Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.

Background: People living with cystic fibrosis in Denmark had early, universal access to triple modulator treatment with elexacaftor/tezacaftor/ivacaftor. Close monitoring allowed us to assess the impact of treatment on lung function and progression of lung disease in an unselected nationwide cystic fibrosis population from 6 years of age.

Methods: Data were analysed using linear mixed-effect models to assess changes in levels and annual rates of change (slopes) in percent predicted (pp) forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF) between the 12 months pre-treatment and treatment periods.

Changes in exercise capacity in people with Cystic Fibrosis after one year of Elexacaftor/Tezacaftor/Ivacaftor treatment - A Danish prospective cohort.

Background: Cystic Fibrosis (CF) is an inherited multiorgan disease that causes lung damage and early death. People with CF (pwCF) experience diminished exercise capacity compared to the general population. This is due to an accelerated decline in lung function resulting from recurrent lung infections, declining lung function and nutritional challenges.

Lung Function in Fontan Patients Over a Ten-Year Period: Is the Fontan Circulation Impairing Lung Development?

Few studies have investigated how the Fontan circulation affects lung function, and no studies have investigated the development of lung function over longer time in these patients. We aimed to describe the development of lung function in Fontan patients over a 10-year period. Pulmonary function tests (PFT), including spirometry and diffusion capacity for Carbon Monoxide (DLCO) and Nitric Oxide (DLNO), were conducted in a Danish Fontan cohort in 2011 (PFT-I).

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.

Automatic analysis of bronchus-artery dimensions to diagnose and monitor airways disease in cystic fibrosis.

Background: Cystic fibrosis (CF) lung disease is characterised by progressive airway wall thickening and widening. We aimed to validate an artificial intelligence-based algorithm to assess dimensions of all visible bronchus-artery (BA) pairs on chest CT scans from patients with CF.

Methods: The algorithm fully automatically segments the bronchial tree; identifies bronchial generations; matches bronchi with the adjacent arteries; measures for each BA-pair bronchial outer diameter (B), bronchial lumen diameter (B), bronchial wall thickness (B) and adjacent artery diameter (A); and computes B/A, B/A and B/A for each BA pair from the segmental bronchi to the last visible generation.

Exercise capacity in the Danish Fontan population remains stable after ten years of follow-up - is physical activity the key to success?

Background: Most Fontan patients have impaired exercise capacity, and a further decline in exercise capacity over time seems inevitable. However, few longitudinal studies exist, and there is a lack of data from newer eras. We aimed to describe the natural evolution of exercise capacity over a 10-year period in a contemporary, population-based cohort of Danish Fontan patients.

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.

Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis.

Background: The lung clearance index (LCI) is increasingly used as an outcome in clinical trials of patients with mild cystic fibrosis (CF) lung disease. Yet, understanding the impact of standard CF respiratory therapy on LCI is needed. We assessed to what degree withdrawal of nebulised dornase alfa affected LCI in school-age children with CF not receiving CFTR modulators or hydrator therapy.

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.

Prospective longitudinal association between repeated multiple breath washout measurements and computed tomography scores in children with cystic fibrosis.

Background: Progression of structural lung disease (SLD) is a major risk factor for morbidity in patients with cystic fibrosis (CF). We studied changes in SLD and correlations with spirometry and nitrogen multiple breath washout (NMBW) outcomes to explore associations in contemporary evolution between structural and functional abnormalities in CF lung disease.

Methods: Spirometry-controlled chest-CTs using PRAGMA-CF for scoring extent of SLD, spirometry, and NMBW were performed at two-year intervals in school-age children with CF.

Pulmonary function testing in children's interstitial lung disease.

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.

Lung clearance index-triggered intervention in children with cystic fibrosis - A randomised pilot study.

Hypothesis: Using increase in the lung clearance index (LCI) as a trigger for bronchoalveolar lavage (BAL) and associated antimicrobial treatment might benefit clinical outcomes in children with cystic fibrosis (CF).

Methods: A 2-year, longitudinal, interventional, randomized, controlled pilot study with quarterly visits in 5-18 years old children with CF. LCI and z-scores for the forced expired volume in 1 s (zFEV) and body mass index (zBMI) were obtained at every visit, CF Questionnaire-revised (CFQ-R) yearly and BAL and chest computed tomography at first and last visit.

Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study.

Background: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients.

Methods: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally.

Long-Term Lung Function and Exercise Capacity in Postinfectious chILD.

Severe postinfectious diffuse pulmonary disease may clinically mimic other entities of children's interstitial lung disease and is clinically challenging comprising various disease severities despite treatment. Long-term lung function trend and physical capacity in children with postinfectious diffuse pulmonary disease are rarely reported. We investigated trends in pulmonary function by long-term follow-up and assessed physical capacity in such patients.

The impact of mannose-binding lectin polymorphisms on lung function in primary ciliary dyskinesia.

Objective: Primary ciliary dyskinesia (PCD) is a congenital lung disease that leads to recurrent and chronic lung infection. The resulting inflammation causes lung damage and declines in lung function. Mannose-binding lectin (MBL) is a first line host defense protein of importance for the innate immunity.

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

: 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. : Children and young adults with a confirmed diagnosis of PCD were included in this single-centre, prospective, observational, longitudinal study.

Variation in treatment strategies for the eradication of Pseudomonas aeruginosa in primary ciliary dyskinesia across European centers.

Primary ciliary dyskinesia (PCD) is a rare disease causing motile cilia dysfunction, recurrent airway infection, and bronchiectasis. Airway infection management strategies are borrowed from cystic fibrosis. The aim of this study is to describe the management of airway infection with Pseudomonas aeruginosa ( PA) in children and adults with PCD across European centers.

Ventilation inhomogeneity and NO and CO diffusing capacity in ex-premature school children.

Aim: Ex-premature school children show mild-to-moderate airway obstruction and decreased CO diffusing capacity. Multiple breath nitrogen washout (N2MBW) and NO diffusing capacity (DLNO) measurements may provide new insight into long-term pulmonary and vascular impairment in bronchopulmonary dysplasia (BPD).

Methods: We examined a randomly selected group of 70 ex-premature children (gestational age <28 weeks or birth weight <1500 g; 42 with and 28 without BPD) and 38 term-born healthy controls of 8-13 years of age.

Variability of monthly nitrogen multiple-breath washout during one year in children with cystic fibrosis.

Background: Knowledge of between-session variability of nitrogen multiple-breath washout (NMBW) indices is crucial when designing longitudinal interventional studies and in disease monitoring using NMBW as end-point. Such information is currently sparse.

Methods: Monthly triplets of NMBW were prospectively obtained from 14 children with CF during one year.

Fractional exhaled nitric oxide and multiple breath nitrogen washout in preschool healthy and asthmatic children.

Introduction: Objectively assessing pulmonary disease is challenging in preschool children with asthma. We evaluated the feasibility of measuring fractional exhaled nitrogen oxide (FeNO) and multiple breath nitrogen washout (NMBW) in children. We compared their capacities for discriminating between children with asthma and healthy controls.

Association between spirometry controlled chest CT scores using computer-animated biofeedback and clinical markers of lung disease in children with cystic fibrosis.

: Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF).

Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium: a simple methodological approach for ex vivo studies of primary ciliary dyskinesia.

Background: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical surface facing the outside and accessible for analysis of ciliary function.

Methods: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls.

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia.

Background: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs.

Methods: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics.