspiratory muscle recruitment patterns and increasing inspiratory load remains unclear. Furthermore, the effect of breathing instructions on diaphragm activity at various inspiratory loads is unknown.</div></div><div><h3>Objective</h3><div>To investigate the recruitment activity of the diaphragm and sternocleidomastoid (SCM) muscle under increased inspiratory pressure loading, with and without diaphragmatic breathing instructions, in healthy young adults.</div></div><div><h3>Methods</h3><div>Participants were invited to breathe, in random order, 6 sets of 10 breaths at inspiratory loads of 30 % to 80 % maximal inspiratory pressure (MIP), in 10 % increments. The measurement process was repeated with a specific focus of diaphragmatic descent during inspiration. During each targeted breath, recordings of surface electromyography of the right SCM muscle and thickness of the right hemi-diaphragm measured by ultrasonography were undertaken concurrently.</div></div><div><h3>Results</h3><div>Sixty-two adults (31 males, age: 23±3 years) participated in the study. Irrespective of breathing instructions, computed diaphragm thickening fraction (DTf) increased with increasing inspiratory load but peaked at 50 % MIP and declined with increasing load to 80 % MIP. SCM recruitment increased with increasing inspiratory load to 80 % MIP. Forced inspiration with diaphragmatic breathing was associated with a higher DTf and lower SCM muscle activity. The above pattern was similar for both male and female participants. Female participants produced higher SCM activity compared with males but only at inspiration loads below 50 % MIP.</div></div><div><h3>Conclusions</h3><div>In a cohort of young healthy adults, magnitude of diaphragmatic effort was greatest at 50 % MIP but declined with increasing inspiratory load to 80 % MIP. Forced inspiration combined with focused diaphragmatic breathing accentuated diaphragm contraction and reduced SCM muscle contribution. Our findings show that diaphragmatic muscle recruitment is non-linear and that the generic clinical prescription of an IMT program may need to be reconfigured.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104365"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569288","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 : 2024-10-29DOI: 10.1016/j.resp.2024.104364
Sabino Guglielmini , Elena Wiggli , Felix Scholkmann , Martin Wolf
Significance
Cerebral blood flow is influenced by respiration, primarily through changes in the CO2 concentration of arterial blood.
Aim
The objective of this study was to investigate the effect of changes in arterial CO2 concentration induced by respiratory changes on oxygenation and hemodynamics in the cerebral and extracerebral tissue layers of the forehead.
Approach
We used systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) to assess changes in forehead hemodynamics and oxygenation as well as systemic physiology in 20 healthy subjects. All participants performed two respiratory tasks (breath-holding and hyperventilation).
Results
In our SPA-fNIRS study we found that changes in breathing affected hemodynamics and oxygenation in both the extracerebral and cerebral tissue layers of the forehead in characteristic ways, depending on the two respiratory tasks.
Conclusion
The results show that extracerebrovascular reactivity (ECVR) exists in parallel with the well-known cerebrovascular reactivity (CVR). CVR and ECVR must be considered when performing fNIRS neuroimaging studies involving changes in respiration.
{"title":"Hemodynamics and vascular oxygenation measured at the forehead during changes in respiration: A SPA-fNIRS study","authors":"Sabino Guglielmini , Elena Wiggli , Felix Scholkmann , Martin Wolf","doi":"10.1016/j.resp.2024.104364","DOIUrl":"10.1016/j.resp.2024.104364","url":null,"abstract":"<div><h3>Significance</h3><div>Cerebral blood flow is influenced by respiration, primarily through changes in the CO<sub>2</sub> concentration of arterial blood.</div></div><div><h3>Aim</h3><div>The objective of this study was to investigate the effect of changes in arterial CO<sub>2</sub> concentration induced by respiratory changes on oxygenation and hemodynamics in the cerebral and extracerebral tissue layers of the forehead.</div></div><div><h3>Approach</h3><div>We used systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) to assess changes in forehead hemodynamics and oxygenation as well as systemic physiology in 20 healthy subjects. All participants performed two respiratory tasks (breath-holding and hyperventilation).</div></div><div><h3>Results</h3><div>In our SPA-fNIRS study we found that changes in breathing affected hemodynamics and oxygenation in both the extracerebral and cerebral tissue layers of the forehead in characteristic ways, depending on the two respiratory tasks.</div></div><div><h3>Conclusion</h3><div>The results show that extracerebrovascular reactivity (ECVR) exists in parallel with the well-known cerebrovascular reactivity (CVR). CVR and ECVR must be considered when performing fNIRS neuroimaging studies involving changes in respiration.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104364"},"PeriodicalIF":1.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558619","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}
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