Automated Oxygen Administration Alleviates Dyspnea in Patients Admitted with Acute Exacerbation of COPD: A Randomized Controlled Trial.

Objective: Devices for Automated Oxygen Administration (AOA) have been developed to optimize the therapeutic benefit of oxygen supplementation. We aimed to investigate the effect of AOA on multidimensional aspects of dyspnea and as-needed consumption of opioids and benzodiazepines, as opposed to conventional oxygen therapy, in hospitalized patients with Acute Exacerbation of COPD (AECOPD). Method and Patients: A multicenter randomized controlled trial across five respiratory wards in the Capital Region of Denmark. Patients admitted with AECOPD (n=157) were allocated 1:1 to either AOA (O2matic Ltd), a closed loop device automatically delivering oxygen according to the patient's peripheral oxygen saturation (SpO2), or conventional nurse-administered oxygen therapy. Oxygen flows and SpO2 levels were measured by the O2matic device in both groups, while dyspnea, anxiety, depression, and COPD symptoms were accessed by Patient Reported Outcomes. Results: Of the 157 randomized patients, 127 had complete data for the intervention. The AOA reduced patients' perception of overall unpleasantness significantly on the Multidimensional Dyspnea Profile (MDP) with a difference in medians of -3 (p=0.003) between the intervention group (n=64) and the control group (n=63). The AOA also provided a significant between group difference in all single items within the sensory domain of the MDP (all p-values≤0.05) as well as in the Visual Analogue Scale - Dyspnea (VAS-D) within the past three days (p=0.013). All between group differences exceeded the Minimal Clinical Important Difference of the MDP and VAS-D, respectively. AOA did not seem to have an impact on the emotional response domain of the MDP, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, or use of as-needed opioids and/or benzodiazepines (all p-values>0.05). Conclusion: AOA reduces both breathing discomfort and physical perception of dyspnea in patients admitted with AECOPD but did not seem to impact the emotional status or other COPD symptoms.

Automated versus manual oxygen administration for patients admitted with acute cardiovascular disease - a study protocol of a randomised controlled trial.

INTRODUCTION: Oxygen treatment of hypoxaemia is considered an essential part of the treatment of patients who are acutely admitted with medical conditions affecting cardiovascular and/or pulmonary function. Despite the important role of oxygen administration for these patients, clinical evidence on how to control supplemental oxygen to avoid hypoxaemia and hyperoxia is limited. We aim to investigate whether an automatic closed-loop oxygen administration system (O2matic) may maintain normoxaemia better than usual care. METHODS: This study will be an investigator-initiated, prospective, randomised clinical trial. The patients are randomised during admission after informed consent is obtained, at a 1:1 ratio with conventional oxygen treatment or O2matic oxygen treatment for 24 hours. The primary outcome is time within the desired peripheral capillary oxygen saturation interval: 92-96%. CONCLUSION: This study will examine the clinical applicability of a novel automated feedback device termed O2matic and assess whether the device is superior to standard care in keeping the patients in the optimal saturation interval. We hypothesise that the O2matic will increase time within the desired saturation interval. FUNDING: Johannes Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by The Danish Heart Foundation. CLINICALTRIALS: gov (ClinicalTrials.gov Identifier: NCT05452863). Registered on 11 July 2022.

Hypoxemia and not hyperoxemia predicts worse outcome in severe COPD exacerbations - an observational study.

