Potential Diaphragm Muscle Weakness-related Dyspnea Persists 2 Years after COVID-19 and Could Be Improved by Inspiratory Muscle Training: Results of an Observational and an Interventional Clinical Trial.

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 H2O [IQR = 75-91] vs. 100 cm H2O [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).

The Effects of Various Approaches to Lobectomies on Respiratory Muscle Strength, Diaphragm Thickness, and Exercise Capacity in Lung Cancer.

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.

Effectiveness of pulmonary rehabilitation programmes and/or respiratory muscle training in patients with post-COVID conditions: a systematic review.

BACKGROUND: The term "post-COVID-19 condition" refers to the symptomatology that appears between four to twelve weeks after Covid-19 infection. These symptoms can persist for weeks or even months, significantly diminishing the quality of life for affected individuals. The primary objective of this study was to assess the effectiveness of pulmonary rehabilitation programs and/or respiratory muscle training on respiratory sequelae in patients with post-COVID condition. METHODS: The literature search was conducted in the following databases: PubMed, PEDro, Embase, Cochrane, Scopus, and Web of Science. Randomized clinical trials were included in which participants were aged 18 years or older. Articles were excluded if at least one of the therapies did not involve pulmonary rehabilitation or respiratory muscle training, if the participants were COVID positive, if studies lacked results, and finally, if interventions were conducted without supervision or at home. This review only encompasses supervised non-virtual interventions. This study adheres to the PRISMA statement and has been registered in the PROSPERO database (CRD42023433843). RESULTS: The outcomes obtained in the included studies are assessed across the following variables: Exercise capacity using the 6-minute walk test, Dyspnea, fatigue, Pulmonary function, Maximum inspiratory pressure, and Quality of life. CONCLUSION: Despite the absence of a specific treatment at present, it was evident from this review that a well-structured pulmonary rehabilitation program that incorporates both aerobic and muscular strength exercises along with techniques and inspiratory muscle exercises was the most effective form of treatment.

Respiratory performance in Duchenne muscular dystrophy: Clinical manifestations and lessons from animal models.

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.

Chronic N-acetyl cysteine treatment does not improve respiratory system performance in the mdx mouse model of Duchenne muscular dystrophy.

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.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

Respiratory Muscle Strength Is Related to Handgrip Performance in Community-Dwelling Persons Aged 80+ from the BUTTERFLY Study.

INTRODUCTION: This study aimed to evaluate the association of respiratory muscle strength with sarcopenia and its indicators in the oldest old. METHODS: Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and sarcopenia-related factors (handgrip strength and appendicular lean mass) were evaluated in a cohort of n = 286 (45.5% female) non-frail, community-dwelling persons aged 83.6 ± 3.0 years (age range 80-97 years). RESULTS: The sample presented a sarcopenia prevalence of 32.2%. Sarcopenic subjects showed comparable MIP and MEP as non-sarcopenic ones (female: MIP 43.9 ± 18.9 vs. 50.3 ± 19.5, p = 0.053; MEP 63.0 ± 23.0 vs. 69.2 ± 19.1, p = 0.067; male: MIP, 65.1 ± 24.4 vs. 64.4 ± 23.9, p = 0.433; MEP 87.7 ± 33.3 vs. 93.8 ± 30.9, p = 0.124). Statistically significant but very low associations were found between grip strength and MIP (r = 0.193 for male, p < 0.05 and r = 0.257 for female participants, p < 0.01) and MEP (r = 0.200 for male, p < 0.01 and r = 0.191 for female participants, p < 0.05). Lean mass was significantly correlated to MIP and MEP in female (r = 0.253, p < 0.01 and r = 0.343, p < 0.01, respectively), whereas this association was not found in male participants. Grip strength was the only statistically significant predictor of MEP (r2 = 0.212, p < 0.001), while MIP was independently predicted by age, male sex, and grip strength (r2 = 0.177, p < 0.001). CONCLUSIONS: Peripheral muscle strength is a statistically significant, albeit weak predictor for respiratory muscle strength in well-functioning, community-dwelling persons aged 80+. When confronted to a low grip strength, one should be aware of concomitant respiratory muscle weakness, as this is a known risk factor for atelectasis and pneumonia. Given the relatively low association with handgrip strength, respiratory muscle strength testing might be indicated.

