Erratum: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

An erratum was issued for: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion. The Authors section was updated from: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation to: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Nick Maskell4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation.

Pleural disease.

The incidence of pleural disease is increasing and the mortality and morbidity is high. Many recent RCTs have resulted in evidence-based guidelines published in 2023, pointing towards a more individualized and specialized management. Most patients with pleural disease are admitted at the A and E but can be managed in outpatient clinics. Thus, there is a need to establish specialized, multidisciplinary pleural clinics to ensure optimal, individualized and evidence-based management of the increasing number of patients with pleural disease in Denmark, as argued in this review.

Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

Local anesthetic thoracoscopy (LAT) is a minimally invasive diagnostic procedure gaining recognition among chest physicians for managing undiagnosed pleural effusions. This single-port procedure is conducted with the patient under mild sedation and involves a contralateral decubitus position. It is performed in a sterile setting, typically a bronchoscopy suite or surgical theater, by a single operator with support from a procedure-focused nurse and a patient-focused nurse. The procedure begins with a thoracic ultrasound to determine the optimal entry point, usually in the IV-V intercostal space along the midaxillary line. Lidocaine/mepivacaine, with or without adrenaline, is used to anesthetize the skin, thoracic wall layers, and parietal pleura. A designated trocar and cannula are inserted through a 10 mm incision, reaching the pleural cavity with gentle rotation. The thoracoscope is introduced through the cannula for systematic inspection of the pleural cavity from the apex to the diaphragm. Biopsies (typically six to ten) of suspicious parietal pleura lesions are obtained for histopathological evaluation and, when necessary, microbiological analysis. Biopsies of the visceral pleura are generally avoided due to the risk of bleeding or air leaks. Talc poudrage may be performed before inserting a chest tube or indwelling pleural catheter through the cannula. The skin incision is sutured, and intrapleural air is removed using a three-compartment or digital chest drainage system. The chest tube is removed once there is no airflow, and the lung has satisfactorily re-expanded. Patients are usually discharged after 2-4 h of observation and followed up on an outpatient basis. Successful LAT relies on careful patient selection, preparation, and management, as well as operator education, to ensure safety and a high diagnostic yield.

High-pressure NIV for acute hypercapnic respiratory failure in COPD: improved survival in a retrospective cohort study.

INTRODUCTION: Updated treatment guidelines for acute hypercapnic respiratory failure (AHRF) in chronic obstructive pulmonary disease (COPD) with non-invasive ventilation (NIV) in 2016 recommended a rapid increase in inspiratory positive airway pressure (IPAP) to 20 cm H2O with possible further increase for patients not responding. Previous guidelines from 2006 suggested a more conservative algorithm and maximum IPAP of 20 cm H2O. AIM: To determine whether updated guidelines recommending higher IPAP during NIV were related with improved outcome in patients with COPD admitted with AHRF, compared with NIV with lower IPAP. METHODS: A retrospective cohort study comparing patients with COPD admitted with AHRF requiring NIV in 2012-2013 and 2017-2018. RESULTS: 101 patients were included in the 2012-2013 cohort with low IPAP regime and 80 patients in the 2017-2018 cohort with high IPAP regime. Baseline characteristics, including age, forced expiratory volume in 1 s (FEV1), pH and PaCO2 at initiation of NIV, were comparable. Median IPAP in the 2012-2013 cohort was 12 cm H2O (IQR 10-14) and 20 cm H2O (IQR 18-24) in the 2017-2018 cohort (p<0.001). In-hospital mortality was 40.5% in the 2012-2013 cohort and 13.8% in the 2017-2018 cohort (p<0.001). The 30-days and 1-year mortality were significantly lower in the 2017-2018 cohort. With a Cox model 1 year survival analysis, adjusted for age, sex, FEV1 and pH at NIV initiation, the HR was 0.45 (95% CI 0.27 to 0.74, p=0.002). CONCLUSION: Short-term and long-term survival rates were substantially higher in the cohort treated with higher IPAP. Our data support the current strategy of rapid increase and higher pressure.

Physiological changes related to 10 weeks of singing for lung health in patients with COPD.

