Pediatric Pulmonology 2024 year in review: Rare and diffuse lung disease

Pediatric Pulmonology 2024 year in review: Rare and diffuse lung disease | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Pediatric Pulmonology This is a preprint and has not been peer reviewed. Data may be preliminary. 7 March 2025 V1 Latest version Share on Pediatric Pulmonology 2024 year in review: Rare and diffuse lung disease Authors : Pi Chun Cheng 0000-0002-2809-5799 [email protected] , Deborah R. Liptzin 0000-0002-3667-1856 , Katiana Garagozlo 0009-0004-8437-7979 , and Andrew T. Barber Authors Info & Affiliations https://doi.org/10.22541/au.174137406.62552861/v1 Published Pediatric Pulmonology Version of record Peer review timeline 393 views 193 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The field of pediatric rare and diffuse lung diseases continues to advance, with ongoing research deepening our understanding of the diagnosis and treatment of conditions such as children’s interstitial and diffuse lung disease (chILD), non-cystic fibrosis (CF) bronchiectasis, and pulmonary complications of childhood cancer. Recent publications in Pediatric Pulmonology and other journals in 2024 have highlighted new insights into the pathophysiology, disease progression, and emerging diagnostic tools for these rare lung conditions, as well as innovative therapeutic approaches. This review features these important advancements within the context of current diagnostic practices and clinical care for pediatric patients with rare and diffuse lung diseases. Pediatric Pulmonology 2024 year in review: Rare and diffuse lung disease Authors; Pi Chun Cheng 1,2 , Deborah R Liptzin 3 , Katiana Garagozlo 4 , Andrew T Barber 5 Affiliations; 1. Division of Pediatric Pulmonology, Allergy, and Sleep Medicine, Riley Hospital for Children, Indianapolis, Indiana 2. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 3. University of Washington School of Mediine Department of Pediatrics 4. Department of Pediatrics, Division pf Pediatric Pulmonology, University of South Florida Morsani College of Medicine, Tampa, Florida, USA 5. Virginia Commonwealth University Correspondence: Pi Chun Cheng, MD, MS Division of Pediatric Pulmonology, Allergy, and Sleep Medicine Riley Hospital for Children Indiana University School of Medicine Address: 705 Riley Hospital Drive ROC 4270 Indianapolis, IN 46202, United States Email: [email protected] Phone: (317) 948-7208 Fax: (317) 944-5791 Keywords: bronchiectasis; bronchiolitis obliterans syndrome; interstitial lung disease; primary ciliary dyskinesia; stem cell transplantation Acknowledgement: None of the authors have a conflict of interest to disclose Abstract: The field of pediatric rare and diffuse lung diseases continues to advance, with ongoing research deepening our understanding of the diagnosis and treatment of conditions such as children’s interstitial and diffuse lung disease (chILD), non-cystic fibrosis (CF) bronchiectasis, and pulmonary complications of childhood cancer. Recent publications in Pediatric Pulmonology and other journals in 2024 have highlighted new insights into the pathophysiology, disease progression, and emerging diagnostic tools for these rare lung conditions, as well as innovative therapeutic approaches. This review features these important advancements within the context of current diagnostic practices and clinical care for pediatric patients with rare and diffuse lung diseases. Introduction In the past year, significant progress has been made in our understanding of fields including children’s interstitial and diffuse lung disease (chILD), non-cystic fibrosis (CF) bronchiectasis, and pulmonary complications of childhood cancer. Our research and clinical communities continue to recognize the importance of collaboration to advance our understanding of these conditions and improve patient care. This is increasingly seen both within centers through multidisciplinary care and through the rapid development of research and clinical care networks and multicenter registries. Although diagnosing these conditions remains challenging, advances in genetic sequencing and imaging techniques have enhanced our understanding. 1 Emerging therapies, such as antifibrotics like nintedanib and pirfenidone, show promise for treating these disorders in children. Children’s interstitial and diffuse lung disease chILD includes a diverse array of rare respiratory disorders. The US national chILD registry recently reported 717 cases across 23 sites, emphasizing the value of collaboration in studying rare lung diseases. 