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INTRODUCTION: Public health measures to reduce the transmission of COVID-19 have required various changes in life-style, including loss or risk to employment and social isolation. We wished to assess how these measured effected 30-45 year old smokers at risk of COPD participating in the BLF Early COPD cohort study METHODS: At enrolment, participants were aged 30-45 years, tobacco smokers with >10 pack-year smoking history, FEV1=>80% predicted and a BMI < 35kg/m2. Participants were seen face-to-face in clinic pre-COVID. During lock-down, they were posted questionnaires and contacted by telephone. The last clinic visit took place on the 12 March 2020, remote visits took place between 16 April and 28 Sep. 260 individuals at six sites (25 Belfast, 38 Birmingham, 25 Edinburgh, 101 London, 27 Manchester and 44 Nottingham) were asked about smoking habits. The MRC chronic bronchitis questionnaire, COPD Assessment test (CAT), Leicester cough questionnaire, Hospital Anxiety and Depression questionnaire were completed in writing by the participant and returned by post or photographed and returned by email. At enrolment, the post-BD FEV1 was 3.81 (SD 0.8) litres, 101% (11) of GLI predicted. Comparisons were made by paired t-tests and chi-squared tests. RESULTS: Level of anxiety increased from 6.74 (SD 4.4) to 7.37 (SD 4.7, n=233; p=0.010) during lock-down; depression scores increased from 4.30 (3.9) to 5.14 (SD 4.1; n=233; p

Pulmonary surfactant protein D (SP-D) is an important component of the pulmonary innate immune system with the ability to dampen cigarette smoke-induced lung inflammation. However, cigarette smoking mediates translocation of SP-D from the lung to the blood, and serum SP-D (sSP-D) has therefore previously been suggested as marker for smoke-induced lung injury. In support of this notion, associations between high sSP-D and low lung function measurements have previously been demonstrated in smokers and in chronic obstructive lung disease (COPD). The present investigations employ a 12-yr longitudinal Danish twin study to test the hypothesis that baseline sSP-D variation has the capacity to identify smokers with normal baseline lung function who are at high risk of significant future smoke-induced lung function decline. We find that sSP-D is significantly increased in those with normal lung function at baseline who develop lung function decline during follow-up compared with those who stay lung healthy. Moreover, we demonstrate that it is the smoke-induced baseline sSP-D level, and not the constitutional level, which has capacity as biomarker, and which is linearly increased with the decline in lung function during follow-up. In conclusion, we here present first observation of increased sSP-D for identification of high-risk smokers.

Background Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 have been associated with an altered sensitivity to glucocorticoids, and thus may alter the therapeutic effects of glucocorticoids. We investigated the prevalence of adrenal suppression after treatment with glucocorticoids and evaluated whether GR SNPs were associated with altered risks of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). Methods In an observational prospective cohort study, we recruited 78 patients with severe COPD receiving 5 days glucocorticoid treatment for an exacerbation of COPD. In total, 55% of these patients were also receiving regular inhaled corticosteroids (ICS). Adrenal function was evaluated with a corticotropin test 30 days after the exacerbation. Patients were genotyped for Bcl1, N363S, ER22/23EK, and 9β SNPs. Results The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 30 days after glucocorticoid treatment was 4/78 (5%). There was no difference between carriers and non-carriers of the polymorphisms (Bcl1, 9β, ER22/23K, and N363S) in corticotropin stimulated plasma-cortisol concentrations. In the haplotype analyses, we included the 50 patients who had a high-sensitivity (76%), a low-sensitivity (4%), or a wild-type (20%) GR haplotype. There was no difference in the frequency of adrenal suppression or metabolic disorders between the two stratified groups: (a) high-sensitivity (Bcl1 and/or N363S) haplotypes vs. (b) low-sensitivity (9β and/or ER22/23K) plus wild-type haplotypes (p > 0.05). Carriers of the high-sensitivity GR gene haplotype exhibited a steeper decline in stimulated P-cortisol with increased ICS dose (slope, –1.35 vs. 0.94; p = 0.17), compared to the group with low-sensitivity or wild-type haplotypes, respectively. Conclusions In total, 5% of patients exhibited insufficient adrenal function. The Bcl1 and N363S polymorphisms did not seem to increase the risk of glucocorticoid suppression or metabolic disorders in adults treated with glucocorticoids for COPD exacerbations.

Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor’s consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biomarkers that in patients with SARS-Cov-2 infection are able to; (1) identify patients in most need of medical care prior to admittance to an intensive care unit (ICU), and; (2) identify patients post-infection at risk of developing persistent fibrosis of lungs with subsequent impaired quality of life and increased morbidity and mortality. An intense amount of research have focused on wound healing and Extracellular Matrix (ECM) remodelling of the lungs related to lung function decline in pulmonary fibrosis (PF). A range of non-invasive serological biomarkers, reflecting tissue remodelling, and fibrosis have been shown to predict risk of acute exacerbations, lung function decline and mortality in PF and other interstitial lung diseases (Sand et al. in Respir Res 19:82, 2018). We suggest that lessons learned from such PF studies of the pathological processes leading to lung function decline could be used to better identify patients infected with SARS-Co-V2 at most risk of acute deterioration or persistent fibrotic damage of the lung and could consequently be used to guide treatment decisions.

