Lung retransplantation after initial single lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a rare non-infectious bronchopulmonary complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with an unfavorable prognosis. This article presents a case of effective BOS treatment after allo-HSCT with therapeutic response achievement in a short time.

Long-term survival after lung transplantation (LTx) is still hampered by the development of chronic allograft dysfunction (CLAD). Bronchiolitis obliterative syndrome (BOS), the most common phenotype of CLAD, is thought to arise from repeated injuries to graft epithelial cells, leading to fibrous scarring of small airways. Thus far, there is no approved treatment for BOS disease. Based on both animal/human studies in LTx and the demonstrated efficacy of the TKI nintedanib treatment in idiopathic pulmonary fibrosis (IPF), nintedanib is a candidate molecule capable of stopping the fibroproliferative process in BOS. Hence, the rationale to conduct a nintedanib trial in LTx recipients with BOS is based on (i) an unmet medical need due to poor survival after BOS diagnosis; (ii) the demonstrated fibrotic pathways in BOS; and (iii) the proven efficacy of nintedanib in IPF. The INFINITIx-BOS study is an investigator-initiated, national multicentric, phase II, superiority, parallel-group, double-blind, comparative randomized clinical trial. A total of 80 recipients with progressive BOS within the prior year, at least at 6 months post-LTx, will be randomized to receive either nintedanib (150 mg bid) or placebo for a period of 6 months, in addition to maintenance immunosuppressive therapy left to their physician's discretion with 4 dedicated visits. The primary endpoint is the slope of decline over 6 months of treatment. The secondary endpoints are change in 6-min walk test, SGRQ, graft failure, SPO2, and safety events over 6 months, which will be compared between the two arms. Based on a fibrotic pattern partially shared between IPF and BOS, this randomized INFINITIx-BOS trial has the potential to demonstrate an additional strategy with nintedanib as a targeted-fibrotic pathway associated with BOS. NCT03283007, first posted 11 September 2017. Protocol version identifier No. 6-0, 8 September 2023.

China's growing healthcare system, serving over 1.4 billion people, has witnessed remarkable progress in organ transplantation, including among pediatric patients. This review provides a comprehensive overview of pediatric transplantation in China, summarizing national trends, regulatory frameworks, clinical outcomes, and ongoing challenges. Data were obtained from the Report on Organ Donation and Transplantation in China (RODTC) between 2015 and 2024. Pediatric patients were defined as those under 18 years of age. Following the 2015 reforms establishing voluntary citizen donation as the only legitimate organ source, China has developed a robust national regulatory and ethical framework under the National Health Commission. The China Organ Transplant Response System (COTRS) ensures transparent allocation, with a 2018 policy granting priority to pediatric recipients and mandating that organs from donors under 18 be preferentially allocated to pediatric patients. From 2015 to 2024, pediatric kidney, liver, and lung transplants increased 4.9-, 2.1-, and 7.5-fold, respectively; pediatric heart transplantation increased 2.5-fold from 2019 to 2024. In 2019, child donors represented 8.20% of deceased donors. Leading indications included non-ischemic cardiomyopathy for heart, bronchiolitis obliterans for lung, biliary atresia and metabolic liver disease for liver, and glomerulonephritis for kidney transplantation. Reported survival rates were favorable, with 5-year patient survival of 70.0% for heart and 95.5% for kidney transplants. Major transplant centers are concentrated in Shanghai, Guangzhou, Zhengzhou, and Beijing. Four national registries ensure lifelong follow-up and quality monitoring. Pediatric organ transplantation in China has advanced rapidly under strengthened ethical oversight and allocation reforms prioritizing children. Despite significant growth, challenges remain in data accessibility, regional disparities, and donor shortages. Continued policy refinement, registry expansion, and regional collaboration-particularly with Hong Kong and Macao-are essential to further improve access and outcomes for pediatric transplant recipients.