Objectives: For patients admitted with an acute exacerbation of COPD (AECOPD) and a need for supplementary oxygen therapy, to determine if peripheral oxygen saturation < 88% (hypoxemia) or >92% (hyperoxemia), within first 24 hours of admission, is associated with 'treatment failure' or fewer days alive and out of hospital within 14 days after admission. Design: A retrospective multicenter observational study, reviewing consecutive data on SpO2, oxygen, and drug administration at three predefined time points, on adverse events in patients admitted with COPD between December 2019 and June 2020. Multivariable logistic regression analysis, Mann Whitney U- and Chi-square-test were used. Setting: Acute hospital setting, across four different hospitals in the capital region of Denmark. Participants: Patients with a confirmed diagnosis of COPD admitted with an acute exacerbation and an oxygen need within the first 24 hours admission. Results: In total 289 COPD patients were included. The median age was 74.8 years [interquartile range (IQR):69.6 to 81.8], 191 were female and 132 patients experienced 'treatment failure'. A minimum of one episode of hypoxemia (SpO2 < 88%) within first 24 hours was associated with having a low number (≤4) of days alive and out of hospital within 14 days after admission: OR 2.4 (95%CI 1.2 to 4.8), p = 0.02, absolute risk 44% vs. 26% p = 0.01, Chi-square. Comparable results were observed after 30 days of follow-up: OR 2.6 (95% CI 1.0 to7.1), p = 0.05. A minimum of one measurement of hyperoxemia (SpO2 > 92%), within first 24 hours of admission was not associated with low number of days alive and out of hospital within 14 days OR 1.0 (95% CI 0.5 to 2.1) nor at 30 days. Conclusion: For admitted patients with AECOPD, being hypoxemic ever within the first 24 hours after admission is associated with a substantially increased risk of a poor prognosis.

Patients' Perspective on Automated Oxygen Administration during Hospitalization for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Qualitative Study Nested in a Randomized Controlled Trial.

Recently, health technology systems offering monitoring of the peripheral oxygen saturation level and automated oxygen administration (AOA) have emerged. AOA has been shown to reduce duration of hypoxemia and the length of hospital stay, but the patients' perspective on AOA has not been investigated. This qualitative study, based on the interpretive description methodology, aimed to explore how patients hospitalized with exacerbation of chronic obstructive pulmonary disease (COPD) experience being treated with AOA. Eighteen patients treated with AOA were included in the study. Data was collected during admission or in the patients' homes using semi-structured interviews focusing on patients' experiences of AOA using the word "robot" as used by patients. The findings revealed two themes "adaptation of behavior to the robot" and "robots can make patients feel safe but not cared for" and six subthemes. Our findings illustrate how patients were willing to compromise their own therapy and thereby safety by avoiding behavior triggering AOA alarms and disturbing their fellow patients and the health care professionals. Adherence, defined as patients' consistency in taking their medications as prescribed, becomes an important point of attention for health professionals when applying individualized robotic therapies such as AOA to patients with COPD. To support patients in the process of managing adherence to therapeutic technology, we propose a person-centered care approach that, through education and communication with the patients, generates an understanding of how they can self-manage AOA and its alarms without activating avoiding behavior that threatens their treatment and recovery.

Hospital admission for COVID-19 pneumonitis - long-term impairment in quality of life and lung function.

BACKGROUND AND AIM: Knowledge of long-term consequences of severe COVID-19 pneumonitis is of outmost importance. Our aim was, therefore, to assess the long-term impact on quality of life and lung function in adults hospitalized with severe COVID-19. METHODS: All patients hospitalized with COVID-19 pneumonitis at Copenhagen University Hospital-Hvidovre, Denmark, were invited to participate in the study 4-5 months after discharge. Of the 160 invited 128 responded positively (80%). Medical history and symptoms were assessed, and patients rated impact on quality of life and functional status with EuroQol-5D-5L and Post Covid Functional Scale. Lung function was assessed by dynamic spirometry and measurement of diffusing capacity. RESULTS: Fatigue, dyspnea, cough and cognitive dysfunction were the most common symptoms. Of 128 patients, 85% had at least one symptom, and 51% reported two or more symptoms. Self-rated Quality of life was impaired assessed by EuroQol 5D-5L, with dimensions 'Pain or discomfort' (61%) and 'Usual activities' (54%) mostly affected. Functional status was significantly worse than before COVID-19 assessed by Post-COVID Functional Scale. Among lung function parameters, diffusing capacity was most affected, with 45% having diffusing capacity < 80% of predicted. CONCLUSION: Fatigue, respiratory symptoms and cognitive symptoms are highly common months after hospitalization for severe COVID-19. Compared to pre-COVID-19, functional status and usual activities continued to be impaired. In line with this, almost half of the patients were found to have impaired diffusing capacity.

Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD. METHODS: We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses. RESULTS: A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001). CONCLUSION: Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.

Management of COVID-19-Associated Acute Respiratory Failure with Alternatives to Invasive Mechanical Ventilation: High-Flow Oxygen, Continuous Positive Airway Pressure, and Noninvasive Ventilation.

Patients admitted to hospital with coronavirus disease 2019 (COVID-19) may develop acute respiratory failure (ARF) with compromised gas exchange. These patients require oxygen and possibly ventilatory support, which can be delivered via different devices. Initially, oxygen therapy will often be administered through a conventional binasal oxygen catheter or air-entrainment mask. However, when higher rates of oxygen flow are needed, patients are often stepped up to high-flow nasal cannula oxygen therapy (HFNC), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or invasive mechanical ventilation (IMV). BiPAP, CPAP, and HFNC may be beneficial alternatives to IMV for COVID-19-associated ARF. Current evidence suggests that when nasal catheter oxygen therapy is insufficient for adequate oxygenation of patients with COVID-19-associated ARF, CPAP should be provided for prolonged periods. Subsequent escalation to IMV may be implemented if necessary.

Effect of Automated Oxygen Titration during Walking on Dyspnea and Endurance in Chronic Hypoxemic Patients with COPD: A Randomized Crossover Trial.

The need for oxygen increases with activity in patients with COPD and on long-term oxygen treatment (LTOT), leading to periods of hypoxemia, which may influence the patient's performance. This study aimed to evaluate the effect of automated oxygen titration compared to usual fixed-dose oxygen treatment during walking on dyspnea and endurance in patients with COPD and on LTOT. In a double-blinded randomised crossover trial, 33 patients were assigned to use either automated oxygen titration or the usual fixed-dose in a random order in two walking tests. A closed-loop device, O2matic delivered a variable oxygen dose set with a target saturation of 90-94%. The patients had a home oxygen flow of (mean ± SD) 1.6 ± 0.9 L/min. At the last corresponding isotime in the endurance shuttle walk test, the patients reported dyspnea equal to median (IQR) 4 (3-6) when using automated oxygen titration and 8 (5-9) when using fixed doses, p < 0.001. The patients walked 10.9 (6.5-14.9) min with automated oxygen compared to 5.5 (3.3-7.9) min with fixed-dose, p < 0.001. Walking with automated oxygen titration had a statistically significant and clinically important effect on dyspnea. Furthermore, the patients walked for a 98% longer time when hypoxemia was reduced with a more well-matched, personalised oxygen treatment.

COVID-19 and acute respiratory failure treated with CPAP.

Introduction: Patients admitted with COVID-19 often have severe hypoxemic respiratory insufficiency and it can be difficult to maintain adequate oxygenation with oxygen supplementation alone. There is a physiological rationale for the use of Continuous Positive Airway Pressure (CPAP), and CPAP could keep some patients off mechanical ventilation. We aimed to examine the physiological response to CPAP and the outcome of this treatment. Methods: Data from all patients admitted with COVID-19 and treated with CPAP, from March to July 2020 were collected retrospectively. CPAP was initiated on a medical ward when oxygen supplementation exceeded 10 liters/min to maintain oxygen saturation (SpO2) ≥92%. CPAP was administered with full face masks on a continuous basis until stable improvement in oxygenation or until intubation or death. Results: CPAP was initiated in 53 patients (35 men, 18 women) with a median (IQR) age of 68 (57-78) years. Nine patients were not able to tolerate the CPAP treatment. Median duration for the 44 patients receiving CPAP was 3 (2-6) days. The PaO2/FiO2 ratio was severely reduced to an average of 101 mmHg at initiation of treatment. A positive response of CPAP was seen on respiratory rate (p = 0.002) and on oxygenation (p < 0.001). Of the 44 patients receiving CPAP, 12 (27%) avoided intubation,13 (29%) were intubated, and 19 (43%) died. Of the patients with a ceiling of treatment in the ward (26 of 53) only 2 survived. Older age and high initial oxygen demand predicted treatment failure. Discussion: CPAP seems to have positive effect on oxygenation and respiratory rate in most patients with severe respiratory failure caused by COVID-19. Treatment with CPAP to severely hypoxemic patients in a medical ward is possible, but the prognosis for especially elderly patients with high oxygen requirement and with a ceiling of treatment in the ward is poor.

