Impact and timing of pulmonary rehabilitation in patients undergoing bronchoscopic lung volume reduction with endobronchial valves: A multicentre randomized controlled trial in patients with severe emphysema.

BACKGROUND AND OBJECTIVE: Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone. METHODS: We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life. RESULTS: Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone. CONCLUSION: The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.

Severity of Airflow Obstruction Based on FEV1/FVC vs FEV1% of Predicted in the General US Population.

RATIONALE: According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. OBJECTIVE: To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. METHODS: Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. RESULTS: STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. CONCLUSIONS: FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Lung-function trajectories: relevance and implementation in clinical practice.

Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.

All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study.

BACKGROUND: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. OBJECTIVES: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). DESIGN: Population-based prospective cohort study. METHODS: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC ⩾ 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC ⩾ 0.70 and FVC ⩾ 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. RESULTS: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. CONCLUSION: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.

All-cause and cause specific mortality in relation to different lung function patterns and sex; normal, obstructive and restricted lung functionChronic airway obstruction and restrictive spirometry pattern are associated with mortality, but sex specific patterns have hardly been evaluated.Aim: To study possible sex-dependent differences of all-cause and cause-specific mortality among men and women with chronic airway obstruction and restrictive spirometry pattern, respectively, compared to that of normal lung function.Methods: Individuals with chronic airway obstruction, restrictive spirometry pattern and normal lung function were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-04. Mortality data were collected through April 2016, totally covering 19,000 patient-years of observation time. We analyzed the Hazard Ratios for all-cause and cause-specific death comparing chronic airway obstruction and restrictive spirometry pattern to that of normal lung function, adjusting for age, body mass index, sex, smoking habits and pack-years. Similar analyses were conducted separately for men and women.Results: The hazard for all-cause mortality was higher in both chronic airway obstruction and restrictive spirometry pattern than in normal lung function and, the higher hazards were male-driven. In chronic airway obstruction the hazard of respiratory and cardiovascular deaths higher than in those with normal lung function. The increased hazard of respiratory death was significant in women while the increased hazard of cardiovascular death was significant in men. In restrictive spirometry pattern, the higher hazard for respiratory but not cardiovascular death persisted after adjustment, similarly in both sexes.Conclusions: The higher hazard for all-cause mortality in chronic airway obstruction and restrictive spirometry pattern than in normal lung function was male-driven. Chronic airway obstruction associated with respiratory death in women and cardiovascular death in men, while restrictive pattern associated with respiratory death, similarly in both sexes.

Treatable traits in advanced emphysema patients eligible for bronchoscopic lung volume reduction with endobronchial valves.

INTRODUCTION: Patients with advanced emphysema eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV) are characterized by severe static lung hyperinflation, which can be considered a treatable trait. Other treatable traits (TTs), which are assumed to be present in this highly selected patient group, have not been studied in detail nor how they may affect health-related quality of life (HRQL). AIMS: We aimed to evaluate a spectrum of TTs in COPD patients eligible for EBV treatment and their association with HRQL. METHODS: The SoLVE study (NCT03474471) was a prospective multicenter randomized controlled trial to examine the impact of pulmonary rehabilitation in COPD patients receiving EBV. The presence/absence of 16 TTs was based on pre-defined thresholds. HRQL was assessed with the St. George's Respiratory Questionnaire (SGRQ). Subjects were stratified into two groups, using the median split method, into higher or lower SGRQ total score. Logistic regression assessed the odds ratio (OR) of having a higher SGRQ total score per TT. RESULTS: Ninety-seven subjects were included, the mean number of TTs per patient was 8.1 ± 2.5. Low physical activity (95%), poor exercise capacity (94%) and severe fatigue (75%) were the most prevalent TTs. The sum of TTs present in a subject was associated with the SGRQ total score (r = 0.53; p < 0.001). Severe fatigue, depression, and anxiety were predictors of having a higher SGRQ total score. CONCLUSIONS: A high prevalence and co-occurrence of multiple TTs were identified in emphysema patients eligible for EBV. Patients with a higher number of TTs were more likely to have worse HRQL.

Recent advances in bronchoscopic lung volume reduction for severe COPD patients.