There are limited longer-term follow-up data on bronchiolitis obliterans (BOS)- and retransplant-free survival among patients who underwent lung transplantation for COVID-related lung disease. To evaluate overall, retransplant-free, and BOS- and retransplant-free survival in a national cohort of COVID lung transplant recipients (LTRs). We identified all US adult LTRs in the Scientific Registry of Transplant Recipients who underwent transplant for COVID-related lung disease between August 2020 and February 2025. We used propensity score matching (PSM) to construct balanced cohorts of COVID LTRs and non-COVID group D (restrictive lung disease) LTRs, comparing overall, transplant-free, and BOS- and retransplant-free survival in the 2 populations. There were 605 LTRs with COVID lung disease and 8809 with non-COVID group D diagnoses. Among patients with at least a 3-year follow-up time, survival was 79.1% in COVID LTRs and 73.7% in non-COVID LTRs. In a PSM cohort of 451 matched pairs, overall survival (LTR; hazard ratio [HR], 0.81; 95% CI, 0.60-1.10; P = .17) and retransplant-free survival (HR, 0.81; 95% CI, 0.60-1.09; P = .16) did not differ between the groups. Among non-COVID LTRs, 51 (16.0%) developed BOS, and 56 (16.3%) COVID LTRs developed BOS. Overall, 122 (33.7%) non-COVID LTRs died, were retransplanted, or developed BOS, and 110 (29.1%) COVID LTRs died, were retransplanted, or developed BOS. COVID LTRs had improved retransplant- and BOS-free survival compared to non-COVID LTRs (HR, 0.76; 95% CI, 0.58-0.98; P = .04), driven by 8 fewer deaths in the COVID LTR cohort. COVID acute respiratory distress syndrome LTRs had similar overall, retransplant-free, and BOS- and retransplant survival as COVID fibrosis LTRs. In this national cohort study, there was no significant difference in overall and retransplant-free survival for COVID LTRs compared to non-COVID, restrictive lung disease LTRs at a median follow-up time of 2.5 years. COVID LTRs, however, had slightly lower hazard for BOS- and retransplant-free survival.

From the archives of MD Anderson Cancer Center: Paraneoplastic autoimmune multiorgan syndrome (PAMS) associated with stroma-rich Castleman disease.

Pulmonary Function Deficit and Clinical Associations in Childhood Acute Lymphoblastic Leukaemia Survivors: A National Retrospective ALL-STAR Lungs Cohort Study.

Bronchiolitis Obliterans as a Delayed Sequela of Mycoplasma pneumoniae Complicated by Stevens-Johnson Syndrome in a Pediatric Patient.

Does the Macrophage Take the Central Stage in Obliterative Bronchiolitis?

Bronchiolitis Obliterans or Busulfan-Induced Lung Injury? A Pediatric Case of Hematopoietic Stem Cell Transplantation.

The non-infectious pulmonary complications idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS) are important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). To identify risk factors for these complications, we retrospectively analyzed baseline characteristics and longitudinal data from 633 pediatric and young adult allo-HCT recipients. Risk factors for IPS included non-malignant diagnosis (HR 2.97; 95% CI 1.27-6.97; P = 0.01) and adenovirus reactivation (HR 2.75; 95% CI 1.24-6.14; P = 0.01). Conditioning with busulfan-cyclophosphamide ±melphalan (BuCy ±Mel) associated with increased IPS risk compared to busulfan-fludarabine ±clofarabine (HR 5.15; 95% CI 2.36-11.24; P < 0.001) and non-myeloablative regimens (HR 9.78; 95% CI 2.48-38.61; P = 0.001). BuCy ±Mel conditioning also related to increased BOS risk relative to total body irradiation (TBI)(HR 5.11; 95%CI 1.65-15.83; P = 0.005) and non-myeloablative regimens (HR 19.68; 95% CI 2.53-155.76; P = 0.005). Moreover, elevated endothelial activation and stress index (EASIX), white blood cell, and lymphocyte counts before day 100 post-transplant correlated with IPS. For BOS, high EASIX and increased activated or effector memory CD4 + T-cells were additional significant correlates. In conclusion, IPS and BOS were associated with both distinct and overlapping risk factors in this study. These findings may inform future strategies to identify high-risk patients and develop targeted preventive interventions.