Effects of different inspiratory muscle training protocols on functional exercise capacity and respiratory and peripheral muscle strength in patients with chronic kidney disease: a randomized study.

BACKGROUND: Pathological changes were observed in the diaphragm due to abnormal renal function in chronic kidney disease (CKD). Inspiratory muscle training (IMT) has been suggested for patients with CKD; however, the most appropriate intensity for IMT has not been determined. Therefore, this study aimed to investigate the effects of different IMT protocols on respiratory muscle strength, quadriceps femoris muscle strength (QMS), handgrip muscle strength (HGS), functional exercise capacity, quality of life (QoL), pulmonary function, dyspnoea, fatigue, balance, and physical activity (PA) levels in patients with CKD. METHODS: This randomized, controlled, single-blind study included 47 patients and they were divided into three groups: Group 1 (n = 15, IMT with 10% maximal inspiratory pressure (MIP)), Group 2 (n = 16, IMT with 30% MIP), and Group 3(n = 16; IMT with 60% MIP). MIP, maximal expiratory pressure (MEP), 6-min walking test (6-MWT), QMS, HGS, QoL, pulmonary function, dyspnoea, fatigue, balance, and PA levels were assessed before and after eight weeks of IMT. RESULTS: Increases in MIP, %MIP, 6-MWT distance, and %6-MWT were significantly higher in Groups 2 and 3 than in Group 1 after IMT (p < 0.05). MEP, %MEP, FEF25-75%, QMS, HGS, and QoL significantly increased; dyspnoea and fatigue decreased in all groups (p < 0.05). FVC, PEF, and PA improved only in Group 2, and balance improved in Groups 1 and 2 (p < 0.05). CONCLUSIONS: IMT with 30% and 60% MIP similarly improves inspiratory muscle strength and functional exercise capacity. IMT with 30% is more effective in increasing PA. IMT is a beneficial method to enhance peripheral and expiratory muscle strength, respiratory function, QoL and balance, and reduce dyspnoea and fatigue. IMT with %30 could be an option for patients with CKD who do not tolerate higher intensities. TRIAL REGISTRATION: This study was retrospectively registered (NCT06401135, 06/05/2024).

The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis.

BACKGROUND: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. METHODS: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. RESULTS: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. CONCLUSIONS: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. TRIAL REGISTRATION: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Establishing an optimal diagnostic criterion for respiratory sarcopenia using peak expiratory flow rate.

BACKGROUND: The skeletal muscle changes as aging progresses, causing sarcopenia in the older adult population, which affects the respiratory muscles' mass, strength, and function. The optimal cut-off point of peak expiratory flow rate (PEFR) for respiratory sarcopenia (RS) diagnosis in accordance with sarcopenia identification is needed. AIM: To establish an optimal cut-off point of PEFR for RS diagnosis in community-dwelling Asian older women. METHODS: Sarcopenia diagnostic indicators were evaluated according to the Asian Working Group for Sarcopenia 2019 (AWGS) criteria. The respiratory parameters composed of respiratory muscle strength and respiratory function were evaluated by assessing maximal inspiratory pressure (MIP), percent predicted forced vital capacity (Pred FVC), and PEFR. RESULTS: A total of 325 community-dwelling older women were included in this study. PEFR was negatively associated with RS (OR: 0.440; 95% CI: 0.344-0.564). The area under the curve (AUC) of PEFR was 0.772 (p < 0.001). The optimal cut-off point of PEFR for RS diagnosis was 3.4 l/s (sensitivity, 63.8%; specificity, 77.3%). Significant differences were found between the robust, possible sarcopenia, sarcopenia, and RS groups in terms of both sarcopenia diagnostic indicators and respiratory parameters (p < 0.05). CONCLUSIONS: The cut-off point of PEFR can be used as a reasonable standard for RS diagnosis. This study finding can serve as a cornerstone for developing concrete criteria of RS in older women, supporting clinical judgment, which is crucial for providing appropriate treatment through accurate diagnosis.

