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Introduction: Respiratory dysfunction is a notable complication in stroke patients, in which the diaphragm, as the primary respiratory muscle, directly influences lung function. Repetitive peripheral magnetic stimulation (rPMS) is a new, non-invasive approach that is used to treat brain and nerve problems. Few studies have examined the effect of magnetic stimulation on the phrenic nerve, breathing and diaphragm in stroke patients. This study aims to assess the effect of magnetic phrenic nerve stimulation on respiratory muscle function and lung function in adults with stroke. The results of this study may provide a promising approach to managing respiratory dysfunction in stroke patients., Methods and Analysis: This randomised controlled trial is designed to compare the effectiveness of bilateral magnetic phrenic nerve stimulation (rPMS) and conventional rehabilitation training in enhancing respiratory muscle strength, lung function indicators, diaphragmatic excursion and diaphragm thickness in patients with respiratory muscle weakness. Thirty patients admitted to the First Hospital of Fujian Medical University will be included in this study. Participants in the intervention group will undergo daily bilateral magnetic phrenic nerve stimulation for 2 weeks. Stimulation will be administered at a frequency of 25 Hz, with a pulse duration of 1.1 s and an inter-pulse interval of 5.9 s, for 5 days each week. Primary outcome measures will be assessed at baseline and after 2 weeks (end of the intervention) to evaluate the efficacy of rPMS compared with conventional rehabilitation techniques., Ethics and Dissemination: Before commencing the study, all participants will receive a comprehensive explanation of the study procedures, including the assessments. They will also be provided informed consent forms for review, completion and signing. This study was approved by the Ethics Committee for Research at the First Affiliated Hospital of Fujian Medical University (No.: MRCTA, ECFAH of FMU [2021]641, dated 10 November 2023) (Appendix Ⅰ & Ⅱ). The trial protocol will strictly adhere to the Uniform Standards for Reporting of Trials (CONSORT) statement. The trial has been registered with the Chinese Clinical Trial Registry.Dissemination of individual findings for each participant will be available at the end of the study. The findings will be disseminated to different interest groups, participants or other patients with respiratory dysfunction through journal papers and/or conference presentations. The results of the primary trial will be submitted for publication in a peer-reviewed journal., Registration: ChiCTR2300075669, registered on 12 September 2023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infantile botulism is a potentially life-threatening neuromuscular disorder. It presents with descending paralysis that can involve the diaphragm and cause respiratory failure. Neurally adjusted ventilatory assist (NAVA) provides synchronized bilevel positive pressure by using electrical diaphragmatic (Edi) signals. Diaphragmatic paresis is thought to be a contraindication for using NAVA. However, the use of a NAVA catheter allows continuous assessment of diaphragm activity in infantile botulism. We discuss a case of infantile botulism in an infant from central Pennsylvania who presented with poor oral feeding, hypothermia, and lethargy and progressed to develop apnea and acute respiratory failure. The infant was intubated and mechanically ventilated. A diagnosis of infantile botulism was confirmed through the detection of botulinum toxin in the infant's stool, and the infant was treated with botulism immune globulin neutralizing antibodies. During his recovery phase, a NAVA catheter was placed, which allowed monitoring of Edi signals to gauge the return of diaphragm activity and to assist with the assessment of extubation readiness. We describe the trends in this infant's Edi signals following administration of globulin neutralizing antibodies and the successful transition to invasive, and subsequently, noninvasive NAVA. Our report demonstrates the clinical utility of monitoring diaphragmatic activity using a NAVA catheter and that NAVA provided adequate respiratory support to an infant during the recovery phase of infantile botulism., (Copyright © 2024 by the American Academy of Pediatrics.)

Patients with myotonia congenita suffer from slowed muscle relaxation caused by hyperexcitability. The diaphragm is only mildly affected in myotonia congenita; discovery of the mechanism underlying its resistance to myotonia could identify novel therapeutic targets. Intracellular recordings from two mouse models of myotonia congenita revealed the diaphragm had less myotonia than either the extensor digitorum longus (EDL) or the soleus muscles. A mechanism contributing to resistance of the diaphragm to myotonia was reduced depolarization of the interspike membrane potential during repetitive firing of action potentials, a process driven by build-up of K + in small invaginations of muscle membrane known as t-tubules. We explored differences between diaphragm and EDL that might underlie reduction of K + build-up in diaphragm t-tubules. Smaller size of diaphragm fibres, which promotes diffusion of K + out of t-tubules, was identified as a contributor. Intracellular recording revealed slower repolarization of action potentials in diaphragm suggesting reduced Kv conductance. Higher resting membrane conductance was identified suggesting increased Kir conductance. Computer simulation found that a reduction of Kv conductance had little effect on K + build-up whereas increased Kir conductance lessened build-up, although the effect was modest. Our data and computer simulation suggest opening of K + channels during action potentials has little effect on K + build-up whereas opening of K + channels during the interspike interval slightly lessens K + build-up. We conclude that activation of K + channels may lessen myotonia by opposing depolarization to action potential threshold without worsening K + build-up in t-tubules. KEY POINTS: In mouse models of the muscle disease myotonia congenita, the diaphragm has much less myotonia (muscle stiffness) than the extensor digitorum longus or soleus muscles. Identifying why the diaphragm is resistant to myotonia may help in developing novel therapy. We found the reason the diaphragm has less myotonia is that it is less prone to depolarization caused by K + build-up in t-tubules during repetitive firing of action potentials. Smaller fibre size contributes to resistance to K + build-up with differences in K + currents playing little role. Our data suggest drugs that open K + channels may be effective in treating myotonia as they may lessen excitability without worsening K + build-up in t-tubules., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Patients with acute respiratory distress syndrome (ARDS) require periods of deep sedation and mechanical ventilation, leading to diaphragm dysfunction. Our study seeks to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) and mechanical ventilation changes the degree of diaphragm injury and cytokines concentration in a preclinical ARDS model. Moderate ARDS was induced in pigs using oleic acid, followed by ventilation for 12 h post-injury with volume-control at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH 2 O, respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV + TTDN50%, n = 6) or every breath (MV + TTDN100%, n = 6). One group received ventilation only (MV, n = 6). Full-thickness diaphragm and quadricep muscle biopsies were taken at study end. Samples were fixed and stained with hematoxylin and eosin and a point-counting technique was applied to calculate abnormal muscle area fraction. Cytokine concentrations were measured in homogenized tissue using porcine-specific enzyme-linked immunosorbent assay (ELISA) and compared with serum samples. Percentage of abnormal diaphragm tissue was different between MV [8.1% (6.0-8.8)] versus MV + TTDN50% [3.4% (2.1-4.8)], P = 0.010 and MV versus MV + TTDN100% [3.1% (2.5-4.0)], P = 0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups ( P < 0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant ( P = 0.025). TTDN, delivered in synchrony with mechanical ventilation, mitigated diaphragm injury, as evidenced by less abnormal tissue in the diaphragm samples, in pigs with oleic acid-induced ARDS and is an exciting tool for lung and diaphragm-protective ventilation. NEW & NOTEWORTHY This study adds to our understanding of applying transvenous diaphragm neurostimulation synchronously with mechanical ventilation by examining its effects on diaphragm muscle injury and cytokine concentration patterns in pigs with acute respiratory distress syndrome (ARDS). We observed that using this therapy for 12 h post lung injury mitigated ventilator-induced diaphragm injury and changed the pattern of cytokine concentration measured in diaphragm tissue. These findings suggest that transvenous diaphragm neurostimulation is an exciting tool for lung and diaphragm protective ventilation.

Introduction/aims: Phrenic neuropathy (PhN) impairs diaphragm muscle function, causing a spectrum of breathing disability. PhN etiologies and their natural history are ill-defined. This knowledge gap hinders informed prognosis and management decisions. This study aims to help fill this knowledge gap on PhN etiologies, outcomes, and recovery patterns, especially in the context of nonsurgical clinical practice., Methods: This was a retrospective study from two interdisciplinary clinics, physiatry and neurology based. Patients were included if PhN was identified, and other causes of hemi-diaphragm muscle dysfunction excluded. Patients were followed serially at the discretion of the neuromuscular-trained neurologist or physiatrist. Recovery was assessed using pulmonary function tests (PFTs), diaphragm muscle ultrasound (US) thickening ratio, and patient-reported outcomes in patients presenting within 2 years of PhN onset., Results: We identified 151 patients with PhN. The most common etiologies were idiopathic (27%), associated with cardiothoracic procedure (24%), and intensive care unit (17%). Of these patients, 117 (77%) were evaluated within 2 years of PhN onset. Of patients included in outcome analyses, 64% saw improvement on serial US, 50% on serial PFTs and 79% reported symptomatic improvement at an average of 15, 16, and 17 months, respectively., Discussion: A clear majority of PhN patients show improvement in diaphragm muscle function, but on average, improvements took 15-17 months depending on the assessment type. These insights are vital for developing tailored treatments and can guide physicians in prognosis and decision-making, especially if more invasive interventions are being considered., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

This case explores Cheyne-Stokes respiration (CSR), a breathing pattern common in heart failure and brain injury patients. Using diaphragmatic ultrasound, the study assesses a 74-year-old patient with heart failure exhibiting CSR during sleep. Diaphragmatic excursion patterns reveal the characteristic crescendo-decrescendo pattern of CSR., (© 2024 Wiley Periodicals LLC.)

