Rationale Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. Objectives This study investigated diaphragm muscle strength in patients after COVID-19 and its relationship to unexplained dyspnea on exertion. Methods Fifty patients previously hospitalized with COVID-19 (14 female, age 58 ± 12 yr, half of whom were treated with mechanical ventilation, and half of whom were treated outside the ICU) were evaluated using pulmonary function testing, 6-minute-walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm function data were compared with values from a healthy control group. Measurements and Main Results Moderate or severe dyspnea on exertion was present at 15 months after hospital discharge in approximately two-thirds of patients. No significant pulmonary function or echocardiography abnormalities were detected. Twitch transdiaphragmatic pressure was significantly impaired in patients previously hospitalized with COVID-19 compared with control subjects, independent of initial disease severity (14 ± 8 vs. 21 ± 3 cm H 2 O in mechanically ventilated patients vs. control subjects [ P = 0.02], and 15 ± 8 vs. 21 ± 3 cm H 2 O in nonventilated patients vs. control subjects [ P = 0.04]). There was a significant association between twitch transdiaphragmatic pressure and the severity of dyspnea on exertion ( P = 0.03). Conclusions Diaphragm muscle weakness was present 15 months after hospitalization for COVID-19 even in patients who did not require mechanical ventilation, and this weakness was associated with dyspnea on exertion. The current study, therefore, identifies diaphragm muscle weakness as a correlate for persistent dyspnea in patients after COVID-19 in whom lung and cardiac function are normal. Clinical trial registered with www.clinicaltrials.gov (NCT 04854863).

<b><i>Background and objective:</i></b> The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood. <b><i>Methods:</i></b> Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (<i>n</i> = 34). <b><i>Results:</i></b> Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to &#x3c;15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (<i>p</i> &#x3c; 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO₂] &#x3c;90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO₂, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all <i>p</i> &#x3e; 0.05). Right ventricular (RV) end-diastolic (<i>r</i> = −0.39; <i>p</i> = 0.03) and end-systolic (<i>r</i> = −0.36; <i>p</i> = 0.04) volumes were inversely correlated with mean nocturnal SpO₂ but not with measures of OSA severity or daytime clinical variables. <b><i>Conclusion:</i></b> OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO₂, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.

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

Evidence from both animal and human studies now supports the development of ventilator-induced diaphragm dysfunction (VIDD) starting as early as 24 h after initiation of mechanical ventilation in the intensive care unit (ICU). However, although the concept of VIDD is now widely accepted, there remain several unanswered questions regarding its pathophysiology, rate of development, and (potentially) recovery after mechanical ventilation.This state-of-the-art opinion article briefly explains VIDD and provides an update on its clinical and prognostic relevance. It then focusses on state-of-the-art diagnostic approaches to determine diaphragm function, strength, and control (neural and peripheral), highlights knowledge gaps relevant to VIDD, and discusses the use of diaphragm pacing for VIDD prevention. It is suggested that future research projects in mechanically ventilated patients would ideally use both cortical and cervical phrenic nerve stimulation studies over time (including also diaphragm electromyography) as the gold standard techniques. This approach has not yet been utilized in a longitudinally designed study in the ICU. Application of these gold standard techniques would allow better understanding of the true pathophysiology and rate of development of VIDD. Notably, these techniques would be superior to diaphragm ultrasound, which yields surrogate markers of diaphragm function only without any direct measure of diaphragm strength or control. It is also suggested that such translational research would further advance understanding of diaphragm pacing as a very promising treatment option for VIDD.

This article explains the comprehensive state of the art assessment of sympathetic (SNA) and vagal nerve activity recordings in humans and highlights the precise mechanisms mediating increased SNA and its corresponding presumed clinical determinants and therapeutic potential in the context of chronic obstructive pulmonary disease (COPD). It is known that patients with COPD exhibit increased muscle sympathetic nerve activity (MSNA), as measured directly using intraneural microelectrodes—the gold standard for evaluation of sympathetic outflow. However, the underlying physiological mechanisms responsible for the sympathoexcitation in COPD and its clinical relevance are less well understood. This may be related to the absence of a systematic approach to measure the increase in sympathetic activity and the lack of a comprehensive approach to assess the underlying mechanisms by which MSNA increases. The nature of sympathoexcitation can be dissected by distinguishing the heart rate increasing properties (heart rate and blood pressure variability) from the vasoconstrictive drive to the peripheral vasculature (measurement of catecholamines and MSNA) (Graphical Abstract Figure 1). Invasive assessment of MSNA to the point of single unit recordings with analysis of single postganglionic sympathetic firing, and hence SNA drive to the peripheral vasculature, is the gold standard for quantification of SNA in humans but is only available in a few centres worldwide because it is costly, time consuming and requires a high level of training. A broad picture of the underlying pathophysiological determinants of the increase in sympathetic outflow in COPD can only be determined if a combination of these tools are used. Various factors potentially determine SNA in COPD (Graphical Abstract Figure 1): Obstructive sleep apnoea (OSA) is highly prevalent in COPD, and leads to repeated bouts of upper airway obstructions with hypoxemia, causing repetitive arousals. This probably produces ongoing sympathoexcitation in the awake state, likely in the “blue bloater” phenotype, resulting in persistent vasoconstriction. Other variables likely describe a subset of COPD patients with increase of sympathetic drive to the heart, clinically likely in the “pink puffer” phenotype. Pharmacological treatment options of increased SNA in COPD could comprise beta blocker therapy. However, as opposed to systolic heart failure a similar beneficial effect of beta blocker therapy in COPD patients has not been shown. The point is made that although MSNA is undoubtedly increased in COPD (probably independently from concomitant cardiovascular disease), studies designed to determine clinical improvements during specific treatment will only be successful if they include adequate patient selection and translational state of the art assessment of SNA. This would ideally include intraneural recordings of MSNA and—as a future perspective—vagal nerve activity all of which should ideally be assessed both in the upright and in the supine position to also determine baroreflex function.