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

RATIONALE: Diaphragm muscle weakness might underly persistent exertional dyspnea despite normal lung/cardiac function in individuals previously hospitalized for acute COVID-19 illness. OBJECTIVES: Firstly, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea two years after hospitalization for COVID-19, and secondly to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID. METHODS: ~2 years after hospitalization for COVID-19, 30 individuals (11 female, median age 58 [interquartile range (IQR) 51-63] years) 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. RESULTS: At median 31 [IQR 23-32] months after hospitalization, 21/30 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 [IQR 75-91] vs. 100 [IQR 81-113] cmH2O; p=0.02), inspiratory muscle fatiguability (time to task failure 365 [IQR 284-701] vs. 983 [IQR 551-1494] sec; 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: 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

[Non-invasive Mechanical Ventilation in Acute Respiratory Failure. Clinical Practice Guidelines - on behalf of the German Society of Pneumology and Ventilatory Medicine]. / S2k-Leitlinie Nichtinvasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

[The Difficult Airway with Tracheostomy - Manufacturing of an Individualized Tracheal Tube with Modern Imaging and 3D Printing]. / Der schwierige Atemweg mit Tracheostoma.

Case discussion of a 51-year-old female patient with ventilator dependency due to Charcot-Marie-Tooth-Hoffmann syndrome (HMSN I) and cervical spinal fusion with complex tracheal canula management. Following 16 years of noninvasive ventilation due to chronic hypercapnic failure with 24 hour dependency on the ventilator, an elective surgical tracheostomy and switch to invasive ventilation was carried out. Because of severe cervical scoliosis, common tracheal canulae could not provide an adequate fit. With development of a 3D model according to the CT scans of the patient, an individualized tracheal tube was customized that provided excellent ventilatory results and the ability to speak during invasive ventilation.

Surface EMG-based quantification of inspiratory effort: a quantitative comparison with Pes.

BACKGROUND: Inspiratory patient effort under assisted mechanical ventilation is an important quantity for assessing patient-ventilator interaction and recognizing over and under assistance. An established clinical standard is respiratory muscle pressure [Formula: see text], derived from esophageal pressure ([Formula: see text]), which requires the correct placement and calibration of an esophageal balloon catheter. Surface electromyography (sEMG) of the respiratory muscles represents a promising and straightforward alternative technique, enabling non-invasive monitoring of patient activity. METHODS: A prospective observational study was conducted with patients under assisted mechanical ventilation, who were scheduled for elective bronchoscopy. Airway flow and pressure, esophageal/gastric pressures and sEMG of the diaphragm and intercostal muscles were recorded at four levels of pressure support ventilation. Patient efforts were quantified via the [Formula: see text]-time product ([Formula: see text]), the transdiaphragmatic pressure-time product ([Formula: see text]) and the EMG-time products (ETP) of the two sEMG channels. To improve the signal-to-noise ratio, a method for automatically selecting the more informative of the sEMG channels was investigated. Correlation between ETP and [Formula: see text] was assessed by determining a neuromechanical conversion factor [Formula: see text] between the two quantities. Moreover, it was investigated whether this scalar can be reliably determined from airway pressure during occlusion maneuvers, thus allowing to quantify inspiratory effort based solely on sEMG measurements. RESULTS: In total, 62 patients with heterogeneous pulmonary diseases were enrolled in the study, 43 of which were included in the data analysis. The ETP of the two sEMG channels was well correlated with [Formula: see text] ([Formula: see text] and [Formula: see text] for diaphragm and intercostal recordings, respectively). The proposed automatic channel selection method improved correlation with [Formula: see text] ([Formula: see text]). The neuromechanical conversion factor obtained by fitting ETP to [Formula: see text] varied widely between patients ([Formula: see text]) and was highly correlated with the scalar determined during occlusions ([Formula: see text], [Formula: see text]). The occlusion-based method for deriving [Formula: see text] from ETP showed a breath-wise deviation to [Formula: see text] of [Formula: see text] across all datasets. CONCLUSION: These results support the use of surface electromyography as a non-invasive alternative for monitoring breath-by-breath inspiratory effort of patients under assisted mechanical ventilation.

