Search

Background: Chronic Obstructive Pulmonary Disease (COPD) is a disease with high morbidity and mortality globally. Exacerbations of COPD are major contributors to disease progression and a decline in health-related quality of life (HRQoL). High-flow nasal cannula (HFNC) oxygen therapy is an innovative therapy that provides humidified and heated blended air and oxygen through a nasal cannula. There is some preliminary evidence supporting the effectiveness of HFNC in managing COPD exacerbations, but there are limited data on its effectiveness when used at home for patients with stable, severe COPD. The aim of the present study is to test the hypothesis that home HFNC can decrease the COPD exacerbations rate and hospital admissions and improve HRQoL measures in severe COPD patients with frequent COPD exacerbations. Methods: In a prospective proof-of-concept interventional multicenter study, 40 GOLD stage III and IV COPD patients with a high disease burden (≥2 exacerbations treated with antibiotics and/or corticosteroids) and ≥1 hospital admission in the last year were included. Patients were given instructions on the usage of HFNC by a ventilation practitioner during a group session. The flow rate was 25–30 L/min and FiO2 was 21–35%. Outcome measures included the COPD exacerbations rate, hospital admissions, in-hospital days, Medical Research Council dyspnea (MRC) score, Clinical COPD Questionnaire (CCQ) score, Hospital Anxiety Depression Scale (HADS) scores and capillary pCO2. Repeated analysis of variance (ANOVA) was used to analyze the data. Significant effects identified in the ANOVA were further examined using Student's t-tests. Results: After 1 year, 27 patients could be evaluated. The COPD exacerbations rate decreased by 1.40 (mean difference ± SD: 1.40 ± 2.09; p = 0.002), hospital admissions decreased by 0.96 admissions per year (0.96 ± 1.37; p = 0.001), and in-hospital days decreased by 7.22 days (7.22 ± 9.26; p = 0.001). Capillary pCO2 decreased by 0.02 kPa (0.02 ± 0.52; p = 0.85). The CCQ score decreased by 0.06 (0.06 ± 0.96; p = 0.76). The MRC dyspnea score decreased by 0.04 (0.04 ± 0.80; p = 0.81). The HADS anxiety score decreased by 0.63 (0.63 ± 3.12; p = 0.31). And finally, the HADS depression score decreased by 0.32 (0.32 ± 3.48; p = 0.64). There was a significant difference between the normocapnic (capillary pCO2 < 6.0 kPa) group and the hypercapnic group in terms of change in the CCQ score (−0.24 ± 0.55 and 0.49 ± 1.32 decrease, respectively, p = 0.05) and the HADS depression score (−0.76 ± 1.86 and 2.20 ± 4.75 decrease, respectively, p = 0.03) after 1 year of HFNC treatment. Conclusions: One-year-long HFNC therapy significantly decreased the COPD exacerbations rate, hospital admissions, and in-hospital days in severe COPD patients with a high disease burden and frequent COPD exacerbations irrespective of them having hypercapnia and with the HRQoL measures only improving in the hypercapnic group. This may imply that severe COPD patients with a high disease burden and frequent COPD exacerbations, irrespective being hypercapnic, are candidates for treatment with home HFNC oxygen therapy. [ABSTRACT FROM AUTHOR]

We investigated the efficacy and safety of a high-flow nasal cannula (HFNC) at different flow rates compared to noninvasive ventilation (NIV) in patients with acute chronic obstructive pulmonary disease (COPD) exacerbations. This prospective, randomized, single-blind study assigned patients to one of three study groups. The NIV group (n = 47) received bilevel positive airway pressure. The HFNC-30 (n = 44) and HFNC-50 (n = 46) groups received HFNC therapy at flow rates of 30 and 50 L/min, respectively. Demographic and clinical characteristics and arterial blood gas parameters before and 30, 60, and 120 min after treatment were compared among the treatment groups. This study included 137 consecutive patients with acute exacerbations of COPD, comprising 90 males and 47 females, with a mean age of 68.1 ± 10.5 years. A total of 21 patients (15.33 %) were intubated, and the overall mortality rate was 10.2 %. The mean PaCO 2 levels on admission were 64.69 ± 10.81, 61.51 ± 9.03, and 62.29 ± 9.87 in the NIV, HFNC-30, and HFNC-50 groups, respectively, with no significant differences observed (p = 0.372). A significant reduction in mean PaCO 2 was observed in all treatment groups at 30, 60, and 120 min (p < 0.05 for all). However, the ΔPaCO 2 at 60 min was significantly higher in the HFNC-30 group compared to the NIV group (p = 0.042). Additionally, neither intubation rates nor 28-day mortality differed among the treatment groups (p = 0.368 and p = 0.775, respectively). HFNC was not inferior to NIV in improving arterial blood gas parameters, particularly PaCO 2 in patients with COPD exacerbations, especially those with hypercarbia. Moreover, HFNC at a flow rate of 30 L/min was superior to NIV for reducing PaCO 2 levels at 60 min. National Library of Medicine Clinical Trial Registry; No.: NCT06495086 ; URL: https://clinicaltrials.gov/study/NCT06495086 [ABSTRACT FROM AUTHOR]

Astrid Berena Herrera Lopez,1 Carlos A Torres-Duque,2 Alejandro Casas Herrera,3 María Patricia Arbeláez,4 Horacio Riojas-Rodríguez,5 José Luis Texcalac-Sangrador,6 Néstor Y Rojas,7 Laura Andrea Rodriguez-Villamizar8 1Facultad de Medicina, Universidad de los Andes, Bogotá D.C, Colombia, Universidad de Antioquia, Medellín, Antioquia, Colombia; 2CINEUMO, Fundación Neumológica Colombiana, Bogotá, Colombia; 3AIREPOC Programa, Fundación Neumológica Colombiana, Bogotá, Colombia; 4Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, Antioquia, Colombia; 5Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México; 6Centro de Investigación en Salud Poblacional. Instituto Nacional de Salud Pública, Ciudad de México, México; 7Departamento de Ingeniería Química y Ambiental, Universidad Nacional de Colombia, Bogotá, Colombia; 8Departamento de Salud Pública, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga, ColombiaCorrespondence: Astrid Berena Herrera Lopez, Email ab.herrera@uniandes.edu.co; astrid.herreral@udea.edu.coBackground: Exacerbations of chronic obstructive pulmonary disease (COPD-E) have been associated with levels of air pollution. The occurrence of COPD-E is associated with increased mortality in this population.Purpose: To determine the association between long-term exposure to PM2.5 and NO2, and the frequency of COPD-E in patients belonging to AIREPOC, an institutional integrated care program for COPD in Bogota, Colombia.Patients and Methods: Retrospective cohort study included patients with COPD living in Bogotá, between 2018 and 2021, who received health care in the AIREPOC program. Each patient´s home address was geolocated. Information from local air quality network stations was used to estimate daily and annual mean PM2.5 and NO2 exposure level for each patient using the inverse distance squared weighted regression (IDWR) method. The effect of PM2.5 and NO2 concentrations categorized at 15 μg/m3 and 25 μg/m3 respectively on the frequency of COPD-E was estimated using a zero-truncated negative binomial model adjusted for potential confounders. Goodness-of-fit was assessed by residuals.Results: During the observation period, 580 COPD-E occurred in 722 patients. Significant associations were found between COPD-E and NO2 concentrations ≥ 25 μg/m3 (incidence density ratio, RDI: 1.29, 95% CI: 1.02– 1.67) after adjustment for sun exposure, COPD severity, depression, and ambient humidity. No association was found between the frequency of COPD-E and PM2.5 concentrations ≥ 15μg/m3.Conclusion: Prolonged exposure to high levels of NO2 increases the frequency of COPD exacerbations in patients residing in Bogotá. These results highlight the importance of strengthening air quality control measures and educating people with COPD to know and interpret the local air quality indices and to follow the recommendations derived from its alterations. Keywords: air pollution, long-term effect, chronic obstructive pulmonary disease, COPD exacerbations, negative binomial regression truncated at zero