PURPOSE OF REVIEW: Bronchoscopic lung volume reduction (BLVR) is a novel and effective treatment for a specific phenotype of chronic obstructive pulmonary disease (COPD) characterized by advanced emphysema with static lung hyperinflation and severe breathlessness. This review aims to provide an overview of the recent advances made in BLVR. RECENT FINDINGS: For achieving optimal outcomes with BLVR, patient selection and target lobe identification is crucial. BLVR has recently also been established to improve pulmonary function, exercise capacity and quality of life in COPD patients falling outside the standard treatment criteria, including patients with moderate hyperinflation, chronic hypercapnic failure or with very low diffusion capacity. In a cluster analysis, target lobe characteristics like emphysema destruction, air trapping and perfusion were found to be important discriminators between responders and non-responders. A potential survival benefit has been demonstrated in BLVR-treated patients when compared to non-treated patients. Long-term outcomes showed sustained outcomes of BLVR; however, effects decline over time, probably due to disease progression. SUMMARY: BLVR using one-way endobronchial valves has become a guideline treatment offered in specialized intervention centres for a specific subgroup of COPD patients. Recent studies further characterize responders, describe extrapulmonary effects of BLVR and show positive long-term outcomes and a potential survival benefit.

High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

COPD and multimorbidity: recognising and addressing a syndemic occurrence.

Most patients with chronic obstructive pulmonary disease (COPD) have at least one additional, clinically relevant chronic disease. Those with the most severe airflow obstruction will die from respiratory failure, but most patients with COPD die from non-respiratory disorders, particularly cardiovascular diseases and cancer. As many chronic diseases have shared risk factors (eg, ageing, smoking, pollution, inactivity, and poverty), we argue that a shift from the current paradigm in which COPD is considered as a single disease with comorbidities, to one in which COPD is considered as part of a multimorbid state-with co-occurring diseases potentially sharing pathobiological mechanisms-is needed to advance disease prevention, diagnosis, and management. The term syndemics is used to describe the co-occurrence of diseases with shared mechanisms and risk factors, a novel concept that we propose helps to explain the clustering of certain morbidities in patients diagnosed with COPD. A syndemics approach to understanding COPD could have important clinical implications, in which the complex disease presentations in these patients are addressed through proactive diagnosis, assessment of severity, and integrated management of the COPD multimorbid state, with a patient-centred rather than a single-disease approach.

Hospital Admission Rates in Patients with COPD Throughout the COVID-19 Pandemic.

Purpose: Several studies report decreased hospital admissions for acute exacerbations of COPD (AECOPD) during the COVID-19 pandemic. However, there are no studies that compare AECOPD admissions with admissions for respiratory infections, including COVID-19. This study aimed to examine hospital admission rates for AECOPD, pneumonia, influenza, and COVID-19 among COPD patients, before and during the COVID-19 pandemic. Patients and Methods: We obtained anonymized data on hospital admissions of patients with COPD and a primary diagnosis code for AECOPD, pneumonia, influenza, or COVID-19, from the hospital patient admission register at a large Swedish hospital. The study compared the pandemic period (February 2020-March 2022) to a period before the pandemic (June 2017-January 2020). Sequential phases of the pandemic were evaluated separately. Monthly admission rates were compared using Poisson regression, controlling for admission month. Results: Comparing monthly admission rates during the pandemic with the prepandemic period, incidence rate ratios were 0.72 for AECOPD (95% CI 0.67-0.77; p<0.001), 0.56 for pneumonia (95% CI 0.49-0.62; p<0.001), 0.18 for influenza during the winter period (95% CI 0.10-0.30; p<0.001) and 0.79 for total COPD admissions, including COVID-19 (95% CI 0.75-0.84; p<0.001). The study showed significantly lower rate ratios for AECOPD, pneumonia, and total COPD admissions during the first, second, third, and fifth (Omicron) waves. No significant effect on admissions was seen after the withdrawal of restriction measures. Conclusion: There was a significant reduction in the overall rate of hospital admissions among COPD patients for AECOPD, pneumonia, and respiratory viral infections during the pandemic despite the rise in COVID-19 admissions. However, prepandemic admission levels returned in the post-restriction period.

Regular Inhaled Corticosteroids Use May Protect Against Severe COVID-19 Outcome in COPD.

