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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

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.

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., 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.

Introduction: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6MBW commonly viewed as the reference method. The use of N2MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N2signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2MBW,corrected—such as tidal volume reduction during N2 washout with pure O2. Method: This was a longitudinal multicenter cohort study. SF6MBW and N2MBW 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 SF6MBW. 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 N2MBWcorrected, compared to SF6MBW (−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

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.