2 There is a slight male predominance (54%), consistent with previous reports of increased respiratory morbidity in males. 3 Neuroendocrine cell hyperplasia of infancy (NEHI) was the most common (22.7%), followed by connective tissue and immune mediated disorders (16.5%), surfactant metabolism dysfunction (12%), bronchiolitis obliterans (11%), and alveolar hemorrhage (9.2%). Disease severity varied significantly. Pulmonary hypertension occurred in 5%, death in 6% (most commonly due to immune/connective tissue disorders and bronchiolitis obliterans), and 3% underwent lung transplantation. No deaths occurred in NEHI cases. Nearly half the patients experienced failure to thrive, underscoring the need for nutritional and respiratory support. This registry represents the largest longitudinal cohort of chILD conditions in the United States to date, establishing a strong framework for collaboration among centers dedicated to enhancing the understanding and treatment of these rare disorders. Lung biopsy can aid in diagnosing chILD but must be balanced by the potential complications. Levy et al. 4 conducted a retrospective study in the intensive care unit from 1995-2022, reviewing 31 biopsies with a mean age of 18 days. A diagnosis was made in 25 out of 31 cases (80%). A change in management occurred in 12 patients, with four patients being started on corticosteroids and eight patients were eventually placed in palliative care. Complications occurred in nine individuals, including two deaths. The authors suggested that lung biopsy may provide a quicker diagnosis than genetic testing and may also reveal a diagnosis when genetics are negative. However, it should still be noted that lung biopsy has several disadvantages, including risk for complications, reliance upon access to an experienced pathologist, and the potential for an inconclusive diagnosis. In a separate study, Wee et al. 5 reviewed post-operative mortality rate in pediatric lung biopsies in Ontario, Canada. 1474 pediatric patients underwent lung biopsy between 2000 and 2019. Overall 30-day post lung biopsy mortality was 5.1%. Mortality was significantly higher with open lung biopsy compared to video assisted thoracoscopic biopsy (OR 13.13). Mortality was higher in patients under 3 months and those with more comorbidities (OR 6.04 and 1.15, respectively). This manuscript highlights that video assisted thoracoscopic lung biopsy is generally safe, especially in patients older than 3 months and with fewer comorbidities. NEHI is a form of chILD, characterized by tachypnea, hypoxemia, crackles, and failure to thrive. 6 Distinct chest CT findings associated with NEHI include air trapping and ground glass opacities (GGOs), predominantly in the right middle lobe, lingula, and/or perihilar regions. 6-7 Miraftabi et al. 8 provided a critical examination of the histopathologic characteristics of NEHI, noting that the original histopathologic criteria may not apply uniformly to all patients with this condition. This study detailed the GGO ratios in children with NEHI, consisting of 11 patients with biopsy-confirmed NEHI and another 11 with a clinical history suggestive of NEHI but with biopsy results inconsistent with the diagnosis. Interestingly, the maximum GGO ratio calculated in this cohort did not correlate with the percentage of pulmonary neuroendocrine cells (PNECs) observed in the biopsies, despite being from anatomically similar regions. This finding is consistent with prior studies that areas of GGO do not necessarily correspond with increased PNECs. 9 Furthermore, one patient presented with clinical characteristics typical of NEHI, alongside consistent biopsy findings, yet lacked imaging results indicative of the condition. This raised concerns about the possibility of an alternative disease process involving increased PNECs rather than NEHI. It is worth considering that the identified areas of GGOs may represent normal lung tissue on expiratory scans, while the areas exhibiting air trapping may be the true pathological findings, and therefore biopsies of the GGOs would not be expected to have increased PNECs. This manuscript underscores the significant gaps in our understanding of NEHI in children. In a separate commentary, Griese et al. 10 reviewed the developmental conditions manifesting in infancy, which encompass persistent tachypnea of infancy (PTI), pulmonary interstitial glycogenosis (PIG), and NEHI. The authors emphasized the importance of recognizing the developmental nature of these disorders and argue for the use of PTI as the preferred label over NEHI, citing the rarity of lung biopsies and the lack of a definitive causal relationship between PNECs and PTI. The commentary encouraged pediatricians to avoid superficial diagnoses and instead to search for associated and underlying conditions with the help of clinical expertise and genetic testing. To expand upon our current diagnostic capabilities, Marczak et al. 11 investigated the utility of various serum biomarkers in diagnosing NEHI in children compared with healthy controls. They observed that children with NEHI had elevated serum levels of KL-6 compared to healthy controls, although these levels were relatively low. Elevated levels of KL-6 have been associated with various forms of chILD. 