Nationwide lung function monitoring from infancy in newborn-screened children with cystic fibrosis.

Background: Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. Methods: This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. Results: 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Conclusions: Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.

Behavioural side effects of inhaled corticosteroids among children and adolescents with asthma.

BACKGROUND: Inhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor's clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors. METHODS: First, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region. RESULTS: EMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA. CONCLUSION: Behaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.

Characteristics and impact of exercise-induced laryngeal obstruction: an international perspective.

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathlessness and wheeze yet is frequently misdiagnosed as asthma. Insight regarding the demographic characteristics, laryngeal abnormalities and impact of EILO is currently limited, with data only available from individual centre reports. The aim of this work was to provide a broader perspective from a collaboration between multiple international expert centres. METHODS: Five geographically distinct clinical paediatric and adult centres (3 Denmark, 1 UK, 1 USA) with an expertise in assessing unexplained exertional breathlessness completed database entry of key characteristic features for all cases referred with suspected EILO over a 5-year period. All included cases completed clinical asthma workup and continuous laryngoscopy during exercise (CLE) testing for EILO. RESULTS: Data were available for 1007 individuals (n=713 female (71%)) with a median (range) age of 24 (8-76) years, and of these 586 (58%) were diagnosed with EILO. In all centres, EILO was frequently misdiagnosed as asthma; on average there was a 2-year delay to diagnosis of EILO, and current asthma medication was discontinued in 20%. Collapse at the supraglottic level was seen in 60%, whereas vocal cord dysfunction (VCD) was only detected/visualised in 18%. Nearly half (45%) of individuals with EILO were active participants in recreational-level sports, suggesting that EILO is not simply confined to competitive/elite athletes. CONCLUSION: Our findings indicate that key clinical characteristics and the impact of EILO/VCD are similar in globally distinct regions, facilitating improved awareness of this condition to enhance recognition and avoid erroneous asthma treatment.

[Childhood asthma: Danish guidelines for diagnosis and treatment]. / Astma hos børn.

These clinical guidelines were developed by the Danish Pediatric Asthma Center in collaboration with the Danish Paediatric Society. Key messages in the guidelines are: 1) Inhaled steroids are the most effective preventive medication and are first choice in children with persistent symptoms. 2) There is rarely indication for more than low to moderate doses of inhaled steroids as preventive medication. 3) There is insufficient evidence for preventive medication in pre-school children with intermittent asthma; a trial of leukotriene-receptor-antagonists or inhaled steroids could be done.

[Shared care--integrated cooperation across the sector boundaries about patient's course. Modern health care system cooperates]. / "Shared care"--et integreret samarbejde om patientforløb på tvaers af sektorgraenserne. Det moderne sundhedsvaesen samarbejder.

Shared care programmes have been introduced in Denmark for areas, such as diabetes, asthma, and dementia. Over a three-year period, the communication and co-operation between the health sectors have improved. Specific demands on hospital referral and discharge letters have resulted in improved quality of contents and structure. This review shows that there is limited ongoing research on shared care and that the end points including formulations like "improved co-operation" have been too broad. Almost no research is available on specific improvements obtained by shared care. The study shows that implementation of shared care research programmes with specific end points is very extensive. Only 10 per cent of the present studies have specific end points, and 75 per cent of these show positive effects of shared care programmes. The GP Consulting System in Denmark has proved most useful in the progress of shared care. Future research in shared care should focus on specific end points, in which analyses of patient's course are fundamental in an effort to obtain improvements.

[Research activities of junior physicians]. / Yngre laegers forskningsaktivitet.

INTRODUCTION: Since 1991, the Danish Junior Doctors' Association has carried out annual investigations among its members in regard to education. In 2001, the questionnaire included a special section about scientific activities. MATERIALS AND METHODS: The investigation included approximately 70 questions which were sent to all members of the Danish Junior Doctors' Association. A total of 76.2% answered the questionnaire. The age of the junior doctors and the year of graduating are comparable in the investigations from 1993 to 2001. RESULTS: 52.7% of the junior doctors make research in their spare time, and 47.1% have published at least once as primary researcher. The comparison of the investigations from 1993 to 2001 shows a significant fall in the average publications per doctor and in the number of doctors with at least one published paper. From 1999, there were 7% doctors less with one published paper (chi 2 = 53.4; p < 0.001). The average number of published articles per primary researcher has declined from 6.69/doctor in 1993 to 2.48/doctor in 2001 (t = -25.04, p < 0.001). As a whole, 11.9% of all junior doctors had a PhD-degree and 3.0% had a doctor's degree. 7.6% were in the process of a PhD-study. The number of junior doctors with a PhD is significantly rising. The number of doctors seeking positions at universities is less than 2%, the rest seek clinical education and work. DISCUSSION: The publication rate has declined over the past ten years, which has many reasons. One reason is the increasing number of PhD-degrees and an increase in the impact factor, which means qualitative research improvement. A changed procedure in the postgraduate education is a factor as well. The low recruitment of junior doctors for pregraduate education seems to be a constant problem.