Background: Extubation failure is a crucial issue for acute respiratory distress syndrome (ARDS). Ultrasound of the lung and diaphragm is individually valuable for predicting extubation outcomes. We aimed to determine whether combined lung and diaphragmatic ultrasound could improve the accuracy of predicting the extubation of ARDS patients., Methods: This was a prospective cohort study of ARDS patients who were ready for extubation. The lung ultrasound score (LUS), diaphragmatic displacement (DD), diaphragm thickening fraction (DTF), and diaphragmatic-rapid shallow breathing index (D-RSBI) were measured at the end of the spontaneous breathing trial. The primary outcome was extubation success. Logistic regression was used to combine these indicators, and the predictive performance of the single and combined indicators was evaluated through receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow Ĉ-test, and the Brier score. Multivariate logistic regression was used to determine the association between combined ultrasound indicators and extubation success., Results: This study enrolled 132 eligible patients from January 2019 to December 2022. A total of 71% (94/132) of patients were successfully extubated from mechanical ventilation. The combination of LUS and D-RSBI had the largest area under the ROC curves, the lowest Brier score, and the greatest calibration. After formula transformation, LUS + 2.43 × D-RSBI ≤ 14.273 was significantly associated with extubation success in ARDS patients., Conclusions: In ARDS patients receiving mechanical ventilation, the combination of LUS and D-RSBI was more accurate than a single parameter alone in predicting extubation outcomes. This combined approach could help refine extubation protocols in critical care. Clinical trial registration This study is registered online with the Chinese Clinical Trial Registry (ChiCTR), http://www.chictr.org.cn , ChiCTR1800019340 (Registration time: 2018/11/06)., (© 2024. The Author(s).)

Background and Purpose: Diabetic polyneuropathy is a long-standing microvascular complication of diabetes that affects the postural control and functional mobility of patients. There are other microvascular complications, including pulmonary complications that reduce lung function. Multifactorial Inspiratory Muscle Training (IMT) can act as a home-based technique targeted to affect both these complications. This study aims to determine the effects of IMT on respiratory and functional parameters in diabetic polyneuropathy patients., Methods: This is a Pre-Test Post-Test Randomized Controlled Trial (NCT#04947163) with 62 diabetic polyneuropathy patients. Each was randomly assigned to the IMT or sham-IMT group. Both the groups performed OTAGO exercises , with the sham-IMT group performing IMT at 15% of baseline maximal inspiratory pressure (MIP), whereas IMT were trained at 50% of baseline MIP as an initial intensity, which was increased as per the tolerance of patients. Both groups performed training for 12 weeks. The study investigated diaphragmatic strength, pulmonary function, functional capacity through 6MWT, 30s sit to stand test and anterior trunk muscle endurance tested through sit up test as outcome variables. Data was analysed on SPSS v26 at the significance level of 0.0.5., Results: The IMT group significantly improved diaphragmatic strength, pulmonary function, 6MWT and anterior trunk muscle endurance when compared to the sham-IMT group., Conclusion: The study concluded that home-based IMT can improve pulmonary parameters including diaphragmatic strength and lung function as well as functional parameters including functional capacity in patients with diabetic polyneuropathy. The study was registered at ClinicalTrials.gov, NCT#04947163., (© 2024 John Wiley & Sons Ltd.)

Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life-saving intervention for patients in respiratory failure, an unintended side-effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is labelled as 'ventilator-induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox-regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV-induced changes in the structure/function of diaphragm muscle and discusses the cell-signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Background: Chronic respiratory failure is a common cause of ventilator dependence in the intensive care unit (ICU). The causes of chronic respiratory failure include primary disease or complications, such as ICU-acquired weakness. Traditional practice requires patients to remain immobile and bedridden; however, recent evidence suggests that early adequate exercise promotes recovery without increasing risks. In this study, we explored the efficacy of planned progressive abdominal sandbag training in promoting the successful withdrawal of patients with chronic respiratory failure from mechanical ventilation., Methods: This study was conducted between April 2019 and November 2020. Patients were recruited and divided into two groups: abdominal sandbag training group and control group (no training). The training group participated in a 3-month daily pulmonary rehabilitation program, which involved a 30-min session of progressive sandbag loading on the upper abdomen as a form of diaphragmatic resistant exercise. The pressure support level of the ventilator was adjusted to maintain a tidal volume of 8 mL/kg. To investigate the effect of abdominal sandbag training on patients with chronic respiratory failure, we compared tidal volume, shallow breathing index, maximum respiratory pressure, and diaphragm characteristics between the training and control groups., Results: This study included 31 patients; of them, 17 (54.8 %) received abdominal sandbag training and 14 (45.2 %) did not. No significant between-group difference was found in baseline characteristics. Compared with the control group, the training group exhibited considerable improvements in ventilation-related parameters (p < 0.001): the tidal volume markedly increased (p = 0.012), rapid shallow breathing index declined (p = 0.016), and maximum respiratory pressure increased (p < 0.001) in the training group. The diaphragm motion value (p = 0.048) and diaphragm thickness (p = 0.041) were greater in the training group than in the control group. Nine patients (52.9 %) in the training group were removed from the ventilator compared with 1 (7.1 %) in the control group (p = 0.008)., Conclusion: Abdominal sandbag training may be beneficial for patients dependent on a ventilator. The training improves the function of the diaphragm muscle, thereby increasing tidal volume and reducing the respiratory rate and rapid shallow breathing index, thus facilitating withdrawal from ventilation. This training approach may also improve the thickness and motion of the diaphragm and the rate of ventilator detachment., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Diaphragmatic dysfunction is a common problem in patients who have been mechanically ventilated., Objectives: The study aimed to evaluate the effectiveness of inspiratory muscle training (IMT) on diaphragm muscle thickness and function in mechanically ventilated patients., Material and Methods: A single-blind trial was conducted. Twenty patients were randomly assigned to either the conventional physiotherapy (CP) group or to the IMT group for 5 days following extubation. The CP group received only CP, while the IMT group received CP in addition to IMT. Ten healthy controls (HCs) underwent IMT. Maximum inspiratory pressure (MIP) and physical function were recorded. Diaphragm excursion (DE), diaphragm thickness at the end of inspiration (Tdi), diaphragm thickness at the end of expiration (Tde), peak contraction velocity (PCV), and peak relaxation velocity (PRV) were evaluated with ultrasonography before and after the intervention., Results: The IMT group and HCs showed significant improvements in DE (p = 0.005; p = 0.005, respectively), PCV (p = 0.028; p = 0.015, respectively) and PRV (p = 0.029; p = 0.020, respectively) after 5 days of IMT. A significant increase in MIP was recorded in all groups after the intervention (CP: p = 0.044; IMT: p = 0.005; HC: p < 0.001). There was a significant improvement in the Medical Research Council (MRC) and the Physical Function in Intensive Care Test (PFIT) scores in both the CP and IMT groups (p < 0.001 and p < 0.001, respectively)., Conclusions: Inspiratory muscle training improves diaphragmatic functions, including MIP, diaphragm excursion, PCV, and PRV. We think that IMT applied after extubation may serve as a tool to prevent and facilitate the recovery of diaphragmatic function.

