Opportunistic screening for COPD among socially marginalized patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease associated with premature death. Tobacco exposure is the main risk factor, but lower socioeconomic status, early life insults, and occupational exposures are also important risk factors. Socially marginalized people, facing homelessness, substance use disorder, and mental illness, are likely to have a higher risk of developing COPD, and, furthermore, experience barriers to healthcare access and consequently poorer outcomes. OBJECTIVE: This study aims to assess COPD prevalence and the impact of opportunistic screening among hospitalized patients who are in contact with hospital social nurses. These patients constitute a group of patients with a high prevalence of psychiatric and somatic diseases, substance use, low life expectancy, and are socially marginalized. METHODS: The present prospective longitudinal study includes a clinical examination at baseline. Participants will have spirometry done and be interviewed regarding risk factors, socioeconomic conditions, and respiratory symptoms. The 5-year follow-up assessment incorporates data from baseline and register data over the 5 years, including information on morbidity, use of COPD medication, hospital contacts, mortality, and socioeconomic factors. ANTICIPATED RESULTS: Referral for further diagnostic work-up and management after the screening, including COPD treatment and smoking cessation support, is expected to improve survival rates. The study is still enrolling patients. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov , NCT04754308 with study status: "enrolling".

Biomarker-guided withdrawal of inhaled corticosteroids in asthma patients with a non-T2 inflammatory phenotype - a randomized controlled trial study protocol.

BACKGROUND: Non-T2 asthma is characterized by the absence of elevated type 2 inflammatory biomarkers such as blood-eosinophils, total and allergen-specific Immunoglobulin E and Fractional exhaled Nitric Oxide (FeNO). According to guidelines, inhaled corticosteroids (ICS) are the cornerstone of asthma management. However, ICS treatment is associated with a risk of local side effects, including hoarseness and thrush, and long-term high-dose therapy may cause systemic adverse effects. Furthermore, whereas treatment with ICS is highly effective in T2 asthma, studies have shown a markedly reduced ICS efficacy in patients with a lower degree of T2 inflammation, thus posing a clinical challenge in this subgroup of patients. Hence, owing to the ICS dosage step-up approach in current clinical guidelines, patients with low T2 biomarkers are at risk of being exposed to high doses of ICS, and by that at risk of side effects. Thus, an ICS-treatment regime guided by biomarkers that reflects the inflammatory phenotype is warranted in order to reduce the corticosteroid burden in patients with non-T2 asthma. This study combines a panel of non-T2 inflammatory markers (low periostin, low blood-eosinophils, and low FeNO), to determine if this group of patients can maintain asthma control during ICS withdrawal. METHODS: This is an ongoing prospective multicenter open-label randomized, controlled trial aiming to assess if ICS can be safely tapered in patients with non-T2 asthma. The patients are randomized 1:1 to either standard of care or an ICS tapering regimen (n = 55 in each group) where the initial ICS dose is reduced by 50% for 8 weeks followed by total ICS removal. The primary endpoint is change in asthma control questionnaire (ACQ) from baseline to post-tapered ICS. The secondary endpoints are time from baseline to drop-out caused by loss of asthma control, changes in serum-periostin, blood-eosinophils, FeNO, Forced Expiratory Volume in 1 s (FEV1) and in sputum-eosinophils. DISCUSSION: This study aims to provide data on ICS tapering in non-T2 asthma patients and to contribute to a more individualized and corticosteroid-sparing treatment regime in this group of patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03141424. Registration date: May 5th, 2017.

Pulmonary telerehabilitation vs. conventional pulmonary rehabilitation - a secondary responder analysis.

Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups in 134 patients with COPD randomised (1:1) to either home-based PTR or traditional hospital-based outpatient PR. Difference between PTR and PR on 6MWD response proportion could not be shown at 10 (OR=0.72, CI=0.34 to 1.51, p=0.381) or 62 weeks (OR=1.12, CI=0.40 to 3.14, p=0.834). While the evidence and knowledge of PTR accumulate, outpatient supervised PR for now remains the standard of care, with home-based PTR as a strong secondary option for those unable to attend out-patient programmes.

Impact of offspring and their educational level on readmission and death among older adults with chronic obstructive pulmonary disease: a nationwide cohort study using multistate survival models.