German National Guideline for Treating Chronic Respiratory Failure with Invasive and Non-Invasive Ventilation: Revised Edition 2017 - Part 1.

Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010, the German Respiratory Society (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin, DGP) has leadingly published the Guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure." However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the Guidelines. For this reason, the updated Guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease-specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the Guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning. In the current Guidelines, different societies as well as professional and expert associations have been involved when compared to the 2010 Guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.

German National Guideline for Treating Chronic Respiratory Failure with Invasive and Non-Invasive Ventilation - Revised Edition 2017: Part 2.

Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010, the German Respiratory Society (DGP) has leadingly published the guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure." However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the guidelines. For this reason, the updated guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease-specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning. In the current guidelines, different societies as well as professional and expert associations have been involved when compared to the 2010 guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.

Walking with Non-Invasive Ventilation Does Not Prevent Exercise-Induced Hypoxaemia in Stable Hypercapnic COPD Patients.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) in addition to supplemental oxygen improves arterial oxygenation, walking distance and dyspnea when applied during exercise in stable hypercapnic COPD patients. The aim of the current study was to investigate whether NPPV without supplemental oxygen is capable of preventing severe exercise-induced hypoxemia in these patients when applied during walking. METHODS AND RESULTS: 15 stable hypercapnic COPD patients (FEV1 29.9 ± 15.9%) performed two 6-minute walk tests (6MWT) with a rollator in a randomized cross-over design: using either supplemental oxygen (2.4 ± 0.7 L/min) or NPPV (inspiratory/expiratory positive airway pressure of 28.2 ± 2.8 / 5.5 ± 1.5 mbar) without supplemental oxygen. RESULTS: 10 patients were able to complete both 6MWT. 6MWT with supplemental oxygen resulted in no changes for PO2 (pre: 67.3 ± 11.2 mmHg vs. post: 65.6 ± 12.0 mmHg, p = 0.72) whereas PCO2 increased (pre: 50.9 ± 8.1 mmHg vs. post: 54.3 ± 10.0 mmHg (p < 0.03). During 6MWT with NPPV PO2 significantly decreased from 66.8 ± 7.2 mmHg to 55.5 ± 10.6 mmHg (p < 0.02) whereas no changes occurred in PCO2 (pre: 50.6 ± 7.5 mmHg vs. post: 53.0 ± 7.1 mmHg; p = 0.17). Walking distance tended to be lower in 6MWT with NPPV compared to 6MWT with supplemental oxygen alone (318 ± 160 m vs. 377 ± 108 m; p = 0.08). CONCLUSION: The use of NPPV during walking without the application of supplemental oxygen does not prevent exercise-induced hypoxemia in patients with stable hypercapnic COPD.

The combination of exercise and respiratory training improves respiratory muscle function in pulmonary hypertension.

PURPOSE: Increased dyspnea and reduced exercise capacity in pulmonary arterial hypertension (PAH) can be partly attributed to impaired respiratory muscle function. This prospective study was designed to assess the impact of exercise and respiratory training on respiratory muscle strength and 6-min walking distance (6MWD) in PAH patients. METHODS: Patients with invasively confirmed PAH underwent 3 weeks of in-hospital exercise and respiratory training, which was continued at home for another 12 weeks. Medication remained constant during the study period. Blinded observers assessed efficacy parameters at baseline (I) and after 3 (II) and 15 weeks (III). Respiratory muscle function was assessed by twitch mouth pressure (TwPmo) during nonvolitional supramaximal magnetic phrenic nerve stimulation. RESULTS: Seven PAH patients (4 women; mean pulmonary artery pressure 45 ± 11 mmHg, median WHO functional class 3.1 ± 0.4, idiopathic/associated PAH n = 5/2) were included. The training program was feasible and well tolerated by all patients with excellent compliance. TwPmo was I: 0.86 ± 0.37 kPa, II: 1.04 ± 0.29 kPa, and III: 1.27 ± 0.44 kPa, respectively. 6MWD was I: 417 ± 51 m, II: 509 ± 39 m, and III: 498 ± 39 m, respectively. Both TwPmo (+0.41 ± 0.34 kPa, +56 ± 39 %) and 6MWD (+81 ± 30 m, +20 ± 9 %) increased significantly in the period between baseline and the final assessment (pairwise comparison: p = 0.012/<0.001; RM-ANOVA considering I, II, III: p = 0.037/<0.001). CONCLUSIONS: Exercise and respiratory training as an adjunct to medical therapy may be effective in patients with PAH to improve respiratory muscle strength and exercise capacity. Future, randomized, controlled trials should be carried out to further investigate these findings.

