Cervical spinal cord hemisection impacts sigh and the respiratory reset in male rats.

Cervical spinal cord injury impacts ventilatory and non-ventilatory functions of the diaphragm muscle (DIAm) and contributes to clinical morbidity and mortality in the afflicted population. Periodically, integrated brainstem neural circuit activity drives the DIAm to generate a markedly augmented effort or sigh-which plays an important role in preventing atelectasis and thus maintaining lung function. Across species, the general pattern of DIAm efforts during a normal sigh is variable in amplitude and the extent of post-sigh "apnea" (i.e., the post-sigh inter-breath interval). This post-sigh inter-breath interval acts as a respiratory reset, following the interruption of regular respiratory rhythm by sigh. We examined the impact of upper cervical (C2 ) spinal cord hemisection (C2 SH) on the transdiaphragmatic pressure (Pdi ) generated during sighs and the post-sigh respiratory reset in rats. Sighs were identified in Pdi traces by their characteristic biphasic pattern. We found that C2 SH results in a reduction of Pdi during both eupnea and sighs, and a decrease in the immediate post-sigh breath interval. These results are consistent with partial removal of descending excitatory synaptic inputs to phrenic motor neurons that results from C2 SH. Following cervical spinal cord injury, a reduction in the amplitude of Pdi during sighs may compromise the maintenance of normal lung function.

Maximum abdominal excursion assessment using an abdominal excursion measuring device: Reliability and validity of a new device for simple and quantitative assessment of respiratory function.

This study aimed to verify the reliability and validity of abdominal expansion and respiratory function measurements. Forty healthy adult males underwent lung capacity, effort lung capacity, respiratory muscle strength, cough strength, diaphragm ultrasound, and abdominal expansion measurements. Abdominal expansion was measured using a device developed to accurately evaluate abdominal movements and calculate maximum abdominal expansion on the ventral side (AE-max: the difference between maximal abdominal contraction at the same time as maximal-effort expiration and maximal abdominal expansion at the same time as maximal-effort inspiration). Intra- and inter-rater reliabilities of the AE-max measurements were examined, the paired t-test was used for assessing the ratios of the expansion and contraction displacement components in AE-max, and regression analysis was used to obtain equations for predicting maximum inspiratory pressure (MIP) based on AE-max. Both intra- and inter-rater reliabilities were high. Criterion-related validity showed that AE-max was associated with all respiratory function parameters, especially MIP, and a high percentage of expansion displacement. Regression analysis showed that AE-max was significantly associated with MIP. Based on its association with MIP, the large proportion of expansion displacement in AE-max, and the results of the multiple regression analysis, we conclude that AE-max is a helpful measure for estimating MIP.

Trans-spinal magnetic stimulation induces co-activation of the diaphragm and biceps in healthy subjects.

The present study was designed to examine the effect of trans-spinal magnetic stimulation on bilateral respiratory and forelimb muscles in healthy subjects. Two wings of a figure-of-eight magnetic coil were placed on the dorsal vertebrae, from the fifth cervical to the second thoracic dorsal vertebra with a center at the seventh cervical vertebra. The surface electromyograms of bilateral diaphragm and biceps were recorded in response to trans-spinal magnetic stimulation with 20%-100% maximum output of the stimulatory device in male (n = 12) and female participants (n = 8). Trans-spinal magnetic stimulation can induce a co-activation of bilateral diaphragm and biceps when the stimulation intensity is above 60%. The onset latency was comparable between the left and right sides of the muscles, suggesting bilateral muscles could be simultaneously activated by trans-spinal magnetic stimulation. In addition, the intensity-response curve of the biceps was shifted upward compared with that of the diaphragm in males, indicating that the responsiveness of the biceps was greater than that of the diaphragm. This study demonstrated the feasibility of utilizing trans-spinal magnetic stimulation to co-activate the bilateral diaphragm and biceps. We proposed that this stimulatory configuration can be an efficient approach to activate both respiratory and forelimb muscles.

Modulatory effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity following cervical spinal cord contusion in the rat.