Purpose: Population-based studies provide conflicting evidence about how inhaled corticosteroids (ICS) impact COVID-19 outcomes among COPD patients. We investigated whether regular ICS exposure affects risk, severity, or survival in SARS-CoV-2 infection, using a nationwide linked Swedish population register database. Patients and Methods: During January-December 2020, we studied two defined Swedish adult populations - Whole population [≥40 years] (N = 5243479), and COPD subpopulation [≥40 years] (N = 133372), in three study cohorts, respectively: 1. Overall cohort (index date 1 Jan 2020), 2. COVID-19 diagnosed sub-cohort (index date = diagnosis date), and 3. COVID-19 hospitalized sub-cohort (index date = admission date). Regular exposure was defined as ≥3 ICS prescriptions in the year before index. Hazard ratios (HRs) for outcomes (COVID-19 onset, hospitalization, ICU admission, or death) related to ICS exposure were estimated using Cox regression. Confounding was controlled by propensity score methods applying Average Treatment effect in the Treated (ATT) weighting. Results: Regular ICS use was associated with only very slightly increased onset of COVID-19, hospitalization, ICU admission, and death in the overall whole population cohort and in the overall COPD subpopulation cohort, except for ICU admission (marginally non-significant HRs, up to 1.13); and no clear increase in the diagnosed sub-cohorts. However, in the COVID-19 hospitalized COPD sub-cohort, ICS therapy showed reduced risks against progression to ICU admission and death, significant for death (HR 0.82 95% CI [0.67-0.99]). Conclusion: For COPD patients, ICS therapy offers some protection against progression to ICU admission and death among COVID-19 hospitalized patients. Our findings alleviate concerns about increased risks of COVID-19 by ICS treatment and provide evidence supporting the continuation of ICS therapy for COPD patients.

Activation of the Complement and Coagulation Systems in the Small Airways in Asthma.

BACKGROUND: Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma. OBJECTIVES: We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control. METHOD: Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry. RESULTS: 53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways. CONCLUSIONS: The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.

Pre- and post-vaccination characteristics and risk factors for COVID-19 outcomes in a Swedish population-based cohort of COPD patients.

Rationale: Evidence on risk factors for Coronavirus disease 2019 (COVID-19) outcomes among patients with COPD in relation to COVID-19 vaccination remains limited. The objectives of the present study were to characterise determinants of COVID-19 infection, hospitalisation, intensive care unit (ICU) admission and death in COPD patients in their unvaccinated state compared to when vaccinated. Methods: We included all COPD patients in the Swedish National Airway Register (SNAR). Events of COVID-19 infection (test and/or healthcare encounter), hospitalisation, ICU admission and death were identified from 1 January 2020 to 30 November 2021. Using adjusted Cox regression, associations between baseline sociodemographics, comorbidities, treatments, clinical measurements and COVID-19 outcomes, during unvaccinated and vaccinated follow-up time, were analysed. Results: The population-based COPD cohort included 87 472 patients, among whom 6771 (7.7%) COVID-19 infections, 2897 (3.3%) hospitalisations, 233 (0.3%) ICU admissions and 882 (1.0%) COVID-19 deaths occurred. During unvaccinated follow-up, risk of COVID-19 hospitalisation and death increased with age, male sex, lower education, non-married status and being foreign-born. Comorbidities increased risk of several outcomes, e.g. respiratory failure for infection and hospitalisation (adjusted hazard ratios (HR) 1.78, 95% CI 1.58-2.02 and 2.51, 2.16-2.91, respectively), obesity for ICU admission (3.52, 2.29-5.40) and cardiovascular disease for mortality (2.80, 2.16-3.64). Inhaled COPD therapy was associated with infection, hospitalisation and death. COPD severity was also associated with COVID-19, especially hospitalisation and death. Although the risk factor panorama was similar, COVID-19 vaccination attenuated HRs for some risk factors. Conclusion: This study provides population-based evidence on predictive risk factors for COVID-19 outcomes and highlights the positive implications of COVID-19 vaccination for COPD patients.

Differential Response to 12 Weeks of Once-Daily Tiotropium/Olodaterol Fixed Dose Combination in Patients with COPD: A Multidimensional Response Profiling in the TORRACTO Study.

Purpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM). Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 µg) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O. Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline. Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.

The AGE-RAGE Axis and the Pathophysiology of Multimorbidity in COPD.

Chronic obstructive pulmonary disease (COPD) is a disease of the airways and lungs due to an enhanced inflammatory response, commonly caused by cigarette smoking. Patients with COPD are often multimorbid, as they commonly suffer from multiple chronic (inflammatory) conditions. This intensifies the burden of individual diseases, negatively affects quality of life, and complicates disease management. COPD and comorbidities share genetic and lifestyle-related risk factors and pathobiological mechanisms, including chronic inflammation and oxidative stress. The receptor for advanced glycation end products (RAGE) is an important driver of chronic inflammation. Advanced glycation end products (AGEs) are RAGE ligands that accumulate due to aging, inflammation, oxidative stress, and carbohydrate metabolism. AGEs cause further inflammation and oxidative stress through RAGE, but also through RAGE-independent mechanisms. This review describes the complexity of RAGE signaling and the causes of AGE accumulation, followed by a comprehensive overview of alterations reported on AGEs and RAGE in COPD and in important co-morbidities. Furthermore, it describes the mechanisms by which AGEs and RAGE contribute to the pathophysiology of individual disease conditions and how they execute crosstalk between organ systems. A section on therapeutic strategies that target AGEs and RAGE and could alleviate patients from multimorbid conditions using single therapeutics concludes this review.

Clinical impact of routine sleep assessment by peripheral arterial tonometry in patients with COPD.

Background: Coexisting obstructive sleep apnoea (OSA) in patients with COPD, defined as overlap syndrome (OVS), is prevalent and underdiagnosed. Routine assessment of OSA is not common practice in COPD care. Our study assessed the clinical impact of sleep assessment by peripheral arterial tonometry (PAT) in COPD patients. Methods: 105 COPD patients (mean age 68.1±9 years, body mass index (BMI) 28.3±6.0 kg·m-2, 44% males, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I to IV in 2%, 40%, 42% and 16%, respectively) underwent assessment at an outpatient COPD clinic including anthropometrics, arterial blood gas (ABG) and spirometry in this clinical cohort study. PAT-based sleep studies were performed. Predictors of OVS and ABG were determined. Rapid eye movement (REM) sleep-related OSA (REM-OSA) was analysed in OVS. Results: 49 COPD patients (47%) suffered from moderate to severe OSA (OVS group, mean apnoea-hypopnoea index 30.8±18 events·h-1, REM-oxygen desaturation index (REM-ODI) 26.9±17 events·h-1). OVS was more prevalent in males compared to females (59% and 37%, p=0.029, respectively). Age (70.1±8 versus 66.3±10 years), BMI (30.0±6 versus 26.4±7 kg·m-2) and hypertension prevalence (71% versus 45%) were elevated (all p<0.03, respectively), while deep sleep (12.7±7% and 15.4±6%, p=0.029) and mean overnight oxygenation (90.6±3% and 92.3±2%, p=0.003) were lower in OVS compared to COPD alone. REM-ODI was independently associated with daytime arterial carbon dioxide tension (P aCO2 ) (ß=0.022, p<0.001). REM-OSA was associated with an elevated prevalence of atrial fibrillation compared to no REM-OSA (25% and 3%, p=0.022). Conclusions: OVS was highly prevalent, specifically in obese males. REM-related OSA showed strong association with elevated daytime P aCO2 and prevalent cardiovascular disease. PAT was feasible for sleep assessment in COPD.

Exacerbation Risk and Mortality in Global Initiative for Chronic Obstructive Lung Disease Group A and B Patients with and without Exacerbation History.

