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. Since 2020 the CFTR-modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved for pwCF aged 12 and above in Denmark. Initial experiences with the medication have shown promising results, including improved lung function and disease stability. To date a limited number of studies have evaluated the impact of CFTR-modulators on exercise capacity in pwCF. OBJECTIVE: The study aims to assess the impact of one year of ETI treatment, without any further intervention, on exercise capacity measured through cardiopulmonary exercise test (CPET) in pwCF aged 12 years and above. METHODS: A Danish prospective registry cohort study including pwCF from CF-Center Copenhagen, Copenhagen University Hospital and CF-Center Aarhus, Aarhus University Hospital. Participants underwent CPET before initiating ETI and at follow up one year later. Primary outcomes were VO2 peak (ml/kg/min), secondary outcomes were VO2 peak (ml/min), VO2 peak (% pred), watt-max, HR-max and saturation at max. The difference between baseline and follow-up was assessed using a paired-sample t-test and regression analyses were applied to relevant outcomes. RESULTS: We included 229 pwCF in the analyses. An increase in oxygen uptake, VO2 peak (ml/kg/min) from baseline to follow-up was observed; 0.6, 95% CI [0.06; 1.09] p = 0.03. Moreover, significant increase was noted for all other CPET outcomes. Regression analysis showed that changes in FEV1% pred and BMI could explain some of the differences, 0.05 ml/kg/min, 95% CI [0.01, 0.1] p = 0.02 and -0.5 ml/kg/min, 95% CI [-0.8, -0.2] p = 0.002 respectively. CONCLUSION: Among Danish pwCF we found a significant, but not clinically relevant, increase in oxygen uptake, after one year of ETI treatment.

Long-term effects of high-dose systemic corticosteroids on growth and bone mineral density in patients treated for childhood interstitial lung disease (chILD).

BACKGROUND: Children's interstitial lung disease (chILD) is a rare and potentially life-threatening condition. For many chILD conditions, systemic corticosteroids (sCCS) are considered the primary treatment despite a broad spectrum of potential side effects. AIM: We aimed to determine the long-term effects of sCCS treatment on growth, bone mineral density (BMD), and body composition after chILD. MATERIALS AND METHODS: This descriptive cross-sectional single-center study included patients diagnosed with chILD before the age of 18 years treated with sCCS in the period 1998-2020. Dual-energy X-ray absorptiometry, anthropometric measurements, bone age determination, and blood tests were performed in 53 (55% males) of 89 eligible patients. RESULTS: Median (range) age was 19.3 (6.4;30.7 years). Participants received a median (range) cumulative sCCS dose of 1144 (135; 6178) mg over a 2.0 (0.1; 13.8) years period and latest dose was administered 11.7 (1.2; 19.6) years before follow-up. Mean delta height (height standard deviation scores [SDS] - target height SDS) was reduced at sCCS treatment initiation (mean: -0.55, 95% confidence interval [CI]: -0.91; -0.20, p < .005) and at sCCS treatment cessation (mean: -0.86, 95% CI:-1.22; -0.51, p < .001), but normalized in the majority at follow-up (mean: -0.29, 95% CI:-0.61; 0.03, p = .07). Mean (SD) BMD z-score for the spine and whole body was -0.34 (1.06) and 0.52 (1.13), with no significant correlation to sCCS dose. Excess body fat (>30% in females, >25% in males) was found in 58% of patients. CONCLUSION: Long-term treatment with sCCS did not cause significant long-term reduction of height but showed subtle effects on fat mass percentage and BMD. Given the severity of chILD, the observed long-term effects of sCCS on growth and BMD appear acceptable.

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.

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.

Diffuse alveolar hemorrhage in children with interstitial lung disease: Determine etiologies!