BACKGROUND: It is well described that there is social inequality in the disease course of chronic obstructive pulmonary disease (COPD), but the impact of social relations is less explored. We aimed to investigate the impact of adult offspring and their educational level on readmission and death among older adults with COPD. METHODS: In total, 71 084 older adults born 1935-53 with COPD diagnosed at age ≥65 years in 2000-2018 were included. Multistate survival models were performed to estimate the impact of adult offspring (offspring (reference) vs no offspring) and their educational level (low, medium or high (reference)) on the transition intensities between three states: COPD diagnosis, readmission and all-cause death. RESULTS: During follow-up, 29 828 (42.0%) had a readmission and 18 504 (26.0%) died with or without readmission. Not having offspring was associated with higher hazards of death without readmission (HRwomen: 1.52 (95% CI: 1.39 to 1.67), HRmen: 1.29 (95% CI: 1.20 to 1.39)) and a higher hazard of death after readmission for women only (HRwomen: 1.19 (95% CI: 1.08 to 1.30). Having offspring with low educational level was associated with higher hazards of readmission (HRwomen: 1.12 (95% CI: 1.06 to 1.19)), (HRmen: 1.06 (95%CI: 1.002 to 1.12)), death without readmission (HRwomen: 1.24 (95% CI: 1.11 to 1.39)), HRmen: 1.16 (95% CI: 1.05 to 1.29) and death after readmission for men only (HRmen: 1.15 (95% CI: 1.05 to 1.25)). Having offspring with medium educational level was associated with a higher hazard of death without readmission for women (HRwomen: 1.11 (95% CI: 1.02 to 1.21)). CONCLUSION: Adult offspring and their educational level were associated with higher risk of readmission and death among older adults with COPD.

Sleep Quality and Self-Reported Symptoms of Anxiety and Depression Are Associated with Physical Activity in Patients with Severe COPD.

Sleep quantity, quality and symptoms of depression or anxiety potentially affect the level of daily physical activity (PAL) and plausibly counteracts benefits from pulmonary rehabilitation programs. Their collective impact on PAL is sparsely investigated, particularly in patients with severely progressed chronic obstructive pulmonary disease (COPD). Aim: To investigate if sleep quantity, quality and symptoms from self-reported hospital anxiety and depression scores (HADS) are associated with PAL. Methods: In this exploratory cross-sectional study data were analysed from 148 participants with COPD; GOLD grade II-IV; GOLD group B to D (52% female, mean 69.7 ± SD of 8.4 years, FEV1% predicted 33.6 ± 10.9, 6MWD 327 ± 122 m, CAT 20 ± 7 points), eligible for conventional outpatient hospital-based pulmonary rehabilitation. Participants had sleep and PAL measured 24 h per day for five consecutive days with an activPAL monitor. Adjusted negative binomial regression was applied to investigate the associations with PAL. Results: Participants walked median (25th, 75th percentile) of 2358 (1325.75; 3822.25) steps per day and 14% walked >5000 steps per day on average. Time in bed (TIB) were a median (25th, 75th percentile) of 8.3 (7.1; 9.7) hours and numbers of nocturnal sleeping bouts (NSB) were 1.5 (0.8; 3), Anxiety (HADS-A) and depression (HADS-D) scores were median (25th, 75th percentile) of 5 (3; 8) points and 3 (2; 6) points, respectively, whereof 29% (HADS-A) and 15% (HADS-D) reported scores ≥8 points indicating significant symptoms. The fully adjusted rate ratio (RR) for steps per day for TIB (hours) [RR 0.97 (95% CI: 0.92; 1.02)], NSB (numbers) [RR 1.02 (95% CI: 0.97; 1.07)] were not significantly associated with number of steps per day, while there was a significantly association with number of steps per day for HADS-A [RR 1.04 (95% CI: 1.01; 1.07)] and HADS-D [RR 0.95 (95% CI: 0.91; 0.99)]. Conclusion: This exploratory cross-sectional study found a statistically significant association between HADS-A and HADS-D with numbers of steps per day in patients with severe COPD.