Rationale: Risk stratification of patients according to chronic obstructive pulmonary disease severity is clinically important and forms the basis of therapeutic recommendations. No studies have examined the association for Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and group B patients with (A1 and B1, respectively) and without (A0 and B0, respectively) an exacerbation in the past year with future exacerbations, hospitalizations, and mortality in perspective with the new GOLD ABE classification. Objectives: The aim was to examine the association between GOLD A0, A1, B0, B1, and E patients and future exacerbations, respiratory and cardiovascular hospitalizations, and mortality. Methods: In this nationwide cohort study, we identified patients with a diagnosis of chronic obstructive pulmonary disease, aged ⩾30 years, and registered in the Swedish National Airway Register between January 2017 and August 2020. Patients were stratified in GOLD groups A0, A1, B0, B1, and E and were followed until January 2021 for exacerbations, hospitalizations, and mortality in national registries. Measurements and Main Results: The 45,350 eligible patients included 25% A0, 4% A1, 44% B0, 10% B1, and 17% E. Moderate exacerbations, all-cause and respiratory hospitalizations, and all-cause and respiratory mortality increased by GOLD group A0-A1-B0-B1-E, except for moderate exacerbations, which were higher in A1 than in B0. Group B1 had a substantially higher hazard ratio for future exacerbation (2.56; 95% confidence interval [95% CI] 2.40-2.74), all-cause hospitalization (1.28; 1.21-1.35), and respiratory hospitalization (1.44; 1.27-1.62), but not all-cause (1.04; 0.91-1.18) or respiratory (1.13; 0.79-1.64) mortality than group B0. The exacerbation rate for group B1 was 0.6 events per patient-year versus 0.2 for group B0 (rate ratio, 2.55; 95% CI, 2.36-2.76). Results were similar for group A1 versus group A0. Conclusions: Stratification of GOLD A and B patients with one or no exacerbation in the past year provides valuable information on future risk, which should influence treatment recommendations for preventive strategies.

Biomarker-based clustering of patients with chronic obstructive pulmonary disease.

Rationale: COPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways. Methods: 213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster. Results: Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load. Conclusions: These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.

Endothelial function in patients with COPD: an updated systematic review of studies using flow-mediated dilatation.

INTRODUCTION: Cardiovascular disease is a significant cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be involved in cardiovascular disease pathogenesis, and multiple studies report endothelial dysfunction in COPD. This article summarized the current knowledge on endothelial function in COPD patients. AREAS COVERED: Databases were screened until November 2022 for studies using ultrasound-based flow-mediated dilation in patients with stable COPD. Pooled effect sizes were calculated using random effects model. Meta-regression analyses assessed the effects of demographic and clinical variables. EXPERT OPINION: 34 studies were identified (1365 COPD patients; 617 controls). Pooled analysis demonstrated an impaired endothelial-dependent (-2.33%; 95%CI -3.30/-1.35; p < 0.001) and endothelial-independent dilation (-3.11%; 95%CI -5.14/-1.08; p = 0.003) in COPD patients when compared to non-COPD controls. Meta-regression identified that higher age, worse severity of airflow obstruction, and current smoking were significantly associated with impaired endothelial function. Studies evaluating the effects of pharmacological and non-pharmacological interventions on endothelial function in COPD patients demonstrated conflicting results.

Gender Differences in Vitamin D Status and Determinants of Vitamin D Insufficiency in Patients with Chronic Obstructive Pulmonary Disease.

Low vitamin D levels are common in Chronic Obstructive Pulmonary Disease (COPD) and have been associated with various adverse COPD-related outcomes. Recent data on vitamin D status in representative COPD cohorts in Scandinavia is lacking. This study aimed to assess vitamin D status and determinants of vitamin D insufficiency in patients with COPD who were attending a specialist secondary care COPD clinic in Southwestern Sweden. All patients who visited the COPD clinic for their first medical visit during two periods, 2017−2018 and 2021, were included in this observational study. Measurements of 25-Hydroxyvitamin D (25(OH)D), clinical data and documentation of supplements containing vitamin D were collected retrospectively from patients' medical records. Multivariable logistic regression analysis was performed to identify determinants of the primary outcome, vitamin D insufficiency (25(OH)D < 50 nmol/L). A total of 667 patients were included, and 33% had vitamin D insufficiency. The median 25(OH)D was 62 nmol/L (43.5−83.1 nmol/L). Vitamin D insufficiency was related to the male gender, current smoking habits, a lack of supplements containing vitamin D and the winter season for blood sampling. In conclusion, vitamin D insufficiency is common in patients with COPD. Men had significantly lower levels of vitamin D but took vitamin D-containing supplements less frequently compared to women. Our findings can help clinicians to identify patients who are at risk of vitamin D insufficiency and allow correction with supplementation where appropriate.