Respiratory muscle function in interstitial lung disease.

Interstitial lung diseases limit daily activities, impair quality of life and result in (exertional) dyspnoea. This has mainly been attributed to a decline in lung function and impaired gas exchange. However, the contribution of respiratory muscle dysfunction to these limitations remains to be conclusively investigated. Interstitial lung disease patients and matched controls performed body plethysmography, a standardised 6-min walk test, volitional tests (respiratory drive (P0.1), global maximal inspiratory mouth occlusion pressure (PImax), sniff nasal pressure (SnPna) and inspiratory muscle load) and nonvolitional tests on respiratory muscle function and strength (twitch mouth and transdiaphragmatic pressure during bilateral magnetic phrenic nerve stimulation (TwPmo and TwPdi)). 25 patients and 24 controls were included in the study. PImax and SnPna remained unaltered (both p>0.05), whereas P0.1 and the load on the inspiratory muscles were higher (both p<0.05) in interstitial lung disease patients compared with controls. TwPmo and TwPdi were lower in interstitial lung disease patients (mean±sd TwPmo 0.86±0.4 versus 1.32±0.4, p<0.001; TwPdi 1.34±0.6 versus 1.88±0.5, p=0.022). Diaphragmatic force generation seems to be impaired in this cohort of interstitial lung disease patients while global respiratory muscle strength remains preserved. Central respiratory drive and the load imposed on the inspiratory muscles are increased. Whether impaired respiratory muscle function impacts morbidity and mortality in interstitial lung disease patients needs to be investigated in future studies.

The effect of continuous positive airway pressure on stair-climbing performance in severe COPD patients.

Stair climbing is associated with dynamic pulmonary hyperinflation and the development of severe dyspnea in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess whether (i) continuous positive airway pressure (CPAP) applied during stair climbing prevents dynamic hyperinflation and thereby reduces exercise-induced dyspnea in oxygen-dependent COPD-patients, and (ii) the CPAP-device and oxygen tank can be carried in a hip belt. In a randomised cross-over design, oxygen-dependent COPD patients performed two stair-climbing tests (44 steps): with supplemental oxygen only, then with the addition of CPAP (7 mbar). The oxygen tank and CPAP-device were carried in a hip belt during both trials. Eighteen COPD patients were included in the study. Although all patients could tolerate stair climbing with oxygen alone, 4 patients were unable to perform stair climbing while using CPAP. Fourteen COPD patients (mean FEV1 36 ± 14% pred.) completed the trial and were analyzed. The mean flow rate of supplemental oxygen was 3 ± 2 l/min during stair climbing. Lung hyperinflation, deoxygenation, hypoventilation, blood lactate production, dyspnea and the time needed to manage stair climbing were not improved by the application of CPAP (all p > 0.05). However, in comparison to climbing with oxygen alone, limb discomfort was reduced when oxygen was supplemented with CPAP (p = 0.008). In conclusion, very severe COPD patients are able to carry supporting devices such as oxygen tanks or CPAP-devices in a hip belt during stair climbing. However, the application of CPAP in addition to supplemental oxygen during stair climbing prevents neither exercise-induced dynamic hyperinflation, nor dyspnea.

Model-Based Estimation of Inspiratory Effort Using Surface EMG.

OBJECTIVE: The quantification of inspiratory patient effort in assisted mechanical ventilation is essential for the adjustment of ventilatory assistance and for assessing patient-ventilator interaction. The inspiratory effort is usually measured via the respiratory muscle pressure (P mus) derived from esophageal pressure (P es) measurements. As yet, no reliable non-invasive and unobtrusive alternatives exist to continuously quantify P mus. METHODS: We propose a model-based approach to estimate P mus non-invasively during assisted ventilation using surface electromyographic (sEMG) measurements. The method combines the sEMG and ventilator signals to determine the lung elastance and resistance as well as the neuromechanical coupling of the respiratory muscles via a novel regression technique. Using the equation of motion, an estimate for P mus can then be calculated directly from the lung mechanical parameters and the pneumatic ventilator signals. RESULTS: The method was applied to data recorded from a total of 43 ventilated patients and validated against P es-derived P mus. Patient effort was quantified via the P mus pressure-time-product (PTP). The sEMG-derived PTP estimated using the proposed method was highly correlated to P es-derived PTP ([Formula: see text]), and the breath-wise deviation between the two quantities was [Formula: see text]. CONCLUSION: The estimated, sEMG-derived P mus is closely related to the P es-based reference and allows to reliably quantify inspiratory effort. SIGNIFICANCE: The proposed technique provides a valuable tool for physicians to assess patients undergoing assisted mechanical ventilation and, thus, may support clinical decision making.

Early Detection of Lung Cancer Using Small RNAs.

INTRODUCTION: Lung cancer remains the deadliest cancer in the world, and lung cancer survival is heavily dependent on tumor stage at the time of detection. Low-dose computed tomography screening can reduce mortality; however, annual screening is limited by low adherence in the United States of America and still not broadly implemented in Europe. As a result, less than 10% of lung cancers are detected through existing programs. Thus, there is a great need for additional screening tests, such as a blood test, that could be deployed in the primary care setting. METHODS: We prospectively recruited 1384 individuals meeting the National Lung Screening Trial demographic eligibility criteria for lung cancer and collected stabilized whole blood to enable the pipetting-free collection of material, thus minimizing preanalytical noise. Ultra-deep small RNA sequencing (20 million reads per sample) was performed with the addition of a method to remove highly abundant erythroid RNAs, and thus open bandwidth for the detection of less abundant species originating from the plasma or the immune cellular compartment. We used 100 random data splits to train and evaluate an ensemble of logistic regression classifiers using small RNA expression of 943 individuals, discovered an 18-small RNA feature consensus signature (miLung), and validated this signature in an independent cohort (441 individuals). Blood cell sorting and tumor tissue sequencing were performed to deconvolve small RNAs into their source of origin. RESULTS: We generated diagnostic models and report a median receiver-operating characteristic area under the curve of 0.86 (95% confidence interval [CI]: 0.84-0.86) in the discovery cohort and generalized performance of 0.83 in the validation cohort. Diagnostic performance increased in a stage-dependent manner ranging from 0.73 (95% CI: 0.71-0.76) for stage I to 0.90 (95% CI: 0.89-0.90) for stage IV in the discovery cohort and from 0.76 to 0.86 in the validation cohort. We identified a tumor-shed, plasma-bound ribosomal RNA fragment of the L1 stalk as a dominant predictor of lung cancer. The fragment is decreased after surgery with curative intent. In additional experiments, results of dried blood spot collection and sequencing revealed that small RNA analysis could potentially be conducted through home sampling. CONCLUSIONS: These data suggest the potential of a small RNA-based blood test as a viable alternative to low-dose computed tomography screening for early detection of smoking-associated lung cancer.