BACKGROUND CONTEXT: Magnetic stimulation can noninvasively modulate the neuronal excitability through different stimulatory patterns. PURPOSE: The present study hypothesized that trans-spinal magnetic stimulation with intermittent theta burst stimulatory pattern can modulate respiratory motor outputs in a pre-clinical rat model of cervical spinal cord injury. STUDY DESIGN: In vivo animal study. METHODS: The effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity was assessed in adult rats with unilateral cervical spinal cord contusion at 2 weeks postinjury. RESULTS: The results demonstrated that unilateral cervical spinal cord contusion significantly attenuated the inspiratory activity and motor evoked potential of the diaphragm. Trans-spinal magnetic intermittent theta burst stimulation significantly increased the inspiratory activity of the diaphragm in cervical spinal cord contused rats. Inspiratory bursting was also recruited by trans-spinal magnetic intermittent theta burst stimulation in the rats without diaphragmatic activity after cervical spinal cord injury. In addition, trans-spinal magnetic intermittent theta burst stimulation is associated with increases in oxygen consumption and carbon dioxide production. CONCLUSIONS: These results suggest that trans-spinal magnetic intermittent theta burst stimulation can induce respiratory neuroplasticity. CLINICAL SIGNIFICANCE: We propose that trans-spinal theta burst magnetic stimulation may be considered a potential rehabilitative strategy for improving the respiratory activity after cervical spinal cord injury. This will require future clinical study.

Diaphragmatic electromyography in infants: an overview of possible clinical applications.

Preterm infants often experience breathing instability and a hampered lung function. Therefore, these infants receive cardiorespiratory monitoring and respiratory support. However, the current respiratory monitoring technique may be unreliable for especially obstructive apnea detection and classification and it does not provide insight in breathing effort. The latter makes the selection of the adequate mode and level of respiratory support difficult. Electromyography of the diaphragm (dEMG) has the potential of monitoring heart rate (HR) and respiratory rate (RR), and it provides additional information on breathing effort. This review summarizes the available evidence on the clinical potential of dEMG to provide cardiorespiratory monitoring, to synchronize patient-ventilator interaction, and to optimize the mode and level of respiratory support in the individual newborn infant. We also try to identify gaps in knowledge and future developments needed to ensure widespread implementation in clinical practice. IMPACT: Preterm infants require cardiorespiratory monitoring and respiratory support due to breathing instability and a hampered lung function. The current respiratory monitoring technique may provide unreliable measurements and does not provide insight in breathing effort, which makes the selection of the optimal respiratory support settings difficult. Measuring diaphragm activity could improve cardiorespiratory monitoring by providing insight in breathing effort and could potentially have an important role in individualizing respiratory support in newborn infants.

Non-Invasive Assessment of Abdominal/Diaphragmatic and Thoracic/Intercostal Spontaneous Breathing Contributions.

(1) Background: Technically, a simple, inexpensive, and non-invasive method of ascertaining volume changes in thoracic and abdominal cavities are required to expedite the development and validation of pulmonary mechanics models. Clinically, this measure enables the real-time monitoring of muscular recruitment patterns and breathing effort. Thus, it has the potential, for example, to help differentiate between respiratory disease and dysfunctional breathing, which otherwise can present with similar symptoms such as breath rate. Current automatic methods of measuring chest expansion are invasive, intrusive, and/or difficult to conduct in conjunction with pulmonary function testing (spontaneous breathing pressure and flow measurements). (2) Methods: A tape measure and rotary encoder band system developed by the authors was used to directly measure changes in thoracic and abdominal circumferences without the calibration required for analogous strain-gauge-based or image processing solutions. (3) Results: Using scaling factors from the literature allowed for the conversion of thoracic and abdominal motion to lung volume, combining motion measurements correlated to flow-based measured tidal volume (normalised by subject weight) with R2 = 0.79 in data from 29 healthy adult subjects during panting, normal, and deep breathing at 0 cmH2O (ZEEP), 4 cmH2O, and 8 cmH2O PEEP (positive end-expiratory pressure). However, the correlation for individual subjects is substantially higher, indicating size and other physiological differences should be accounted for in scaling. The pattern of abdominal and chest expansion was captured, allowing for the analysis of muscular recruitment patterns over different breathing modes and the differentiation of active and passive modes. (4) Conclusions: The method and measuring device(s) enable the validation of patient-specific lung mechanics models and accurately elucidate diaphragmatic-driven volume changes due to intercostal/chest-wall muscular recruitment and elastic recoil.

[Research advances on neurally adjusted ventilatory assist].

Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to diverse modes of assisted ventilation. Conventional mechanical ventilators depend on flow sensors and pneumatic pressure and controllers to complete the respiratory cycle. Neurally adjusted ventilatory assist (NAVA) is a new form of assisted ventilation in recent years, which monitors the electrical activity of the diaphragm (EAdi) to provide an appropriately level of pressure support. And EAdi is the best available signal to sense central respiratory drive and trigger ventilatory assist. Unlike other ventilation modes, NAVA breathing instructions come from the center. Therefore, NAVA have the synchronous nature of the breaths and the patient-adjusted nature of the support. Compared with traditional ventilation mode, NAVA can efficiently unload respiratory muscles, relieve the risk of ventilator-induced lung injury (VILI), improve patient-ventilator coordination, enhance gas exchange, increase the success rate of weaning, etc. This article reviews the research progress of NAVA in order to provide theoretical guidance for clinical applications.

Diaphragm and core stabilization exercises in low back pain: A narrative review.

INTRODUCTION: Core stabilization is a vital concept in clinical rehabilitation (including low back pain rehabilitation) and competitive athletic training. The core comprises of a complex network of hip, trunk and neck muscles including the diaphragm. AIMS: The paper aims to discuss the role of the diaphragm in core stability, summarize current evidence and put forth ideal core training strategies involving the diaphragm. METHOD: Narrative review RESULTS: The diaphragm has a dual role of respiration and postural control. Evidence suggests that current core stability exercises for low back pain are superior than minimal or no treatment, however, no more beneficial than general exercises and/or manual therapy. There appears to be a higher focus on the transversus abdominis and multifidi muscles and minimal attention to the diaphragm. We propose that any form of core stabilization exercises for low back pain rehabilitation should consider the diaphragm. Core stabilization program could commence with facilitation of normal breathing patterns and progressive systematic restoration of the postural control role of the diaphragm muscle. CONCLUSION: The role of the diaphragm is often overlooked in both research and practice. Attention to the diaphragm may improve the effectiveness of core stability exercise in low back pain rehabilitation.

Neuromotor control of spontaneous quiet breathing in awake rats evaluated by assessments of diaphragm EMG stationarity.

The neuromotor control of the diaphragm muscle (DIAm) is dynamic. The activity of the DIAm can be recorded via electromyography (EMG), which represents the temporal summation of motor unit action potentials. Our goal in the present study was to investigate DIAm neuromotor control during quiet spontaneous breathing (eupnea) in awake rats by evaluating DIAm EMG at specific temporal locations defined by motor unit recruitment and derecruitment. We evaluated the nonstationarity of DIAm EMG activity to identify DIAm motor unit recruitment and derecruitment durations. Combined with assessments of root mean square (RMS) and sum of squares (SS) EMG, the durations of these phases provide physiological information about the temporal aspects of motor control. During eupnea in awake rats (n = 10), the duration of motor unit recruitment comprised 61 ± 19 ms of the onset-to-peak duration (214 ± 62 ms) of the DIAm RMS EMG. The peak-to-offset duration of DIAm EMG activity was 453 ± 96 ms, with a terminating period of derecruitment of 161 ± 44 ms. The burst duration was 673 ± 128 ms. Both the RMS EMG amplitude and the SS EMG were higher at the completion of motor unit recruitment than at the start of motor unit derecruitment, suggesting that offset discharge rates were lower than onset discharge rates. Our analyses provide novel insights into the time domain aspects of DIAm neuromotor control and allow indirect estimates of the contribution of recruitment and frequency to RMS EMG amplitude during eupnea in awake rats.NEW & NOTEWORTHY We characterized three phases of neuromotor control-motor unit recruitment, sustained activity, and derecruitment-based on statistical assessments of stationarity of the diaphragm muscle (DIAm) EMG activity in awake rats. Our findings may allow indirect estimates of the contribution of motor unit recruitment and frequency coding toward generating force and provide novel insights about the temporal aspects of DIAm neuromotor control and descending respiratory drive in unanesthetized animals.

Cardiorespiratory monitoring with a wireless and nonadhesive belt measuring diaphragm activity in preterm and term infants: A multicenter non-inferiority study.

