Mucopolysaccharidosis (MPS IIIA) mice have increased lung compliance and airway resistance, decreased diaphragm strength, and no change in alveolar structure.

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease.NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.

Ultrasonographic Assessment of Diaphragm Function to Predict Need for Mechanical Ventilation and its Liberation in Patients with Neuromuscular Disorders: An Observational Cohort Pilot Study.

BACKGROUND: Management of assisted ventilation and determining the optimal timing for discontinuation presents a significant clinical obstacle in patients affected by neuromuscular (NM) diseases. This study aimed to evaluate the efficacy of ultrasound in appraising diaphragmatic function for predicting the necessity of intubation and determining the opportune moment to discontinue mechanical ventilation (MV) in patients with NM disorders. METHODS: The study was conducted in adult patients with NM diseases requiring inpatient care in the high-dependency neurology ward and the intensive care unit. Ultrasonographic assessment of diaphragmatic excursion (DE) and diaphragmatic thickness fraction (DTF) was conducted at the patient's bedside every 48 h for ventilated patients and every 72 h for nonventilated patients until they were weaned from the ventilator or discharged home. Qualitative data are expressed as percentages or numbers, and quantitative data are represented as mean ± standard deviation. Unpaired t-tests were employed to compare continuous variables, and χ2 tests were used for categorical variables. Contingency table analysis was used to compute relative risks in comparing the baseline DE and DTF with the sequential changes in these values. RESULTS: In cases in which the baseline left DE measured less than 1 cm, the relative risk for the requirement of ventilation was 2.5 times higher, with a confidence interval of 0.62-0.99 (P = 0.19). Notably, a bilateral reduction in DE within the initial 48 h of admission was identified as predictive of need for intubation. When comparing ventilated and nonventilated patients, it was observed that the mean DE values for the left and right sides in ventilated patients (0.74 and 0.79) were significantly lower than those in nonventilated patients (1.3 and 1.66), with corresponding P values of 0.05 and 0.01, respectively. Furthermore, a decline in right DE by more than 50% within 72 h of admission presented a relative risk of 3.3 for the necessity of ventilation, with a confidence interval of 1.29-8.59 (P = 0.01). Duration of ventilation ranged from 2 to 45 days, with an average of 13.14 days, whereas the mean ventilator-free days recorded was 13.57. Notably, a sequential increase in bilateral DE correlated with an extended duration of ventilator-free days. CONCLUSIONS: The presence of a baseline left DE of less than 1 cm, a consecutive decrease in DE measurements within 48 h, and a comparative reduction in right DE of more than 50% within the initial 3 days are indicators associated with the requirement for MV in patients with NM disease. Furthermore, the upward trajectory of DE in mechanically ventilated patients is linked to an increased number of days free from ventilator support, suggesting its potential to forecast earlier weaning.

Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS.

Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea.This prospective case-control study was registered under the trial registration number NCT04854863 April, 22 2021.

MRI-assessed diaphragmatic function can predict frequent acute exacerbation of COPD: a prospective observational study based on telehealth-based monitoring system.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have considerably high mortality and re-hospitalisation rate. Diaphragmatic dysfunction (DD) is common in COPD patients. However, whether diaphragmatic dysfunction is related to acute exacerbation is yet to be elucidated. This study aimed to evaluate the diaphragm function by magnetic resonance imaging (MRI) in COPD patients and assess whether the impact of DD may help predict AECOPD. METHODS: 20 healthy adult volunteers and 80 COPD patients were enrolled. The diaphragms function parameters were accessed by MRI. Patients were guided to start self-management by the Telehealth-based monitoring system following the enrolment. Events of acute exacerbation of COPD were recorded by the system and confirmed by healthcare providers. Binary univariate and multivariate logistic regression analyses were performed to investigate the factors associated with the frequency of AECOPD. Receiver operating characteristic (ROC) curves were further used to assess the value of prediction indexes. RESULTS: Fifty-nine COPD patients completed a one-year follow-up based on the Telehealth-based monitoring system. The clinical outcomes showed that the diaphragm function parameters at the end of maximal breathing were lower in the COPD group than in the healthy control group (P < 0.05). ANOVA showed significant differences among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages for diaphragm function parameters, including chest wall motion, lung area, upper-lower diameter, and the diaphragm thickening fraction at the end of maximal breathing (P < 0.05). Moreover, significant differences in diaphragm function parameters were observed between patients with infrequent AECOPD (n = 28) and frequent AECOPD (n = 31) based on the frequency of AECOPD (P < 0.05). The diaphragm thickening fraction and the chest wall motion were associated with AECOPD after adjusting for age, sex, BMI, and lung functions, and the combination of predictions showed better accuracy in predicting the frequency of AECOPD. CONCLUSIONS: In COPD patients, diaphragm function parameters correlate with the severity of airflow limitation. The diaphragm thickening fraction and the chest wall motion were associated with the frequency of AECOPD and can predict it.