BACKGROUND: Singing for Lung Health (SLH) was non-inferior to physical exercise training in improving 6-minute walking test distance (6MWD) and quality of life (St. George's Respiratory Questionnaire (SGRQ)) within a 10-week pulmonary rehabilitation (PR) programme for COPD in our recent randomised controlled trial (RCT) (NCT03280355). Previous studies suggest that singing improves lung function, respiratory control and dyspnoea, however this has not yet been convincingly confirmed. Therefore, this study aimed to explore the impact of SLH on physiological parameters and the associations with achieving the minimal important difference (MID) in 6MWD and/or SGRQ. METHODS: We conducted post hoc, per-protocol analyses mainly of the SLH group of the RCT, exploring associations with 6MWD and SGRQ results by stratifying into achieving versus not-achieving 6MWD-MID (≥30 m) and SGRQ-MID (≤-4 points): changes in lung function, inspiratory muscle strength/control, dyspnoea, and heart rate response using logistic regression models. Further, we explored correlation and association in achieving both 6MWD-MID and SGRQ-MID (or in neither/nor) using Cohen's κ and Cochran-Mantel-Haenszel Test. RESULTS: In the SLH study group (n=108), 6MWD-MID was achieved by 31/108 (29%) and in SGRQ by 53/108 (49%). Baseline factors associated with achieving MID in either outcome included short baseline 6MWD and high body mass index. Achieving 6MWD-MID was correlated with improved heart rate response (OR: 3.14; p=0.03) and achieving SGRQ-MID was correlated with improved maximal inspiratory pressure (OR: 4.35; p=0.04). Neither outcome was correlated with significant spirometric changes. Agreement in achieving both 6MWD-MID and SGRQ-MID was surprisingly insignificant. CONCLUSIONS: This explorative post hoc study suggests that SLH is associated with physiological changes after short-term PR for COPD. Future physiological studies will help us to understand the mechanisms of singing in COPD. Our study furthermore raises concern about poor agreement between subjective and objective benefits of PR despite state-of-the-art tools.

Flavonoid intakes inversely associate with COPD in smokers.

INTRODUCTION: Higher flavonoid intakes are beneficially associated with pulmonary function parameters; however, their association with chronic obstructive pulmonary disease (COPD) is unknown. This study aimed to examine associations between intakes of 1) total flavonoids, 2) flavonoid subclasses and 3) major flavonoid compounds with incident COPD in participants from the Danish Diet, Cancer and Health study. METHODS: This prospective cohort included 55 413 men and women without COPD, aged 50-65 years at recruitment. Habitual flavonoid intakes at baseline were estimated from a food frequency questionnaire using Phenol-Explorer. Danish nationwide registers were used to identify incident cases of COPD. Associations were modelled using restricted cubic splines within Cox proportional hazards models. RESULTS: During 23 years of follow-up, 5557 participants were diagnosed with COPD. Of these, 4013 were current smokers, 1062 were former smokers and 482 were never-smokers. After multivariable adjustments, participants with the highest total flavonoid intakes had a 20% lower risk of COPD than those with the lowest intakes (quintile 5 versus quintile 1: HR 0.80, 95% CI 0.74-0.87); a 6-22% lower risk was observed for each flavonoid subclass. The inverse association between total flavonoid intake and COPD was present in both men and women but only in current smokers (HR 0.77, 95% CI 0.70-0.84) and former smokers (HR 0.82, 95% CI 0.69-0.97), not never-smokers. Furthermore, higher flavonoid intakes appeared to lessen, but not negate, the higher risk of COPD associated with smoking intensity. CONCLUSION: Dietary flavonoids may be important for partially mitigating the risk of smoking-related COPD. However, smoking cessation should remain the highest priority.

Use of Singing for Lung Health as an alternative training modality within pulmonary rehabilitation for COPD: a randomised controlled trial.