Background Systemic corticosteroid administration for severe acute exacerbations of COPD (AECOPD) reduces the duration of hospital stays. Corticosteroid-sparing regimens have showed non-inferiority to higher accumulated dose regimens regarding re-exacerbation risk in patients with AECOPD. However, it remains unclear whether 14-day or 2–5-day regimens would result in shorter admission durations and changes in mortality risk. We explored this by analysing the number of days alive and out of hospital based on two randomised controlled trials with different corticosteroid regimens. Methods We pooled individual patient data from the two available multicentre randomised trials on corticosteroid-sparing regimens for AECOPD: the REDUCE (n = 314) and CORTICO-COP (n = 318) trials. In the 14-day regimen group, patients were older, fewer patients received pre-treatment with antibiotics and more patients received pre-treatment with systemic corticosteroids. Patients randomly allocated to the 14-day and 2–5-day regimens were compared, with adjustment for baseline differences. Results The number of days alive and out of hospital within 14 days from recruitment was higher for the 2–5 day regimen group (mean 8.4 days; 95% confidence interval [CI] 8.0–8.8) than the 14-day regimen patient group (4.2 days; 95% CI3.4–4.9; p p p p = 0.15), new or aggravated hypertension (OR 1.5; 95% CI 0.9–2.7; p = 0.15), or mortality risk (HR 0.8; 95% CI 0.4–1.5; p = 0.45) during the 6-month follow-up period. Conclusion 14-day corticosteroid regimens were associated with longer hospital stays and fewer days alive and out of hospital within 14 days, with no apparent 6-month benefit regarding death or admission to ICU in COPD patients. Our results favour 2–5 day regimens for treating COPD exacerbations. However, prospective studies are needed to validate these findings.

Background: Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 have been associated with an altered sensitivity to glucocorticoids (GC), and thus may affect the therapeutic effects of GCs. We investigated the prevalence of adrenal suppression after treatment with GCs and evaluated whether GR SNPs were associated with the risk of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). Methods: In an observational prospective cohort study, we recruited 77 patients with severe COPD receiving five days GC treatment for an exacerbation of COPD. 49% of patients also received regular inhaled corticosteroids. Adrenal function was evaluated with a corticotropin test 30 days after the exacerbation. Patients were genotyped for Bcl1, N363S, ER22/23EK and 9β SNPs. Results: The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 1 month after GC treatment was 4/77 (5%). There was no correlation between high-sensitivity (p-value 0.79) or low-sensitivity (p-value 0.26) GR haplotypes and stimulated cortisol levels for COPD patients treated with GCs. There was no difference between adrenal suppression and metabolic disorders in COPD patients stratified for high vs. low GC-sensitivity GR haplotypes plus wild type (p-value > 0.05). Corticotropin stimulated P-cortisol did not differ between carriers and non-carriers for Bcl1, 9β, ER22/23K and N363S. For carriers of the high sensitivity GR gene haplotype, the association between inhaled corticosteroid dose and stimulated P-cortisol concentrations was more inverse (slope –0.25 vs. -0.10) than in patients with the low sensitivity haplotype. Conclusions: Five percent of patients had an insufficient adrenal function. The Bcl1 and N363S polymorphisms do not seem to increase the risk of adrenal suppression or metabolic disorders in adults treated with corticosteroids for COPD exacerbations.Trial Registration: The trial was registered at clinicaltrials.gov (NCT03140761) at May 4, 2017 with URL https://clinicaltrials.gov/ct2/show/NCT03140761.

It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5 May 2020, and the instruments used to measure these outcomes. Significant heterogeneity was observed in the selection of outcomes and instruments. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality (72.5%) and adverse events (55.6%), while hospital admission (50.8%) and viral detection/load (55.6%) are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for greater consistency, to enable decision makers to compare and contrast studies.

The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities. COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities. Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD. First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection? Secondly, do inhaled corticosteroids offer protection against COVID-19? And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients? This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19., This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19 https://bit.ly/36PKzEO

Introduction: Patients with coronavirus disease (COVID-19) and pneumonitis often have hypoxemic respiratory failure and a need of supplementary oxygen. Guidelines recommend controlled oxygen, for most patients with a recommended interval of SpO2 between 92 and 96%. We aimed to determine if closed-loop control of oxygen was feasible in patients with COVID-19 and could maintain SpO2 in the specified interval. Methods: Patients were prospectively enrolled in an observational study on a medical ward dedicated to patients with COVID-19. Closed-loop controlled oxygen was delivered by O2matic® which can deliver 0–15 liters/min and adjusts flow every second based on 15 seconds averaging of SpO2 measured by pulse oximetry. Lung function parameters were measured at admission. Results: Fifteen patients (six women, nine men) participated in the study. Average age was 72 years. Lung function was severely impaired with FEV1, FVC and PEF reduced to approximately 50%. The average stay on the ward was 3.2 days and O2matic was used on average for 66 hours, providing 987 hours of observation. O2matic maintained SpO2 in the desired interval for 82.9% of the time. Time with SpO2 > 2% below interval was 5.1% and time with SpO2 > 2% above interval was 0.6%. Conclusion: Closed-loop control of oxygen to patients with COVID-19 is feasible and can maintain SpO2 in the specified interval in the majority of time. Closed-loop automated control could be of particular benefit for patients in isolation with decreased visibility, surveillance and monitoring. Further studies must examine the clinical benefits.

Rationale:Individuals that will develop chronic obstructive pulmonary disease(COPD) could be identified at an early age before clinical manifestations appear. Objective:We investigated risk of Clinical COPD 10 years later in young adults from the general population with and without Early COPD with a focus on smoking exposure. Methods:We included 14,870 individuals aged 20-100 from the Copenhagen General Population Study with spirometry 10 years apart. Early COPD was defined as baseline forced expiratory volume in 1second(FEV1)/forced vital capacity(FVC)

Patients with very severe chronic obstructive pulmonary disease (COPD) conduct their everyday lives under shortness of breath. The aim of this study was to explore telemediated exercise training to patients at home, with the conduct of everyday life as a theoretical framework. Based on ethnographic fieldwork involving a hospital, two municipalities, and homes of 11 patients from 2013 to 2017, this article shows how telemediated training became part of patients’ and partners’ everyday lives and the prioritization of time and resources for basic activities. Most of the patients found telemediated training meaningful, that it can work as an agent of hope in holding on to essential everyday life activities, but also that it may be experienced as burdensome and disciplining. The physiotherapists’ understanding of the patients’ circumstances and needs for rehabilitation changed. The article argues that telemediated training should be offered as part of a palliative approach for those severely affected by COPD.