High-protein diet during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

INTRODUCTION: The prevalence of cachexia in patients with chronic obstructive pulmonary disease (COPD) is high and associated with reduced quality of life, increased mortality and morbidity. We aimed to test the effect of a high protein diet combined with exercise on fat-free mass (FFM), functional capacity, symptom burden and dyspnoea. METHODS: Outpatients with COPD and severe or very severe (GOLD grade III-IV) disease and malnutrition commencing pulmonary rehabilitation were randomised to a high-protein diet or standard care. FFM was measured by bio-impedance analysis (BIA), mid-upper arm circumference (MUAC) and mid-thigh circumference (MTC), peripheral muscle function by six-minute walking distance (6MWD) and handgrip strength (HGS), symptoms by the COPD Assessment Trial (CAT) and dyspnoea by the Medical Research Council dyspnoea scale and Borg scores; all at baseline and after 12 weeks. RESULTS: Ten out of 13 randomised patients completed the trial. The intervention group was superior to the control group with respect to 6MWD (97 ± 93 m, p = 0.04) at 12 weeks. No differences were observed between the groups in HGS, anthropometrics, symptom burden or dyspnoea. CONCLUSION: In patients with COPD attending rehabilitation, a high protein diet combined with physical exercise had a clinically relevant effect on walking distance. FUNDING: none. TRIAL REGISTRATION: NCT04888182.

A systematic review of blood eosinophils and continued treatment with inhaled corticosteroids in patients with COPD.

Inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD) has been debated for 20 years. In our systematic literature review and meta-analysis, we addressed the following: Should patients with COPD and a blood eosinophil count (EOS) of, respectively, a) < 150 cells/µl, b) 150-300 cells/µl, and c) > 300 cells/µl continue treatment with ICS? Protocol registered in PROSPERO (CRD42020178110) and funded by the Danish Health Authority. We searched Medline, Embase, CINAHL and Cochrane Central on 22nd July 2020 for randomized controlled trials (RCT) of ICS treatment in patients with COPD (≥40 years, no current asthma), which analyzed outcomes by EOS count and where >50% of patients used ICS prior. We used the GRADE method. Meta-analyzes for the outcomes were divided into EOS subgroups and analyzed for differences. We identified 11 RCTs with a total of 29,654 patients. A significant difference (p < 0.00001) between the three subgroups' reduction of risk of moderate to severe exacerbation was found. Rate ratios for EOS counts: <150 cells/µL was 0.88 (95%CI: 0.83, 0.94); 150-300 cells/µL was 0.80 (95%CI: 0.69, 0.94); >300 cells/µL was 0.57 (95%CI: 0.49, 0.66). Overall, the certainty of the effect estimates was low to very low due to risk of bias, unexplained heterogeneity, few RCTs, and wide confidence intervals. A clear correlation was demonstrated between effect of continued ICS treatment (number of exacerbations, lung function, and quality of life) and increasing EOS count. Our meta-analyses suggested that treatment with ICS seemed beneficial for everyone except patients with EOS count below 150 cells/µl.

Beta-Blockers in High-Risk Outpatients with Chronic Obstructive Pulmonary Disease are Associated with All-Cause Mortality - The STATUETTE Cohort Study.

Background: Beta-blockers have been proposed to improve COPD-related outcomes, yet studies report conflicting results. We aimed to investigate the effect of beta blockers on time-to-first exacerbation and all-cause mortality in high-risk COPD outpatients. Methods: All COPD outpatients managed at the Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Denmark in 2016 were followed for 3.5 years in this retrospective, registry-based cohort study. Outcomes were time-to-first acute exacerbation of COPD (AECOPD) or death. The association was estimated using time-varying crude and multivariable Cox proportional hazard regression adjusted for age, sex, BMI, use of COPD medication, smoking status, cardiovascular disease and COPD severity. Results: The cohort comprised 950 COPD outpatients, mean age 71 (SD 11) years, and FEV1 44% predicted (IQR 33%; 57%). The annual exacerbation rate was 0.88 (SD 1.68) and 211 patients (22%) had a history of hospitalization requiring AECOPD within 12 months. Of the enrolled patients, 247 (26%) were prescribed beta blockers. Beta-blocker use was associated, although with borderline significance, with increased all-cause mortality (HR 1.37 (95% CI, 0.99 to 1.89, p = 0.059)). On the other hand, beta blocker use did not reduce the risk of AECOPD (HR = 0.89 (95% CI 0.71 to 1.10; p = 0.270)), which remained non-significant after stratifying for severity of exacerbations. Conclusion: We found an association between beta blocker use and all-cause mortality in high-risk COPD outpatients. No association was found between beta blocker use and risk of AECOPD.

Characteristics of COPD Patients Prescribed ICS Managed in General Practice vs. Secondary Care.

