Introduction: Besides dyspnoea and cough, patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis may experience distressing non-respiratory symptoms, such as fatigue or muscle weakness. However, whether and to what extent symptom burden differs between patients with IPF or sarcoidosis and individuals without respiratory disease remains currently unknown. Objectives: To study the respiratory and non-respiratory burden of multiple symptoms in patients with IPF or sarcoidosis and to compare the symptom burden with individuals without impaired spirometric values, FVC and FEV1 (controls). Methods: Demographics and symptoms were assessed in 59 patients with IPF, 60 patients with sarcoidosis and 118 controls (age ≥18 years). Patients with either condition were matched to controls by sex and age. Severity of 14 symptoms was assessed using a Visual Analogue Scale. Results: 44 patients with IPF (77.3% male; age 70.6±5.5 years) and 44 matched controls, and 45 patients with sarcoidosis (48.9% male; age 58.1±8.6 year) and 45 matched controls were analyzed. Patients with IPF scored higher on 11 symptoms compared to controls (p<0.05), with the largest differences for dyspnoea, cough, fatigue, muscle weakness and insomnia. Patients with sarcoidosis scored higher on all 14 symptoms (p<0.05), with the largest differences for dyspnoea, fatigue, cough, muscle weakness, insomnia, pain, itch, thirst, micturition (night, day). Conclusions: Generally, respiratory and non-respiratory symptom burden is significantly higher in patients with IPF or sarcoidosis compared to controls. This emphasizes the importance of awareness for respiratory and non-respiratory symptom burden in IPF or sarcoidosis and the need for additional research to study the underlying mechanisms and subsequent interventions.
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INTRODUCTION: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.METHODS: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.FINDINGS: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2).INTERPRETATION: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality.
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Subcutaneous emphysema, pneumothorax and pneumomediastinum are well-known complications of invasive ventilation in patients with acute hypoxemic respiratory failure. We determined the incidences of air leaks that were visible on available chest images in a cohort of critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease of 2019 (COVID-19) in a single-center cohort in the Netherlands. A total of 712 chest images from 154 patients were re-evaluated by a multidisciplinary team of independent assessors; there was a median of three (2–5) chest radiographs and a median of one (1–2) chest CT scans per patient. The incidences of subcutaneous emphysema, pneumothoraxes and pneumomediastinum present in 13 patients (8.4%) were 4.5%, 4.5%, and 3.9%. The median first day of the presence of an air leak was 18 (2–21) days after arrival in the ICU and 18 (9–22)days after the start of invasive ventilation. We conclude that the incidence of air leaks was high in this cohort of COVID-19 patients, but it was fairly comparable with what was previously reported in patients with acute hypoxemic respiratory failure in the pre-COVID-19 era.
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Background: INTELLiVENT-adaptive support ventilation (ASV) is an automated closed-loop mode of invasive ventilation for use in critically ill patients. INTELLiVENT-ASV automatically adjusts, without the intervention of the caregiver, ventilator settings to achieve the lowest work and force of breathing. Aims: The aim of this case series is to describe the specific adjustments of INTELLiVENT-ASV in patients with acute hypoxemic respiratory failure, who were intubated for invasive ventilation. Study design: We describe three patients with severe acute respiratory distress syndrome (ARDS) because of COVID-19 who received invasive ventilation in our intensive care unit (ICU) in the first year of the COVID-19 pandemic. Results: INTELLiVENT-ASV could be used successfully, but only after certain adjustments in the settings of the ventilator. Specifically, the high oxygen targets that are automatically chosen by INTELLiVENT-ASV when the lung condition ‘ARDS’ is ticked had to be lowered, and the titration ranges for positive end expiratory pressure (PEEP) and inspired oxygen fraction (FiO2) had to be narrowed. Conclusions: The challenges taught us how to adjust the ventilator settings so that INTELLiVENT-ASV could be used in successive COVID-19 ARDS patients, and we experienced the benefits of this closed-loop ventilation in clinical practice. Relevance to clinical practice: INTELLiVENT-ASV is attractive to use in clinical practice. It is safe and effective in providing lung-protective ventilation. A closely observing user always remains needed. INTELLiVENT-ASV has a strong potential to reduce the workload associated with ventilation because of the automated adjustments.
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BackgroundHigh-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as in patients receiving ventilation.MethodsWe applied a broadened definition of ARDS in a multicenter, observational study in adult critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), wherein the requirement for a minimal level of 5 cm H2O PEEP with ventilation is replaced by a minimal level of airflow rate with HFNO, and compared baseline characteristics and outcomes between patients receiving HFNO and patients receiving ventilation. The primary endpoint was ICU mortality. We also compared outcomes in risk for death groups using the PaO2/FiO2 cutoffs as used successfully in the original definition of ARDS. Secondary endpoints were hospital mortality; mortality on days 28 and 90; need for ventilation within 7 days in patients that started with HFNO; the number of days free from HFNO or ventilation; and ICU and hospital length of stay.ResultsOf 728 included patients, 229 patients started with HFNO and 499 patients with ventilation. All patients fulfilled the broadened Berlin definition of ARDS. Patients receiving HFNO had lower disease severity scores and lower PaO2/FiO2 than patients receiving ventilation. ICU mortality was lower in receiving HFNO (22.7 vs 35.6%; p = 0.001). Using PaO2/FiO2 cutoffs for mild, moderate and severe arterial hypoxemia created groups with an ICU mortality of 16.7%, 22.0%, and 23.5% (p = 0.906) versus 19.1%, 37.9% and 41.4% (p = 0.002), in patients receiving HFNO versus patients receiving ventilation, respectively.ConclusionsUsing a broadened definition of ARDS may facilitate an earlier diagnosis of ARDS in patients receiving HFNO; however, ARDS patients receiving HFNO and ARDS patients receiving ventilation have distinct baseline characteristics and mortality rates.Trial registration: The study is registered at ClinicalTrials.gov (identifier NCT04719182).
