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.

Cryotherapy in the paediatric airway: Indications, success and safety.

BACKGROUND AND OBJECTIVE: Cryotherapy in interventional bronchoscopy is a new treatment modality, which has recently been made available for the paediatric airway. Lack of experience and safety concerns have led to hesitant adaptation. The aim of this study was to assess indications, success rates and complications of airway cryotherapy in children. METHODS: Bronchoscopists from medical centre performing cryotherapy in patients between 0 and 18 years were invited to participate in a prospective study based on an online questionnaire. Patient and participant data were collected between June 2020 and June 2021. RESULTS: A total of 69 cryotherapy procedures were performed in 57 patients a for three main indications: Biopsy (30), restoration of airway patency (23) and foreign body aspiration (16). The overall success rate was 93%, the remaining 7% were performed for foreign body removal and required a switch of technique. Restoration of airway patency was successfully applied in various pathologies, including mucus plugs, bronchial casts and post traumatic stenosis. The diagnostic yield of transbronchial biopsies was 96%. No severe complications were encountered; one pneumothorax following a cryobiopsy required a chest drain for 48 h. No child was admitted to intensive care or died from a procedural complication. CONCLUSION: In this largest paediatric case collection to date, cryotherapy was safe and carried a high success rate. Cryobiopsy compares favourably to the widely used forceps biopsy and could replace it in the future. Paediatric bronchoscopists are encouraged to add cryotherapy to their armamentarium of airway interventions.

Validation of nasal tracheal aspiration in children with lung disease.

BACKGROUND: Nasal tracheal aspiration (NTA) is a frequently used diagnostic method to assess of infections in the lower airways. However, the validity of the method has not previously been compared to bronchoalveolar lavage (BAL) in non-intubated children with a lung disease. We hypothesised that NTA performed by health professionals using the nares vocal cord distance to be placed at the entrance of the trachea, will result in same finding of bacteria in the lower airways as the gold standard of BAL. METHODS: In a prospective study, 173 paired samples of NTA and BAL were obtained between June 2016 to August 2018. Samples were collected from all patients undergoing bronchoscopy with spontaneous breathing during general anaesthesia. This study compares the microbiological results from the cultures obtained by investigating complete concordance i.e. identical pathogenic bacteria and coherence i.e. absence or presence of pathogenic bacteria growth between NTA and BAL. RESULTS: Samples were collected in 164 patients, 158 children between 21 days and 18 years of age and six young adults still treated at the paediatric department. The overall similarity (complete agreement) was found in 49% [41-56], sensitivity was 35% [27-45], specificity was 66% [55-76], positive predictive value was 36% [27-46] and negative predictive value was 64% [54-64] concerning complete pathogenic bacteria concordance. If we only considered coherence growth of pathogenic bacteria, similarity was 71% [63-79], sensitivity was 74% [64-81], specificity was 66% [55-76], positive predictive value was 75% [65-82] and negative predictive value was 65% [54-75]. Patients with cystic fibrosis showed a similarity of 88% [73-95], a sensitivity of 92% [76-99], a specificity of 71% [36-95], a positive predictive value of 92% [76-99] and a negative predictive value of 71% [36-95] concerning coherence growth of pathogenic bacteria. CONCLUSION: The study indicates that NTA compared to BAL as the gold standard is not clinically useful to assess positive findings of specific bacteria in the lower airway tract. Statistically significantly increased sensitivity and positive predictive value were found in cystic fibrosis patients concerning coherence growth. The clinical usage of NTA remains important as negative findings are of clinical value. However, BAL continues to be preferred as a significantly superior diagnostic tool.

National multi-centre study found a low prevalence of severely impaired lung function in children and adolescents.