Background: Diaphragm dysfunction is associated with weaning outcomes in mechanical ventilation patients, in the case of diaphragm dysfunction, the accessory respiratory muscles would be recruited. The main purpose of this study is to explore the performance of parasternal intercostal muscle thickening fraction in relation to diaphragmatic thickening fraction ratio (TFic 1 /TFdi 2 ) for predicting weaning outcomes, and compare its accuracy with D-RSBI in predicting weaning failure., Materials and Methods: We prospectively enrolled consecutive patients from 7/2022-5/2023. We measured TFic, TFdi, and diaphragmatic excursion (DE 3 ) by ultrasound and calculated the TFic/TFdi ratio and diaphragmatic rapid shallow breathing index (D-RSBI 4 ). Receiver-operator characteristic (ROC 5 ) curves evaluated the accuracy of the TFic/TFdi ratio and D-RSBI in predicting weaning failure., Results: 161 were included in the final analysis, 114 patients (70.8%) were successfully weaned from mechanical ventilation. The TFic/TFdi ratio (AUROC = 0.887 (95% CI: 0.821-0.953)) was superior to the D-RSBI (AUROC = 0.875 (95% CI: 0.807-0.944)) for predicting weaning failure., Conclusions: The TFic/TFdi ratio predicted weaning failure with high accuracy and outperformed the D-RSBI., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Effects of sequential increase in airway resistance: no, low (5 kPa.s/l), high (24 kPa.s/l), and complete block in the inspiratory or expiratory phase of mechanically induced cough on the cough motor pattern were studied in 16 anesthetized (pentobarbital) spontaneously breathing cats (3.70±0.15 kg, 11♂, 5♀). Esophageal pressure and electromyographic activities of the diaphragm during inspiration and abdominal muscles during expiration were analyzed. No significant changes in the number of coughs occurred. Inspiratory occlusion caused a prolongation of cough inspiratory phase, cough inspiratory diaphragm activity, and all cough-related activity. Inspiratory occlusion along with high resistance increased inspiratory esophageal pressure amplitude, total cough cycle duration and the time between maximum activity of the diaphragm and abdominal muscles. High expiratory resistance and occlusion resulted in increased cough expiratory esophageal pressure amplitude, a longer active portion of cough expiration, and cough abdominal activity. Expiratory occlusion also prolonged cough expiratory phase, all cough activity, and total cough cycle. Significantly increased airway resistance and occlusion induce secondary, in addition to mechanical, changes in cough by significantly modulating the generated cough motor pattern. A certain level of resistance appears to be successfully compensated, resulting in minimal changes in coughing characteristics, including expiratory airflow and the rising time of the airflow. Afferent feedback from the respiratory tract, particularly volume feedback, represents a significant factor in modulating cough, mainly under various pathological conditions in the respiratory system., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The ultrasound study of diaphragm function represents a valid method that has been extensively studied in recent decades in various fields, especially in intensive care, emergency, and pulmonology settings. Diaphragmatic function is pivotal in these contexts due to its crucial role in respiratory mechanics, ventilation support strategies, and overall patient respiratory outcomes. Dysfunction or weakness of the diaphragm can lead to respiratory failure, ventilatory insufficiency, and prolonged mechanical ventilation, making its assessment essential for patient management and prognosis in critical care and emergency medicine. While several studies have focused on diaphragmatic functionality in the context of intensive care, there has been limited attention within the field of anesthesia. The ultrasound aids in assessing diaphragmatic dysfunction (DD) by measuring muscle mass and contractility and their potential variations over time. Recent advancements in ultrasound imaging allow clinicians to evaluate diaphragm function and monitor it during mechanical ventilation more easily. In the context of anesthesia, early studies have shed light on the patho-physiological mechanisms of diaphragm function during general anesthesia. In contrast, more recent research has centered on evaluating diaphragmatic functionality at various phases of general anesthesia and by comparing diverse types of procedures or anatomical position during surgery. The objectives of this current review are to highlight the use of diaphragm ultrasound for the evaluation of diaphragmatic function during perioperative anesthesia and surgery. Specifically, we aim to examine the effects of anesthetic agents, surgical techniques, and anatomical positioning on diaphragmatic function. We explore how ultrasound aids in assessing DD by measuring muscle mass and contractility, as well as their potential variations over time. Additionally, we will discuss recent advancements in ultrasound imaging that allow clinicians to evaluate diaphragm function and monitor it during mechanical ventilation more easily., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mechanical ventilation (MV) can cause diaphragmatic injury and ventilator induced diaphragmatic dysfunction (VIDD). Diaphragm ultrasonography (DU) is increasingly used to assess diaphragmatic anatomy, function and pathology of patients receiving MV in the pediatric intensive care unit (PICU). We report the poor contractile ability of diaphragm during ventilation of critically ill patients in our PICU and the association to prolonged length of MV and PICU stay., Methods: Patients who received MV within 24 h of admission to the PICU, expected to undergo continuous MV for more than 48 h and succeeded to extubate were included in the study. DU monitoring was performed daily after the initiation of MV until extubation. Diaphragm thickening fraction (DTF) measured by DU was used as an indicator of diaphragmatic contractile activity. Patients with bilateral DTF = 0% during DU assessment were allocated into the severe VIDD group (n = 26) and the rest were into non-severe VIDD group (n = 29). The association of severe VIDD with individual length of MV, hospitalization and PICU stay were analyzed., Results: With daily DU assessment, severe VIDD occurred on 2.9 ± 1.2 days after the initiation of MV, and lasted for 1.9 ± 1.7 days. Values of DTF of all patients recovered to > 10% before extubation. The severe VIDD group had a significantly longer duration (days) of MV [12.0 (8.0-19.3) vs. 5.0 (3.5-7.5), p < 0.001] and PICU stay (days) [30.5 (14.9-44.5) vs. 13.0 (7.0-24.5), p < 0.001]. The occurrence of severe VIDD, first day of severe VIDD and length of severe VIDD were significantly positively associated with the duration of MV and PICU stay. The occurrence of severe VIDD on the second and third days after initiation of MV significantly associated to longer PICU stay (days) [43.0 (9.0-70.0) vs. 13.0 (3.0-40.0), p = 0.009; 36.0 (17.0-208.0) vs. 13.0 (3.0-40.0), p = 0.005, respectively], and the length of MV (days) was significantly longer in those with severe VIDD on the third day after initiation of MV [16.5 (7.0-29.0) vs. 5.0 (2.0-22.0), p = 0.003]., Conclusions: Daily monitoring of diaphragmatic function with bedside ultrasonography after initiation of MV is necessary in critically ill patients in PICU and the influences and risk factors of severe VIDD need to be further studied. (355 words)., (© 2024. The Author(s).)

Background: Patients with a tracheostomy and difficult weaning from invasive mechanical ventilation constitute a challenging problem in critical care. An increased duration of ventilation may lead to diaphragmatic dysfunction and a noninvasive assessment of the diaphragm, such as ultrasound, attracts interest in the clinical practice. We evaluated the relationship of ultrasound-derived indices with weaning outcome and with established indices of respiratory strength and load in subjects who are tracheostomized and undergoing weaning., Methods: This prospective study was conducted at an academic ICU in Greece. Twenty subjects with tracheostomy and difficult weaning, during a spontaneous breathing trial, underwent time synchronous diaphragmatic sonography and esophageal manometry, to assess diaphragmatic excursion and thickening fraction, esophageal and transdiaphragmatic pressures, pressure-time product of the esophageal pressure, and maximum inspiratory pressure. The primary outcome was liberation from mechanical ventilation at 48 h. The relationship of diaphragmatic ultrasound with esophageal pressure-derived indices was also evaluated., Results: Weaning from invasive ventilation failed in 10 subjects. Diaphragmatic excursion exhibited a significant difference between weaning success and failure (1.34 ± 0.56 versus 0.79 ± 0.44; P = .044), a strong correlation with transdiaphragmatic pressure (r = 0.7, P = .02), and a moderate correlation with the pressure-time product of the esophageal pressure (r = 0.65, P = .02) and the maximum inspiratory pressure (r = 0.66, P = .02). Transdiaphragmatic pressure presented the highest area under the curve (0.97). However, when transdiaphragmatic pressure was compared with diaphragmatic excursion (area under the curve, 0.84) for predictive accuracy, no significant difference was found., Conclusions: Diaphragmatic excursion is a valuable tool for the assessment of diaphragmatic strength, respiratory load, and weaning prediction., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