12-13 While biomarkers like KL-6 hold diagnostic potential, their precision remains uncertain. Extensive research network has facilitated a deeper understanding of the natural history of many chILD conditions. Diesler et al. 14 reviewed 36 adult patients with pathogenic variants, SFTPC and ABCA3, followed in the French rare lung disease network (OrphaLung). This is an unusually large cohort of patients followed over a 10-year period. While patients were generally diagnosed as adults (median age 34 years, IQR 19.3-44.2), 5 of them did have a history of neonatal respiratory distress, 2 with pathogenic variants in SFTPC and 3 with pathogenic variants in ABCA3 . Most (82%) of the patients with pathogenic variants in SFTPC had a family history of ILD, which is not surprising as these are autosomal dominant disorders. Only 29% of those with pathogenic variants in ABCA3 had similar family histories, which is also not surprising given that they are autosomal recessive disorders. Interestingly, 77% of the patients with pathogenic variants in SFTPC were male, but only 21% of those with pathogenic variants in ABCA3 were male. Patients typically presented with dyspnea (86%), crackles (86%), clubbing (56%), and cough (53%), and there was no difference between the groups in clinical presentation evaluated. In patients with pulmonary function test (PFT) data, low forced vital capacity (FVC) was observed in 83% of those with SFTPC variants and 100% of those with ABCA3 variants. Additionally, 96% of patients exhibited reduced diffusion. The authors noted that the patients with pathogenic variants in SFTPC experienced 1.87% decline in FVC annually; those with ABCA3 pathogenic variants experienced a 0.72% annual decline in FVC. Median time to death or lung transplant was 10 years in the SFTPC group and was not reached at the end of follow-up period in the ABCA3 group. CT scans mostly showed unclassified pattern of fibrosing ILD with “unclassifiable pattern with predominance of GGO” (44%) and “unclassifiable pattern- GGO and cysts” (32%). Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in both ABCA3 and SFTPC groups. This study illustrates significant lung disease and morbidities associated with individuals with SFTPC and ABCA3 variants. Further disease surveillance is needed to understand the progression and prognosis of individuals with chILD conditions. DeBoer et al. 15 provided a comprehensive review of pediatric pulmonary fibrosis, highlighting the need for precise imaging-based diagnostic criteria. The authors review the differences between imaging findings in children and adults, and they present the imaging definition used in the InPedILD trial, assessing nintedanib in children. They stressed the importance of imaging in monitoring disease progression and propose that better diagnostic criteria are essential for future therapeutic trials. This is a timely discussion of pediatric pulmonary fibrosis in light of new therapeutics and introduces several important questions and challenges we will face as we study these therapeutics in the pediatric population. The limited pharmacological options for pediatric chILD are evolving. Nintedanib is an intracellular inhibitor of tyrosine kinases that has demonstrated a slowing in the decline in FVC in adults with fibrosing ILD. 16 In the landmark InPedILD trial evaluating nintedanib in children and adolescents, Maher and colleagues performed a separate analysis in this population to evaluate effect of nintedanib on FVC before unblinding was performed. 17 They used Bayesian statistical methods to partially extrapolate evidence from adults to estimate treatment effect on FVC in the pediatric population. The investigators found a median difference in adjusted change in FVC % predicted of 1.63 (95% credible interval -0.69, 3.40) between nintedanib and placebo. The probability of the treatment effect of nintedanib being greater than 0 was 95.5%, which fulfilled the authors’ prespecified 90% evidence level. Preliminary results suggest nintedanib may slow FVC decline in children, though more research is needed. Bayesian statistical methods have been useful in extrapolating adult data to predict treatment effects in this small, underpowered population. New therapies for chILD conditions have emerged. Yang and colleagues reported 2 cases of children with ABCA3 deficiency who had clinical improvement in oxygen dependence after treatment of Cyclosporine A (CsA). 