AIM: As no data to our knowledge exist, the aim of the study was to describe the national prevalence and characteristics of Danish children and adolescents with severely impaired lung function. METHODS: We performed a descriptive, cross-sectional Danish multi-centre study. Children and adolescents between 6 and 18 years old demonstrating severely impaired lung function from 2015 to 2018, defined by forced expiratory volume in 1 second (FEV1 ) <60% or who had lung transplantation, were eligible for inclusion. RESULTS: This study included 113 children with a mean age (standard deviation) of 12.9 years (3.5 years). The prevalence of severely impaired lung function was approximately 13 in 100,000. The mean (standard deviation) FEV1 was 46.1% (10.1%) of predicted, and z-score was -4.5 (0.8). The most frequent diagnosis was cystic fibrosis (20.4%), followed by asthma (19.5%) and bronchiolitis obliterans (16.8%), while almost 25% had different elements of airway malformations or non-pulmonary conditions. Two adolescents with cystic fibrosis underwent lung transplantation. CONCLUSION: The estimated prevalence of severely impaired lung function in Danish children and adolescents was low, and extremely, few children underwent lung transplantation. The most frequent diagnosis was cystic fibrosis, while almost 25% had different elements of airway malformations or non-pulmonary conditions, which may require clinical attention.

Early procedural training increases anesthesiology residents' clinical production: a comparative pre-post study of the payoff in clinical training.

BACKGROUND: Competency-based education has been shown to enhance clinical skills, improve patient care, and reduce number of complications resulting in a better return on investments. Residents constitute an important workforce at many hospitals. Yet, the effect of training on residents' contribution to production in patient care is scarcely studied. This study evaluated the effects of early competency-based procedural training on residents' contribution to patient care in central venous catheterization and spinal and epidural anesthesia. METHODS: The design was a non-randomized cohort study of first-year anesthesiology residents. The intervention group received additional early focused skills training while three control groups received traditional competency-based education. The residents' contributions to patient care were compared between the intervention group (n = 20), a historical control group (n = 19), and between a contemporary control group (n = 7) and a historical control group (n = 7) from different departments. The residents' vs specialists' procedural production share was compared between years within each study group. We calculated specialist time saved compared to the time spent providing additional skills training in the intervention group. RESULTS: We found statistically significant increases in residents' vs specialists' share of total production after the intervention for epidural anesthesia: 2015: 0.51 (0.23, 0.70) to 2017: 0.94 (0.78, 1.05), p = 0.011 and central venous catheterization: 2015: 0.30 (0.23, 0.36) to 2016: 0.46 (0.35, 0.55), p = .008; and to 2017: 0.64 (0.50, 0.79), p = 0.008. Comparison between residents and specialists on production of the three procedures before and after the intervention showed a surplus of 21 h of freed specialist time per year. CONCLUSIONS: Early procedural training results in more productive residents and freed specialist time for additional supervision, other clinical tasks or research. This provides empirical support for a positive correlation between early focused training and increased independent production among residents.

Reversible lung fibrosis in a 6-year-old girl after long term nitrofurantoin treatment.

BACKGROUND: Pulmonary side effects are well known, including lung fibrosis, in elderly patients treated with long-term nitrofurantoin to prevent urinary tract infections and secondary renal injury. However, pulmonary side effects have only been reported rarely in paediatric cases, despite nitrofurantoin being a first line prophylactic treatment of recurrent childhood urinary tract infection. CASE PRESENTATIONS: A 6-year-old girl was admitted to the hospital with dyspnea, general fatigue, loss of appetite and need for nasal oxygen treatment after long-term nitrofurantoin treatment. A computed tomography scan of the chest showed lung fibrosis. A biopsy confirmed this diagnosis. We suspected the fibrosis to be caused by the nitrofurantoin treatment. Thorough examinations reveal no other explanations. Nitrofurantoin was discontinued and the girl was treated with methylprednisolone. After 17 month a new scan and lung function test showed total regression of the lung fibrosis. CONCLUSIONS: This case underlines that risk of severe side effects should be taken in to account before initiation of long-term nitrofurantoin treatment in children.

The use of direct oral challenge to confirm allergies to penicillin class antibiotics in Danish children.