Inhaled corticosteroids (ICS) for COPD have been much debated. Our aim was to investigate characteristics of ICS prescribed COPD patients managed only in general practice compared to those also managed in secondary care. Participating general practitioners recruited patients with COPD (ICPC 2nd ed. code R95) currently prescribed ICS (ACT code R03AK and R03BA). Data on demographics, comorbidities, smoking habits, spirometry, dyspnea score and exacerbation history were retrieved from medical records. Logistic regression analysis was applied to detect predictors associated with management in secondary care. 2,279 COPD patients (45% males and mean age 71 years) were recruited in primary care. Compared to patients managed in primary care only (n = 1,179), patients also managed in secondary care (n = 560) were younger (p = 0.013), had lower BMI, more life-time tobacco exposure (p = 0.03), more exacerbations (p < 0.001) and hospitalizations (p < 0.001) and lower FEV1/FVC-ratio (0.59 versus 0.52, respectively). Compared to patients managed in only primary care, logistic regression analysis revealed that management also in secondary care was associated to MRC-score ≥3 (OR 2.70; 95% CI 1.50-4.86; p = 0.001), FEV1%pred (OR 0.98; 95% CI 0.95 to 0.99; p = 0.036), and systemic corticosteroids for COPD exacerbation (OR 1.44; 95% CI 1.10-1.89; p = 0.008). In COPD patients prescribed ICS recruited in primary care, patients also managed in secondary care had more respiratory symptoms, lower lung function and exacerbations treated with systemic corticosteroids indicating that the most severe COPD patients, in general, are referred for specialist care.

Systemic Corticosteroids and the Risk of Venous Thromboembolism in Patients with Severe COPD: A Nationwide Study of 30,473 Outpatients.

Due to frequent exacerbations, many patients with chronic obstructive pulmonary disease (COPD) are exposed to oral corticosteroids (OCS), which may be thrombogenic. We evaluated the risk of hospitalisation with venous thromboembolism (VTE) and death in patients with acute exacerbation of COPD (AECOPD) treated with long and short OCS regimens. In this nationwide cohort study of 30,473 COPD outpatients treated for AECOPD, we compared the risk of VTE hospitalisation and all-cause mortality within 6 months in OCS dose of >250 mg vs. ≤250 mg. A multivariable Cox proportional hazard regression was used to estimate the risk. The incidence of VTE hospitalisations was 0.23%. A long OCS treatment course was associated with an increased risk of VTE compared to a short course (hazard ratio (HR) 1.69, [95% confidence interval (CI) 1.05 to 2.72], p < 0.031). A higher risk of all-cause mortality was seen in the group of COPD patients treated with a long OCS course (HR 1.71, [95% CI 1.63 to 1.79], p < 0.0001). The risk of reported VTE hospitalisation was higher among AECOPD patients treated with long courses of OCS, but the absolute risk was low, suggesting under-reporting of the condition.

Inter-Day Test-Retest Reproducibility of the CAT, CCQ, HADS and EQ-5D-3L in Patients with Severe and Very Severe COPD.

INTRODUCTION: In patients with COPD, the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and EuroQol 5D (EQ-5D-3L) are widely used patient reported outcome measures (PROMs) of respiratory symptoms, anxiety, depression and quality of life. Despite established validity, responsiveness and minimal important change (MIC), the reproducibility and especially important agreement parameters remain unreported in these frequently used PROMs. The aim of this study was to investigate the inter-day test-retest reliability and agreement of the CAT, CCQ, HADS and EQ-5D-3L in patients with severe and very severe COPD (FEV1 <50%) eligible for hospital-based pulmonary rehabilitation. PATIENTS AND METHODS: Fifty patients (22 females, mean [SD] age 67 [9] yrs.; FEV1 32[9] %; 6-minute walk distance 347 [102] meters; CAT 21 [6] points; BMI: 26 [6] kg/m2) completed the questionnaires (CAT, CCQ, HADS, EQ-5D-3L) in combination with functional performance test instructed by one assessor on test-day one (T1) and by another assessor 7-10 days later on test-day two (T2). RESULTS: The inter-day test-retest reliability ICC was 0.88 (LL95CI: 0.80) for CAT; 0.69 (LL95CI: 0.46) for CCQ; 0.86 (LL95CI: 0.75) and 0.90 (LL95CI: 0.82) for HADS-anxiety (A) and depression (D) and 0.87 (LL95CI: 0.76) for EQ-5D-VAS. The corresponding agreements within a single measurement (standard error of measurement, SEM) and for repeated measurement errors (smallest real difference, SRD) were respectively 2.1 and 2.9 points for CAT; 0.5 and 0.7 points for CCQ total; 1.3 and 1.9 points for HADS-A; 0.9 and 1.3 points for HADS-D and 6.8 and 9.7 VAS-score for EQ-5D-3L, respectively. Ceiling/flooring effect was present in <5% for all questionnaires. CONCLUSION: In patients with severe and very severe COPD, the CAT, CCQ, HADS and EQ-5D-3L questionnaires presented moderate to excellent inter-day test-retest reliability, and no floor or ceiling effect was documented for any of the questionnaires. Only CAT and HADS had an acceptable SRD below the established MIC for assessing change over time on group level, and none of the PROMS were fit to assess individual changes over time.

Statins in High-Risk Chronic Obstructive Pulmonary Disease Outpatients: No Impact on Time to First Exacerbation and All-Cause Mortality - The STATUETTE Cohort Study.

BACKGROUND: Statins have, due to their anti-inflammatory properties, been suggested to potentially improve chronic obstructive pulmonary disease (COPD) outcomes. We aimed to investigate the effect of statins on time to first exacerbation and all-cause mortality in high-risk COPD outpatients. METHODS: All outpatients with COPD seen at the Department of Respiratory Medicine, Copenhagen University Hospital Amager and Hvidovre, Denmark in 2016 were identified and followed for 3.5 years in this retrospective, registry-based cohort study of time to first acute exacerbation of COPD (AECOPD) or death. AECOPD was defined as a rescue course of oral corticosteroid and/or hospital admission. The association was estimated using time-varying crude and multivariable Cox proportional hazard regression. RESULTS: The cohort comprised 950 COPD outpatients, mean (SD) age 71 (11) years, and FEV1 44% predicted (IQR 33%; 57%). The annual exacerbation rate was 0.88 (1.68) and 211 patients (22%) had a history of hospital admission for AECOPD in the 12 months prior to index date. Three hundred and ninety-three patients (41.4%) were defined as statin users, with 131 (33.3%) having filled the first prescription for statin after index date. Statin use was not associated with reduced risk of AECOPD. When stratifying for moderate and severe exacerbations in a sub-analysis in the same model, statin use did not have an increased HR for exacerbation of either severity (HR = 1.02 (95% CI 0.85to 1.24; p = 0.811) and HR = 1.07 (95% CI 0.89 to 1.29; p = 0.492) respectively). Statin use was not associated with all-cause mortality (HR 1.05 (95% CI, 0.75 to 1.47, p = 0.777)). CONCLUSION: We did not find any association between statin use and risk of AECOPD or all-cause mortality. The result adds to the evidence that an aggressive approach with statin treatment upfront is not beneficial in COPD, unless prescribed according to current guidelines for cardiovascular diseases.

[Smoking is associated with health risks even when cessation is before the age of 30 years].

It is broadly believed that smokers who have ceased to smoke before the age of 30 years, have no excess health risk compared with never-smokers. As summarised in this review, large, prospective cohort studies show, that this holds true regarding all-cause mortality for men, whereas the risk of dying remains slightly elevated for women, who quit smoking early. The risk of lung cancer also remains elevated. Smoking also increases the risk of physical and mental problems in youth. The evidence is strongest regarding infertility, impotence, reproductive health outcomes, cardio-vascular and respiratory symptoms.

COPD patients prescribed inhaled corticosteroid in primary care: time for re-assessment based on exacerbation rate and blood eosinophils?

BACKGROUND AND OBJECTIVE: Inhaled corticosteroid (ICS) therapy for COPD should be guided by exacerbations and blood-eosinophils according to the GOLD 2020 strategy document. In the present study, we applied these recent recommendations in a large cohort of COPD patients recruited from general practice. METHODS: The participating general practitioners (n = 144) recruited patients with a diagnosis of COPD currently prescribed ICS and reported data on exacerbation history and blood-eosinophils. Clinical variables were compared using two-sample t-tests. RESULTS: The study cohort comprised 1,567 COPD patients (44% males and mean age 72 years). In the past 12 months, 849 (54%) of the COPD patients currently prescribed ICS had no exacerbation, whereas 383 (24%) and 328 (21%) patients, respectively, had a history of one exacerbation and two or more exacerbations. Compared to patients with one or no exacerbation, patients with ≥ 2 exacerbations (21%) per year reported more dyspnea (p < 0.001) and had higher degree of airflow obstruction (p < 0.001). Among patients with no and at least one exacerbation within the preceding 12 months, 30% and 26%, respectively, had a blood-eosinophil count ≥ 0.3 × 109/L. In patients with two or more exacerbations within the last 12 months, 77% had a blood-eosinophil count of ≥ 0.1 × 109/L. Furthermore, 166 patients (11%) had at least one hospital admission due to COPD exacerbation, and a blood-eosinophil count of ≥ 0.1 × 109/L. CONCLUSION: This study of a large cohort of COPD patients currently prescribed inhaled corticosteroids suggests the need for re-evaluating the management strategy to increase benefit and reduce adverse effects of ICS treatment in COPD patients managed in primary care.

Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial.

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.

12-months follow-up of pulmonary tele-rehabilitation versus standard pulmonary rehabilitation: A multicentre randomised clinical trial in patients with severe COPD.

Between March 2016 and October 2017, we randomised 134 patients with severe COPD from 8 hospitals in the Capital Region of Denmark to participate in either standardised, outpatient pulmonary rehabilitation (control group) or on-line, supervised and home-based tele-rehabilitation (intervention group). We found no difference between the groups in the primary outcome: six minutes walking distance (6MWD) after completion of the programme. The current study presents results from the 12-month follow-up with assessment of the 6MWD and analyses of hospitalisation and mortality. There were no significant differences between or within the groups in the 6MWD one year after completion of the programme.

TOB-STOP-COP (TOBacco STOP in COPd trial): study protocol-a randomized open-label, superiority, multicenter, two-arm intervention study of the effect of "high-intensity" vs. "low-intensity" smoking cessation intervention in active smokers with chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. METHODS: This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. DISCUSSION: The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.

[Statins and COPD: relationship with inflammation, exacerbations and mortality].

The role of statins on the disease course of COPD is controversial. Observational studies have shown a reduction in mortality and exacerbations, but results of randomised clinical trials (RCTs) of statin treatment and its effect on adverse outcomes are conflicting. Recent meta-analyses suggest the need for further RCTs including COPD patients both with and without concurrent cardiovascular disease (CVD). As there are no known detrimental effects of statins in COPD patients, we conclude in this review, that statins should be prescribed more frequently in these patients due to the common co-morbidity with CVD.

Comparison of Characteristics Between ICS-Treated COPD Patients and ICS-Treated COPD Patients with Concomitant Asthma: A Study in Primary Care.

Background and Objective: Inhaled corticosteroids (ICS) for COPD has been much debated. Our aim was to identify characteristics associated with prescribing ICS for patients with COPD alone compared to those with concomitant asthma in general practice. Patients and Methods: Participating general practitioners (GPs) (n=144) recruited patients with COPD (ICPC 2nd ed. code R95) currently prescribed ICS (ACT code R03AK and R03BA). Data, if available, on demographics, smoking habits, spirometry, COPD medication, dyspnea score, and exacerbation history were retrieved from the medical records. Logistic regression analysis was used to identify possible differences in characteristics between patients with COPD alone compared to those having a concomitant diagnosis of asthma. Results: A total of 2.289 (45% males) COPD patients on ICS were recruited. Compared to patients with COPD alone (n=1.749), those with COPD and concomitant asthma (n=540) were younger (p<0.001), had higher BMI, higher FEV1/FVC ratio, higher blood eosinophil count and less life-time tobacco exposure (36 and 26 pack-years, respectively). Compared to COPD alone, logistic regression analysis showed that COPD with concomitant asthma was significantly associated to age (OR 0.94; CI 0.92 to 0.97; p<0.001), pack-years of smoking (OR 0.98; CI 0.97 to 0.99; p<0.001), %pred (OR 1.02; CI 1.00 to 1.03; p=0.005), and doctor-diagnosed depression (OR 2.59; CI 1.20 to 5.58; p=0.015). Conclusion: In COPD patients currently prescribed ICS, the presence of concomitant asthma was associated with being younger, having less tobacco exposure, more preserved lung function and a higher likelihood of doctor-diagnosed depression compared to COPD alone.

High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD.

Introduction: The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD. Methods: This retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein. Results: suPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40-1.85; p<0.0001) and 3.40 (95% CI 2.64-4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/µL) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39-0.62; p<0.0001) compared with patients with <150 cells/µL. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/µL) group. Conclusion: In this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.