Increased serum SP-D in identification of high-risk smokers at high risk of COPD.

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

Incidence of primary spontaneous pneumothorax: a validated, register-based nationwide study.

OBJECTIVES: The incidence of primary spontaneous pneumothorax is partly unknown. Commonly quoted estimates were published decades ago and recent large-scale epidemiological publications lack validation. We validated the pneumothorax diagnosis in a national registry and estimated the incidence of primary spontaneous pneumothorax in young patients. METHODS: Complete data on patients with an assigned pneumothorax diagnosis was retrieved from the National Danish Patient Registry. Initially, we validated the diagnosis in a selected population: all patient charts with an assigned pneumothorax diagnosis from one cardiothoracic department over a 25-year period (1984-2008) were reviewed. Subsequently, the national incidence of primary spontaneous pneumothorax in young, healthy individuals was estimated by restricting our population to patients ≤40 years of age admitted during a 5-year period (2009-2014). We performed a systematic read-though of patient charts in 50% of the complete national cohort to ensure that we only included patients with their first episode of primary spontaneous pneumothorax. RESULTS: Validation revealed a poor inter-rater agreement (κ=0.08). Therefore, we abstained from further analysis on directly retrieved data from the national database. Subsequently, a systematic re-evaluation of 7022 patients revealed an incidence rate of 12.3 cases per 100 000 (95% CI 11.5-13.1) in males and 2.2 cases per 100 000 (95% CI 1.9-2.6) in females (male/female ratio 5.9). Compared with the general Danish population, pneumothorax patients had a lower body mass index (p<0.001) and smoked more than the Danish population in general (p<0.001). CONCLUSIONS: The incidence of primary spontaneous pneumothorax in a validated national study was lower than previously reported.

Danish respiratory society position paper: palliative care in patients with chronic progressive non-malignant lung diseases.

Background:  Chronic non-malignant lung diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) result in reduced quality of life (QoL), a high symptom burden and reduced survival. Patients with chronic non-malignant lung disease often have limited access to palliative care. The symptom burden and the QoL of these patients resembles patients with cancer and the general palliative approach is similar. However, the disease trajectory is often slow and unpredictable, and the palliative effort must be built on accessibility, continuity and professional competences. The Danish Health Authority as well as the WHO recommends that there is access to palliative care for all patients with life-threatening diseases regardless of diagnosis. In 2011, the Danish Health Authority requested that the national medical societies would to formulate guidelines for palliation. Methods: In 2015, a group of members of the Danish Respiratory Society (DRS) was appointed for this purpose. It was composed of experienced ILD and COPD researchers as well as clinicians from different parts of Denmark. A literature review was made, a draft was prepared, and all recommendations were agreed upon unanimously. Results: The Danish version of the position paper was finally submitted for review and accepted by all members of DRS. Conclusion: In this position paper we provide recommendations on the terminology of chronic and terminal lung failure, rehabilitation and palliative care, advanced care planning, informal caregivers and bereavement, symptom management, the imminently dying patient, and organization of palliative care for patients with chronic non-malignant lung diseases.

[Treatment limitations or discontinuation in patients with benign pulmonary diseases].

The decision to limit or discontinue treatment is a difficult issue, which all physicians will face. Timely communication with information on treatment possibilities and limitations, respectful listening to patients' and informal caregivers' wishes and early palliation is recommended in a stable phase. In some situations, it is better to stop life-prolonging treatment and optimise quality of life in patients with benign pulmonary diseases. Decision on treatment limitations or discontinuation is best taken at a conference and should be based on the patient's wishes, the disease stage and progression and potential reversible components.

[Treatment of stable chronic obstructive pulmonary disease].

In 2012, The Danish Society of Respiratory Medicine gave birth to their most recent guideline regarding chronic obstructive pulmonary disease (COPD). Much has happened since, and in late 2017 an update has been published. Chapters have been deleted, and new ones added. The major alteration has been in the section concerning treatment with inhalation medication - now aiming at an easy stepwise up-titration of long-acting medicine as well as a guide of how to down-titrate inhaled corticosteroids. This review mainly focuses on how to treat stable COPD according to The Danish Society of Respiratory Medicine.

Surgical treatment versus conventional chest tube drainage in primary spontaneous pneumothorax: a randomized controlled trial.