[A preliminary study on the evaluation of diaphragm function by ultrasound in patients with invasive mechanical ventilation].

Objectives: To study the feasibility of using ultrasound to evaluate diaphragm function in patients with invasive mechanical ventilation. Methods: From March to December 2017, 40 adult patients with acute respiratory distress syndrome who were admitted to the Department of Critical Care Medicine, Xiangya Hospital, Central South University for more than 48 hours were included. Diaphragmatic excursion and thickness of bilateral anterior, middle and posterior parts were measured by ultrasound for 5 consecutive days. Results: (1) Compared with the diaphragmatic excursion of the right [anterior: (11.05±3.04) mm; middle: (12.08±2.71) mm; posterior: (11.51±3.33) mm] and left [anterior: (13.63±7.52) mm; middle: (15.44±7.52) mm; posterior: (14.76±6.93) mm] sides on day 1, the diaphragmatic excursion of the right [anterior: (8.90±3.65) mm; middle: (10.02±4.24) mm; posterior: (10.25±4.38) mm] and left [anterior: (9.82±1.96) mm; middle: (11.60±1.13) mm; posterior: (11.52±1.98) mm] sides decreased significantly on day 3 (P<0.05). Bilateral anterior, middle and posterior diaphragmatic excursion recovered on day 5, and was higher than the baseline levels on day 1, with the left middle and posterior diaphragmatic excursion changing most significantly. (2) Compared with day 1, 2, 3, the thickening fraction of bilateral anterior, middle and posterior diaphragm were significantly decreased on day 4, with the left middle part [day 1: (33.87±14.34)%; day 2: (37.26±13.91)%; day 3: (30.56±14.27)%; day 4: (15.53±5.68)%] and the left posterior part [day 1: (35.50±15.69)%; day 2: (39.84±15.32)%; day 3: (29.06±14.96)%; day 4: (13.30±5.79)%] changing most significantly (P<0.05). The thickening fractions of left anterior, middle and posterior diaphragm recovered on day 5 compared with that on day 4, but still lower than those on day 1 (P<0.05). Conclusions: It is feasible to evaluate the diaphragm function in patients with invasive mechanical ventilation by ultrasound, which can provide guidance for preventing diaphragmatic atrophy and withdrawing from mechanical ventilation.

[Effect of different mechanical ventilation modes on patient-ventilator synchrony and diaphragm function in rabbit model of acute respiratory distress syndrome].

