Severe COPD Exacerbations Research Articles

Deterioration Patterns in Patients Admitted for Severe COPD Exacerbation

Background: Chronic obstructive pulmonary disease (COPD) exacerbations represent significant clinical events marked by worsening respiratory symptoms, often necessitating changes in medication or hospitalization. Identifying patterns of exacerbation and understanding their clinical implications are critical for improving patient outcomes. This study aimed to identify exacerbation patterns in COPD patients using variations in the COPD Assessment Test (CAT) scores and compare clinical characteristics and comorbidities among patients with different exacerbation patterns. Methods: An observational study was conducted involving COPD patients admitted for severe exacerbations. The administered CAT questionnaire referred to two periods: 1) the period during hospital admission and 2) the stable period two months prior to admission. Results: Fifty patients (60% male, mean age 70.5 years, standard deviation [SD] 9.6) were included; of these, eight (16%) were active smokers. Significant worsening in CAT scores during the exacerbation compared to the stable period was observed (25 vs. 13.5, p < 0.001). Three exacerbation patterns were identified: increased cough and sputum (cluster 1); increased dyspnea and activity limitation (cluster 2); and poorer sleep quality and lower energy (cluster 3). No significant differences were found regarding demographics and lung function. Conclusions: Three distinct exacerbation patterns were identified in COPD patients based on CAT score variations, suggesting that exacerbations are heterogeneous events. Future studies with larger sample sizes and prospective follow-up are necessary to validate these findings and explore their clinical and prognostic implications.

Chronic obstructive pulmonary disease and its treatment in the Russian Federation: Results of a cross-sectional assessment from the CORSAIR observational study

Abstract Up-to-date data on patients with chronic obstructive pulmonary disease (COPD) in the Russian Federation are necessary to improve medical care effectiveness.This article presents the results of the retrospective part and the cross-sectional assessment of the CORSAIR study, which aimed to assess the distribution of COPD patients in the Russian population by symptom severity and exacerbation risk as per GOLD (2020) classification groups A, B, C, D.Methods. The observational multicenter study CORSAIR included a cross-sectional assessment with data collection during the previous 12 months (retrospective part) and subsequent follow-up for 12 months (prospective part). Data from 704 patients obtained at 18 study sites from August 2021 to November 2022 are presented. At the first visit, the physician recorded medical history, clinical data on the disease course, and COPD therapy, assessed compliance of treatment with national guidelines, and determined whether treatment change was needed considering the predominant treatable trait (dyspnea or exacerbation).Results. Upon inclusion, most patients had severe COPD symptoms (mMRC score ≥ 2; САТ score ≥ 10) and severe and very severe airflow obstruction (GOLD III and GOLD IV; FEV1 < 50% оf predicted). More than half of the patients had at least one moderate or severe COPD exacerbation within the previous 12 months. As per the GOLD (2020) classification, 57.2% of patients belonged to Group B (severe symptoms and low risk of exacerbations) and 30.3% to Group D (severe symptoms and high risk of exacerbations). 58.8% of patients received treatment that was not compliant with national clinical guidelines in force at the study initiation. 31.7% of patients had not COPD control. Blood eosinophil count was above 300 cells/μL in 15.1% of patients.Conclusion. In most cases, patients had severe COPD symptoms with frequent exacerbations, and the prescribed treatment did not comply with national clinical guidelines. These data will be analyzed alongside the prospective study results.

Does Long-Term Oxygen Therapy Reduce Exacerbations in Chronic Obstructive Pulmonary Disease? A Meta-Analysis

Background: Chronic obstructive pulmonary disease (COPD) exacerbations contribute significantly to morbidity, mortality, and healthcare costs. While long-term oxygen therapy (LTOT) is a standard treatment for severe resting hypoxemia in COPD, its impact on exacerbations remains unclear. This meta-analysis aimed to evaluate the effect of LTOT on the frequency and severity of COPD exacerbations. Methods: A systematic search of PubMed, Embase, and Cochrane Library was conducted (January 2018 to December 2023) for randomized controlled trials (RCTs) comparing LTOT to no LTOT in COPD patients. The primary outcome was the rate of moderate to severe COPD exacerbations. Secondary outcomes included hospitalization due to exacerbations and all-cause mortality. The risk of bias was assessed using the Cochrane Risk of Bias tool. A random-effects model was used to pool data, and heterogeneity was assessed using the I² statistic. Results: Nine RCTs with 2,949 participants were included. LTOT was associated with a statistically significant reduction in the rate of moderate to severe exacerbations (Rate Ratio [RR] 0.72; 95% Confidence Interval [CI] 0.67 to 0.78; p < 0.000001), representing an estimated 28% reduction. LTOT also significantly reduced hospitalization for exacerbations (RR 0.69; 95% CI 0.61 to 0.79; p < 0.000001) and all-cause mortality (RR 0.71; 95% CI 0.57 to 0.89; p = 0.003). Conclusion: LTOT significantly reduces the frequency of moderate to severe COPD exacerbations, related hospitalizations, and all-cause mortality. These findings support LTOT use in eligible COPD patients to improve clinical outcomes.

Trends in COPD severe exacerbations, and all-cause and respiratory mortality, before and after implementation of newer long-acting bronchodilators in a large population-based cohort

BackgroundLittle is known about the trends in morbidity and mortality at the population level that followed the introduction of newer once-daily long-acting bronchodilators for COPD. The purpose of the study was to evaluate whether the availability of new bronchodilators was associated with changes in the temporal trends in severe COPD exacerbations and mortality between 2007 and 2018 in the older population with COPD; and whether this association was homogeneous across sex and socioeconomic status classes.MethodsWe used an interrupted time-series and three segments multivariate autoregressive models to evaluate the adjusted changes in slopes (i.e., trend effect) in monthly severe exacerbation and mortality rates after 03/2013 and 02/2015 compared to the tiotropium period (04/2007 to 02/2013). Cohorts of individuals > 65 years with COPD were created from the nationally representative database of the Quebec Integrated Chronic Disease Surveillance System in the province of Quebec, Canada. Whether these trends were similar for men and women and across different socioeconomic status classes was also assessed.ResultsThere were 130,750 hospitalizations for severe exacerbation and 104,460 deaths, including 24,457 (23.4%) respiratory-related deaths, over the study period (928,934 person-years). Significant changes in trends were seen after 03/2013 for all-cause mortality (-1.14%/month;95%CI -1.90% to -0.38%), which further decreased after 02/2015 (-1.78%/month;95%CI -2.70% to -0.38%). Decreases in respiratory-related mortality (-2.45%/month;95%CI -4.38% to -0.47%) and severe exacerbation (-1,90%/month;95%CI -3.04% to -0.75%) rates were only observed after 02/2015. These observations tended to be more pronounced in women than in men and in higher socioeconomic status groups (less deprived) than in lower socioeconomic status groups (more deprived).ConclusionsThe arrival of newer bronchodilators was chronologically associated with reduced trends in severe exacerbation, all-cause and respiratory-related mortality rates among people with COPD > 65 years. Our findings document population benefits on key patient-relevant outcomes in the years following the introduction of newer once-daily long-acting bronchodilators and their combinations, which were likely multifactorial. Public health efforts should focus on closing the gap between lower and higher socioeconomic status groups.

Suppression of the DNA repair enzyme NEIL2 promotes persistent inflammation and genomic damage in subjects with stable COPD and during severe exacerbations.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease that is an independent risk factor for lung cancer. NEIL2, a DNA glycolase involved in DNA repair during transcription, has also been associated with an increased incidence of malignancies in humans. NEIL2 knockout mouse models have demonstrated increased inflammation and oxidative DNA damage in the lungs after exposure to an inflammatory insult, but data are lacking regarding NEIL2 function in individuals with stable COPD and during severe acute exacerbations of COPD (AECOPD). We investigated whether NEIL2 levels and oxidative DNA damage to the transcribed genome are altered in individuals with stable COPD and AECOPD. The study was conducted at a single center in the US. Eligible subjects underwent a one-time 30 cc venous blood draw. The population consisted of 50 adults: 16 with stable COPD, 11 hospitalized for AECOPD, and 23 volunteers. We analyzed blood leukocytes for NEIL2 mRNA and DNA damage by RT-qPCR and LA-qPCR, respectively, in all groups. Plasma levels of seven biomarkers, CXCL1, CXCL8, CXCL9, CXCL10, CCL2, CCL11 and IL-6, were analyzed in the COPD groups using a magnetic bead panel (Millipore®). The NEIL2 mRNA levels were lower in individuals with stable COPD and AECOPD than in controls (0.72 for COPD, p = 0.0289; 0.407 for AECOPD, p = 0.0002). The difference in NEIL2 mRNA expression between the stable COPD group and AECOPD group was also statistically significant (p < 0.001). The fold change in DNA lesions per 10 kb of DNA was greater in the stable COPD (9.38, p < 0.0008) and AECOPD (15.81, p < 0.0004) groups than in the control group. The difference in fold change was also greater in the AECOPD group versus stable COPD p < 0.0236). Biomarker levels were not significantly different between the COPD groups. NEIL2 levels were correlated with plasma eosinophil levels in the stable COPD group (r = 0.737, p < 0.0027). NEIL2 mRNA levels are significantly reduced in COPD subjects and are associated with increased DNA damage and inflammation. These results reveal a mechanism that promotes persistent airway inflammation and oxidative genomic damage and increases the risk of malignancy in this population.

Effect of Triple Therapy on Cardiovascular and Severe Cardiopulmonary Events in COPD: A Post-hoc Analysis of a Randomized, Double-Blind, Phase 3 Clinical Trial (ETHOS).

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of cardiovascular and cardiopulmonary events. In the Phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality versus dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Further, the effect of BGF on time to first severe exacerbation has not been reported. Objective: Assess the effects of BGF 320/18/9.6 μg (BGF 320) and other ICS-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from ETHOS. Methods: Patients with moderate-to-very severe COPD and a history of exacerbations were randomized to twice-daily BGF 320, BGF 160/18/9.6 μg, BFF 320/9.6 μg, or GFF 18/9.6 µg (GFF). Time to first severe COPD exacerbation was a pre-specified endpoint; post-hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event (MACE), time to first cardiovascular adverse event (AE) of special interest (CVAESI), time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for CVAESI (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate-to-very severe COPD.

Benefits of budesonide/glycopyrronium/formoterol fumarate dihydrate on lung function and exacerbations of COPD: a post-hoc analysis of the KRONOS study by blood eosinophil level and exacerbation history

BackgroundJapanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count – focusing on blood EOS count 100 to < 300 cells/mm3 – as a function of exacerbation history and COPD severity.MethodsIn KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12–24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses.ResultsAmong patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD.ConclusionsThese post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations.Trial registrationClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).

Efficacy and safety of simultaneous combined Zephyr and Spiration valve therapy in patients with advanced pulmonary emphysema

BackgroundEndoscopic lung volume reduction with valves is a minimally invasive treatment strategy for patients with severe pulmonary emphysema. Two valve systems are currently available: Zephyr and Spiration valves. As these can be implanted simultaneously in the same procedure, the question arose as to the effect on lung function, exercise capacity and subjective disease perception after combined valve treatment. MethodsWe conducted a retrospective analysis of 108 patients with combined, simultaneous treatment of Zephyr and Spiration valves. The decision on which and how many valves to implant was based on the individual patient anatomy. Effects on lung function, exercise capacity and atelectasis formation as well as complications were evaluated 90- and 180-days post-treatment (90d-FU and 180d-FU). ResultsAt 90d-FU (n = 90), the mean change was 86.7 ± 183.7 mL for FEV1 and -645.3 ± 1276.5 mL for RV, with responder rates of 39.8 % and 46.5 %, respectively. Complete atelectasis occurred in 16.7 % and partial atelectasis in 25.5 % of patients. Six-minute walking distance increased by 27.00 m [-1.50 – 68.50m]. The rates of pneumothorax (10.2 %) 6 months after treatment were not higher than in randomized controlled trials (RCTs). Likely due to the inclusion of high-risk patients, there was a higher incidence of severe COPD exacerbation (21.3 %) and pneumonia (12.0 %) compared to RCTs. ConclusionsThe combined implantation of Zephyr and Spiration valves resulted in significant clinical and functional improvements with an acceptable risk profile. Therefore, the ability to combine both valve types in severe emphysema could be a promising option in endoscopic lung volume reduction.

Predictive score for in-hospital mortality in patients with severe acute exacerbations of COPD

Predictive score for in-hospital mortality in patients with severe acute exacerbations of COPD

Early and late effects of volatile sedation with sevoflurane on respiratory mechanics of critically ill COPD patients

BackgroundThe objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation.MethodsProspective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint.ResultsSixteen patients were enrolled and were sedated for 126 h(61–228) in the propofol group and 207 h(171–216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8–21.6) in the propofol group and 20.4cmH2O/l/s(18.6–26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176–290) in the propofol group and 73 ml(35–126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1–3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups.ConclusionsIn critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.

Outcomes among patients with chronic obstructive pulmonary disease after recovery from COVID-19 infection of different severity

While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95–10.15, p < 0.001) and 6.77 (95% CI = 2.08–22.00, p = 0.001) respectively. Patients with severe COVID-19 infection had significantly increased risks of increase in severe COPD exacerbation frequency with adjusted odds ratios of 4.73 (95% CI = 1.55–14.41, p = 0.006) non-COVID-19 respiratory mortality from COPD exacerbation or pneumonia with adjusted hazard ratio of 11.25 (95% CI = 2.98–42.45, p < 0.001). After recovery from COVID-19, worsening of COPD control from worsening of dyspnea, increase in severe exacerbation frequency to non-COVID-19 respiratory mortality (COPD exacerbation and pneumonia) was observed among patients with severe COVID-19. Mild to moderate COVID-19 was also associated with symptomatic deterioration.

Assessment of phosphatemia at admission to the intensive care unit to predict mechanical ventilation among patients with acute exacerbation of chronic obstructive pulmonary disease: a retrospective cohort study.

Hypophosphatemia has been reported to impair diaphragmatic function in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the role of dysphosphatemia at admission [plasmatic phosphate concentration at intensive care unit (ICU) admission (T0-Ph)] to the ICU and respiratory outcomes among patients with severe acute COPD exacerbation. We aimed to assess the value of T0-Ph as a predictive factor of invasive mechanical ventilation (MV) during ICU stay. We retrospectively included consecutive patients admitted to the ICU for a severe acute exacerbation of COPD between May 2015 and December 2018. Logistic multivariate regression analysis was performed to identify association between T0-Ph and the need for invasive MV during the ICU stay. We included 198 patients of whom 132 (67%) were male. The median age was 70 [interquartile range (IQR), 61-77] years. Nine (4.5%) patients died in the ICU. Median T0-Ph was significantly higher among patients requiring invasive MV as compared to non-intubated patients [1.23 (IQR, 1.07-1.41) and 1.09 (IQR, 0.91-1.27) mmol/L; P=0.005]. By multivariate analysis, pneumonia [odds ratio (OR) =6.42; 95% confidence interval (CI): 2.78-15.96; P<0.0001) and a history of intubation (OR =3.33; 95% CI: 0.97-11.19; P=0.05) were independently associated with the need for invasive MV, whereas T0-Ph was not (OR =1.75; 95% CI: 0.72-4.44; P=0.22). T0-Ph was significantly higher in patients requiring invasive MV. However, T0-Ph was not associated with the need for invasive MV in multivariate analysis.

Development of a novel cell-free DNA fragmentomics assay for monitoring disease progression in real-time for stage IV cancer patients.

e14544 Background: Advances in oncology have improved treatment response rates and overall survival. Many treatments, even targeted therapies, can fail to deliver an initial response to stage IV patients. We aimed to evaluate cfDNA as a biomarker of non-response to therapy in metastatic cancer. Methods: Blood samples were prospectively collected in Streck tubes at baseline and 12 - 21 days after initiating treatment, along with detailed clinical data, including imaging assessments captured in a cohort of metastatic non-small-cell lung (50), small-cell lung (8), breast (21), and colorectal (51) cancer study participants. To determine the fragmentation pattern of the DNA in the patient plasma, cfDNA was extracted using QIAamp Circulating Nucleic ACID Kit (Qiagen). cfDNA fragment concentrations were quantitated using two multiplexed qPCR assays on a QuantStudio 5. Primers and probes for the qPCR assay were designed using the high copy number retrotransposons Alu and SVA, represented across all 23 chromosomes. The two assays were performed on each specimen: an &gt;80bp, &gt;265bp and internal positive control (IPC) assay and an &gt;105bp, &gt;265bp with IPC assay. Following analytic validation of the assays, specimens from all participants were analyzed. The results from both assays were combined and merged with the clinical results and statistically analyzed. Results: 130 patients were included in the analysis. The qPCR assays work across all tumor and therapy types analyzed. A logit regression model was developed which calculates the likelihood that a patient’s cancer is progressing. The area under the ROC is 0.93 with a p-value of &lt;0.001. Results clustered above the logit value of 0.65 (n=15) are all progressors by imaging (PPV=100.0%). All logit values below 0.045 (n=69) are non-progressors by imaging (NPV=0.0%). Bootstrap resampling (1,000 iterations) suggests a 99.3% PPV at the 0.9 logit cut point. Healthy subjects (9) and patients with a variety of conditions (33) known to create elevated fragmented levels of cfDNA were also analyzed to determine which patients are not appropriate patients for the assay. Results indicate patients with following conditions within 10 days of a blood draw should be excluded: stroke, myocardial infarction, severe acute autoimmune event, and severe acute COPD exacerbation; and patients treated with a chemotherapy agent (i.e., methotrexate) within 10 days of a blood draw. Conclusions: These data support the value of a blood-based biopsy test for evaluating cancer cfDNA. cfDNA fragment assay is applicable to lung, colorectal, and breast cancer, and is agnostic to any mutation status. The cfDNA fragment analysis is a promising biomarker to monitor patient treatment and save time and the expense of clinically ineffective therapies, allowing the medical oncologist to evaluate the response to therapy in real-time and provide the best care possible for the patient.

#2075 Impact of chronic obstructive pulmonary disease on the outcomes of hemodialysis patients

Abstract Background and Aims Chronic obstructive pulmonary disease, COPD, is a common cause of morbidity and mortality. Comorbidities are frequent among COPD patients, some of which are explained by shared risk factors of smoking and increased age. Chronic kidney disease, leading to end-stage renal disease requiring hemodialysis (HD) is not uncommon in patients with COPD, and vice-versa. The prevalence and the impact of coexistence of COPD among HD patients was not extensively described. We aimed to measure the prevalence of COPD among a cohort of HD patients, and study how it relates to significant outcomes of mortality, morbidity, including unplanned hospital admissions, and kidney transplantation (KT). Method A retrospective study of subjects who initiated HD during 2015-2018. Participants were categorized into one of two groups, with or without COPD. Clinical, laboratory and pulmonary function tests data were extracted from medical records, as were outcomes of mortality, morbidity, and KT (until December 31st, 2021, or until death). Results Forty-three of 234 were diagnosed with COPD (18.4%). Their average FEV1%pred was 60%. Thirty-eight subjects in the COPD group (88.4%) were hospitalized for severe COPD exacerbations during a mean follow-up of 36.1 months, averaging 3.6 severe exacerbations per patient. Despite this, maintenance inhaler therapy was underutilized. All-cause mortality rates were higher for HD patients with COPD (72.1% vs. 47.1%, p=0.003), as were rates of acute coronary syndrome (39.5% vs. 23.6%, p=0.026). Conclusion COPD is common among HD patients and is associated with significant morbidity and increased mortality.