OBJECTIVES: Primary spontaneous pneumothorax frequently recurs after chest tube management. Evidence is lacking whether patients may benefit from surgery following their first episode. METHODS: We performed a multicentre, randomized trial and enrolled young, otherwise healthy patients admitted with their first episode of primary spontaneous pneumothorax and treated using conventional chest tube drainage. Patients underwent high-resolution computed tomography on fully expanded lungs, and using web-based randomization, we assigned patients to continued conservative chest tube treatment or chest tube treatment followed by video-assisted thoracoscopic surgery (VATS) with the resection of bullae/blebs and mechanical pleurodesis. Patients were stratified into 2 groups based on the presence of bullae ≥1 cm on high-resolution computed tomography. The primary end point was readmission with ipsilateral recurrence. Secondary end points were complications and length of hospitalization. RESULTS: Between 1 August 2009 and 4 November 2016, we screened 457 patients, of whom 373 were eligible for inclusion and 181 were enrolled: male/female ratio = 5.0. We identified 88 patients with blebs <1 cm: 50 were randomly assigned to chest tube treatment and 38 to VATS. Ninety-three patients had bullae ≥1 cm: 43 were randomly assigned to chest tube treatment and 50 to VATS. Forty-three (23.8%) patients experienced recurrence during the follow-up period. Overall, recurrence was significantly lower following VATS when compared with conventional chest tube treatment (P = 0.0012). When stratified by bullae size, VATS proved significantly better for bullae ≥1 cm (P = 0.014). We observed a size-response relationship with increased risk of recurrence for larger bullae (P = 0.013). CONCLUSIONS: Surgery was an effective treatment to prevent recurrence in patients with their first presentation of primary spontaneous pneumothorax and should be the standard of care when high-resolution computed tomography demonstrates bullae ≥2 cm. Clinical trial registration: ClinicalTrial.gov: NCT 02866305.

A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol.

BACKGROUND: The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects. Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome. METHODS: This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage. DISCUSSION: This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02857842 , 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.

Cannabis increased the risk of primary spontaneous pneumothorax in tobacco smokers: a case-control study.

OBJECTIVES: Previous smaller case series suggested that cannabis smoking may cause spontaneous pneumothorax, but this finding remains controversial. We investigated the possible association between smoking tobacco and cannabis and the risk of having a primary spontaneous pneumothorax in a large, homogeneous cohort of young, healthy individuals. METHODS: In a case-control study, we prospectively investigated young (≤40 years) patients admitted in Western Denmark from 2009 to 2016 with their first episode of primary spontaneous pneumothorax. Baseline characteristics and smoking habits including both tobacco and cannabis were obtained from questionnaires presented on admittance. We compared our findings with those of a population-based control group matched by age, sex and geographical area. Calculated odds ratios were compared using the Fisher's exact test for small frequencies and the χ2 test or the Mann-Whitney test for larger frequencies. RESULTS: A total of 416 patients participated (male/female ratio = 3.9). We observed a significantly increased risk of primary spontaneous pneumothorax in daily smokers compared with female never smokers (odds ratio = 8.10, 95% confidence interval: 4.61-14.14, P < 0.001) and male never smokers (odds ratio = 4.85, 95% confidence interval: 3.23-7.19, P < 0.001). The combination of smoking both cannabis and tobacco in men increased the risk of spontaneous pneumothorax significantly (odds ratio = 8.74, 95% confidence interval: 4.30-19.51, P < 0.001). In contrast, the cannabis habits of female patients did not differ from those of the Danish population in general. CONCLUSIONS: Combined smoking of tobacco and cannabis significantly aggravates the risk of having a primary spontaneous pneumothorax in young men compared to both never smokers and daily smokers.

Recurrent Primary Spontaneous Pneumothorax is Common Following Chest Tube and Conservative Treatment.

INTRODUCTION: Previous studies on primary spontaneous pneumothorax reported variable recurrence rates, but they were based on heterogeneous patient populations including secondary pneumothorax. We investigated young patients with primary spontaneous pneumothorax exclusively and used a national registry to track readmissions and calculate independent predictors of recurrence. METHODS: A prospective cohort study of consecutive young patients who were admitted over a 5-year period with their first episode of primary spontaneous pneumothorax and treated conservatively with a chest tube. Baseline characteristics were obtained from questionnaires presented on admittance. All patients were discharged with fully expanded lungs on chest radiography. Patient charts were identified in the national electronic patient registry for detailed information on readmissions due to recurrent spontaneous pneumothorax. RESULTS: We included 234 patients. Male/female = ratio 5/1. After a median observation period of 3.6 years (range 1-6 years), recurrent pneumothorax was observed in 54 %. Ipsilateral recurrence was the most common (79 %) but 30 % also experienced contralateral pneumothorax during the study period. Females had a significantly higher age at debut (p < 0.01) and experienced significantly more recurrences over time (p < 0.01). Low body weight (<60 kg) was an independent predictor of recurrence and patients with repeated recurrences were significantly younger at debut (p = 0.01). CONCLUSIONS: Primary spontaneous pneumothorax in younger patients with their first episode had a much higher recurrence rate than previously reported. Every doctor who treats patients with primary spontaneous pneumothorax should be aware and patients informed.