BACKGROUND: Pulmonary rehabilitation (PR) is a cornerstone in chronic obstructive pulmonary disease (COPD) management. However, PR adherence is generally low, and barriers include availability, economic issues, motivation and an inability to attend or perform physical training. Therefore, alternative, evidence-based PR activities are required. Singing may have benefits for quality of life (QoL), respiratory control and well-being in COPD, but the impact on the PR key outcome, physical exercise capacity, is uncertain. METHODS: In this randomised controlled trial (NCT03280355), we investigated the effectiveness of 10 weeks of PR, including either "Singing for Lung Health" (SLH) training or standard physical exercise training (PExT). The primary outcome was a change in exercise capacity (6-min walk distance (6MWD)) from baseline to post-PR. Secondary outcomes were changes in QoL (St George's Respiratory Questionnaire (SGRQ)), Hospital Anxiety and Depression Score (HADS), lung function, dyspnoea and adherence. RESULTS: We included 270 COPD patients, and 195 completed the study. Demographics across groups were comparable, and both groups improved significantly in 6MWD and SGRQ score. SLH was non-inferior to PExT in improving 6MWD (mean±sd 13.1±36.3 m versus 14.1±32.3 m, p=0.81; difference 1.0 m, 95% CI -7.3-9.3 m) with 21.8% and 25.0%, respectively (p=0.57), reaching the 6MWD minimal important difference of 30 m. We found no significant between-group differences concerning SGRQ, HADS, lung function, dyspnoea or adherence. CONCLUSION: Our study suggests that SLH is non-inferior to PExT in improving 6MWD during a 10-week PR programme. Future studies addressing reproducibility, long-term effects and health economics are needed.

Heterogeneity in Danish lung choirs and their singing leaders: delivery, approach, and experiences: a survey-based study.

OBJECTIVES: Singing is considered a beneficial leisure time intervention for people with respiratory diseases, and lung choirs have gained increasing attention. However, there is no available guideline on preferred methodology, and hence, outcomes, delivery, and benefits are unclear. The present study investigated for the first time ever emerged delivery, approach, and experiences in Danish lung choirs and their singing leaders, hypothesising the array to be heterogeneous, without disease-specific approach, and a challenging field to navigate for the singing leaders. SETTING: An online survey comprising 25 questions was performed individually, May 2017, in Denmark. PARTICIPANTS: Current singing leaders of Danish lung choirs, identified by hand searches on the internet. In total, 33 singing leaders in formal and informal settings were identified and 20 (67%) responded. PRIMARY AND SECONDARY OUTCOME MEASURES: Distribution in content, delivery, and approach; level of disease-specific knowledge and modification; experience of challenges and benefits. Quantitative variables were counted, and an inductive content analysis approach was used for the qualitative study component. RESULTS: The lung choirs were heterogeneous concerning setting, duration, and content. The approach was traditional without disease-specific content or physical activity. Most singing leaders held various academic degrees in music, but lacked skills in lung diseases. However, they experienced lung choirs as a highly meaningful activity, and reported that participants benefited both musically, psychosocially, and physically. Singing leaders were enthusiastic regarding potentials in the 'arts-and-health' cross-field and experienced an expansion of their role and overall purpose, professionally as well as personally. However, they also experienced insecurity, inadequacy, and isolation, and requested methodological guidelines, formal support, and peer network. CONCLUSION: Danish lung choirs are led without any disease-specific guideline or methodological approach. Further studies are needed to develop and distribute a preferred methodological approach. TRIAL REGISTRATION NUMBER: This study is linked to clinical trial number NCT03280355 and was performed prior to data collection and results of the clinical trial.

Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. TRIAL DESIGN: This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. PARTICIPANTS: 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. INCLUSION CRITERIA: • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. INTERVENTION AND COMPARATOR: Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 MAIN OUTCOMES: • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") RANDOMISATION: The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). BLINDING (MASKING): Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study requires 226 patients randomised 1:1 with 113 in each group. TRIAL STATUS: Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Metoprolol Versus Carvedilol in Patients With Heart Failure, Chronic Obstructive Pulmonary Disease, Diabetes Mellitus, and Renal Failure.

This study compared the survival and the risk of heart failure (HF), chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), hypoglycemia, and renal failure (RF) hospitalizations in geriatric patients exposed to carvedilol or metoprolol. Data sources were Danish administrative registers. Patients aged ≥65 and having HF, COPD, and DM were followed for 1 year from the first ß-blocker prescription redemption. Patients' characteristics were used to 1:1 propensity score match carvedilol and metoprolol users. A Cox regression model was used to compute the hazard ratio (HR) of study outcomes. For statistically significant associations, a conditional inference tree was used to assess predictors most associated with the outcome. In total, 1,424 patients were included. No statistically significant differences were observed for survival (HR 0.86; 95% confidence interval [CI] 0.67 to 1.11, p = 0.240) between carvedilol/metoprolol users. The same applied to COPD (HR 0.88; 95% CI 0.75 to 1.05, p = 0.177), DM (HR 0.95; 95% CI 0.82 to 1.10, p = 0.485), hypoglycemia (HR 0.88; 95% CI 0.47 to 1.67, p = 0.707), and RF (HR 1.25; 95% CI 0.93 to 1.69, p = 0.142) hospitalizations. Carvedilol users had a 38% higher hazard then metoprolol users of HF hospitalization during the follow-up period (HR 1.38; 95% CI 1.19 to 1.60, p <0.001). Artificial intelligence identified carvedilol exposure as the most important predictor for HF hospitalization. In conclusion, we found an increased risk of HF hospitalization for carvedilol users with this triad of diseases but no statistically significant differences in survival or risk of COPD, DM, hypoglycemia, and RF hospitalizations.