The respiratory muscles in chronic obstructive pulmonary disease (COPD) patients have reduced strength and resistance, leading to loss of the functional ability of these muscles. Lung hyperinflation is one of the main alterations, and air trapping is the main factor limiting diaphragmatic mobility (DM) in these patients; however, its correlation with functional parameters, exercise capacity, and indicators of disease severity remains underexplored. This study aimed to assess DM in stable COPD patients and relate the findings with parameters such as the 6-minute walk test distance, forced expiratory volume in 1 second (FEV1) %predicted, residual volume (RV) %predicted, and dyspnea. An observational cohort study was conducted to measure DM using ultrasound both at rest (DMrest) and during deep inspiration (DMmax). Forty-nine patients with stable COPD were included in this study. There was a correlation between DMmax and FEV1 %predicted (R = 0.36; P = .012), RV %predicted (r = -0.42; P = .01), RV/total lung capacity (r = -0.61; P < .001), and distance reached in the 6MWT (R = 0.46; P = .001). Patients with a modified Medical Research Council score <2 exhibited greater DM than those with a score ≥2 (mean difference = 13.20 ± 4.6 mm; P = .0059). Similarly, patients with a Body Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity index ≤4 showed greater DM (61.95 mm) than those with a Body Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity index >4 (47.89 mm; mean difference = 14.05 ± 5.3 mm; 95% confidence interval = 25.09-3.01 mm). DM is correlated with bronchial obstruction (FEV1), lung hyperinflation (RV and RV/total lung capacity), exercise capacity, and dyspnea in patients with COPD, suggesting its utility as an evaluative tool in this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: During mechanical ventilation, post-insufflation diaphragm contractions (PIDCs) are non-physiologic and could be injurious. PIDCs could be frequent during reverse-triggering, where diaphragm contractions follow the ventilator rhythm. Whether PIDCs happens with different modes of assisted ventilation is unknown. In mechanically ventilated patients with hypoxemic respiratory failure, we aimed to examine whether PIDCs are associated with ventilator settings, patients' characteristics or both., Methods: One-hour recordings of diaphragm electromyography (EAdi), airway pressure and flow were collected once per day for up to five days from intubation until full recovery of diaphragm activity or death. Each breath was classified as mandatory (without-reverse-triggering), reverse-triggering, or patient triggered. Reverse triggering was further subclassified according to EAdi timing relative to ventilator cycle or reverse triggering leading to breath-stacking. EAdi timing (onset, offset), peak and neural inspiratory time (Ti neuro ) were measured breath-by-breath and compared to the ventilator expiratory time. A multivariable logistic regression model was used to investigate factors independently associated with PIDCs, including EAdi timing, amplitude, Ti neuro , ventilator settings and APACHE II., Results: Forty-seven patients (median[25%-75%IQR] age: 63[52-77] years, BMI: 24.9[22.9-33.7] kg/m 2 , 49% male, APACHE II: 21[19-28]) contributed 2 ± 1 recordings each, totaling 183,962 breaths. PIDCs occurred in 74% of reverse-triggering, 27% of pressure support breaths, 21% of assist-control breaths, 5% of Neurally Adjusted Ventilatory Assist (NAVA) breaths. PIDCs were associated with higher EAdi peak (odds ratio [OR][95%CI] 1.01[1.01;1.01], longer Ti neuro (OR 37.59[34.50;40.98]), shorter ventilator inspiratory time (OR 0.27[0.24;0.30]), high peak inspiratory flow (OR 0.22[0.20;0.26]), and small tidal volumes (OR 0.31[0.25;0.37]) (all P ≤ 0.008). NAVA was associated with absence of PIDCs (OR 0.03[0.02;0.03]; P < 0.001). Reverse triggering was characterized by lower EAdi peak than breaths triggered under pressure support and associated with small tidal volume and shorter set inspiratory time than breaths triggered under assist-control (all P < 0.05). Reverse triggering leading to breath stacking was characterized by higher peak EAdi and longer Ti neuro and associated with small tidal volumes compared to all other reverse-triggering phenotypes (all P < 0.05)., Conclusions: In critically ill mechanically ventilated patients, PIDCs and reverse triggering phenotypes were associated with potentially modifiable factors, including ventilator settings. Proportional modes like NAVA represent a solution abolishing PIDCs., (© 2024. The Author(s).)

Introduction: Weaning patients from mechanical ventilation is crucial in the management of acute respiratory failure (ARF). Spontaneous breathing trials (SBT) are used to assess readiness for extubation, but extubation failure remains a challenge. Diaphragmatic function, measured by electrical activity of the diaphragm (EAdi), may provide insights into weaning outcomes., Materials and Methods: This prospective, observational study included difficult-to-wean patients undergoing invasive mechanical ventilation. EAdi was recorded before, during, and after extubation. Patients were categorized into extubation success and failure groups based on reintubation within 48 h. Statistical analysis assessed EAdi patterns and predictive value., Results: Thirty-one patients were analyzed, with six experiencing extubation failure. Overall, EAdi increased significantly between the phases before the SBT, the SBT and post-extubation period, up to 24 h (p < 0.001). EAdi values were higher in the extubation failure group during SBT (p = 0.01). An EAdi > 30 μV during SBT predicted extubation failure with 92% sensitivity and 67% specificity. Multivariable analysis confirmed EAdi as an independent predictor of extubation failure., Conclusions: In difficult-to-wean patients, EAdi increases significantly between the phases before the SBT, the SBT and post-extubation period and is significantly higher in patients experiencing extubation failure. An EAdi > 30 μV during SBT may enhance extubation failure prediction compared to conventional parameters. Advanced monitoring of diaphragmatic function could improve weaning outcomes in critical care settings., (© 2024. The Author(s).)

Introduction/aims: Point-of-care ultrasound of the diaphragm is highly sensitive and specific in the detection of neuromuscular diaphragmatic dysfunction. In some patients with neuromuscular diaphragmatic dysfunction, paradoxical thinning of the diaphragm during inspiration is observed on ultrasound; however, its frequency, electrodiagnostic associations, and prognostic significance remain uncertain., Methods: Medical records of patients presenting to two electrodiagnostic laboratories (Mayo Clinic, Rochester, Minnesota and University of Alberta, Edmonton, Alberta) from January 1, 2022 to December 31, 2022, for evaluation of suspected neuromuscular respiratory failure, were reviewed., Results: 214 patients were referred and 19 patients excluded due to incomplete information. Of 195 patients (384 hemidiaphragms), 104 had phrenic neuropathy, 12 had myopathy, and 79 had no evidence of neuromuscular disease affecting the diaphragm. Paradoxical thinning occurred in 31 (27%) patients with neuromuscular diaphragmatic dysfunction and was unilateral in 30, the majority (83%) having normal contralateral ultrasound. Phrenic nerve conduction studies and diaphragm electromyography results did not distinguish patients with paradoxical thinning versus without. Most patients (71%) with paradoxical thinning required non-invasive ventilation (NIV), including 16 with unilateral paradoxical thinning. Paradoxical thinning and BMI ≥30 kg/m 2 were risk factors for requiring NIV in multivariable logistic regression analysis, with odds ratios of 2.887 (95% CI:1.166, 7.151) and 2.561 (95% CI: 1.186, 5.532), respectively., Discussion: Paradoxical thinning of the diaphragm occurs in patients with prominent neuromuscular diaphragmatic dysfunction, most commonly from phrenic neuropathy, and is a significant risk factor for requiring NIV. Unilateral paradoxical thinning is sufficient for needing NIV. BMI ≥30 kg/m 2 additionally increases risk of requiring NIV in patients with neuromuscular diaphragmatic dysfunction., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Rationale: Diaphragm muscle weakness might underlie persistent exertional dyspnea, despite normal lung and cardiac function in individuals who were previously hospitalized for acute coronavirus disease (COVID-19) illness. Objectives: The authors sought, first, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea 2 years after hospitalization for COVID-19 and, second, to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID. Methods: Approximately 2 years after hospitalization for COVID-19, 30 individuals (11 women, 19 men; median age, 58 years; interquartile range [IQR] = 51-63) underwent comprehensive (invasive) respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to 6 weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. The primary endpoint was change in inspiratory muscle fatiguability immediately after IMT. Measurements and Main Results: At a median of 31 months (IQR = 23-32) after hospitalization, 21 of 30 individuals reported relevant persistent exertional dyspnea. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were potentially related to exertional dyspnea. Compared with sham control, IMT improved diaphragm and inspiratory muscle function (sniff transdiaphragmatic pressure, 83 cm H 2 O [IQR = 75-91] vs. 100 cm H 2 O [IQR = 81-113], P  = 0.02), inspiratory muscle fatiguability (time to task failure, 365 s [IQR = 284-701] vs. 983 s [IQR = 551-1,494], P  = 0.05), diaphragm voluntary activation index (79% [IQR = 63-92] vs. 89% [IQR = 75-94], P  = 0.03), and dyspnea (Borg score, 7 [IQR = 5.5-8] vs. 6 [IQR = 4-7], P  = 0.03). Improvements persisted for 6 weeks after IMT completion. Conclusions: To the best of the authors' knowledge, this study is the first to identify a potential treatment for persisting exertional dyspnea in long COVID and provide a possible pathophysiological explanation for the treatment benefit. Clinical trial registered with www.clinicaltrials.gov (NCT04854863, NCT05582642).

Background: The most common surgery for non-small cell lung cancer is lobectomy, which can be performed through either thoracotomy or video-assisted thoracic surgery (VATS). Insufficient research has examined respiratory muscle function and exercise capacity in lobectomy performed using conventional thoracotomy (CT), muscle-sparing thoracotomy (MST), or VATS. This study aimed to assess and compare respiratory muscle strength, diaphragm thickness, and exercise capacity in lobectomy using CT, MST, and VATS., Methods: The primary outcomes were changes in respiratory muscle strength, diaphragm thickness, and exercise capacity. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were recorded for respiratory muscle strength. The 6-min walk test (6MWT) was used to assess functional exercise capacity. Diaphragm thickness was measured using B-mode ultrasound., Results: The study included 42 individuals with lung cancer who underwent lobectomy via CT (n = 14), MST (n = 14), or VATS (n = 14). Assessments were performed on the day before surgery and on postoperative day 20 (range 17-25 days). The decrease in MIP (p < 0.001), MEP (p = 0.003), 6MWT (p < 0.001) values were lower in the VATS group than in the CT group. The decrease in 6MWT distance was lower in the MST group than in the CT group (p = 0.012). No significant differences were found among the groups in terms of diaphragmatic muscle thickness (p > 0.05)., Conclusion: The VATS technique appears superior to the CT technique in terms of preserving respiratory muscle strength and functional exercise capacity. Thoracic surgeons should refer patients to physiotherapists before lobectomy, especially patients undergoing CT. If lobectomy with VATS will be technically difficult, MST may be an option preferable to CT because of its impact on exercise capacity., (© 2024. The Author(s).)

Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disease. Lack of dystrophin in skeletal muscles leads to intrinsic weakness, injury, subsequent degeneration and fibrosis, decreasing contractile function. Dystropathology eventually presents in all inspiratory and expiratory muscles of breathing, severely curtailing their critical function. In people with DMD, premature death is caused by respiratory or cardiac failure. There is an urgent need to develop therapies that improve quality of life and extend life expectancy in DMD. Surprisingly, there is a dearth of information on respiratory control in animal models of DMD, and respiratory outcome measures are often limited or absent in clinical trials. Characterization of respiratory performance in murine and canine models has revealed extensive remodelling of the diaphragm, the major muscle of inspiration. However, significant compensation by extradiaphragmatic muscles of breathing is evident in early disease, contributing to preservation of peak respiratory system performance. Loss of compensation afforded by accessory muscles in advanced disease is ultimately associated with compromised respiratory performance. A new and potentially more translatable murine model of DMD, the D2.mdx mouse, has recently been developed. Respiratory performance in D2.mdx mice is yet to be characterized fully. However, based on histopathological features, D2.mdx mice might serve as useful preclinical models, facilitating the testing of new therapeutics that rescue respiratory function. This review summarizes the pathophysiological mechanisms associated with DMD both in humans and in animal models, with a focus on breathing. We consider the translational value of each model to human DMD and highlight the urgent need for comprehensive characterization of breathing in representative preclinical models to better inform human trials., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Assessing cough effectiveness, using Cough Peak Flow, is crucial for patients with Neuromuscular Diseases, such as Amyotrophic Lateral Sclerosis. Impaired cough function can contribute to respiratory decline and failure. The goal of the study is to determine the correlation between diaphragmatic excursion and cough expiratory phase, potentially utilizing ultrasonographic indices to estimate Cough Peak Flow in these patients. Twenty-two patients were enrolled in this study. The upward displacement of the diaphragm was measured with ultrasonography during voluntary cough expiration and Cough Peak Flow was simultaneously measured. A multivariable linear regression model was built to quantify the association between Cough Peak Flow and diaphragm expiratory excursion. There is significative relationship between Cough Peak Flow and diaphragm excursion with a Pearson's r coefficient of 0.86 observed in the patients group. Multiple linear regression analysis for Cough Peak Flow (Adjusted R 2 = 0.86) revealed significant associations between Cough Peak Flow and expiratory excursion (adjusted β-coefficient: 64.78, 95 %, CI: 51.50-78.07, p<0.001) and sex (adjusted β-coefficient: -69.06; 95 % CI: -109.98 to -28.15, p=0.001). Our results predict the cough effectiveness by using M-mode diaphragmatic sonography with a potentially significant impact on therapeutic choices., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Recent studies have highlighted the recognition of diaphragmatic dysfunction as a significant factor contributing to respiratory disturbances in severely ill COVID-19 patients. In the field of noninvasive respiratory support, high-flow nasal cannula (HFNC) has shown effectiveness in relieving diaphragm dysfunction. This study aims to investigate the diaphragmatic response to HFNC in patients with COVID-19 pneumonia by utilizing ultrasound., Methods: This retrospective study was conducted in a medical-surgical intensive care unit (ICU) at a tertiary care center in Buenos Aires, Argentina (Sanatorio de Los Arcos) over a 16-month period (January 2021-June 2022). The study included patients admitted to the ICU with a diagnosis of COVID-19 pneumonia who were deemed suitable candidates for HFNC therapy by the attending physician. Diaphragm ultrasound was conducted, measuring diaphragmatic excursion (DE) both before and during the utilization of HFNC for these patients., Results: A total of 10 patients were included in the study. A statistically significant decrease in respiratory rate was observed with the use of HFNC (p = 0.02), accompanied by a significant increase in DE (p = 0.04)., Conclusion: HFNC leads to a reduction in respiratory rate and an increase in DE as observed by ultrasound in patients with COVID-19 pneumonia, indicating promising enhancements in respiratory mechanics. However, further research is required to validate these findings., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Aging is associated with inspiratory muscle dysfunction; however, the impact of aging on diaphragm blood flow (BF) regulation, and whether sex differences exist, is unknown. We tested the hypotheses in young animals that diaphragm BF and vascular conductance (VC) would be greater in females and that aging would decrease the diaphragm's ability to increase BF with contractions. Young (4-6 mo) and old (22-24 mo) Fischer 344 rats were divided into four groups: young female (YF, n = 7), young male (YM, n = 8), old female (OF, n = 9), and old male (OM, n = 9). Diaphragm BF (mL/min/100 g) and VC (mL/mmHg/min/100 g) were determined, via fluorescent microspheres, at rest and during 1 Hz contractions. In YF versus OF, aging blunted the increase in medial costal diaphragm BF (44 ± 5% vs. 16 ± 12%; P < 0.05) and VC (43 ± 7% vs. 21 ± 12%; P < 0.05). Similarly, in YM versus OM, aging blunted the increase in medial costal diaphragm BF (43 ± 6% vs. 24 ± 12%; P < 0.05) and VC (50 ± 6% vs. 34 ± 10%; P < 0.05). In female rats, age increased dorsal costal diaphragm BF, whereas in male rats, age increased crural diaphragm BF ( P < 0.05). Compared with age-matched females, dorsal costal diaphragm BF was lower in YM and OM ( P < 0.05). In conclusion, aging results in an inability to augment medial costal diaphragm BF and alters regional diaphragm BF distribution in response to muscular contractions. Furthermore, sex differences in regional diaphragm BF are present in young and old animals. NEW & NOTEWORTHY This is the first study, to our knowledge, to demonstrate that old age impairs the hyperemic response and alters blood flow distribution in the diaphragm of both female and male rats. In addition, this investigation provides novel evidence of sex differences in regional diaphragm blood flow distribution with contractions. The data presented herein suggest that aging compromises diaphragm vascular function and provides a potential mechanism for the diaphragm contractile dysfunction associated with old age.

Patients with acute respiratory distress syndrome often require mechanical ventilation to maintain adequate gas exchange and to reduce the workload of the respiratory muscles. Although lifesaving, positive pressure mechanical ventilation can potentially injure the lungs and diaphragm, further worsening patient outcomes. While the effect of mechanical ventilation on the risk of developing lung injury is widely appreciated, its potentially deleterious effects on the diaphragm have only recently come to be considered by the broader intensive care unit community. Importantly, both ventilator-induced lung injury and ventilator-induced diaphragm dysfunction are associated with worse patient-centered outcomes., Competing Interests: Disclosure Dr Goligher reports receiving personal fees for consulting and/or advisory board activities from Getinge, Lungpacer, Zoll, Baxter, Bioage, Stimit, Vyaire, Drager, and Heecap., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Invasive mechanical ventilation (MV) is one of the most practiced interventions in the intensive care unit (ICU) and is unmistakably lifesaving for children with acute respiratory failure (ARF). However, if delivered inappropriately (i.e. ignoring the respiratory system mechanics and not targeted to the need of the individual patient at a specific time point in the disease trajectory), the side effects will outweigh the benefits. Decades of experimental and clinical investigations have resulted in a better understanding of three important detrimental effects of MV. These are ventilation-induced lung injury (VILI), patient self-inflicted lung injury (P-SILI), and ventilation-induced diaphragmatic injury (VIDD). VILI, P-SILI, and VIDD have in common that they occur when there is either too much or too little ventilatory assistance.Conclusion: The purpose of this review is to give the paediatrician an overview of the challenges to prevent these detrimental effects and titrate MV to the individual patient needs., (© 2024. The Author(s).)

