OPTIMAL: Titration of anti-IL5 biologics in severe asthma - An open label randomised controlled trial.

BACKGROUND: Anti-interleukin 5 (anti-IL5) biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL5 biologic. METHODS: In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible. RESULTS: Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17% (p=0.13)). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout. CONCLUSIONS: This study serves as a proof-of-concept for titration of anti-IL5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future.

Surfactant protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage.

Variation in surfactant protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The association between serum SP-D (sSP-D) and expiratory lung function was assessed in a cross-sectional design in a Danish twin population (n = 1,512, 18-72 yr old). The adjusted heritability estimates for expiratory lung function, associations between SP-D gene (SFTPD) single-nucleotide polymorphisms or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 s and forced vital capacity in the presence of current tobacco smoking but not in nonsmokers. The two SFTPD single-nucleotide polymorphisms, rs1923536 and rs721917, and haplotypes, including these single-nucleotide polymorphisms or rs2243539, were inversely associated with expiratory lung function in interaction with smoking. In conclusion, SP-D is phenotypically and genetically associated with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive pulmonary disease initiation and development.

Surfactant protein D, Club cell protein 16, Pulmonary and activation-regulated chemokine, C-reactive protein, and Fibrinogen biomarker variation in chronic obstructive lung disease.

Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction. The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessment of patients, prediction of risk, and guidance of treatment. The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD. The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease and hard clinical outcomes, their modification by interventions, and whether changes in clinical outcomes are reflected by changes in the biomarker.

Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies.

BACKGROUND: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. RESEARCH QUESTION: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? STUDY DESIGN AND METHODS: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment. RESULTS: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy. INTERPRETATION: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy.

Network of doctors for multimorbidity and diabetes - the NOMAD intervention: protocol for feasibility trial of multidisciplinary team conferences for people with diabetes and multimorbidity.

BACKGROUND: The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity. METHODS: A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial. DISCUSSION: A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future. ADMINISTRATIVE INFORMATION: Protocol version: 01 TRIAL REGISTRATION: NCT05913726 - registration date: 21 June 2023.

Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register.

BACKGROUND: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. OBJECTIVE: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. METHODS: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. RESULTS: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. CONCLUSION: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Incidence of community-acquired pneumonia hospitalisation in persons with bronchiectasis during the COVID-19 lockdown in Denmark: a retrospective cohort study.

BACKGROUND: Persons with bronchiectasis have a high risk of community-acquired pneumonia. Social distancing measures, implemented to prevent the spreading of SARS-CoV-2, could potentially reduce the incidence of other infectious diseases. RESEARCH QUESTION: Was the COVID-19 lockdown period, along with accompanying social distancing measures, associated with reduced hospital admissions for community-acquired pneumonia and decreased overall mortality rates among individuals with bronchiectasis? METHODS: Social distancing measures were introduced in Denmark by 12 March 2020 and were preserved until 20 May 2020 (social distancing period), after which the measures were gradually dismissed. The study included all adults (≥18 years) with bronchiectasis residing in Denmark. Confirmed cases of SARS-CoV-2 infection were excluded. We retrospectively investigated the incidence of community-acquired pneumonia hospital admission, death of all causes and respiratory antibiotic treatment in the 10-week social distancing period in 2020, compared with the same dates in 2019. 9344 persons were included in the study. RESULTS: In the social distancing period, the incidence rate of pneumonia-hospitalisation per 10 000 person-weeks was 9.2 compared with 13.8 in the reference period. This reduction corresponds to an incidence rate ratio (IRR) of 0.67 (95% CI 0.51 to 0.88, p<0.01). Mortality was unchanged (IRR 0.90, 95% CI 0.61 to 1.32, p=0.58). Fewer persons received respiratory antibiotics (IRR 0.85, 95% CI 0.78 to 0.94, p<0.001). CONCLUSION: The social distancing period was associated with a lower incidence of community-acquired pneumonia hospitalisations and respiratory antibiotic treatments in persons with bronchiectasis while all-cause mortality remained unchanged.

Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study.

Background: Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome. Methods: Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma. Results: In our registry of 56,523 patients with COPD, 5,661 collected promethazine (n = 3,723) or melatonin (n = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, p < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, p < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine (p = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, p<0.0001). Conclusions: Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.

Hospitalization for chronic obstructive pulmonary disease and pneumonia: association with the dose of inhaled corticosteroids. A nation-wide cohort study of 52 100 outpatients.