Alexander Evans,1 Yasir Tarabichi,2 Wilson D Pace,3,4 Barry Make,5 Nicholas Bushell,6 Victoria Carter,7 Ku-Lang Chang,8 Chester Fox,9 MeiLan K Han,10 Alan Kaplan,11,12 Janwillem WH Kocks,13– 15 Chantal Le Lievre,6 Alexander Roussos,6 Neil Skolnik,10,16 Joan B Soriano,17 Barbara P Yawn,10 David Price1,6,7,18 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Center for Clinical Informatics Research and Education, MetroHealth, Cleveland, OH, USA; 3DARTNet Institute, Aurora, CO, USA; 4Department of Family Medicine, Anschutz Medical Campus University of Colorado, Aurora, CO, USA; 5Department of Medicine, National Jewish Hospital, Denver, CO, USA; 6Optimum Patient Care, Brisbane, Queensland, Australia; 7Optimum Patient Care, Oakington, Cambridge, UK; 8Lucas Research, a Centricity Research Company, Morehead City, NC, USA; 9University at Buffalo, Buffalo, NY, USA; 10University of Minnesota, Minneapolis, MN, USA; 11Family Physician Airways Group of Canada, Stouffville, Ontario, Canada; 12University of Toronto, Toronto, Canada; 13General Practitioners Research Institute, Groningen, the Netherlands; 14Groningen Research Institute Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 15Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 16Abington Jefferson Health, Jenkintown, PA, USA; 17School of Medicine, Universitat de les Illes Balears, Palma, Spain; 18Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, Singapore, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Preserved ratio impaired spirometry (PRISm) represents a population with spirometry results that do not meet standardized COPD obstruction criteria, yet present with high respiratory symptom burden and might benefit from respiratory management and treatment. We aimed to determine prevalence of PRISm in US primary care patients diagnosed with COPD, describe their demographic, clinical, and CT scan characteristics.Methods: An observational registry study utilizing the US APEX COPD registry, composed of patients diagnosed with COPD aged 35+ years. Demographic and clinical data were collected from EHRs and complemented by questionnaires. Multivariable logistic regression was performed to assess whether PRISm predicts lung function decline.Results: Prevalence of PRISm within a primary care population clinically diagnosed with COPD was 23.6% (678/2866, 95% CI 22.0– 25.1). Those with PRISm were more likely female (55.9% vs 46.9%), younger (66.3± 11.1 vs 69.2± 10.3 years), with a greater mean BMI (33.5± 9.2 vs 27.8± 7.2 kg/m2), more often African American or Hispanic (37.2% vs 26.3%), and with fewer current smokers (33.1% vs 36.8%) when compared to those meeting COPD spirometry criteria (all p< 0.05). Compared to COPD GOLD 0 patients, individuals with PRISm had greater BMI (33.5± 9.2 vs 30.6± 7.8), and were more likely current smokers (33.1% vs 23.4%), both p< 0.05. Patients with PRISm had similar respiratory symptoms (chronic bronchitis, CAT, and mMRC) to overall COPD patients, but more frequently than GOLD 0 COPD patients (p< 0.01). Emphysema was more commonly reported in CT scans from patients with PRISm 70.3% (260/369, 95% CI 65.8– 75.3) than those with GOLD 0 COPD 64.1% (218/340, 95% CI 58.8– 69.2) (p< 0.05). PRISm status was not predictive of lung function decline.Interpretation: One in four primary care patients with clinically diagnosed COPD in a large US registry fulfil the spirometric definition of PRISm rather than COPD, but suffers from emphysema in CT and significant respiratory symptoms.Keywords: APEX, COPD, PRISm, US primary care, COPD exacerbations, electronic health records, patient reported outcomes

The coronary artery calcium score (CACS) and ratio of the pulmonary artery to aorta diameters (PA:A ratio) measured from chest CT scans have been established as predictors of cardiovascular events and COPD exacerbations, respectively. However, little is known about the reciprocal relationship between these predictors and outcomes. Furthermore, the prognostic implications of COPD subtypes on clinical outcomes remain insufficiently characterized. How can these two chest CT scan-derived parameters predict subsequent cardiovascular events and COPD exacerbations in different COPD subtypes? Using COPDGene study data, we assessed prospective cardiovascular disease (CVD) and COPD exacerbation risk in participants with COPD (Global Initiative for Chronic Obstructive Lung Disease spirometric grades 2-4), focusing on CACS and PA:A ratio at study enrollment, with logistic regression models. These outcomes were analyzed in three COPD subtypes: 1,042 participants with non-emphysema-predominant COPD (NEPD; low attenuation area at −950 Hounsfield units [LAA-950] < 5%), 1,324 participants with emphysema-predominant COPD (EPD; LAA-950 ≥ 10%), and 465 participants with intermediate emphysema COPD (IE; 5% ≤ LAA-950 < 10%). Our study indicated significantly higher overall risk for cardiovascular events in participants with higher CACS (≥ median; OR, 1.61; 95% CI, 1.30-2.00) and increased COPD exacerbations in those with higher PA:A ratios (≥ 1; OR, 1.80; 95% CI, 1.46-2.23). Notably, participants with NEPD showed a stronger association between these indicators and clinical events compared to EPD (with CACS/CVD, NEPD vs EPD: OR, 2.02 vs 1.41; with PA:A ratio/COPD exacerbation, NEPD vs EPD: OR, 2.50 vs 1.65); the difference in ORs between COPD subtypes was statistically significant for CACS/CVD. Two chest CT scan parameters, CACS and PA:A ratio, hold distinct predictive values for cardiovascular events and COPD exacerbations that are influenced by specific COPD subtypes. ClinicalTrials.gov; No.: NCT00608764 ; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Introduction: Air pollution poses a risk for people with Chronic Obstructive Pulmonary Disease (COPD). This study estimated the short-term effect of variations in air pollutant concentrations on exacerbations of COPD (COPD-E) in Bogotá, Colombia. Methods: We performed an ecological time series study from 2014 to 2021 to evaluate the short-term effect of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) levels on COPD-E treated in the emergency and hospitalization services. Daily counts of patients with COPD-E discharge diagnoses were obtained from the National Health Information System, and daily measurements of PM2.5, NO2, and O3 concentrations and meteorological data were obtained from air monitoring stations. A Generalized Additive Model was used with Distributed Lag Non-Linear Models to control for confounders. Results: An increase of 10 μg/m3 in PM2.5 and O3 was associated with increased COPD-E admissions (lagged 0-3 days) with Relative Risk (RR) of 1.04 (95%CI: 1.02 -1.07) and RR:1.03 (95%CI:1.01 – 1.04), respectively. During the rainy season and minimum temperature of the series, for every 10 μg/m3 increase in PM2.5 concentration, COPD-E admissions (lagged 0-3 days) increased with RR 1.03 (95%CI: 1.01-1.06). A higher magnitude of association was observed in men (PM2.5, 1.04 95%CI:1.01 – 1.06 and O3, 1.04 95%CI:1.02 – 1.05, lag 0-7 days) than in women. Conclusions: A higher air pollution was associated with more COPD-E. These results highlight the importance of actions aimed at improving air quality. [ABSTRACT FROM AUTHOR]

Abstract Background Little 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. Methods We 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. Results There 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). Conclusions The 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.

