Severe Acute Exacerbation Of COPD Research Articles

AERIFY-1/-2: 2 phase 3 randomised controlled trials of itepekimab in former smokers with moderate-to-severe COPD

BackgroundAccumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of chronic obstructive pulmonary disease (COPD). In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.MethodsThe study designs of AERIFY-1 and AERIFY-2 are described in this article.Results and conclusion:The primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomized, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimabversusplacebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40–85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack year smoking history, and ≥6 months since smoking cessation for former smokers. The primary endpoint is the annualized rate of moderate or severe acute exacerbation of COPD. Secondary endpoints include change from baseline in pre- and post-bronchodilator FEV1, and annualized frequency of severe exacerbations. Symptomatic endpoints include Evaluating Respiratory Symptoms in COPD, and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.

Reliability of comorbidity indices as predictive indicators for frequent severe chronic obstructive pulmonary disease exacerbations.

The relationship between comorbidities and chronic obstructive pulmonary disease (COPD) is two-sided. As the number of comorbidities increases, frequency of acute exacerbations of COPD (AECOPD) consequently increases. Comorbidity indices can be used to evaluate comorbidities while managing COPD patients. We aimed to compare comorbidity indices such as the Charlson comorbidity index (CCI), comorbidities in COPD index (COMCOLD) and COPD specific comorbidity test (COTE) regarding exacerbation frequency. Participants hospitalized for AECOPD were included in this bidirectional case-control study. Exacerbation severity, frequency, further exacerbations over a one-year follow-up period and CCI, COMCOLD, and COTE scores were recorded. High and low comorbidity groups were compared regarding AECOPD frequency, severity, and further exacerbations. Ninety-two patients were enrolled. The frequency of AECOPD was significantly higher in high-comorbidity groups (p= 0.026 for CCI; 0.015 for COTE; 0.012 for COMCOLD) than that in low-comorbidity groups. Severe AECOPD was significantly higher in all high-comorbidity groups according to the indices. Median number of exacerbations during the one-year follow-up period was significantly higher in the high-comorbidity groups defined by CCI [0 (0-4) vs. 1 (0-4), p<0.001 and COMCOLD 0 (0-4) vs. 1 (0-3), p= 0.007]. Comorbidities are among the most important risk factors for AECOPD. Managing comorbidities begins with their identification, followed by appropriate interventions. Therefore, using at least one comorbidity index during assessment ensures that comorbidities are not overlooked during diagnostic and therapeutic processes. CCI, COTE, and COMCOLD comorbidity indices can be used in predicting COPD exacerbations.

Diagnostic yield of viral multiplex PCR during acute exacerbation of COPD admitted to the intensive care unit: a pilot study

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of admission to the intensive care unit, often triggered by a respiratory tract infection of bacterial or viral aetiology. Managing antibiotic therapy in this context remains a challenge. Respiratory panel molecular tests allow identifying viral aetiologies of AECOPD. We hypothesized that the systematic use of a respiratory multiplex PCR (mPCR) would help antibiotics saving in severe AECOPD. Our objectives were to describe the spectrum of infectious aetiologies of severe AECOPD, using a diagnostic approach combining conventional diagnostic tests and mPCR, and to measure antibiotics exposure. The study was bicentric, prospective, observational, and included 105 critically ill patients with a severe AECOPD of presumed infectious aetiology, in whom a respiratory mPCR with a viral panel was performed in addition to conventional microbiological tests. Altogether, the microbiological documentation rate was 50%, including bacteria alone (19%), respiratory viruses alone (16%), and mixed viruses and bacterial species (16%). The duration of antibiotic therapy was shorter in patients without documented bacterial infection (5.6 vs. 9 days; P = 0.0006). This pilot study suggests that molecular tests may help for the proper use of anti-infective treatments in critically ill patients with severe AECOPD.