To the Editors: A 7-year-5-month-old girl presented to a tertiary medical center in Taiwan with a 1-month history of persistent cough and progressive dyspnea. Four weeks prior, Mycoplasma pneumoniae (MP) pneumonia was laboratory-confirmed (serum MP immunoglobulin [Ig]M positive; IgG 1:1280). Despite a course of doxycycline, her condition worsened. Upon emergency admission, she was hypoxemic with an SpO2 of 89%–92% on room air. Physical examination revealed bilateral diffuse wheezing, coarse crackles and subcostal retractions. Initial chest radiograph (Fig. 1A) showed peribronchial thickening with bilateral emphysematous changes suggestive of air trapping. Laboratory workup showed a white blood cell count of 11,900/μL and C-reactive protein <0.4 mg/dL. She failed to respond to empiric intravenous antibiotics and bronchodilators. Pulmonary function testing demonstrated very severe obstruction, with an forced expiratory volume in the first second at 24% of the predicted value. Advanced imaging was pursued to confirm the diagnosis of postinfectious bronchiolitis obliterans (PIBO). Chest high-resolution computed tomography (HRCT) (Fig. 1B) definitively confirmed the diagnosis by showing ground-glass opacities and a classic mosaic attenuation pattern in the right middle lobe and left lower lobe, characteristic of small airway obliteration. Nuclear medicine lung perfusion scan shows multiple perfusion defects over bilateral lung fields, which are compatible with HRCT findings of PIBO. Echocardiography confirmed no pulmonary hypertension with a fair ejection fraction.FIGURE 1.: Diagnostic imaging progression of postinfectious bronchiolitis obliterans (PIBO). A: Chest radiograph anteroposterior view reveals peribronchial thickening predominantly in the right lower lung and right upper lung. Besides, bilateral emphysematous changes and hyperinflation are noticed, indicating significant air trapping. B: Chest high-resolution computed tomography (HRCT) with transverse section reveals ground-glass opacities and a pathognomonic mosaic attenuation pattern in the right middle lobe and left lower lobe. This pattern combines bronchial wall thickening, air trapping and small airway obliteration.The patient was treated with mini-pulse steroid therapy (Methylprednisolone 10 mg/kg/d × 3 days/month for a total of 6 courses in the following 6 months) and the FAM protocol (fluticasone, azithromycin, and montelukast). She stabilized and was discharged on day 20 with an SpO2 improving to 93%–97%. At a 15-month follow-up, despite completing 6 steroid pulses, pulmonary function testings showed persistent small airway obstruction, but her clinical images kept improving, both chest X-ray and HRCT. She could exercise without tachypnea and no need for any oxygen supply. She remains under outpatient follow-up. This case is believed to be the first published report of MP-induced PIBO in Taiwan. While PIBO is a well-documented sequela of viral insults like adenovirus, MP is a potent atypical agent capable of inducing permanent airway obliteration through intraluminal fibrosis and an exaggerated immune response.1–5 PIBO is usually misdiagnosed as refractory asthma; however, a bronchodilator has no effect in PIBO case.6 In Taiwan, MP infection is common in children, and both macrolide resistance in laboratory studies and infection in younger age in epidemiology were noticed.7,8 Literature indicates that MP-related PIBO often follows a “latent” period where the patient appears to recover from pneumonia before developing chronic small airway obstruction. Diagnosis is often delayed more than 6 months because initial chest radiographs may only show nonspecific inflammatory signs or hyperinflation. Chest HRCT remains the gold standard for diagnosis, as the mosaic attenuation pattern accurately reflects regional air trapping.9,10 Early recognition of MP-related PIBO and comprehensive management are essential to mitigate long-term sequelae and may have better outcomes.

Background and aimDeployment-related constrictive bronchiolitis (DRCB), a chronic fibrotic small airway disease, has been reported in military personnel following deployment to Southwest Asia and Afghanistan. Veterans diagnosed with DRCB indicate exposure to inhalational hazards, yet the molecular pathophysiology of this disorder remains enigmatic. Club cells are local progenitors critical for repair of small airway epithelium after inhalational injury. We have previously modeled DRCB using transgenic CC-DTA mice in which sustained club cell injury induces murine constrictive bronchiolitis (mCB) that recapitulates many of the histopathologic abnormalities observed in DRCB including peribronchiolar inflammation and fibrosis. The aim of the current study was to identify molecular pathways activated at the site of injury during the development of mCB.MethodsCC-DTA and control mice were exposed to doxycycline on protocol day 0–10 to induce club cell injury. Protein digital spatial profiling restricted to small airways was performed on lung sections harvested on protocol day 0, 10, and 20 and targeted a panel of 57 proteins focused on immune modulation and MAPK signaling.ResultsSustained club cell injury mediated small airway wall thickening due to enhanced deposition of subepithelial collagen fibers. Principal component analysis separated small airways of CC-DTA from control mice on day 10 and 20. Upregulated protein expression in small airways of CC-DTA versus control mice was found to be most numerous and prominent on day 20 and included an array of proteins involved in myeloid or lymphoid cell activation, signal transduction in response to extracellular stress stimuli, and regulation of cell proliferation, differentiation and survival. Immunofluorescence validated an increase in programmed death-ligand 1+ (PD-L1+) cells and in phosphorylated-p90 ribosomal S6 kinase+ (p-p90RSK+, a downstream effector of the MAPK/ERK pathway) epithelial cells in response to sustained club cell injury.ConclusionWe identified features of chronic innate and adaptive immune activation and aberrant collagen deposition within injured small airways during the development of mCB. Further, our findings implicate the PD-1/PD-L1 axis and the MAPK/ERK pathway in the pathogenesis of DRCB and may reveal potential therapeutic targets for combating this disease.