OBJECTIVE: Diffuse alveolar hemorrhage (DAH) in children is a rare condition resulting from different underlying diseases. This study aimed at describing characteristics and diagnostic measures in children with ILD (children's interstitial lung disease, chILD) and DAH to improve the diagnostic approach by increasing clinician's awareness of diagnostic shortcomings. PATIENTS AND METHODS: A retrospective data analysis of patients with ILD and DAH treated in our own or collaborating centers between 01/07/1997 and 31/12/2020 was performed. Data on clinical courses and diagnostic measures were systematically retrieved as case-vignettes and investigated. To assess suitability of diagnostic software-algorithms, the Human Phenotype Ontology (HPO) was revised and expanded to optimize conditions of its associated tool the "Phenomizer." RESULTS: For 97 (74%) of 131 patients, etiology of pulmonary hemorrhage was clarified. For 34 patients (26%), no underlying condition was found (termed as idiopathic pulmonary hemorrhage, IPH). Based on laboratory findings or clinical phenotype/comorbidities, 20 of these patients were assigned to descriptive clusters: IPH associated with autoimmune features (9), eosinophilia (5), renal disease (3) or multiorgan involvement (3). For 14 patients, no further differentiation was possible. CONCLUSION: Complete and sometimes repeated diagnostics are essential for establishing the correct diagnosis in children with DAH. We suggest assignment of patients with IPH to descriptive clusters, which may also guide further research. Digital tools such as the Phenomizer/HPO are promising, but need to be extended to increase diagnostic accuracy.

Acute exacerbations in children's interstitial lung disease.

INTRODUCTION: Acute exacerbations (AEs) increase morbidity and mortality of patients with chronic pulmonary diseases. Little is known about the characteristics and impact of AEs on children's interstitial lung disease (chILD). METHODS: The Kids Lung Register collected data on AEs, the clinical course and quality of life (patient-reported outcomes - PRO) of rare paediatric lung diseases. Characteristics of AEs were obtained. RESULTS: Data of 2822 AEs and 2887 register visits of 719 patients with chILD were recorded. AEs were characterised by increased levels of dyspnoea (74.1%), increased respiratory rate (58.6%) and increased oxygen demand (57.4%). Mostly, infections (94.4%) were suspected causing an AE. AEs between two register visits revealed a decline in predicted FEV1 (median -1.6%, IQR -8.0 to 3.9; p=0.001), predicted FVC (median -1.8%, IQR -7.5 to 3.9; p=0.004), chILD-specific questionnaire (median -1.3%, IQR -3.6 to 4.5; p=0.034) and the physical health summary score (median -3.1%, IQR -15.6 to 4.3; p=0.005) compared with no AEs in between visits. During the median observational period of 2.5 years (IQR 1.2-4.6), 81 patients died. For 49 of these patients (60.5%), mortality was associated with an AE. CONCLUSION: This is the first comprehensive study analysing the characteristics and impact on the clinical course of AEs in chILD. AEs have a significant and deleterious effect on the clinical course and health-related quality of life in chILD.

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.

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 .

First patient with ILNEB syndrome due to pathogenic variants in ITGA3 surviving to adulthood.

Interstitial Lung disease, Nephrotic syndrome and Epidermolysis Bullosa, also referred to as ILNEB syndrome is an extremely rare autosomal recessive condition, caused by pathogenic variants in ITGA3. 11 patients have previously been diagnosed with ILNEB syndrome of whom 7 died in infancy or early childhood. We report the only patient with ILNEB syndrome who survived past adolescence, partly due to a double lung transplant. Additionally, our patient showed oral, nasal and gynecological symptoms not previously reported in patients with ILNEB syndrome.

[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.

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.

Oliver McFarlane syndrome: two new cases and a review of the literature.

BACKGROUND: Oliver McFarlane syndrome is a rare syndrome. Clinical presentations include trichomegaly, chorioretinal degeneration, pituitary hormone deficits, and neurological manifestations. Genetic analysis has recently placed this syndrome within the group of PNPLA6-related disorders. Here, we describe two new individuals and review the previously published cases. MATERIALS AND METHODS: Clinical investigations were carried out in accordance with local guidelines and clinical information was retrieved from medical records. Genetic studies were carried out using next-generation sequencing based clinical exome sequencing. A PubMed literature search was performed with a review of the published clinical cases of Oliver McFarlane syndrome. RESULTS: Our first individual was a 36-year-old woman with 32 years of follow up and our second individual was a 3-year-old boy. Both individuals were born preterm and presented with prolonged neonatal respiratory distress, trichomegaly, early growth retardation, retinopathy and sparse depigmented hair. So far, none of our cases have demonstrated cognitive impairment or progressive neurological symptoms, but the child revealed persistent abnormal lung structure. Both individuals were compound heterozygous for pathogenic PNPLA6 variants, one of which was novel. We found other 31 clinically documented published cases. CONCLUSIONS: Our two new unrelated cases of Oliver McFarlane Syndrome demonstrate early ophthalmological and systemic findings of this rare syndrome and the progressive nature of the retinopathy with a long follow-up. PNPLA6-related disorders are a phenotypically highly heterogenous group where alterations in the phosphatidylcholine metabolism can lead to manifestations in different tissues with no clear genotype-phenotype correlation.