18 However, as the authors stated, these improvements may have been secondary to other concurrent medications. They next studied CsA in vitro on these two variants and found improvement in trafficking and ABCA3 + vesicle size for both, as well as an additive effect when combined with hydroxychloroquine. Nayır Büyükşahin et al. 19 reported a case where atorvastatin was used to treat pulmonary alveolar proteinosis (PAP) in a school-aged girl with granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor deficiency. This patient had previously undergone 19 whole lung lavages before starting atorvastatin. During nearly two years of follow-up, her symptoms resolved with atorvastatin. Statins have been proposed as a potential treatment for PAP in adults, likely by increasing cholesterol excretion from alveolar macrophages and reducing alveolar cholesterol levels. 20 This case suggests that statins may be a promising treatment for PAP, but larger controlled studies are needed to confirm their efficacy. Liptzin et al. 21 reviewed the use of non-invasive ventilation (NIV) for 2 patients with pathologic variants in SFTPC . Previously these types of patients were managed with invasive ventilation via tracheostomy with consideration for lung transplantation. 22-23 This review highlighted the successful use of NIV, which can reduce medical complexity while permitting developmental therapies. Systemic corticosteroids are commonly used in chILD. Ring et al. 24 evaluated the long-term effects of systemic corticosteroids on height, bone mineral density (BMD), and body composition in 53 individuals with chILD. The investigators found that while height decreased during treatment, it improved at follow-up after cessation of treatment. No association was found between delta height and cumulative systemic corticosteroid dose. Similarly, there was no association between spine BMD z-score, total BMD z-score, or total body fat and cumulative systemic corticosteroid exposure. The authors concluded steroid side effects seem acceptable given the severity of chILD, though long-term effects should remain monitored. Many rheumatologic conditions are associated with lung involvement. Systemic juvenile idiopathic arthritis-associated lung disease (sJIA-LD) is a life-threatening disease with high morbidity and motality. 25-26 Huang et al. 27 conducted a prospective cohort study of 41 patients with sJIA and lung disease. Fifteen percent had trisomy 21. Over 75% experienced at least one episode of macrophage activation syndrome (MAS). The median age of sJIA diagnosis was 1.5 years, and the median age of lung disease diagnosis was 3 years. The cohort had a lower mortality rate compared to other studies, with 93% surviving at the last follow-up (median follow-up of 2.9 years, range 0.2-15.5 years); 3 out of 41 patients died. Despite the lower mortality rate, 37% had progression in lung disease requiring chronic oxygen therapy or ventilatory support. CT scans showed septal thickening (64%), lymphadenopathy (44%), and GGOs (41%). Patients with GGOs were more likely to need respiratory support, although this was not statistically significant. Eighty-four percent had the HLA-DRB1*15 allele, associated with drug reaction with eosinophilia and systemic symptoms (DRESS). Patients had elevated IL-18 levels, and some had elevated CXCL9 concentrations, which did not correlate with MAS or IL-18 levels. Matrix metallopeptidase 7 (MMP7) was significantly higher in children with sJIA-LD compared to those without lung disease. Matt et al. 28 investigated the outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) in children with refractory sJIA-LD. This international, retrospective cohort study included data from 13 patients with sJIA-LD from nine centers. There was high transplant related mortality with four (31%) patients dying within 1 year of HSCT. However, all surviving patients had complete response with no active features of sJIA, no corticosteroids or other immunosuppressive therapy use, and no supplemental oxygen dependence at a median follow-up of 16 months. This study showed that HSCT may offer significant clinical benefits in children with refractory