Objective: To observe the effect of different modes of mechanical ventilation on patient-ventilator synchrony and diaphragm function in rabbits with acute respiratory distress syndrome(ARDS). Methods: Eighteen New Zealand rabbit models of ARDS were induced by intratracheal infusion hydrochloric acid until the oxygenation index (PaO(2)/FiO(2)) was less than 200 mmHg, and then divided into three groups with random number: assisted-controlled mechanical ventilation (A/C) group, pressure support ventilation (PSV) group and neurally adjusted ventilatory assist (NAVA) group. All of them were ventilated for four hours with the targeted tidal volume (V(T)) (6 ml/kg) and the positive end-expiratory pressure (PEEP) titrated with the maximum oxygenation method. Gas exchange, pulmonary mechanics and patient-ventilator synchrony were determined during 4 h of ventilation and the concentrations of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) in diaphragm were measured after 4 h of ventilation. The q test was used for the multiple comparison of the sample mean. Results: There were no significant differences in PaO(2)/FiO(2) between three groups during ventilation 1-4 h (F=1.029, P>0.05). The V(T) in NAVA group was obviously lower than that in PSV group and the respiratory rate (RR) and the electrical activity of diaphragm(EAdi) were higher than those in A/C group(all P<0.05).The trigger delay and off cycle delay the in NAVA group were markedly lower than those in A/C and PSV group during ventilation 1-4 h(F=14.312, 9.342, both P<0.05). Asynchrony index in NAVA group (3.1%±1.0%) was obviously lower than those in A/C group (22.3%±5.2%) and PSV group(8.4%±2.3%) (F=7.192, P<0.05). In NAVA group, peak EAdi (EAdi(peak)) and peak airway pressure (Ppeak) were markedly correlated (r=0.97±0.16, P<0.05), while Ppeak delivery in A/C and PSV group was not correlated to EAdi(peak) (r=0.38±0.13,0.46±0.15, both P>0.05).Compared with A/C group, the concentration of MDA in the diaphragm in NAVA group was obviously lower(P<0.05). SOD and GSH level inthe diaphragm in NAVA group were both obviously higher than those in A/C group (both P<0.05). Conclusions: It is helpful to avoid eccentric contraction of diaphragm, lessen oxidative stress and alleviate ventilator-related diaphragm dysfunction by keeping spontaneous breathing as far as possible and subject-ventilator synchrony when ventilation in ARDS with NAVA.

Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis.

BACKGROUND: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in patients with acute severe tracheal stenosis, yet data supporting the clinical use of H2-O2 are insufficient. OBJECTIVES: To evaluate the efficacy and safety of breathing H2-O2 in acute severe tracheal stenosis. METHODS: Thirty-five consecutive patients with severe acute tracheal stenosis were recruited in this prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4 consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1) for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary endpoint was inspiratory effort as assessed by diaphragm electromyography (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in the ambient environment was obtained with 12 monitors. Adverse reactions during the inhalation were recorded. RESULTS: The mean reduction in the EMGdi under H2-O2 was 10.53 ± 6.83%. The EMGdi significantly decreased during 2 H2-O2 inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3) (52.95 ± 15.00 vs. 42.46 ± 13.90 vs. 53.20 ± 14.74 vs. 42.50 ± 14.12% for Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77 ± 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and resistance parameters of IOS but not vital signs. No adverse reactions occurred. H2 was undetectable in the environment throughout the procedure. CONCLUSIONS: Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe tracheal stenosis and can be used for this purpose safely.

Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury.

Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5-21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100-200 µA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable "closed-loop-like" ISMS approaches to sustain ventilation after severe SCI.NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals.

Different effects of cardiac and diaphragm function assessed by ultrasound on extubation outcomes in difficult-to-wean patients: a cohort study.

BACKGROUND: Ultrasound is a convenient tool to evaluate cardiac and diaphragm function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed in predicting extubation outcomes independently, however their different roles in the weaning process have not been determined until now. METHODS: We designed a cohort study to preform diaphragm ultrasound and TTE before and after the spontaneous breathing trial (SBT) in difficult-to-wean patients. Patients considered for enrollment should succeed on a SBT and have been extubated. They were followed up with the events of respiratory failure within 48 h, and divided into the respiratory failure and extubation success subgroups. Relevant risk factors predicting respiratory failure were analysed by a multivariate logistic regression model. Then, each subgroup was assessed with respect to re-intubation within 1 week, and divided into the re-intubation and non-intubation subgroups. Furthermore, relevant risk factors predicting re-intubation were also analysed in each subgroup. The area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic curve. RESULTS: Among 60 patients, 29 cases developed respiratory failure within 48 h, and 14 cases were re-intubated or died within 1 week, respectively. Multivariate logistic regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular ejection fraction were associated with respiratory failure. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥ 12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively. Furthermore, in the respiratory failure subgroup only DE (average) after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P = 0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively. CONCLUSIONS: E/Ea (average) after SBT could help predict respiratory failure within 48 h. However, DE (average) after SBT could help predict re-intubation within 1 week in the respiratory failure subgroup.

