Pulmonary fibrosis may begin in infancy: from childhood to adult interstitial lung disease.

BACKGROUND: Childhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available. METHODS AND RESULTS: This review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered. CONCLUSIONS: There is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood.

Bronchiolitis: Increased severity in the post-COVID-19 era.

INTRODUCTION: Acute bronchiolitis is a pressing public health concern, leading to numerous infant hospitalizations worldwide annually. The notable decrease in bronchiolitis hospitalizations during the COVID-19 pandemic sparked concerns about a potential resurgence post-pandemic. Questions also arose about the severity of post-pandemic cases compared to prepandemic ones. This study aimed to compare bronchiolitis severity before and after the COVID-19 pandemic, alongside changes in the epidemiology of bronchiolitis viral agents. MATERIAL AND METHODS: We conducted a retrospective analysis of medical records concerning infants under 12 months hospitalized for acute bronchiolitis in our pediatric pulmonology department over a period of 5 years: 2 pre-COVID years (2018-2020), the COVID year (2020), and 2 post-COVID years (2021-2023). Clinical and laboratory data were collected using standardized forms. RESULTS: Hospital admissions exhibited comparable rates pre- and post-COVID but witnessed a decline during the COVID period. Post-COVID, bronchiolitis severity increased, with longer hospitalization durations (p < 0.001) and increased oxygen therapy (p = 0.04), coinciding with a surge in the prevalence of RSV infections (p = 0.01). Patients testing positive for RSV were significantly younger (p = 0.005) and exhibited more severe symptoms. DISCUSSION AND CONCLUSION: This study reveals a significant increase in bronchiolitis severity and a rise in RSV cases following the COVID pandemic. The implementation of preventive measures such as nirsevimab is crucial to alleviate the burden of respiratory illnesses in vulnerable populations. Continued vigilance and research are needed to address the evolving challenges of bronchiolitis in the post-COVID era.

Clues for improvement of research in objective structured clinical examination.

While objective clinical structured examination (OSCE) is a worldwide recognized and effective method to assess clinical skills of undergraduate medical students, the latest Ottawa conference on the assessment of competences raised vigorous debates regarding the future and innovations of OSCE. This study aimed to provide a comprehensive view of the global research activity on OSCE over the past decades and to identify clues for its improvement. We performed a bibliometric and scientometric analysis of OSCE papers published until March 2024. We included a description of the overall scientific productivity, as well as an unsupervised analysis of the main topics and the international scientific collaborations. A total of 3,224 items were identified from the Scopus database. There was a sudden spike in publications, especially related to virtual/remote OSCE, from 2020 to 2024. We identified leading journals and countries in terms of number of publications and citations. A co-occurrence term network identified three main clusters corresponding to different topics of research in OSCE. Two connected clusters related to OSCE performance and reliability, and a third cluster on student's experience, mental health (anxiety), and perception with few connections to the two previous clusters. Finally, the United States, the United Kingdom, and Canada were identified as leading countries in terms of scientific publications and collaborations in an international scientific network involving other European countries (the Netherlands, Belgium, Italy) as well as Saudi Arabia and Australia, and revealed the lack of important collaboration with Asian countries. Various avenues for improving OSCE research have been identified: i) developing remote OSCE with comparative studies between live and remote OSCE and issuing international recommendations for sharing remote OSCE between universities and countries; ii) fostering international collaborative studies with the support of key collaborating countries; iii) investigating the relationships between student performance and anxiety.

ERS statement on transition of care in childhood interstitial lung diseases.

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.

Scimitar syndrome with vein stenosis in an infant.

Scimitar syndrome is characterised by right lung hypoplasia and abnormal pulmonary venous return, known as the 'scimitar vein'. We report the case of an infant girl with scimitar syndrome who developed a severe respiratory distress mimicking asthma. Pulmonary hypertension (PH) was diagnosed, attributed to scimitar vein stenosis and a left-to-right shunt. Scimitar vein stenosis, a rare complication of scimitar syndrome, can lead to severe PH, highlighting the importance of prompt management in specialised care centres.