Bronchitis obliterans is a major complication of Mycoplasma pneumoniae pneumonia (MPP) with bronchial casts. This retrospective study aimed to identify predictors of pediatric bronchitis obliterans (PBO) in patients with mycoplasma pneumoniae pneumonia (MPP) complicated by bronchial casts. We screened 236 hospitalized children with MPP and bronchial casts on bronchoscopy between June 2018 and June 2023, of whom 197 were included in the analysis, including 49 with PBO and 148 without PBO. The clinical features, laboratory data, radiological findings, and bronchoscopic features of the children in the PBO and non-PBO groups were compared. Children in the PBO group had a significantly higher incidence of pleural effusion, more severe radiological abnormalities, and higher C-reactive protein level, white blood cell count, erythrocyte sedimentation rate (ESR), and immunoglobulin M level than those in non-PBO group. Additionally, children in the PBO group were more likely to have delayed bronchoscopy (> 13.5 days). Multivariable logistic regression analysis revealed that ESR > 57.5mm/h (OR: 3.833, P = 0.001), pulmonary consolidation > 2/3 of a lobe (OR: 2.453, P = 0.036) and delayed bronchoscopy (OR 5.827, P < 0.001) were significant predictors of PBO in patients with MPP complicated by bronchial casts.These three indicators combined had a sensitivity of 0.571, specificity of 0.885, and area under the curve of 0.766 for predicting PBO.

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder with rare but potentially fatal respiratory complications. We present an exceptional documented case of TEN with severe bronchial obstruction successfully treated with tocilizumab and ruxolitinib in an 11-year-old patient. Despite early methylprednisolone pulse therapy, a repeat bronchoscopy showed progressive obstruction of proximal bronchial lumen by synechiae and mucosal membranes. Following multidisciplinary discussion, treatment was intensified with tocilizumab and ruxolitinib, resulting in marked respiratory improvement and decreased proinflammatory cytokines in bronchoalveolar lavage. No adverse effects were observed during 8months of follow-up. Recent research supports Janus kinase inhibitors as targeted therapy in TEN.

ObjectivesCladribine, a synthetic analog of deoxyadenosine, exhibits potent activity against hematological malignancies. While cladribine-containing regimens combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been proposed as a potential strategy to improve outcomes in relapsed or refractory (R/R) acute myeloid leukemia (AML), additional clinical evidence is needed, particularly in pediatric populations. This single-center retrospective study aimed to describe the efficacy and safety of a cladribine-based conditioning regimen for allo-HSCT in children with R/R AML.Materials and methodsClinical data of 16 children with R/R AML who underwent allo-HSCT following a cladribine-based conditioning regimen at our hospital from October 2020 to June 2024 were analyzed retrospectively. Key outcomes included hematopoietic reconstruction, regimen-related toxicity (RRT), cumulative incidence of graft-versus-host disease (GVHD), infection profiles, overall survival (OS), disease-free survival (DFS), relapse rate, and non-relapse mortality (NRM). Flow-cytometry minimal residual disease (MRD) results before HSCT were collected and analyzed as an additional key baseline index.ResultsAll 16 patients attained hematopoietic reconstruction, with pre-transplant flow-cytometry MRD negative in 13 cases (81.25%) and positive (MRD ≥0.01%) in three cases (18.75%). The median time of neutrophil and platelet engraftment was 12 (10–16) days and 15 (10–25) days, respectively. The incidence of I/II grade RRT was 31.3% (oral cavity: three cases, liver: two cases), with no III/IV grade RRT observed. The cumulative incidence of acute GVHD (aGVHD) was 50.0% (grade I/II skin: five cases, grade IIIl: three cases). Among 15 evaluable patients, the cumulative incidence of chronic GVHD (cGVHD) was 26.7% (local skin: three cases, ocular keratoconjunctivitis sicca: one case). Post-transplant infections occurred in 31.3% of patients, predominantly viral pathogens: one case of BK virus-associated hemorrhagic cystitis, one case of BK virus combined with bacterial infection, and three cases of cytomegalovirus (CMV) DNAemia. The median follow-up time was 28.03 (11.67–55.34) months (follow-up cutoff: 30 June 2024). Using the Kaplan–Meier method, the 1-year OS rate was 87.5% (95% CI: 65.2%−96.4%), and the 1-year DFS rate was 87.4% (95% CI: 64.9%−96.3%). The relapse rate and NRM were both 6.3% (95% CI: 0.8%−29.1%); the NRM case was confirmed as bronchiolitis obliterans syndrome (BOS) induced by pulmonary cGVHD.ConclusionIn this small single-center retrospective series, the cladribine-based conditioning regimen was associated with favorable hematopoietic reconstruction, mild RRT, and promising survival outcomes in children with R/R AML, even in partial patients with pre-transplant MRD positivity. However, due to the limited sample size, single-arm design, and lack of a control group, conclusions regarding superiority (e.g., improved OS or reduced relapse) cannot be drawn. Larger prospective multi-center studies are required to validate these preliminary findings.