Clinical Characteristics and Frequency of Chronic Obstructive Pulmonary Disease Exacerbations in Korean Patients: Findings From the KOCOSS Cohort 2012-2021.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exert a substantial burden on patients and healthcare systems; however, data related to the frequency of AECOPD in the Korean population are limited. Therefore, this study aimed to describe the frequency of severe, and moderate or severe AECOPD, as well as clinical and demographic characteristics of patients with chronic obstructive pulmonary disease (COPD) in South Korea. Data from patients aged > 40 years with post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ≤ 70% of the normal predicted value from the Korea COPD Subgroup Study database were analyzed (April 2012 to 2021). The protocol was based on the EXAcerbations of COPD and their OutcomeS International study. Data were collected retrospectively for year 0 (0-12 months before study enrollment) based on patient recall, and prospectively during years 1, 2, and 3 (0-12, 13-24, and 25-36 months after study enrollment, respectively). The data were summarized using descriptive statistics. Data from 3,477 Korean patients (mean age, 68.5 years) with COPD were analyzed. Overall, most patients were male (92.3%), former or current smokers (90.8%), had a modified Medical Research Council dyspnea scale score ≥ 1 (83.3%), and had moderate airflow limitation (54.4%). The mean body mass index (BMI) of the study population was 23.1 kg/m², and 27.6% were obese or overweight. Hypertension was the most common comorbidity (37.6%). The mean blood eosinophil count was 226.8 cells/μL, with 21.9% of patients having ≥ 300 cells/μL. A clinically insignificant change in FEV1 (+1.4%) was observed a year after enrollment. Overall, patients experienced a mean of 0.2 severe annual AECOPD and approximately 1.1 mean moderate or severe AECOPD. Notably, the rates of severe AECOPD remained generally consistent over time. Compared with patients with no exacerbations, patients who experienced severe exacerbations had a lower mean BMI (21.7 vs. 23.1 kg/m²; P < 0.001) and lower lung function parameters (all P values < 0.001), but reported high rates of depression (25.5% vs. 15.1%; P = 0.044) and anxiety (37.3% vs. 16.7%; P < 0.001) as a comorbidity. Findings from this Korean cohort of patients with COPD indicated a high exacerbation burden, which may be attributable to the unique characteristics of the study population and suboptimal disease management. This highlights the need to align clinical practices with the latest treatment recommendations to alleviate AECOPD burden in Korea. ClinicalTrials.gov Identifier: NCT05750810.

Respiratory Infection Triggering Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Data are scarce on respiratory infections during severe acute exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to investigate respiratory infection patterns in the intensive care unit (ICU) and identify variables associated with infection type and patient outcome. A retrospective, single-centre cohort study. All patients admitted (2015-2021) to our ICU for severe acute exacerbation of COPD were included. Logistic multivariable regression analysis was performed to predict factors associated with infection and assess the association between infection and outcome. We included 473 patients: 288 (60.9%) had respiratory infection and 139 (29.4%) required invasive mechanical ventilation. Eighty-nine (30.9%) had viral, 81 (28.1%) bacterial, 34 (11.8%) mixed, and 84 (29.2%) undocumented infections. Forty-seven (9.9%) patients died in the ICU and 67 (14.2%) in hospital. Factors associated with respiratory infection were temperature (odds ratio [+1°C]=1.43, P=0.008) and blood neutrophils (1.07, P=0.002). Male sex (2.21, P=0.02) and blood neutrophils were associated with bacterial infection (1.06, P=0.04). In a multivariable analysis, pneumonia (cause-specific hazard=1.75, P=0.005), respiratory rate (1.17, P=0.04), arterial partial pressure of carbon-dioxide (1.08, P=0.04), and lactate (1.14, P=0.02) were associated with the need for invasive MV. Age (1.03, P=0.03), immunodeficiency (1.96, P=0.02), and altered performance status (1.78, P=0.002) were associated with hospital mortality. Respiratory infections, 39.9% of which were bacterial, were the main cause of severe acute exacerbation of COPD. Body temperature and blood neutrophils were single markers of infection. Pneumonia was associated with the need for invasive mechanical ventilation but not with hospital mortality, as opposed to age, immunodeficiency, and altered performance status.

Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Are There Significant Differences Between Hospitalized and Emergency Department Patients?

Current guidelines define a severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as an increase in symptoms requiring hospital admission or emergency department (ED) visit. Little is known about whether or not subjects requiring hospitalization and those needing only ED care have similar patient profiles and if their clinical outcomes appear comparable. The main goals of this study were to compare the demographic and clinical characteristics of patients treated for an AECOPD with an inpatient admission versus an ED visit and to review if hospital resource utilization was different between the 2 groups after discharge. Subjects treated in 2022 at Montfort Hospital for an AECOPD were reviewed. Patient demographic information was collected in addition to spirometry results and blood eosinophil counts on file. Supplemental oxygen use and medication lists were also recorded. Patients with an initial hospital admission were compared to those requiring only ED care with univariate and multivariate analyses. We also assessed if subjects were again treated for an AECOPD up to 6 months post initial discharge, and if so, the type of hospital visits (hospitalization or ED). A total of 135 individuals necessitated hospitalization and 79 received ED care for the treatment of an AECOPD. On univariate analysis, patients requiring an inpatient stay appeared older and were more likely to have spirometry results on file. A greater proportion of hospitalized individuals were on supplemental oxygen and prescribed at least one long-acting inhaled medication. These studied variables remained significant after multivariate logistic regression analysis. Subjects with an initial inpatient admission were also more likely to require hospitalization upon repeat presentation for a severe AECOPD. Given the important differences observed in both patient characteristics and hospital resource utilization, this study supports considering an AECOPD requiring inpatient admission versus an ED visit as distinct categories of events.

Physical status, symptoms and health-related quality of life during a severe exacerbation of COPD: Recovery and discriminative capacity for future events

ObjectiveSevere acute exacerbations of chronic obstructive pulmonary disease (AECOPD) can have a negative impact on functional capacity, symptoms and health-related quality of life (HRQOL). This study aimed to i) investigate the recovery of muscle strength, functional capacity, symptoms, and HRQOL in patients after a severe AECOPD; ii) compare with matched patients with stable COPD (SCOPD); and iii) assess whether these assessments at hospital discharge could discriminate patients’ risk for future events. MethodsThis observational study assessed patients with AECOPD during hospital discharge (T1) and one month after discharge (T2). Patients with SCOPD were assessed once. Quadriceps force, handgrip strength, short physical performance battery (SPPB), 6-min walk distance (6 MWD), COPD assessment test (CAT), London chest activity of daily living (LCADL), modified medical research council, checklist individual strength-fatigue, patient health questionnaire, and physical activity (Actigraph) were measured. Exacerbation-related readmission and mortality within six months and 1-year were collected. ResultsForty-four patients with AECOPD were matched with 44 patients with SCOPD. At T2, a significant improvement was found for the SPPB total score, 6 MWD, CAT score, and LCADL score. Compared to patients with SCOPD, a worse LCADL score was found at T2 in patients with AECOPD. Patients with AECOPD that were readmitted or died had a worse SPPB classification and five-repetition sit-to-stand test at T1. ConclusionPatients after severe AECOPD improved in functional capacity and HRQOL one month after hospital discharge, but ADL performance was still worse compared to SCOPD. Patients who were readmitted or died had significantly worse scores on functional tests at hospital discharge.

Development and feasibility of an exercise training program in primary care for patients with COPD experiencing an acute exacerbation

BackgroundStarting rehabilitation soon after an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is crucial to diminish the detrimental effects of this acute event on muscle function. However, uptake in outpatient pulmonary rehabilitation is low. ObjectivesTo design and test a feasible, acceptable and accessible exercise training program (ETP) in primary care for patients experiencing an AECOPD. Design(1) A literature review and qualitative study to develop an ETP and (2) A feasibility study of the ETP implemented in primary care. Methods(1) The development of the ETP proceeded in several phases with input from different stakeholders through focus group discussions. (2) Patients experiencing a moderate or severe AECOPD were included and followed the ETP for two weeks with a physiotherapist in primary care. Interviews with the participants took place and patients were given the choice to complete the eight-week program. Results(1) Six discussion sessions took place. The ETP contained a flexible set of progressively more difficult exercises applicable in a primary care practice. (2) Eight patients experiencing a moderate (n = 1) or severe (n = 7) AECOPD were included. Patients started the first physiotherapy session 5 (2−6) days after the start of their symptoms or hospital discharge. Seven patients wanted to complete the ETP. ConclusionsAn ETP in primary care is feasible, acceptable and accessible for patients experiencing a moderate or severe AECOPD, and for physiotherapists. The effectiveness of this ETP on muscle function and physical activity is currently under investigation in a RCT. Contribution of the Paper•Alternative forms of rehabilitation are needed to tackle the current challenges of rehabilitation after an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).•Input from different stakeholders was incorporated to develop a feasible ETP.•This paper provides a feasible, acceptable and accessible ETP developed for patients recovering from a moderate or severe AECOPD.•This is the first ETP developed for implementation in primary care in patients suffering from an AECOPD.

