Association of Bronchial Artery Embolization with Disease Recurrence in paediatric Idiopathic Pulmonary Hemosiderosis: A Retrospective Cohort Study

Association of Bronchial Artery Embolization with Disease Recurrence in paediatric Idiopathic Pulmonary Hemosiderosis: A Retrospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Bronchial Artery Embolization with Disease Recurrence in paediatric Idiopathic Pulmonary Hemosiderosis: A Retrospective Cohort Study shan luo, Yuan Yuan, Hongyan Chen, Jing Liu, Shuolin Li, Li Sun, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8821027/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract OBJECTIVE This study aimed to characterize pediatric idiopathic pulmonary hemosiderosis (IPH) and assess whether adding bronchial artery embolization (BAE) to glucocorticoid (GC) therapy reduces the cumulative risk of disease recurrence. METHODS We conducted a retrospective cohort study of children with IPH between January 2003 and January 2020 from a single center. Demographic, clinicopathologic, therapeutic, and outcomes data were extracted. The primary outcome was cumulative recurrence of hemorrhage, analysed using the Andersen-Gill models. The secondary outcomes included time to first recurrence and change in hemoglobin levels from baseline to six months after treatment. RESULTS A total of 63 patients were included, with 44 (70%) receiving BAE plus GC treatment and 19 (30%) receiving GC treatment alone. The median age at diagnosis was 4.6 years (interquartile range: 2.1–7.6), and 28 (44%) were female. During a median follow-up period of 36 months (range, 0.7–120), 87 relapses occurred in the GC with BAE group versus 24 in the GC without BAE group. The adjusted hazard ratio was 1.66 (95% confidence interval [CI], 0.58–4.74) for the GC with BAE group compared with GC alone. The corresponding hazard ratio for time to first recurrence was 0.98 (95% CI, 0.39–2.44). Changes in hemoglobin levels did not differ significantly between the two groups (–20.5 [95% CI, − 27.4 to − 0.7] vs − 14.0 [95% CI, − 26.7 to 14.4], mean difference − 6.5 [95% CI, − 19.0 to 6.0], P = 0.30). CONCLUSIONS Our data do not support the addition of BAE to conventional GC therapy as routine primary treatment for pediatric IPH. Idiopathic pulmonary hemosiderosis children bronchial artery embolization Figures Figure 1 Figure 2 INTRODUCTION Idiopathic pulmonary hemosiderosis (IPH) is an rare cause of diffuse alveolar hemorrhage (DAH)( 1 ). Rudolph Virchow provided the first postmortem description of this condition as early as 1864( 2 ). In select pediatric populations, the incidence of IPH varies between 0.24 and 1.26 patients per million, with a mortality rate of up to 50%( 3 , 4 ). IPH is characterized by the triad of hemoptysis, iron deficiency anemia, and pulmonary infiltrates on chest imaging. However, recent studies show that IPH has diverse clinical manifestations and the classic triad of IPH is not always present in children( 5 – 7 ). Glucocorticosteroids, also known as corticosteroids (CS), are the drugs of choice for both acute episodes and long-term maintenance, as they reduce capillary permeability and inhibit immune-mediated injury( 1 , 8 , 9 ). IPH is also a common cause of hemoptysis in children( 5 ). Moderate to severe hemoptysis that does not respond to medical therapy is an indication for bronchial artery embolization (BAE)( 10 ); however, the application of BAE in patients with IPH remains limited( 11 ). Due to concerns about the side effects of standard drug treatments for IPH, there is currently no effective non-pharmacological alternative. Interventional diagnostics and therapies may offer additional insights into both the etiology and management of IPH. This study aimed to describe the clinical characteristics of patients with IPH and to explore the association between the addition of BAE to conventional glucocorticoid (GC) treatment and cumulative recurrence in children with IPH. What’s Known on This Subject BAE effectively controls acute pediatric pulmonary hemorrhage, including IPH, a rare cause with recurrent alveolar bleeding. However, long-term recurrence rates post-BAE and associated factors in IPH remain poorly understood. What This Study Adds The study suggests that combining BAE with glucocorticoid therapy may not affect either the time to first recurrence or the cumulative risk of recurrence. PATIENTS AND METHODS Patient Population We conducted an observational cohort study to evaluate the current use of BAE among patients with IPH undergoing GC therapy and the association of BAE with disease recurrence. Eligible patients were identified through a systematic review of electronic health records of Children’s Hospital of Fudan University using the International Classification of Diseases, Tenth Revision code E83.100x005 + J99.8* between January 2003 and January 2020. Patients with IPH were defined as follows: ( 1 ) respiratory symptoms such as cough and hemoptysis, accompanied by iron deficiency anaemia, chest radiograph or chest computed tomography (CT) showed diffuse flocculation or ground glass changes in the lungs (Suppl. Figure 1 and Suppl. Figure 2); ( 2 ) hemosiderin cells were found in sputum gastric fluid or bronchoalveolar lavage fluid (Suppl. Figure. 3); ( 3 ) patients with secondary pulmonary hemorrhage with clear cause of oral and nasal hemorrhage and iron deficiency anaemia were excluded. All study protocols were reviewed and approved by the Institutional Research Ethics Committee of the Children’s Hospital of Fudan University. Exposure The primary exposure variable was undergoing BAE as adjunctive therapy. For the GC with BAE group, the patients first underwent a specific GC-based treatment protocol; BAE was subsequently carried out at an appropriate time point during the treatment course. In contrast, the GC without BAE group only received the GC treatment, following the same GC-dosing regimen as the other group but without the BAE procedure. The patients were grouped based on their historical medical records, as no randomization was performed in this retrospective study. The follow-up period ranged from 0.7 to 120 months, during which cumulative recurrence was closely monitored to assess the impact of the exposure variables. Covariates Age was included as a covariate as different age groups have varying physical functions and recovery abilities, influencing cumulative recurrence risk. Sex is an important covariate; due to physiological and hormonal differences between sexes, responses to BAE treatment and recurrence patterns may vary. The degree of anaemia is a covariate as it affects oxygen supply and tissue repair, potentially linked to cumulative recurrence risk. Imaging findings serve as covariates, visually showing disease characteristics and severity, with different manifestations implying different progressions and affecting recurrence rates. A comprehensive consideration of these covariates enables a more accurate analysis of their relationships with cumulative recurrence, facilitates the assessment of disease recurrence risk, and supports the development of effective prevention and treatment strategies. Outcomes The primary outcome was the cumulative recurrence after treatment. The secondary outcomes included the first recurrence, as well as the within-group and between-group comparisons of hemoglobin levels. Recurrence was defined as a decrease in hemoglobin accompanied by coughing up hemoptysis, along with new exudates visible on chest radiograph or chest CT. Recurrence was recorded from the time of discharge following the initial hospital admission. Statistical Analysis Baseline characteristics between groups were presented and compared by standardized mean difference( 12 – 15 ), with 0.2, 0.5, and 0.8 correspond to small, medium, and large effect sizes, respectively. During the follow-up, seven patients were diagnosed with secondary pulmonary hemorrhage. We plotted Kaplan-Meier curves for both first recurrence and cumulative recurrence using sensitivity analysis. For the primary outcome analysis, we performed analysis using the Anderson Gill recurrent events model to estimate the cumulative recurrence risk. This approach was employed to account for correlated recurrent events while assessing the association between individual covariates and time-to-event outcomes. The Cox regression model was used to estimate the first recurrence. Independent sample or paired t-test was used to statistically analyze the hemoglobin content of patients in the GC with BAE group and the GC without BAE group after 0 and 6 months of follow-up. All statistical analyses were two-sided, and P < 0.05 was considered statistically significant. Data were analyzed using SPSS (version 27.0) and R statistical software (version 4.4.2). RESULTS Baseline Characteristics This systematic search yielded 73 unique patient records, which were individually reviewed to ensure standardized validation against the diagnostic criteria for IPH. Ten patients were excluded due to insufficient post-discharge follow-up duration. By the final follow-up in January 2025, 63 patients were identified as having been hospitalized with IPH. Data abstraction was performed by a single reviewer to maintain consistency (Figure 1). The study consisted of 63 patients with IPH. The median age of diagnosis was 4.6 years (interquartile range [IQR]: 2.1–7.6 years), the median age of onset was 3.8 years (IQR: 1.5–6.5 years), and 28 (44.4%) of the patients were female. In the GC with BAE group, the median age at diagnosis was 3.8 years (IQR: 2.0–7.0 years), and the median age at onset was 3.2 years (IQR: 1.5–6.0 years). In the GC without BAE group, the median age at diagnosis was 5.5 years (IQR: 2.5–9.5 years), and the median age at onset was 4.8 years (IQR: 1.0–6.8 years). The median follow-up time was 36.0 months (range: 0.7–120.0 months). Among the baseline characteristics, slight differences were observed between the two groups in age at diagnosis (SMD = 0.29) and presence of patchy density on imaging (SMD = 0.28). The SMD for other baseline characteristics were all < 0.2, indicating that the two groups were generally comparable at baseline (Table 1). BAE Manifestations Anomalous bronchial arterial anatomical features: (1) there were nine anomalous origin bronchial arteries in total, including three branches from the right internal mammary artery, and one branch each from the thyrocervical trunk, subclavian artery, brachiocephalic trunk, right internal