A roadmap to precision treatments for familial pulmonary fibrosis.

Interstitial lung diseases (ILDs) in adults and children (chILD) are a heterogeneous group of lung disorders leading to inflammation, abnormal tissue repair and scarring of the lung parenchyma often resulting in respiratory failure and death. Inherited factors directly cause, or contribute significantly to the risk of developing ILD, so called familial pulmonary fibrosis (FPF), and monogenic forms may have a poor prognosis and respond poorly to current treatments. Specific, variant-targeted or precision treatments are lacking. Clinical trials of repurposed drugs, anti-fibrotic medications and specific treatments are emerging but for many patients no interventions exist. We convened an expert working group to develop an overarching framework to address the existing research gaps in basic, translational, and clinical research and identified areas for future development of preclinical models, candidate medications and innovative clinical trials. In this Position Paper, we summarise working group discussions, recommendations, and unresolved questions concerning precision treatments for FPF.

High risk of lung cancer in surfactant-related gene variant carriers.

BACKGROUND: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers. METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers. RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer (SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and SFTPA1/SFTPA2 variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1-44.7). CONCLUSIONS: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

BACKGROUND AND OBJECTIVE: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. METHODS: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. RESULTS: We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52-72]) and DLco was 44% ([35-50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground-glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DLCO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DLCO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow-up in the ABCA3 group. CONCLUSION: SFTPC and ABCA3-associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground-glass opacities and/or cysts is frequently found in these rare conditions.

Objectives for algorithmic decision-making systems in childhood asthma: Perspectives of children, parents, and physicians.

Objectives: To identify with children, parents and physicians the objectives to be used as parameters for algorithmic decision-making systems (ADMSs) adapting treatments in childhood asthma. Methods: We first conducted a qualitative study based on semi-structured interviews to explore the objectives that children aged 8-17 years, their parents, and their physicians seek to achieve when taking/giving/prescribing a treatment for asthma. Following the grounded theory approach, each interview was independently coded by two researchers; reconciled codes were used to assess code frequency, categories were defined, and the main objectives identified. We then conducted a quantitative study based on questionnaires using these objectives to determine how children/parents/physicians ranked these objectives and whether their responses were aligned. Results: We interviewed 71 participants (31 children, 30 parents and 10 physicians) in the qualitative study and identified seven objectives associated with treatment uptake and five objectives associated with treatment modalities. We included 291 participants (137 children, 137 parents, and 17 physicians) in the quantitative study. We found little correlation between child, parent, and physician scores for each of the objectives. Each child's asthma history influenced the choice of scores assigned to each objective by the child, parents, and physician. Conclusion: The identified objectives are quantifiable and relevant to the management of asthma in the short and long term. They can therefore be incorporated as parameters for future ADMS. Shared decision-making seems essential to achieve consensus among children, parents, and physicians when choosing the weight to assign to each of these objectives.

Lung biopsies in infants and children in critical care situation.

INTRODUCTION: Lung biopsy is considered as the last step investigation for diagnosing lung diseases; however, its indication must be carefully balanced with its invasiveness. The present study aims to evaluate the diagnostic yield of lung biopsy in critically ill patients hospitalized in the pediatric intensive care unit (ICU). MATERIAL AND METHODS: Children who underwent a lung biopsy in the ICU between 1995 and 2022 were included. Biopsies performed in the operating room and post-mortem biopsies were excluded. RESULTS: Thirty-one patients were included, with a median age of 18 days (2 days to 10.8 years); 21 (67.7%) were newborns. All patients required invasive mechanical ventilation, 26 (89.7%) had a pulmonary hypertension, and 22 (70.9%) were placed under extracorporeal membrane oxygenation (ECMO). The lung biopsy led to a diagnosis in 81% of the patients. The diagnostic reliability seemed to decrease with age (95% in newborns, 71% in 1 month to 2 years and 0/3 patients aged over 2 years old). Diffuse developmental disorders of the lung accounted for 15 (49%) patients, primarily alveolar capillary dysplasia, followed by surfactant disorders in 5 (16%) patients. Complications occurred in 9/31 (29%) patients including eight under ECMO, with massive hemorrhages in seven cases. DISCUSSION AND CONCLUSION: In critical situations, lung biopsy should be performed. Lung biopsy is a reliable diagnostic procedure for neonates in critical situation when a diffuse developmental disorder of the lung is suspected. The majority of lung biopsy complication was associated with the use of ECMO. The prospective evaluation of the complications of such procedure under ECMO, and particularly over 10 days of ECMO and in children over 2-year-old remains to be ascertained.