Is There a Direct Effect Between the Plication of the Myoaponeurotic Layer and the Force of Inspiratory and Expiratory Muscles After Abdominoplasty?

OBJECTIVE: Abdominoplasty may generate an increase in the intra-abdominal pressure (IAP) and consequently an alteration in the pulmonary ventilation. The purpose of this study was to evaluate the potential alterations in the maximal static inspiratory pressure (MIP) and maximal static expiratory pressure (MEP) after abdominoplasty. METHODS: Thirty-three female patients, aged between 18 and 60, with type III/B Nahas abdominal deformity that underwent abdominoplasty with plication of the anterior rectus and external oblique aponeurosis were selected. The MIP and MEP were measured using a mouthpiece. This is a simple way to indirectly gauge inspiratory and expiratory muscle strength. Measurements were performed before surgery and on the 2nd, 7th, 15th, and 180th postoperative day. In addition, IAP was measured before abdominoplasty and after the placement of compression garment. The MIP and MEP were compared using analysis of variance, followed by the Bonferroni multiple comparison test pairing the different points in time. Paired Student's t test was used for comparing IAP measurements. Pearson's correlation test was used to compare MIP and MEP variations with IAP variation. Results were considered statistically significant when P ≤ 0.05. RESULTS: A decrease was observed in MEP on the 2nd day, with a return close to normal values on the 15th day. In opposition MIP had a surprisingly increase on the 15th postoperative day (129 cmH2O), normalizing 180 days after the operation. A leap in IAP values was revealed at the end of the surgical procedure. It was not possible to establish a positive correlation between the increase of IAP and the alterations of MIP and MEP. CONCLUSIONS: There is a decrease in maximum expiratory pressure on the very early postoperative day (2nd postoperative day) and an increase in maximum inspiratory pressure on the 15th postoperative day in patients who underwent abdominoplasty. There was no correlation between the IAP and maximum respiratory pressure variations, both inspiratory and expiratory.

The Application of Self-Made Disseminating and Descending Breathing Exercises in Home Rehabilitation of Stable COPD.

To investigate the clinical effects and application value of self-made disseminating and descending breathing exercises on home rehabilitation of patients with stable chronic obstructive pulmonary disease (COPD). Seeking to generate concepts for creating novel, convenient, and efficient COPD prognosis rehabilitation exercises aimed at enhancing the well-being and rehabilitation confidence of both COPD patients and their families. A total of 70 COPD patients admitted to our outpatient department from July 2019 to September 2021 were randomly divided into the exercise group (n = 35) and the control group (n = 35). The control group received routine breathing training, while the exercise group was treated with self-made disseminating and descending breathing exercises. The respiratory function, including pulmonary function (FVC, FEV1, FEV1/FVC) and respiratory muscle strength (MIP, MEP), exercise tolerance (6-min walking distance, 6MWT), Modified Medical Research Council Dyspnea Scale (mMRC, Borg), COPD quality of life score (CAT, SGRQ), anxiety and depression scores (HAMA, HAMD) were compared between the two groups after 12-week exercise. After 12-week training, the FEV1, MIP, and MEP in the exercise group were significantly higher than those in the control group (p < 0.001), and the 6MWT was significantly increased in the exercise group compared to the control group (p < 0.001); while the mMRC, Borg score, the scores of CAT, SGRQ, HAMA, and HAMD were found significantly lower than those in the control group (p < 0.001). The self-made disseminating and descending breathing exercises can improve respiratory function and reduce symptoms of dyspnea in COPD patients, while enhancing exercise tolerance and relieving anxiety and depression, and are worthy of clinical application.

"Effects of threshold respiratory muscle training on respiratory muscle strength, pulmonary function and exercise endurance after stroke: a meta-analysis".

