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RationalePulmonary 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).ObjectiveTo 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 MethodsIn 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 resultsThe 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 pConclusionPTR 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 numberClinicalTrials.gov (NCT02667171), 28 January 2016.

Background: Due to repeated exacerbations a large group of patients with chronic obstructive pulmonary disease (COPD) are often exposed to oral corticosteroids (OCS). Corticosteroids may be thrombogenic. We evaluated the risk of venous thromboembolia and death in patients with acute exacerbation of COPD (AECOPD) according to two different dosing regimens.Method: This was a nationwide observational cohort study of outpatients with COPD with a 6 month follow up time. It was based on a linked administrative registry data between January 1st 2010 and 28th February 2018. In total 30.473 patients treated with either short course (250mg) of OCS for AECOPD were included in the study. Cox proportional hazard regression was used to estimate the risk of VTE hospitalization or all-cause mortality.Results: The incidence of VTE was low. However, long course of OCS was associated with an increased risk of VTE compared to short course, (HR 1.73, CI 1.08 to 2.79; p < 0.0001). Furthermore, we found a higher risk of all-cause mortality in the long course group, HR 1.62 (CI 1.57 to 1.62; p

The subject of this review is alpha-1-antitrypsin deficiency (A1AD), which is a rare hereditary disease with great impact in adults, especially smokers, quality of life and longevity. Early diagnosis is crucial for treatment outcome. The primary care physician should refer patients younger than 50-years-old with COPD or emphysema, familiar accumulation of A1AD or liver cirrhosis of unknown cause. Most important treatment is smoking cessation, pulmonary rehabilitation and inhaled medication according to current guidelines. Substitution treatment with alpha-1-antitrypsin is now an option after its approval by the Danish medical council in January 2020.

Background Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for COVID-19. Methods Placebo-controlled double-blind randomised multicentre trial. Patients ≥18 years, admitted to hospital for≤48 h (not intensive care) with a positive SARS-CoV-2 RT-PCR test, were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14). Results After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on February 1, 2021. A total of 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median of 9.0 DAOH14 (IQR, 3–11) versus. 9.0 DAOH14 (IQR, 7–10) in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for 1 patient in the intervention group versus. 2 patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for 9 patients in the intervention group versus. 6 patients receiving placebo (p=0.57). Conclusions The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19., There are no beneficial or harmful effects from the combined intervention of hydroxychloroquine and azithromycin for hospitalised patients with confirmed coronavirus disease 2019 (COVID-19).

Objectives The aim of this study was to establish whether early pulmonary rehabilitation after severe exacerbation of chronic obstructive pulmonary disease (COPD) reduces mortality and hospital admissions, and increases physical performance and quality of life compared to rehabilitation initiated later in the stable phase of COPD. Methods In a randomised controlled trial of 150 patients hospitalised with an exacerbation of COPD, participants were allocated to pulmonary rehabilitation either within 2 weeks after discharge or the same rehabilitation programme but initiated 2 months after discharge. Results Early pulmonary rehabilitation did not prolong time to first hospital admission or time to death (hazard ratio 0.79, 95% CI 0.47–1.23, p=0.33) compared to rehabilitation in stable phase. However, 2 months after inclusion, pulmonary rehabilitation resulted in a significantly better improvement in the incremental shuttle walk test (33.9 m, 95% CI 4.18–63.7, p=0.02) compared to that in the stable phase. The difference in the endurance shuttle walk test was of borderline significance (140 s, 95% CI −2.03–282.76, p=0.05), but there was no significant difference concerning the COPD assessment test (−1.43 points, 95% CI −3.44–0.59, p=0.17). Conclusion Early pulmonary rehabilitation after acute exacerbation of COPD led to a faster improvement in physical performance compared to rehabilitation initiated later in the stable phase, but did not improve survival or prolong time to hospital readmission., Early pulmonary rehabilitation shortly after #AECOPD leads to a faster recovery in physical performance than initiated in the stable phase. Adherence to rehabilitation is significantly higher when initiated shortly after an exacerbation. http://bit.ly/2S7XsT9