Background Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy. Methods The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits. Results CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group. Conclusion Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients. Trial registration ClinicalTrials.gov Identifier: NCT02857842. Submitted August 2nd, 2016.

Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy in patients with obstructive lung disease. However, due to strict inclusion criteria and the conditions required for ascertaining statistical significance, the patients included typically represent as little as 5% of the general obstructive lung disease population. Thus, studies in broader patient populations are becoming increasingly important. These can be randomised effectiveness trials or observational studies providing data on real-world treatment effectiveness and safety data that complement efficacy RCTs. In this review we describe the features associated with the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the real-world clinical practice setting. We also discuss how RCTs and observational studies have reported opposing outcomes with several treatments and inhaler devices due to differences in study design and the variations in patients recruited by different study types. Whilst observational studies are not without weaknesses, we outline recently developed tools for defining markers of quality of observational studies. We also examine how observational studies are capable of providing valuable insights into disease mechanisms and management and how they are a vital component of research into obstructive lung disease. As we move into an era of personalised medicine, recent observational studies, such as the NOVEL observational longiTudinal studY (NOVELTY), have the capacity to provide a greater understanding of the value of a personalised healthcare approach in patients in clinical practice by focussing on standardised outcome measures of patient-reported outcomes, physician assessments, airway physiology, and blood and airway biomarkers across both primary and specialist care., Observational studies can support RCTs in influencing clinical practice in the field of obstructive lung disease https://bit.ly/36YWu0W

Background: European population cohorts continue to expand our understanding of chronic airways disease and inter-study collaboration may help address the inevitable limitations of study size, duration, era and geography. Towards this aim, CADSET has collated data from ten major general population European cohorts: Asklepios; Copenhagen City Heart Study; Copenhagen General Population Study; ECRHS; HUNT; LEAD; Lifelines, OLIN, Rotterdam Study and WSAS. We included males and females aged 20 to 95 years with baseline demographic and spirometry data.Results: Data from 262,829 individuals (44% male) from multiple European countries provided good coverage across all adult ages (Fig.1A). Recruitment occurred in every year from 1976 through 2020. 23% were current-smokers and 42% were never-smokers, a pattern varying with advancing age (Fig.1B). The prevalence of airflow limitation varied according to whether lower limit of normal (LLN) or Interpretation: These results fit with previous reports, however the size, geographical reach and span of recruitment provided by this collaboration provides a unique opportunity to explore chronic airways disease development. Together, we are now pursuing research questions previously beyond the scope of individual cohort studies.

Background: NOVELTY (NCT02760329) is a global, prospective, observational study of patients with a physician-assigned diagnosis of asthma and/or COPD. Pre- and post-bronchodilator (BD) spirometry was performed at baseline. Objective: To compare spirometric markers of airflow obstruction and reversibility across the spectrum of obstructive lung disease. Methods: Pre- and post-BD FEV1, FVC, FEV1/FVC, FEF25-75%, PEFR and BD reversibility (FEV1 increase ≥200 mL and ≥12%) were compared across physician-assigned diagnosis and severity groups. Results: In the 9,180 patients assessed, mean pre-BD FEV1, FEF25-75% and PEFR, and post-BD FEV1/FVC decreased with increasing severity (Table). Across all severities, spirometric markers were lower in patients with COPD vs asthma; asthma+COPD lay in between. Reversibility was similar across all diagnoses and severities, with a greater FEV1 reversibility with more severe disease. BD reversibility was comparable across all groups, but was lower for those with severe COPD vs severe asthma and asthma+COPD for FEF25-75% and PEFR. Conclusions: Increasing physician-assigned severity was associated with greater airflow limitation across all spirometric measures, particularly in patients with COPD. However, reversibility did not differentiate asthma from COPD. The use of reversibility criteria to distinguish diagnoses for entry into clinical trials must be questioned.

Background: NOVELTY (NCT02760329) is a global, prospective, observational study of patients with a physician diagnosis or suspected diagnosis of asthma and/or COPD. Objective: To describe the characteristics of patients with physician-assigned COPD without airflow obstruction or with Preserved Ratio but Impaired Spirometry (PRISm). Methods: We compared characteristics of patients with COPD (no diagnostic criteria specified) without airflow obstruction, with PRISm or with GOLD 1 airflow limitation (Table). Results: Of 3,198 patients with COPD and available post-bronchodilator spirometry, 424 (13.3%) were without airflow obstruction, 288 (9.0%) had PRISm and 314 (9.8%) had GOLD 1. Patients without airflow obstruction and patients with PRISm were younger, more often female, more obese and had earlier onset of symptoms and less smoking exposure than the GOLD 1 group (Table). Patients without airflow obstruction were more likely to have physician-assigned mild COPD than patients with PRISm. However, comorbidity, cough, breathlessness, exacerbations, patient-reported symptomatic worsening and inhaled corticosteroid prescription were frequent in all groups. Conclusions: Patients were frequently diagnosed with (and treated for) COPD without meeting standard spirometric criteria. These patients had risk factors and symptoms suggestive of airways disease. The prognosis and natural history of such patients are poorly understood.