Early telemedicine training and counselling after hospitalization in patients with severe chronic obstructive pulmonary disease: a feasibility study.

BACKGROUND: An essential element in the treatment of patients with chronic obstructive pulmonary disease (COPD) is rehabilitation, of which supervised training is an important part. However, not all individuals with severe COPD can participate in the rehabilitation provided by hospitals and municipal training centres due to distance to the training venues and transportation difficulties. The aim of the study was to assess the feasibility of an individualized home-based training and counselling programme via video conference to patients with severe COPD after hospitalization including assessment of safety, clinical outcomes, patients' perceptions, organisational aspects and economic aspects. METHODS: The design was a pre- and post-test intervention study. Fifty patients with severe COPD were included. The telemedicine training and counselling included three weekly supervised exercise sessions by a physiotherapist and up to two supervised counselling and training sessions in energy conservation techniques by an occupational therapist. The telemedicine videoconferencing equipment was a computer containing a screen, a microphone, an on/off switch and a volume control. RESULTS: Thirty seven (74%) participants completed the programme, with improvements in health status assessed by the Clinical COPD Questionnaire and physical performance assessed by a sit-to-stand test and a timed-up-and-go test. There were no cases of patient fall or emergency contact with a general practitioner during the telemedicine training sessions. The study participants believed the telemedicine training and counselling was essential for getting started with being physically active in a secure manner. The business case showed that under the current financing system, the reimbursement to the hospital was slightly higher than the hospital expenditures. Thus, the business case for the hospital was positive. The organizational analysis indicated that the perceptions of the staff were that the telemedicine service had improved the continuity of the rehabilitation programme for the patients and enabled the patients' everyday lives to be included in the treatment. CONCLUSIONS: This study showed that home-based supervised training and counselling via video conference is safe and feasible and that telemedicine can help to ensure more equitable access to supervised training in patients with severe COPD. TRIAL REGISTRATION: Clinical Trials NCT02085187 (Date of registration 10.03.2014).

Reorganisation of acute referral to an emergency department resulted in fewer admissions for chronic obstructive pulmonary disease but in higher rates of non-invasive ventilation.

INTRODUCTION: We performed an audit on all admissions with chronic obstructive pulmonary disease (COPD) in ex-acerbation to the Department of Emergency Medicine, Odense University Hospital (DEM) in the second half of 2012 to evaluate if an organisational change had altered visitation, treatment, initiation of non-invasive ventilation (NIV) and monitoring. We chose not to include the entire year to avoid data influenced by organisational start-up difficulties. The hypothesis was that NIV was initiated according to guidelines to the same extent as prior to the implementation of DEM. METHODS: Data from medical records were retrieved from two COPD cohorts: 1) all patients admitted to DEM between 1 July and 31 December 2012 and 2) all patients admitted to the Medical Emergency Ward, Odense University Hospital (MEW) in 2010. RESULTS: There were 300 eligible admissions comprising 236 unique patients in DEM in the second half of 2012 compared with 393 admissions in MEW in the second half of 2010, a 24% reduction. The groups were similar in gender and age, but patients admitted in 2012 had higher registered co-morbidity rates, but no significant difference in lung function values. NIV was indicated in 91 admissions (30%) and initiated in 58 admissions (19.3%) in 2012. By comparison NIV was indicated in 193 admissions (24%) and initiated in 151 admissions (18.8%) in 2010. CONCLUSION: There was a statistically significant increase in NIV indication without initiation of treatment in 2012 (28 admissions; 9.3%) compared with 2010 (36 admissions; 4.5%), but no referrals to the intensive care unit or deaths were registered during the hospitalisation in either of the groups, but one patient died within 30 days after admission from the DEM. FUNDING: This project was funded by an Odense University Hospital research grant. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (record no. 2011-41-6459).

Serum vitamin D in patients with chronic obstructive lung disease does not correlate with mortality--results from a 10-year prospective cohort study.