thoracic artery, descending aorta, and aortic arch; (2) pulmonary vascular malformation in seven cases: two cases of bronchial artery - pulmonary vein fistula, four cases of bronchial artery - pulmonary artery fistula, and one case of diffuse hyperplasia of the left and right bronchial artery with pulmonary artery fistula. Signs of bleeding (Suppl. Figure 4): (1) 31 cases showed indirect bleeding signs; (2) one case demonstrated direct bleeding signs; (3) 11 cases displayed both direct and indirect bleeding signs. The direct signs of hemorrhage were the exudation of contrast medium in lung parenchyma, and the indirect signs were the enlargement, expansion, and disorder of the lesion vessels. Adverse Event and Other Outcomes Among the 44 patients who received BAE, one patient developed intracranial embolism after surgery, which was manifested as coma and occasional involuntary shaking of both upper limbs. The cranial magnetic resonance imaging is shown in Suppl. Figure 5. After treatment, the patient improved and was discharged from hospital. The patient is currently able to perform fine motor tasks and trot, and is off hormonal therapy. No complications were observed following BAE in the other patients. Seven patients were diagnosed with secondary pulmonary hemorrhage, including one patient with trisomy 21 syndrome, two with ANCA-associated vasculitis (AAV), two with interstitial pneumonia with autoimmune features (IPAF, multidisciplinary diagnosis), one with juvenile idiopathic arthritis (JIA), and one with TNNT2 gene mutation (potentially associated). Cumulative Recurrence and First Recurrence between Two Groups In the initial assessment of recurrence risk between the two groups (Figure 2 A and B), Kaplan-Meier curves (first recurrence) and Andersen-Gill recurrent event models (cumulative recurrence) demonstrated no statistically significant differences over the entire follow-up period (all P >0.05). A sensitive analysis excluding the seven cases diagnosed subsequently as having pulmonary hemorrhage during follow-up yielded similar association estimates. BAE and Cumulative Recurrence Risk Among the 63 patients, the median time to cumulative recurrence was 38.0 (range: 0.7–109.1) months in the GC with BAE group and 29.1 (range: 1.0–120.0) months in the GC without BAE group, 87 recurrent events were observed in the GC with BAE group and 24 in the GC without BAE group. BAE was not associated with a decreased cumulative recurrence risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 0.58–4.74]). The association between BAE and cumulative recurrence risk was of a similar magnitude when models were stratified by the age of onset (HR, 0.81[95% CI, 0.54–1.21]), the age of treatment (HR, 1.17[95% CI, 0.74–1.83]). The degree of anaemia was associated with a decreased risk of cumulative recurrence compared to normal hemoglobin level：mild (HR, 0.68[95% CI, 0.47–0.98])，moderate (HR, 0.77[95% CI, 0.62–0.96])，severe (HR, 0.72[95% CI, 0.53–0.97]). Female sex was associated with an increased risk of cumulative recurrence compared to male sex (HR, 1.92[95% CI, 1.66–2.24]). Among the 56 patients, the median time to cumulative recurrence was 50.1 (range: 0.7–109.1) months in the GC with BAE group and 29.1 (range: 1.0–120.0) months in the GC without BAE group, 72 recurrent events were observed in the GC with BAE group and 23 in the GC without BAE group. BAE was not associated with a decreased cumulative recurrence risk (HR, 1.65[95% CI, 0.51–5.36]). The association between BAE and cumulative recurrence risk was of a similar magnitude when models were stratified by the age of onset (HR, 0.85[95% CI, 0.58–1.23]), and the age of treatment (HR, 1.10[95% CI, 0.73–1.67]). The degree of anaemia was associated with a decreased risk of cumulative recurrence compared to normal hemoglobin level: mild (HR, 0.44[95% CI, 0.27–0.70]), severe (HR, 0.71[95% CI, 0.51–1.00]). Female sex was associated with an increased risk of cumulative recurrence compared to male sex (HR, 1.91[95% CI, 1.70–2.17]) (Table 2). BAE and Associations for First Recurrence Among the 63 patients, the median time to first recurrence was 30.8 (range, 0.7–109.1) months in the GC with BAE group and 18.0 (range, 1.0–120.0) months in the GC without BAE group. Of the 56 patients, the median follow-up was 46.5 (range, 0.7–109.1) months in GC with BAE group and 19.5 (range, 1.0-183.1) months in the GC without BAE group. In univariate analysis, BAE was not associated with a decreased risk of first recurrence (HR, 1.01 [95% CI, 1.04 (0.44–2.50)]). After adjusting for clinicopathologic characteristics, including sex, the age of onset, the age of diagnosis and the degree of anaemia, BAE was not associated with a decreased risk of first recurrence (HR, 0.98[95% CI, 0.39–2.44]) (Table 2). BAE and hemoglobin levels 6 moths after treatment Hemoglobin levels improved significantly after treatment in both groups: the BAE group ( P <0.001), and the treatment without BAE group ( P =0.04). However, there was no significant difference in the changes in hemoglobin levels between the two groups ( P =0.30) (Table 3). Sensitivity Analyses of BAE and Recurrence After excluding seven patients diagnosed with secondary hemorrhage during the follow-up period, we conducted a sensitivity analysis. There was no statistical significance in either the time to first recurrence ( P =0.92) or the cumulative recurrence time ( P =0.36) (Figure 2 C and D). DISCUSSION In this single-centre retrospective cohort study, we characterized the clinical characteristics of patients with IPH and then compared the outcomes between GC with BAE treatment and GS alone using three measures: cumulative recurrence, first recurrence and hemoglobin level improvement within six months post-intervention. Our analysis did not demonstrate the clear superiority of BAE over conventional medical therapy among these evaluated parameters. The typical triad of IPH is recurrent hemoptysis, iron deficiency anaemia, and diffuse pulmonary infiltrates( 16 , 17 ). In our study, 12 children (19.0%) presented withanaemia at disease onset without any respiratory symptoms. Therefore, IPH should be considered in the different diagnosis of children with unexplained anaemia refractory to iron supplementation( 18 ). The severity of anaemia in patients with IPH correlates with disease progression, particularly during acute exacerbations( 19 ). Compared with chest radiographs, chest CT is a better choice for diagnosing IPH. Therefore, for anaemia that cannot be explained by haematological diseases, we recommend chest CT to assist in the diagnosis. The common vascular malformations causing pulmonary hemorrhage are pulmonary arteriovenous malformations, hereditary hemorrhagic telangiectasia (HHT/Osler-Weber-Rendu Syndrome), bronchial-pulmonary artery fistula, and pulmonary capillary hemangiomatosis. In cases where bronchial artery-pulmonary artery fistula or bronchial artery-pulmonary vein fistula is detected, recurrence may still occur after embolization. We propose that such vascular malformations may represent secondary changes in IPH, potentially related to underlying vascular inflammation. In some patients who underwent bronchial arteriography, signs of bleeding or a vagal bronchial artery were observed. Normally the bronchial artery is slender and most commonly originates between the upper margin of T 5 and the lower margin of T 6 on the thoracic aorta( 20 ). In our study, nine vagal bronchial arteries with ectopic origins were identified. Evidence of bleeding was observed in 24 patients indirectly and 12 patients directly. At present, the etiology of IPH is still unclear, but most scholars believe that the immune mechanism plays an important role in the pathogenesis of the disease( 9 , 21 – 25 ). After long-term follow-up, six patients were found to have associated autoimmune diseases. Their angiographic findings were similar to those of other patients with IPH. One patient underwent four angiograms, which revealed lesion thickening accompanied by diffuse small vessel hyperplasia, a vagal bronchial artery, and vascular recanalization. Based on these findings, we believe that the abnormal pulmonary vascular changes represent non-specific secondary alterations in IPH. A French study found that 17/25 children with IPH tested positive for autoantibodies at onset, including 50% positive for anti-smooth muscle antibodies, 45% for ANA, and 40% for ANCA; two cases were positive( 26 ). Additionally, IPH has been associated with IgA deficiency. Since IgA plays an important role in mucosal immunity, it’s deficiency may link IPH to other autoimmune diseases. Severe complications of BAE include spinal cord injury and ectopic embolism, such as intracranial or coronary embolism. The most serious complication is spinal infarction, with an incidence rate of 0.19%( 27 ). In our study, one of the 44 patients who received BAE had intracranial ectopic embolization, which indicates that the application of interventional techniques in children with IPH carries certain risks( 11 ).Six patients received two or more embolization procedures. Post-embolization imaging revealed vascular rerouting, which we attribute to compensatory hyperplasia of adjacent vessels supplying the lesion, diffuse neovascularization, or collateral circulation formation. Notably, these newly formed vessels exhibited thin and fragile walls, rendering them prone to rupture under systemic circulation pressure, thereby contributing to recurrent hemoptysis( 28 ). Consequently, no significant improvement in the change of hemoglobin levels was observed between the two groups. Additionally, underlying pulmonary inflammatory lesions may predispose to bronchopulmonary fistula formation. In the present study, the findings indicate that the two treatment approaches are comparable in mitigating the recurrence risk. Given the complex pathogenesis of IPH, which involves multiple interacting factors, neither pharmacotherapy nor BAE can fundamentally alter the relapse process of the disease. In the analysis of cumulative risk factors for recurrence, females exhibited a higher risk of multiple recurrences. We hypothesize that this may be related to an association between IPH and autoimmune diseases, such as JIA and IPAF, which are more prevalent in females. In contrast, AAV has no obvious tendency to occur in children( 29 , 30 ), which may be the reason for the high risk of cumulative recurrence in females. Lower hemoglobin levels at diagnosis are more likely