BACKGROUND: A high number of children are referred to pediatric departments with a suspected allergic reaction to antibiotics. The prevalence of true allergy is considered to be significantly lower than shown from clinical history and symptoms alone. This study investigated the historical use of direct oral challenges at three specialist pediatric departments in Denmark. METHODS: In this retrospective medical record review study, 141 children (69 boys and 72 girls) with a clinical history of suspected penicillin class allergy were investigated. A standardized questionnaire for drug allergy was completed in the beginning of the investigation, which also included a skin prick test (SPT), measurement of IgE to different types of penicillin, and a drug challenge (DC). RESULTS: Only four (2.8%) of the patients referred for further investigation in our study had a positive DC. We found no correlation between a positive DC, positive SPT or elevated specific IgE. None of the patients with a positive DC reacted with a rash alone prior to investigation. CONCLUSIONS: Allergy to penicillin in children is rare and probably overestimated. In children reacting to penicillin with a rash alone, our study indicated that the rash was probably not related to allergy and treatment should thus be continued.

The effects of graduate competency-based education and mastery learning on patient care and return on investment: a narrative review of basic anesthetic procedures.

BACKGROUND: Despite the widespread implementation of competency-based education, evidence of ensuing enhanced patient care and cost-benefit remains scarce. This narrative review uses the Kirkpatrick/Phillips model to investigate the patient-related and organizational effects of graduate competency-based medical education for five basic anesthetic procedures. METHODS: The MEDLINE, ERIC, CINAHL, and Embase databases were searched for papers reporting results in Kirkpatrick/Phillips levels 3-5 from graduate competency-based education for five basic anesthetic procedures. A gray literature search was conducted by reference search in Google Scholar. RESULTS: In all, 38 studies were included, predominantly concerning central venous catheterization. Three studies reported significant cost-effectiveness by reducing infection rates for central venous catheterization. Furthermore, the procedural competency, retention of skills and patient care as evaluated by fewer complications improved in 20 of the reported studies. CONCLUSION: Evidence suggests that competency-based education with procedural central venous catheterization courses have positive effects on patient care and are both cost-effective. However, more rigorously controlled and reproducible studies are needed. Specifically, future studies could focus on organizational effects and the possibility of transferability to other medical specialties and the broader healthcare system.

Training in motivational interviewing in obstetrics: a quantitative analytical tool.

OBJECTIVE: To examine whether a 3-day training course in motivational interviewing, which is an approach to helping people to change, could improve the communication skills of obstetric healthcare professionals in their interaction with obese pregnant women. DESIGN: Intervention study. SETTING: The Region of Southern Denmark. METHODS: Eleven obstetric healthcare professionals working with obese pregnant women underwent a 3-day course in motivational interviewing techniques and were assessed before and after training to measure the impact on their overall performance as well as the effect on specific behavioral techniques observed during interviews. FINDINGS: With a few exceptions, the participants changed their behavior appropriate to the motivational interviewing technique. The participants made more interventions towards the principles of motivational interviewing (adherent and nonadherent interventions). Furthermore, the participants asked fewer closed and more open questions before training in motivational interview. In the assessment of proficiency and competency, most of the participants scored higher after the training in motivational interviewing. CONCLUSIONS: Training in motivational interviewing improves healthcare professionals' proficiency and competency when communicating with obese pregnant women, albeit that the effect was not universal.

The experience of pregnant women with a body mass index >30 kg/m² of their encounters with healthcare professionals.

OBJECTIVE: To examine the experience of women with a pre-pregnant BMI >30 kg/m², in their encounters with healthcare professionals during pregnancy. DESIGN: Qualitative study using a phenomenological methodology approach. SETTING: Face-to-face interviews with pregnant women in their own home who were referred from their general practitioner to specialist antenatal follow-up at their local hospital. SAMPLE: Sixteen women with pre-pregnant BMI >30 kg/m². METHODS: Qualitative in-depth interviews. Participant's experiences of their encounters with health care professionals were recorded verbatim, transcribed and analysed using a phenomenological approach. RESULTS: Two main themes were identified, an accusatorial response from healthcare professionals and a lack of advice and helpful information on how being obese and pregnant might affect the women's health and that of their child. CONCLUSIONS: Pregnant women with obesity may experience prejudice from healthcare professionals. These women felt they were treated with a lack of respect, an accusatorial response, and the feeling that information which could have been helpful was not forthcoming. Communication between obese pregnant woman and healthcare professionals appears to be lacking. Improved training in communication skills, less judgemental behaviour and better dissemination of information from healthcare professionals working with pregnant women with obesity are needed.

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.

Diffuse alveolar haemorrhage in children: an international multicentre study.