Background: Blood eosinophil count (bEOS) is an important biomarker in obstructive lung disease. NOVELTY (NCT02760329) is a global, prospective, observational study with potential to identify obstructive lung disease phenotypes associated with differential outcomes, using biomarkers and clinical features. Objective: To evaluate factors associated with bEOS in patients with either physician-assigned asthma or COPD in NOVELTY. Methods: A cross-sectional analysis of associations between a single bEOS measurement and other baseline characteristics was performed using univariate and multivariate regression models. Results: Of 4,538 patients with data, the geometric mean (SE) bEOS was 0.16 (0.002) x109/L. Of these, 864 (19%) had EOS ≥300 cells/µL (23% asthma; 14% COPD). High bEOS was positively associated with male sex, ≥2 symptom worsenings in prior 3 months, FeNO, FEV1 reversibility, obesity and frequent mucoid cough, in both asthma and COPD (Figure). For asthma, positive associations with higher bEOS were observed for reduced lung function and physician-assessed severity; for COPD, positive associations were observed with current/former smokers. Associations with FeNO and frequent mucoid cough persisted in multivariate models for both diagnoses. Conclusions: Higher bEOS was independently associated with higher FeNO and presence of frequent mucoid cough regardless of physician-assigned asthma or COPD.

Background: Glucocorticoids (GCs) are widely used in patients with acute exacerbation of COPD. Single-nucleotide polymorphism (SNP) of the GC receptor gene (NR3C1) has been associated with individual differences in GC sensitivity and may be linked to response to GC-treatment. Objectives: i) Assess the prevalence of adrenal suppression (AS) in severe COPD patients 1 month after GCs course for exacerbation ii) Whether high GC sensitivity SNPs (BclI-G or N363S-G) is associated with increased AS and metabolic syndrome compared with SNPs associated with low GC sensitivity(ER22/23EK, 9β, wild type and mixed type). Methods: Observational prospective cohort study, we recruited 76 patients between 2017—2019 with severe COPD treated with 5 days of GCs. All patients were genotyped for all 4 SNPs. Results: AS frequency (corticotropin stimulated P-cortisol≤420 nmol/l) was 5.4% after 1-month. No difference was observed in baseline characteristics, the frequency of AS or other metabolic outcomes (figure 1) between high GC sensitivity and the low GC sensitivity genotypes. Conclusions: Carrier status of the BclI-G or N363S-G alleles was not associated with the development of AS or metabolic syndrome at 1-month after completing GC treatment, suggesting that genotyping for these SNPs can not identify COPD patients with a high risk of side effects.

Introduction: Severe COPD exacerbations requiring hospitalizations or resulting in death clearly impose a serious prognostic and economic impact on patients and healthcare systems who seek to prevent and treat them. Aims and Objectives: We evaluated the effect of triple therapy with extra-fine beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) pressurized metered dose inhaler (pMDI) on reducing the severe COPD exacerbation rate compared to non-triple (non-TT) including non-ICS-containing maintenance inhalation therapies. Methods: Analysis of pooled data from 3 phase III multinational, randomized, parallel group trials comparing 52 weeks treatment with BDP/FF/GB 100/6/12.5 µg 2 inhalations bid to BDP/FF (TRILOGY), tiotropium (TRINITY) and indacaterol/glycopyrronium (TRIBUTE) in symptomatic patients on prior non-TT with severe or very severe COPD and history of moderate or severe exacerbation in the past year. Results: 445 patients experienced 535 severe exacerbations and were considered in this analysis. 202 received BDP/FF/GB, 243 received non-TT (BDP/FF, TIO, IND/GLY), and of those, 168 received non-ICS-containing therapies (TIO, IND/GLY). The adjusted rate ratio of severe exacerbation with BDP/FF/GB was 0.769 (95%CI: 0.632, 0.936, p=0.009) vs non-TT and 0.745 (95%CI: 0.592, 0.937, p=0.012) vs non-ICS-containing therapies. Conclusions: Treatment with extra-fine BDP/FF/GB pMDI effectively reduced the rate of severe COPD exacerbations vs non-triple (by 23.1%) and non-ICS containing (by 25.5%) therapies in symptomatic patients.

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state, intra-alveolar accumulation of fibrin and basement membrane destruction. The aim of this study was to investigate if serological assessment of these processes were associated with COPD progression. Methods: Plasmin-mediated degradation of cross-linked fibrin (X-FIB), an end-product of fibrinogen, and MMP-mediated degradation of type IV collagen (C4Ma3) were assessed in plasma of 984 COPD subjects from the ECLIPSE cohort. Biomarker data were dichotomized into high vs low by ROC analysis. Cox proportional hazards regression assessed predictive value of the biomarkers alone and in combination for all-cause mortality after 2 years. Results: High levels of plasma X-FIB and C4Ma3 were associated with increased risk of mortality as compared with low levels, with hazard ratios of 4.88 (95% CI 2.28-10.47) and 4.68 (1.40-15.71), respectively. The combination of markers of fibrin cross-linking and collagen IV degradation increased the hazard ratio to 7.35 (3.48-15.55). Additionally, X-FIB was associated with emphysema while C4Ma3 was associated with acute exacerbations. Conclusions: Serological assessments of lung remodeling related to the abnormal epithelial repair in COPD are associated with a poor prognosis. The combination of two different aspects of COPD pathology, elevated wound healing and basement membrane destruction, may improve prediction. Method: GSK (ECLIPSE; SCO104960, NCT00292552); The Danish Agency for Science, Technology, and Innovation; The Danish Research Foundation; NIHR Manchester Biomedical Research Centre.