to draw attention from both parents and clinicians, which may subsequently influence the risk of cumulative recurrence. This study has some limitations. First, as a single-centre study with a small sample size, its generalizability is limited, and the findings are exploratory. Second, due to its observational design, potential residual confounding cannot be ruled out. Third, recall bias may be inherent in the outcomes; however, during data collection, medical history inquiries were repeatedly cross-checked with outpatient follow-up data to minimize this risk. CONCLUSIONS This study firstly compared IPH recurrence between patients treated with the addition of BAE and those receiving traditional GC therapy alone. Our analysis did not reveal a significant association between the addition of BAE and recurrence outcomes compared with conventional hormone therapy. Given these findings, we suggest that clinicians carefully weigh the potential benefits and limitations of BAE when managing IPH. Declarations Ethics approval and consent to participate Ethical approval This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of Children's Hospital of Fudan University (approval number: 2022307A). The ethics committee waived the requirement for informed consent due to the retrospective nature of the study and anonymized patient data. Consent for publication All the authors consent to the publication of this research. Availability of data and material The datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions, but are available from the corresponding author on reasonable request. Competing interests The authors have no conflicts of interest to disclose. Funding This study was supported by National Natural Science Foundation of China (No. 82200264). Authors information Shan Luo and Yuan Yuan contribute equally to the paper. Authors and Affiliations Shan Luo: [email protected] , Department of Pediatrics, Jinshan Hospital, Fudan University, Shanghai, China, 201508 Yuan Yuan: [email protected] , Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Hongyan Chen: [email protected] , Clinical Epidemiology Research Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China,201102 Jing Liu: [email protected] , Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Shuolin Li: [email protected] , Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Li Sun: [email protected] , Department of Rheumatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Xuecun Liang: [email protected] , Department of Cardiology, Children's Hospital of Fudan University , National Children's Medical Center, Shanghai, China, 201102 Quanli Shen: [email protected] , Department of Radiology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Lian Chen: [email protected] , Department of Pathology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Aizhen Lu: [email protected] , Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Xiaobo Zhang: [email protected] , Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Libo Wang: [email protected] , Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China, 201102 Corresponding author : Libo Wang, Department of Respiratory Medicine, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Minhang District, Shanghai, China, [ [email protected] ]. Authors' contributions Shan Luo conceptualized and designed the study, drafted the initial manuscript, and collected data, carried out the initial analyses. Yuan Yuan conceptualized and designed the study, written the introductory section, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content. Hongyan Chen provided suggestions for statistical method modification, critically reviewed and revised the manuscript. The results are based on the multidisciplinary team of pulmonary hemorrhage, including Department of Respiratory Medicine, Department of Rheumatology, Department of Cardiology, Department of Radiology and Department of Pathology, work around the diagnosis of IPH, assessment of indications for intervention, and follow-up, with specific contributions as follows: Jing Liu, Shuolin Li, Aizhen Lu, Xiaobo Zhang& Libo Wang: leaded the initial diagnostic evaluation of children with IPH, responsible for collecting the patient's clinical symptom history, leading the follow-up monitoring of respiratory function and symptom changes. Li Sun: participated in IPH etiology investigation, focus on the completion of autoimmune disease-related examinations. Xuecun Liang: responsible for the study and judgment of interventional indications, leading the implementation of interventional therapy. Quanli Shen: provided imaging support for the diagnosis and condition assessment of IPH, interprets imaging data including chest computed tomography (CT) and digital subtraction angiography (DSA), and offers imaging evidence for diagnosis, formulation of interventional plans, and judgment of disease progression during follow-up. Lian Chen: responsible for issuing the pathological diagnosis report of hemosiderin in bronchoalveolar lavage fluid (BALF), and providing pathological support for the confirmed diagnosis of IPH. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Acknowledgements We acknowledge all the patients and their families for their participation in this study. References Milman N, Pedersen FM. Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and diagnosis. Respir Med. 1998;92(7):902–7. Saeed MM, Woo MS, MacLaughlin EF, Margetis MF, Keens TG. 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Baseline Characteristics of patients Characteristic Patients，No.(%) All GC with BAE GC without BAE SMD Total 63(100) 44(70) 19(30) Age at diagnosis, median (IQR), y 4.6(2.1,7.6) 3.8(2.0,7.0) 5.5(2.5,9.5) 0.29 Age at onset of symptoms, median (IQR), y 3.8(1.5,6.5) 3.2(1.5,6.0) 4.8(1.0,6.8) 0.17 Female 28(44) 19(43) 9(47) 0.08 Normal hemoglobin 4(6) 2(5) 2(11) 0.001 Mild anemia 9(14) 8(18) 1(5) Moderate anemia 23(37) 15(34) 8(42) Severe anemia 27(43) 19(43) 8(42) Chest imaging Acute stage Flocculent shadow 2(3) 1(2) 1(5) 0.17 Patchy density 27(43) 17(39) 10(53) 0.28 Opacity 30(48) 20(46) 10(53) 0.14 Chronic recurrent stage Fine particle shadow 9(14) 7(16) 2(11) 0.16 Nodules 6(10) 4(9) 2(11) 0.05 Ground glass 15(24) 10(23) 5(26) 0.08 Grid change 5(8) 3(7) 2(11) 0.14 Chronic crisis stage Septal thickening 9(14) 7(16) 2(11) 0.16 SMD: Standardized mean difference, SMD is the preferred way to describe imbalances in data that are descriptive of the sample. SMD of 0.2, 0.5, and 0.8 correspond to small effect, medium effect, and large effect, respectively. IQR:interquartile range. Table2. Association of BAE With First and Cumulative Recurrence Risk Among Children with Idiopathic Pulmonary Hemosiderosis First Recurrence Risk （63patients 44:19） First Recurrence Risk （56patients 38:18） Hazard Ratio (95%CI) a P Value Hazard Ratio (95%CI) a P Value BAE 0.98(0.39-2.44) 0.966 0.97(0.36-2.64) 0.959 Sex Female 1.76(0.81-3.85) 0.155 1.85(0.77-4.44) 0.167 Male 1[Reference] 1[Reference] Age Age of Onset 0.89(0.69-1.14) 0.360 0.91(0.72-1.16) 0.461 Age of Diagnosis 1.10(0.82-1.48) 0.512 1.06(0.79-1.42) 0.692 Anemia Mild 1.15(0.21-6.34) 0.869 1.58(0.15-15.89) 0.699 Moderate 0.83(0.16-4.20) 0.822 1.46(0.17-12.47) 0.731 Severe 0.98(0.18-5.19) 0.977 1.44(0.15-13.24) 0.747 Normal 1[Reference] 1[Reference] Characteristic Cumulative Recurrence Risk （63patients 44:19） Cumulative Recurrence Risk （56patients 38:18） Hazard Ratio (95%CI) a P Value Hazard Ratio (95%CI) a P Value BAE 1.66(0.58-4.74) 0.341 1.65(0.51-5.36) 0.402 Sex Female 1.92(0.89-4.20) 0.098 1.92(0.81-4.56) 0.140 Male 1[Reference] 1[Reference] Age Age of Onset 0.81(0.54-1.23) 0.322 0.85(0.58-1.23) 0.380 Age of Diagnosis 1.17(0.75-1.83) 0.494 1.11(0.73-1.67) 0.633 Anemia Mild 0.68(0.22-2.06) 0.495 0.43(0.11-1.73) 0.238 Moderate 0.78(0.25-2.37) 0.657 0.93(0.27-3.19) 0.910 Severe 0.72(0.23-2.24) 0.569 0.71(0.18-2.81) 0.627 Normal 1[Reference] 1[Reference] a Hazard ratios derived from the Andersen-Gill model with robust sandwich covariance estimator (or proportional means model) adjusted for all listed covariates; CI:confidence interval Table3. Changes in hemoglobin levels from baseline to 6 months. Baseline mean±SD 6 months mean±SD Changes (95%CI) Mean difference (95%CI) P value GC without BAE 89.3±27.0 103.3±27.5 -14.0±27.7 (-27.4,-0.7) -6.5 （-19.0,6.0） 0.30 GC with BAE 97.0±21.7 117.5±18.6 -20.5±20.3 (-26.7,14.4) CI:confidence interval Supplementary Files supplementaryfigure1.docx Suppl. Figure 1. Chest radiography manifestations of IPH A: Extensive exudative lesions in both lungs; B: Diffuse miliary exudation in the right lung; C: Diffuse fine granular shadow in both lungs; D: Miliary granular shadows and flaky dense shadows. supplementaryfigure2.docx Suppl. Figure 2. Computer tomography manifestations of IPH A: Diffuse exudation or ground glass shadows; B: Diffuse like millet grains; C: Diffuse interstitial changes; D: Honeycomb like bubble shadow, both lungs are diffusely filled with ground-glass opacities, small granular shadows and grid shadows, with multiple cystic translucent opacities. supplementaryfigure3.docx Suppl. Figure 3. HE (A) and iron-stained (B) hemosiderin-laden macrophages in BALF supplementaryfigure4.docx Suppl. Figure 4. Angiographic Imaging of IPH A: Right bronchopulmonary fistula; B: Densely stained lung parenchyma; C: Left bronchial artery hyperplasia. supplementaryfigure5.docx Suppl. Figure 5. Adverse Reactions of BAE A&B: Computer tomography shows multiple patchy low-density shadows; C&D: magnetic resonance imaging displays multiple patchy hyperintense shadows. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8821027","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":615992415,"identity":"17869306-f0c7-4991-82a3-d4dcff32df68","order_by":0,"name":"shan luo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACPiBmBmIeNmbmgw8SKmoIa2GDapHhY29LNnhw5hjxWmzkeM6YST5sYSZCi0Ty4c8FNXd42CQSzCoSG9gY+Nu7EwhoSUuTnnHsGUhL2o3EHTIMEmfObiCgJceMmYftMEjLsRuJZ9gYDCRyCWox/szzD6Qlsa0gsY2ZKC0G0rxtQC08h9kYiNPC8yxNmrcPqIW9jVki4cwxHoJ+4WcHhhjPt8P28s38Hz/+qKiR42/vxa8FA/CQpnwUjIJRMApGAVYAAOm8P8EOn/CAAAAAAElFTkSuQmCC","orcid":"","institution":"Jinshan Hospital of Fudan University","correspondingAuthor":true,"prefix":"","firstName":"shan","middleName":"","lastName":"luo","suffix":""},{"id":615992416,"identity":"3439cc6f-3166-4a4c-9a74-238932fcaf71","order_by":1,"name":"Yuan Yuan","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Yuan","suffix":""},{"id":615992417,"identity":"46d18da0-b3b1-42e3-a00a-53788d260645","order_by":2,"name":"Hongyan Chen","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Hongyan","middleName":"","lastName":"Chen","suffix":""},{"id":615992418,"identity":"7ec7de43-ad84-44ac-9296-e20184bfc306","order_by":3,"name":"Jing Liu","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Liu","suffix":""},{"id":615992419,"identity":"ac4580f2-2dc0-4ce6-b308-d300708f1911","order_by":4,"name":"Shuolin Li","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Shuolin","middleName":"","lastName":"Li","suffix":""},{"id":615992420,"identity":"da74c659-d45b-4493-b0fe-a3f6c88aad3b","order_by":5,"name":"Li Sun","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Sun","suffix":""},{"id":615992425,"identity":"e820aae9-633a-4af2-b5c9-7371c7794046","order_by":6,"name":"Xuecun Liang","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xuecun","middleName":"","lastName":"Liang","suffix":""},{"id":615992427,"identity":"4c428129-49d1-4eab-a429-ba852814223c","order_by":7,"name":"Quanli Shen","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Quanli","middleName":"","lastName":"Shen","suffix":""},{"id":615992428,"identity":"3228f7ab-8ed8-4d88-aa90-820d8b5b8784","order_by":8,"name":"Lian Chen","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Lian","middleName":"","lastName":"Chen","suffix":""},{"id":615992429,"identity":"05dc980c-066f-470e-b249-10ddc0d964b3","order_by":9,"name":"Aizhen Lu","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Aizhen","middleName":"","lastName":"Lu","suffix":""},{"id":615992431,"identity":"34017367-5556-4d2d-85ed-9ff09a50d458","order_by":10,"name":"Xiaobo Zhang","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xiaobo","middleName":"","lastName":"Zhang","suffix":""},{"id":615992432,"identity":"887b4114-cd77-48e7-b6e1-f55d69e470d3","order_by":11,"name":"Libo Wang","email":"","orcid":"","institution":"Shanghai Medical University Children's Hospital: Children's Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Libo","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2026-02-08 11:06:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8821027/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8821027/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106311133,"identity":"058a990e-cad5-4fd0-8eb0-93b85d701a28","added_by":"auto","created_at":"2026-04-07 10:28:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":109999,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patients with idiopathic pulmonary hemosiderosis (IPH) included in the study\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/b240ae1d43117a3c2dfebe37.png"},{"id":106404356,"identity":"1a213987-a501-43a9-a6ea-e05b2f3c23aa","added_by":"auto","created_at":"2026-04-08 09:15:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":351047,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier Curves Showing First Recurrence-Free Survival and Cumulative Recurrence-Free Survival in the GC With BAE Group and the GC Without BAE Group\u003c/p\u003e\n\u003cp\u003eA and B: All IPH patients are included in cumulative recurrence-free Survival and first recurrence-free survival analyses, C and D: Sensitivity analyses are performed for cumulative recurrence-free Survival and first recurrence-free survival analyses. A and C: No. at risk was number of events at risk, B and D: No. at risk was patient-time units at risk.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/15742dcde9da5b7b411e118f.png"},{"id":107707921,"identity":"1e15625a-eb9a-4c60-9f9a-2cb951ca964b","added_by":"auto","created_at":"2026-04-24 09:21:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":749498,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/0f0851d4-16ab-4baa-9afa-8882e5e813e8.pdf"},{"id":106311069,"identity":"7a10e114-63bb-4277-a681-b9afed615343","added_by":"auto","created_at":"2026-04-07 10:28:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":525966,"visible":true,"origin":"","legend":"\u003cp\u003eSuppl. Figure 1. Chest radiography manifestations of IPH\u003c/p\u003e\n\u003cp\u003eA: Extensive exudative lesions in both lungs; B: Diffuse miliary exudation in the right lung; C: Diffuse fine granular shadow in both lungs; D: Miliary granular shadows and flaky dense shadows.\u003c/p\u003e","description":"","filename":"supplementaryfigure1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/1e0359bcd5d49e083e3c0674.docx"},{"id":106311079,"identity":"d68670ee-e583-488b-8971-f4fdbfee49d0","added_by":"auto","created_at":"2026-04-07 10:28:08","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":490520,"visible":true,"origin":"","legend":"\u003cp\u003eSuppl. Figure 2. Computer tomography manifestations of IPH\u003c/p\u003e\n\u003cp\u003eA: Diffuse exudation or ground glass shadows; B: Diffuse like millet grains; C: Diffuse interstitial changes; D: Honeycomb like bubble shadow, both lungs are diffusely filled with ground-glass opacities, small granular shadows and grid shadows, with multiple cystic translucent opacities.\u003c/p\u003e","description":"","filename":"supplementaryfigure2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/600c000afd27ca030c4013ce.docx"},{"id":106311196,"identity":"f988328f-9308-4cef-ac9a-42c8a84c31c1","added_by":"auto","created_at":"2026-04-07 10:28:35","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":361802,"visible":true,"origin":"","legend":"\u003cp\u003eSuppl. Figure 3. HE (A) and iron-stained (B) hemosiderin-laden macrophages in BALF\u003c/p\u003e","description":"","filename":"supplementaryfigure3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/166c2ffafdb4055c580edac7.docx"},{"id":106311108,"identity":"67b17bea-fd4e-42e4-ac1d-e0779bab02c1","added_by":"auto","created_at":"2026-04-07 10:28:21","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":246578,"visible":true,"origin":"","legend":"\u003cp\u003eSuppl. Figure 4. Angiographic Imaging of IPH\u003c/p\u003e\n\u003cp\u003eA: Right bronchopulmonary fistula; B: Densely stained lung parenchyma; C: Left bronchial artery hyperplasia.\u003c/p\u003e","description":"","filename":"supplementaryfigure4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/15b8c68a971c4135d2c1c1a8.docx"},{"id":106311109,"identity":"15469341-4b19-4c7e-91cd-4dacb42980ad","added_by":"auto","created_at":"2026-04-07 10:28:21","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":772747,"visible":true,"origin":"","legend":"\u003cp\u003eSuppl. Figure 5. Adverse Reactions of BAE\u003c/p\u003e\n\u003cp\u003eA\u0026amp;B: Computer tomography shows multiple patchy low-density shadows;\u003c/p\u003e\n\u003cp\u003eC\u0026amp;D: magnetic resonance imaging displays multiple patchy hyperintense shadows.\u003c/p\u003e","description":"","filename":"supplementaryfigure5.docx","url":"https://assets-eu.researchsquare.com/files/rs-8821027/v1/ae6b2b34e8c338d2e40e018c.docx"}],"financialInterests":"","formattedTitle":"Association of Bronchial Artery Embolization with Disease Recurrence in paediatric Idiopathic Pulmonary Hemosiderosis: A Retrospective Cohort Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eIdiopathic pulmonary hemosiderosis (IPH) is an rare cause of diffuse alveolar hemorrhage (DAH)(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Rudolph Virchow provided the first postmortem description of this condition as early as 1864(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In select pediatric populations, the incidence of IPH varies between 0.24 and 1.26 patients per million, with a mortality rate of up to 50%(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). IPH is characterized by the triad of hemoptysis, iron deficiency anemia, and pulmonary infiltrates on chest imaging. However, recent studies show that IPH has diverse clinical manifestations and the classic triad of IPH is not always present in children(\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGlucocorticosteroids, also known as corticosteroids (CS), are the drugs of choice for both acute episodes and long-term maintenance, as they reduce capillary permeability and inhibit immune-mediated injury(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). IPH is also a common cause of hemoptysis in children(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Moderate to severe hemoptysis that does not respond to medical therapy is an indication for bronchial artery embolization (BAE)(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e); however, the application of BAE in patients with IPH remains limited(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDue to concerns about the side effects of standard drug treatments for IPH, there is currently no effective non-pharmacological alternative. Interventional diagnostics and therapies may offer additional insights into both the etiology and management of IPH. This study aimed to describe the clinical characteristics of patients with IPH and to explore the association between the addition of BAE to conventional glucocorticoid (GC) treatment and cumulative recurrence in children with IPH.\u003c/p\u003e\n\u003ch3\u003eWhat’s Known on This Subject\u003c/h3\u003e\n\u003cp\u003eBAE effectively controls acute pediatric pulmonary hemorrhage, including IPH, a rare cause with recurrent alveolar bleeding. However, long-term recurrence rates post-BAE and associated factors in IPH remain poorly understood.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eWhat This Study Adds\u003c/h2\u003e \u003cp\u003eThe study suggests that combining BAE with glucocorticoid therapy may not affect either the time to first recurrence or the cumulative risk of recurrence.\u003c/p\u003e \u003c/div\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatient Population\u003c/h2\u003e \u003cp\u003eWe conducted an observational cohort study to evaluate the current use of BAE among patients with IPH undergoing GC therapy and the association of BAE with disease recurrence. Eligible patients were identified through a systematic review of electronic health records of Children\u0026rsquo;s Hospital of Fudan University using the International Classification of Diseases, Tenth Revision code E83.100x005\u0026thinsp;+\u0026thinsp;J99.8* between January 2003 and January 2020. Patients with IPH were defined as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) respiratory symptoms such as cough and hemoptysis, accompanied by iron deficiency anaemia, chest radiograph or chest computed tomography (CT) showed diffuse flocculation or ground glass changes in the lungs (Suppl. Figure\u0026nbsp;1 and Suppl. Figure\u0026nbsp;2); (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) hemosiderin cells were found in sputum gastric fluid or bronchoalveolar lavage fluid (Suppl. Figure. 