BACKGROUND: Recent studies have found vitamin D (25-OHD) deficiency and insufficiency to be common among patients with COPD. Serum level of 25-OHD seems to correlate to pulmonary function, COPD disease staging, and increased susceptibility to respiratory infections. We wanted to investigate whether vitamin D deficiency or insufficiency was associated with mortality rate in patients suffering from advanced COPD. METHODS: 25-OHD serum levels were measured in 462 patients suffering from moderate to very severe COPD. Patients were stratified into three groups according to serum levels of 25-OHD. Outcome measure was mortality in a 10 year follow-up period. Kaplan-Meier curves (KM) were plotted and mortality hazard ratios (HR) were calculated using Cox Proportional Hazard regression (Cox PH). RESULTS: Serum 25-OHD deficiency and insufficiency were prevalent. We were unable to demonstrate any association between baseline serum levels of 25-OHD and mortality rate. We found an association between mortality and age [HR 1.05 (CI 95%: 1.03-1.06)], Charlson score [HR 1.49 (CI 95%: 1.06-2.09)], increasing neutrophil count [HR 1.05 (CI 95%: 1.02-1.09)], severe [HR 1.41 (CI 95%: 1.06-1.86)]/very severe COPD [HR 2.19 (CI 95%: 1.58-3.02)] and a smoking history of more than 40 pack years [HR 1.27 (CI 95%: 1.02-1.70)]. CONCLUSIONS: Serum level of 25-OHD does not seem to be associated with mortality rate, suggesting no or only a minor role of 25-OHD in disease progression in patients with moderate to very severe COPD.

[Implementation of non invasive ventilation in respiratory ward in patients with exacerbations of chronic obstructive pulmonary disease]. / Implementering af noninvasiv ventilation på en lungemedicinsk afdeling hos patienter med kronisk obstruktiv lungesygdom i eksacerbation.

INTRODUCTION: Non Invasive Ventilation (NIV) has been shown to lower the mortality rate from 22% to 9% when given as an additional treatment to selected chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure and hypercapnia. Risk of intubation has been shown to fall from 33% to 14%. In February 2004 NIV was added as a treatment modality in a respiratory ward to patients with exacerbation of COPD after initial stabilization with standard treatment: oxygen, bronchodilators, systemic steroids and, if indicated, antibiotics. We present the results of NIV treatment. MATERIALS AND METHODS: Over a period of one year there were 906 admissions (555 patients) registered with COPD when discharged from the respiratory department, and 80 NIV patient courses (71 patients; two patients received NIV three times and five patients twice) were registered. Failure of the treatment was defined as reference to the Intensive Care Unit (ICU) for further treatment or death. RESULTS: Three patients did not have COPD. A group of patients (13) were admitted directly to the ICU and received NIV in the respiratory ward after discharge from the ICU. A total of 19 patients receiving NIV were not evaluated as ICU candidates. There were 45 patients (ICU candidates) receiving NIV, 36 of which (80%) were treated successfully. Six patients were referred to the ICU (13.3%). Two patients died in the ICU and a third patient died in the ward (6.7%). In all, 11 patients died. CONCLUSION: In selected COPD patients with acute respiratory failure and hypercapnia NIV is a safe and life-saving treatment applicable to the respiratory ward.

HLA haplotypes in dizygotic twin pairs: are dizygotic twins more similar than sibs?

It has been suggested that dizygotic twin pairs share two HLA haplotypes more often than ordinary siblings and thus might be genetically more alike. We tested this hypothesis in dizygotic twin pairs from the Danish Twin Registry. A total of 114 (60 female and 54 male) same-sexed healthy twin pairs aged 18-45 years participated. Dizygosity was established by means of DNA sequencing of nine polymorphic markers. HLA-A, B and Cw specificities were typed with serology, and if data were inconclusive, with DNA typing. If twin partners had the same HLA-types, they were assumed to share two haplotypes. If they had 1 HLA A, B and C antigen group in common they were assumed to share one haplotype and if they had no HLA types in common they were assumed to share zero haplotypes. Since HLA-types from parents were unavailable we could not test for identity-by-descent and thus had a risk of overestimating the number of twins sharing two haplotypes. A Chi-square test was used to compare observed numbers in each haplotype sharing group with the expected numbers. Twenty-nine (expected 28.5) twin pairs had two HLA-types in common, 52 (expected 57) had one HLA-type in common and 33 (expected 28.5) had zero HLA-types in common, p = 0.56. Our data show that DZ twins are not more similar than sibs from different pregnancies in general.