[Diagnostic approach and evaluation of hospitalized patients with COVID-19].

COVID-19 is the infectious disease caused by coronavirus SARS-CoV-2. The most common symptoms of COVID-19 are dry cough, tiredness and fever. Most patients recover from COVID-19 within a few weeks, but some patients have symptoms lasting for weeks or even months after recovery from acute illness, such as fatigue, shortness of breath and cough. This is a review of what we currently know about the clinical disease and its severity as well as which diagnostic strategies are recommended during and after hospital admission.

[Clinical management of hospitalised patients with COVID-19].

COVID-19 is the infectious disease caused by SARS-CoV-2. This is a review of the current treatment strategies available for patients with COVID-19 during hospital admission. Patients requiring hospitalisation frequently suffer from respiratory failure and may require oxygen therapy. Insufficient response to oxygen may be an indication, that other modalities such as high-flow nasal cannula, continuous positive airway pressure or mechanical ventilation are needed. The only medical treatments currently being used are remdesivir and dexamethasone.

Antibiotic treatment in acute exacerbation of COPD: patient outcomes with amoxicillin vs. amoxicillin/clavulanic acid-data from 43,636 outpatients.

BACKGROUND: For antibiotic treatment of Acute exacerbations of COPD (AECOPD) the National guidelines in Denmark recommend either first choice amoxicillin 750 mg TID (AMX) or amoxicillin with clavulanic acid 500 mg/125 mg TID (AMC). Addition of clavulanic acid offers a broader spectrum; opposite, AMX alone in a higher dose may offer more time above MIC. The aim of this study was to determine which of these regimens is associated with better outcome. METHODS: The Danish Registry of COPD (DrCOPD), a nationwide outpatient COPD registry, was crosslinked with medication data and hospital contacts. The first prescription of AMX or AMC after inclusion in DrCOPD was used as exposure variable. Adjusted Cox proportional hazards models were used to analyze the risk of hospitalization or death (combined) within 30 days and other endpoints. RESULTS: For the first treatment of AECOPD 12,915 received AMX, and 30,721 patients received AMC. AMX was associated with a decreased risk of pneumonia hospitalization or death (aHR 0.6, 95% CI 0.5-0.7; p < 0.0001) compared to AMC. CONCLUSION: In AECOPD, empirically adding clavulanic acid to amoxicillin is not associated with a better outcome; it seems safe for these patients to be treated with amoxicillin alone.

Automatic oxygen titration with O2matic® to patients admitted with COVID-19 and hypoxemic respiratory failure.

INTRODUCTION: Patients with coronavirus disease (COVID-19) and pneumonitis often have hypoxemic respiratory failure and a need of supplementary oxygen. Guidelines recommend controlled oxygen, for most patients with a recommended interval of SpO2 between 92 and 96%. We aimed to determine if closed-loop control of oxygen was feasible in patients with COVID-19 and could maintain SpO2 in the specified interval. METHODS: Patients were prospectively enrolled in an observational study on a medical ward dedicated to patients with COVID-19. Closed-loop controlled oxygen was delivered by O2matic® which can deliver 0-15 liters/min and adjusts flow every second based on 15 seconds averaging of SpO2 measured by pulse oximetry. Lung function parameters were measured at admission. RESULTS: Fifteen patients (six women, nine men) participated in the study. Average age was 72 years. Lung function was severely impaired with FEV1, FVC and PEF reduced to approximately 50%. The average stay on the ward was 3.2 days and O2matic was used on average for 66 hours, providing 987 hours of observation. O2matic maintained SpO2 in the desired interval for 82.9% of the time. Time with SpO2 > 2% below interval was 5.1% and time with SpO2 > 2% above interval was 0.6%. CONCLUSION: Closed-loop control of oxygen to patients with COVID-19 is feasible and can maintain SpO2 in the specified interval in the majority of time. Closed-loop automated control could be of particular benefit for patients in isolation with decreased visibility, surveillance and monitoring. Further studies must examine the clinical benefits.