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. METHODS: A single-centre, randomised, controlled, parallel group study to determine effects of one month's withdrawal of nebulised dornase alfa (intervention) in 5-18 years old children with CF. Remaining chronic maintenance therapy stayed unchanged. Outcome measures were assessed at two visits one month apart. Primary outcome was absolute change in LCI. Secondary outcomes were FEV1, FEF25-75 and CF Questionnaire-revised (CFQ-R) respiratory symptom score. Possible harmful effects were assessed by comparing the occurrence of pulmonary exacerbations between groups. RESULTS: Twenty-eight children (median age 10.4 [interquartile range: 7.6; 13.5] years) with CF received standard care (n = 14) or intervention (n = 14). Compared with the control group, LCI increased (worsened) 1.74 (95% confidence interval: 0.62; 2.86) during withdrawal of dornase alfa, while FEV1 (-6.8% predicted) and FEF25-75 (-13.1% predicted) decreased significantly. Change in CFQ-R respiratory symptom score and the occurrence of pulmonary exacerbations did not differ significantly between groups. CONCLUSIONS: One month's withdrawal of dornase alfa caused increasing ventilation inhomogeneity and deteriorating FEV1 and FEF25-75 in school-age children with mild CF. Hence, adherence to dornase alfa optimally needs to be addressed when using LCI and spirometric parameters as endpoints, even in short-term clinical trials.

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 (N2MBW) 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 N2MBW were performed at two-year intervals in school-age children with CF. RESULTS: Fifty-seven children aged 6-18 years were included. No significant progression in mean PRAGMA-CF scores was observed. Half of the children showed improvement in the proportion of bronchiectasis (%Bx). Lung Clearance Index (LCI) and the second moment ratio (M2) increased significantly and baseline values correlated significantly with SLD at follow-up (p ≤ 0.0002). The correlation between the change in M2 (∆M2) and the change in total SLD was R = 0.27 (p = 0.048). We found high negative predictive values (100%) for ∆M2<10% to exclude progression in SLD. For stable or improving values of LCI and M2, the predicted probability for progression in SLD was 16% and 14%, respectively (upper 95% confidence limit: 33%). Evolution in N2MBW and CT outcomes was discordant in half of the children. CONCLUSIONS: We found no progression in SLD over 2 years in school-age children with CF, in contrast to both LCI and M2, which along with discordant outcomes in half of the children underlines that N2MBW and CT assess different aspects of CF lung disease. However, stable outcomes from N2MBW were associated with stable structural lung disease.

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.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.

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 (zFEV1) 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. Children in the intervention group had BAL performed if LCI increased >1 unit from a fixed baseline value established at first visit. If the presence of a pathogen was documented in the BAL fluid, treatment was initiated/altered accordingly. RESULTS: Twenty-nine children with CF were randomized to the control (n = 14) and intervention group (n = 15). The median (interquartile range) number of BAL procedures per child was 2.5 (2.0; 3.0) and 6.0 (4.0; 7.0) in the control and intervention group, respectively. There was no significant difference between groups in slope for the primary outcome LCI; difference was 0.21 (95% confidence interval: -0.45; 0.88) units/year. Likewise, there was no significant difference between groups in slope for the secondary outcomes zFEV1, zBMI, CFQ-R respiratory symptom score and the proportion of total disease and trapped air on chest computed tomography. CONCLUSIONS: LCI-triggered BAL and associated antimicrobial treatment did not benefit clinical outcomes in a small cohort of closely monitored school-age children with CF.