3); (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) patients with secondary pulmonary hemorrhage with clear cause of oral and nasal hemorrhage and iron deficiency anaemia were excluded. All study protocols were reviewed and approved by the Institutional Research Ethics Committee of the Children\u0026rsquo;s Hospital of Fudan University.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExposure\u003c/h3\u003e\n\u003cp\u003eThe primary exposure variable was undergoing BAE as adjunctive therapy. For the GC with BAE group, the patients first underwent a specific GC-based treatment protocol; BAE was subsequently carried out at an appropriate time point during the treatment course. In contrast, the GC without BAE group only received the GC treatment, following the same GC-dosing regimen as the other group but without the BAE procedure. The patients were grouped based on their historical medical records, as no randomization was performed in this retrospective study. The follow-up period ranged from 0.7 to 120 months, during which cumulative recurrence was closely monitored to assess the impact of the exposure variables.\u003c/p\u003e\n\u003ch3\u003eCovariates\u003c/h3\u003e\n\u003cp\u003eAge was included as a covariate as different age groups have varying physical functions and recovery abilities, influencing cumulative recurrence risk. Sex is an important covariate; due to physiological and hormonal differences between sexes, responses to BAE treatment and recurrence patterns may vary. The degree of anaemia is a covariate as it affects oxygen supply and tissue repair, potentially linked to cumulative recurrence risk. Imaging findings serve as covariates, visually showing disease characteristics and severity, with different manifestations implying different progressions and affecting recurrence rates. A comprehensive consideration of these covariates enables a more accurate analysis of their relationships with cumulative recurrence, facilitates the assessment of disease recurrence risk, and supports the development of effective prevention and treatment strategies.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was the cumulative recurrence after treatment. The secondary outcomes included the first recurrence, as well as the within-group and between-group comparisons of hemoglobin levels. Recurrence was defined as a decrease in hemoglobin accompanied by coughing up hemoptysis, along with new exudates visible on chest radiograph or chest CT. Recurrence was recorded from the time of discharge following the initial hospital admission.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eBaseline characteristics between groups were presented and compared by standardized mean difference(\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), with 0.2, 0.5, and 0.8 correspond to small, medium, and large effect sizes, respectively. During the follow-up, seven patients were diagnosed with secondary pulmonary hemorrhage. We plotted Kaplan-Meier curves for both first recurrence and cumulative recurrence using sensitivity analysis. For the primary outcome analysis, we performed analysis using the Anderson Gill recurrent events model to estimate the cumulative recurrence risk. This approach was employed to account for correlated recurrent events while assessing the association between individual covariates and time-to-event outcomes. The Cox regression model was used to estimate the first recurrence. Independent sample or paired t-test was used to statistically analyze the hemoglobin content of patients in the GC with BAE group and the GC without BAE group after 0 and 6 months of follow-up. All statistical analyses were two-sided, and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Data were analyzed using SPSS (version 27.0) and R statistical software (version 4.4.2).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003ch2\u003eBaseline Characteristics\u003c/h2\u003e\n\u003cp\u003eThis systematic search yielded 73 unique patient records, which were\u0026nbsp;individually reviewed to ensure standardized validation against the diagnostic criteria for IPH. Ten patients were excluded due to insufficient post-discharge follow-up duration. By the final follow-up in January 2025, 63 patients were identified as having been hospitalized with IPH. Data abstraction was performed by a single reviewer\u0026nbsp;to maintain consistency (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe study consisted of 63 patients with IPH.\u0026nbsp;The median age of diagnosis was 4.6 years (interquartile range [IQR]: 2.1\u0026ndash;7.6 years), the median age of onset was 3.8 years (IQR: 1.5\u0026ndash;6.5 years), and 28 (44.4%) of the patients were female. In the GC with BAE group, the median age at diagnosis was 3.8 years (IQR: 2.0\u0026ndash;7.0 years), and the median age at onset was 3.2 years (IQR: 1.5\u0026ndash;6.0 years). In the GC without BAE group, the median age at diagnosis was 5.5 years (IQR: 2.5\u0026ndash;9.5 years), and the median age at onset was 4.8 years (IQR: 1.0\u0026ndash;6.8 years). The median follow-up time was 36.0 months (range: 0.7\u0026ndash;120.0 months). Among the baseline characteristics, slight differences were observed between the two groups in age at diagnosis (SMD = 0.29) and\u0026nbsp;presence of patchy density\u0026nbsp;on imaging\u0026nbsp;(SMD = 0.28). The SMD\u0026nbsp;for other baseline characteristics were all \u0026lt; 0.2, indicating that the two groups were\u0026nbsp;generally comparable\u0026nbsp;at baseline\u0026nbsp;(Table 1).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eBAE Manifestations\u003c/h2\u003e\n\u003cp\u003eAnomalous bronchial arterial anatomical features: (1) there were nine anomalous origin bronchial arteries in total, including three branches from the right internal mammary artery, and one branch\u0026nbsp;each from the thyrocervical trunk, subclavian artery, brachiocephalic trunk, right internal thoracic artery, descending aorta, and aortic arch; (2) pulmonary vascular malformation in seven cases: two cases of bronchial artery - pulmonary vein fistula, four cases of bronchial artery - pulmonary artery fistula, and one case of diffuse hyperplasia of the left and right bronchial artery with pulmonary artery fistula. Signs of bleeding (Suppl. Figure 4): (1) 31 cases showed indirect bleeding signs; (2) one case demonstrated direct bleeding signs; (3) 11 cases displayed both direct and indirect bleeding signs. The direct signs of hemorrhage were the exudation of contrast medium in lung parenchyma, and the indirect signs were the enlargement, expansion, and disorder of the lesion vessels.\u003c/p\u003e\n\u003ch2\u003eAdverse Event and Other Outcomes\u003c/h2\u003e\n\u003cp\u003eAmong the 44 patients who received BAE, one patient developed intracranial embolism after surgery, which was manifested as coma and occasional involuntary shaking of both upper limbs. The cranial magnetic resonance imaging is shown in\u0026nbsp;Suppl.\u0026nbsp;Figure\u0026nbsp;5. After treatment, the patient improved and was discharged from hospital.\u0026nbsp;The patient is currently able to perform fine motor tasks and trot, and is off hormonal\u0026nbsp;therapy. No complications\u0026nbsp;were observed following BAE in the other patients.\u003c/p\u003e\n\u003cp\u003eSeven patients were diagnosed with secondary pulmonary hemorrhage, including one patient with trisomy 21 syndrome, two with ANCA-associated vasculitis (AAV), two with interstitial pneumonia with autoimmune features (IPAF, multidisciplinary diagnosis), one with juvenile idiopathic arthritis (JIA), and one with \u003cem\u003eTNNT2\u003c/em\u003e gene mutation (potentially associated).\u003c/p\u003e\n\u003ch2\u003eCumulative Recurrence and First Recurrence between Two Groups\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eIn the initial assessment of recurrence risk between the two groups (Figure 2 A and B), Kaplan-Meier curves (first recurrence) and Andersen-Gill recurrent event models (cumulative recurrence) demonstrated no statistically significant differences over the entire follow-up period (all \u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). A sensitive analysis excluding the seven cases diagnosed subsequently as having pulmonary hemorrhage during follow-up yielded similar association estimates.\u003c/p\u003e\n\u003ch2\u003eBAE and Cumulative Recurrence Risk\u003c/h2\u003e\n\u003cp\u003eAmong the 63 patients, the median time to cumulative recurrence was 38.0 (range: 0.7\u0026ndash;109.1) months in the GC with BAE group and 29.1 (range: 1.0\u0026ndash;120.0) months in the GC without BAE group, 87 recurrent events were observed in the GC with BAE group and 24 in the GC without BAE group. BAE was not associated with a decreased cumulative recurrence risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 0.58\u0026ndash;4.74]). The association between BAE and cumulative recurrence risk was of a similar magnitude when models were stratified by the age of onset (HR, 0.81[95% CI, 0.54\u0026ndash;1.21]), the age of treatment (HR, 1.17[95% CI, 0.74\u0026ndash;1.83]). The degree of anaemia was associated with a decreased risk of cumulative recurrence compared to normal hemoglobin level：mild (HR, 0.68[95% CI, 0.47\u0026ndash;0.98])，moderate (HR, 0.77[95% CI, 0.62\u0026ndash;0.96])，severe (HR, 0.72[95% CI, 0.53\u0026ndash;0.97]). Female sex was associated with an increased risk of cumulative recurrence compared to male sex (HR, 1.92[95% CI, 1.66\u0026ndash;2.24]).\u003c/p\u003e\n\u003cp\u003eAmong the 56 patients, the median time to cumulative recurrence was 50.1 (range: 0.7\u0026ndash;109.1) months in the GC with BAE group and 29.1 (range: 1.0\u0026ndash;120.0) months in the GC without BAE group, 72 recurrent events were observed in the GC with BAE group and 23 in the GC without BAE group.