Background: Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome. Methods: A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years. Results: Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0-12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function. Conclusions: Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.

Risk Factors for Non-Adherence to Inhaled Corticosteroids in Preschool Children with Asthma.

Non-adherence to asthma controllers increases morbidity among school-aged children. This study aimed to determine non-adherence risk factors in preschool children with asthma. We investigated 172 children <6 years diagnosed with asthma in 2018 and analyzed baseline characteristics and loss of control events extracted from the medical records for four years following diagnosis. At end of follow-up, 79 children had a prescription of inhaled corticosteroids (ICS) and were included in the analyses. Adherence was assessed in a two-year period through pharmacy claims using percentage of days covered (PDC) analyzed dichotomously with non-adherence defined as PDC < 80% and using adherence ratio (AR) defined as days with medical supply divided by days without. Of the 79 children, 59 (74.7%) were classified as non-adherent. In analyses adjusted for sex, age and exacerbations prior to inclusion, adherence was positively associated with having had a loss of control event requiring a step-up in asthma controller (aAR:2.34 [1.10;4.98], p = 0.03), oral corticosteroids (aAR:2.45 [1.13;5.34], p = 0.026) or redeeming a short-acting b2-agonist prescription (aAR:2.91 [1.26;6.74], p = 0.015). Further, atopic comorbidity was associated with increased adherence (aAR:1.18 [1.01;1.37], p = 0.039), whereas having a first degree relative with asthma was associated with worse adherence (aAR:0.44 [0.23;0.84], p = 0.015). This study found poor adherence to ICS among three quarters of preschool children with asthma. Increasing adherence was associated with atopic comorbidity and loss of control events, whereas lower adherence was associated with atopic predisposition. These findings should be considered to improve adherence in preschool children with asthma.

Contemporary N2 and SF6 multiple breath washout in infants and toddlers with cystic fibrosis.

INTRODUCTION: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6 MBW commonly viewed as the reference method. The use of N2 MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N2  signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2 MBW,corrected-such as tidal volume reduction during N2 washout with pure O2 . METHOD: This was a longitudinal multicenter cohort study. SF6 MBW and N2 MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N2,original and N2,corrected for comparison with SF6 MBW. RESULTS: Mean functional residual capacity, FRCN2,corrected was 14.3% lower than FRCN2, original , and 1.0% different from FRCSF6 . Lung clearance index, LCIN2,corrected was 25.2% lower than LCIN2,original , and 7.3% higher than LCISF6 . Mean (SD) tidal volume decreased significantly during N2 MBWcorrected , compared to SF6 MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCIN2,corrected and LCISF6 . The absolute differences in LCI increased significantly with higher LCISF6 (0.63/LCISF6 ) and (0.23/LCISF6 ), respectively, for N2,original and N2,corrected , but the relative differences were stable across disease severity for N2,corrected , but not for N2,original . CONCLUSION: Only minor residual differences between FRCN2,corrected and FRCSF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N2 MBW did not affect differences. The corrected N2 MBW can now be used with confidence in young children with CF, although not interchangeably with SF6 .

Effect of "motivational interviewing" on quality of care measures in screen detected type 2 diabetes patients: a one-year follow-up of an RCT, ADDITION Denmark.

OBJECTIVE. "Motivational interviewing" (MI) has shown to be broadly applicable in the management of behavioural problems and diseases. Only a few studies have evaluated the effect of MI on type 2 diabetes treatment and none has explored the effect of MI on target-driven intensive treatment. METHODS. Patients were cluster-randomized by GPs, who were randomized to training in MI or not. Both groups received training in target-driven intensive treatment of type 2 diabetes. The intervention consisted of a 1½-day residential course in MI with half-day follow-up twice during the first year. Blood samples, case record forms, national registry files, and validated questionnaires from patients were obtained. RESULTS. After one year significantly improved metabolic status measured by HbA1c (p < 0.01) was achieved in both groups. There was no difference between groups. Medication adherence was close to 100% within both treatment groups. GPs in the intervention group did not use more than an average of 1.7 out of three possible MI consultations. CONCLUSION. The study found no effect of MI on metabolic status or on adherence of medication in people with screen detected type 2 diabetes. However, there was a significantly improved metabolic status and excellent medication adherence after one year within both study groups. An explanation may be that GPs in the control group may have taken up core elements of MI, and that GPs trained in MI used less than two out of three planned MI consultations. The five-year follow-up of this study will reveal whether MI has an effect over a longer period.

Identifying parents with risky alcohol consumption habits in a paediatric unit--are screening and brief intervention appropriate methods?

BACKGROUND: There is no systematic identification of parents with excessive alcohol use who have a child admitted to hospital. Children in families with excessive alcohol issues form a high risk group as substantial alcohol consumption has a damaging influence on a child emotionally, cognitively, socially and physically. Alcohol consumption is a sensitive issue, and health staff needs knowledge, qualifications and adequate training in communicating with parents about this taboo. AIM: • To identify specific patterns in subgroups of parents by comparing results from screening and demographic variables • To identify systematic patterns in staff members by demographic variables to decide whether these factors influence the screening results. METHODS: During 1 year, screening and brief intervention (SBI) was accomplished, including health staff conducting dialogues with parents of a hospitalized child using motivational interviewing (MI) and screening for risky alcohol behaviour by Cut down, Annoyance from others, feel Guilty, Early-morning Craving (CAGE)-C. Data were analysed by descriptive statistics, and relationships were tested with a statistical significance level of 0.05, using SPSS (version 16.0). RESULTS: Motivational dialogues with 779 parents were conducted by 43 staff members, and 11% of the parents were screened positive for risky alcohol behaviour. Drinking alcohol 4 days a week or more and drinking alcohol outside mealtimes were main risk factors. Parents' gender was the strongest predictor of screening positive and OR was 6.8 for men (CI 4.03-11.74) compared to women, p<0.0001. An OR of 1.2 for parents' age (CI 1.02-1.42) indicates the risk of screening positive increases with age, p=0.027. CONCLUSIONS: Brief intervention using CAGE-C and MI has proven successful in mapping parents' alcohol consumption patterns and in identifying parents with risky alcohol consumption habits. Health staff is able to manage health promotion and prevention when having the right competences and when being supervised.

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome Manifesting as Lymphocytic Interstitial Pneumonia and Treatment-Resistant Bullous Pemphigoid.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare immune deficiency with a broad clinical presentation. IPEX syndrome causes dysfunctional regulatory T cells, increasing the risk of autoimmune diseases. In this case report, we describe a 7-year-old boy with lymphocytic interstitial pneumonia and bullous pemphigoid who was recently diagnosed with IPEX syndrome.

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.

National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia: the ALL-STAR study protocol.

INTRODUCTION: More than 90% of patients diagnosed with childhood acute lymphoblastic leukaemia (ALL) today will survive. However, half of the survivors are expected to experience therapy-related chronic or late occurring adverse effects, reducing quality of life. Insight into underlying risk trajectories is warranted. The aim of this study is to establish a Nordic, national childhood ALL survivor cohort, to be investigated for the total somatic and psychosocial treatment-related burden as well as associated risk factors, allowing subsequent linkage to nation-wide public health registers. METHODS AND ANALYSIS: This population-based observational cohort study includes clinical follow-up of a retrospective childhood ALL survivor cohort (n=475), treated according to a common Nordic ALL protocol during 2008-2018 in Denmark. The study includes matched controls. Primary endpoints are the cumulative incidence and cumulative burden of 197 health conditions, assessed through self-report and proxy-report questionnaires, medical chart validation, and clinical examinations. Secondary endpoints include organ-specific outcome, including cardiovascular and pulmonary function, physical performance, neuropathy, metabolic disturbances, hepatic and pancreatic function, bone health, oral and dental health, kidney function, puberty and fertility, fatigue, and psychosocial outcome. Therapy exposure, acute toxicities, and host genome variants are explored as risk factors. ETHICS AND DISSEMINATION: The study is approved by the Regional Ethics Committee for the Capital Region in Denmark (H-18035090/H-20006359) and by the Danish Data Protection Agency (VD-2018-519). Results will be published in peer-reviewed journals and are expected to guide interventions that will ameliorate the burden of therapy without compromising the chance of cure.