Beta-blocker, aspirin, and statin usage after first-time myocardial infarction in patients with chronic obstructive pulmonary disease: a nationwide analysis from 1995 to 2015 in Denmark.

AIMS: To determine whether beta-blockers, aspirin, and statins are underutilized after first-time myocardial infarction (MI) in patients with chronic obstructive pulmonary disease (COPD) compared with patients without COPD. Further, to determine temporal trends and risk factors for non-use. METHODS AND RESULTS: Using Danish nationwide registers, we performed a cross-sectional study investigating the utilization of beta-blockers, aspirin, and statins after hospitalization for first-time MI among patients with and without COPD from 1995 to 2015. Risk factors for non-use were examined in multivariable logistic regression models. During 21 years of study, 140 278 patients were included, hereof 13 496 (9.6%) with COPD. Patients with COPD were less likely to use beta-blockers (53.2% vs. 76.2%, P < 0.001), aspirin (73.9% vs. 78.8%, P < 0.001), and statins (53.5% vs. 61.9%, P < 0.001). Medication usage increased during the study period but in multivariable analyses, COPD remained a significant predictor for non-use: odds ratio (95% confidence interval) for non-use of beta-blockers 1.86 (1.76-1.97); aspirin 1.24 (1.16-1.32); statins 1.50 (1.41-1.59). Analyses stratified by ST-segment elevation myocardial infarction (STEMI) and non-STEMI showed similar undertreatment of COPD patients. Risk factors for non-use of beta-blockers in COPD included increasing age, female sex, and increasing severity of COPD (frequent exacerbations, use of multiple inhaled medications, and low lung function). Similar findings were demonstrated for aspirin and statins. CONCLUSION: Beta-blockers, and to a lesser extent aspirin and statins, were systematically underutilized by patients with COPD following hospitalization for MI despite an overall increase in the utilization over time. Increasing severity of COPD was a risk factor for non-use of the medications.

Beta-blocker choice and exchangeability in patients with heart failure and chronic obstructive pulmonary disease: an Italian register-based cohort study.

Clinical guidelines suggest that for patients with heart failure and concurrent chronic obstructive pulmonary disease (COPD), metoprolol/bisoprolol/nebivolol should be preferred over carvedilol. However, studies suggest a high proportion of carvedilol usage that remains unexplained. Therefore, we aimed to investigate the predictors of carvedilol choice in patients with heart failure and COPD that were naïve to carvedilol or metoprolol/bisoprolol/nebivolol. Caserta Local Health Unit databases (Italy) were used as data sources. Age, sex, chronic/acute comorbidities, and co-medications were included in a logistic regression model to assess predictors of carvedilol choice. Chronic comorbidities include those defined in the Elixhauser comorbidity index and all hospitalizations within two years prior to the first beta-blocker prescription. Comedications include all redeemed prescriptions within one year prior to the beta-blocker prescription. Kernel density estimations were used to assess the overlap in propensity and preference scores distributions for receiving carvedilol and thereby potential beta-blocker exchangeability. Totally, 10091 patients composed the study population; 2011 were exposed to carvedilol. The overlapping of propensity scores distributions was 57%. Accordingly, the exchangeability was not reached. Atrioventricular block (Odds Ratio, OR 8.20; 95% Confidence Interval, 95% CI 1.30-51.80), cerebrovascular thrombosis (OR 7.06; 95% CI 1.14-43.68), chronic kidney disease (OR 4.32; 95% CI 1.16-16.02), and acute heart failure (OR 1.97; 95% CI 1.28-3.03) hospitalizations were statistically significantly associated with carvedilol choice. Analogously, human insulin (OR 3.00; 95% CI 1.24-7.24), fondaparinux (OR 2.47; 95% CI 1.17-5.21) or strontium ranelate (OR 2.03; 95% CI 1.06-3.90) redeemed prescriptions. In conclusion, this study suggests the absence of beta-blockers exchangeability and a preferential choice of carvedilol in patients with heart failure, COPD and concurrent chronic kidney disease, atrioventricular block, cerebrovascular thrombosis, acute heart failure or redeeming human insulin, fondaparinux or strontium ranelate prescriptions. Therefore, it suggests that choice of prescribing carvedilol over metoprolol/bisoprolol/nebivolol is driven by differences in comorbidities and co-treatments.

COPD exacerbations: the impact of long versus short courses of oral corticosteroids on mortality and pneumonia: nationwide data on 67 000 patients with COPD followed for 12 months.

Introduction: A large group of patients with chronic obstructive pulmonary disease (COPD) are exposed to an overload of oral corticosteroids (OCS) due to repeated exacerbations. This is associated with potential serious adverse effects. Therefore, we evaluated the impact of a recommended reduction of OCS duration in 2014 on the risk of pneumonia hospitalisation and all-cause mortality in patients with acute exacerbation of COPD (AECOPD). Methods: This was a nationwide observational cohort study that was based on linked administrative registry data between 1 January 2010 and 31 October 2017. 10 152 outpatients with COPD (median age 70 years) treated with either a short (≤250 mg) or long course (>250 mg) of OCS for AECOPD were included in the study. Cox proportional hazards regression models were used to derive an estimation of multivariable adjusted HRs (aHRs) for pneumonia hospitalisation or all-cause mortality combined and pneumonia hospitalisation and all-cause mortality, separately. Results: The long course of OCS treatment for AECOPD was associated with an increased 1-year risk of pneumonia hospitalisation or all-cause mortality (aHR 1.3, 95% CI 1.1 to 1.4; p<0.0001), pneumonia hospitalisation (aHR 1.2, 95% CI 1.0 to 1.3; p=0.0110) and all-cause mortality (aHR 1.8, 95% CI 1.5 to 2.2; p<0.0001) as compared with the short course of OCS treatment. These results were confirmed in several sensitivity analyses. Conclusion: The change of recommendations from long courses to short courses of OCS for AECOPD in 2014 was strongly associated with a decrease in pneumonia admissions and all-cause mortality, in favour of short courses of OCS.

NIV for acute respiratory failure in COPD: high in-hospital mortality is determined by patient selection.

Introduction: Hospital mortality among chronic obstructive pulmonary disease (COPD) patients receiving NIV for acute respiratory failure has shown to be significantly higher in clinical settings than in the randomized trials (RCTs) which clinical guidelines are based on. This may be due to the quality of care of NIV or patient selection. In daily clinical practice, we include patients with terminal pulmonary disease with a do-not-intubate (DNI) or a do-not-resuscitate (DNR) order with a high mortality risk compared to highly selected patients in RCTs. The aim of this study was to determine the role of patient selection for in-hospital mortality among patients receiving NIV for acute respiratory failure of COPD. Methods: We conducted a retrospective study including all patients receiving acute NIV due to acute respiratory failure at the respiratory wards in 2012-2013 at two hospitals in Greater Copenhagen. Results: Overall in-hospital mortality rate was 30%. In patients with a DNI/DNR order, mortality was 59% and in patients with no limitations in treatment 2%. Patients who fulfilled the exclusion criteria of the RCT by Plant et al. had a mortality of 41% compared to 25% in the remaining population. Conclusions: High overall in-hospital mortality reflects that patient selection in clinical practice is very different from RCT. Quality of acute NIV treatment seems acceptable in clinical practice for patients with less severe COPD and no limitations in treatment. Higher mortality in patients with DNI/DNR order may be due to inefficient NIV treatment for these patients with more severe COPD.

Comparison of Long-Term Clinical Implications of Beta-Blockade in Patients With Obstructive Airway Diseases Exposed to Beta-Blockers With Different ß1-Adrenoreceptor Selectivity: An Italian Population-Based Cohort Study.