\u003c/p\u003e\n\u003cp\u003eBAE was not associated with a decreased cumulative recurrence risk (HR, 1.65[95% CI, 0.51\u0026ndash;5.36]). The association between BAE and cumulative recurrence risk was of a similar magnitude when models were stratified by the age of onset (HR, 0.85[95% CI, 0.58\u0026ndash;1.23]), and the age of treatment (HR, 1.10[95% CI, 0.73\u0026ndash;1.67]). The degree of anaemia was associated with a decreased risk of cumulative recurrence compared to normal hemoglobin level: mild (HR, 0.44[95% CI, 0.27\u0026ndash;0.70]), severe (HR, 0.71[95% CI, 0.51\u0026ndash;1.00]). Female sex was associated with an increased risk of cumulative recurrence compared to male sex (HR, 1.91[95% CI, 1.70\u0026ndash;2.17]) (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eBAE and Associations for First Recurrence\u003c/h2\u003e\n\u003cp\u003eAmong the 63 patients, the median time to first recurrence was 30.8 (range, 0.7\u0026ndash;109.1) months in the GC with BAE group and 18.0 (range, 1.0\u0026ndash;120.0) months in the GC without BAE group. Of the 56 patients, the median follow-up was 46.5 (range, 0.7\u0026ndash;109.1) months in GC with BAE group and 19.5 (range, 1.0-183.1) months in the GC without BAE group. In univariate analysis, BAE was not associated with a decreased risk of first recurrence (HR, 1.01 [95% CI, 1.04 (0.44\u0026ndash;2.50)]).\u0026nbsp;After adjusting for clinicopathologic characteristics, including sex, the age of onset, the age of diagnosis and the degree of anaemia, BAE was not associated with a decreased risk of first recurrence (HR, 0.98[95% CI, 0.39\u0026ndash;2.44]) (Table 2).\u003c/p\u003e\n\u003ch2\u003eBAE and hemoglobin levels 6 moths after treatment\u003c/h2\u003e\n\u003cp\u003eHemoglobin levels improved significantly after treatment in both groups: the BAE group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), and the treatment without BAE group (\u003cem\u003eP\u003c/em\u003e=0.04). However, there was no significant difference in the changes in hemoglobin levels between the two groups (\u003cem\u003eP\u003c/em\u003e=0.30) (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity Analyses of BAE and Recurrence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter excluding\u0026nbsp;seven\u0026nbsp;patients diagnosed with secondary\u0026nbsp;hemorrhage during the follow-up period, we conducted a sensitivity analysis. There was no statistical significance in either the time to first recurrence (\u003cem\u003eP\u003c/em\u003e=0.92) or the cumulative recurrence time (\u003cem\u003eP\u003c/em\u003e=0.36) (Figure 2 C and D).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this single-centre retrospective cohort study, we characterized the clinical characteristics of patients with IPH and then compared the outcomes between GC with BAE treatment and GS alone using three measures: cumulative recurrence, first recurrence and hemoglobin level improvement within six months post-intervention. Our analysis did not demonstrate the clear superiority of BAE over conventional medical therapy among these evaluated parameters.\u003c/p\u003e \u003cp\u003eThe typical triad of IPH is recurrent hemoptysis, iron deficiency anaemia, and diffuse pulmonary infiltrates(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In our study, 12 children (19.0%) presented withanaemia at disease onset without any respiratory symptoms. Therefore, IPH should be considered in the different diagnosis of children with unexplained anaemia refractory to iron supplementation(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The severity of anaemia in patients with IPH correlates with disease progression, particularly during acute exacerbations(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Compared with chest radiographs, chest CT is a better choice for diagnosing IPH. Therefore, for anaemia that cannot be explained by haematological diseases, we recommend chest CT to assist in the diagnosis.\u003c/p\u003e \u003cp\u003eThe common vascular malformations causing pulmonary hemorrhage are pulmonary arteriovenous malformations, hereditary hemorrhagic telangiectasia (HHT/Osler-Weber-Rendu Syndrome), bronchial-pulmonary artery fistula, and pulmonary capillary hemangiomatosis. In cases where bronchial artery-pulmonary artery fistula or bronchial artery-pulmonary vein fistula is detected, recurrence may still occur after embolization. We propose that such vascular malformations may represent secondary changes in IPH, potentially related to underlying vascular inflammation. In some patients who underwent bronchial arteriography, signs of bleeding or a vagal bronchial artery were observed. Normally the bronchial artery is slender and most commonly originates between the upper margin of T 5 and the lower margin of T 6 on the thoracic aorta(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our study, nine vagal bronchial arteries with ectopic origins were identified. Evidence of bleeding was observed in 24 patients indirectly and 12 patients directly.\u003c/p\u003e \u003cp\u003eAt present, the etiology of IPH is still unclear, but most scholars believe that the immune mechanism plays an important role in the pathogenesis of the disease(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). After long-term follow-up, six patients were found to have associated autoimmune diseases. Their angiographic findings were similar to those of other patients with IPH. One patient underwent four angiograms, which revealed lesion thickening accompanied by diffuse small vessel hyperplasia, a vagal bronchial artery, and vascular recanalization. Based on these findings, we believe that the abnormal pulmonary vascular changes represent non-specific secondary alterations in IPH. A French study found that 17/25 children with IPH tested positive for autoantibodies at onset, including 50% positive for anti-smooth muscle antibodies, 45% for ANA, and 40% for ANCA; two cases were positive(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Additionally, IPH has been associated with IgA deficiency. Since IgA plays an important role in mucosal immunity, it\u0026rsquo;s deficiency may link IPH to other autoimmune diseases.\u003c/p\u003e \u003cp\u003eSevere complications of BAE include spinal cord injury and ectopic embolism, such as intracranial or coronary embolism. The most serious complication is spinal infarction, with an incidence rate of 0.19%(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In our study, one of the 44 patients who received BAE had intracranial ectopic embolization, which indicates that the application of interventional techniques in children with IPH carries certain risks(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).Six patients received two or more embolization procedures. Post-embolization imaging revealed vascular rerouting, which we attribute to compensatory hyperplasia of adjacent vessels supplying the lesion, diffuse neovascularization, or collateral circulation formation. Notably, these newly formed vessels exhibited thin and fragile walls, rendering them prone to rupture under systemic circulation pressure, thereby contributing to recurrent hemoptysis(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Consequently, no significant improvement in the change of hemoglobin levels was observed between the two groups. Additionally, underlying pulmonary inflammatory lesions may predispose to bronchopulmonary fistula formation.\u003c/p\u003e \u003cp\u003eIn the present study, the findings indicate that the two treatment approaches are comparable in mitigating the recurrence risk. Given the complex pathogenesis of IPH, which involves multiple interacting factors, neither pharmacotherapy nor BAE can fundamentally alter the relapse process of the disease. In the analysis of cumulative risk factors for recurrence, females exhibited a higher risk of multiple recurrences. We hypothesize that this may be related to an association between IPH and autoimmune diseases, such as JIA and IPAF, which are more prevalent in females. In contrast, AAV has no obvious tendency to occur in children(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), which may be the reason for the high risk of cumulative recurrence in females. Lower hemoglobin levels at diagnosis are more likely to draw attention from both parents and clinicians, which may subsequently influence the risk of cumulative recurrence.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, as a single-centre study with a small sample size, its generalizability is limited, and the findings are exploratory. Second, due to its observational design, potential residual confounding cannot be ruled out. Third, recall bias may be inherent in the outcomes; however, during data collection, medical history inquiries were repeatedly cross-checked with outpatient follow-up data to minimize this risk.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis study firstly compared IPH recurrence between patients treated with the addition of BAE and those receiving traditional GC therapy alone. Our analysis did not reveal a significant association between the addition of BAE and recurrence outcomes compared with conventional hormone therapy. Given these findings, we suggest that clinicians carefully weigh the potential benefits and limitations of BAE when managing IPH.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003ch3\u003eEthical approval\u003c/h3\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of Children\u0026apos;s Hospital of Fudan University (approval number: 2022307A). The ethics committee waived the requirement for informed consent due to the retrospective nature of the study and anonymized patient data.\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eAll the authors consent to the publication of this research.\u003c/p\u003e\n\u003ch3\u003eAvailability of data and material\u003c/h3\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors have no conflicts of interest to disclose.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis study was supported by National Natural Science Foundation of China (No. 82200264).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShan Luo and Yuan Yuan contribute equally to the paper.\u003c/p\u003e\n\u003ch3\u003eAuthors and Affiliations\u003c/h3\u003e\n\u003cp\u003eShan \u0026nbsp;Luo: [email protected], Department of Pediatrics, Jinshan Hospital, Fudan University, Shanghai, China, 201508\u003c/p\u003e\n\u003cp\u003eYuan Yuan: [email protected], Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eHongyan Chen: [email protected], Clinical Epidemiology Research Unit, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China,201102\u003c/p\u003e\n\u003cp\u003eJing Liu: [email protected], Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eShuolin Li: [email protected],\u003c/a\u003e Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eLi Sun: [email protected], Department of Rheumatology, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eXuecun Liang: [email protected], Department of Cardiology, Children\u0026apos;s Hospital of Fudan University , National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eQuanli Shen: [email protected], Department of Radiology, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eLian Chen: [email protected], Department of Pathology, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eAizhen Lu: [email protected], Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eXiaobo Zhang: [email protected], Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003eLibo Wang: [email protected], Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center, Shanghai, China, 201102\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e:\u0026nbsp;Libo Wang,\u0026nbsp;Department of Respiratory Medicine, Children\u0026apos;s Hospital of Fudan University, National Children\u0026apos;s Medical Center,\u0026nbsp;399 Wanyuan Road, Minhang District, Shanghai, China, [[email protected]].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShan Luo conceptualized and designed the study, drafted the initial manuscript, and collected data, carried out the initial analyses.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eYuan Yuan conceptualized and designed the study, written the introductory section, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003eHongyan Chen provided suggestions for statistical method modification, critically reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eThe results are based on the multidisciplinary team of pulmonary hemorrhage, including Department of Respiratory Medicine, Department of Rheumatology, Department of Cardiology, Department of Radiology and Department of Pathology, work around the diagnosis of IPH, assessment of indications for intervention, and follow-up, with specific contributions as follows: \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJing Liu, Shuolin Li, Aizhen Lu, Xiaobo Zhang\u0026amp;\u0026nbsp;Libo Wang: leaded the initial diagnostic evaluation of children with IPH, responsible for collecting the patient\u0026apos;s clinical symptom history, leading the follow-up monitoring of \u0026nbsp;respiratory function and symptom changes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLi Sun: participated in IPH etiology investigation, focus on the completion of autoimmune disease-related examinations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eXuecun Liang: responsible for the study and judgment of interventional indications, leading the implementation of interventional therapy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQuanli Shen: provided imaging support for the diagnosis and \u0026nbsp;condition assessment of IPH, interprets imaging data including chest computed \u0026nbsp;tomography (CT) and digital subtraction angiography (DSA), and offers imaging evidence for diagnosis, formulation of interventional plans, and judgment of disease progression during follow-up.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLian Chen: responsible for issuing the pathological diagnosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ereport of hemosiderin in bronchoalveolar lavage fluid (BALF), and providing \u0026nbsp;pathological support for the confirmed diagnosis of IPH.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eWe acknowledge all the patients and their families for their participation in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMilman N, Pedersen FM. 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Idiopathic pulmonary hemosiderosis: A state of the art review. Respir Med. 2021;176:106234.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSyha R, Benz T, Hetzel J, Spengler W, Kohlh\u0026auml;ufl MJ, Gatidis S, et al. Bronchial Artery Embolization in Hemoptysis: 10-Year Survival and Recurrence-Free Survival in Benign and Malignant Etiologies - A Retrospective Study. Rofo. 2016;188(11):1061\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao QM, Zhao L, He L, Wu L, Lu Y, Chu C, et al. Bronchial Artery Embolization in Pediatric Pulmonary Hemorrhage: A Single-Center Experience. J Vasc Interv Radiol. 2020;31(7):1103\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang D, Dalton JE. A unified approach to measuring the effect size between two groups using SAS\u0026reg;. 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMark DB, Lee KL, Harrell FE. Jr. Understanding the Role of P Values and Hypothesis Tests in Clinical Research. JAMA Cardiol. 2016;1(9):1048\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Statistical power analysis for the behavioral sciences; 1988.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas LE, Pencina MJ. Do Not Over (P) Value Your Research Article. JAMA Cardiol. 2016;1(9):1055.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaha BK, Chong WH. Lung transplant to manage end-stage lung disease due to idiopathic pulmonary hemosiderosis: A review of the literature. Respir Investig. 2022;60(1):82\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaFreniere K, Gupta V. Idiopathic Pulmonary Hemosiderosis. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright \u0026copy; 2025. StatPearls Publishing LLC.; 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiu KK, Li R, Lam SY. Unexplained childhood anaemia: idiopathic pulmonary hemosiderosis. Hong Kong Med J. 2015;21(2):172\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eButt A, Ahmed R, Sheikh MDA, Khan O, Iqbal N, Rahman AJ et al. Idiopathic pulmonary hemosiderosis - A rare cause of chronic anemia. Monaldi Arch Chest Dis. 2020;90(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIttrich H, Klose H, Adam G. Radiologic management of haemoptysis: diagnostic and interventional bronchial arterial embolisation. Rofo. 2015;187(4):248\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaha BK. Is It Time to Call Idiopathic Pulmonary Hemosiderosis by the Correct Name: Immune-Mediated Pulmonary Hemosiderosis? Am J Med Sci. 2021;361(6):809\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreitas A, Senra V, Marinho A, Guedes M. Chronic alveolar haemorrhage in a paediatric patient: a diagnostic and treatment challenge. BMJ Case Rep. 2015;2015.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErko\u0026ccedil;oğlu M, Civelek E, Kocabaş CN. Unusual presentation: Concurrent IgA deficiency and idiopathic pulmonary hemosiderosis. Pediatr Pulmonol. 2016;51(10):E34\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlanco A, Solis P, Gomez S, Valbuena C, Telleria JJ. Antineutrophil cytoplasmic antibodies (ANCA) in idiopathic pulmonary hemosiderosis. Pediatr Allergy Immunol. 1994;5(4):235\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaha BK, Bonnier A, Chenna P, Milman NT. Prevalence of autoantibodies in pediatric patients with idiopathic pulmonary hemosiderosis: a scoping review of the literature in the period 1980\u0026ndash;2021. Clin Rheumatol. 2022;41(4):977\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaytard J, Nathan N, de Blic J, Fayon M, Epaud R, Deschildre A, et al. New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare(\u0026reg;) cohort. Orphanet J Rare Dis. 2013;8:161.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoon W, Kim JK, Kim YH, Chung TW, Kang HK. Bronchial and nonbronchial systemic artery embolization for life-threatening hemoptysis: a comprehensive review. Radiographics. 2002;22(6):1395\u0026ndash;409.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIshikawa H, Ohbe H, Omachi N, Morita K, Yasunaga H. Spinal Cord Infarction after Bronchial Artery Embolization for Hemoptysis: A Nationwide Observational Study in Japan. Radiology. 2021;298(3):673\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng L, Yang T, Yang K, Yu G, Li J, Xiang W, et al. Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Front Immunol. 2022;13:891822.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraney BA, Fischer A. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc. 2019;16(5):525\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ch2\u003eTable1. Baseline Characteristics of patients\u003c/h2\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"696\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 212px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003ePatients，No.(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eGC with BAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eGC without BAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eSMD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e63(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e44(70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e19(30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eAge at diagnosis, median (IQR), y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e4.6(2.1,7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3.8(2.0,7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e5.5(2.5,9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eAge at onset of symptoms, median (IQR), y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e3.8(1.5,6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3.2(1.5,6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e4.8(1.0,6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e28(44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e19(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e9(47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eNormal hemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e4(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e2(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eMild anemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e9(14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e8(18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003eModerate anemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e23(37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e15(34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e8(42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003ca href=\"http://www.youdao.com/w/severe/#keyfrom=E2Ctranslation\"\u003eSevere\u003c/a\u003e anemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e27(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e19(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e8(42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eChest imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eAcute stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eFlocculent