sJIA-LD, with a substantial proportion of patients experiencing disease remission and improvement in lung function. However, HSCT also carries significant risks, including infection, graft-versus-host disease (GVHD), and death. Further research is necessary to refine patient criteria and long-term outcomes. As sJIA carries significant morbidities, novel therapies that improve the functioning and quality of life in individuals with sJIA are needed. Inspiratory muscle training (IMT) showed promise in improving lung function and exercise capacity in children with sJIA. Sarac et al. 29 found higher FVC, FEV1, and VO2peak in IMT-treated patients, suggesting it could be a useful therapy for improving respiratory function in JIA. In addition to exploring novel therapies, healthcare delivery methods for chILD conditions were also explored. Multidisciplinary team meetings (MDTm) have been increasingly used in diagnosing and managing rare diseases. Cassibba et al. 30 demonstrated the effectiveness of MDTm in diagnosing and managing rare diseases, confirming 100% of NEHI, surfactant metabolism disorder, and PAP diagnoses and reducing undefined chILD cases from 44% to 20%. Corrections to chILD etiology were suggested for 55 children (25%). This study underscores the importance of MDTm in improving diagnostic accuracy, treatment, and outcomes for rare diseases. Garagozlo et al. 31 assessed ICD-10 coding for ChILD provided by the American Thoracic Society (ATS) and found high specificity but low positive predictive value. This study represents the first known validation of ICD-10 codes for chILD, acknowledging that chILD syndrome does not directly equate to chILD diagnoses. The study suggests that a unifying ICD-10 code for chILD, such as J84.848 (other ILD of childhood), might better identify this complex and heterogeneous patient population. Griese et al. 32 used the chILD-EU registry to compare patient- and caregiver-reported health-related quality of life (HrQoL) scores, finding good agreement on physical health but less so on emotional and social domains. This highlights the importance of addressing psychosocial well-being alongside medical care for those affected by chILD. Non-CF bronchiectasis and primary ciliary dyskinesia In the past year, significant advancements have been made in the understanding and management of non-CF bronchiectasis. Mills et al. 33 conducted a retrospective study of 142 children with bronchiectasis, defined by a bronchoarterial ratio > 0.8 on CT imaging, and found that 40.1% had complete radiographic resolution and 39.4% showed improvement. Factors associated with radiographic resolution included younger age at diagnosis, fewer affected lobes, lower bronchoarterial ratio, lower modified Reiff score, presence of cylindrical bronchiectasis, and fewer courses of intravenous antibiotics per year. Conversely, the presence of Pseudomonas aeruginosa was associated with non-resolution. This study underscores the potential for bronchiectasis resolution in children with appropriate management. Primary ciliary dyskinesia (PCD) is a rare but likely underdiagnosed genetic disorder that affects motile cilia which leads to impaired mucociliary clearance and recurrent respiratory infections. Diagnosis involves a combination of clinical evaluation, nasal nitric oxide (nNO) measurement, genetic testing, and specialized analyses of cilia structure and function. 34 Carr and colleagues evaluated the diagnostic utility of nNO testing as a first-line tool, finding it effectively ruled out PCD in 75% of children (with nNO value above the cutoff of 77nL/min). 35 Additionally, repeated low nNO values in 8 individuals (11% of those tested) suggested a probable diagnosis of PCD despite negative confirmatory testing. The diagnostic capability for younger children with PCD is currently limited, particularly since young children may not be able to reliably perform nNO testing. Koucký et al. 36 conducted infant pulmonary function tests (iPFT) in 15 infants with PCD (median age 35.9 weeks) and compared the results to 16 healthy infant controls (median age 39.0 weeks). The study found that infants with PCD had lower maximal expiratory flow at functional residual capacity (FRCbox) and V’maxFRC compared to controls. Approximately 40% of infants with PCD had abnormal iPFT results, whereas no control subjects had any abnormalities. This study demonstrated that PFTs deficits start very early in life for patients with PCD. Individual PCD-causing genes are known to have specific defects in ciliary ultrastructure as well as ciliary beat pattern and frequency. The use of high-speed