Guideline for the management of COVID-19 patients during hospital admission in a non-intensive care setting.

INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has presented health-care systems worldwide with novel challenges and experiences and evidence is emerging during the pandemic. Patients requiring hospitalization frequently suffer from respiratory failure of different severities. AIM: The aim of this guideline is the treatment of patients with SARS CoV-2 (COVID-19) in hospital; in particular, it addresses the treatment of respiratory failure treated in general Internal Medical- and Pulmonary Medical wards. RESULTS: Elderly patients and patients with chronic disease are particularly vulnerable to COVID-19. Target oxygen saturation should be between 92% and 96% in patients without chronic lung diseases. Treatment with >5 L oxygen/min should be in close collaboration with intensive care colleagues and >15 l/min preferably in intensive care units. High-flow nasal canula (HFNC) and long-term Continuous Positive Airway Pressure (CPAP) are recommended for patients not responding to conventional oxygen therapy. Non-invasive ventilation (NIV) is only recommended for selected patients, such as those with a ceiling of treatment or patients presenting with hypercapnic failure. With the use of humidification protective equipment as FFP2-3 masks should be used. Nebulized medication should be avoided, and spacers should be used instead. CONCLUSION: Respiratory failure is frequently the cause of hospitalization in patients with COVID-19 and should be monitored closely.

[CPAP for patients with COVID-19].

Continuous positive airway pressure (CPAP) has been suggested as a beneficial treatment for patients with coronavirus disease 2019 (COVID-19). The objective of CPAP treatment is to improve oxygenation, unload respiratory muscles and possibly delay or avoid intubation. This review describes the physiological rationale behind CPAP therapy for patients with COVID-19 and the clinical experience with CPAP, implemented in a medical ward without prior knowledge of the treatment. CPAP has the potential for reducing the burden on intensive care units if implemented on a medical ward by a multidisciplinary approach.

NIV for acute respiratory failure in COPD: high in-hospital mortality is determined by patient selection.

Introduction: Hospital mortality among chronic obstructive pulmonary disease (COPD) patients receiving NIV for acute respiratory failure has shown to be significantly higher in clinical settings than in the randomized trials (RCTs) which clinical guidelines are based on. This may be due to the quality of care of NIV or patient selection. In daily clinical practice, we include patients with terminal pulmonary disease with a do-not-intubate (DNI) or a do-not-resuscitate (DNR) order with a high mortality risk compared to highly selected patients in RCTs. The aim of this study was to determine the role of patient selection for in-hospital mortality among patients receiving NIV for acute respiratory failure of COPD. Methods: We conducted a retrospective study including all patients receiving acute NIV due to acute respiratory failure at the respiratory wards in 2012-2013 at two hospitals in Greater Copenhagen. Results: Overall in-hospital mortality rate was 30%. In patients with a DNI/DNR order, mortality was 59% and in patients with no limitations in treatment 2%. Patients who fulfilled the exclusion criteria of the RCT by Plant et al. had a mortality of 41% compared to 25% in the remaining population. Conclusions: High overall in-hospital mortality reflects that patient selection in clinical practice is very different from RCT. Quality of acute NIV treatment seems acceptable in clinical practice for patients with less severe COPD and no limitations in treatment. Higher mortality in patients with DNI/DNR order may be due to inefficient NIV treatment for these patients with more severe COPD.

Automated oxygen control with O2matic® during admission with exacerbation of COPD.

