Close monitoring and early intervention: management principles for cystic fibrosis in Denmark.

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre-emptive treatment of lung disease and other CF-related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high-dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side-effects and costs.

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.

[Diagnosis and treatment of a multisystemic disorder in children called congenital portosystemic shunts].

Congenital portosystemic shunts (CPSS) are rare malformations, which connect the portal venous system and the systemic circulation. The disorder is discovered at prenatal screening, neonatal cholestasis as an incidental finding or by systemic complications such as pulmonary hypertension, encephalopathies or liver nodules. CPSS are associated to cardiac malformations and several syndromes. Intervention radiology plays a key role in treatment by closure of the shunt, which is indicated, if the patient has complications, the shunt is extrahepatic, or it is still persistent at two years of age, using a two-step approach, as summarised and discussed in this review.

One-year evolution and variability in multiple-breath washout indices in children and young adults with primary ciliary dyskinesia.

Background and objective: Cross-sectional and longer-term studies have demonstrated abnormal yet stable multiple-breath inert gas washout (MBW) indices in patients with primary ciliary dyskinesia (PCD). This study aimed to assess the intermediate term evolution and the between-occasion variability of MBW indices in PCD over 1 year. Methods: Children and young adults with a confirmed diagnosis of PCD were included in this single-centre, prospective, observational, longitudinal study. Over 1 year, nitrogen (N2) MBW and spirometry were performed at three occasions during ordinary scheduled outpatient visits. Trends and variability in lung clearance index (LCI), moment ratios, normalized N2 concentration at six lung volume turnovers, and regional ventilation inhomogeneity indices of the conducting and intra-acinar airways (Scond*VT and Sacin*VT) were analysed using linear mixed models. Results: Forty-two patients, aged 6-29 years (median: 15.4), performed 116 N2 MBW test occasions and 96.6% were technically acceptable. A minimal, although significant, increase in LCI over 1 year (mean: 0.51 units, 95% CI: 0.12-0.91, p = 0.01) was found; while, all other N2 MBW indices and FEV1 remained unchanged. A moderate correlation was observed between LCI and FEV1 (r = -0.47, p = 0.0001). The limits of agreement between tests 1 year apart were for LCI: -1.96 to 2.98; Scond*VT: ± 0.039; Sacin*VT: -0.108 to 0.128. Conclusions: Children and young adults with PCD managed at a specialist centre showed slightly, but significant, increasing LCI and otherwise unchanged ventilation inhomogeneity indices and dynamic volumes over the intermediate term of 1 year. Estimates of the variability of N2 MBW indices may inform sample size calculations of future randomized controlled trials.