Christian Kjer Heerfordt,1 Christian Rønn,1 Josefin Eklöf,1 Pradeesh Sivapalan,1 Zitta Barrella Harboe,2,3 Charlotte Hyldgaard,4 Andreas Fløe,5 Alexander G Mathioudakis,6,7 Mats Christian Højbjerg Lassen,8 Tor Biering-Sørensen,8,9 Jens-Ulrik Stæhr Jensen1,3,10 1Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark; 2 Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital, North Zealand, Hillerød, Denmark; 3Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark; 5Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 6Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK; 7North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; 9Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark; 10PERSIMUNE & CHIP: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Jens-Ulrik Stæhr Jensen, Email jens.ulrik.jensen@regionh.dkBackground: Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear.Methods: This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis.Results: Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82– 1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85– 1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63– 0.82, p< 0.001) and all-cause mortality (HR 0.72, 95% CI 0.61– 0.86, p< 0.001).Conclusion: The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.Keywords: COPD, Inhaled Corticosteroids, Particle size, COPD exacerbations

Richard Hubbard, Victoria Carter, William Henley, David Price Observational and Pragmatic Research Institute, Cambridge, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 5 Coles Lane, Cambridge, CB24 3BA, UK, Email dprice@opri.sg

UNLABELLED: The relationship of circulating testosterone levels with health outcomes in people with chronic obstructive pulmonary disease (COPD) is unknown. AIM: To determine whether serum testosterone levels predict hospitalised acute exacerbations of COPD (H-AECOPD), cardiovascular disease outcome, and mortality in people with COPD. METHODS: Separate analyses were carried out on two observational, multicentre COPD cohorts, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) and Evaluation of the Role of Inflammation in Chronic Airways Disease (ERICA), both of which had serum testosterone measured using a validated liquid chromatography assay at the same laboratory. Data from 1296 male participants in ECLIPSE and 386 male, 239 female participants in ERICA were analysed. All analyses were sex-specific. Multivariate logistic regression was used to determine associations with H-AECOPD during follow-up (3 years ECLIPSE, 4.5 years ERICA), a composite endpoint of cardiovascular hospitalisation and cardiovascular death, and all-cause mortality. RESULTS: Mean (SD) testosterone levels were consistent across cohorts; 459 (197) and 455 (200) ng/dL for males in ECLIPSE and ERICA, respectively, and in ERICA females: 28 (56) ng/dL. Testosterone was not associated with H-AECOPD (ECLIPSE: OR: 0.76, p=0.329, ERICA males: OR (95% CI): 1.06 (0.73 to 1.56), p=0.779, ERICA females: OR: 0.77 (0.52 to 1.12), p=0.178) or cardiovascular hospitalisation and death. Testosterone was associated with all-cause mortality in Global Initiative for Obstructive Lung Disease (GOLD) stage 2 male patients only, in ECLIPSE (OR: 0.25, p=0.007) and ERICA (OR: (95% CI): 0.56 (0.32 to 0.95), p=0.030). CONCLUSIONS: Testosterone levels do not relate to H-AECOPD or cardiovascular outcome in COPD, but are associated with all-cause mortality in GOLD stage 2 COPD male patients, although the clinical significance of this finding is uncertain.

Background: Little 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. Methods: We 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. Results: There 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). Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Background: COPD patients show higher mortality and worse prognosis in the acute phase of COVID-19, and survivors may suffer persistent symptoms that could make them more vulnerable to exacerbations. Objectives: We aimed to evaluate the impact of COVID-19 on the exacerbations, symptoms, quality of life, and mental health of a cohort of COPD patients. Methods: Retrospective case-control single-centre study including all COPD patients from the pulmonary consultation of University Hospital Santa Maria (Lleida, Spain) surviving COVID-19 between March 2020 and September 2021, and similar propensity-score-matched (1:2) COPD patients. Differences in COPD exacerbations, COPD clinical evolution (lung function, dyspnoea, CAT and symptoms), long COVID-19 symptoms, quality of life, and mental health, were assessed at the end of 2021. Results: We included 39 COVID-19 COPD patients and 78 similar non-COVID-19. No differences were found on exacerbations (46(59%) vs. 27(69.2%), p = 0.380), dyspnoea (2 [1; 3] vs. 2 [1; 3], p = 0.921) CAT (14.5 [10.0; 18.8] vs. 13.0 [10.0; 16.0], p = 0.432). Only the prevalence of smell or taste disorders, hair loss and tingling was higher in COVID-19 patients. No differences were found in quality of life or mental health. Conclusions: COPD patients surviving COVID-19 were not at a higher risk of COPD exacerbations nor showed significant changes in COPD clinical evolution, and only showed differences in a few very specific COVID-19 symptoms. These unexpected results suggest that the conditions triggered by the pandemic and its management could have affected COPD patients as much as actually having had COVID-19. [ABSTRACT FROM AUTHOR]

ABSTRACTChronic obstructive pulmonary disease (COPD) is a common chronic respiratory illness in older adults. A major cause of COPD-related morbidity and mortality is acute exacerbation of COPD (AECOPD). Bacteria in the lungs play a role in exacerbation development, and the most common pathogen is non-typeable Haemophilus influenzae (NTHi). A vaccine to prevent AECOPD containing NTHi surface antigens was tested in a clinical trial. This study measured IgG and IgA against NTHi vaccine antigens in sputum. Sputum samples from 40 COPD patients vaccinated with the NTHi vaccine were collected at baseline and 30 days after the second dose. IgG and IgA antibodies against the target antigens and albumin were analyzed in the sputum. We compared antibody signals before and after vaccination, analyzed correlation with disease severity and between sputum and serum samples, and assessed transudation. Antigen-specific IgG were absent before vaccination and present with high titers after vaccination. Antigen-specific IgA before and after vaccination were low but significantly different for two antigens. IgG correlated between sputum and serum, and between sputum and disease severity. Sputum albumin was higher in patients with severe COPD than in those with moderate COPD, suggesting changes in transudation played a role. We demonstrated that immunization with the NTHi vaccine induces antigen-specific antibodies in sputum. The correlation between IgG from sputum and serum and the presence of albumin in the sputum of severe COPD patients suggested transudation of antibodies from the serum to the lungs, although local IgG production could not be excluded.Clinical Trial Registration: NCT02075541

Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death throughout the world. Because of the preventable and treatable nature of the disease along with its prevalence, COPD represents a major public health challenge. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report provides a review of the most current evidence for prevention of COPD as well as the assessment, diagnosis, and treatment of people with the disease. The purpose of this article is to provide a summary of the 2024 revised GOLD Report and current best practices in accordance with the evidence. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI’s), an increase in community treated exacerbations, or healthcare avoidance by patients, are potential reasons. For the current study, the impact of Dutch governmental NPI’s on the COPD exacerbations and respiratory infections rate in patients with severe alpha-1 antitrypsin deficiency (AATD) was analyzed. The patients participated in the NCT04204252 study, a randomized controlled trial evaluating the efficacy and safety of inhaled alpha-1 antitrypsin. Data collected in the time-period from March 2020 until February 2022 was analyzed. In this period the Dutch government imposed variable NPI’s to contain the spread of SARS-CoV-2. Patients were required to document their daily symptoms in an electronic diary. The strictness of the governmental NPI’s was measured by the COVID-19 Stringency Index. 19 patients participated in this study during the analysis period. A total of 40 respiratory infections and COPD exacerbations occurred. The Spearman’s correlation coefficient of the monthly average COVID-19 Stringency Index and respiratory infections and COPD exacerbations rate was −0.316 (p = 0.132). When months known for a low respiratory infection rate were excluded, the correlation coefficient was −0.625 (p = 0.010). This study showed a significant negative correlation between the COPD exacerbations and respiratory infection rate and the COVID-19 Stringency Index in patients with AATD related COPD in the autumn-winter months.

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are detrimental events in the natural history of COPD, but the risk factors associated with future exacerbations in the absence of a history of recent exacerbations are not fully understood. Objectives: To identify risk factors for COPD exacerbations among participants in the Genetic Epidemiology of COPD Study (COPDGene) without a history of exacerbation in the previous year. Methods: We identified participants with a smoking history enrolled in COPDGene who had COPD (defined as forced expiratory volume in 1 second [FEV1]/forced vital capacity < 0.70), no exacerbation in the year before their second study site visit, and who completed at least one longitudinal follow-up questionnaire in the following 36 months. We used univariable and multivariable zero-inflated negative binomial regression models to identify risk factors associated with increased rates of exacerbation. Each risk factor's regression coefficient (β) was rounded to the nearest 0.25 and incorporated into a graduated risk score. Results: Among the 1,528 participants with a smoking history and COPD enrolled in COPDGene without exacerbation in the year before their second study site visit, 508 participants (33.2%) had at least one moderate or severe exacerbation in the 36 months studied. Gastroesophageal reflux disease, chronic bronchitis, high symptom burden (as measured by Modified Medical Research Council Dyspnea Scale and COPD Assessment Test), and lower FEV1% predicted were associated with an increased risk of exacerbation. Each 1-point increase in our graduated risk score was associated with a 25–30% increase in exacerbation rate in the 36 months studied. Conclusions: In patients with COPD without a recent history of exacerbations, gastroesophageal reflux disease, chronic bronchitis, high symptom burden, and lower lung function are associated with increased risk of future exacerbation using a simple risk score that can be used in clinical practice. [ABSTRACT FROM AUTHOR]

An integrated disease management program otherwise called a clinical pathway was recently implemented in Saskatchewan, Canada for patients living with chronic obstructive pulmonary disease (COPD). This study compared the real-world costs and consequences of the COPD clinical pathway program with 2 control treatment programs. The study comprised adult COPD patients in Regina (clinical pathway group, N = 759) matched on propensity scores to 2 independent control groups of similar adults in (1) Regina (historical controls, N = 759) and (2) Saskatoon (contemporaneous controls, N = 759). The study measures included patient-level healthcare costs and acute COPD exacerbation outcomes, both tracked in population-based administrative health data over a one-year follow-up period. Analyses included Cox proportional hazards models and differences in means between groups. The bias-corrected and accelerated bootstrap method was used to calculate 95% confidence intervals (CI). The COPD pathway patients had lower risks of moderate (hazard ratio [HR] =0.57, 95% CI [0.40-0.83]) and severe (HR = 0.43, 95% CI [0.28-0.66]) exacerbations compared to the historical control group, but similar risks compared with the contemporaneous control group. The COPD pathway patients experienced fewer episodes of exacerbations compared with the historical control group (mean difference = −0.30, 95% CI [−0.40, −0.20]) and the contemporaneous control group (mean difference = −0.12, 95% CI [−0.20, −0.03]). Average annual healthcare costs in Canadian dollars were marginally higher among patients in the COPD clinical pathway (mean = $10 549, standard deviation [SD] =$18 149) than those in the contemporaneous control group ($8841, SD = $17 120), but comparable to the historical control group ($10 677, SD = $21 201). The COPD pathway provides better outcomes at about the same costs when compared to the historical controls, but only slightly better outcomes and at a marginally higher cost when compared to the contemporaneous controls. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) is a global health challenge with significant morbidity and mortality. Iron deficiency, including non-anaemic iron deficiency (NAID), has been identified as a potential comorbid in COPD, affecting patient outcomes and disease severity. This study aimed to investigate the prevalence and impact of iron deficiency on the severity and clinical outcomes in COPD patients. Methods: In this descriptive cross-sectional study, 289 individuals diagnosed with COPD were enrolled and underwent comprehensive medical assessments, including haematological tests and spirometry from December 2019 to December 2023. The study focused on measuring iron levels, exercise capacity, and exacerbation frequency, comparing iron-deficient and non-iron-deficient groups. Results: The study found that 46.7% of participants had iron deficiency. Those with iron deficiency showed significantly lower exercise capacity as measured by the six-minute walk distance and experienced a higher frequency of yearly COPD exacerbations. However, no significant differences were observed in airflow limitation and the overall quality of life between the iron-deficient and non-iron-deficient groups. Conclusion: The findings suggest that iron deficiency, particularly NAID, is associated with a more severe progression of COPD, characterized by reduced exercise capacity and increased exacerbation frequency. These results highlight the importance of considering iron deficiency in the management of COPD to potentially improve patient outcomes. [ABSTRACT FROM AUTHOR]

We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-β1 (TGFβ1) receptor kinase that when given orally to patients with idiopathic pulmonary fibrosis (IPF) reversed profibrotic biomarkers in their diagnostic biopsies. Here, we extend these findings to advanced pulmonary fibrosis using cultured precision-cut lung slices from explants of patients with IPF undergoing transplantation. During these experiments, we were surprised to discover that not only did EGCG attenuate TGFβ1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.

Marc Miravitlles,1 Sudeep Acharya,2 Bhumika Aggarwal,2 Frederico LA Fernandes,3 Jorge Dreyse,4 José R Jardim,5 Siwasak Juthong,6 Gur Levy,7 Martin Sivori8 1Pneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus; CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 2Emerging Markets, GlaxoSmithKline, Singapore; 3Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil; 4Internal Medicine and Critical Care Center Departments, Clínica Las Condes and School of Medicine, Universidad Finis Terrae, Santiago, Chile; 5Respiratory Division, Escola Paulista de Medicina, Federal University of São Paulo, Sao Paulo, Brazil; 6Division of Respiratory and Respiratory Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand; 7Emerging Markets, GlaxoSmithKline, Panama City, Panama; 8Pneumonology University Center, School of Medicine, University of Buenos Aires, Argentina, Unit of Pneumonology Hospital “Dr.J.M. Ramos Mejia”, Buenos Aires, ArgentinaCorrespondence: Marc Miravitlles, Pneumology Department, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, Barcelona, 08035, Spain, Tel/Fax +34 932746083, Email marcm@separ.esPurpose: Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management.Methods: The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%.Results: All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (< 30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%).Conclusion: This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.Keywords: SITT, MITT, triple inhaled therapy, Delphi procedure, COPD exacerbations, COPD mortality

Malik A Althobiani,1,2 Bilal Khan,1 Amar J Shah,1,3 Yatharth Ranjan,4 Renata G Mendes,1,5 Amos Folarin,4 Swapna Mandal,1,3 Joanna C Porter,1,6 John R Hurst1,3 1UCL Respiratory, University College London, London, UK; 2Department of Respiratory Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Respiratory Medicine, Royal Free London NHS Foundation Trust, London, UK; 4Department of Health Informatics and Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK; 5Department of Physical Therapy, Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Paulo, Brazil; 6Department of Respiratory Medicine, University College London Hospital (UCLH), London, UKCorrespondence: Malik A Althobiani, UCL Respiratory, University College London, London, UK, Email malik.althobiani.20@ucl.ac.ukObjective: To investigate clinicians’ perspectives on the current use of wearable technology for detecting COPD exacerbations, and to identify potential facilitators and barriers to its adoption in clinical settings.Methods: A mixed-method survey was conducted through an online survey platform involving clinicians working with COPD patients. The questionnaires were developed by an expert panel specialising in respiratory medicine at UCL. The questionnaire evaluated clinicians’ perspectives on several aspects: the current extent of wearable technology utilisation, the perceived feasibility, and utility of these devices, as well as the potential facilitators and barriers that hinder its wider implementation.Results: Data from 118 clinicians were included in the analysis. Approximately 80% of clinicians did not currently use information from wearable devices in routine clinical care. A majority of clinicians did not have confidence in the effectiveness of wearables and their consequent impact on health outcomes. However, clinicians highlighted the potential value of wearables in helping deliver personalised care and more rapid assistance. Ease of use, technical support and accessibility of data were considered facilitating factors for wearable utilisation. Costs and lack of technical knowledge were the most frequently reported barriers to wearable utilisation.Conclusion: Clinicians’ perspectives of the use of wearable technology to detect and monitor COPD exacerbations are variable. While accessibility and technical support facilitate wearable implementation, cost, technical issues, and knowledge act as barriers. Our findings highlight the facilitators and barriers to using wearables in patients with COPD and emphasise the need to assess patients’ perspectives on wearable acceptability.Keywords: wearable technology, COPD exacerbations, clinicians’ perspectives

ObjectivesMuscle wasting is a recognised extra-pulmonary complication in chronic obstructive pulmonary disease and has been associated with increased risk of death. Acute respiratory exacerbations are associated with reduction of muscle function, but there is a paucity of data on their long-term effect. This study explores the relationship between acute respiratory exacerbations and long-term muscle loss using serial measurements of CT derived pectoralis muscle area (PMA).Design and settingParticipants were included from two prospective, longitudinal, observational, multicentre cohorts of ever-smokers with at least 10 pack-year history.ParticipantsThe primary analysis included 1332 (of 2501) participants from Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and 4384 (of 10 198) participants from Genetic Epidemiology of COPD (COPDGene) who had complete data from their baseline and follow-up visits.InterventionsPMA was measured on chest CT scans at two timepoints. Self-reported exacerbation data were collected from participants in both studies through the use of periodic longitudinal surveys.Main outcome measuresAge-related and excess muscle loss over time.ResultsAge, sex, race and body mass index were associated with baseline PMA. Participants experienced age-related decline at the upper end of reported normal ranges. In ECLIPSE, the exacerbation rate over time was associated with an excess muscle area loss of 1.3% (95% CI 0.6 to 1.9, p

The RETRIEVE real-world study examined the effectiveness of triple therapy compared to dual therapy in patients with chronic obstructive pulmonary disease (COPD). The study found that patients who escalated to triple therapy experienced improved lung function and a reduction in exacerbations and hospitalizations compared to those who continued with dual therapy. These findings align with previous randomized controlled trials and highlight the importance of personalized management for high-risk COPD patients. The study was conducted in Greece and was supported by ELPEN Pharmaceutical Co. Inc. [Extracted from the article]

Objectives: This study aimed to quantitatively compare the efficacy and safety of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) and LABA/inhaled corticosteroid (ICS) fixed-dose combinations (FDCs) in preventing moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations. Methods: A literature search was performed using public databases. The time course characteristics of the probability of a moderate or severe exacerbation in stable COPD patients treated with LABA/LAMA and LABA/ICS FDCs were described by the parametric survival function. A random-effects model in a single-arm meta-analysis was used to analyze the incidence of serious adverse events (SAEs) and pneumonia. Results: Twenty studies including 23,955 participants were included. The proportion of participants with a history of COPD exacerbation (%) in the previous year and the postbronchodilator forced expiratory volume in the first second (FEV1) (%predicted) were important factors affecting drug efficacy. After adjusting the above factors to median levels of 100% and 45.5%, respectively, the moderate or severe exacerbation rates at 52 weeks for olodaterol/tiotropium, formoterol/budesonide, indacaterol/glycopyrronium, formoterol/glycopyrronium, vilanterol/fluticasone, salmeterol/fluticasone, and vilanterol/umeclidinium were 38.3%, 41.0%, 42.6%, 47.0%, 47.5%, 47.9%, and 53.0%, respectively. In terms of safety, significant differences were observed among drugs containing different LABA/LAMA FDCs. Conclusions: This study showed that not all LABA/LAMA FDCs were superior to LABA/ICS FDCs in safety and in preventing moderate or severe exacerbations in patients with stable COPD, providing important quantitative information for COPD-related guidelines. [ABSTRACT FROM AUTHOR]

Lung myeloid cells are important in pulmonary immune homeostasis and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Multiparameter immunophenotypic characterization of these cells is challenging because of their autofluorescence and diversity. We evaluated the immunophenotypic landscape of airway myeloid cells in COPD using time of flight mass cytometry. Cells from BAL, which were obtained from never-smokers (n = 8) and smokers with (n = 20) and without (n = 4) spirometric COPD, were examined using a 44-parameter time of flight mass cytometry panel. Unsupervised cluster analysis was used to identify cellular subtypes that were confirmed by manual gating. We identified major populations of CD68+ and CD68- cells with 22 distinct phenotypic clusters, of which 18 were myeloid cells. We found a higher abundance of putative recruited myeloid cells (CD68+ classical monocytes) in BAL from patients with COPD. CD68+ classical monocyte population had distinct responses to smoking and COPD that were potentially related to their recruitment from the interstitium and vasculature. We demonstrate that BAL cells from smokers and subjects with COPD have lower AXL expression. Also, among subjects with COPD, we report significant differences in the abundance of PDL1high and PDL2high clusters and in the expression of PDL1 and PDL2 across several macrophage subtypes suggesting modulation of inflammatory responses. In addition, several phenotypic differences in BAL cells from subjects with history of COPD exacerbation were identified that could inform potential disease mechanisms. Overall, we report several changes to the immunophenotypic landscape that occur with smoking, COPD, and past exacerbations that are consistent with decreased regulation and increased activation of inflammatory pathways.

BackgroundThe relationship between 25-hydroxyvitamin D (25-OH-vitamin D) and COPD outcomes remains unclear. Using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), we determined associations among baseline 25-OH-vitamin D and cross-sectional and longitudinal lung function and COPD exacerbations.MethodsSerum 25-OH-vitamin D level was measured in stored samples from 1,609 SPIROMICS participants with COPD. 25-OH-vitamin D levels were modeled continuously and dichotomized as deficient (< 20 ng/mL) vs not deficient (≥ 20 ng/mL). Outcomes of interest included % predicted FEV1 (current and 1-year longitudinal decline) and COPD exacerbations (separately any and severe, occurring in prior year and first year of follow-up).ResultsVitamin D deficiency was present in 21% of the cohort and was more prevalent in the younger, active smokers, and blacks. Vitamin D deficiency was independently associated with lower % predicted FEV1 (by 4.11%) at enrollment (95% CI, -6.90% to -1.34% predicted FEV1; P = .004), 1.27% predicted greater rate of FEV1 decline after 1 year (95% CI, -2.32% to -0.22% predicted/y; P = .02), and higher odds of any COPD exacerbation in the prior year (OR, 1.32; 95% CI, 1.00-1.74; P = .049). Each 10-ng/mL decrease in 25-OH-vitamin D was associated with lower baseline lung function (-1.04% predicted; 95% CI, -1.96% to -0.12% predicted; P = .03) and increased odds of any exacerbation in the year before enrollment (OR, 1.11; 95% CI, 1.01-1.22; P = .04).ConclusionsVitamin D deficiency is associated with worse cross-sectional and longitudinal lung function and increased odds of prior COPD exacerbations. These findings identify 25-OH-vitamin D levels as a potentially useful marker of adverse COPD-related outcomes.

Introduction: Non-exacerbating patients with chronic obstructive pulmonary disease (COPD) are a less studied phenotype. We investigated clinical characteristics, mortality rates and causes of death among non-exacerbating compared with exacerbating patients with COPD.Methods: We used data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics between 1 January 2004 and 31 December 2018. Ever smokers with a COPD diagnosis with minimum 3 years of baseline information were included. We compared overall using Cox regression and cause-specific mortality rates using competing risk analysis, adjusted for age, sex, deprivation, smoking status, body mass index, GOLD stage and comorbidities. Causes of death were identified using International Classification of Diseases-10 codes.Results: Among 67 516 patients, 17.3% did not exacerbate during the 3-year baseline period. Mean follow-up was 4 years. Non-exacerbators were more likely to be male (63.3% vs 52.4%, p<0.001) and less often had a history of asthma (33.9% vs 43.6%, p<0.001) or FEV1<50% predicted (23.7 vs 31.8%) compared with exacerbators. Adjusted HR for overall mortality in non-exacerbators compared with exacerbators was 0.62 (95% CI 0.56 to 0.70) in the first year of follow-up and 0.87 (95% CI 0.83 to 0.91) thereafter. Non-exacerbating patients with COPD died less of respiratory causes than exacerbators (29.2% vs 40.3%) and more of malignancies (29.4% vs 23.4%) and cardiovascular diseases (26.2% vs 22.9%). HRs for malignant and circulatory causes of death were increased after the first year of follow-up.Discussion: In this primary care cohort, non-exacerbators showed distinct clinical characteristics and lower mortality rates. Non-exacerbators were equally likely to die of respiratory, malignant or cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background and Objective: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with worsening health outcomes and effective treatment of each episode is essential. In this study, we aimed to investigate if plasma levels of heparan sulphate (HS) are associated with the aetiology of AECOPD. Methods: COPD patients (N = 1189), GOLD grade II–IV, from a discovery cohort (N = 638) and from a validation cohort (N = 551), were included in the study. HS and heparanase (HSPE‐1) were measured longitudinally in plasma at stable state, at AECOPD and at 4 weeks follow‐up. Results: Plasma HS was higher in patients with COPD as compared with non‐COPD controls and was significantly increased at AECOPD as compared to stable state (p < 0.001) in the discovery and in the validation cohorts. Four distinct exacerbation groups were classified based on aetiology (no‐infection/bacterial‐infection/viral‐infection/bacterial and viral coinfection) in the validation cohort. The fold‐increase of HS from stable state to AECOPD was associated with the aetiology of exacerbation and was higher in cases with bacterial and viral coinfections. HSPE‐1 was also significantly increased at AECOPD, however, there was no association of HSPE‐1 levels with the aetiology of these events. The probability of having an infection at AECOPD was raised as HS levels increased from stable state to AECOPD. This probability was higher for bacterial infections than viral infections. Conclusion: The results of our study indicate that circulating levels of HS are increased at AECOPD and this increase may be associated with the aetiology of these events. [ABSTRACT FROM AUTHOR]

COPD is a progressive inflammatory process affecting both the airways and alveolar structures of the lungs. Exacerbations of COPD are episodes of acute worsening of this inflammatory process, often triggered by infections. The most severe exacerbations are characterized by substantial air trapping and inspiratory muscle overload, which leads to hypercapnic respiratory failure. Pharmacologic therapies focus on intense bronchodilator administration (usually by aerosol), corticosteroids, and antibiotics. Respiratory life support technologies are often needed for severe exacerbations and range from carefully titrated supplemental O2 administration to positive-pressure ventilation (both invasive and noninvasive). Future life support strategies will likely involve extracorporeal life support technologies. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the impact of an intervention on COPD exacerbations in elderly patients in Poland. The intervention involved sending checklists of recommended COPD interventions to GPs in selected clinics. However, the study found no significant association between the intervention and exacerbations or deaths in COPD patients after one year. The results should be interpreted cautiously due to the study coinciding with the COVID-19 pandemic, and further research on interventions for chronic illness care is needed. [Extracted from the article]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundThe Laboratory-based Intermountain Validated Exacerbation (LIVE) Score is associated with mortality and chronic obstructive pulmonary disease (COPD) exacerbation risk across multiple health systems. However, whether the LIVE Score and its associated risk is a stable patient characteristic is unknown.MethodsWe validated the LIVE Score in a fourth health system. Then we determined the LIVE Score stability in a retrospective cohort of 98 766 patients with COPD in four health systems where it was previously validated. We assessed whether LIVE Scores changed or remained the same over time. Stability was defined as a majority of surviving patients having the same LIVE Score 4 years later.ResultsThe LIVE Score separated patients into three LIVE Score risk groups of low, medium, and high mortality and LIVE Score stability. Mortality ranged from 6.2% for low-risk LIVE to 45.8% for high-risk LIVE (p

Recent reports provide evidence-based guidelines for the withdrawal of inhaled corticosteroids (ICS) in COPD, but data on patients treated with ICS-based triple therapy are sparse and contradictory. We assessed the effect of ICS discontinuation on the incidence of severe exacerbation and pneumonia in a real-world population of patients with COPD who initiated triple therapy. We identified a cohort of patients with COPD treated with LAMA-LABA-ICS triple therapy during 2002–2018, age 50 or older, from the UK’s CPRD database. Subjects who discontinued ICS were matched 1:1 on time-conditional propensity scores to those continuing ICS and followed for one year. Hazard ratios (HR) of severe exacerbation and pneumonia were estimated using Cox regression. The cohort included 42,667 patients who discontinued ICS matched to 42,667 who continued ICS treatment. The hazard ratio of a severe exacerbation with ICS discontinuation relative to ICS continuation was 0.86 (95% CI: 0.78–0.95), while for severe pneumonia it was 0.96 (95% CI: 0.88–1.05). The incidence of severe exacerbation after ICS discontinuation was numerically higher than after continuation among patients with two or more exacerbations in the prior year (HR 1.09; 95% CI: 0.94–1.26) and among those with FEV1

Triple therapy for chronic obstructive pulmonary disease (COPD) is recommended for some patients, but the inhaled corticosteroids (ICS) may differ in effectiveness and safety. We compared budesonide-based and fluticasone-based triple therapy given in two inhalers on the incidence of exacerbation, mortality and severe pneumonia, using an observational study approach. We identified a cohort of patients with COPD, new users of triple therapy given in two inhalers during 2002–2018, age 50 or older, from the UK’s CPRD database, and followed for one year. The hazard ratio (HR) of exacerbation, all-cause death and pneumonia was estimated using the Cox regression model, weighted by fine stratification of the propensity score of treatment initiation. The cohort included 29,716 new users of fluticasone-based triple therapy and 9,646 of budesonide-based. The HR of a first moderate or severe exacerbation with budesonide-based triple therapy was 0.98 (95% CI: 0.94–1.03), relative to fluticasone-based, while for a severe exacerbation it was 0.97 (95% CI: 0.87–1.07). The incidence of all-cause death was lower with budesonide-based therapy among patients with no prior exacerbations (HR 0.80; 95% CI: 0.66–0.98). The HR of severe pneumonia with budesonide-based therapy was 0.84 (95% CI: 0.75–0.95). In a real-world clinical setting of COPD treatment, budesonide-based triple therapy given in two inhalers was generally as effective at reducing exacerbations as fluticasone-based triple therapy. However, the budesonide-based triple therapy was associated with a lower incidence of severe pneumonia and possibly also of all-cause death, especially among patients with no prior exacerbations for whom triple therapy is not recommended. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2035705 .

Carol Bazell,1 Michael Pollack,2 Alejandro P Comellas,3 Sanjay Sethi,4 Maggie Alston,1 Bruce Pyenson,1 Dane Hansen,1 Melissa Caplen,1 Anthony Staresinic,2 John Styczynski,2 Norbert Feigler2 1Milliman, New York, NY, USA; 2BioPharmaceuticals, US Medical Affairs, AstraZeneca, Wilmington, DE, USA; 3Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; 4Department of Medicine, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USACorrespondence: Michael Pollack, BioPharmaceuticals, US Medical Affairs, AstraZeneca, 1800 Concord Pike, Wilmington, DE, 19850, USA, Tel +1 302 886 1253, Email michael.pollack1@astrazeneca.comPurpose: We analyzed population-level administrative claims data for Medicare fee-for-service (FFS) beneficiaries to provide insights on systemic oral corticosteroid (OCS) use patterns and associated health conditions and acute events among patients newly diagnosed with chronic obstructive pulmonary disease (COPD).Background: COPD is a progressive inflammatory disease of the lungs, characterized by acute exacerbations that may lead to increased mortality. Short courses of systemic corticosteroids (SCS) are recommended to reduce recovery time from exacerbations, although SCS use has been associated with increased risk of adverse events.Methods: This study used 2013– 2019 Medicare 100% FFS research identifiable files, which contain all Medicare Parts A, B, and D paid claims incurred by 100% of Medicare FFS beneficiaries. Descriptive statistics for patients newly diagnosed with COPD were analyzed, including OCS use, select health conditions and acute events, and COPD exacerbations. Statistical models were used to analyze the relationship between the incidence of select health conditions and events and cumulative OCS dosage.Results: Of Medicare FFS patients newly diagnosed with COPD, 36% received OCS in the 48 months following diagnosis, and 38% of OCS episodes lasted longer than the recommended 5– 7 days. Patients had a variety of health conditions or acute events in the 24-month period prior to new COPD diagnosis, such as hypertension, depression/anxiety, type 2 diabetes, or osteoporosis, that could heighten the risks of OCS use. Patients treated with > 1000 mg of prednisolone equivalent OCS in the 48 months following COPD diagnosis had a higher incidence of new conditions or events, including cardiovascular disease, heart failure, hypertension, obesity, dyspepsia, infections, and depression/anxiety, than patients with no OCS use.Conclusion: These results highlight the potential risks of OCS in COPD treatment, including prolonged use among complex Medicare patients, and reinforce the importance of preventive treatment strategies and therapy optimization early in the disease course.Keywords: chronic obstructive pulmonary disease, systemic corticosteroids, SCS, OCS, COPD exacerbations, claims analysis

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

Background: COPD exacerbations are a major cause of morbidity and mortality. Although inhaled corticosteroids (ICS) have a role as long-term treatment, their efficacy in exacerbations, particularly as an adjunct to systemic steroids, remains unclear. Methods: In this retrospective observational study, we analyzed data from 870 subjects admitted with COPD exacerbations to a tertiary medical center in Israel from January 2018–January 2023. We investigated the impact of adding ICS to standard systemic steroid treatment on hospital length of stay, intubation rates, and 30-d mortality using propensity score matching to account for confounders. Results: The cohort, after matching, included 354 subjects treated with systemic steroids and ICS and 121 treated with systemic steroids alone. All characteristics were similar between the groups. Our analysis showed no differences in 30-d mortality (7.1% vs 5.8%, P =.63) or secondary outcomes (intubation, hospital length of stay, and readmission rates) between the groups. Subgroup analyses based on different eosinophil levels did not alter these findings. In multivariate analysis among the general cohort, eosinophil count <150 cells/μL (adjusted odds ratio 0.45 [95% CI 0.21–0.87], P =.02) and high Charlson score (adjusted odds ratio 1.19 [95% CI 1.02–1.37], P =.02) were independent predictors for 30-d mortality. Conclusions: Despite the known benefits of ICS in managing chronic COPD, we did not find an added value of ICS to systemic steroids in exacerbations. These results underscore the necessity for individualized treatment strategies and further research into the role of ICS in COPD exacerbations. [ABSTRACT FROM AUTHOR]

BackgroundChronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings.Methods/designWe aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George's Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year. The primary endpoint is SGRQ at 12 months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD.DiscussionThis study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings.Trial registrationNCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).