Supernormal lung function is associated with fewer cardiovascular and respiratory events and a survival benefit independent from major risk factorshttps://bit.ly/371l3ut

Background COPD is a leading cause of mortality. Research Question We hypothesized that applying machine learning to clinical and quantitative CT imaging features would improve mortality prediction in COPD. Study Design and Methods We selected 30 clinical, spirometric, and imaging features as inputs for a random survival forest. We used top features in a Cox regression to create a machine learning mortality prediction (MLMP) in COPD model and also assessed the performance of other statistical and machine learning models. We trained the models in subjects with moderate to severe COPD from a subset of subjects in Genetic Epidemiology of COPD (COPDGene) and tested prediction performance in the remainder of individuals with moderate to severe COPD in COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared our model with the BMI, airflow obstruction, dyspnea, exercise capacity (BODE) index; BODE modifications; and the age, dyspnea, and airflow obstruction index. Results We included 2,632 participants from COPDGene and 1,268 participants from ECLIPSE. The top predictors of mortality were 6-min walk distance, FEV1 % predicted, and age. The top imaging predictor was pulmonary artery-to-aorta ratio. The MLMP-COPD model resulted in a C index ≥ 0.7 in both COPDGene and ECLIPSE (6.4- and 7.2-year median follow-ups, respectively), significantly better than all tested mortality indexes (P Interpretation An MLMP-COPD model outperformed four existing models for predicting all-cause mortality across two COPD cohorts. Performance of machine learning was similar to that of traditional statistical methods. The model is available online at: https://cdnm.shinyapps.io/cgmortalityapp/.

Background Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication. Aspergillus sensitisation may worsen symptoms in COPD. Methods We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC Aspergillus spp. and radiological findings. Given limited data on per-patient annual hospitalisation rates, we assumed a conservative 10.5% estimate. Annual IA mortality in COPD was estimated using the literature rates of 43–72%. A separate literature search assessed the impact of Aspergillus sensitisation on severity of COPD (by FEV1). Results We re-estimated the global prevalence of COPD GOLD stages II-IV at 552,300,599 people (7.39% of the population) with 339,206,893 (8.58%) in Asia, 85,278,783 (8.52%) in the Americas, 64,298,051 (5.37%) in Africa, 59,484,329 (7.77%) in Europe and 4,032,543 (10.86%) in Oceania. An estimated 57,991,563 (10.5%) people with COPD are admitted to hospital annually and of these 753,073 (1.3%) – 2,272,322 (3.9%) develop IA and 540,451–977,082 deaths are predicted annually. Aspergillus sensitisation prevalence in COPD was 13.6% (7.0–18.3%) and not related to lower predicted FEV1% (P > 0.05). Conclusions The prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS., The COS-AECOPD @EuroRespSoc Task Force is developing a core outcome set (COS) for #COPD exacerbation management. COS is an agreed minimum set of clinically important outcomes to be evaluated in all RCTs and can improve their usability and comparability. https://bit.ly/3ftAXk6

Long-acting bronchodilators represent the mainstay of maintenance treatment of chronic obstructive pulmonary disease (COPD). This state-of-the-art review summarizes currently available data on the safety, efficacy, and clinical effectiveness of long-acting bronchodilators and describes their role in the management of COPD, as defined by current national and international guidelines. Data from extensive clinical trials and real-life studies have demonstrated that long-acting beta-2 agonists and long-acting muscarinic antagonists can safely reduce the frequency of exacerbations, alleviate symptoms, and improve quality of life, exercise tolerance, and lung function of patients with COPD. They are recommended as first-line maintenance treatment of COPD.

Background Lung epithelial damage, activation of the wound healing cascade, and remodeling of the extracellular matrix (ECM) play a major role in chronic obstructive pulmonary disease (COPD). The pro-peptide of type VI collagen has been identified as the hormone endotrophin. Endotrophin has been shown to promote fibrosis and inflammation, whereas von Willebrand factor (VWF) is a crucial part of wound healing initiation. Here, we assessed the released and activated form of VWF and endotrophin, the pro-peptide of type VI collagen, serologically to investigate their association with mortality in COPD subjects alone or in combination. Methods One thousand COPD patients with 3 years of clinical follow-up from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort were included. Serum and heparin plasma were collected at 6 months and 1 year, respectively. Competitive ELISA utilizing specific monoclonal antibodies assessed endotrophin/type VI collagen formation (PRO-C6), VWF release (VWF-N), and activated VWF (VWF-A). Biomarker levels were dichotomized into high and low as defined by receiver operating characteristic (ROC) curves based on mortality data. Kaplan-Meier analysis was used to determine hazard ratios for all-cause mortality for biomarkers alone or in combination. Results High levels of PRO-C6, VWF-A, and VWF-N have previously been shown to be individually associated with a higher risk of mortality with hazard ratios of 5.6 (95% CI 2.4–13.1), 3.7 (1.8–7.6), and 4.6 (2.2–9.6), respectively. The hazard ratios increased when combining the biomarkers: PRO-C6*VWFA 8.8 (2.8–27.7) and PRO-C6*VWFN 13.3 (5.6–32.0). Notably, PRO-C6*VWF-N increased more than 2-fold. Conclusion We demonstrated that by combining two pathological relevant aspects of COPD, tissue remodeling, and wound healing, the predictive value of biomarkers for mortality increased notably.

Background Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state with intra-alveolar accumulation of fibrin and alveolar basement membrane destruction. This study aimed to investigate if the combination of two serological biomarkers evaluating these pathological processes could improve the prediction of mortality risk compared to single biomarkers. Methods Matrix metalloproteinase-mediated degradation of the type IV collagen α3 chain (C4Ma3), located in the alveolar basement membrane, and plasmin-mediated degradation of crosslinked fibrin (X-FIB), an end-product of fibrinogen, were assessed serologically in a subset of the ECLIPSE cohort (n = 982). Biomarker data were dichotomized into high versus low at the median. Cox regression and Kaplan-Meier curves were used to analyze the predictive value of having one or two high biomarkers for all-cause mortality over two years. Results COPD participants with high levels of two biomarkers were at significantly higher risk of all-cause mortality with a hazard ratio of 7.66 (95% CI 1.75–33.48; p = 0.007) while participants with one high biomarker were not at significantly higher risk (HR 3.79 [95% CI 0.85–16.94]; p = 0.08). Conclusions A combination of serological biomarkers of alveolar basement membrane destruction and clot resolution was predictive of all-cause mortality in COPD. The combination of two different pathological aspects may strengthen prognostic accuracy and could be used in conjunction with clinical assessment to guide treatment decisions.

