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".

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.

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.

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.

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.

Supervised pulmonary tele-rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicentre trial.

RATIONALE: Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD. Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported. Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR). OBJECTIVE: To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR. METHODS: In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly). Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks' follow-up from baseline. The primary analysis was based on the intention-to-treat principle. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised. The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: -6.6 to 24.9)) or at 22 weeks' follow-up (-5.3 metres (95% CI: -28.9 to 18.3)). More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01). CONCLUSION: PTR was not superior to conventional PR on the 6MWD and we found no differences between groups. As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design. Trial registration number ClinicalTrials.gov (NCT02667171), 28 January 2016.

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.

The biomarkers suPAR and blood eosinophils are associated with hospital readmissions and mortality in asthma - a retrospective cohort study.

INTRODUCTION: Prognostic biomarkers in asthma are needed. The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with asthma control and with prognosis in acutely admitted medical patients. We investigated if suPAR and blood eosinophil counts at the time of admission for asthma are associated with readmission and mortality. METHODS: Our cohort comprised 1341 patients (median age 45.3, IQR 30.1-63.1) acutely admitted with a diagnosis of asthma to Hvidovre Hospital, Denmark (November 2013 to March 2017). Patients had suPAR and blood eosinophils measured at admission. Outcomes were 365-day readmission and all-cause mortality. Logistic regression analysis adjusted for age, sex, C-reactive protein, and Charlson comorbidity score was used to assess the association of the two biomarkers with readmission and all-cause mortality. RESULTS: Compared to event-free patients, patients who were either readmitted (n = 452, 42.3%) or died (n = 57, 5.3%) had significantly higher suPAR concentrations (p < 0.0001) and lower eosinophil counts (p = 0.0031) at admission. The highest odds of readmission or mortality were observed for patients in either the 4th suPAR quartile (p < 0.0001) or with eosinophil counts < 150 cells/µL at admission. Increasing levels of suPAR were associated with 365-day readmission (OR 1.3 [1.0-1.6]; p = 0.05) and mortality (OR 2.9 [1.7-5.1]; p = 0.0002). Eosinophil count > 300 cells/µL was significantly associated with lower odds of readmission (OR 0.64 [0.5-0.9]; p = 0.005) and lower mortality (OR 0.7 [0.6-0.9]; p = 0.0007). CONCLUSIONS: In patients acutely admitted with asthma, elevated suPAR concentrations together with blood eosinophil count < 150 cells/µL at the time of hospital admission were associated with both 365-day all-cause readmission and mortality.

A conflict of interest is strongly associated with tobacco industry-favourable results, indicating no harm of e-cigarettes.

Researchers reach contradictory results when trying to assess the potential harm of e-cigarettes. This study investigated whether the findings and conclusions in papers published on e-cigarettes and health differ depending on whether the authors had a financial conflict of interest (COI) or not. A total of 94 studies (identified in a previous systematic review) that investigated the content of fluid/vapor of e-cigarettes or in vitro experiments were included. The type, level and direction of the financial COI were coded. Abstracts were blinded and evaluated by two assessors. Fischer's Test and Logistic regression analyses were used to investigate the associations between findings of harm/conclusions and COI. All three dimensions of COI showed the same tendency: studies with industry-related COI found potential harm significantly less often than studies without a COI. 95.1% of papers without and 39.4% of papers with a COI found potential harmful effects/substances. Only 7.7% of tobacco industry-related studies found potential harm. The odds of finding of no harm were significantly higher in studies with an industry-related COI (OR 66.92 (95% CI 8.1-552.9)) than in studies without a COI. A strong/moderate COI was associated with very high odds (OR 91.50 (95% CI 10.9-771.4)) of finding of no harm compared with studies with no/weak COI. This blinded assessment showed that almost all papers without a COI found potentially harmful effects of e-cigarettes. There was a strong association between industry-related COI and tobacco- and e-cigarette industry-favourable results, indicating that e-cigarettes are harmless.

COPD patients prescribed inhaled corticosteroid in general practice: Based on disease characteristics according to guidelines?