PURPOSE: It is a challenge to control oxygen saturation (SpO2) in patients with exacerbations of COPD during admission. We tested a newly developed closed-loop system, O2matic®, and its ability to keep SpO2 within a specified interval compared with manual control by nursing staff. PATIENTS AND METHODS: We conducted a crossover trial with patients admitted with an exacerbation of COPD and hypoxemia (SpO2 ≤88% on room air). Patients were monitored with continuous measurement of SpO2. In random order, they had 4 hours with manually controlled oxygen and 4 hours with oxygen delivery controlled by O2matic. Primary outcome was time within a prespecified SpO2 target interval. Secondary outcomes were time with SpO2 <85%, time with SpO2 below target but not <85%, and time with SpO2 above target. RESULTS: Twenty patients were randomized and 19 completed the study. Mean age was 72.4 years and mean FEV1 was 0.72 L (33% of predicted). Patients with O2matic-controlled treatment were within the SpO2 target interval in 85.1% of the time vs 46.6% with manually controlled treatment (P<0.001). Time with SpO2 <85% was 1.3% with O2matic and 17.9% with manual control (P=0.01). Time with SpO2 below target but not <85% was 9.0% with O2matic and 25.0% with manual control (P=0.002). Time with SpO2 above target was not significantly different between treatments (4.6% vs 10.5%, P=0.2). Patients expressed high confidence and a sense of safety with automatic oxygen delivery. CONCLUSION: O2matic was able to effectively control SpO2 for patients admitted with an exacerbation of COPD. O2matic was significantly better than manual control to maintain SpO2 within target interval and to reduce time with unintended hypoxemia.

Barriers for recruitment of patients with chronic obstructive pulmonary disease to a controlled telemedicine trial.

The aim of this analysis is to investigate reasons why patients with chronic obstructive pulmonary disease decline to participate in a controlled trial of telemedicine. Patients with previous chronic obstructive pulmonary disease exacerbations were invited to participate in a 6-month randomized telemedicine trial. For eligible patients, reasons for refusal were registered. Of 560 eligible patients, 279 (50%) declined to participate in the trial, 257 (92%) reported a reason: 53 (20.6%) technical concerns, 164 (63.8%) personal reasons, 17 (6.6%) preferred outpatient clinic visits, and 23 (8.9%) did not want to participate in clinical research. Compared to consenting patients, subjects declining participation were significantly older, more often female, had higher lung function (%predicted), lower body mass index, higher admission-rate for chronic obstructive pulmonary disease in the previous year, and were more often diagnosed with osteoporosis. Many eligible patients decline participating in a controlled tele-healthcare trial and, furthermore, a tailored approach for recruiting females and elderly patients appears appropriate.

A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol.

BACKGROUND: The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects. Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome. METHODS: This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage. DISCUSSION: This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02857842 , 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.

COPD: Mortality and Readmissions in Relation to Number of Admissions with Noninvasive Ventilation.

In severe COPD, patients having survived acute hypercapnic respiratory failure (AHRF) treated with noninvasive ventilation (NIV) have a high mortality and risk of readmissions. The aim was to analyze the prognosis for patients with COPD having survived AHRF and to assess whether previous admissions with NIV predict new ones.We conducted a retrospective follow-up analysis of 201 patients two years after NIV treatment of AHRF. Comparison of time-to-event in patients previously treated with NIV versus patients with no previous NIV treatment. We found a one-year mortality of 33.8% and high risks of: readmission (53.2%), any event (67.7%), and life-threatening events (49.8%). Patients with previous NIV treatments had an increased hazard ratio for life-threatening events: 1.60, p = 0.023 despite having lower in-hospital mortality than patients with no previous NIV treatment (18.9% vs. 33.1%, p = 0.043). We found that having survived one episode of AHRF considerably worsened the prognosis for the affected patients.The prognosis for patients having survived AHRF with NIV treatment is poor: the prognosis worsens with additional episodes of AHRF. Future research and treatment should focus on patients with repeated episodes of AHRF.