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BACKGROUND: The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure.METHODS: We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality.RESULTS: In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88-1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01-1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01-1.30]; P = 0.028).CONCLUSIONS: In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342).
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BACKGROUND The mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain.OBJECTIVE To investigate the association of mechanical power with mortality in ICU patients without ARDS.DESIGN This was an individual patient data analysis that uses the data of three multicentre randomised trials.SETTING This study was performed in academic and nonacademic ICUs in the Netherlands.PATIENTS One thousand nine hundred and sixty-two invasively ventilated patients without ARDS were included in this analysis. The median [IQR] age was 67 [57 to 75] years, 706 (36%) were women.MAIN OUTCOME MEASURES The primary outcome was the all-cause mortality at day 28. Secondary outcomes were the all-cause mortality at day 90, and length of stay in ICU and hospital.RESULTS At day 28, 644 patients (33%) had died. Hazard ratios for mortality at day 28 were higher with an increasing MP, even when stratified for its individual components (driving pressure (P < 0.001), tidal volume (P < 0.001), respiratory rate (P < 0.001) and maximum airway pressure (P = 0.001). Similar associations of mechanical power (MP) were found with mortality at day 90, lengths of stay in ICU and hospital. Hazard ratios for mortality at day 28 were not significantly different if patients were stratified for MP, with increasing levels of each individual component.CONCLUSION In ICU patients receiving invasive ventilation for reasons other than ARDS, MP had an independent association with mortality. This finding suggests that MP holds an added predictive value over its individual components, making MP an attractive measure to monitor and possibly target in these patients.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02159196, ClinicalTrials.gov Identifier: NCT02153294, ClinicalTrials.gov Identifier: NCT03167580.
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BackgroundMechanical ventilation affects the respiratory muscles, but little is known about long-term recovery of respiratory muscle weakness (RMW) and potential associations with physical functioning in survivors of critical illness. The aim of this study was to investigate the course of recovery of RMW and its association with functional outcomes in patients who received mechanical ventilation.MethodsWe conducted a prospective cohort study with 6-month follow-up among survivors of critical illness who received ≥ 48 hours of invasive mechanical ventilation. Primary outcomes, measured at 3 timepoints, were maximal inspiratory and expiratory pressures (MIP/MEP). Secondary outcomes were functional exercise capacity (FEC) and handgrip strength (HGS). Longitudinal changes in outcomes and potential associations between MIP/MEP, predictor variables, and secondary outcomes were investigated through linear mixed model analysis.ResultsA total of 59 participants (male: 64%, median age [IQR]: 62 [53–66]) were included in this study with a median (IQR) ICU and hospital length of stay of 11 (8–21) and 35 (21–52) days respectively. While all measures were well below predicted values at hospital discharge (MIP: 68.4%, MEP 76.0%, HGS 73.3% of predicted and FEC 54.8 steps/2m), significant 6-month recovery was seen for all outcomes. Multivariate analyses showed longitudinal associations between older age and decreased MIP and FEC, and longer hospital length of stay and decreased MIP and HGS outcomes. In crude models, significant, longitudinal associations were found between MIP/MEP and FEC and HGS outcomes. While these associations remained in most adjusted models, an interaction effect was observed for sex.ConclusionRMW was observed directly after hospital discharge while 6-month recovery to predicted values was noted for all outcomes. Longitudinal associations were found between MIP and MEP and more commonly used measures for physical functioning, highlighting the need for continued assessment of respiratory muscle strength in deconditioned patients who are discharged from ICU. The potential of targeted training extending beyond ICU and hospital discharge should be further explored.
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Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
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Aims: This systematic review and meta-analysis evaluates the additional effect of exercise to hypocaloric diet on body weight, body composition, glycaemic control and cardio-respiratory fitness in adults with overweight or obesity and type 2 diabetes. Methods: Embase, Medline, Web of Science and Cochrane Central databases were evaluated, and 11 studies were included. Random-effects meta-analysis was performed on body weight and measures of body composition and glycaemic control, to compare the effect of hypocaloric diet plus exercise with hypocaloric diet alone. Results: Exercise interventions consisted of walking or jogging, cycle ergometer training, football training or resistance training and duration varied from 2 to 52 weeks. Body weight and measures of body composition and glycaemic control decreased during both the combined intervention and hypocaloric diet alone. Mean difference in change of body weight (−0.77 kg [95% CI: −2.03; 0.50]), BMI (−0.34 kg/m2 [95% CI: −0.73; 0.05]), waist circumference (−1.42 cm [95% CI: −3.84; 1.00]), fat-free mass (−0.18 kg [95% CI: −0.52; 0.17]), fat mass (−1.61 kg [95% CI: −4.42; 1.19]), fasting glucose (+0.14 mmol/L [95% CI: −0.02; 0.30]), HbA1c (−1 mmol/mol [95% CI: −3; 1], −0.1% [95% CI: −0.2; 0.1]) and HOMA-IR (+0.01 [95% CI: −0.40; 0.42]) was not statistically different between the combined intervention and hypocaloric diet alone. Two studies reported VO2max and showed significant increases upon the addition of exercise to hypocaloric diet. Conclusions: Based on limited data, we did not find additional effects of exercise to hypocaloric diet in adults with overweight or obesity and type 2 diabetes on body weight, body composition or glycaemic control, while cardio-respiratory fitness improved.
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