OBJECTIVES: International guidelines only advocate the use of inhaled corticosteroids (ICSs) in patients with chronic obstructive pulmonary disease (COPD) experiencing recurring exacerbations and eosinophilic inflammation. However, ICSs are commonly used in patients with COPD and without exacerbations and signs of eosinophilic inflammation, thus possibly increasing the risk of hospitalization for pneumonia. Thus, we aimed to determine the risk of hospitalization for pneumonia associated with increasing cumulated ICS doses among patients with COPD to establish whether there is dose dependency. METHODS: A retrospective cohort study included all patients with COPD treated at a respiratory outpatient clinic in Denmark. The patients were divided into four groups based on their average daily ICS exposure. The dose-response relationship was investigated using a multivariable Cox proportional hazard regression analysis. RESULTS: In total, 52 100 patients were included, who were divided into the no-use (n = 15 755), low-dose (n = 12 050), moderate-dose (n = 12 488), and high-dose (n = 11 807) groups. ICS use was strongly associated with hospitalization for pneumonia (hazard ratio [HR], 1.3; CI, 1.2-1.3) (ICS vs. no ICS). The risk of hospitalization for pneumonia increased with every dosing group step: low dose: HR, 1.1 (CI, 1.0-1.2); moderate dose: HR, 1.2 (CI, 1.1-1.3), and high dose: HR, 1.5 (CI, 1.4-1.6); "no use" was the reference. Sensitivity analyses confirmed these findings. CONCLUSIONS: In the dose-response relationship analysis, ICS dose were associated with a substantially increased risk of hospitalization for pneumonia of up to 50%. Our data support that ICSs should be administered at the lowest possible dose and only to patients with COPD who have a documented need.

Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring Streptococcus pneumoniae Infection. A Multiregional Epidemiological Study.

Background: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users. Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses. Findings: A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with S. pneumoniae during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results. Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring S. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.

The multidisciplinary approach to eosinophilia.

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty-e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.

Physician-led in-hospital multidisciplinary team conferences with multiple medical specialities present - A scoping review.

Introduction: Multidisciplinary Team Conferences (MDTs) are complex interventions in the modern healthcare system and they promote a model of coordinated patient care and management. However, MDTs within chronic diseases are poorly defined. Therefore, the aim of this scoping review was to summarise the current literature on physician-led in-hospital MDTs in chronic non-malignant diseases. Method: Following the PRISMA-ScR guideline for scoping reviews, a search on MDT interventions in adult patients, with three or more medical specialties represented, was performed. Results: We identified 2790 studies, from which 8 studies were included. The majority of studies were non-randomised and focused on a single disease entity such as infective endocarditis, atrial fibrillation, IgG4-related disease, or arterial and venous thrombosis. The main reason for referral was confirmation or establishment of a diagnosis, and the MDT members were primarily from medical specialties gathered especially for the MDT. Outcomes of the included studies were grouped into process indicators and outcome indicators. Process indicators included changes in diagnostic confirmation as well as therapeutic strategy and management. All studies reporting process indicators demonstrated significant changes before and after the MDT. Conclusion: MDTs within chronic diseases appeared highly heterogeneous with respect to structure, reasons for referral, and choice of outcomes. While process indicators, such as change in diagnosis, and treatment management/plan seem improved, such have not been demonstrated through outcome indicators.

Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register.

Background: Phase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma. Methods: This prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication, i.e. recurrent exacerbations and/or use of mOCS. Results: A total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210 versus 30 mL; p<0.0001 and Δ -1.04 versus -0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e. no mOCS and lower ACQ score) and higher blood eosinophils. Conclusions: More than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Temporary immersion bioreactor system for propagation by somatic embryogenesis of hybrid larch (Larix × eurolepis Henry).

Somatic embryogenesis (SE) has high potential for large-scale clonal propagation of conifers. Different types of bioreactor cultures have been tested for the conifer SE process where the temporary immersion bioreactors (TIBs) have proved to be useful across the different developmental steps of the SE process. In the present study the use of TIBs was tested for hybrid larch (Larix × eurolepis Henry). The results showed two-fold increases in both fresh weight (FW) of pro-embryogenic masses (PEMs) and yield of cotyledonary embryos in the TIBs compared to solid medium in plates. For the germination phase, the highest number of roots per plant, the root length and height of plants were also obtained in the TIBs. The results show that the TIB system can be successfully used to support scale up of plant production in all steps of the SE process from proliferation to germination of hybrid larch (Larix × eurolepis Henry).

The role of knowledge in internet-based cognitive behavioural therapy for adolescent depression: Results from a randomised controlled study.