Neural respiratory drive as a physiological biomarker to monitor change during acute exacerbations of COPD.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease have a significant negative impact on both patients and healthcare systems. Currently, there are no physiological biomarkers that effectively monitor clinical change or predict respiratory readmission. Acute exacerbations impose a change in the respiratory muscle load-capacity-drive relationship. It was hypothesised that lack of a fall in neural respiratory drive would identify patients at risk of treatment failure and early hospital readmission. METHODS: An observational study was performed at two UK teaching hospitals. Routine clinical physiological parameters and neural respiratory drive index (NRDI), calculated as the product of second intercostal space parasternal electromyography (EMG) activity normalised to the peak EMG activity during a maximum inspiratory sniff manoeuvre and respiratory rate, were recorded daily from admission to discharge. RESULTS: 30 acutely unwell patients of mean (SD) age 72 (10) years, forced expiratory volume in 1 s 0.60 (1.65) l, NRDI 455 (263) AU and median length of stay 6 days were studied. Changes in NRDI correlated with changes in Borg score (r=+0.60; p<0.001), discriminated between patients deemed to have clinically improved rather than deteriorated (mean difference 339 AU; 95% CI 234 to 444; p<0.001) and identified those patients readmitted within 14 days (mean difference 203 AU; 95% CI 39 to 366; p=0.017). CONCLUSIONS: NRDI is a feasible clinical physiological parameter in patients with an acute exacerbation of chronic obstructive pulmonary disease and can provide useful information on treatment response and risk of readmission.

Proportional assist ventilation improves exercise capacity in patients with obesity.

BACKGROUND: Exercise capacity is reduced in obese patients due to disadvantageous respiratory mechanics that lead to dyspnea. Proportional assist ventilation (PAV) has the potential to unload resistive and elastic burdens of the ventilatory system. OBJECTIVES: The present study aimed to test if PAV can increase endurance and reduce exercise-related dyspnea in obese patients. METHODS: Two symptom-limited exercise tests were performed at 75% of V.O(2max): (1) without PAV and (2) with PAV. Exercise endurance, blood gases, dyspnea and limb discomfort (Borg scale) were assessed. Responders to PAV were defined as those increasing their exercise duration by more than 20%. RESULTS: Eighteen male obese patients (body mass index 35 +/- 5 kg/m(2)) were investigated. Overall, PAV increased exercise duration by 13% (p = 0.037) and improved exercise-induced dyspnea (p = 0.004). In responders (n = 10), PAV increased the exercise duration by 31% from 721 +/- 300 to 1,041 +/- 454 s (p < 0.001) and reduced dyspnea (p = 0.004) as well as limb discomfort (p = 0.016). Following stepwise multiple linear regression analysis, prolonged exercise time with PAV can only be predicted from total lung capacity (p = 0.02), considering total lung capacity, V.O(2max) and body mass index. CONCLUSIONS: PAV applied during exercise led to an overall prolongation in exercise endurance and a reduction in dyspnea in obese patients. There was a broad spectrum of response to PAV, with more than 50% of patients increasing their exercise endurance by a mean of 31%. Therefore, PAV might serve as a novel treatment option to enhance exercise capacity in a subgroup of obese patients in rehabilitation programs.

Impairment of respiratory muscle function in pulmonary hypertension.

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.5; 25 patients with pulmonary arterial hypertension and six patients with chronic thromboembolic PH) and in 31 control subjects (20 females and 11 males) well-matched for gender, age and BMI (body mass index). A 6-min walking test was performed to determine exercise capacity. Volitionally assessed maximal inspiratory (7.5+/-2.1 compared with 6.2+/-2.8 kPa; P=0.04) and expiratory (13.3+/-4.2 compared with 9.9+/-3.4 kPa; P<0.001) mouth pressures, sniff nasal (8.3+/-1.9 compared with 6.6+/-2.2 kPa; P=0.002) and transdiaphragmatic (11.3+/-2.5 compared with 8.7+/-2.5 kPa; P<0.001) pressures, non-volitionally assessed twitch mouth (1.46+/-0.43 compared with 0.97+/-0.41 kPa; P<0.001) and transdiaphragmatic (2.08+/-0.55 compared with 1.47+/-0.72 kPa; P=0.001) pressures during bilateral anterior magnetic phrenic nerve stimulation were markedly lower in patients with PH compared with control subjects. Maximal inspiratory mouth (r=0.58, P<0.001) and sniff transdiaphragmatic (r=0.43, P=0.02) pressures were correlated with the 6-min walking distance in patients with PH. In conclusion, the present study provides strong evidence that respiratory muscle strength is reduced in patients with PH compared with well-matched control subjects. Furthermore, the 6-min walking distance is significantly linked to parameters assessing inspiratory muscle strength.

