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.

Thoracic Ultrasound in COVID-19: Use of Lung and Diaphragm Ultrasound in Evaluating Dyspnea in Survivors of Acute Respiratory Distress Syndrome from COVID-19 Pneumonia in a Post-ICU Clinic.

INTRODUCTION: Dyspnea is a common symptom in survivors of severe COVID-19 pneumonia. While frequently employed in hospital settings, the use of point-of-care ultrasound in ambulatory clinics for dyspnea evaluation has rarely been explored. We aimed to determine how lung ultrasound score (LUS) and inspiratory diaphragm excursion (DE) correlate with patient-reported dyspnea during a 6-min walk test (6MWT) in survivors of COVID-19 acute respiratory distress syndrome (ARDS). We hypothesize higher LUS and lower DE will correlate with dyspnea severity. STUDY DESIGN AND METHODS: Single-center cross-sectional study of survivors of critically ill COVID-19 pneumonia (requiring high-flow nasal cannula, invasive, or non-invasive mechanical ventilation) seen in our Post-ICU clinic. All patients underwent standardized scanning protocols to compute LUS and DE. Pearson correlations were performed to detect an association between LUS and DE with dyspnea at rest and exertion during 6MWT. RESULTS: We enrolled 45 patients. Average age was 61.5 years (57.7% male), with average BMI of 32.3 Higher LUS correlated significantly with dyspnea, at rest (r = + 0.41, p = < 0.01) and at exertion (r = + 0.40, p = < 0.01). Higher LUS correlated significantly with lower oxygen saturation during 6MWT (r = -0.55, p = < 0.01) and lower 6MWT distance (r = -0.44, p = < 0.01). DE correlated significantly with 6MWT distance but did not correlate with dyspnea at rest or exertion. CONCLUSION: Higher LUS correlated significantly with patient-reported dyspnea at rest and exertion. Higher LUS significantly correlated with more exertional oxygen desaturation during 6MWT and lower 6MWT distance. DE did not correlate with dyspnea.

The relationship between diaphragm thickness and the severity of the disease in pregnant patients with Covid-19.

OBJECTIVE: We aimed to investigate whether there is a relationship between diaphragm thickness and disease severity in Covid-19 pregnant subgroups. MATERIAL AND METHODS: In this prospective study 100 pregnant patients were enrolled. Thickness of the diaphragm muscle at end-expiration was measured using B-Mode US. Hemoglobin,WBC, NLR, procalcitonin and LDH levels were measured. RESULTS: There was a statistically significant difference between the groups in terms of diaphragm thickness, and the diaphragm thickness was thinner in the severe disease group (p < 0.001). There was no statistically significant difference between the groups with mild to moderate disease severity (p = 0.708). CONCLUSION: Covid-19 patients who developed serious infection has thinner diaphragms than those who did not. Low diaphragm muscle thickness at the outset of Covid-19 disease, may predispose to poor clinical outcomes. Diaphragmatic ultrasound may be a promising tool to evaluate the risk of Covid-19 disease severity.

Ultrasound imaging assessment of the diaphragm and abdominal muscles in people with a recent history of moderate Covid-19 infection and healthy participants: A cross-sectional pilot study.

Coronavirus disease (Covid-19) is a highly infectious disease caused by the SARS-CoV-2 virus and is associated with a decrease of respiratory, physical, and psychological function, subsequently affecting quality of life. The aim of the present pilot study was to use ultrasound imaging (USI) to evaluate and compare the thickness of the diaphragm and abdominal muscles between individuals recently diagnosed with moderate Covid-19 infection and healthy individuals. METHODS: A cross-sectional observational pilot study was performed. A total sample of 24 participants were recruited from a private medical center (Madrid, Spain): Covid-19 (n = 12) and healthy controls (n = 12). The external oblique (EO), internal oblique (IO), transversus abdominis (TrA), rectus abdominis (RA), interrecti distance (IRD) and diaphragm thickness were assessed using USI during inspiration, expiration and during contraction. RESULTS: USI measurements of the thickness of EO, IO, TrA, RA, IRD and the diaphragm did not differ significantly between groups during inspiration, expiration or during contraction (all P > 0.05). CONCLUSIONS: These preliminary results suggest that the morphology of the abdominal muscles and diaphragm is not altered in people with a recent history of moderate Covid-19 infection.

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.

Evaluation of diaphragm thickness to predict intubation requirement and mortality in critical COVID-19 patients.

OBJECTIVES: To investigate the value of measuring the diaphragm thickness (DT) on thorax computed tomography (CT) at intensive care unit (ICU) admission for predicting intubation requirement and mortality among COVID-19 patients. METHODS: This study was carried out in Ankara City Hospital, Ankara, Turkey, from September 2020 to January 2021, with 94 critical COVID-19 patients. The patients' demographic characteristics, laboratory parameters, DT measurements, mechanical ventilation (MV) requirements, and mortality statuses were retrospectively screened. The relationships between DT on initial CT, MV requirement, and mortality were investigated. RESULTS: Diaphragm thickness was lower in patients who required intubation after ICU admission than in non-intubated patients (p=0.006); it was also lower in non-survivors (p=0.009). The threshold values for MV need was 3.35 mm (p=0.004) and 3.275 mm for mortality (p=0.006), according to the receiver operating characteristic analysis used to assess the predictive potential of DT. The non-survivor group had a greater neutrophil-to-lymphocyte ratio (p=0.026). Absolute neutrophil count (p=0.017), neutrophil-to-lymphocyte ratio (p=0.010), and interleukin-6 levels (p=0.027) were higher among patients requiring MV than among non-intubated patients. CONCLUSION: Mortality and MV requirements can be predicted from DT measurements. Diaphragm thickness can facilitate the identification of high-risk patients on CT evaluation at ICU admission.

Diaphragmatic Dysfunction due to Neuralgic Amyotrophy After SARS-CoV-2 Vaccination: A Case Report.

Neuralgic amyotrophy is an idiopathic neuropathy characterized by acute-onset pain, typically in the upper extremity or shoulder, followed by weakness of the associated muscles. Phrenic nerve involvement is rare. We report a 63-year-old man who presented with dyspnea and right shoulder pain after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. His chest radiograph showed an elevated right hemidiaphragm that was absent before vaccination. A pulmonary function test showed a restrictive pattern with a significant reduction (40%) in forced vital capacity in the supine position. Diaphragm ultrasonography revealed a reduction in both diaphragmatic excursion and a thickening fraction of the right hemidiaphragm. Electrophysiological studies suggested a right upper brachial plexopathy. Considering the temporal relationship between the vaccination and absence of other causes, SARS-CoV-2 vaccination was thought to be the reason for neuralgic amyotrophy with diaphragmatic dysfunction. As there was no evidence of hypoventilation or sleep disturbance that may require noninvasive ventilation, the patient was followed with conservative treatment with analgesics. During 8 months of follow-up, his shoulder pain was relieved significantly but dyspnea improved only slightly. Neuralgic amyotrophy is an under-diagnosed etiology of diaphragmatic dysfunction and should be considered in patients with dyspnea and shoulder pain.

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Association of diaphragm thickness and density measured on chest CT with disease severity in COVID-19 patients.

INTRODUCTION: A decrease in muscle mass of the diaphragm could be a significant risk factor for pneumonia. The aim of our study was to evaluate whether diaphragm thickness (DT) and density measured on chest computed tomography (CT) were associated with clinical course and mortality in adult patients with coronavirus disease 2019 (COVID-19) in emergency department admission. METHODS: We retrospectively analyzed 404 patients with a positive polymerase chain reaction test for COVID-19 and pneumonia findings on chest CT between September 1 and November 1, 2020. Bilateral DT measurements were performed at the level of the celiac artery origin, and the total mean diaphragm thickness (TMDT) was estimated. Hemidiaphragm density was measured at the level of the celiac artery origin. The relationship between demographic characteristics, comorbidities, TMDT, mean hemidiaphragm density (MHD) and clinical outcomes was investigated using the logistic regression analyses. The reliability of the measurement of the two observers was evaluated by intraclass correlation analyses. RESULTS: Intraclass correlation analyses demonstrated almost perfect inter-observer agreement for TMDT and substantial agreement for MHD. There was a statistically significant relationship between the presence of a thinner diaphragm and mortality (p < 0.001). Bilateral diaphragm densities were lower in the patients with severe disease and mortality (p < 0.001). The threshold values of TMDT were 3.67 mm and 3.47 mm for the prediction of ICU admission and mortality, respectively. TMDT (odds ratio [OR]: 0.634, 95% confidence interval [CI]: 0.447-0.901), age (OR: 1.053, 95% CI: 1.027-1.081) and MHD (OR: 0.920, 95% CI: 0.883-0.959) were found to be independent predictors for severe disease in the multivariable model. In addition, MHD (OR: 0.883, 95% CI: 0.827-0.942) and age (OR: 1.040, 95% CI: 1.003-1.078) were independent risk factors for mortality. CONCLUSION: Our study demonstrated that a low diaphragm thickness and density measured on chest CT were associated with severe disease in patients with COVID-19 and could be evaluated as poor prognostic markers.

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.

Diaphragmatic paralysis in COVID-19: a rare cause of postacute sequelae of COVID-19 dyspnoea.

We describe a 56-year-old female patient hospitalised with COVID-19 in April 2020 who had persistent respiratory symptoms after radiographic and microbiologic recovery. X-ray of the chest demonstrated an elevated right hemidiaphragm while fluoroscopy confirmed unilateral diaphragmatic paralysis. Symptoms resolved gradually, concurrent with restoration of right hemidiaphragm function. Thus, we describe a rare cause of postacute sequelae of COVID-19 dyspnoea.

Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 21 consecutive severe post-COVID-19 survivors admitted to an inpatient rehabilitation hospital, 16 (76%) of them had at least one sonographic abnormality of diaphragm muscle structure or function. This corresponded to a significant reduction in diaphragm muscle contractility as represented by thickening ratio (muscle thickness at maximal inspiration/end-expiration) for the post-COVID-19 compared to non-COVID-19 cohorts. These findings may shed new light on neuromuscular respiratory dysfunction as a contributor to prolonged functional impairments after hospitalization for post-COVID-19.

Comprehensive assessment of respiratory function, a step towards early weaning from the ventilator.

Methods for assessing diaphragmatic function can be useful in determining the functional status of the respiratory system and can contribute to determining an individual's prognosis, depending on their pathology. They can also be a useful tool for making objective decisions regarding mechanical ventilation weaning and extubation. Esophageal and transdiaphragmatic pressure measurement, diaphragm ultrasound, diaphragmatic excursion, surface electromyography (sEMG) and some serum biomarkers are of increasing interest and use in clinical and intensive care settings to offer a more objective process for withdrawing mechanical ventilation; especially in the situation that we are experiencing with the increased demand for mechanical ventilation to treat patients with Covid-19-associated viral pneumonia. In this literature review, we updated the clinical and physiological indicators with more evidence to improve ventilator withdrawal techniques. We concluded that, to ensure successful extubation in a way that is useful, cost-effective, practical for health personnel and non-invasive for the patient, further studies of novel techniques such as surface electromyography should be implemented.

Diaphragm and Phrenic Nerve Ultrasound in COVID-19 Patients and Beyond: Imaging Technique, Findings, and Clinical Applications.

The diaphragm, the principle muscle of inspiration, is an under-recognized contributor to respiratory disease. Dysfunction of the diaphragm can occur secondary to lung disease, prolonged ventilation, phrenic nerve injury, neuromuscular disease, and central nervous system pathology. In light of the global pandemic of coronavirus disease 2019 (COVID-19), there has been growing interest in the utility of ultrasound for evaluation of respiratory symptoms including lung and diaphragm sonography. Diaphragm ultrasound can be utilized to diagnose diaphragm dysfunction, assess severity of dysfunction, and monitor disease progression. This article reviews diaphragm and phrenic nerve ultrasound and describes clinical applications in the context of COVID-19.