shadow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e2(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e1(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003ePatchy density\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e27(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e17(39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e10(53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eOpacity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e30(48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e20(46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e10(53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eChronic recurrent stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eFine particle shadow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e9(14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e7(16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eNodules\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e6(10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4(9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eGround glass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e15(24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e10(23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e5(26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eGrid change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e5(8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3(7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eChronic crisis stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003eSeptal thickening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e9(14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e7(16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e2(11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSMD: Standardized mean difference, SMD is the preferred way to describe imbalances in data that are descriptive of the sample. SMD of 0.2, 0.5, and 0.8 correspond to small effect, medium effect, and large effect, respectively. IQR:interquartile range.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003eTable2. Association of BAE With First and Cumulative Recurrence Risk Among Children with Idiopathic Pulmonary Hemosiderosis\u003c/h2\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"119%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 36px;\"\u003e\n \u003cp\u003eFirst Recurrence Risk\u003c/p\u003e\n \u003cp\u003e（63patients 44:19）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 43px;\"\u003e\n \u003cp\u003eFirst Recurrence Risk\u003c/p\u003e\n \u003cp\u003e（56patients 38:18）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eHazard Ratio (95%CI)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25px;\"\u003e\n \u003cp\u003eHazard Ratio (95%CI)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eBAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.98(0.39-2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.97(0.36-2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.76(0.81-3.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.85(0.77-4.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAge of Onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.89(0.69-1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.91(0.72-1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.461\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAge of Diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.10(0.82-1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.06(0.79-1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.15(0.21-6.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.869\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.58(0.15-15.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.83(0.16-4.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.46(0.17-12.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.98(0.18-5.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.44(0.15-13.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 101px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"119%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 36px;\"\u003e\n \u003cp\u003eCumulative Recurrence Risk\u003c/p\u003e\n \u003cp\u003e（63patients 44:19）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 43px;\"\u003e\n \u003cp\u003eCumulative Recurrence Risk\u003c/p\u003e\n \u003cp\u003e（56patients 38:18）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003eHazard Ratio (95%CI)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003eHazard Ratio (95%CI)\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eBAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.66(0.58-4.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.65(0.51-5.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.92(0.89-4.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.92(0.81-4.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAge of Onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.81(0.54-1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.85(0.58-1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAge of Diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1.17(0.75-1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.494\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1.11(0.73-1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.68(0.22-2.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.43(0.11-1.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.78(0.25-2.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.657\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.93(0.27-3.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.910\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e0.72(0.23-2.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.71(0.18-2.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.627\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e1[Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Hazard ratios derived from the Andersen-Gill model with robust sandwich covariance\u003c/p\u003e\n\u003cp\u003eestimator (or proportional means model) adjusted for all listed covariates; CI:confidence interval\u003cstrong\u003e\u003cbr clear=\"all\"\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003eTable3. Changes in hemoglobin levels from baseline to 6 months.\u003c/h2\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"112%\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003cp\u003emean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003eChanges (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eMean difference (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eGC without BAE \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e89.3\u0026plusmn;27.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e103.3\u0026plusmn;27.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e-14.0\u0026plusmn;27.7\u003c/p\u003e\n \u003cp\u003e(-27.4,-0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003e-6.5\u003c/p\u003e\n \u003cp\u003e（-19.0,6.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 8px;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003eGC with BAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e97.0\u0026plusmn;21.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e117.5\u0026plusmn;18.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e-20.5\u0026plusmn;20.3\u003c/p\u003e\n \u003cp\u003e(-26.7,14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCI:confidence interval\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Idiopathic pulmonary hemosiderosis, children, bronchial artery embolization","lastPublishedDoi":"10.21203/rs.3.rs-8821027/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8821027/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eOBJECTIVE\u003c/h2\u003e \u003cp\u003eThis study aimed to characterize pediatric idiopathic pulmonary hemosiderosis (IPH) and assess whether adding bronchial artery embolization (BAE) to glucocorticoid (GC) therapy reduces the cumulative risk of disease recurrence.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective cohort study of children with IPH between January 2003 and January 2020 from a single center. Demographic, clinicopathologic, therapeutic, and outcomes data were extracted. The primary outcome was cumulative recurrence of hemorrhage, analysed using the Andersen-Gill models. The secondary outcomes included time to first recurrence and change in hemoglobin levels from baseline to six months after treatment.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eA total of 63 patients were included, with 44 (70%) receiving BAE plus GC treatment and 19 (30%) receiving GC treatment alone. The median age at diagnosis was 4.6 years (interquartile range: 2.1\u0026ndash;7.6), and 28 (44%) were female. During a median follow-up period of 36 months (range, 0.7\u0026ndash;120), 87 relapses occurred in the GC with BAE group versus 24 in the GC without BAE group. The adjusted hazard ratio was 1.66 (95% confidence interval [CI], 0.58\u0026ndash;4.74) for the GC with BAE group compared with GC alone. The corresponding hazard ratio for time to first recurrence was 0.98 (95% CI, 0.39\u0026ndash;2.44). Changes in hemoglobin levels did not differ significantly between the two groups (\u0026ndash;20.5 [95% CI, \u0026minus;\u0026thinsp;27.4 to \u0026minus;\u0026thinsp;0.7] vs \u0026minus;\u0026thinsp;14.0 [95% CI, \u0026minus;\u0026thinsp;26.7 to 14.4], mean difference \u0026minus;\u0026thinsp;6.5 [95% CI, \u0026minus;\u0026thinsp;19.0 to 6.0], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.30).\u003c/p\u003e\u003ch2\u003eCONCLUSIONS\u003c/h2\u003e \u003cp\u003eOur data do not support the addition of BAE to conventional GC therapy as routine primary treatment for pediatric IPH.\u003c/p\u003e","manuscriptTitle":"Association of Bronchial Artery Embolization with Disease Recurrence in paediatric Idiopathic Pulmonary Hemosiderosis: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 10:27:06","doi":"10.21203/rs.3.rs-8821027/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0885ab8c-d0ff-454d-be95-1ac293b8b49f","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-24T06:47:31+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 10:27:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8821027","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8821027","identity":"rs-8821027","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}