Independence of exercise-induced diaphragmatic fatigue from ventilatory demands.

Exercise-induced diaphragmatic fatigue (DF) manifests after - rather than during - exercise. This suggests that DF reflects post-exercise diaphragm-shielding. This study tested the physiological hypothesis that diaphragmatic force-generation undergoes similar regulations during either whole-body-exercise or controlled hyperventilation, but differs during recovery. Ten trained subjects (VO2(max) 60.3+/-6.4 ml/kg/min) performed: I, cycling exercise (maximal workload: 85% VO2(max)); II, controlled hyperventilation (exercise breathing pattern) followed by recovery. Ergospirometric data and twitch transdiaphragmatic pressure (TwPdi) were consecutively assessed. DF occurred following exercise, while hyperventilation enhanced diaphragmatic force-generation (TwPdi-rest 2.28+/-0.58 vs. 2.52+/-0.54, TwPdi-end-recovery: 1.94+/-0.32 kPa vs. 2.81+/-0.49 kPa, both p<0.05). TwPdi was comparable between the two protocols until recovery (p>0.05, RM-ANOVA) whereby it underwent a progressive increase. In conclusion, TwPdi progressively increases and is subject to similar regulations during exercise versus controlled hyperventilation, but differs markedly during recovery. Here, DF occurred after exercise while TwPdi increased subsequent to hyperventilation. Therefore, ventilatory demands regulate diaphragmatic force-generation during exercise, whereas DF must be attributed to non-ventilatory controlled feedback mechanisms.

Post-exercise diaphragm shielding: a novel approach to exercise-induced diaphragmatic fatigue.

Based on the "post-exercise diaphragm shielding" hypothesis this study tested whether both diaphragmatic force-generation (DFG) and diaphragmatic fatigue (DF) remain unchanged during consecutive exercise-trials. Twelve subjects (V(O2 max) 58.4+/-6.6 ml kg(-1) min(-1)) performed three consecutive exercise-trials (T(alpha)/T(beta)/T(gamma); workload(max) 85% V(O2 max)) each followed by recovery (6 min). Twitch transdiaphragmatic pressure during supramaximal magnetic phrenic nerve stimulation (TwPdi, every 30s), ratings of perceived exertion (RPE, every 90 s) and ergospirometric data (continuously) were assessed throughout the entire protocol (46.5 min). DFG and DF did not differ among all trials (TwPdi-baseline: 2.2+/-0.7 kPa; TwPdi-peak: T(alpha)/T(beta)/T(gamma) 3.1+/-0.7 kPa vs 3.0+/-0.8 kPa vs 3.2+/-0.8 kPa; TwPdi-bottom: T(alpha)/T(beta)/T(gamma) 1.9+/-0.6 kPa vs 2.0+/-0.7 kPa vs 1.8+/-0.5 kPa, both p>0.4, RM-ANOVA). Furthermore, TwPdi revealed close relationships with RPE (r=0.91, p<0.0001) and oxygen uptake (r=0.94, p<0.0001) during exercise. In conclusion, both DFG (baseline-to-peak) and DF (baseline-to-bottom) achieve similar magnitudes during and after consecutive exercise-trials and are closely linked to RPE and oxygen uptake. This suggests that DF neither reflects impaired diaphragmatic function nor impairs exercise performance; rather it is likely to reflect post-exercise diaphragm shielding.

Activation of respiratory muscles during respiratory muscle training.

It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order. Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax). 41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05). DIA was higher applying IPTL compared to IFRL or VIH (p<0.05). IPTL, IFRL and VIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL.