Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS

ERS statement: A core outcome set for clinical trials evaluating the management of COPD exacerbations

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use

Serum uric acid and arterial lactate levels in patients with obstructive sleep apnea syndrome: the effect of CPAP treatment

Objectives: Serum uric acid (UA) and arterial lactate acid (LA) are markers of oxidative stress and tissue hypoxia that are present in patients with obstructive sleep apnea syndrome (OSAS). The aim of the study was to evaluate the associations between UA and LA levels and OSAS characteristics as well as the effect of their levels after continuous positive airway pressure (CPAP) treatment. Methods: This is a retrospective of newly diagnosed patients with OSAS. UA and LA levels were measured the night before the diagnostic sleep study, and 6 months after CPAP therapy. Results: We evaluated 604 individuals with OSAS and 98 controls (i.e. individuals without sleep-related breathing disorders). Baseline median (IQR) serum UA levels were higher in OSAS patients compared to controls; 7.0 (6.4, 8.1) mg/dL vs 6.3 (6.1, 6.4) mg/dL, respectively (p < 0.001). This difference remained significant, after adjustment of serum UA to creatinine ratio (UA/Cr) (p < 0.001). Patients with OSAS had higher LA levels at baseline compared to controls; 2.26 (2.25, 2.31) mmol/L vs 1.90 (1.87, 1.97) mmol/L, respectively (p < 0.001). Both UA and LA levels decreased significantly after CPAP treatment [median (IQR): 7.0 (6.4, 8.1) mg/dL vs 6.4 (6.2, 6.8) mg/dL, p < 0.001 and 2.26 (2.25, 2.31) mmol/L vs 2.08 (2.07, 2.31) mmol/L, p < 0.001]. Several sleep parameters were independent predictors of UA and LA levels. Conclusion: In OSAS patients increased serum UA and arterial LA levels are found. CPAP therapy resulted in significant reductions in levels of both biomarkers. © 2021 Informa UK Limited, trading as Taylor & Francis Group

Statins and outcome after hospitalization for COPD exacerbation: A prospective study

Background: Retrospective studies have shown that the use of statins is associated with reduced mortality and decreased hospitalizations from COPD, but data from prospective studies are lacking. Methods: We followed-up prospectively 245 patients admitted to hospital for exacerbations of COPD (ECOPD) with monthly evaluations for one year. The role of statins on outcomes was evaluated by Cox regression analysis after proper adjustments for age, gender, BMI, current smoking status, Charlson comorbidity index and COPD stage. Health-related quality of life (HRQoL) was evaluated by Saint George's Respiratory Questionnaire. Results: There was no effect of statins on either 30-day or 1-year mortality. Patients receiving statins presented a lower total number of ECOPD during the 1-year follow up (2.1 +/- 2.7 vs. 2.8 +/- 3.2 ECOPD/patient respectively, p = 0.037). After proper adjustments, the use of statins was associated with a lower risk for ECOPD [HR: 0.656 (95% CI: 0.454-0.946)] and severe ECOPD [HR: 0.608 (95%CI: 0.381-0.972)]. The group of statins presented better improvement in HRQoL at 2, 6 and 12 months (p < 0.001). Conclusions: The use of statins in patients hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and severe ECOPD and improved HRQoL These data support a possible beneficial role for these agents in COPD. (C) 2011 Elsevier Ltd. All rights reserved

Serum Surfactant Protein Levels in Patients Admitted to the Hospital with Acute COPD Exacerbation

Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of disease severity and as predictive factors of unfavorable outcomes. The aim of this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D in patients with COPD both during AECOPD and in stability and to test their possible associations with disease severity and with the development of new exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were included. Serum SP levels were measured on admission, at discharge, and on stability. SP-A levels were significantly lower both on admission and at discharge in patients with early relapse compared to those with late or no relapse (29.2 ± 9.1 vs. 43.9 ± 16.9 ng/ml, p = 0.037, and 24.3 ± 2.8 vs. 39.3 ± 14.2 ng/ml, p = 0.011, respectively). SP-B levels were found to have a trend to be higher at discharge and significantly higher on stability in patients experiencing an early relapse compared to those with late or no relapse (52.5 ± 31.6 vs. 31.4 ± 32.3 ng/ml, p = 0.052 and 64.8 ± 32.6 vs. 32.8 ± 25.6 ng/ml, p = 0.024, respectively). Finally, the ROC analysis showed that serum SP-A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of early relapse. Our conclusion is that serum levels of SPs might be related to disease outcomes in COPD patients. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Serum periostin in patients hospitalized for COPD exacerbations

Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory response in patients with asthma, but its predictive role in hospitalized patients with COPD has not been evaluated. The aim of the present observational prospective cohort study was to evaluate the possible role of serum periostin as predictor of outcome in COPD patients hospitalized for AECOPD. Serum periostin was measured on admission and at discharge in patients admitted to the hospital for a COPD exacerbation. Patients were followed-up for 1 year for future exacerbations, hospitalizations and mortality. 155 consecutive patients admitted to the hospital for AECOPD were included to the study. Periostin levels on admission were elevated compared to discharge [34.7 (25.2–52.2) vs. 25.9 (17.4–41.0) ng/mL, p = 0.003], but serum periostin levels did not differ between patients with or without prolonged hospitalization, or those who required non-invasive ventilation, intubation, or died during hospitalization. Frequent exacerbators had higher serum periostin levels at the time of discharge compared to non-frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p &lt; 0.001]. Periostin levels above the median value (25 ng/mL) were not related to the time of next exacerbation, time of next COPD hospitalization, (p = 0.858) or time to death. The role of serum periostin levels as a predictive biomarker of future risk in hospitalized patients with COPD is of limited value. © 2017 Elsevier Lt

The impact of depressive symptoms on recovery and outcome of hospitalised COPD exacerbations

The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in prospective studies. We prospectively enrolled 230 consecutive patients hospitalised for AECOPD, without previous diagnosis of depression. Depressive symptoms were evaluated with Beck&apos;s depression inventory. Pulmonary function tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale were recorded on admission and on days 3, 10 and 40. Patients were evaluated monthly for 1 year. Patients with depressive symptoms required longer hospitalisation (mean±SD 11.6±3.7 versus 5.6&lt;4.1 days, p,0.001). Clinical variables improved during the course of AECOPD, but depressive symptoms on admission had a significant impact on dyspnoea (p&lt;0.001) and CAT score (p50.012) improvement. Patients with depressive symptoms presented more AECOPD (p&lt;0.001) and more hospitalisations for AECOPD (p&lt;0.001) in 1 year. In multivariate analysis, depressive symptoms were an independent predictor of mortality (hazard ratio 3.568, 95% CI 1.302-9.780) and risk for AECOPD (incidence rate ratio (IRR) 2.221, 95% CI 1.573-3.135) and AECOPD hospitalisations (IRR 3.589, 95% CI 2.319-5.556) in 1 year. The presence of depressive symptoms in patients admitted for AECOPD has a significant impact on recovery and is related to worse survival and increased risk for subsequent COPD exacerbations and hospitalisations in 1 year. © ERS 2013

Blood eosinophils as predictor of outcomes in patients hospitalized for COPD exacerbations: a prospective observational study

Purpose: In the present prospective multicentre observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations. Material and methods: Consecutive patients &amp;gt;40 years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in three groups (&amp;lt;50, 50–149 and ≥150 cells/μL). Patients received standard care and were followed up for a year. Results: A total of 388 patients were included (83.5% male, mean age 72 years). Patients with higher blood eosinophils had less dyspnoea (Borg scale), lower C-reactive protein (CRP) and higher PaO2/FiO2 (partial pressure for oxygen/fraction of inhaled oxygen), and were discharged earlier (median 11 vs. 9 vs. 5 days for patients with &amp;lt;50, 50–149 and ≥150 cells/μL, respectively). Patients with &amp;lt;50 cells/μL presented higher 30-day and 1-year mortality, whereas there were no differences in moderate/severe COPD exacerbations between the three groups. In a post hoc analysis, treatment with inhaled corticosteroids as per physicians’ decision was associated with better exacerbation prevention during follow-up in patients with ≥150 cells/μL. Conclusions: Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker. © 2021 Informa UK Limited, trading as Taylor &amp; Francis Group

SARS-Cov-2 Infection in Severe Asthma Patients Treated With Biologics

Background: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. Objective: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. Methods: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. Results: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors’ suggestion. Conclusion: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19. © 2022 American Academy of Allergy, Asthma & Immunolog