INTRODUCTION: We determined if the heart rate (HR) monitoring performance of a wireless and nonadhesive belt is non-inferior compared to standard electrocardiography (ECG). Secondary objective was to explore the belt's respiratory rate (RR) monitoring performance compared to chest impedance (CI). METHOD: In this multicenter non-inferiority trial, preterm and term infants were simultaneously monitored with the belt and conventional ECG/CI for 24 h. HR monitoring performance was estimated with the HR difference and ability to detect cardiac events compared to the ECG, and the incidence of HR-data loss per second. These estimations were statistically compared to prespecified margins to confirm equivalence/non-inferiority. Exploratory RR analyses estimated the RR trend difference and ability to detect apnea/tachypnea compared to CI, and the incidence of RR-data loss per second. RESULTS: Thirty-nine infants were included. HR monitoring with the belt was non-inferior to the ECG with a mean HR difference of 0.03 beats per minute (bpm) (standard error [SE] = 0.02) (95% limits of agreement [LoA]: [-5 to 5] bpm) (p < 0.001). Second, sensitivity and positive predictive value (PPV) for cardiac event detection were 94.0% (SE = 0.5%) and 92.6% (SE = 0.6%), respectively (p ≤ 0.001). Third, the incidence of HR-data loss was 2.1% (SE = 0.4%) per second (p < 0.05). The exploratory analyses of RR showed moderate trend agreement with a mean RR-difference of 3.7 breaths/min (SE = 0.8) (LoA: [-12 to 19] breaths/min), but low sensitivities and PPV's for apnea/tachypnea detection. The incidence of RR-data loss was 2.2% (SE = 0.4%) per second. CONCLUSION: The nonadhesive, wireless belt showed non-inferior HR monitoring and a moderate agreement in RR trend compared to ECG/CI. Future research on apnea/tachypnea detection is required.

Chloroquine impairs maximal transdiaphragmatic pressure generation in old mice.

Aging results in increased neuromuscular transmission failure and denervation of the diaphragm muscle, as well as decreased force generation across a range of motor behaviors. Increased risk for respiratory complications in old age is a major health problem. Aging impairs autophagy, a tightly regulated multistep process responsible for clearing misfolded or aggregated proteins and damaged organelles. In motor neurons, aging-related autophagy impairment may contribute to deficits in neurotransmission, subsequent muscle atrophy, and loss of muscle force. Chloroquine is commonly used to inhibit autophagy. We hypothesized that chloroquine decreases transdiaphragmatic pressure (Pdi) in mice. Old mice (16-28 mo old; n = 26) were randomly allocated to receive intraperitoneal chloroquine (50 mg/kg) or vehicle 4 h before measuring Pdi during eupnea, hypoxia (10% O2)-hypercapnia (5% CO2) exposure, spontaneous deep breaths ("sighs"), and maximal activation elicited by bilateral phrenic nerve stimulation (Pdimax). Pdi amplitude and ventilatory parameters across experimental groups and behaviors were evaluated using a mixed linear model. There were no differences in Pdi amplitude across treatments during eupnea (∼8 cm H2O), hypoxia-hypercapnia (∼10 cm H2O), or sigh (∼36 cm H2O), consistent with prior studies documenting a lack of aging effects on ventilatory behaviors. In vehicle and chloroquine-treated mice, average Pdimax was 61 and 46 cm H2O, respectively. Chloroquine decreased Pdimax by 24% compared to vehicle (P < 0.05). There were no sex or age effects on Pdi in older mice. The observed decrease in Pdimax suggests aging-related susceptibility to impairments in autophagy, consistent with the effects of chloroquine on this important homeostatic process.NEW & NOTEWORTHY Recent findings suggest that autophagy plays a role in the development of aging-related neuromuscular dysfunction; however, the contribution of autophagy impairment to the maintenance of diaphragm force generation in old age is unknown. This study shows that in old mice, chloroquine administration decreases maximal transdiaphragmatic pressure generation. These chloroquine effects suggest a susceptibility to impairments in autophagy in old age.

Volitional inspiration is mediated by two independent output channels in the primary motor cortex.

The diaphragm is a multifunctional muscle that mediates both autonomic and volitional inspiration. It is critically involved in vocalization, postural stability, and expulsive core-trunk functions, such as coughing, hiccups, and vomiting. In macaque monkeys, we used retrograde transneuronal transport of rabies virus injected into the left hemidiaphragm to identify cortical neurons that have multisynaptic connections with phrenic motoneurons. Our research demonstrates that representation of the diaphragm in the primary motor cortex (M1) is split into two spatially separate and independent sites. No cortico-cortical connections are known to exist between these two sites. One site is located dorsal to the arm representation within the central sulcus and the second site is lateral to the arm. The dual representation of the diaphragm warrants a revision to the somatotopic map of M1. The dorsal diaphragm representation overlaps with trunk and axial musculature. It is ideally situated to coordinate with these muscles during volitional inspiration and in producing intra-abdominal pressure gradients. The lateral site overlaps the origin of M1 projections to a laryngeal muscle, the cricothyroid. This observation suggests that the coordinated control of laryngeal muscles and the diaphragm during vocalization may be achieved, in part, by co-localization of their representations in M1. The neural organization of the two diaphragm sites underlies a new perspective for interpreting functional imaging studies of respiration and/or vocalization. Furthermore, our results provide novel evidence supporting the concept that overlapping output channels within M1 are a prerequisite for the formation of muscle synergies underlying fine motor control.

Recording of a left ventricle assist device electrical current with a neurally adjusted ventilation assist (NAVA) catheter: a small case series.

BACKGROUND: Neurally Adjusted Ventilatory Assist (NAVA) is an adaptive ventilation mode that recognizes electromyographic diaphragmatic activation as a sensory input to control the ventilator. NAVA may be of interest in prolonged mechanical ventilation and weaning, as it provides effort-adapted support, improves patient-ventilator synchronization, and allows additional monitoring of neuromuscular function and drive. Ventricular assist devices (VAD), especially for the left ventricle (LVAD), are increasingly entering clinical practice, and intensivists are faced with distinct challenges such as the interaction between the system and other measures of organ support. CASE PRESENTATION: We present two cases in which a NAVA mode was intended to support ventilator weaning in patients with recent LVAD implantation (HeartMate III®). However, in these patients, the electrical activity of the diaphragm (Edi) could not be used to control the ventilator, because the LVAD current detected by the catheter superposed the Edi current, making usage of this mode impossible. DISCUSSION/CONCLUSIONS: An implanted LVAD can render the NAVA signal unusable for ventilatory support because the LVAD signal can interfere with the recording of electromyographic activation of the diaphragm. Therefore, patients with implanted LVAD may need other modes of ventilation than NAVA for advanced weaning strategies.

[Morphological aspects of diaphragm dysfunction in COVID-19-associated pneumonia]. / Morfologicheskie aspekty disfunktsii diafragmy pri COVID-19-assotsiirovannoi pnevmonii.

OBJECTIVE: To assess morphological changes in the diaphragm and phrenic nerve in patients who died from COVID-19. MATERIAL AND METHODS: In a case-control study, an analysis was made of autopsy material of the diaphragm and phrenic nerve of those who died from COVID-19 infection complicated by SARS-CoV-2-associated pneumonia, confirmed in vivo by the presence of SARS-CoV-2 RNA (Group 1, n=12), and those who died with a diagnosis of acute cerebrovascular accident of the ischemic type without parenchymal respiratory failure (Group 2, n=3). RESULTS: The main histopathological features in the diaphragm of the 1st group were the edema of the pericellular spaces of muscle fibers, edema of perivascular spaces, diapedese hemorrhages, plethora in arteriolas, in most veins and capillaries, red blood clots were revealed; in the diaphragmatic nerve - swelling of the perineral space, severe edema around the nerve fibers inside the nerve trunk. In the diaphragm of group 2, edema of pericellular spaces of muscle fibers and edema of perivascular spaces were less pronounced (p<0.001), hemorrhages were not determined; in the diaphragmatic nerve, moderate edema of the perineral space, mild swelling inside the nerve trunk around the nerve fibers was revealed (p<0.001). The glycogen content in the muscle cells of group 1 is significantly lower compared to group 2 (p<0.001). CONCLUSION: The study confirms the characteristic pathological picture of organ damage in COVID-19. However, the leading pathological mechanism of organ damage requires further investigation.

Thoracic Mobilization and Respiratory Muscle Endurance Training Improve Diaphragm Thickness and Respiratory Function in Patients with a History of COVID-19.