During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI’s), an increase in community treated exacerbations, or healthcare avoidance by patients, are potential reasons. For the current study, the impact of Dutch governmental NPI’s on the COPD exacerbations and respiratory infections rate in patients with severe alpha-1 antitrypsin deficiency (AATD) was analyzed. The patients participated in the NCT04204252 study, a randomized controlled trial evaluating the efficacy and safety of inhaled alpha-1 antitrypsin. Data collected in the time-period from March 2020 until February 2022 was analyzed. In this period the Dutch government imposed variable NPI’s to contain the spread of SARS-CoV-2. Patients were required to document their daily symptoms in an electronic diary. The strictness of the governmental NPI’s was measured by the COVID-19 Stringency Index. 19 patients participated in this study during the analysis period. A total of 40 respiratory infections and COPD exacerbations occurred. The Spearman’s correlation coefficient of the monthly average COVID-19 Stringency Index and respiratory infections and COPD exacerbations rate was −0.316 (p = 0.132). When months known for a low respiratory infection rate were excluded, the correlation coefficient was −0.625 (p = 0.010). This study showed a significant negative correlation between the COPD exacerbations and respiratory infection rate and the COVID-19 Stringency Index in patients with AATD related COPD in the autumn-winter months. [ABSTRACT FROM AUTHOR]

Medical practice is built on the foundations of evidence-based medicine. Hence, the more common the clinical intervention, the more comprehensive the evidence on which that intervention should be based. Although the widespread adoption of a national early warning score in the UK has led to improvements in the delivery of care, it should be considered as providing a foundation that can be refined and developed, and there is still a need for critical reflection and evaluation of early warning scores, particularly for individuals with chronic respiratory disease, in order to optimise patient monitoring, predict deterioration and guide intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent respiratory disease associated with significant health decline and economic burdens. Pulmonary rehabilitation is an effective intervention, but securing adherence to exercise is difficult, particularly for frail and disabled patients, challenged by leaving their home. Home-based exercise is an emerging alternative for persons with COPD, but long-term adherence is unclear. This study aims to investigate the effects, experiences and acceptability of long-term home-based cycling for patients with COPD post exacerbation., Methods and Analyses: This cluster randomised controlled trial will recruit hospitalised patients with COPD following hospitalisation following exacerbation of COPD. Participants will be referred to acute rehabilitation for 8 weeks at discharge. After rehabilitation, participants are randomised in clusters of five into 1 year of home-based cycling with the goal of cycling from Aalborg to Paris, or into the control group, who will receive standard care. Data will be collected at baseline, postrehabilitation/intervention initiation, at 6 and 12 months. Primary outcome is physical performance, while secondary outcomes include daily activity levels, lung function, mobility, frailty, symptom severity, health-related quality of life, survival rates and readmissions. A qualitative substudy will uncover experiences from participants. Daily activity levels will be measured using leg-mounted triaxial accelerometers. Other parameters will be tested with physical tests, questionnaires and interviews. The study aims to include 50 patients, with 25 participants in each group. A cost-effectiveness analysis will assess the impact on disease prevention and hospitalisation., Ethics and Dissemination: This study, approved by The North Denmark Region Committee on Health Research Ethics (N-20230008) and compliant with the Helsinki Declaration, includes annual safety and progress reporting of potential adverse events. Results will be disseminated through peer-reviewed publications, conference presentations and community outreach to ensure accessibility to participants, healthcare professionals and the public., Trial Registration Number: NCT06235502 and Northern Jutland trial register (F2023-066)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: Patients recovering from severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a 30-day readmission rate of 20%. This study evaluated the feasibility of conducting a randomised controlled trial to evaluate clinical, patient-reported and physiological effects of home high-flow therapy (HFT) in addition to usual medical therapy, in eucapnic patients recovering from AECOPD to support the design of a phase 3 trial., Methods: A mixed-methods feasibility randomised controlled trial (quantitative primacy, concurrently embedded qualitative evaluation) (ISRCTN15949009) recruiting consecutive non-obese patients hospitalised with AECOPD not requiring acute non-invasive ventilation. Participants were randomised to receive usual care or usual care and home HFT (37°C, 30 L/min) with weekly home-based follow-up for 4 weeks to collect data on: device usage, breathlessness (modified Borg scale, visual analogue scale, Multidimensional Dyspnoea Profile), health-related quality of life (COPD Assessment Test (CAT), Clinical COPD Questionnaire), pulse oximetry, spirometry and inspiratory capacity, parasternal electromyography and actigraphy. Semistructured interviews were conducted in week 4. Trial progression criteria were: ≥40% of eligible patients randomised, ≤20% attrition, ≥70% complete data, and no device-related serious adverse events (SAE)., Results: 18 of 45 eligible patients were randomised (age 69±5 years, 44% female, body mass index 23±5 kg/m 2 , forced expiratory volume in 1 second 32±12%). One withdrew following non-respiratory hospitalisation. Complete outcome measures were collected in >90% of home assessments. There were no device-related SAE. Daily HFT usage was 2.7±2.2 hours in week 1, falling to 2.3±1.4 hours by week 4. Temperature and flow settings were modified for comfort in 6 cases. Higher HFT usage was associated with lower symptom burden (CAT p=0.01). Interviews highlighted ease of device use, reduced salbutamol usage, and improved sputum production and clearance., Conclusions: The data from this feasibility study support the progression to a phase 3 randomised clinical trial investigating the effect of home (HFT) on admission-free survival in COPD patients recovering from a severe exacerbation., Trial Registration Number: The study received ethical approval (REC19/LO/0194) and was prospectively registered (ISRCTN15949009)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Exacerbation of chronic obstructive pulmonary disease (COPD) is associated with disease progression and increased mortality. Periodontal disease is a risk factor for exacerbation of COPD, but little is known about the role of periodontopathic bacteria in this process. Here, we investigated the effects of intratracheal administration of Fusobacterium nucleatum, a periodontopathic bacteria species, on COPD exacerbation in elastase‐induced emphysematous mice. The administration of F. nucleatum to elastase‐treated mice enhanced inflammatory responses, production of alveolar wall destruction factors, progression of emphysema, and recruitment of mucin, all of which are symptoms observed in patients with COPD exacerbation. Hence, we propose that F. nucleatum may play a role in exacerbation of COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic disease associated with recurring exacerbations, which influence morbidity and mortality for the patient, while placing significant resource burdens on healthcare systems. Non-invasive ventilation (NIV) in a domiciliary setting can help prevent admissions, but the economic evidence to support NIV use is limited.Methods: A Markov model-based cost-utility analysis from the UK National Health Service perspective compared the cost-effectiveness of domiciliary NIV with usual care for two end-stage COPD populations; a stable COPD population commencing treatment with no recent hospital admission; and a posthospital population starting treatment following admission to hospital for an exacerbation. Hospitalisation rates in patients receiving domiciliary NIV compared with usual care were derived from randomised controlled studies in a recent systematic review. Other model parameters were updated with recent evidence.Results: At the threshold of £20 000 per quality-adjusted life-year (QALY) domiciliary NIV is 99.9% likely cost-effective in a posthospital population, but unlikely (4%) to be cost-effective in stable populations. The incremental cost-effective ratio (ICER) was £11 318/QALY gained in the posthospital population and £27 380/QALY gained in the stable population. Cost-effectiveness estimates were sensitive to longer-term readmission and mortality risks, and duration of benefit from NIV. Indeed, for stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) for stage 4 patients, or with higher mortality and exacerbation risks, ICERs were close to the £20 000/QALY threshold.Conclusion: Domiciliary NIV is likely cost-effective for posthospitalised patients, with uncertainty around the cost-effectiveness of domiciliary NIV in stable patients with COPD on which further research should focus. [ABSTRACT FROM AUTHOR]