In a primary care setting, our aim was to investigate characteristics of patients classified as having chronic obstructive pulmonary disease (COPD) and currently being prescribed inhaled corticosteroids (ICSs). The electronic patient record system in each participating general practice was searched for patients coded as COPD (ICPC, Second Edition code R95) and treated with ICS (ACT code R03AK and R03BA, that is, ICS in combination with a long-acting ß2-agonist) or ICS as monotherapy. Data, if available, on demographics, smoking habits, spirometry, COPD medication, symptom score, blood eosinophils, co-morbidity and exacerbation history were retrieved from the medical records for all identified cases. Of all patients registered in the 138 participating general practices, 12.560 (3%) were coded as COPD, of whom 32% were prescribed ICS. The final study sample comprised 2.289 COPD patients currently prescribed ICS (98% also prescribed long-acting ß2-agonist), with 24% being coded as both COPD and asthma. Post-bronchodilator spirometry was available in 79% (mean forced expiratory volume in 1 second 60% pred (standard deviation (SD) 23.3)), symptom severity score in 53% (mean Medical Research Council score 2.7 (SD 1.1)) and 56% of the COPD patients had had no exacerbation in the previous year (and 45% not within the 2 previous years). Blood eosinophils were measured in 67% of the patients. Information on severity of airflow limitation was missing in 15% of the patients, and the combined information on symptom severity and exacerbation history was missing in in 46%. Most of the patients (74%) were managed only by their general practitioner. Although only one-third of the COPD patients were prescribed ICSs, our findings from this study of a large cohort of patients prescribed ICSs for COPD in general practice suggest that more detailed assessment of diagnosis and disease characteristics is likely to improve the risk-benefit ratio of maintenance therapy with ICSs in COPD patients managed in primary care.

Soluble urokinase plasminogen activator receptor predicts mortality in exacerbated COPD.

BACKGROUND: The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in severe acute and chronic medical conditions and has been associated with short-term mortality. The role of suPAR in predicting risk of death following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has never been studied. We hypothesized that increased suPAR is an independent predictor of short-term mortality in patients admitted to hospital with COPD or acute respiratory failure. METHODS: This retrospective cohort study from a university hospital in the Capital Region of Denmark included 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnosis, who had plasma suPAR measured at the time of admission between November 18th, 2013 to September 30th, 2015 and followed until December 31st, 2015. Primary outcomes were 30- and 90-days all-cause mortality. Association of suPAR and mortality was investigated by Cox regression analyses adjusted for age, sex, CRP values and Charlson comorbidity index. RESULTS: For patients with AECOPD or underlying COPD, median suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P < 0.0001). Increasing suPAR levels independently predicted 30-day mortality in patients with COPD with a hazard ratio of 2.0 (95% CI 1.7-2.4) but not respiratory failure. CONCLUSIONS: In this large group of acutely admitted patients with COPD, elevated suPAR levels were associated with increased risk of mortality. The study supports the value of suPAR as a marker of poor prognosis.

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 109, Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

Lower mortality after early supervised pulmonary rehabilitation following COPD-exacerbations: a systematic review and meta-analysis.

BACKGROUND: Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management. We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program. Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate. METHODS: We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool. RESULTS: We included 13 randomized trials (801 participants). Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])). Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [- 6.85 to - 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])). Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate. Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power. CONCLUSION: Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation. Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months. Therefore, we recommend early supervised PR to patients with COPD-related exacerbations. PR should be initiated during hospital admission or within 4 weeks after hospital discharge.

Oral prednisolone for 4 days does not increase exercise tolerance in men with COPD.

One of the primary objectives in management of chronic obstructive pulmonary disease (COPD) is preventing decrease in lung function and reducing the annual number of acute exacerbations of COPD (AECOPD). An oral course of systemic corticosteroids is a commonly used treatment in AECOPD. We hypothesize that this treatment also increases exercise performance and decreases muscle fatigue. In a randomized double-blinded, parallel, placebo-controlled trial, we investigated 14 men (8 on prednisolone 37.5 mg vs. 6 on placebo) with severe and very severe COPD. For 5 consecutive days, the patients performed a submaximal endurance test measuring time to exhaustion (TTE, primary endpoint), spirometry, maximal inspiratory and expiratory pressure and maximal isometric contraction of the quadriceps femoris muscle (maximum voluntary contraction (MVC)). At visits 2, 3 and 4, a fatigue protocol was carried out after 40 minutes of cycling at 40% of maximal effort. No differences between groups were found for TTE, lung function or maximal inspiratory or expiratory pressure, however, patients on prednisolone showed significant increased MVC: median 5.15 [3.35; 9.15] against placebo: -2 [-5.57; 3.95] ( p = 0.03). This finding indicates an impact of corticosteroids on muscle groups being exposed to submaximal endurance.

COPD online-rehabilitation versus conventional COPD rehabilitation - rationale and design for a multicenter randomized controlled trial study protocol (CORe trial).

