Severe COPD Exacerbations Research Articles

Admission blood eosinophil count, inpatient death and death at 1 year in exacerbating patients with COPD

BackgroundBlood eosinophil counts have been studied in patients with stable chronic obstructive pulmonary disease (COPD) and are a useful biomarker to guide inhaled corticosteroid use. Less is known about eosinophil...

Systemic and functional effects of continuous azithromycin treatment in patients with severe chronic obstructive pulmonary disease and frequent exacerbations.

Continuous treatment with azithromycin may lead to fewer acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but little is known of its impact on systemic and functional outcomes in real-life settings. This was a multicenter prospective observational study of patients with severe COPD who started treatment with azithromycin. Tests were compared at baseline and after 3 and 12 months of treatment. These included lung function tests, a 6-min walking test (6MWT), and enzyme-linked immunosorbent assays of serum and sputum markers, such as interleukins (IL-6, IL-8, IL-13, IL-5), tumor necrosis factor receptor 2 (TNFR2), and inflammatory markers. Incidence rate ratios (IRR) and their 95% confidence intervals (95% CI) are reported. Of the 478 eligible patients, the 42 who started azithromycin experienced reductions in AECOPDs (IRR, 0.34; 95% CI, 0.26-0.45) and hospitalizations (IRR, 0.39; 95% CI, 0.28-0.49). Treatment was also associated with significant improvement in the partial arterial pressure of oxygen (9.2 mmHg, 95% CI 1.4-16.9) at 12 months. While TNFR2 was reduced significantly in both serum and sputum samples, IL-13 and IL-6 were only significantly reduced in serum samples. Moreover, an elevated serum and sputum IL-8 level significantly predicted good clinical response to treatment. Continuous azithromycin treatment in a cohort of patients with severe COPD and frequent exacerbations can significantly reduce the number and severity of exacerbations and improve gas exchange. Treatment changes the pattern of microorganism isolates and decreases the inflammatory response. Of note, IL-8 may have utility as a predictor of clinical response to azithromycin treatment.

Prognostic value of the post-exercise heart rate recovery and BHDE-index in chronic obstructive pulmonary disease

BackgroundThe BODE index, consisting of body mass index (B), airflow obstruction (O), dyspnea score (D), and exercise capacity (E), can predict outcomes in COPD. However, when spirometry was restricted to prevent cross-infection such as COVID-19 pandemic, a modified index would be needed. Because cardiovascular dysfunction is associated with poor clinical outcomes in COPD, we conducted a novel BHDE-index by replacing spirometry with post-exercise heart rate recovery (HRR, H) and evaluated its predictive performance in this observational study.MethodsFrom January 2019 to December 2019, enrolled patients were analyzed as a derivation cohort for the setup of the model. This model was verified in another group of patients generated between January 2020 and December 2020, as the validation cohort. The post exercise HRR was defined as the difference of heart rate immediately after and 1 min after test cessation.ResultsA total of 447 patients with COPD were enrolled. Patients with abnormal HRR were older, with more severe airway obstruction, severe airway symptoms, faster resting heart rate, shorter 6-min walk distance and higher frequency of severe acute exacerbation in previous one year. The prediction performance of the BHDE-index for one-year severe COPD exacerbation was similar to that of the BODE-index in both the derivation and validation groups [area under the receiver operating characteristic curve (AUROC) 0.76 vs. 0.75, p = 0.369; AUROC 0.74 vs. 0.79, p = 0.05]. The prediction performance for 1 year mortality was also similar between BHDE-index and BODE-index in both cohorts [AUROC 0.80 vs. 0.77, p = 0.564; 0.76 vs. 0.70, p = 0.234]. Univariate and multivariate analyses also showed that the BHDE-index was an independent and important predictor of annual severe COPD exacerbation in the derivation and validation cohorts.ConclusionsThe BHDE-index is a good and easy-to-perform prediction model for the risk of severe acute exacerbation and 1-year mortality in COPD wherever spirometry results are unavailable.

Acceptability, Appropriateness and Feasibility of a Nurse-Led Integrated Care Intervention for Patients with Severe Exacerbation of COPD from the Healthcare Professional's Perspective - A Mixed Method Study.

To improve inpatient care and self-management in patients with severe acute exacerbations of COPD, we implemented a nurse-led behavioral intervention. This study aimed to assess implementation outcomes from the perspective of the healthcare professionals (HCP) who delivered it. Using an explanatory sequential mixed method approach, we conducted an online questionnaire and two small group interviews. We applied descriptive statistics for quantitative data, a framework analysis for qualitative data, and a mixed methods matrix to integrate the results. A total of 19 of 27 invited participants answered the online questionnaire; 9 of 19 participated in the group interviews. The intervention's overall acceptability, appropriateness, and feasibility was rated high to very high (median 5/5; 4/5 and 4/5). Enablers to implementation included general recognition of the need for specialized care, sufficient knowledge of the intervention by HCP, and strong interprofessional collaboration. Main barriers included the lack of resident physician's resources and difficulties in adaptability. While the acceptance of the intervention was very high, the perceived appropriateness and feasibility were affected by its complexity. The availability of a knowledgeable interprofessional core team is a strategy that supports the implementation of complex interventions.

Real-world comparative effectiveness of three single-inhaler dual bronchodilators for the treatment of COPD.

Single-inhaler dual bronchodilators are now recommended as initial treatment of COPD for patients with multiple exacerbations or with moderate or severe dyspnoea. It is unclear whether there are differences in effectiveness among commonly used dual bronchodilators. We identified a cohort of COPD patients, aged ≥40 years, treated during 2017-2020, from the UK Clinical Practice Research Datalink, a real-world practice setting. Inhaled corticosteroid-naïve patients initiating vilanterol-umeclidinium (VIL-UME) were compared with those initiating olodaterol-tiotropium (OLO-TIO) or indacaterol-glycopyrronium (IND-GLY) dual bronchodilators primarily on the incidence of moderate and severe COPD exacerbation over 1 year, and corresponding hazard ratios (HRs), after adjustment by propensity score weighting. The cohort included 15 224 initiators of VIL-UME, 5536 initiators of OLO-TIO and 5059 initiators of IND-GLY. The HR of a moderate or severe exacerbation with VIL-UME was 0.91 (95% CI 0.85-0.97) compared with OLO-TIO and 0.96 (95% CI 0.89-1.03) compared with IND-GLY. The risk of severe exacerbation was not different for VIL-UME when compared with OLO-TIO (HR 1.04, 95% CI 0.86-1.26) and IND-GLY (HR 1.05, 95% CI 0.86-1.28). All-cause mortality was lower with VIL-UME compared with IND-GLY (HR 0.82, 95% CI 0.68-0.98), but not compared with OLO-TIO (HR 0.87, 95% CI 0.72-1.04). In a real-world setting of COPD treatment, the three dual bronchodilator combinations were similarly effective on the risk of a severe exacerbation of COPD. However, the VIL-UME and IND-GLY combinations may confer slightly superior effectiveness than OLO-TIO on the risk of moderate or severe exacerbation. The potential lower mortality with VIL-UME warrants further investigation.

Chronic Obstructive Pulmonary Disease Exacerbations and Pneumonia Hospitalizations Among New Users of Combination Maintenance Inhalers

Clinical guidelines on chronic obstructive pulmonary disease (COPD) recommend inhalers containing long-acting muscarinic antagonists (LAMAs) and long-acting β-agonists (LABAs) over inhalers containing inhaled corticosteroids (ICSs) and LABAs. However, data from randomized clinical trials comparing these combination inhalers (LAMA-LABAs vs ICS-LABAs) have been conflicting and raised concerns of generalizability. To assess whether LAMA-LABA therapy is associated with reduced COPD exacerbations and pneumonia hospitalizations compared with ICS-LABA therapy in routine clinical practice. This was a 1:1 propensity score-matched cohort study using Optum's Clinformatics Data Mart, a large commercial insurance-claims database. Patients must have had a diagnosis of COPD and filled a new prescription for a combination LAMA-LABA or ICS-LABA inhaler between January 1, 2014, and December 31, 2019. Patients younger than 40 years were excluded, as were those with a prior diagnosis of asthma. The current analysis was performed from February 2021 to March 2023. Combination LAMA-LABA inhalers (aclidinium-formoterol, glycopyrronium-formoterol, glycopyrronium-indacaterol, tiotropium-olodaterol, or umeclidinium-vilanterol) and combination ICS-LABA inhalers (budesonide-formoterol, fluticasone-salmeterol, fluticasone-vilanterol, or mometasone-formoterol). The primary effectiveness outcome was first moderate or severe COPD exacerbation, and the primary safety outcome was first pneumonia hospitalization. Propensity score matching was used to control for confounding between the 2 groups. Logistic regression analysis was used to estimate propensity scores. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models stratified on matched pairs. Among 137 833 patients (mean [SD] age, 70.2 [9.9] years; 69 530 [50.4%] female) (107 004 new ICS-LABA users and 30 829 new LAMA-LABA users), 30 216 matched pairs were identified for the primary analysis. Compared with ICS-LABA use, LAMA-LABA use was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation (HR, 0.92; 95% CI, 0.89-0.96) and a 20% reduction in the rate of first pneumonia hospitalization (HR, 0.80; 95% CI, 0.75-0.86). These findings were robust across a range of prespecified subgroup and sensitivity analyses. In this cohort study, LAMA-LABA therapy was associated with improved clinical outcomes compared with ICS-LABA therapy, suggesting that LAMA-LABA therapy should be preferred for patients with COPD.

Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts

BackgroundIn some patients with chronic obstructive pulmonary disease (COPD), type 2 inflammation may increase exacerbation risk and may be indicated by elevated blood eosinophil counts. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation.MethodsIn a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of at least 300 per microliter and an elevated exacerbation risk despite the use of standard triple therapy to receive dupilumab (300 mg) or placebo subcutaneously once every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations of COPD. Key secondary and other end points that were corrected for multiplicity were the change in the prebronchodilator forced expiratory volume in 1 second (FEV1) and in the scores on the St. George’s Respiratory Questionnaire (SGRQ; range, 0 to 100, with lower scores indicating a better quality of life) and the Evaluating Respiratory Symptoms in COPD (E-RS–COPD; range, 0 to 40, with lower scores indicating less severe symptoms).ResultsA total of 939 patients underwent randomization: 468 to the dupilumab group and 471 to the placebo group. The annualized rate of moderate or severe exacerbations was 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95% CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 by a least-squares (LS) mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112) with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a difference that was sustained through week 52. At week 52, the SGRQ score had improved by an LS mean of −9.7 (95% CI, −11.3 to −8.1) with dupilumab and −6.4 (95% CI, −8.0 to −4.8) with placebo (LS mean difference, −3.4; 95% CI, −5.5 to −1.3; P=0.002). The E-RS–COPD score at week 52 had improved by an LS mean of −2.7 (95% CI, −3.2 to −2.2) with dupilumab and −1.6 (95% CI, −2.1 to −1.1) with placebo (LS mean difference, −1.1; 95% CI, −1.8 to −0.4; P=0.001). The numbers of patients with adverse events that led to discontinuation of dupilumab or placebo, serious adverse events, and adverse events that led to death were balanced in the two groups.ConclusionsAmong patients with COPD who had type 2 inflammation as indicated by elevated blood eosinophil counts, those who received dupilumab had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; BOREAS ClinicalTrials.gov number, NCT03930732.)

Synergistic effects of COVID-19 and Pseudomonas aeruginosa in chronic obstructive pulmonary disease: a polymicrobial perspective.

This article discusses the connection between the novel coronavirus disease 2019 (COVID-19) caused by the coronavirus-2 (SARS-CoV-2) and chronic obstructive pulmonary disease (COPD). COPD is a multifaceted respiratory illness that is typically observed in individuals with chronic exposure to chemical irritants or severe lung damage caused by various pathogens, including SARS-CoV-2 and Pseudomonas aeruginosa. The pathogenesis of COPD is complex, involving a variety of genotypes and phenotypic characteristics that result in severe co-infections and a poor prognosis if not properly managed. We focus on the role of SARS-CoV-2 infection in severe COPD exacerbations in connection to P. aeruginosa infection, covering pathogenesis, diagnosis, and therapy. This review also includes a thorough structural overview of COPD and recent developments in understanding its complicated and chronic nature. While COVID-19 is clearly linked to emphysema and chronic bronchitis at different stages of the disease, our understanding of the precise interaction between microbial infections during COPD, particularly with SARS-CoV-2 in the lungs, remains inadequate. Therefore, it is crucial to understand the host-pathogen relationship from the clinician's perspective in order to effectively manage COPD. This article aims to provide a comprehensive overview of the subject matter to assist clinicians in their efforts to improve the treatment and management of COPD, especially in light of the COVID-19 pandemic.

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.

Pulmonary rehabilitation after severe exacerbation of COPD: a nationwide population study

BackgroundAcute exacerbations of chronic obstructive pulmonary disease (COPD) lead to a significant reduction in quality of life and an increased mortality risk. Current guidelines strongly recommend pulmonary rehabilitation (PR) after a severe exacerbation. Studies reporting referral for PR are scarce, with no report to date in Europe. Therefore, we assessed the proportion of French patients receiving PR after hospitalization for COPD exacerbation and factors associated with referral.MethodsThis was a national retrospective study based on the French health insurance database. Patients hospitalized in 2017 with COPD exacerbation were identified from the exhaustive French medico-administrative database of hospitalizations. In France, referral to PR has required as a stay in a specialized PR center or unit accredited to provide multidisciplinary care (exercise training, education, etc.) and admission within 90 days after discharge was assessed. Multivariate logistic regression was used to assess the association between patients’ characteristics, comorbidities according to the Charlson index, treatment, and PR uptake.ResultsAmong 48,638 patients aged ≥ 40 years admitted for a COPD exacerbation, 4,182 (8.6%) received PR within 90 days after discharge. General practitioner’s (GP) density (number of GPs for the population at regional level) and PR center facilities (number of beds for the population at regional level) were significantly correlated with PR uptake (respectively r = 0.64 and r = 0.71). In multivariate analysis, variables independently associated with PR uptake were female gender (aOR 1.36 [1.28–1.45], p < 0.0001), age (p < 0.0001), comorbidities (p = 0.0013), use of non-invasive ventilation and/or oxygen therapy (aOR 1.52 [1.41–1.64], p < 0.0001) and administration of long-acting bronchodilators (p = 0.0038).ConclusionThis study using the French nationally exhaustive health insurance database shows that PR uptake after a severe COPD exacerbation is dramatically low and must become a high-priority management strategy.

Exacerbations Predict Severe Cardiovascular Events in Patients with COPD and Stable Cardiovascular Disease-A Nationwide, Population-Based Cohort Study.

Patients with chronic obstructive pulmonary disease (COPD) commonly present with cardiovascular disease (CVD). We investigated the association between COPD exacerbations and major cardiovascular (CV) events in a COPD population with a history of CVD. This population-based and register-based cohort study identified all Danish COPD patients aged ≥40 years who visited a hospital-based, pulmonary outpatient clinic for COPD between 1st January, 2010, and 31st December, 2016, from a nationwide COPD registry. Patients with a history of a major CV event 36‒6 months prior to their COPD measurement date and no CV event 6 months before this date were included. During a 6-month assessment period, the risks of a new CV event (hospitalization with fatal/non-fatal stroke, myocardial infarction, or heart failure) and moderate and severe COPD exacerbations were evaluated. Odds ratios with 95% confidence intervals for CV events and death were estimated using adjusted logistic regression models. Of the 1501 COPD patients included, 55% experienced a COPD exacerbation and 13% experienced both an exacerbation and a CV event during follow-up (6 months). The odds of a CV event were 1.5 times higher in patients with a moderate exacerbation and more than 6-times higher in those with a severe exacerbation vs patients with no exacerbation(s). The majority of CV events occurred within 30 days post exacerbation in patients who experienced both an exacerbation and a CV event. In total, 113 patients died during the study period: 28% of deaths were caused by CVD and 72% by reasons other than CVD, mostly COPD. In patients with known CVD, severe COPD exacerbations are associated with increased odds of major CV events that occur within 30 days post exacerbation, highlighting the need to prevent exacerbations in COPD patients with concomitant CVD to potentially improve both respiratory and CV health.

The impact of COPD on the private healthcare system in Brazil: an economic analysis

Objective: To assess healthcare resource utilization and hospitalization costs of patients with chronic obstructive pulmonary disease (COPD) exacerbations in the Brazilian private healthcare system. Methods: A retrospective cohort study, considering data from an administrative database of a private company (Orizon). Patients aged ≥40 years old and with at least one COPD-related claim identified by the ICD-10 code (J40 to J44) at any time during the eligibility period (January/2010 to December/2013) were included in the analysis. Follow-up was performed until December/2014, death or inactivation of a health plan. Sociodemographic characteristics, number of emergency visits, hospital admissions (number and length of stay), length of hospital stay in an intensive care unit (ICU), number of severe COPD exacerbations, therapeutic approach, and hospitalization costs were assessed. Results: The analysis included 8,254 COPD patients. Emergency visits, hospital admission, and exacerbation rates were 0.4, 0.2, and 0.1 per person-year, respectively. The mean length of hospital stays and the length of stay of patients requiring or not ICU stay were 16.6 (SD = 77.0), 8.7 (SD = 36.9), and 27.6 (SD = 109.7), respectively. Mean costs associated to emergency department visits and hospitalizations were 258.2 BRL (SD = 383.1) and 38,165.4 BRL (SD = 124,683.5), respectively. Hospitalizations costs without ICU stay were 11,810.1 BRL (SD = 31,144.1) and 74,585.3 BRL (SD = 182,808.1) for those with ICU utilization. Conclusion: Costs for COPD management during disease exacerbation are very high and may reach almost 75 thousand BRL per hospitalization. The prevention of COPD exacerbations and better disease control may reduce the economic burden on the private healthcare system in Brazil.

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.

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.

Application of the Rome severity classification of COPD exacerbations in a real-world cohort of hospitalised patients.

Recently, the Rome classification was proposed in which objective and readily measurable variables were integrated to mark exacerbations of COPD (ECOPD) severity. The aim of this study is to investigate the distribution of a real-world patient population with hospitalised ECOPD according to the current classification across the newly proposed severity classification. We assume that a significant proportion of hospitalised patients will have a mild or moderate event. The Rome classification was applied to a cohort of 364 COPD patients hospitalised at the Department of Respiratory Medicine of Maastricht University Medical Center (MUMC) with a severe ECOPD. Differences in in-hospital, 30- and 90-day mortality were compared between mild, moderate and severe ECOPD according to the new classification. Moreover, data were stratified by the different severity classes and compared regarding general disease characteristics and clinical parameters. According to the Rome proposal, 52 (14.3%) patients had a mild ECOPD, 204 (56.0%) a moderate and 108 (29.7%) a severe ECOPD. In-hospital mortality in mild, moderate and severe events was 3.8%, 6.9% and 13.9%, respectively. Most clinical parameters indicated a significantly worse condition in patients classified in the severe group, compared to those in mild or moderate groups. Most of the events, traditionally all classified as severe because of the hospitalisation, were classified as moderate, while almost 15% were mild. The results of this study provide insight into the heterogeneity of hospitalised ECOPD and show that the newly proposed Rome criteria can differentiate between events with different short-term mortality rates.

Cognitive function and inhaler technique following recovery from exacerbations of COPD.

Cognitive impairment is highly prevalent in COPD outpatients during the post-exacerbation recovery period and is associated with poor inhaler technique https://bit.ly/3XkCvCv.

Оптимальное лечение инфекционного риносинусита как инструмент профилактики обострений ХОБЛ

Background: many studies report on the association between upper and lower respiratory infections. Various theories explain this association. In particular, some evidence demonstrates that nasal symptoms in diseases of the nasal cavity and paranasal sinuses affect exacerbations of chronic obstructive pulmonary disease (COPD). Therefore, treatment for rhinosinusitis improves the overall health and quality of life of these patients. Aim: to assess the clinical efficacy, tolerability, and safety of a combined antibacterial, anti-inflammatory, and vasoconstrictive drug in mild and moderate acute rhinosinusitis and concomitant COPD. Patients and Methods: this study enrolled 50 male and female patients aged 41–65 years. The primary examination included complaints and history taking, examination, instrumental tests for ENT organs, and pulmonary consultation. All patients underwent digital diaphanoscopy during the first visit to rule out acute exudative rhinosinusitis. In addition, all patients filled out a subjective assessment questionnaire. Treatment continued for 10 days with an interim examination on day 5±1 after starting treatment. Study group patients received a combined drug Polydexa with phenylephrine (1 injection into each nostril 4 times daily for 10 days) and irrigation with isotonic saline. The control group patients received 2 doses of mometasone furoate twice daily into each nostril for 10 days and irrigation with isotonic saline. Topical vasoconstrictors were allowed to be used as needed. Results: significant differences in the improvement of inflammatory symptoms between the groups were reported as early as by the second visit. The effect occurred earlier and was more significant at all treatment steps in the study group. A natural association between upper respiratory infection (acute rhinosinusitis), treatment strategy choice, and COPD exacerbation was revealed. Meanwhile, more COPD exacerbations were detected in the control group than in the study group (7 vs. 4). Conclusion: in mild and moderate acute rhinosinusitis and concomitant COPD, the combined drug Polydexa with phenylephrine reduces the rate and severity of COPD exacerbations. KEYWORDS: rhinosinusitis, nasal symptoms, upper and lower respiratory tract inflammation, Haemophilus influenzae, chronic obstructive pulmonary disease, phenylephrine, neomycin sulfate, polymixin B. FOR CITATION: Ovchinnikov A.Yu., Miroshnichenko N.A., Nikolaeva Yu.O., Zaitsev A.A. Optimal treatment for infectious rhinosinusitis as a tool to prevent COPD exacerbations. Russian Medical Inquiry. 2023;7(8):511–517 (in Russ.). DOI: 10.32364/2587-6821-2023-7-8-6.

When is LABA/LAMA Better than LAMA in GOLD Group B or D Patients for Reducing Acute Exacerbations of COPD?

Long-acting β2-agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown. With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095-0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749). The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms.

Development of the ESEx index: a tool for predicting risk of recurrent severe COPD exacerbations.

In chronic obstructive pulmonary disease (COPD), multiple recurrent severe exacerbations that require hospitalization can occur. These events are strongly associated with death and other clinical complications. We aimed to develop a prognostic model that could identify patients with COPD that are at risk of multiple recurrent severe exacerbations within 3 years. Prospective cohort. The derivation cohort comprised patients with stable, moderate-to-severe COPD. Multivariable logistic regression analyses were performed to develop the final model. Based on regression coefficients, a simplified index (ESEx) was established. Both, model and index, were assessed for predictive performance by measuring discrimination and calibration. Over 3 years, 16.4% of patients with COPD experienced at least three severe recurrent exacerbations. The prognostic model showed good discrimination of high-risk patients, based on three characteristics: the number of severe exacerbations in the previous year, performance in the five-repetition sit-to-stand test, and in the 6-minute-walk test. The ESEx index provided good level of discrimination [areas under the receiver operating characteristic curve (AUCs): 0.913]. The ESEx index showed good internal validation for the identification of patients at risk of three recurrent severe COPD exacerbations within 3 years. These tools could be used to identify patients who require early interventions and motivate patients to improve physical performance to prevent recurrent exacerbations.

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

ABSTRACT 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.