The burden of severe exacerbations, their relationship to clinical outcomes and the use of health resources in the Russian population of patients with chronic obstructive pulmonary disease: a subanalysis of the Russian population of EXACOS International Study

According to the literature, the risk of death in patients with chronic obstructive pulmonary disease (COPD) increases with both frequency and severity of the disease exacerbations. However, the clinical burden and healthcare resource utilization associated with severe COPD exacerbations in the Russian population have not been adequately studied.The aim of this study was to assess the clinical burden of severe COPD in Russia by examining the relationship between frequency of severe exacerbations, clinical outcomes, and healthcare utilization among the Russian patients.Methods. The EXACOS International Study on Exacerbations and Outcomes was an observational, cross-sectional study that collected retrospective data from medical records over a five-year period. The study population included a broad range of COPD patients monitored by pulmonologists. The purpose of the study was to assess the frequency of severe exacerbations that were defined as hospitalizations (with or without admission to an intensive care unit) or emergency department visits due to worsening of COPD symptoms.Results. A total of 326 patients with COPD were included (mean age: 64.8 years, 87.1% male). Most participants had moderate (137 (42.0%)) or severe COPD (135 (41.4%)), as well as comorbidities (275 (84.4%)). The most common comorbidities included hypertension, heart failure, and diabetes. During the study period, 120 (40.0%), 158 (48.5%), and 247 (75.8%) patients received courses of oral corticosteroids, injectable corticosteroids and antibiotics, respectively. 250 (76.7%) patients experienced at least one severe COPD exacerbation, with a total of 1,026 events; and 102 (31.3%) had more than 3 exacerbations. The annual number of exacerbations increased from 128 in 2019 to 294 in 2021 (p &lt; 0.0001), and the proportion of patients with severe exacerbations also increased from 23.6% in 2009 to 54.7% in 2021.Conclusion. The high clinical burden of severe COPD exacerbations among the Russian population indicates a significant need for further research into factors leading to these events, modification of these factors and optimization of therapy to prevent the exacerbations.

AERIFY-1/2: two 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 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.DiscussionThe primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, 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 end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.

Monocyte distribution width (MDW) and DECAF: two simple tools to determine the prognosis of severe COPD exacerbation

Monocyte distribution width (MDW) has been associated with inflammation and poor prognosis in various acute diseases. Chronic obstructive pulmonary disease (COPD) exacerbations (ECOPD) are associated with mortality. The objective of this study was to evaluate the utility of the MDW as a predictor of ECOPD prognosis. This retrospective study included patient admissions for ECOPD. Demographic, clinical and biochemical information; intensive care unit (ICU) admissions; and mortality during admission were recorded. A total of 474 admissions were included. MDW was positively correlated with the DECAF score (r = 0.184, p < 0.001) and C-reactive protein (mg/dL) (r = 0.571, p < 0.001), and positively associated with C-RP (OR 1.115 95% CI 1.076–1.155, p < 0.001), death (OR 9.831 95% CI 2.981– 32.417, p < 0.001) and ICU admission (OR 11.204 95% CI 3.173–39.562, p < 0.001). High MDW values were independent risk factors for mortality (HR 3.647, CI 95% 1.313–10.136, p = 0.013), ICU admission (HR 2.550, CI 95% 1.131–5.753, p = 0.024), or either mortality or ICU admission (HR 3.084, CI 95% 1.624–5.858, p = 0.001). In ROC analysis, a combined MDW–DECAF score had better diagnostic power (AUC 0.777 95% IC 0.708–0.845, p < 0.001) than DECAF (p = 0.023), MDW (p = 0.026) or C-RP (p = 0.002) alone. MDW is associated with ECOPD severity and predicts mortality and ICU admission with a diagnostic accuracy similar to that of DECAF and C-RP. The MDW– DECAF score has better diagnostic accuracy than MDW or DECAF alone in identifying mortality or ICU admission.