Dissecting the role of the myofilament in diaphragm dysfunction during the development of heart failure in mice.

Dyspnea and reduced exercise capacity, caused, in part, by respiratory muscle dysfunction, are common symptoms in patients with heart failure (HF). However, the etiology of diaphragmatic dysfunction has not been identified. To investigate the effects of HF on diaphragmatic function, models of HF were surgically induced in CD-1 mice by transverse aortic constriction (TAC) and acute myocardial infarction (AMI), respectively. Assessment of myocardial function, isolated diaphragmatic strip function, myofilament force-pCa relationship, and phosphorylation status of myofilament proteins was performed at either 2 or 18 wk postsurgery. Echocardiography and invasive hemodynamics revealed development of HF by 18 wk postsurgery in both models. In vitro diaphragmatic force production was preserved in all groups while morphometric analysis revealed diaphragmatic atrophy and fibrosis in 18 wk TAC and AMI groups. Isometric force-pCa measurements of myofilament preparations revealed reduced Ca(2+) sensitivity of force generation and force generation at half-maximum and maximum Ca(2+) activation in 18 wk TAC. The rate of force redevelopment (ktr) was reduced in all HF groups at high levels of Ca(2+) activation. Finally, there were significant changes in the myofilament phosphorylation status of the 18 wk TAC group. This includes a decrease in the phosphorylation of troponin T, desmin, myosin light chain (MLC) 1, and MLC 2 as well as a shift in myosin isoforms. These results indicate that there are multiple changes in diaphragmatic myofilament function, which are specific to the type and stage of HF and occur before overt impairment of in vitro force production.

Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort.

RATIONALE: Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown. OBJECTIVES: To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon. METHODS: In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound. MEASUREMENTS AND MAIN RESULTS: Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison). CONCLUSIONS: Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.

Does inspiratory muscle training improve lung function and quality of life in people with inclusion body myositis? A pilot study.

Inclusion body myositis is the most common acquired myositis in adults, predominantly weakening forearm flexor and knee extensor muscles. Subclinical respiratory muscle weakness has recently been recognised in people with inclusion body myositis, increasing their risk of respiratory complications. Inspiratory muscle training, a technique which demonstrates efficacy and safety in improving respiratory function in people with neuromuscular disorders, has never been explored in those with inclusion body myositis. In this pilot study, six adults with inclusion body myositis (age range 53 to 81 years) completed eight weeks of inspiratory muscle training. Measures of respiratory function, quality of life, sleep quality and a two-minute walk test were performed pre and post-intervention. All participants improved their respiratory function, with maximal inspiratory pressure, sniff nasal inspiratory pressure and forced vital capacity increasing by an average of 50 % (p = .002), 43 % (p = .018) and 13 % (p = .003) respectively. No significant change was observed in quality of life, sleep quality or two-minute walk test performance. No complications occurred due to inspiratory muscle training This pilot study provides the first evidence that inspiratory muscle training may be safe and effective in people with Inclusion Body Myositis, potentially mitigating the complications of poor respiratory function.

Ultrasound Evaluation of Onset Core Muscle Activity in Subjects with Non-Specific Lower Back Pain and Without Lower Back Pain: An Observational Case-Control Study.

Lower back pain (LBP) has been the leading cause of disability since 1990. Objectives: The main objective of this observational case-control study was to evaluate, using ultrasound, whether there were differences in the onset and ratio of core muscle contraction between subjects with non-specific chronic lower back pain and healthy subjects. Methods: A total of 60 participants (52% women), split between those with non-specific chronic lower back pain (n = 26) and healthy (n = 34) subjects, were recruited. Initial muscle contraction of the lateral abdominal wall, pelvic floor, lumbar multifidus, and respiratory diaphragm was measured using ultrasound. The abdominal drawing-in maneuver, contralateral arm elevation, the Valsalva maneuver, and voluntary contraction of the pelvic floor in seated and standing positions were performed. The muscle thickness of the lateral abdominal wall and lumbar multifidus and excursion of the pelvic floor and diaphragm at rest and during testing were also analyzed. Results: No differences were found between the groups in the initial contraction. Statistically significant differences were found in the following variables: diaphragm excursion (p = 0.032, r = 0.277) and lumbar multifidus ratio (p = 0.010, r = 0.333) in the standing-abdominal retraction maneuver; pelvic floor excursion (p = 0.012, r = 0.325) in the standing-contralateral arm raise; and transverse abdominis ratio (p = 0.033, r = 0.275) in the sitting-contralateral arm raise. A statistically significant interaction between the groups and body mass index was observed in resting diaphragm excursion (p = 0.018, partial eta squared = 0.096) during sitting-voluntary pelvic floor contraction. Conclusions: It cannot be concluded that there is a specific pattern of core activation in any of the groups. However, statistically significant differences were found in the contraction indexes of the lumbopelvic musculature.

Ultrasound assessment of the respiratory system using diaphragm motion-volume indices.

Background: Although previous studies have determined limit values of normality for diaphragm excursion and thickening, it would be beneficial to determine the normal diaphragm motion-to-inspired volume ratio that integrates the activity of the diaphragm and the quality of the respiratory system. Methods: To determine the normal values of selected ultrasound diaphragm motion-volume indices, subjects with normal pulmonary function testing were recruited. Ultrasound examination recorded diaphragm excursion on both sides during quiet breathing and deep inspiration. Diaphragm thickness was also measured. The inspired volumes of the corresponding cycles were systematically recorded using a spirometer. The indices were calculated using the ratio excursion, or percentage of thickening, divided by the corresponding breathing volume. From this corhort, normal values and limit values for normality were determined. These measurements were compared to those performed on the healthy side in patients with hemidiaphragm paralysis because an increase in hemidiaphragm activity has been previously demonstated in such circumstances. Results: A total of 122 subjects (51 women, 71 men) with normal pulmonary function were included in the study. Statistical analysis revealed that the ratio of excursion, or percentage of thickening, to inspired volume ratio significantly differed between males and females. When the above-mentioned indices using excursion were normalized by body weight, no gender differences were found. The indices differed between normal respiratory function subjects and patients with hemidiaphragm paralysis (27 women, 41 men). On the paralyzed side, the average ratio of the excursion divided by the inspired volume was zero. On the healthy side, the indices using the excursion and the percentage of thickening during quiet breathing or deep inspiration were significantly increased comparedto patients with normal lung function. According to the logistic regression analysis, the most relevant indice appeared to be the ratio of the excursion measured during quiet breathing to the inspired volume. Conclusion: The normal values of the diaphragm motion-volume indices could be useful to estimate the performance of the respiratory system. Proposed indices appear suitable in a context of hyperactivity.

Temporal evolution of diaphragm thickness and diaphragm excursion among subjects hospitalized with COVID-19: A prospective observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has an affinity for the angiotensin-converting enzyme 2 (ACE2) receptors, which are present abundantly on the diaphragm. This study aims to describe temporal changes in diaphragmatic thickness and excursion using ultrasonography in subjects with acute COVID-19. METHODS: This prospective observational study included adults hospitalized with COVID-19 in the past 48 hours. The diaphragm thickness at end-expiration (DTE), diaphragm thickening fraction (DTF), and diaphragm excursion during tidal breathing (DE) and maximal inspiration (DEmax) were measured using ultrasonography daily for 5 days. The changes in DTE, DTF, DE, and Demax from day 1 to day 5 were assessed. RESULTS: This study included 64 adults (62.5% male) with a mean (SD) age of 50.2 (17.5) years. A majority (91%) of the participants had mild or moderate illness. The median (IQR) DTE, DTF (%), DE and Demax on day 1 were 2.2 (1.9, 3.0) mm, 21.5% (14.2, 31.0), 19.2 (16.5, 24.0) mm, and 26.7 (22.0, 30.2) mm, respectively. On day 5, there was a significant reduction in the DTE (p=0.002) with a median (IQR) percentage change of -15.7% (-21.0, 0.0). The DTF significantly increased on day 5 with a median (IQR) percentage change of 25.0% (-19.2, 98.4), p=0.03. There was no significant change in DE and Demax from day 1 to day 5, with a median (IQR) percentage change of 3.6% (-5.2, 15) and 0% (-6.7, 5.9), respectively. CONCLUSIONS: Non-intubated patients with COVID-19 exhibited a temporal decline in diaphragm thickness with increase in thickening fraction over 5 days of hospital admission. Further research is warranted to assess the impact of COVID-19 pneumonia on diaphragmatic function.