Background Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH. Methods We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices. Results PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (−212 mL [95% confidence interval, −308 to −116 mL]), lower forced vital capacity (−208 mL [−322 to −93 mL]), and airflow limitation (aOR, 2.62 [1.58–4.36]) (all P Conclusion IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden. Their diagnosis, assessment and management remain suboptimal and unchanged for decades. Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically. This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes. This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. ispartof: THORAX vol:75 issue:6 pages:520-527 ispartof: location:England status: published

RationaleThere are no validated measures of disease activity in COPD. Since “active” disease is expected to have worse outcomes (e.g.mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality.MethodsWe investigated 1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; 2) whether these variables inter-relate; and 3) if any clinical, imaging and/or biological marker measured cross-sectionally at baseline relates to any activity component.ResultsResults showed that 1) after 1 year, hospitalisation for COPD, exacerbation frequency, worsening of body mass index, airflow obstruction, dyspnoea and exercise (BODE) index or health status (St George's Respiratory Questionnaire (SGRQ)) and persistence of systemic inflammation were significantly associated with 8-year mortality; 2) at 3 years, the same markers, plus forced expiratory volume in 1 s (FEV1) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; 3) changes in FEV1, inflammatory cytokines and CT emphysema were not inter-related, while the multidimensional indices (BODE and SGRQ) showed modest correlations; and 4) changes in these markers could not be predicted by any baseline cross-sectional measure.ConclusionsIn COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores and FEV1decline are independent markers of disease activity associated with 8-year all-cause mortality. These disease activity markers are generally independent and not predictable from baseline measurements.

IntroductionBoth stable chronic obstructive pulmonary disease (COPD) and acute exacerbations represent leading causes of death, disability and healthcare expenditure. They are complex, heterogeneous and their mechanisms are poorly understood. The role of respiratory viruses has been studied extensively but is still not adequately addressed clinically. Through a rigorous evidence update, we aim to define the prevalence and clinical burden of the different respiratory viruses in stable COPD and exacerbations, and to investigate whether viral load of usual respiratory viruses could be used for diagnosis of exacerbations triggered by viruses, which are currently not diagnosed or treated aetiologically.Methods and analysisBased on a prospectively registered protocol, we will systematically review the literature using standard methods recommended by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group. We will search Medline/PubMed, Excerpta Medica dataBASE (EMBASE), the Cochrane Library, the WHO’s Clinical Trials Registry and the proceedings of relevant international conferences on 2 March 2020. We will evaluate: (A) the prevalence of respiratory viruses in stable COPD and exacerbations, (B) differences in the viral loads of respiratory viruses in stable COPD vs exacerbations, to explore whether the viral load of prevalent respiratory viruses could be used as a diagnostic biomarker for exacerbations triggered by viruses and (C) the association between the presence of respiratory viruses and clinical outcomes in stable COPD and in exacerbations.Ethics and disseminationEthics approval is not required since no primary data will be collected. Our findings will be presented in national and international scientific conferences and will be published in peer reviewed journals. Respiratory viruses currently represent a lost opportunity to improve the outcomes of both stable COPD and exacerbations. Our work aspires to ‘demystify’ the prevalence and clinical burden of viruses in stable COPD and exacerbations and to promote clinical and translational research.PROSPERO registration numberCRD42019147658.

The DisEntangling Chronic Obstructive pulmonary Disease Exacerbations clinical trials NETwork: #DECODE_NET. Vision statement of an emerging, global network aiming to conduct collaborative clinical research on COPD exacerbation management @ERSpublicationshttps://bit.ly/36kISgp

We wish to thank Britton et al. for responding to our editorial and giving us an opportunity to clarify our position as well as correct a few misunderstandings. We definitely share the same goal which is to relieve Europe and the rest of the world from the terrible results of the tobacco epidemic. We also do not “blankly oppose e-cigarettes”; however, we strongly advocate against a harm reduction strategy including e-cigarettes as well as heated tobacco products [1]. As clinicians we all see reluctant smokers where e-cigarettes can be tried as a last resort for getting off cigarette smoking - but that is of little relevance for a general harm reduction strategy. We also agree that the UK has achieved a lot in the area of smoking cessation but would argue that this has been achieved by impressive tobacco control – not by the use of e-cigarettes and that countries like Australia, that has banned nicotine-containing e-cigarettes, has achieved similar results. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Pisinger has nothing to disclose. Conflict of interest: Dr. Vestbo reports personal fees from AstraZeneca, grants and personal fees from Boehringer-Ingelheim, personal fees from Chiesi, personal fees from GSK, personal fees from Novartis, outside the submitted work; and his son is an employee of Chiesi.

Background Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls. Methods PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of >1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta. Results In total, 900 PWH were included, and 44 (5%) had a pulmonary artery–aorta ratio (PA:A) >1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76–10.65; P = .001) and injection drug use (IDU) (4.90; 1.00–18.46; P = .03) were associated with higher odds of having a PA:A >1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A >1 (adjusted odds ratio, 1.89; 95% confidence interval, .92–3.85; P = .08). Conclusions A PA:A >1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU.