Background and Objectives: Common problems in people with COVID-19 include decreased respiratory strength and function. We investigated the effects of thoracic mobilization and respiratory muscle endurance training (TMRT) and lower limb ergometer (LE) training on diaphragm thickness and respiratory function in patients with a history of COVID-19. Materials and Methods: In total, 30 patients were randomly divided into a TMRT training group and an LE training group. The TMRT group performed thoracic mobilization and respiratory muscle endurance training for 30 min three times a week for 8 weeks. The LE group performed lower limb ergometer training for 30 min three times a week for 8 weeks. The participants' diaphragm thickness was measured via rehabilitative ultrasound image (RUSI) and a respiratory function test was conducted using a MicroQuark spirometer. These parameters were measured before the intervention and 8 weeks after the intervention. Results: There was a significant difference (p < 0.05) between the results obtained before and after training in both groups. Right diaphragm thickness at rest, diaphragm thickness during contraction, and respiratory function were significantly more improved in the TMRT group than in the LE group (p < 0.05). Conclusions: In this study, we confirmed the effects of TMRT training on diaphragm thickness and respiratory function in patients with a history of COVID-19.

Proof of concept of an accelerometer as a trigger for unilateral diaphragmatic pacing: a porcine model.

BACKGROUND: Unilateral diaphragmatic paralysis in patients with univentricular heart is a known complication after pediatric cardiac surgery. Because diaphragmatic excursion has a significant influence on perfusion of the pulmonary arteries and hemodynamics in these patients, unilateral loss of function leads to multiple complications. The current treatment of choice, diaphragmatic plication, does not lead to a full return of function. A unilateral diaphragmatic pacemaker has shown potential as a new treatment option. In this study, we investigated an accelerometer as a trigger for a unilateral diaphragm pacemaker (closed-loop system). METHODS: Seven pigs (mean weight 20.7 ± 2.25 kg) each were implanted with a customized accelerometer on the right diaphragmatic dome. Accelerometer recordings (mV) of the diaphragmatic excursion of the right diaphragm were compared with findings using established methods (fluoroscopy [mm]; ultrasound, M-mode [cm]). For detection of the amplitude of diaphragmatic excursions, the diaphragm was stimulated with increasing amperage by a cuff electrode implanted around the right phrenic nerve. RESULTS: Results with the different techniques for measuring diaphragmatic excursions showed correlations between accelerometer and fluoroscopy values (correlation coefficient 0.800, P < 0.001), accelerometer and ultrasound values (0.883, P < 0.001), and fluoroscopy and ultrasound values (0.816, P < 0.001). CONCLUSION: The accelerometer is a valid method for detecting diaphragmatic excursion and can be used as a trigger for a unilateral diaphragmatic pacemaker.

Size-dependent differences in mitochondrial volume density in phrenic motor neurons.

Neuromotor control of diaphragm muscle (DIAm) motor units is dependent on an orderly size-dependent recruitment of phrenic motor neurons (PhMNs). Slow (type S) and fast, fatigue resistant (type FR) DIAm motor units, which are frequently recruited to sustain ventilation, comprise smaller PhMNs that innervate type I and IIa DIAm fibers. More fatigable fast (type FF) motor units, which are infrequently recruited for higher force, expulsive behaviors, comprise larger PhMNs that innervate more type IIx/IIb DIAm fibers. We hypothesize that due to the more frequent activation and thus higher energy demand of type S and FR motor units, the mitochondrial volume density (MVD) of smaller PhMNs is greater compared with larger PhMNs. In eight adult (6 mo old) Fischer 344 rats, PhMNs were identified via intrapleural injection of Alexa488-conjugated cholera toxin B (CTB). Following retrograde CTB labeling, mitochondria in PhMNs were labeled by transdural infusion of MitoTracker Red. PhMNs and mitochondria were imaged using multichannel confocal microscopy using a ×60 oil objective. Following optical sectioning and three-dimensional (3-D) rendering, PhMNs and mitochondria were analyzed volumetrically using Nikon Elements software. Analysis of MVD in somal and dendritic compartments was stratified by PhMN somal surface area. Smaller PhMNs (likely S and FR units) had greater somal MVDs compared with larger PhMNs (likely FF units). By contrast, proximal dendrites or larger PhMNs had higher MVD compared with dendrites of smaller PhMNs. We conclude that more active smaller PhMNs have a higher mitochondrial volume density to support their higher energy demand in sustaining ventilation.NEW & NOTEWORTHY Type S and FR motor units, comprising smaller phrenic motor neurons (PhMNs) are regularly activated to perform indefatigable ventilatory requirements. By contrast, type FF motor units, comprising larger PhMNs, are infrequently activated to perform expulsive straining and airway defense maneuvers. This difference in activation history is mirrored in the mitochondrial volume density (MVD), with smaller PhMNs having higher MVD than larger PhMNs. In proximal dendrites, this trend was reversed, with larger PhMNs having higher MVD than smaller PhMNs, likely due to the maintenance requirements for the larger dendritic arbor of FF PhMNs.

Diaphragmatic ultrasonography in patients with IPF: Is diaphragmatic structure and mobility related to fibrosis severity and pulmonary functional changes?

Introduction: There is evidence to suggest that dyspnea and impaired exercise capacity are associated with respiratory muscle dysfunction in idiopathic pulmonary fibrosis (IPF) patients. We aimed to evaluate the functions of the diaphragm with ultrasonography (US) and to determine the correlation of the data obtained with the pulmonary function parameters of the patients, exercise capacity, and the extent of fibrosis radiologically. Materials and Methods: Diaphragmatic mobility, thickness, and thickening fraction (TF) were measured by ultrasonography in IPF patients and the control group. The correlation between these measurements, pulmonary function tests (PFT), six-minute walking test (6MWT), mMRC score, and total fibrosis score (TFS) was evaluated. Result: Forty-one IPF patients and twenty-one healthy volunteers were included in the study. No difference was found between the patient and control groups in diaphragmatic mobility during quiet breathing (QB) on ultrasound (2.35 cm and 2.56 cm; p= 0.29). Diaphragmatic mobility during deep breathing (DB) was found to be lower in the patient group when compared to the control group (5.02 cm and 7.66 cm; p<0.0001). Diaphragmatic thickness was found to be higher during QB and DB in IPF patients (0.33 cm and 0.31 cm, p= 0.043; 0.24 cm and 0.22 cm, p= 0.045). No difference was found between the two groups in terms of thickening fraction (39.37%, 44.16%; p= 0.49). No significant correlation was found between US measurements and PFT, 6MWT, mMRC score, and TFS in IPF patients (p> 0.05). Conclusions: The functions of the diaphragm do not appear to be affected in patients with mild-to-moderate restrictive IPF. This study showed that there was no relationship between diaphragmatic functions and respiratory function parameters and the extent of fibrosis. Further studies, including advanced stages of the disease, are needed to understand the changes in diaphragmatic functions in IPF and to determine whether this change is associated with respiratory function parameters and the extent of fibrosis.

Reference values of diaphragmatic dimensions in healthy children aged 0-8 years.

Diaphragmatic thickness (Tdi) and diaphragm thickening fraction (dTF) are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children are scarce. We determined reference values of Tdi and dTF using ultrasound in healthy children aged 0-8 years old and assessed their reproducibility. In a prospective, observational cohort, Tdi and dTF were measured on ultrasound images across four age groups comprising at least 30 children per group: group 1 (0-6 months), group 2 (7 months-1 year), group 3 (2-4 years) and group 4 (5-8 years). Ultrasound images of 137 healthy children were included. Mean Tdi at inspiration was 2.07 (SD 0.40), 2.09 (SD 0.40), 1.69 (SD 0.30) and 1.72 (SD 0.30) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at expiration was 1.64 (SD 0.30), 1.67 (SD 0.30), 1.38 (SD 0.20) and 1.42 (SD 0.20) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at inspiration and mean Tdi at expiration for groups 1 and 2 were significantly greater than those for groups 3 and 4 (both p < 0.001). Mean dTF was 25.4% (SD 10.4), 25.2% (SD 8.3), 22.8% (SD 10.9) and 21.3% (SD 7.1) for group 1, 2, 3 and 4, respectively. The intraclass correlation coefficients (ICC) representing the level of inter-rater reliability between two examiners performing the ultrasounds was 0.996 (95% CI 0.982-0.999). ICC of the inter-rater reliability between the raters in 11 paired assessments was 0.989 (95% CI 0.973-0.995).   Conclusion: Ultrasound measurements of Tdi and dTF were highly reproducible in healthy children aged 0-8 years.    Trial registration: ClinicalTrials.gov identifier (NCT number): NCT04589910. What is Known: • Diaphragmatic thickness and diaphragm thickening fraction are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children to compare these with are scarce. What is New: • We determined normal values of diaphragmatic thickness and diaphragm thickening fraction using ultrasound in 137 healthy children aged 0-8 years old. The diaphragmatic thickness of infants up to 1 year old was significantly greater than that of children from 2 to 8 years old. Diaphragmatic thickness decreased with an increase in body surface area. These normal values in healthy children can be used to assess changes in respiratory muscle thickness in mechanically ventilated children.