BET inhibition blunts antibody production and macrophage-mediated fibrosis to restore lung function in murine cGVHD.

Post-transplant Cyclophosphamide Reduces Bronchiolitis Obliterans Syndrome Risk Through Chronic Graft-versus-Host Disease Prevention: A Multicenter Cohort Study.

To investigate the relevant risk factors for bronchitis obliterans and develop a predictive nomogram for bronchitis obliterans in children with severe Mycoplasma pneumoniae pneumonia(SMPP). This was a retrospective study. This study analyzed the clinical data of Xingtai People's Hospital, Xingtai Emergency Center children with SMPP from September 2021 to September 2025, and categorized them into the bronchitis obliterans and PB groups. SPSS 26.0 statistical software was used for data organization and analysis. Four hundred and sixty-four children with SMPP were finally included, of which 27(5.8%) children with PB were complicated by bronchitis obliterans. According to the chi square test and Mann Whitney U test, it was found that the gender, age, duration of fever, duration of cough, white blood cells, neutrophils, eosinophils CRP, alanine aminotransferase IL-6, IL-10, the comparison of tumor necrosis factor, APTT, D-dimer, aspartate aminotransferase, immunoglobulin E, and immunoglobulin G showed no statistically significant differences(P>0.05). The lactate dehydrogenase levels in patients with bronchitis obliterans were higher than those in patients with PB(P<0.05). The immunoglobulin A levels in patients with bronchitis obliterans were lower than those in patients with(P<0.05). The results showed that a higher level of LDH was an independent risk factor for bronchitis obliterans, while a higher level of immunoglobulin A was an independent protective factor for bronchitis obliterans. The increase of lactate dehydrogenase is an independent risk factor for bronchitis obliterans. The lactate dehydrogenase and immunoglobulin A have good sensitivity and specificity for building a nomogram prediction model for the risk of bronchitis obliterans.

Bronchiolitis obliterans syndrome (BOS) is a severe pulmonary complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with limited therapeutic options once refractory to standard immunosuppression. We conducted a pilot study from January 2018 to December 2024, enrolling consecutive patients with BOS defined by NIH criteria who failed glucocorticoids and calcineurin inhibitors for ≥4 weeks. Sixteen patients received salvage therapy with ruxolitinib 5 mg twice daily and nintedanib 150 mg twice daily (RN cohort) in continuous 28-day cycles for up to six cycles, while 37 contemporary patients served as controls. At baseline, NIH lung scores in the RN cohort were 18.8% NIH 1, 18.8% NIH 2, and 62.5% NIH 3. The median number of treatment cycles was 3.5 (range, 1-6). At 3 months, 11 patients (68.8%) achieved ≥10% improvement in %FEV1 from baseline (median = 26.5%, range = 15.6%-58.2%). By NIH lung response criteria, the overall response rate (ORR) was 62.5% (12.5% complete response, 50.0% partial response) in the RN cohort versus 13.5% (5.4% complete, 8.1% partial) in controls. Notably, hematologic toxicities were less frequent with RN therapy than in controls. These findings suggest that low-dose ruxolitinib combined with nintedanib is an effective and well-tolerated salvage regimen for BOS after allo-HSCT and warrant confirmation in a prospective phase II study.