The role of vaccination in COPD: influenza, SARS-CoV-2, pneumococcus, pertussis, RSV and varicella zoster virus.

Exacerbations of COPD are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression and death. At least 70% of COPD exacerbations are infectious in origin, with respiratory viruses identified in approximately 30% of cases. Despite long-standing recommendations to vaccinate patients with COPD, vaccination rates remain suboptimal in this population.Streptococcus pneumoniae is one of the leading morbidity and mortality causes of lower respiratory tract infections. The Food and Drug Administration recently approved pneumococcal conjugate vaccines that showed strong immunogenicity against all 20 included serotypes. Influenza is the second most common virus linked to severe acute exacerbations of COPD. The variable vaccine efficacy across virus subtypes and the impaired immune response are significant drawbacks in the influenza vaccination strategy. High-dose and adjuvant vaccines are new approaches to tackle these problems. Respiratory syncytial virus is another virus known to cause acute exacerbations of COPD. The vaccine candidate RSVPreF3 is the first authorised for the prevention of RSV in adults ≥60 years and might help to reduce acute exacerbations of COPD. The 2023 Global Initiative for Chronic Lung Disease report recommends zoster vaccination to protect against shingles for people with COPD over 50 years.

Examining changes in vascular function, arterial stiffness and systemic inflammation during hospitalization and recovery from an acute exacerbation of chronic obstructive pulmonary disease

An acute exacerbation of COPD (AECOPD) is associated with increased risk of cardiovascular (CV) events. The elevated risk during an AECOPD may be related to changes in vascular function, arterial stiffness, and systemic inflammation; the time course of these measures and their corresponding recovery are poorly understood. Further, physical activity is reduced during an AECOPD, and physical activity may influence the cardiovascular responses to an AECOPD. The purpose of the study was to examine the acute impact of an AECOPD requiring hospitalization on vascular function, arterial stiffness, and systemic inflammation and examine whether physical activity modulates these variables during recovery. Patients hospitalized for an AECOPD were prospectively recruited and compared to control patients with stable COPD. Vascular function, arterial stiffness, and systemic inflammation (CRP, IL-6) were measured at hospital admission, hospital discharge and within 14 days of discharge. Physical activity was electronically tracked daily while in hospital and for 7 days following discharge using a Fitbit. One hundred and twenty-one patients with an AECOPD requiring hospitalization and 33 control patients with stable COPD were enrolled in the study. Vascular function was significantly lower, and systemic inflammation higher at hospital admission in patients with an AECOPD compared to stable COPD. Significant improvements in vascular function and inflammation were observed within 14 days of hospital discharge; however, vascular function remained lower than stable COPD. Physical activity was low at admission and increased following discharge; however, physical activity was unrelated to measures of vascular function or inflammation at any time point. An AECOPD requiring hospitalization is associated with impaired vascular function that persists during recovery. These findings provide a mechanistic link to help explain the enduring increase in CV risk and mortality following a severe AECOPD event.Clinical trial registration: ClinicalTrials.gov #NCT01949727; Registered: 09/20/2013.

COPD Exacerbation: Why It Is Important to Avoid ICU Admission.