Accuracy of urgency allocation in patients with shortness of breath calling out-of-hours primary care: a cross-sectional study

BackgroundIn out-of-hours primary care (OHS-PC), semi-automatic decision support tools are often used during telephone triage. In the Netherlands, the Netherlands Triage Standard (NTS) is used. The NTS is mainly expert-based and evidence on the diagnostic accuracy of the NTS’ urgency allocation against clinically relevant outcomes for patients calling with shortness of breath (SOB) is lacking.MethodsWe included data from adults (≥18 years) who contacted two large Dutch OHS-PC centres for SOB between 1 September 2020 and 31 August 2021 and whose follow-up data about final diagnosis could be retrieved from their own general practitioner (GP).The diagnostic accuracy (sensitivity and specificity with corresponding 95% confidence intervals (CI)) of the NTS’ urgency levels (high (U1/U2) versus low (U3/U4/U5) and ‘final’ urgency levels (including overruling of the urgency by triage nurses or supervising general practitioners (GPs)) was determined with life-threatening events (LTEs) as the reference. LTEs included, amongst others, acute coronary syndrome, pulmonary embolism, acute heart failure and severe pneumonia.ResultsOut of 2012 eligible triage calls, we could include 1833 adults with SOB who called the OHS-PC, mean age 53.3 (SD 21.5) years, 55.5% female, and 16.6% showed to have had a LTE. Most often severe COVID-19 infection (6.0%), acute heart failure (2.6%), severe COPD exacerbation (2.1%) or severe pneumonia (1.9%).The NTS urgency level had a sensitivity of 0.56 (95% CI 0.50–0.61) and specificity of 0.61 (95% CI 0.58–0.63). Overruling of the NTS’ urgency allocation by triage nurses and/or supervising GPs did not impact sensitivity (0.56 vs. 0.54, p = 0.458) but slightly improved specificity (0.61 vs. 0.65, p < 0.001).ConclusionsThe semi-automatic decision support tool NTS performs poorly with respect to safety (sensitivity) and efficiency (specificity) of urgency allocation in adults calling Dutch OHS-PC with SOB. There is room for improvement of telephone triage in patients calling OHS-PC with SOB.Trial registrationThe Netherlands Trial Register, number: NL9682.

Relation between airway cellular and bacterial findings and severity of COPD exacerbations: A multicentric study

&lt;b&gt;Aim: &lt;/b&gt;To evaluate the relationships between sputum and bronchoalveolar lavage (BAL) cellular and bacterial findings and severity of exacerbation of chronic obstructive pulmonary disease (ECOPD).&lt;br /&gt; &lt;b&gt;Patients &amp;amp; methods: &lt;/b&gt;A cross-section study was conducted on 307 patients with ECOPD. They underwent sputum and BAL inflammatory cell count and bacterial culture.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; Patients with severe ECOPD have significantly higher neutrophils percentage (neut.%), lower lymphocytes percentage (lymph.%), lower eosinophils percentage (eosin.%) and higher neutrophil/lymphocyte ratio (NLR) as compared to patients with mild ECOPD. It was also shown that patients with severe ECOPD had significantly higher BAL neut.%, lower lymph.%, lower eosin.%, and higher NLR as compared to the other two subgroups. Also, patients with severe ECOPD have significantly higher frequency of cases with monomicrobial (71.30% vs. 36.10%) and polymicrobial (21.25% vs. 2.10%) growths in comparison to patients with mild ECOPD.&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;Cellular and bacterial findings in sputum and BAL are related to severity of ECOPD.

Elucidating the risk of cardiopulmonary consequences of an exacerbation of COPD: results of the EXACOS-CV study in Germany

BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) represent a period of vulnerability. This study explored the association between time periods following an exacerbation and the risk of severe cardiovascular (CV)...