videomicroscopy (HSVM) to evaluate ciliary beat pattern and frequency as a diagnostic test remains controversial. However, there remain significant limitations in other PCD diagnostic tests. One such limitation is that the identification of ciliary ultrastructure defects relies on human interpretation. A retrospective study by Pifferi et al. 37 used soft computing analysis to correlate ciliary ultrastructure with ciliary beat pattern and frequency in 212 individuals with PCD. The study found significant concordance between ultrastructural defects and functional ciliary features, suggesting that soft computing methods may assist in identifying PCD-causing genes and evaluating variants of unknown significance. Given the challenges in PCD diagnosis, it is essential to continue training pathologists in this expertise to ensure accurate diagnosis and advancement in PCD research. Chowdhary et al. 38 introduced the Specific PCD Evaluation by CT (SPEC) score, a novel CT scoring system for PCD. The study involved 30 patients with PCD, with a median age of 17 years. The SPEC score assessed various lung structural changes, including bronchiectasis, bronchial wall thickening, mucous plugging, atelectasis, air trapping, and interlobar septal thickening. Scores ranged from 0 to 60, with a strong negative correlation identified between the SPEC score and PFTs (FVC, FEV1, and FEV1/FVC ratio). The SPEC score offers a promising tool for monitoring longitudinal changes in CT scans and evaluating the efficacy of interventions in PCD patients. The integration of advanced imaging techniques and artificial intelligence-driven technology holds great promise for enhancing the diagnosis and disease surveillance of PCD with hopes of earlier detection, more accurate monitoring, and personalized treatment strategies. Advances in genetic sequencing, such as whole genome sequencing (WGS), have identified novel PCD-related genes. A European study evaluated the utility of WGS in diagnosing PCD in eight individuals with low nNO and abnormal ciliary biopsy results. WGS provided a genetic diagnosis in all cases, identifying pathogenic deletions (3-13 kb) in three individuals and a de novo missense variant in the novel gene TUBB4B , which is autosomal dominant. 39 Similarly, Gardner et al. 40 described two infants with high clinical suspicion of PCD, despite negative multigene panels, were diagnosed with pathogenic variants in DNAAF6 after expanded molecular genetic analysis. These studies underscore the value of advanced genetic testing in cases of negative PCD gene panels when PCD is strongly suspected. In microbiome research, Ademhan Tural et al. 41 explored the airway microbiota of PCD patients. Bacterial ribosomal DNA was extracted from sputum and nasal samples of 14 PCD patients (seven pairs of siblings) and nine parents. Culture-dependent analyses could not detect many of the bacterial species identified with culture-independent methods, suggesting that the airway microbiota of PCD patients have more diverse bacterial communities than previously indicated. Additionally, sibling pairs showed no more community similarities than nonsibling PCD patients. Several studies described novel and rare clinical presentations of PCD. Schreck et al. 42 examined the reproductive health care of individuals with PCD, utilizing data from the international COVID-PCD database. With a cohort primarily of adults (69%), the study revealed that fertility care remains an under addressed area, with only 12% referred by their PCD specialist. Half of the adults reported receiving fertility care, but a significant proportion (over 1/3) felt that all patients with PCD should be routinely referred to a fertility specialist. The study also highlighted considerable gaps in patient satisfaction and information provision, with only 56% of those who consulted a fertility specialist expressing satisfaction. The authors advocated for integrating fertility care as a routine part of PCD management, emphasizing that PCD specialists should initiate referrals at diagnosis or at transition to adult care. Kennelly et al. 43 sought to establish the prevalence of tracheobronchomalacia (TBM) in children with PCD in a single center. This study found that 69% of the 32 PCD patients exhibited some form of airway malacia, which is significantly higher than the general population but comparable to the prevalence seen in CF. 44 While the study was limited by its small sample size and retrospective design, it suggests clinicians should consider TBM in the management of children with PCD. Pulmonary complications of childhood cancer