BackgroundDifferent airflow limitation criteria are often used to diagnose COPD. We investigated head-to-head whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) (FEV1/FVC 1/FVC Methods108 246 individuals aged 20–100 years randomly selected from the general population were followed from 2003 through 2018 to determine risk of COPD exacerbations, respiratory mortality and all-cause mortality. LLN criteria used equations from Global Lung Initiative (GLI), National Health and Nutrition Examination Survey (NHANES), European Community for Steel and Coal (ECSC) and Copenhagen City Heart Study (CCHS)/Copenhagen General Population Study (CGPS).ResultsPrevalence of airflow limitation was 17% for GOLD, 8.6% for GLI, 10% for NHANES, 8.2% for ECSC and 14% for CCHS/CGPS. During 14.4 years follow-up, we observed 2745 COPD exacerbations, 762 respiratory deaths and 10 338 all-cause deaths. Comparing individuals with versus without airflow limitation, HRs for COPD exacerbations were 17 (95% CI 14 to 20) for GOLD, 21 (18 to 24) for GLI, 20 (17 to 23) for NHANES, 21 (18 to 24) for ECSC and 18 (16 to 21) for CCHS/CGPS. Corresponding HRs for respiratory mortality were 3.7 (3.1 to 4.3), 6.4 (5.6 to 7.5), 5.7 (4.9 to 6.6), 6.2 (5.3 to 7.2) and 4.5 (3.9 to 5.2), and for all-cause mortality 1.5 (1.4 to 1.5), 1.9 (1.8 to 2.0), 1.8 (1.7 to 1.9), 1.9 (1.8 to 2.0) and 1.7 (1.6 to 1.7), respectively. Differences in Harrell’s C were minute for these outcomes; nonetheless, Harrell’s C was slightly higher for LLN criteria compared with GOLD for mortality outcomes.ConclusionsThe prevalence of airflow limitation ranged from 8% to 17% using GOLD and four different LLN criteria; however, identified individuals with the five different criteria had similar risk of COPD exacerbations and mortality.

Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant- and fungal-derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.

Background: Elevated eosinophils in COPD is recognized as a potential risk factor for exacerbations, but the prognostic role of elevated eosinophils during exacerbations of COPD is unclear. We investigated short-term and long-term outcomes in patients with exacerbations of eosinophilic phenotype, compared with patients with low blood eosinophils. Methods: A single-centre retrospective study of all patients admitted for a COPD exacerbation to Bispebjerg University Hospital in 2010–2011 was established by linking inpatient data with national patient and prescription registries, with a three-year follow-up period. Elevated eosinophils were defined as a blood eosinophil level at admission of ≥0.30 × 109 cells/L. Results: A total of 811 patients were included; 13.2% had an eosinophilic exacerbation. The eosinophilic group had less need for non-invasive ventilation, shorter inpatient stay, and lower in-hospital mortality, compared to the non-eosinophilic group. However, the eosinophilic and non-eosinophilic groups showed similar risks of readmission (incidence rate ratio[95], 0.99 [0.73–1.36]). Three-year mortality was high in both groups, although lower in the eosinophilic group (40% vs. 54%, p = 0.006). Conclusions: COPD exacerbations in patients with high blood eosinophil have a better short-term prognosis without higher risk of subsequent exacerbation. Eosinophilic exacerbations have also a lower three-year mortality.

There is an emerging role for blood eosinophil count (EOS) as a biomarker to guide inhaled corticosteroid (ICS) therapy in COPD. Since ICS administration could influence EOS, we hypothesised that change in EOS following treatment with ICS may predict outcomes of long-term therapy.In a post hoc analysis of ISOLDE, a 3-year, double-blind trial comparing 500 µg fluticasone propionate twice daily with placebo in 751 patients with moderate-to-severe COPD, we evaluated whether the initial changes in EOS during ICS treatment were predictive of ICS treatment response.EOS change within 1 year after the introduction of ICS was strongly predictive of treatment response. A suppressed EOS was associated with treatment effect. Characteristically, in patients with EOS suppression of ≥200 cells·μL−1, ICS use was associated with a decelerated rate of decline of forced expiratory volume in 1 s (FEV1), by 32 mL·year−1, and a 30% reduction in the exacerbation rate. In contrast, in patients experiencing an increase in EOS of ≥200 cells·μL−1, ICS use was associated with an accelerated rate of decline of FEV1, by 37 mL·year−1 and an 80% increase in the exacerbation rate (pThese findings suggest that EOS change after ICS administration may predict clinical response to ICS therapy in patients with moderate-to-severe COPD at risk of exacerbations. ICS administration may be associated with more frequent exacerbations and an accelerated lung function decline in the 20% of patients in whom EOS increases after the administration of ICS. These hypothesis-generating observations will need validation in prospectively designed studies.The ISOLDE trial was conducted before the ICJME recommended a prospective registration of RCT protocols.

Objectives: Cardiovascular disease is often associated with COPD. Lung density quantification of images obtained from cardiac computed tomography (CT) scans would allow simultaneous evaluation of emphysema and coronary artery calcification score and provide further mechanistic insight into the relationship between these syndromes.Patients and methods: We assessed the agreement between lung density indices obtained by cardiac and full-lung CT scans. Paired cardiac and chest CT scans were assessed in 156 individuals with and without airflow limitation. Quantitative threshold indices of low attenuation area (LAA) and 15th percentile density index (PD15) were compared in terms of precision using Spearman’s correlation coefficient, accuracy using concordance correlation coefficient (CCC), and relative accuracy using P15 and P30. We also assessed the relationship between visually and quantitatively determined emphysema and used receiver operating characteristic curves to evaluate the ability of lung density indices to discriminate airflow limitation.Results: Correlation coefficients between lung density indices obtained from cardiac and chest CT scans were 0.49 for percent LAA (%LAA)-950 and 0.71 for PD15. Corresponding values for CCC, P15, and P30 were 0.33, 3.2, and 5.1, respectively, for %LAA-950, and 0.34, 17.3, and 37.8, respectively, for PD15. For both cardiac and chest CT scans, visually determined emphysema was associated with higher %LAA-950 and lower PD15, and the ability of %LAA-950 and PD15 to discriminate airflow limitation were comparable.Conclusion: Although chest CT imaging is preferable, cardiac CT imaging may also be used for lung emphysema quantification where association measures are of primary interest. Objectives: Cardiovascular disease is often associated with COPD. Lung density quantification of images obtained from cardiac computed tomography (CT) scans would allow simultaneous evaluation of emphysema and coronary artery calcification score and provide further mechanistic insight into the relationship between these syndromes.Patients and methods: We assessed the agreement between lung density indices obtained by cardiac and full-lung CT scans. Paired cardiac and chest CT scans were assessed in 156 individuals with and without airflow limitation. Quantitative threshold indices of low attenuation area (LAA) and 15th percentile density index (PD15) were compared in terms of precision using Spearman’s correlation coefficient, accuracy using concordance correlation coefficient (CCC), and relative accuracy using P15 and P30. We also assessed the relationship between visually and quantitatively determined emphysema and used receiver operating characteristic curves to evaluate the ability of lung density indices to discriminate airflow limitation.Results: Correlation coefficients between lung density indices obtained from cardiac and chest CT scans were 0.49 for percent LAA (%LAA)-950 and 0.71 for PD15. Corresponding values for CCC, P15, and P30 were 0.33, 3.2, and 5.1, respectively, for %LAA-950, and 0.34, 17.3, and 37.8, respectively, for PD15. For both cardiac and chest CT scans, visually determined emphysema was associated with higher %LAA-950 and lower PD15, and the ability of %LAA-950 and PD15 to discriminate airflow limitation were comparable.Conclusion: Although chest CT imaging is preferable, cardiac CT imaging may also be used for lung emphysema quantification where association measures are of primary interest.