BACKGROUND AND OBJECTIVES: Clients' knowledge about their condition and treatment is considered crucial for general health improvement, and knowledge acquisition is an essential part in internet-based cognitive behavioural therapy (ICBT). Yet, little is known about the role of knowledge and how it influences treatment outcome. This study aimed to examine if explicit knowledge increased following ICBT for adolescent depression, if knowledge gain would be associated with symptom reduction, and if pre-existing knowledge predicted changes in depressive symptoms. METHODS: Seventy-one adolescents were randomised to a therapist-supported ICBT or a attention control condition. A measure of depression (BDI-II) and a knowledge test dealing with depression, comorbid anxiety, and its CBT-treatment were administered before and after treatment. RESULTS: Significant improvements in knowledge were observed following ICBT compared to the attention control (between-group Cohen's d = 1.25, 95% CI [0.67-1.79]). On average, participants in the treatment group answered 1.4 more questions correctly at post treatment compared to the control group. No relation between change in knowledge and change in depressive symptoms could be observed. Knowledge scores at baseline were high for both groups, with participants answering approximately 75% of the questions correct. A higher level of initial knowledge level predicted poorer treatment response (Parson's r = -0.38, p = .048). CONCLUSIONS: The findings indicate that knowledge about basic concepts and principles about depression, anxiety, and CBT increases following ICBT. This increase in knowledge was not related to change in depressive symptoms, indicating that knowledge is a different construct. The results also suggest that clients who are more knowledgeable prior to treatment might benefit less from ICBT. In sum, the results highlight the need to further examine the role of knowledge in ICBT.

Plasma microfibrillar-associated protein 4 is not prognostic of emphysema progression but is associated with cardiovascular disease history and mortality in COPD patients.

Circulating MFAP4 is a relevant biomarker to identify COPD patients at risk of death and cardiovascular comorbidity after smoking cessation http://ow.ly/6vnL30o8t1g.

Chat- and internet-based cognitive-behavioural therapy in treatment of adolescent depression: randomised controlled trial.

BACKGROUND: Depression is a major contributor to the burden of disease in the adolescent population. Internet-based interventions can increase access to treatment. AIMS: To evaluate the efficacy of internet-based cognitive-behavioural therapy (iCBT), including therapist chat communication, in treatment of adolescent depression. METHOD: Seventy adolescents, 15-19 years of age and presenting with depressive symptoms, were randomised to iCBT or attention control. The primary outcome was the Beck Depression Inventory II (BDI-II). RESULTS: Significant reductions in depressive symptoms were found, favouring iCBT over the control condition (F(1,67) = 6.18, P < 0.05). The between-group effect size was Cohen's d = 0.71 (95% CI 0.22-1.19). A significantly higher proportion of iCBT participants (42.4%) than controls (13.5%) showed a 50% decrease in BDI-II score post-treatment (P < 0.01). The improvement for the iCBT group was maintained at 6 months. CONCLUSIONS: The intervention appears to effectively reduce symptoms of depression in adolescents and may be helpful in overcoming barriers to care among young people. DECLARATION OF INTEREST: N.T. and G.A. designed the programme. N.T. authored the treatment material. The web platform used for treatment is owned by Linköping University and run on a non-for-profit basis. None of the authors receives any income from the programme.

The Swedish Twin Registry in the third millennium: an update.

The Swedish Twin Registry was first established in the late 1950s. Today it includes more than 170,000 twins--in principle, all twins born in Sweden since 1886. In this article we describe some ongoing and recently completed projects based on the registry. In particular, we describe recent efforts to screen all twins born between 1959 and 1985, and young twin pairs when they turn 9 and 12 years of age. For these studies, we present initial frequencies of common conditions and exposures.

Microfibrillar-associated protein 4: a potential biomarker of chronic obstructive pulmonary disease.

BACKGROUND: Microfibrillar-associated protein 4 (MFAP4) is a matricellular glycoprotein that co-localises with elastic fibres and is highly expressed in the lungs. The aim of this study was to test the hypothesis that plasma MFAP4 (pMFAP4) reflects clinical outcomes in chronic obstructive pulmonary disease (COPD). METHODS: pMFAP4 was measured by an AlphaLISA immunoassay in stable COPD (n = 69) at baseline and at follow-up until 24 months after inclusion and in acute exacerbations of COPD (AECOPD) (n = 14) at baseline and until 6 months after inclusion. RESULTS: The majority of patients (89%) were in GOLD II and III. Multiple linear regressions showed positive associations between pMFAP4 and the Global initiative for Obstructive Lung Disease (GOLD) grade (p = 0.01), modified Medical Research Council score (p < 0.0001) and BODE index (p = 0.04). Negative associations were found with 6-min walking distance (p = 0.04) and bronchodilator-induced reversibility (p = 0.02). The pMFAP4 levels varied less than 25% between the baseline and a 3 month follow-up in 83% of the patients. The pMFAP4 levels appeared unaffected in the acute phase of severe AECOPD but rose to an increased stable level within one month after hospitalization. CONCLUSION: Increased pMFAP4 was associated to the severity in COPD and has the potential to serve as a stable disease biomarker. This observation warrants confirmation in a larger longitudinal COPD population.