Chronic obstructive pulmonary disease (COPD) is one of the major causes of morbidity and mortality worldwide. Hospitalization due to acute exacerbations of COPD (AECOPD) is a relevant health problem both for its impact on disease outcomes and on health system resources. Severe AECOPD causing acute respiratory failure (ARF) often requires admission to an intensive care unit (ICU) with endotracheal intubation and invasive mechanical ventilation. AECOPD also acts as comorbidity in critically ill patients; this condition is associated with poorer prognoses. The prevalence reported in the literature on ICU admission rates ranges from 2 to 19% for AECOPD requiring hospitalization, with an in-hospital mortality rate of 20-40% and a re-hospitalization rate for a new severe event being 18% of the AECOPD cases admitted to ICUs. The prevalence of AECOPD in ICUs is not properly known due to an underestimation of COPD diagnoses and COPD misclassifications in administrative data. Non-invasive ventilation in acute and chronic respiratory failure may prevent AECOPD, reducing ICU admissions and disease mortality, especially when associated with a life-threating episode of hypercapnic ARF. In this review, we report on up to date evidence from the literature, showing how improving the knowledge and management of AECOPD is still a current research issue and clinical need.

In-hospital antibiotic use for severe chronic obstructive pulmonary disease exacerbations: a retrospective observational study

BackgroundThe use of antibiotics in mild to severe acute exacerbations of chronic obstructive pulmonary disease (COPD) remains controversial.AimTo explore in-hospital antibiotic use in severe acute exacerbations of COPD (AECOPD), to analyze determinants of in-hospital antibiotic use, and to investigate its association with hospital length of stay (LOS) and in-hospital mortality.MethodsA retrospective, observational study was conducted in Ghent University Hospital. Severe AECOPD were defined as hospitalizations for AECOPD (ICD-10 J44.0 and J44.1) discharged between 2016 and 2021. Patients with a concomitant diagnosis of pneumonia or ‘pure’ asthma were excluded. An alluvial plot was used to describe antibiotic treatment patterns. Logistic regression analyses identified determinants of in-hospital antibiotic use. Cox proportional hazards regression analyses were used to compare time to discharge alive and time to in-hospital death between antibiotic-treated and non-antibiotic-treated AECOPD patients.ResultsIn total, 431 AECOPD patients (mean age 70 years, 63% males) were included. More than two-thirds (68%) of patients were treated with antibiotics, mainly amoxicillin-clavulanic acid. In multivariable analysis, several patient-related variables (age, body mass index (BMI), cancer), treatment-related variables (maintenance azithromycin, theophylline), clinical variables (sputum volume and body temperature) and laboratory results (C-reactive protein (CRP) levels) were associated with in-hospital antibiotic use independent of sputum purulence, neutrophil counts, inhaled corticosteroids and intensive care unit of which CRP level was the strongest determinant. The median hospital LOS was significantly longer in antibiotic-treated patients (6 days [4–10]) compared to non-antibiotic-treated patients (4 days [2–7]) (p < 0.001, Log rank test). This was indicated by a reduced probability of hospital discharge even after adjustment for age, sputum purulence, BMI, in-hospital systemic corticosteroid use and forced expiratory volume in one second (FEV1) (adjusted hazard ratio 0.60; 95% CI 0.43; 0.84). In-hospital antibiotic use was not significantly associated with in-hospital mortality.ConclusionsIn this observational study in a Belgian tertiary hospital, in-hospital antibiotic use among patients with severe AECOPD was determined by the symptom severity of the exacerbation and the underlying COPD severity as recommended by the guidelines, but also by patient-related variables. Moreover, in-hospital antibiotic use was associated with a longer hospital stay, which may be linked to their disease severity, slower response to treatment or 'harm' due to antibiotics.Trial registrationNumber: B670201939030; date of registration: March 5, 2019.

The Influence of Air Pollution on Non-Infectious Hospitalizations for Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Time-Series from Serbia

The available data on the impact of air pollution on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are inconsistent. We investigated the influence of air pollution on the number of severe AECOPD hospitalizations of non-infectious etiology in patients residing in Novi Sad, Serbia. In this time-series, we used a quasi-Poisson generalized linear model in conjunction with distributed lag non-linear models, after controlling for lag days, seasonal and long-term trends, and meteorological factors (air temperature and humidity), to estimate the relative risk (RR) of AECOPD hospitalization for each increase of 10 μg/m3 in the air pollutant concentration. A total of 552 AECOPD hospitalizations were registered during 2017–2022. With each 10 μg/m3 increase in the selected air pollutants’ concentration, the cumulative RR (lags0–7) in single-predictor models for AECOPD admission were 1.52 (95% CI 0.98–2.35) for PM10, 1.44 (95% CI 0.93–2.25) for PM2.5, 1.13 (95% CI 0.87–1.47) for SO2, and 0.99 (95% CI 0.69–1.42) for NO2. Similar results were found in multi-predictor models as well as in group analyses between smokers and non-smokers. In conclusion, no significant associations between exposure to air pollutants and the daily AECOPD admissions were found. There is an obvious need for additional research on the topic.

