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Objective: The signal transducer and activator of transcription 3 (STAT3) gain-offunction (GOF) syndrome (STAT3-GOF) is an inborn error of immunity (IEI) characterized by diverse manifestations of immune dysregulation that necessitate systemic immunomodulatory treatment. The blockade of the interleukin-6 receptor and/or the inhibition of the Janus kinases has been commonly employed to treat diverse STAT3-GOF-associated manifestations. However, evidence on long-term treatment outcome, especially in the case of adult patients, is scarce. Methods: Clinical data, including laboratory findings and medical imaging, were collected from all seven patients, diagnosed with STAT3-GOF, who have been treated at the Hannover University School, focusing on those who received a Janus kinase (JAK) inhibitor (JAKi). Previously published cases of STAT3-GOF patients who received a JAKi were evaluated, focusing on reported treatment efficacy with respect to diverse STAT3-GOF-associated manifestations of immune dysregulation and safety. Results: Five out of seven patients diagnosed with STAT3-GOF were treated with a JAKi, each for a different indication. Including these patients, outcomes of JAKi treatment have been reported for a total of 41 patients. Treatment with a JAKi led to improvement of diverse autoimmune, inflammatory, or lymphoproliferative manifestations of STAT3-GOF and a therapeutic benefit could be documented for all except two patients. Considering all reported manifestations of immune dysregulation in each patient, complete remission was achieved in 10/41 (24.4%) treated patients. Conclusions: JAKi treatment improved diverse manifestations of immune dysregulation in the majority of STAT3-GOF patients, representing a promising therapeutic approach. Long-term follow-up data are needed to evaluate possible risks of prolonged treatment with a JAKi. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: No data on healthcare utilisation and associated costs for the many rare entities of children's interstitial lung diseases (chILD) exist. This paper portrays healthcare utilisation structures among individuals with chILD, provides a pan-European estimate of a 3-month interval per-capita costs and delineates crucial cost drivers.Methods: Based on longitudinal healthcare resource utilisation pattern of 445 children included in the Kids Lung Register diagnosed with chILD across 10 European countries, we delineated direct medical and non-medical costs of care per 3-month interval. Country-specific utilisation patterns were assessed with a children-tailored modification of the validated FIMA questionnaire and valued by German unit costs. Costs of care and their drivers were subsequently identified via gamma-distributed generalised linear regression models.Results: During the 3 months prior to inclusion into the registry (baseline), the rate of hospital admissions and inpatient days was high. Unadjusted direct medical per capita costs (€19 818) exceeded indirect (€1 907) and direct non-medical costs (€1 125) by far. Country-specific total costs ranged from €8 713 in Italy to €28 788 in Poland. Highest expenses were caused by the disease categories 'diffuse parenchymal lung disease (DPLD)-diffuse developmental disorders' (€45 536) and 'DPLD-unclear in the non-neonate' (€47 011). During a follow-up time of up to 5 years, direct medical costs dropped, whereas indirect costs and non-medical costs remained stable.Conclusions: This is the first prospective, longitudinal study analysing healthcare resource utilisation and costs for chILD across different European countries. Our results indicate that chILD is associated with high utilisation of healthcare services, placing a substantial economic burden on health systems. [ABSTRACT FROM AUTHOR]

Background/purpose:  Gastroesophageal reflux disease (GERD) after lung transplantation (LuTx) can lead to chronic lung allograft dysfunction. Our aim was to assess the prevalence of GERD in pediatric LuTx recipients and to investigate the impact of medical and surgical GERD treatment on lung function., Methods:  Ethical approval was obtained. Data of all consecutive patients who underwent LuTx from 2013 to 2023 and aged < 18 years at the time of the study were prospectively collected. A GERD diagnostic algorithm was established, including assessment of symptoms (vomiting, heartburn, regurgitation, cough, recurrent airway infections), bronchoscopy, forced expiratory volume in 1 second, and pH impedance. Further investigations included upper gastrointestinal series and esophagogastroduodenoscopy. Patients with GERD underwent medical treatment or fundoplication. Lung function was monitored., Results:  Thirty-six patients (2 months-18 years, 50% male) were included. Twenty-nine (80%) underwent spirometry, 16 (45%) pH impedance study, and 14 (39%) esophagogastroduodenoscopy. Twenty-two (61%) had no GERD symptoms and 12 (33%) showed normal pH impedance study or esophagogastroduodenoscopy. Fourteen (39%) patients had GERD symptoms, all 9 tested symptomatic patients (25%) had pathological GERD-specific diagnostics. Three (8%) patients underwent fundoplication after a median of 1.6 years (range 1.1-5.7 years) post-LuTx without surgical complications. After a median follow-up of 2.3 years (range 1.3-2.8 years) post-fundoplication, all ( n  = 3) had complete remission of GERD symptoms and lung function improvement. Lung function decline was observed in 6 (67%) of the tested symptomatic patients on proton-pump inhibitors (PPIs) treatment., Conclusion:  Over one-third of our patients presented with GERD symptoms after LuTx. Symptoms and lung function may be reliable GERD indicators. Given the high prevalence of GERD, we suggest a routine posttransplant diagnostic algorithm including pH impedance study. Eighty percent of all symptomatic patients had a lung function decline despite PPI. Fundoplication is safe and may improve long-term outcome in pediatric LuTx recipients., Competing Interests: None declared., (Thieme. All rights reserved.)

Interstitial lung diseases (ILD) are a heterogeneous group of rare diffuse diseases affecting the lung parenchyma in children and adults. Childhood interstitial lung diseases (chILD) are often diagnosed at very young age, affect the developing lung, and can have different presentations and prognosis compared to adult forms of these diseases. In addition, chILD in many cases may apparently remit, and have a better response to therapy and better prognosis than adult ILD. Many affected children will reach adulthood with minimal activity or clinical remission of the disease. They need continuing care and follow-up from childhood to adulthood if the disease persists and progresses over time, but also if they are asymptomatic and in full remission. Therefore, for every chILD patient an active transition process from paediatric to adult care should be guaranteed. This European Respiratory Society (ERS) statement provides a review of the literature and current practice concerning transition of care in chILD. It draws on work in existing transition care programmes in other chronic respiratory diseases, disease-overarching transition-of-care programmes, evidence on the impact of these programmes on clinical outcomes, current evidence regarding long-term remission of chILD as well as the lack of harmonisation between the current adult ILD and chILD classifications impacting on transition of care. While the transition system is well established in several chronic diseases, such as cystic fibrosis or diabetes mellitus, we could not find sufficient published evidence on transition systems in chILD. This statement summarises current knowledge, but cannot yet provide evidence-based recommendations for clinical practice., Competing Interests: Conflict of interest: P. Pohunek reports consulting fees, travel support and advisory board participation with AstraZeneca and GlaxoSmithKline, and lecture honoraria from GlaxoSmithKline, Chiesi and AstraZeneca; outside the submitted work. E. Manali reports lecture honoraria from Boehringer Ingelheim, Elpen, Demo, CSL Behring and Hoffman La Roche, and travel support from Boehringer Ingelheim, Hoffman La Roche, Elpen and CSL Behring, outside the submitted work. F. Chua reports lecture honoraria and travel support from Boehringer Ingelheim, and advisory board participation with Boehringer Ingelheim and the National Institute for Care Excellence (NICE), UK, outside the submitted work. R. Epaud reports consulting fees from AstraZeneca, lecture honoraria from GSK, AstraZeneca and Menarini, travel support from GSK, and AstraZeneca, and advisory board participation with AstraZeneca and Novartis, outside the submitted work. C. Gilbert reports a leadership role with ChILD Lung Foundation, outside the submitted work. M. Griese reports grants, lecture honoraria, advisory board participation and adjudication board participation with Boehringer Ingelheim, outside the submitted work. V. Koucký reports advisory board participation with Boehringer Ingelheim, outside the submitted work. N. Nathan reports grants from Million Dollar Bike Ride project (for Neuroendocrine Cell Hyperplasia of Infancy: Genetic basis of neuroendocrine cell hyperplasia of infancy), Chancellerie des Universités: Legs Poix (Molecular and phenotypic characterisation of interstitial lung disease, number 2022000594) and RespiFIL (development of an e-learning module for CT-scan in childhood interstitial lung diseases and development of an online platform for the collection of quality of life and transition questionnaires in rare lung disease), lecture honoraria from La lettre du Pneumologue, and travel support from ERS, outside the submitted work. S. Papiris reports lecture honoraria from Boehringer Ingelheim, Elpen, Demo, Pfizer and Hoffman La Roche, and travel support from Boehringer Ingelheim and Elpen. S. Terheggen-Lagro reports advisory board participation with Roche, outside the submitted work. All other authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Childhood interstitial lung disease (chILD) is a heterogeneous group of mostly chronic respiratory disorders. Assessment of health-related quality of life (HrQoL) in chILD has become increasingly important in clinical care and research. The aim of this study was to assess differences between patient-reported (self) and caregiver-reported (proxy) HrQoL scores., Methods: This study used data obtained from the chILD-EU Register. After inclusion (baseline), the patient's health status was followed up at predefined study visits. At each study visit, caregivers and patients were handed validated, age-specific HrQoL questionnaires. HrQoL data entered at baseline were used to compare self- and proxy-reported HrQoL scores. For the longitudinal analysis, we compared HrQoL scores between the baseline and the next follow-up visit., Results: No differences between patient- and caregiver-reported HrQoL scores were found for school functioning, chILD-specific questionnaire score, and physical health summary score. Self-reported HrQoL scores were higher for the subscales emotional functioning (77.4 vs. 70.7; p < .001), social functioning (81.9 vs. 76.2; p < .001), as well as psycho-social summary score (76.5 vs. 71.8; p < .001) and total score (74.7 vs. 70.8; <.001). The longitudinal analysis showed that a significant change in a patient-reported HrQoL score resulted in a significant change in a caregiver-reported HrQoL score after a mean time of 11.0 months (SD 9.4)., Conclusions: We found a good agreement between children- and caregiver-related HrQoL scores. In chILD, caregivers are able to sense changes in children's HrQoL scores over time and may be used as a proxy for children unable to complete HrQoL questionnaires., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Childhood interstitial lung diseases (chILDs) are rare and heterogeneous diseases with significant morbidity and mortality. An accurate and quick aetiological diagnosis may contribute to better management and personalised treatment. On behalf of the European Respiratory Society Clinical Research Collaboration for chILD (ERS CRC chILD-EU), this review summarises the roles of the general paediatrician, paediatric pulmonologists and expert centres in the complex diagnostic workup. Each patient's aetiological chILD diagnosis must be reached without prolonged delays in a stepwise approach from medical history, signs, symptoms, clinical tests and imaging, to advanced genetic analysis and specialised procedures including bronchoalveolar lavage and biopsy, if necessary. Finally, as medical progress is fast, the need to revisit a diagnosis of "undefined chILD" is stressed., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2023.)