BACKGROUND: Most studies on improvements in respiratory muscle strength, activities of daily living (ADL) and quality of life (QoL) in stroke patients receiving threshold respiratory muscle training (TRMT) have small sample sizes, and some studies have contradictory results. OBJECTIVES: To evaluate the effectiveness of TRMT on respiratory muscle strength, pulmonary function and exercise endurance in stroke patients. MATERIALS AND METHODS: PubMed, Cochrane Library, Physical Therapy Evidence Database (PEDro), Embase (via OVID) and Web of Science databases were searched for randomized controlled trial (RCT) from inception to January 17, 2024. The primary outcome was maximum inspiratory pressure (MIP) or maximum expiratory pressure (MEP). Secondary outcomes included pulmonary function measured by forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF), and exercise endurance measured by 6-minute walk test (6MWT). RESULTS: A total of eight randomized controlled trials(RCTs), including 305 persons, were included in this study. The training time ranged from 3 weeks to 10 weeks. Among them, the intervention group in 4 studies used inspiratory muscle training, and the other 4 studies used inspiratory muscle training and expiratory muscle training. For the primary outcome, TRMT significantly improved MIP (mean=14.68 cmH2O, 95 %CI=2.28 to 27.09 cmH2O, P=0.02) and MEP (mean=9.37 cmH2O, 95 %CI=2.89 to 15.84 cmH2O, P=0.005) in stroke patients. Regarding the secondary outcomes, TRMT improved FVC, FEV1 and 6MWT (P<0.05) but did not significantly improve PEF. CONCLUSION: TRMT improved inspiratory muscle strength and expiratory muscle strength, improved exercise endurance, and improved FVC and FEV1 of pulmonary function but did not significantly improve PEF.

Low-Medium and High-Intensity Inspiratory Muscle Training in Critically Ill Patients: A Systematic Review and Meta-Analysis.

Background and objectives: Mechanical ventilation is often used in intensive care units to assist patients' breathing. This often leads to respiratory muscle weakness and diaphragmatic dysfunction, causing weaning difficulties. Inspiratory muscle training (IMT) has been found to be beneficial in increasing inspiratory muscle strength and facilitating weaning. Over the years, different protocols and devices have been used. Materials and Methods: The aim of this systematic review and meta-analysis was to investigate the effectiveness of low-medium (LM-IMT) and high-intensity (H-IMT) threshold inspiratory muscle training in critically ill patients. A systematic literature search was performed for randomized controlled trials (RCTs) in the electronic databases Google Scholar, PubMed, Scopus, and Science Direct. The search involved screening for studies examining the effectiveness of two different intensities of threshold IMT in critically ill patients published the last 10 years. The Physiotherapy Evidence Database (PEDro) scale was chosen as the tool to assess the quality of studies. A meta-analysis was performed where possible. Results: Fourteen studies were included in the systematic review, with five of them having high methodological quality. Conclusions: When examining LM-IMT and H-IMT though, neither was able to reach statistically significant improvement in their maximal inspiratory pressure (MIP), while LM-IMT reached it in terms of weaning duration. Additionally, no statistical difference was noticed in the duration of mechanical ventilation. The application of IMT is recommended to ICU patients in order to prevent diaphragmatic dysfunction and facilitate weaning from mechanical ventilation. Therefore, further research as well as additional RCTs regarding different protocols are needed to enhance its effectiveness.

Compensatory responses to increased mechanical abnormalities in COPD during sleep.