BACKGROUND: Treatment with systemic corticosteroids in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is associated with debilitating adverse effects. Therefore, strategies to reduce systemic corticosteroid exposure are urgently required and might be offered by a personalised biomarker-guided approach to treatment. The aim of this study was to determine whether an algorithm based on blood eosinophil counts could safely reduce systemic corticosteroid exposure in patients admitted to hospital with acute exacerbations of COPD.METHODS: We did a multicentre, randomised, controlled, open-label, non-inferiority trial at the respiratory departments of three different university-affiliated hospitals in Denmark. Eligible participants were patients included within 24h of admission to the participating sites, aged at least 40 years, with known airflow limitation (defined as a post-bronchodilator FEV1/forced vital capacity [FVC] ratio ≤0·70) and a specialist-verified diagnosis of COPD, who were designated to start on systemic corticosteroids by the respiratory medicine physician on duty. We randomly assigned patients (1:1) to either eosinophil-guided therapy or standard therapy with systemic corticosteroids. Both investigators and patients were aware of the group assignment. All patients received 80 mg of intravenous methylprednisolone on the first day. The eosinophil-guided group were from the second day given 37·5 mg of prednisolone oral tablet daily (for a maximum of up to 4 days) on days when their blood eosinophil count was at least 0·3 × 109 cells per L. On days when the eosinophil count was lower, prednisolone was not administered. If a patient was discharged during the treatment period, a treatment based on the last measured eosinophil count was prescribed for the remaining days within the 5-day period (last observation carried forward). The control group received 37·5 mg of prednisolone tablets daily from the second day for 4 days. The primary outcome was the number of days alive and out of hospital within 14 days after recruitment, assessed by intention to treat (ITT). Secondary outcomes included treatment failure at day 30 (ie, recurrence of acute exacerbation of COPD resulting in emergency room visits, admission to hospital, or need to intensify pharmacological treatment), number of deaths on day 30, and duration of treatment with systemic corticosteroids. The non-inferiority margin was 1·2 days (SD 3·8). This trial is registered at ClinicalTrials.gov, number NCT02857842, and was completed in January, 2019.FINDINGS: Between Aug 3, 2016, and Sept 30, 2018, 159 patients in the eosinophil-guided group and 159 patients in the control group were included in the ITT analyses. There was no between-group difference for days alive and out of hospital within 14 days after recruitment: mean 8·9 days (95% CI 8·3-9·6) in the eosinophil-guided group versus 9·3 days (8·7-9·9) in the control group (absolute difference -0·4, 95% CI -1·3 to 0·5; p=0·34). Treatment failure at 30 days occurred in 42 (26%) of 159 patients in the eosinophil-guided group and 41 (26%) of 159 in the control group (difference 0·6%, 95% CI -9·0 to 10·3; p=0·90). At 30 days nine patients (6%) of 159 in the eosinophil-guided group and six (4%) of 159 in the control group had died (difference 1·9%, 95% CI -2·8 to 6·5; p=0·43). Median duration of systemic corticosteroid therapy was lower in the eosinophil-guided group: 2 days (IQR 1·0 to 3·0) compared with 5 days (5·0 to 5·0) in the control group, pINTERPRETATION: Eosinophil-guided therapy was non-inferior compared with standard care for the number of days alive and out of hospital, and reduced the duration of systemic corticosteroid exposure, although we could not entirely exclude harm on some secondary outcome measures. Larger studies will help to determine the full safety profile of this strategy and its role in the management of COPD exacerbations.FUNDING: The Danish Regions Medical Fund and the Danish Council for Independent Research.

Background: Patients admitted with an exacerbation of COPD has a high risk of readmission with new exacerbations. To improve patient wellbeing and safety we designed an outpatient program with home visits and a call line. Objectives: Primary goal was to improve wellbeing and safety, secondary goal was to reduce readmission after a COPD exacerbation. Design/Methods: A longitudinal observational study. All patients discharged after an exacerbation was offered the program for 6 months i.e. 1) home visits by an experienced pulmonary nurse 7 and 180 days after discharge. 2) A nurse-led telephone during working hours for any kind of questions and assistance for treatment of exacerbations. 3) A COPD information folder with a self-manage treatment plan if appropriate. Medical treatment in acute and stable phase followed GOLD strategy of 2007 Results: Of the 262 eligible patients 132 were enrolled. 95 patients completed, 14 were excluded during the study period, 23 died during the period. 30-days readmission was 28 (21,2%) and 1-year readmission was 83 (62,9%); 30-days mortality was 11 (8,33%) and 1-year mortality was 43 (32,6%). From day 7 to 180, SGRQ improved by 4.3 points (P=0.003); no change was found in FEV1, FVC or MRC, although 7 (7,3%) did have a change in FEV1 by more than 400 ml indicating an asthmatic component. BMI improved 0,45 (P=0,02). Conclusion: The study showed no difference in readmission and mortality compared to Danish National Data, which was expectable with a relative small cohort. SGRQ and BMI improved significantly. 7% had possible asthma with more than 400 ml improvement in FEV1, and possible need of inhaled corticosteroid.

Whether subjects heterozygous for alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for development of obstructive pulmonary disease (OPD) has been discussed for the past three decades. Both cohort and case-control studies have reached different conclusions, with the major problems being small sample sizes. A cohort of heterozygotes with the phenotype PiMZ was retrieved from the Danish Alpha(1)-Antitrypsin Deficiency Registry. Ten matched controls for each PiMZ subject were identified from the files of the Danish Central Population Registry. Cases and controls were subsequently linked to the files of the Danish Hospital Discharge Registry, and relative risk for OPD was calculated. In the cohort of 1,551 PiMZ subjects (11,678 person-years), we identified 47 subjects with a discharge diagnosis of OPD, as compared with 206 subjects with this diagnosis in the control group (109,748 person-years), yielding a relative risk (RR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.0). This increased risk was present in both men and women and in all age groups; however, it was significant only in the age group from 40 to 79 yr. Of the 1,551 PiMZ subjects, 565 (36%) were first-degree relatives of PiZ index cases, and it appeared that only this group was at increased risk of hospital admission for OPD (RR: 3.4, 95% CI: 2.2 to 5.3). We conclude that alpha(1)-AT heterozygotes of phenotype PiMZ are at increased risk of hospital admission for OPD if they are first-degree relatives of PiZ index cases only, and that other, yet unknown genetic or environmental factors contribute to the development of lung disease.

Background : Chronic obstructive pulmonary disease (COPD) patients who have had an episode of acute hypercapnic respiratory failure (AHRF) have a large 1-year risk of death or readmission. Acute non-invasive ventilation (NIV) has been shown to be an effective treatment of AHRF; and long-term NIV (LTNIV) has been shown to be an effective treatment of chronic respiratory failure in stable hypercapnic COPD. We investigated the effects of LTNIV in a group of patients with severe, unstable COPD: frequent admissions and multiple previous episodes of AHRF treated with NIV. Methods : We conducted a retrospective analysis of 20 COPD patients treated with LTNIV after two or more episodes of AHRF during 1 year. Results : The mean number of AHRF episodes decreased from 2.44 in the year prior to LTNIV initiation to 0.44 in the year following ( p< 0.0001). The median number of admissions decreased from 5.19 to 1.88 ( p= 0.0092). Four patients (20%) died in 1 year. LTNIV tended to reduce arterial CO 2 . No changes were found in lung function. Conclusions : LTNIV seems effective in reducing recurrent AHRF and readmissions in a highly select group of patients with severe, unstable COPD and frequent AHRF. Keywords: COPD; ventilation; respiratory failure; hypercapnia; exacerbations (Published: 31 March 2016) Citation: European Clinical Respiratory Journal 2016, 3: 28303 - http://dx.doi.org/10.3402/ecrj.v3.28303

Bispebjerg Hospital, Department of Pulmonary Medicine, tuberculosis referral center for the Municipality of Copenhagen.To evaluate routine procedure for the management of liver injury during antituberculosis treatment.From 1983-1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with standard Danish treatment for tuberculosis. From 1983-1986 they received a three-drug (9-month) regimen and from 1986-1993 a four-drug (6-month) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinamide. Data from a retrospective chart review.An increase in aspartate aminotransferase (AST) of more than twice the upper limit of normal (ULN) was recorded in 127 patients (16%). 66 had elevated AST before treatment; most of these were men with a daily alcohol consumption in excess of 60 g. In the remaining 61 patients (8%) AST increased during antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 x ULN (range 2-25 x ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reintroduce it fully in 14 (12 excessive alcohol consumers). Only 16 patients (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P0.05), seven were jaundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was confirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepatotoxicity.In spite of an increase in AST levels to approximately 6 x ULN during antituberculosis treatment, the drugs can be continued or reintroduced in full in most cases. Risk factors of hepatotoxicity included old age, female sex and extensive tuberculosis, and not alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.

Setting : Department of Pulmonary Medicine P, Bispebjerg Hospital, Copenhagen, Denmark. Objective : To study the ability of two proteins secreted from Mycobacterium tuberculosis , MPT-64 and MPT-59 to induce delayed type hypersensitivity (DTH) reactions following intradermal administration. Design : In a small scale clinical investigation, skin reactions to these antigens were compared to reactions to tuberculin PPD RT23 in 1) patients with active tuberculosis, 2) BCG vaccinated healthy subjects with close contact with tuberculous patients, and 3) BCG vaccinated healthy subjects without contact with tuberculous patients. Tests for in vitro reactivity to these antigens were carried out in similar groups. Results : All subjects gave positive reaction to tuberculin PPD RT23, whereas approximately half of the subjects in each of the three groups reacted to MPT-59. Two subjects (one patient with tuberculosis and one healthy bacille Calmette-Guerin vaccinated subject without patient contact) reacted to MPT-64. The studies of cell proliferation and induction of interferon-γ (IFN-γ) following stimulation with tuberculin PPD and MPT-64 supported this profile of reactivity. Conclusion : None of the experimental skin test antigens had properties superior to tuberculin PPD RT23 in humans. The failure of MPT-64 to induce delayed type hypersensitivity reactions in the majority of tuberculosis patients is discussed, in view of the potent reactivity to MPT-64 in tuberculous guinea pigs.

BACKGROUND: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy.METHODS: Multi-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases.DISCUSSION: Though previous studies of long-term noninvasive ventilation have shown conflicting results, we believe the treatment can reduce mortality and readmissions when applied in patients with previous need of acute ventilatory support, regardless of persistent hypercapnia.TRIAL REGISTRATION: clinicaltrials.org: NCT01513655 16-Jan-2012.

Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P