Acute Exacerbation of COPD.

This case is targeted to emergency medicine residents of all levels. Shortness of breath (SOB) is one of the top ten most common chief complaints seen in the Emergency Department, accounting for close to 10% of presenting complaints.1 An acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a frequent culprit, accounting for roughly 15.4 million visits and 730,000 hospitalizations per year.2 The diagnosis of treatment of mild to moderate AECOPD can be relatively uncomplicated; however, multiple factors can increase the complexity of management and pose additional challenges that the emergency physician (EP) must be prepared for. Severe AECOPD can necessitate the need for both Non-invasive positive pressure ventilator (NIPPV) such as bi-level positive airway pressure (BiPAP) as well as emergent intubation. Furthermore, managing the ventilator settings in patients with an AECOPD is far from routine, requiring an intricate understanding of pulmonary physiology.3. By the end of this simulation, learners will be able to (1) assess for causes of severe shortness of breath, (2) manage severe COPD exacerbation by administering appropriate medications, (3) identify worsening clinical status and initiate NIPPV, (4) assess the causes of hypoxia after establishing endotracheal intubation and, (5) identify indication for needle decompression and perform chest tube thoracostomy. This simulation was conducted with a high-fidelity mannequin with a separate low fidelity chest tube mannequin that allowed for hands-on practice placing a chest tube. A total of 16 PGY-1 residents participated in the simulated patient encounter. Following the simulation and debrief session, all residents were sent a Likert scale survey via surveymonkey.com to assess the educational quality of the simulation. The survey contained the following questions; 1) Overall, this simulation was realistic and could represent a patient presentation in the Emergency Department, 2) Overall, the case contained complexity that challenged me as a learner, 3) This case helped to expand my medical knowledge, 4) I feel more confident in diagnosing and treating AECOPD, 5) I feel more confident in recognizing the indications for NIPPV and intubation, 6) This simulation offered an opportunity to improve my procedural skills, 7) I feel more confident in setting up the ventilator, 8) I feel more confident in addressing ventilator alarms. Following the simulation and debrief session, all the participants (n=16), were provided a survey to assess the educational quality of the simulation. There were a total of 12 respondents and a hundred percent of them agreed or strongly agreed that the case contained complexity that challenged them. All of the respondents agreed that the simulation case was realistic and that the case helped expand their medical knowledge. Furthermore, all the learners agreed or strongly agreed that the case helped them in improving their procedural skills. This case combines a mixture of high fidelity and medium fidelity components to encompass both clinical knowledge and procedural skills. This case is effective in expanding beyond the basic approach to managing an AECOPD patient and forces learners to address clinical deterioration, escalate airway interventions, manage ventilator settings, and address ventilator alarms, including placement of a chest tube. Residents commented that this case was very realistic and particularly challenging because it highlighted gaps in their clinical knowledge and procedural skills. Residents were most challenged by identifying when to escalate care as well as how to manage ventilator settings in AECOPD patients. Acute exacerbation COPD, intubation, positive pressure ventilation, ventilator alarms, chest tube thoracostomy.

EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies

IntroductionIn patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD),...

Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial

BackgroundPatients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders.Methods and analysisThis study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.

A pooled analysis of the risk prediction models for mortality in acute exacerbation of chronic obstructive pulmonary disease.