Alicia Gayle,1 Scott Dickinson,2 Kevin Morris,1 Chris Poole,1 Alexander G Mathioudakis,3 Jørgen Vestbo3,4 1Market Access, Boehringer Ingelheim Ltd, Bracknell, UK; 2Medical and Scientific Affairs, Boehringer Ingelheim Ltd, Bracknell, UK; 3Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 4Manchester Academic Health Sciences Centre, Manchester University NHS Foundation Trust, Manchester, UK Purpose: The changes in grading of disease severity and treatment recommendations for patients with COPD in the 2017 GOLD strategy may present an opportunity for reducing treatment burden for the patients and costs to the health care system. The aim of this study was to assess the implications of the GOLD 2017 grading system in terms of change in distribution across GOLD groups A–D for existing patients in UK primary care and estimate the potential cost savings of implementing GOLD 2017 treatment recommendations in UK primary care.Patients and methods: Using electronic health record data from the Clinical Practice Research Datalink (CPRD), patients aged ≥35 years with spirometry-confirmed COPD, receiving care during 2016, were included. The cohort was graded according to the GOLD 2017 groups (A–D), and treatment costs were calculated, according to corresponding recommendations, to observe the difference in actual vs predicted costs.Results: When applying GOLD 2013 criteria, less than half of the cohort (46%) was assigned to GOLD A or B, as compared to 86% when applying the GOLD 2017 grading. The actual mean annual maintenance treatment cost was £542 per patient vs a predicted £389 for treatment according to the 2017 GOLD strategy.Conclusion: There is a potential to make significant cost savings by implementing the grading and treatment recommendations from the 2017 GOLD strategy. Keywords: COPD, GOLD, severity, economicsErratumfor this paper has been published.&nbsp

Objectives Chronic obstructive pulmonary disease (COPD) is underdiagnosed in the general population and possibly also in people living with HIV (PLWH). We evaluated the diagnostic performance of symptoms and risk factors for assessment of airflow limitation in PLWH and in uninfected controls. Methods Spirometry was performed in the Copenhagen Comorbidity in HIV Infection (COCOMO) study and Copenhagen General Population Study (CGPS), and airflow limitation was defined by forced expiratory volume in 1 s/forced vital capacity < lower limit of normal. We calculated the sensitivity, specificity, predictive values and area under the curve (AUC) of symptoms and risk factors for assessment of airflow limitation in PLWH and uninfected controls. Results A total of 1083 PLWH and 12 074 uninfected controls were included in the study. The sensitivity for sputum, chronic cough, breathlessness, wheezing, current and cumulative smoking and self‐reported COPD was higher, but the specificity lower, in PLWH than in uninfected controls. The negative and positive predictive values were largely similar between the groups. The AUCs were similar or slightly higher in PLWH and highest for > 20 pack‐years smoked [0.65; 95% confidence interval (CI) 0.58–0.72] and wheezing (0.64; 95% CI 0.57–0.71). A summed score for five variables was associated with slightly higher AUC in PLWH compared with uninfected controls [0.71 (95% CI 0.63–0.79) versus 0.65 (95% CI 0.63–0.68), respectively; P = 0.06]. Conclusions Clinical variables were relatively poor discriminators of airflow limitation in PLWH and uninfected controls. Active COPD case finding by screening for symptoms and relevant exposures, as recommended in the general population, is likely to yield similar diagnostic power in PLWH.

Aims To characterize the relationship between blood pressure (BP) or heart rate and mortality and morbidity in chronic obstructive pulmonary disease (COPD). Methods and results We performedpost hoc analysis of baseline BP or heart rate and all-cause mortality and cardiovascular events in the SUMMIT trial. SUMMIT was a randomized double-blind outcome trial of 16 485 participants (65 ± 8 years, 75% male, and 47% active smokers) enrolled at 1368 sites in 43 countries. Participants with moderate COPD with or at risk for cardiovascular disease (CVD) were randomized to placebo, long-acting beta agonist, inhaled corticosteroid, or their combination. All-cause mortality increased in relation to high systolic [≥140 mmHg; hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12–1.45] or diastolic (≥90 mmHg; HR 1.35, 95% CI 1.14–1.59) BP and low systolic ( Conclusion A ‘U-shaped’ relationship between BP and all-cause mortality and cardiovascular events exists in patients with COPD and heightened cardiovascular risk. A linear relationship exists between heart rate and all-cause mortality and cardiovascular events in this population. These findings extend the prognostic importance of BP to this growing group of patients and raise concerns that both high and low BP may pose health risks.