Childhood cancer survivors are at risk of pulmonary morbidity due to lung-toxic treatments, including specific chemotherapy, radiotherapy, and surgery. Longitudinal data on lung function over time is limited. Kasteler et al. 45 conducted a multicenter study of 183 Swiss childhood cancer survivors diagnosed between 1990 and 2012. The study found nearly 50% of survivors had at least one abnormal PFT, with restrictive patterns in 22%. FEV1 and FVC showed no significant long-term changes, though survivors who underwent thoracic surgery had persistently lower values. This study concluded that reduced pulmonary function was frequent in childhood cancer survivors. Long-term surveillance of this vulnerable population is needed. Many children undergo allogeneic HSCT for the treatment of malignant and non-malignant conditions. Pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common non-infectious pulmonary complication. Current guidelines lack standardized post-HSCT monitoring and rely on spirometry, which can be difficult for many children. ATS developed a clinical practice guideline to address the detection of BOS in children following HSCT. 46 The guideline emphasizes pre-HSCT PFTs including spirometry, lung volumes, and DLCO, and active post-transplant surveillance PFTs at routine intervals based on the risk of BOS. It recommends complementary diagnostic tools, including multiple breath washout, chest CT, bronchoscopy with bronchoalveolar lavage (BAL), and lung biopsy. New pediatric BOS criteria have been proposed, including considerations for both children who can and cannot perform spirometry. This document provides an evidence-based approach to the detection of post-HSCT BOS in children. It also underscores the need for multi-center prospective studies to assess surveillance methods and biomarkers for early detection of BOS. The role of flexible bronchoscopy with BAL in children with leukemia or post-HSCT is not well established. Georgescu et al. 47 evaluated the diagnostic yield and complications related to bronchoscopy in a single center study. Results showed that 77% of bronchoscopies provided diagnostic information, with 65% identifying infectious pathogens, 23% detecting mucus plugging, and 10% with pulmonary hemorrhage. BAL changed antimicrobial therapy in 45% of cases, with complications being rare and minor, underscoring its utility and safety in managing pulmonary complications in this group. Conclusions In 2024 we continued to push the boundaries of our knowledge surrounding chILD, non-CF bronchiectasis, and pulmonary complications of childhood cancer. Critical to this endeavor is the continued multicenter collaboration in research. Groups such as the North American chILD Research Network (chILDRN), European Research Collaboration for Children’s Interstitial Lung Disease (chILD-EU), and the Children’s Interstitial Lung Disease Respiratory Network of Australia and New Zealand (chILDRANZ) are crucial in advancing the clinical and genetic knowledge of these rare conditions. The future is promising for research and care of children with rare and diffuse lung diseases. References: 1. Spielberg, D. R., Weinman, J., & DeBoer, E. M. (2024). Advancements in imaging in ChILD. Pediatric pulmonology , 59 (9), 2276–2285. https://doi.org/10.1002/ppul.26487 2. Nevel, R. J., Deutsch, G. H., Craven, D., Deterding, R., Fishman, M. P., Wambach, J. A., Casey, A., Krone, K., Liptzin, D. R., O’Connor, M. G., Kurland, G., Taylor, J. B., Gower, W. A., Hagood, J. S., Conrad, C., Tam-Williams, J. B., Fiorino, E. K., Goldfarb, S., Sadreameli, S. C., Nogee, L. M., … chILD Registry Collaborative (2024). 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Pediatric pulmonology , 59 (1), 129–136. https://doi.org/10.1002/ppul.26726 Information & Authors Information Version history V1 Version 1 07 March 2025 Peer review timeline Published Pediatric Pulmonology Version of Record 17 Apr 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Pediatric Pulmonology Keywords bronchiectasis bronchiolitis obliterans syndrome interstitial lung disease primary ciliary dyskinesia stem cell transplantation Authors Affiliations Pi Chun Cheng 0000-0002-2809-5799 [email protected] Indiana University Division of Pediatric Pulmonology Allergy and Sleep Medicine View all articles by this author Deborah R. Liptzin 0000-0002-3667-1856 University of Washington Department of Pediatrics View all articles by this author Katiana Garagozlo 0009-0004-8437-7979 University of South Florida Department of Pediatrics View all articles by this author Andrew T. 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