PURPOSE: To assess whether night-time increases in mechanical loading negatively impact respiratory muscle function in COPD and whether compensatory increases in inspiratory neural drive (IND) are adequate to stabilize ventilatory output and arterial oxygen saturation, especially during sleep when wakefulness drive is withdrawn. METHODS: 21 patients with moderate-to-severe COPD and 20 age-/sex-matched healthy controls (CTRL) participated in a prospective, cross-sectional, one-night study to assess the impact of COPD on serial awake, supine inspiratory capacity (IC) measurements and continuous dynamic respiratory muscle function (esophageal manometry) and IND (diaphragm electromyography, EMGdi) in supine sleep. RESULTS: Supine inspiratory effort and EMGdi were consistently twice as high in COPD versus CTRL (p < 0.05). Despite overnight increases in awake total airways resistance and dynamic lung hyperinflation in COPD (p < 0.05; not in CTRL), elevated awake EMGdi and respiratory effort were unaltered in COPD overnight. At sleep onset (non-rapid eye movement sleep, N2), EMGdi was decreased versus wakefulness in COPD (- 43 ± 36%; p < 0.05) while unaffected in CTRL (p = 0.11); however, respiratory effort and arterial oxygen saturation (SpO2) were unchanged. Similarly, in rapid eye movement (stage R), sleep EMGdi was decreased (- 38 ± 32%, p < 0.05) versus wakefulness in COPD, with preserved respiratory effort and minor (2%) reduction in SpO2. CONCLUSIONS: Despite progressive mechanical loading overnight and marked decreases in wakefulness drive, inspiratory effort and SpO2 were well maintained during sleep in COPD. Preserved high inspiratory effort during sleep, despite reduced EMGdi, suggests continued (or increased) efferent activation of extra-diaphragmatic muscles, even in stage R sleep. CLINICAL TRIAL INFORMATION: The COPD data reported herein were secondary data (Placebo arm only) obtained through the following Clinical Trial: "Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease" ( https://clinicaltrials.gov/ct2/show/NCT02429765 ; NCT02429765).

Oxygen supplementation during exercise improves leg muscle fatigue in chronic fibrotic interstitial lung disease.

BACKGROUND: Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease (f-ILD). It remains unclear whether patients' severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O2) supplementation can ameliorate these abnormalities. METHODS: Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients' Tlim. Patients repeated the exercise test on supplemental O2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO2)). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue. RESULTS: Patients showed severe hypoxaemia (lowest O2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=-0.59±0.21 %/kJ vs -0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O2 was associated with a significant increase in muscle (HbO2), leading to a reduced decrease in ∆Tw in patients (-0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O2 significantly improved leg discomfort (p=0.005). CONCLUSION: O2 supplementation during exercise improves leg muscle oxygenation and fatigue in f-ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population.

Associations of CT evaluations of antigravity muscles, emphysema and airway disease with longitudinal outcomes in patients with COPD.

Multiple CT indices are associated with disease progression and mortality in patients with COPD, but which indices have the strongest association remain unestablished. This longitudinal 10-year observational study (n=247) showed that the emphysema severity on CT is more closely associated with the progression of airflow limitation and that a reduction in the cross-sectional area of erector spinae muscles (ESMCSA) on CT is more closely associated with mortality than the other CT indices, independent of patient demographics and pulmonary function. ESMCSA is a useful CT index that is more closely associated with long-term mortality than emphysema and airway disease in patients with COPD.

Five-year outcome of respiratory muscle weakness at intensive care unit discharge: secondary analysis of a prospective cohort study.

PURPOSE: To assess the association between respiratory muscle weakness (RMW) at intensive care unit (ICU) discharge and 5-year mortality and morbidity, independent from confounders including peripheral muscle strength. METHODS: Secondary analysis of the prospective 5-year follow-up of the EPaNIC cohort (ClinicalTrials.gov: NCT00512122), limited to 366 patients screened for respiratory and peripheral muscle strength in the ICU with maximal inspiratory pressure (MIP) after removal of the artificial airway, and the Medical Research Council sum score. RMW was defined as an absolute value of MIP <30 cmH2O. Associations between RMW at (or closest to) ICU discharge and all-cause 5-year mortality, and key measures of 5-year physical function, comprising respiratory muscle strength (MIP), hand-grip strength (HGF), 6 min walk distance (6MWD) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36), were assessed with Cox proportional hazards and linear regression models, adjusted for confounders including peripheral muscle strength. RESULTS: RMW was present in 136/366 (37.2%) patients at ICU discharge. RMW was not independently associated with 5-year mortality (HR with 95% CI 1.273 (0.751 to 1.943), p=0.352). Among 156five-year survivors, those with, as compared with those without RMW demonstrated worse physical function (MIP (absolute value, cmH2O): 62(42-77) vs 94(78-109), p<0.001; HGF (%pred): 67(44-87) vs 96(68-110), p<0.001; 6MWD (%pred): 87(74-102) vs 99 (80-111), p=0.009; PF-SF-36 (score): 55 (30-80) vs 80 (55-95), p<0.001). Associations between RMW and morbidity endpoints remained significant after adjustment for confounders (effect size with 95% CI: MIP: -23.858 (-32.097 to -15.027), p=0.001; HGF: -18.591 (-30.941 to -5.744), p=0.001; 6MWD (transformed): -1587.007 (-3073.763 to -179.253), p=0.034; PF-SF-36 (transformed): 1.176 (0.144-2.270), p=0.036). CONCLUSIONS: RMW at ICU discharge is independently associated with 5-year morbidity but not 5-year mortality.