Purpose: Obstructive sleep apnea (OSA) is characterized by recurrent upper airway narrowing or collapse during sleep. Continuous positive airway pressure (CPAP) remains the preferred treatment in selected patients and masks' choice plays an important role for subsequent respiratory events' reduction. It is known that oronasal masks are not as effective at opening the upper airway compared to nasal ones. Thus, the objective of this study was to investigate differences in US-assessed diaphragmatic excursion (DE) using oronasal vs. nasal CPAP masks., Methods: This observational study included 50 OSA patients presenting a moderate to severe apnea-hypopnea index and requiring CPAP treatment. All participants received US evaluations on diaphragm motion during their oronasal and nasal CPAP trial at equal positive end-expiratory pressure level., Results: The difference of DE switching mask during CPAP was assessed by using the non-parametric Wilcoxon signed-rank test. A statistically significant increase in US- assessed DE was found when shifting from oronasal to nasal mask (p-value < 0.01). Linear regression models revealed that increased neck circumference and more severe AHI were associated with decreased DE when shifting to an oronasal mask., Conclusion: This study evaluated the acute impact on US-assessed DE after changing CPAP route from oronasal to nasal mask. Our results suggest that the nasal type should be the more suitable option for most patients with OSA, especially those with higher nasal circumference. Diaphragmatic motion throughout US may become a practical tool to help in the choice of the fittest mask in patients undergoing CPAP., Competing Interests: Declarations Ethical approval All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee (name of institute/committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study. Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Codeine was microinjected into the area of the Kölliker-Fuse nucleus and the adjacent lateral parabrachial nucleus, within the pontine respiratory group in 8 anesthetized cats. Electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD), esophageal pressures (EP), and blood pressure were recorded and analyzed during mechanically induced tracheobronchial cough. Unilateral microinjections of 3.3 mM codeine (3 injections, each 37 ± 1.2 nl) had no significant effect on the cough number. However, the amplitudes of the cough ABD EMG, expiratory EP and, to a lesser extent, DIA EMG were significantly reduced. There were no significant changes in the temporal parameters of the cough. Control microinjections of artificial cerebrospinal fluid in 6 cats did not show a significant effect on cough data compared to those after codeine microinjections. Codeine-sensitive neurons in the rostral dorsolateral pons contribute to controlling cough motor output, likely through the central pattern generator of cough., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diaphragmatic myoclonus is a rare motor disorder that affects muscle tone. It is characterized by involuntary movements of the abdominal wall and rhythmic, repetitive contractions of the accessory or respiratory muscles, all of which are innervated by the cervical nerve roots., Case Description: We reviewed the case of a 57-year-old male patient who underwent surgery for a left cerebellar hemorrhage. He exhibited persistent myoclonus in the palate, jaw, and thoracoabdominal region. Following treatment, there was a significant reduction in flutter amplitude in these areas., Conclusion: The clinical rarity and variability of presentations often make diagnosis challenging and delayed. It is believed that this condition stems from abnormal excitation within the central nervous system or neural pathways that involve the phrenic nerve. Another potential mechanism is the direct irritation of the diaphragm. Ultrasound, chest fluoroscopy, and electromyography (EMG) can support the diagnosis. Various pharmacological and surgical treatments have been tried, yet specific treatment guidelines are still lacking., (© 2024. The Author(s).)

Background: When the work load of the respiratory muscles increases and/or their capacity decreases in individuals with COPD, respiratory muscle activation increases to maintain gas exchange and respiratory mechanics, and perception of dyspnea occurs. The present study aimed to compare diaphragm and accessory respiratory muscle activation during normal breathing, pursed-lip breathing, and breathing control in different dyspnea relief positions, supine and side lying., Methods: A cross-sectional study design was used. Sixteen individuals with COPD age between 40-75 y were included. Pulmonary function was evaluated by spirometry, muscle activation by surface electromyography, and dyspnea by the modified Borg scale. Muscle activation was measured in the diaphragm, scalene, sternocleidomastoid, and parasternal muscles. The evaluation was made in the dyspnea relief positions (sitting leaning forward, sitting leaning forward at a table, leaning forward with back against a wall, standing leaning forward, and high lying), seated erect, supine, and side lying., Results: There were significant differences between the 8 positions ( P < .001). There was no significant difference in muscle activation between sitting leaning forward and sitting leaning forward at a table position with analyzing post hoc test results ( P > .99 for each muscle). However, muscle activation was lower in these 2 positions than in the other positions ( P < .001 for each muscle). Muscle activation was greater in the supine position than in the other positions ( P < .001 for each muscle). No difference was observed in muscle activation between the seated erect, leaning forward with back against a wall, standing leaning forward, high-lying, or side-lying positions ( P > .05 for each muscle with a minimum P value of .09)., Conclusions: The use of sitting leaning forward and sitting leaning forward at a table positions together with breathing control may help people with COPD to achieve more effective dyspnea relief and greater energy efficiency., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed to predict extubation outcomes. However, few studies focused on the predicting value of E/Ea and DE at different positions during a spontaneous breathing trial (SBT), as well as the effects of △E/Ea and △DE (changes in E/Ea and DE during a SBT)., Methods: This study was a reanalysis of the data of 60 difficult-to-wean patients in a previous study published in 2017. All eligible participants were organized into respiratory failure (RF) group and extubation success (ES) group within 48 h after extubation, or re-intubation (RI) group and non-intubation (NI) group within 1 week after extubation. The risk factors for respiratory failure and re-intubation including E/Ea and △E/Ea, DE and △DE at different positions were analyzed by multivariate logistic regression, respectively. The receiver operating characteristic (ROC) curves of E/Ea (septal, lateral, average) and DE (right, left, average) were compared with each other, respectively., Results: Of the 60 patients, 29 cases developed respiratory failure within 48 h, and 14 of those cases required re-intubation within 1 week. Multivariate logistic regression showed that E/Ea were all associated with respiratory failure, while only DE (right) and DE (average) after SBT were related to re-intubation. There were no statistic differences among the ROC curves of E/Ea at different positions, nor between the ROC curves of DE. No statistical differences were shown in △E/Ea between RF and ES groups, while △DE (average) was remarkably higher in NI group than that in RI group. However, multivariate logistic regression analysis showed that △DE (average) was not associated with re-intubation., Conclusions: E/Ea at different positions during a SBT could predict postextubation respiratory failure with no statistical differences among them. Likewise, only DE (right) and DE (average) after SBT might predict re-intubation with no statistical differences between each other., (© 2024. The Author(s).)

In experiments on the motor nerve endings of the diaphragm of transgenic FUS mice with a model of amyotrophic lateral sclerosis at the pre-symptomatic stage of the disease, the processes of transmitter release and endocytosis of synaptic vesicles were studied. In FUS mice, the intensity of transmitter release during high-frequency stimulation of the motor nerve (50 imp/sec) was lowered. At the same duration of stimulation, the loading of fluorescent dye FM1-43 was lower in FUS mice. However, at the time of stimulation, during which an equal number of quanta are released in wild-type and FUS mice, no differences in the intensity of dye loading were found. Thus, endocytosis is not the key factor in the mechanism of synaptic dysfunction in FUS mice at the pre-symptomatic stage., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Severe chronic obstructive pulmonary disease (COPD) often results in hyperinflation and flattening of the diaphragm. An automated computed tomography (CT)-based tool for quantifying diaphragm configuration, a biomarker for COPD, was developed in-house and tested in a large cohort of COPD patients., Methods: We used the LungQ platform to extract the lung-diaphragm intersection, as direct diaphragm segmentation is challenging. The tool computed the diaphragm index (surface area/projected surface area) as a measure of diaphragm configuration on inspiratory scans in a COPDGene subcohort. Visual inspection of 250 randomly selected segmentations served as a quality check. Associations between the diaphragm index, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, forced expiratory volume in 1 s (FEV1) % predicted, and CT-derived emphysema scores were explored using analysis of variance and Pearson correlation., Results: The tool yielded incomplete segmentation in 9.2% (2.4% major defect, 6.8% minor defect) of 250 randomly selected cases. In 8431 COPDGene subjects (4240 healthy; 4191 COPD), the diaphragm index was increasingly lower with higher GOLD stages (never-smoked 1.83 ± 0.16; GOLD-0 1.79 ± 0.18; GOLD-1 1.71 ± 0.15; GOLD-2: 1.67 ± 0.16; GOLD-3 1.58 ± 0.14; GOLD-4 1.54 ± 0.11) (p < 0.001). Associations were found between the diaphragm index and both FEV1% predicted (r = 0.44, p < 0.001) and emphysema score (r = -0.36, p < 0.001)., Conclusion: We developed an automated tool to quantify the diaphragm configuration in chest CT. The diaphragm index was associated with COPD severity, FEV1%predicted, and emphysema score., Relevance Statement: Due to the hypothesized relationship between diaphragm dysfunction and diaphragm configuration in COPD patients, automatic quantification of diaphragm configuration may prove useful in evaluating treatment efficacy in terms of lung volume reduction., Key Points: Severe COPD changes diaphragm configuration to a flattened state, impeding function. An automated tool quantified diaphragm configuration on chest-CT providing a diaphragm index. The diaphragm index was correlated to COPD severity and may aid treatment assessment., (© 2024. The Author(s).)

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model - the mdx mouse - is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function., Competing Interests: Declaration of Competing Interest CAG is an advisor to Sarepta Therapeutics and an advisor and co-founder of Tune Therapeutics. CAG and JRH are inventors on patents and patent applications related to genome editing. AMB is an employee and stakeholder of Fulcrum Therapuetics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chronic neck pain (CNP) is a prevalent musculoskeletal condition including notable impairments in respiratory function. The diaphragm, serving dual roles in respiration and spinal stability, is intricately linked to the cervical spine through fascial, neurophysiological, and biomechanical connections. However, to date, none has investigated the diaphragm function in patients with CNP., Objectives: To investigate the diaphragm function, respiratory muscle strength, and pulmonary function in patients with CNP. In addition, their associations were also examined., Design: A case-control study., Methods: A total of 54 participants were recruited including 25 patients with CNP (CNP group) and 29 healthy adults (CON group). Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ), and respiratory muscle strength represented by maximal inspiratory (MIP) and maximal expiratory pressure (MEP), as well as diaphragm function including ultrasonographic measures of mobility and thickness changes during maximal inspiration and expiration were assessed in all participants. Additionally, the intensity of pain and disability were evaluated using a Visual Analog Scale and Neck Disability Index only in patients with CNP., Results: Significant reductions of the FVC, FEV 1 , MIP, and MEP were found in the CNP group compared to the CON group (p < 0.05). The diaphragm mobility and thickness changes were also significantly decreased in the CNP group than the CON group with medium effect sizes (p < 0.05). Only diaphragm thickness change was positively correlated with FVC, FEV 1 , and MEP in patients with CNP. Furthermore, MEP showed the strongest contribution to diaphragm thickness change based on the regression analysis., Conclusions: Impaired diaphragm function, respiratory muscle strength, and pulmonary function were observed in patients with CNP. Patients with smaller diaphragm thickness change had poorer pulmonary function and reduced maximal expiratory muscle strength. Diaphragm assessment and intervention may be considered in CNP management., Competing Interests: Declarations of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Duchenne muscular dystrophy (DMD) is characterised by respiratory muscle injury, inflammation, fibrosis and weakness, ultimately culminating in respiratory failure. The dystrophin-deficient mouse model of DMD (mdx) shows evidence of respiratory muscle remodelling and dysfunction contributing to impaired respiratory system performance. The antioxidant N-acetylcysteine (NAC) has been shown to exert anti-inflammatory and anti-fibrotic effects leading to improved respiratory muscle performance in a range of animal models of muscle dysfunction, including mdx mice, following short-term administration (2 weeks). We sought to build on previous work by exploring the effects of chronic NAC administration (3 months) on respiratory system performance in mdx mice. One-month-old male mdx mice were randomised to receive normal drinking water (n = 30) or 1% NAC in the drinking water (n = 30) for 3 months. At 4 months of age, we assessed breathing in conscious mice by plethysmography followed by ex vivo assessment of diaphragm force-generating capacity. Additionally, diaphragm histology was performed. In separate studies, in anaesthetised mice, respiratory electromyogram (EMG) activity and inspiratory pressure across a range of behaviours were determined, including assessment of peak inspiratory pressure-generating capacity. NAC treatment did not affect force-generating capacity of the mdx diaphragm. Collagen content and immune cell infiltration were unchanged in mdx + NAC compared with mdx diaphragms. Additionally, there was no significant effect of NAC on breathing, ventilatory responsiveness, inspiratory EMG activity or inspiratory pressure across the range of behaviours from basal conditions to peak system performance. We conclude that chronic NAC treatment has no apparent beneficial effects on respiratory system performance in the mdx mouse model of DMD suggesting limited potential of NAC treatment alone for human DMD., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background & Aims: Abdominal distention results from abdominophrenic dyssynergia (ie, diaphragmatic contraction and abdominal wall relaxation) in patients with disorders of gut-brain interaction. This study aimed to validate a simple biofeedback procedure, guided by abdominothoracic wall motion, for treating abdominal distention., Methods: In this randomized, parallel, placebo-controlled trial, 42 consecutive patients (36 women and 6 men; ages 17-64 years) with meal-triggered visible abdominal distention were recruited. Recordings of abdominal and thoracic wall motion were obtained using inductance plethysmography via adaptable belts. The signal was shown to patients in the biofeedback group, who were taught to mobilize the diaphragm. In contrast, the signal was not shown to the patients in the placebo group, who were given a placebo capsule. Three sessions were performed over a 4-week intervention period, with instructions to perform exercises (biofeedback group) or to take placebo 3 times per day (control group) at home. Outcomes were assessed through response to an offending meal (changes in abdominothoracic electromyographic activity and girth) and clinical symptoms measured using daily scales for 7 days., Results: Patients in the biofeedback group (n = 19) learned to correct abdominophrenic dyssynergia triggered by the offending meal (intercostal activity decreased by a mean ± SE of 82% ± 10%, anterior wall activity increased by a mean ± SE of 97% ± 6%, and increase in girth was a mean ± SE of 108% ± 4% smaller) and experienced improved clinical symptoms (abdominal distention scores decreased by a mean ± SE of 66% ± 5%). These effects were not observed in the placebo group (all, P < .002)., Conclusions: Abdominothoracic wall movements serve as an effective biofeedback signal for correcting abdominophrenic dyssynergia and abdominal distention in patients with disorders of gut-brain interaction. ClincialTrials.gov, Number: NCT04043208., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect of external diaphragmatic pacing (EDP) combined with inspiratory muscle training on respiratory function in post-stroke patients., Methods: Patients with stroke were enrolled from the First Affiliated Hospital of Soochow University in China between 2021 and 2022. The patients were randomized into an EDP treatment group (control group) or an EDP treatment plus inspiratory muscle training group (experimental group). Each therapy was administered once a day for 6 days per week. The peak inspiratory flow (PIF), maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC% ratio, and diaphragm thickness and mobility were measured and compared between the two groups after 4 weeks., Results: After 4 weeks of intervention, respiratory muscle function indicators including PIF (95% CI: 0.21-1.28, p  = 0.008) and MIP (95% CI: 6.92-25.44, p  = 0.001) significantly improved in the experimental group. Diaphragmatic thickness also significantly increased in the experimental group ( p  < 0.05), while diaphragmatic excursion showed no significant difference between the two groups. Additionally, FVC (95% CI: 0.14-1.14, p  = 0.013) and FEV 1 (95% CI: 0.20-1.06, p  = 0.005) demonstrated a significant increase in the experimental group, whereas FEV 1 /FVC% (95% CI: -0.84 to 9.36, p  = 0.099) exhibited no significant group difference., Conclusion: EDP combined with inspiratory muscle training in individuals with stroke provides greater benefits than EDP alone in terms of respiratory function recovery, except for the parameters of diaphragmatic excursion and FEV 1 /FVC%.

Patients receiving mechanical ventilation in the intensive care unit (ICU) frequently develop contractile weakness of the diaphragm. Consequently, they may experience difficulty weaning from mechanical ventilation, which increases mortality and poses a high economic burden. Because of a lack of knowledge regarding the molecular changes in the diaphragm, no treatment is currently available to improve diaphragm contractility. We compared diaphragm biopsies from ventilated ICU patients ( N = 54) to those of non-ICU patients undergoing thoracic surgery ( N = 27). By integrating data from myofiber force measurements, x-ray diffraction experiments, and biochemical assays with clinical data, we found that in myofibers isolated from the diaphragm of ventilated ICU patients, myosin is trapped in an energy-sparing, super-relaxed state, which impairs the binding of myosin to actin during diaphragm contraction. Studies on quadriceps biopsies of ICU patients and on the diaphragm of previously healthy mechanically ventilated rats suggested that the super-relaxed myosins are specific to the diaphragm and not a result of critical illness. Exposing slow- and fast-twitch myofibers isolated from the diaphragm biopsies to small-molecule compounds activating troponin restored contractile force in vitro. These findings support the continued development of drugs that target sarcomere proteins to increase the calcium sensitivity of myofibers for the treatment of ICU-acquired diaphragm weakness.

Diaphragmatic palsy after lung transplantation has been reported infrequently. Given the role of the diaphragm in respiration, the palsy may play a significant role in the post-surgical recovery as well as morbidity and mortality. This review summarises the current literature to better understand diaphragmatic palsy in the post lung-transplant setting among adults. A thorough literature search was conducted through multiple databases and 91 publications were identified that fit the research question. The review aimed to report the burden of this problem, explore different modalities of diagnosis reported, the effect of various clinical factors and treatment modalities, as well as their effects on outcomes. Additionally, it aimed to highlight the variability, limitations of reported data, and the absence of a standardised approach. This review emphasises the crucial need for more dedicated research to better address this clinical challenge., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurological disorder caused by deleterious CAG repeat expansion in the coding region of the ataxin 7 gene (polyQ-ataxin-7). Infantile-onset SCA7 leads to severe clinical manifestation of respiratory distress, but the exact cause of respiratory impairment remains unclear. Using the infantile-SCA7 mouse model, the SCA7266Q/5Q mouse, we examined the impact of pathological polyQ-ataxin-7 on hypoglossal (XII) and phrenic motor units. We identified the transcript profile of the medulla and cervical spinal cord and investigated the XII and phrenic nerves and the neuromuscular junctions in the diaphragm and tongue. SCA7266Q/5Q astrocytes showed significant intranuclear inclusions of ataxin-7 in the XII and putative phrenic motor nuclei. Transcriptomic analysis revealed dysregulation of genes involved in amino acid and neurotransmitter transport and myelination. Additionally, SCA7266Q/5Q mice demonstrated blunted efferent output of the XII nerve and demyelination in both XII and phrenic nerves. Finally, there was an increased number of neuromuscular junction clusters with higher expression of synaptic markers in SCA7266Q/5Q mice compared with WT controls. These preclinical findings elucidate the underlying pathophysiology responsible for impaired glial cell function and death leading to dysphagia, aspiration, and respiratory failure in infantile SCA7.

Background: In mechanically ventilated patients, diaphragm ultrasound can identify diaphragm weakness and predict weaning failure. We evaluated whether a novel operator-independent ultrasound-based medical device allowing continuous monitoring of the diaphragm (CUSdi) could reliably (1) measure diaphragm excursion (EXdi) and peak contraction velocity (PCVdi), (2) predict weaning outcome, and (3) approximate transdiaphragmatic pressure (Pdi)., Methods: In 49 mechanically ventilated patients, CUSdi was recorded during a 30-min spontaneous breathing trial (SBT), and EXdi and PCVdi were measured. In subgroups of patients, standard ultrasound measurement of EXdi and PCVdi was performed (n = 36), and Pdi derived parameters (peak and pressure time product, n = 30) were measured simultaneously., Results: The agreement bias between standard ultrasound and CUSdi for EXdi was 0.1 cm (95% confidence interval -0.7-0.9 cm). The regression of Passing-Bablok indicated a lack of systematic difference between EXdi measured with standard ultrasound and CUSdi, which were positively correlated (Rho = 0.84, p < 0.001). Weaning failure was observed in 54% of patients. One, two and three minutes after the onset of the SBT, EXdi was higher in the weaning success group than in the failure group. Two minutes after the onset of the SBT, an EXdi < 1.1 cm predicted weaning failure with a sensitivity of 0.83, a specificity of 0.68, a positive predictive value of 0.76, and a negative predictive value of 0.24. There was a weak correlation between EXdi and both peak Pdi (r = 0.22, 95% confidence interval 0.15 - 0.28) and pressure time product (r = 0.13, 95% confidence interval 0.06 - 0.20). Similar results were observed with PCVdi., Conclusions: Operator-independent continuous diaphragm monitoring quantifies EXdi reliably and can predict weaning failure with an identified cut-off value of 1.1 cm. Trial registration clinicaltrial.gov, NCT04008875 (submitted 12 April 2019, posted 5 July 2019) and NCT03896048 (submitted 27 March 2019, posted 29 March 2019)., (© 2024. The Author(s).)

Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear., Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting., Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably., Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2024 Li et al.)

To observe of the effect of electrical stimulation at the back-shu acupoint with extrinsic diaphragmatic pacing (EDP) mode on respiratory function and extubation success rate in tracheostomized stroke patients. A total of 200 patients who underwent tracheostomy after a stroke from January 2022 to February 2023 were included in this study. They were divided into 2 groups based on whether electroacupuncture was used: the EDP + electroacupuncture group and the EDP group. We assessed the differences in cough reflex scores and clinical lung infection scores between the 2 groups, and measured levels of blood gas analysis indicators, diaphragmatic function, lung function, maximum inspiratory pressure, and maximum expiratory pressure in both groups. The total effective rate in the EDP + electroacupuncture group was 91.00% (91/100), which was higher than the EDP group's 80.00% (80/100) (P < .05). After treatment, both groups showed a decrease in clinical lung infection scores and cough reflex scores compared to before treatment, with the EDP + electroacupuncture group having lower scores than the EDP group (P < .05). After treatment, the pH value, arterial oxygen pressure, and oxygenation index all increased compared to before treatment, with the EDP + electroacupuncture group showing higher values than the EDP group (P < .05). After treatment, both groups showed a decrease in arterial carbon dioxide pressure compared to before treatment, with the EDP + electroacupuncture group having lower PaCO2 levels than the EDP group (P < .05). After treatment, both groups showed an increase in forced vital capacity as a percentage of predicted value (FVC%), diaphragm thickness, diaphragm mobility, maximum inspiratory pressure, maximum expiratory pressure, forced expiratory volume in the first second as a percentage of predicted value (FEV1%), and diaphragm contraction speed compared to before treatment. Additionally, the EDP + electroacupuncture group had higher values in these parameters compared to the EDP group (P < .05). The EDP + electroacupuncture group had a shorter average extubation time and a higher extubation success rate compared to the EDP group (P < .05). The combination of EDP mode and electroacupuncture at the back-shu acupoint appears to be effective in improving lung function and diaphragmatic function in tracheostomized stroke patients. It also leads to a shorter extubation time and higher extubation success rates., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pulmonary disorders affect 40%-80% of individuals with obesity. Respiratory muscle dysfunction is linked to these conditions; however, its pathophysiology remains largely undefined. Mice subjected to diet-induced obesity (DIO) develop diaphragm muscle weakness. Increased intradiaphragmatic adiposity and extracellular matrix (ECM) content correlate with reductions in contractile force. Thrombospondin-1 (THBS1) is an obesity-associated matricellular protein linked with muscular damage in genetic myopathies. THBS1 induces proliferation of fibro-adipogenic progenitors (FAPs) - mesenchymal cells that differentiate into adipocytes and fibroblasts. We hypothesized that THBS1 drives FAP-mediated diaphragm remodeling and contractile dysfunction in DIO. We tested this by comparing the effects of dietary challenge on diaphragms of wild-type (WT) and Thbs1-knockout (Thbs1-/-) mice. Bulk and single-cell transcriptomics demonstrated DIO-induced stromal expansion in WT diaphragms. Diaphragm FAPs displayed upregulation of ECM and TGF-β-related expression signatures and augmentation of a Thy1-expressing subpopulation previously linked to type 2 diabetes. Despite similar weight gain, Thbs1-/- mice were protected from these transcriptomic changes and from obesity-induced increases in diaphragm adiposity and ECM deposition. Unlike WT controls, Thbs1-/- diaphragms maintained normal contractile force and motion after DIO challenge. THBS1 is therefore a necessary mediator of diaphragm stromal remodeling and contractile dysfunction in overnutrition and a potential therapeutic target in obesity-associated respiratory dysfunction.