BACKGROUND: Rehabilitation of patients with chronic obstructive pulmonary disease (COPD) is a key treatment in COPD. However, despite the existing evidence and a strong recommendation from lung associations worldwide, 50% of patients with COPD decline to participate in COPD rehabilitation program and 30-50% drop-out before completion. The main reasons are severe symptoms, inflexible accessibility and necessity for transportation. Currently there are no well-established and evident rehabilitation alternatives. Supervised online screen rehabilitation could be a useful approach to increase accessibility and compliance. The aim of this multicenter RCT study is to compare the potential benefits of a 10-week online COPD rehabilitation program (CORe) with conventional outpatient COPD rehabilitation (CCRe). METHODS: This study is a randomized assessor- and statistician blinded superiority multicenter trial with two parallel groups, employing 1:1 allocation to the intervention and the comparison group.On the basis of a sample size calculation, 134 patients with severe or very severe COPD and eligible to conventional hospital based outpatient COPD rehabilitation will be included and randomized from eight different hospitals. The CORe intervention group receives group supervised resistance- and endurance training and patient education, 60 min, three times/week for 10 weeks at home via online-screen. The CCRe comparison group receives group based supervised resistance- and endurance training and patient education, 90 min, two times/week for 10 weeks (two hospitals) or 12 weeks (six hospitals) in groups at the local hospital. The primary outcome is change in the 6-min walking distance after 10/12 weeks; the secondary outcomes are changes in 30 s sit-to-stand chair test, physical activity level, symptoms, anxiety and depression symptoms, disease specific and generic quality of life. Primary endpoint is 10/12 weeks from baseline, while secondary endpoints are 22, 36, 62 weeks from baseline assessments. DISCUSSION: The study will likely contribute to knowledge regarding COPD tele-rehabilitation and to which extent it is more feasible and thereby more efficient than conventional COPD rehabilitation in patients with severe and very severe COPD. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02667171 . Registration data: January 28th 2016.

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use: Results from an Observational Study (ASSESS).

This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p < 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p < 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p < 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.

Prevalence and management of pulmonary comorbidity in patients with lung and head and neck cancer.

BACKGROUND: The simultaneous presence of cancer and other medical conditions (comorbidity) is frequent. Cigarette smoking is the major risk factor for as well head and neck cancer (HNC) and lung cancer (LC) as chronic obstructive pulmonary disease (COPD). COPD is the most common comorbidity in LC patients, and presence of COPD worsens the prognosis of HNC and LC. COPD is under-diagnosed and under-treated in the Danish population. The aims of this study were to determine the prevalence of COPD in a HNC and LC population, and to determine the need and feasibility of a randomized controlled phase II trial comparing usual care with optimized medical treatment of COPD in cancer patients. MATERIAL AND METHODS: All patients with HNC or LC referred for oncologic treatment in a university hospital during a 10-month period were invited to attend a pulmonary clinic for evaluation of lung function. Patients who were found to have concomitant COPD were randomized to intervention or usual care. Primary endpoints were prevalence of COPD among the referred patients with either LC or HNC, and further whether the patients that were diagnosed with COPD already received treatment in accordance with Danish COPD guidelines. Secondary outcome was feasibility, i.e. the proportion of eligible patients that accepted follow-up in the pulmonary clinic for 24 weeks in addition to oncological treatment. The design of the randomized trail is described in detail. RESULTS: In total 130 patients of whom 65% had LC and 35% HNC have been screened during the first seven months of this ongoing trial. Sixty-eight percent of LC patients and 22% of HNC patients had COPD. All but one of 68 eligible patients accepted randomization. Nearly one third (31%) of the LC and HNC patients with COPD were diagnosed prior to study entry, and of these, only 33% were receiving correct treatment according to current guidelines. CONCLUSION: For patients with LC, and to a lesser extend HNC, there is a need for improved diagnosis and treatment of concomitant COPD. Furthermore, patients found it acceptable to be scheduled for a 24-week follow-up in a pulmonary clinic along with their oncological treatment.

Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study.

BACKGROUND: Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes. METHODS: The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded. RESULTS: The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%. In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001). Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient's physical activity level (p < 0.05 for each period). CONCLUSIONS: More than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.

A qualitative study of integrated care from the perspectives of patients with chronic obstructive pulmonary disease and their relatives.

BACKGROUND: Disease management programmes have been developed for chronic obstructive pulmonary disease (COPD) to facilitate the integration of care across healthcare settings. The purpose of the present study was to examine the experiences of COPD patients and their relatives of integrated care after implementation of a COPD disease management programme. METHODS: Seven focus groups and five individual interviews were held with 34 patients with severe or very severe COPD and two focus groups were held with eight of their relatives. Data were analysed using inductive content analysis. RESULTS: Four main categories of experiences of integrated care emerged: 1) a flexible system that provides access to appropriate healthcare and social services and furthers patient involvement; 2) the responsibility of health professionals to both take the initiative and follow up; 3) communication and providing information to patients and relatives; 4) coordination and professional cooperation. Most patients were satisfied with their care and raised few criticisms. However, patients with more unstable and severe disease tended to experience more problems. CONCLUSIONS: Participant suggestions for optimizing the integration of healthcare included assigning patients a care coordinator, telehealth solutions for housebound patients and better information technology to support interprofessional cooperation. Further studies are needed to explore these and other possible solutions to problems with integrated care among COPD patients. A future effort in this field should be informed by detailed knowledge of the extent and relative importance of the identified problems. It should also be designed to address variable levels of severity of COPD and relevant comorbidities and to deliver care in ways appropriate to the respective healthcare setting. Future studies should also take health professionals' views into account so that interventions may be planned in the light of the experiences of all those involved in the treatment of COPD patients.

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.