Point-of-care lung and diaphragm ultrasound in a patient with spinal muscular atrophy with respiratory distress type 1.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1, OMIM #604,320), is a rare autosomal recessive disease resulting from degeneration of motor neurons in the anterior horns, which leads irreversible diaphragmatic palsy and progressive distal symmetrical muscular weakness. Respiratory distress is the main symptom and is severe, rapidly progressive, and frequently requiring invasive ventilation. Despite diaphragm being one of the target organ of the disease, no specific study has been done using ultrasound.We report diaphragm and lung ultrasound findings of a 13-month-old girl affected by SMARD1 (homozygosis c.1540G > A mutation in IGHMPB2 gene) with respiratory failure requiring permanent mechanical ventilation since birth and we discuss the role of diaphragmatic and lung ultrasound in this category of patients and its clinical implications.

Diaphragm function does not independently predict exercise intolerance in patients with precapillary pulmonary hypertension after adjustment for right ventricular function.

Background: Several determinants of exercise intolerance in patients with precapillary pulmonary hypertension (PH) due to pulmonary arterial hypertension and/or chronic thromboembolic PH (CTEPH) have been suggested, including diaphragm dysfunction. However, these have rarely been evaluated in a multimodal manner. Methods: Forty-three patients with PH (age 58 ± 17 years, 30% male) and 43 age- and gender-matched controls (age 54 ± 13 years, 30% male) underwent diaphragm function (excursion and thickening) assessment by ultrasound, standard spirometry, arterial blood gas analysis, echocardiographic assessment of pulmonary artery pressure (PAP), assay of amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac magnetic resonance (CMR) imaging to evaluate right ventricular systolic ejection fraction (RVEF). Exercise capacity was determined using the 6-min walk distance (6MWD). Results: Excursion velocity during a sniff maneuver (SniffV, 4.5 ± 1.7 vs. 6.8 ± 2.3 cm/s, P<0.01) and diaphragm thickening ratio (DTR, 1.7 ± 0.5 vs. 2.8 ± 0.8, P<0.01) were significantly lower in PH patients versus controls. PH patients with worse exercise tolerance (6MWD <377 vs. ≥377 m) were characterized by worse SniffV, worse DTR, and higher NT-pro-BNP levels as well as by lower arterial carbon dioxide levels and RVEF, which were all univariate predictors of exercise limitation. On multivariate analysis, the only independent predictors of exercise limitation were RVEF (r = 0.47, P=0.001) and NT-proBNP (r = -0.27, P=0.047). Conclusion: Patients with PH showed diaphragm dysfunction, especially as exercise intolerance progressed. However, diaphragm dysfunction does not independently contribute to exercise intolerance, beyond what can be explained from right heart failure.

Predicting extubation readiness by monitoring the electrical activity of the diaphragm after prolonged mechanical ventilation: a pediatric case report.

BACKGROUND: The intensity of the electrical activity of the diaphragm (Edi) correlates with inspiratory effort. The ratio of tidal volume to the Edi is known as neuroventilatory efficiency (NVE) and is used as an index for ventilation efficiency. Here, we present a case showing that Edi and NVE may be effective parameters to predict successful extubation. CASE PRESENTATION: A 6-month-old female infant required prolonged mechanical ventilation after cardiac surgery. Fifty-two days after surgery, her trachea was extubated but required reintubation. Edi monitoring was initiated to assess diaphragm function. The Edi was > 70 mcV just after the reintubation, and her NVE was 1.0 mL/mcV, but gradually decreased. On day 59, her Edi values during the spontaneous breathing trials were 13 mcV with the improvement of NVE (2.5 mL/mcV) and her trachea was extubated without complications. CONCLUSIONS: The Edi and NVE were valuable for deciding the extubation readiness in a long-term mechanically ventilated patient.