The prognosis for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not optimistic, and severe AECOPD leads to an increased risk of mortality. Prediction models help distinguish between high- and low-risk groups. At present, many prediction models have been established and validated, which need to be systematically reviewed to screen out more suitable models that can be used in the clinic and provide evidence for future research. We searched PubMed, EMBASE, Cochrane Library and Web of Science databases for studies on risk models for AECOPD mortality from their inception to 10 April 2022. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). Stata software (version 16) was used to synthesize the C-statistics for each model. A total of 37 studies were included. The development of risk prediction models for mortality in patients with AECOPD was described in 26 articles, in which the most common predictors were age (n = 17), dyspnea grade (n = 11), altered mental status (n = 8), pneumonia (n = 6) and blood urea nitrogen (BUN, n = 6). The remaining 11 articles only externally validated existing models. All 37 studies were evaluated at a high risk of bias using PROBAST. We performed a meta-analysis of five models included in 15 studies. DECAF (dyspnoea, eosinopenia, consolidation, acidemia and atrial fibrillation) performed well in predicting in-hospital death [C-statistic = 0.91, 95% confidence interval (CI): 0.83, 0.98] and 90-day death [C-statistic = 0.76, 95% CI: 0.69, 0.82] and CURB-65 (confusion, urea, respiratory rate, blood pressure and age) performed well in predicting 30-day death [C-statistic = 0.74, 95% CI: 0.70, 0.77]. This study provides information on the characteristics, performance and risk of bias of a risk model for AECOPD mortality. This pooled analysis of the present study suggests that the DECAF performs well in predicting in-hospital and 90-day deaths. Yet, external validation in different populations is still needed to prove this performance.

Impact of Coronavirus Disease 2019-Related Infection Prevention and Control Measures on the Occurrence of COPD Exacerbations During Inpatient Pulmonary Rehabilitation.

A significant reduction in hospitalizations for acute exacerbations of COPD (AECOPDs) has been reported during the coronavirus disease 2019 (COVID-19) pandemic. It remains unclear whether this reduction is the result of health care avoidance by patients, or of infection prevention and control (IPC) measures. Our objective was to explore the impact of COVID-19-related IPC measures on the occurrence of AECOPD in a real-life inpatient pulmonary rehabilitation (PR) setting, thereby ruling out potential effects of health care avoidance. Patients with COPD admitted for 8 weeks of inpatient PR at Ciro (Horn, the Netherlands) between October 2020 and March 2021, the first winter with full COVID-19-related IPC measures,were compared to patients admitted during the same period in previous years (2017-2018, 2018-2019, and 2019-2020). Electronic medical records were retrospectively screened for the occurrence of moderate to severe AECOPDs, drop-out, and mortality. A total of 501 patients with COPD (median age 66.6 [interquartile range (IQR) 60.3-71.9] years, 43.1% male, forced expiratory volume in 1 second [FEV1] 35.9 [26.8-50.6] % predicted) were analyzed. During 2020-2021, 22 patients (31.0%) experienced ≥1 AECOPD compared to 43 patients (33.6%) in 2019-2020, 55 patients (36.9%) in 2018-2019, and 83 patients (54.2%) in 2017-2018. This represents a 25.4% reduction in 2020-2021 compared to the average of the previous 3 periods, p=0.077. No differences in AECOPD severity, drop-out, or mortality were observed. COVID-19-related IPC measures did not significantly reduce the AECOPD rate during inpatient PR in a single-center setting. The current findings suggest that avoidance of health care may be an important factor in the observed reduction of AECOPD-related hospitalizations during the pandemic and that the value of the strict COVID-19-related IPC measures for the prevention of AECOPDs warrants further research.

Trajectories of Severe Exacerbations of Chronic Obstructive Pulmonary Disease and Their Relationship with Mortality Risk.

Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2years before and after the date of the first visit to the respiratory clinic-Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx.

Characteristics of 12-Month Readmission for Hospitalized Patients with COPD: A Propensity Score Matched Analysis of Prospective Multicenter Study.

PurposeHospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups.Patients and MethodsPatients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters.ResultsThe cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P<0.001), the COPD Assessment Test (CAT) score (20 vs 17, P<0.001), the blood eosinophil percentage (1.5 vs 2.0, P<0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥9 years), more symptoms (CAT ≥10), and lower blood eosinophils (Eos <2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations.ConclusionThese analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.