Pulmonary mucoepidermoid carcinoma in a 7-year-old child.

A 7-year-old boy presented with exertional dyspnea and cough, initially misdiagnosed as asthma. Imaging revealed a mass obstructing the left main bronchus, later identified as a pulmonary mucoepidermoid carcinoma (MEC). Following surgical sleeve resection, complete tumor removal occurred without malignancy in surrounding lymph nodes, resulting in symptom resolution without additional therapy. Pulmonary MEC, uncommon in pediatric patients, poses diagnostic challenges due to nonspecific symptoms, resulting in delayed diagnosis. Typically managed via complete surgical resection, MEC offers a favorable prognosis, primarily affecting central airways and requiring conservative surgical approaches to preserve lung tissue. This case underscores the diagnostic challenges of primary pulmonary MEC in pediatric patients. It stresses the need to consider unusual causes in pediatric respiratory symptoms and highlights the critical role of precise diagnostic methods and personalized surgical strategies in managing such rare pulmonary malignancies for optimal outcomes.

CSF2RB mutation-related hereditary pulmonary alveolar proteinosis: the "long and winding road" into adulthood.

Genetic analysis pre-lung transplantation diagnosed a case of hereditary pulmonary alveolar proteinosis (PAP) complicated by fibrosis in adulthood. The need for genetic testing in GM-CSF autoantibody negative and unclassifiable PAP is highlighted. https://bit.ly/3QcsYwM.

An evaluation of an open access iPSC training course: "How to model interstitial lung disease using patient-derived iPSCs".

BACKGROUND: Interstitial lung diseases (ILD) are a group of rare lung diseases with severe outcomes. The COST Innovator Grant aims to establish a first-of-a-kind open-access Biorepository of patient-derived induced pluripotent stem cells (iPSC) and to train researchers in the skills required to generate a robust preclinical model of ILD using these cells. This study aims to describe and evaluate the effectiveness of a training course designed to train researchers in iPSC techniques to model ILD. METHODS: 74 researchers, physicians and stakeholders attended the training course in Dublin in May 2022 with 31 trainees receiving teaching in practical iPSC culturing skills. The training course learners were divided into the Hands-on (16 trainees) and Observer groups (15 trainees), with the Observers attending a supervised live-streamed experience of the laboratories skills directly delivered to the Hands-on group. All participants were asked to participate in an evaluation to analyse their satisfaction and knowledge gained during the Training Course, with means compared using t-tests. RESULTS: The gender balance in both groups was predominantly females (77.4%). The Hands-on group consisted mainly of researchers (75%), whereas all participants of the Observer group described themselves as clinicians. All participants in the Hands-on group were at least very satisfied with the training course compared to 70% of the participants in the Observer group. The knowledge assessment showed that the Hands-on group retained significantly more knowledge of iPSC characteristics and culturing techniques compared to the Observers (* < 0.05; p = 0.0457). A comprehensive learning video detailing iPSC culturing techniques was produced and is included with this manuscript. CONCLUSIONS: The majority of participants were highly or very satisfied with the training course and retained significant knowledge about iPSC characteristics and culturing techniques after attending the training course. Overall, our findings demonstrate the feasibility of running hybrid Hands-on and Observer teaching events and underscore the importance of this type of training programme to appeal to a broad spectrum of interested clinicians and researchers particularly in rare disease. The long-term implications of this type of training event requires further study to determine its efficacy and impact on adoption of iPSC disease modelling techniques in participants' laboratories.