Rationale: Long-term clinical implications of beta-blockade in obstructive airway diseases remains controversial. We investigated if within the first 5 years of treatment patients with heart failure and obstructive airway diseases using non ß1-adrenoreceptor selective beta-blockers have an increased risk of being hospitalized for all-causes, heart failure, and chronic obstructive pulmonary disease (COPD) when compared to patient using selective beta-blockers. Methods: Carvedilol users were propensity matched 1:1 for co-treatments, age, gender, and year of inclusion in the cohort with metoprolol/bisoprolol/nebivolol users. Cox proportional hazard regression model was used to compare all causes, COPD, and heart failure hospitalization or the beta-blocker discontinuation between cohorts. For statistically significant associations, we computed the rate difference and the attributable risk. Results: Overall, 11,844 patients out of the 51,214 (23.1%) were exposed to carvedilol and 39,370 (76.9%) to metoprolol/bisoprolol/nebivolol. Carvedilol users had a higher hazard for heart failure hospitalization (HR 1.29; 95% Confidence Interval [CI] 1.18-1.40) with 106 (95%CI 76-134; p-value < 0.001) additional cases of heart failure hospitalization per 10000 person-years if compared to metoprolol/bisoprolol/nebivolol users. In all, 26.8% (95%CI 22.5-30.9%; p-value < 0.001) of heart failure hospitalizations in the study population could be attributed to being exposed to carvedilol. Carvedilol users had a higher hazard (HR 1.06; 95%CI 1.02-1.10) of discontinuing the pharmacological treatment with 131 (95%CI 62-201; p-value < 0.001) additional cases of beta-blocker discontinuation per 10000 person-years metoprolol/bisoprolol/nebivolol users. In all, 6.5% (95%CI 3.9-9.0%; p-value < 0.001) of beta-blocker discontinuation could be attributed to being exposed to carvedilol. Conclusion: On long-term follow-up period, carvedilol was associated with a higher risk of heart failure hospitalization and discontinuation if compared to metoprolol/bisoprolol/nebivolol users among patients with heart failure and obstructive airway diseases.

COPD: Mortality and Readmissions in Relation to Number of Admissions with Noninvasive Ventilation.

In severe COPD, patients having survived acute hypercapnic respiratory failure (AHRF) treated with noninvasive ventilation (NIV) have a high mortality and risk of readmissions. The aim was to analyze the prognosis for patients with COPD having survived AHRF and to assess whether previous admissions with NIV predict new ones.We conducted a retrospective follow-up analysis of 201 patients two years after NIV treatment of AHRF. Comparison of time-to-event in patients previously treated with NIV versus patients with no previous NIV treatment. We found a one-year mortality of 33.8% and high risks of: readmission (53.2%), any event (67.7%), and life-threatening events (49.8%). Patients with previous NIV treatments had an increased hazard ratio for life-threatening events: 1.60, p = 0.023 despite having lower in-hospital mortality than patients with no previous NIV treatment (18.9% vs. 33.1%, p = 0.043). We found that having survived one episode of AHRF considerably worsened the prognosis for the affected patients.The prognosis for patients having survived AHRF with NIV treatment is poor: the prognosis worsens with additional episodes of AHRF. Future research and treatment should focus on patients with repeated episodes of AHRF.

[Patients with chronic obstructive pulmonary disease and heart disease can benefit from beta-blocker treatment]. / Betablokkere kan gavne patienter med KOL og hjertesygdom

Chronic obstructive pulmonary disease (COPD) and coronary heart disease share smoking as the most important common risk factor and there is a high prevalence of cardiovascular disease among COPD patients. Although cardioselective beta-blockers are safe in treatment of COPD, they are often withheld in these patients. In observational studies, beta-blocker treatment is associated with significantly reduced mortality and reduced risk of exacerbations of COPD. This effect may be caused by the beneficial effect of beta-blockers on heart failure, tachycardia and upregulation of beta-receptors in the airways.

[Severe recurrent carbon monoxide poisoning caused by smoking]. / Svær recidiverende kulilteforgiftning forårsaget af tobaksrygning.

Carbon monoxide (CO) is an odourless, colourless and toxic gas. Sources of CO include car exhaust, charcoal and tobacco smoke. CO binds to haemoglobin forming carboxyhaemoglobin (COHb). Heavy smokers have COHb levels up to 15%. There are reports of COHb levels of 24,2% caused by tobacco use and 28,7% after narghile smoking. A 54-year-old woman with schizophrenia was admitted at the intensive care unit with COHb levels as high as 35% caused by cigarillo smoking. She also presented with severe thiazide-induced hyponatriaemia and high haemoglobin levels.