Inspiratory Muscle Training With an Electronic Resistive Loading Device Improves Prolonged Weaning Outcomes in a Randomized Controlled Trial.

OBJECTIVES: To test if the use of an inspiratory muscle training program with an electronic resistive loading device is associated with benefits as to muscle strength, weaning, and survival in the ICU. DESIGN: Prospective randomized controlled trial. SETTINGS: Study conducted at the ICU of a Navy's hospital, Rio de Janeiro, Brazil, from January 2016 to September 2018. PATIENTS: Tracheostomized patients (18-86 yr) on prolonged weaning. INTERVENTIONS: Participants were assigned to inspiratory muscle training (intervention group) or a traditional T-piece protocol (control group). In the inspiratory muscle training group, participants underwent training with an electronic inspiratory training device (POWERbreathe K-5; Technologies Ltd, Birmingham, United Kingdom). MEASUREMENTS AND MAIN RESULTS: Changes in respiratory muscle strength and rates of ICU survival and weaning success were compared between groups. Forty-eight participants in the inspiratory muscle training group and 53 ones in the control group were included in the final analysis. The inspiratory muscle training was associated with a substantially higher gain on muscle strength as assessed by the maximal inspiratory pressure (70.5 [51.0-82.5] vs -48.0 cm H2O [36.0-72.0 cm H2O]; p = 0.003) and the timed inspiratory effort index (1.56 [1.25-2.08] vs 0.99 cm H2O/s [0.65-1.71 cm H2O/s]; p = 0.001). Outcomes at the 60th day of ICU were significantly better in the intervention group regarding both survival (71.1% vs 48.9%; p = 0.030) and weaning success (74.8% vs 44.5%; p = 0.001). CONCLUSIONS: The use of an inspiratory muscle training program with an electronic resistive loading device was associated with substantial muscle strength gain and positive impacts in two very relevant clinical outcomes: the rates of ICU survival and successful weaning.

Neurally adjusted ventilatory assist as a weaning mode for adults with invasive mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Prolonged ventilatory support is associated with poor clinical outcomes. Partial support modes, especially pressure support ventilation, are frequently used in clinical practice but are associated with patient-ventilation asynchrony and deliver fixed levels of assist. Neurally adjusted ventilatory assist (NAVA), a mode of partial ventilatory assist that reduces patient-ventilator asynchrony, may be an alternative for weaning. However, the effects of NAVA on weaning outcomes in clinical practice are unclear. METHODS: We searched PubMed, Embase, Medline, and Cochrane Library from 2007 to December 2020. Randomized controlled trials and crossover trials that compared NAVA and other modes were identified in this study. The primary outcome was weaning success which was defined as the absence of ventilatory support for more than 48 h. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with accompanying 95% confidence interval (CI) were expressed. RESULTS: Seven studies (n = 693 patients) were included. Regarding the primary outcome, patients weaned with NAVA had a higher success rate compared with other partial support modes (OR = 1.93; 95% CI 1.12 to 3.32; P = 0.02). For the secondary outcomes, NAVA may reduce duration of mechanical ventilation (MD = - 2.63; 95% CI - 4.22 to - 1.03; P = 0.001) and hospital mortality (OR = 0.58; 95% CI 0.40 to 0.84; P = 0.004) and prolongs ventilator-free days (MD = 3.48; 95% CI 0.97 to 6.00; P = 0.007) when compared with other modes. CONCLUSIONS: Our study suggests that the NAVA mode may improve the rate of weaning success compared with other partial support modes for difficult to wean patients.