[Construction of a risk prediction model for bronchiolitis obliterans in children with refractory Mycoplasma pneumoniae pneumonia]. / 难治性肺炎支原体肺炎患儿并发闭塞性细支气管炎风险预测模型的构建.

OBJECTIVES: To explore the establishment of a risk prediction model for concurrent bronchiolitis obliterans (BO) in children with refractory Mycoplasma pneumoniae pneumonia (RMPP). METHODS: A retrospective study included 116 RMPP children treated in the Department of Pediatrics of Xiangya Changde Hospital from June 2021 to December 2023. Eighty-one cases were allocated to the training set and thirty-five cases to the validation set based on a 7:3 ratio. Among them, 26 cases in the training set developed BO, while 55 did not. The multivariate logistic regression was used to select variable factors for constructing the BO risk prediction model. Nomograms were drawn, and the receiver operating characteristic (ROC) curve was used to assess the discriminative ability of the model, while calibration curves and Hosmer-Lemeshow tests evaluated the model's calibration. RESULTS: Multivariate logistic regression analysis indicated that several factors were significantly associated with concurrent BO in RMPP children, including length of hospital stay, duration of fever, atelectasis, neutrophil percentage (NEUT%), peak lactate dehydrogenase (LDH), ferritin, peak C reactive protein (CRP), oxygenation index (PaO2/FiO2), ≥2/3 lung lobe consolidation, pleural effusion, bronchial mucous plugs, bronchial mucosal necrosis, and arterial oxygen partial pressure (PaO2) (P<0.05). ROC curve analysis for the training set indicated an area under the curve of 0.904 with 88% sensitivity and 83% specificity; the validation set showed an area under the curve of 0.823 with 76% sensitivity and 93% specificity. The Hosmer-Lemeshow test's Chi-square values for the training and validation sets were 2.17 and 1.92, respectively, with P values of 0.221 and 0.196, respectively. CONCLUSIONS: The risk prediction model for BO in RMPP children based on logistic regression has good performance. Variables such as length of hospital stay, duration of fever, atelectasis, peak LDH, peak CRP, NEUT%, ferritin, ≥2/3 lung lobe consolidation, pleural effusion, bronchial mucous plugs, bronchial mucosal necrosis, PaO2/FiO2, andPaO2 can be used as predictors.

The Impact of Donor-Recipient Human Leukocyte Antigen Matching on Bronchiolitis Obliterans-Free Survival Among Lung Transplant Recipients With Connective Tissue Diseases.

BACKGROUND: The development of connective tissue disease-associated lung diseases (CTD-LD) occurs in association with specific human leukocyte antigens (HLA). For CTD-LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes. METHODS: Using the Scientific Registry of Transplant Recipients, we assessed whether CTD-LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)-free survival based on the degree of donor HLA matching. This included overall degree of donor-recipient HLA matching, donor-recipient matching at DR loci, and recipient matching with specific donor HLA antigens associated with the development of pulmonary disease in their condition. RESULTS: Among 1413 patients with CTD-ILD, highly HLA-matched donor-recipients did not have worse adjusted survival (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.58-1.51, p = 0.77). Recipients who were fully matched at HLA DR did not have worse survival (HR = 0.82, 95% CI = 0.56-1.19, p = 0.29). Finally, among individual CTD-LD, including rheumatoid arthritis, systemic sclerosis, the idiopathic inflammatory myopathies, and systemic lupus erythematous, transplant with a donor expressing HLA antigens associated with lung manifestations in these conditions was not associated with worse BOS-free survival. CONCLUSIONS: Among transplant recipients with CTD-LD, HLA donor-recipient matching, including at the DR loci, does not result in worse BOS-free survival. Based on these findings, there is no reason to treat these as unacceptable antigens when considering donor offers for CTD-LD candidates.

Impact of Transplant Body Mass Index and Post-Transplant Weight Changes on the Development of Chronic Lung Allograft Dysfunction Phenotypes.

INTRODUCTION: Chronic lung allograft dysfunction (CLAD) is a lung transplant complication for which four phenotypes are recognized: Bronchiolitis obliterans syndrome (BOS), Restrictive allograft syndrome (RAS), mixed and undefined phenotypes. Weight gain is common after transplant and may negatively impact lung function. Study objectives were to describe post-transplant weight trajectories of patients who developed (or did not) CLAD phenotypes and examine the associations between BMI at transplant, post-transplant changes in weight and BMI, and the risk of developing these phenotypes. METHODS: Adults who underwent a bilateral lung transplant between 2000 and 2020 at our institution were categorized as having (or not) one of the four CLAD phenotypes based on the proposed classification system. Demographic, anthropometric, and clinical data were retrospectively collected from medical records and analyzed. RESULTS: Study population included 579 recipients (412 [71.1%] CLAD-free, 81 [14.0%] BOS, 20 [3.5%] RAS, 59 [10.2%] mixed, and 7 [1.2%] undefined phenotype). Weight gains of greater amplitude were seen in recipients with restrictive phenotypes than CLAD-free and BOS patients within the first five years post-transplant. While the BMI category at transplant was not statistically associated with the risk of developing CLAD phenotypes, an increase in weight (Hazard ratio [HR]: 1.04, 95% CI [1.01-1.08]; P = .008) and BMI (HR: 1.13, 95% CI [1.03-1.23]; P = .008) over the post-transplant period was associated with a greater risk of RAS. CONCLUSION: Post-LTx gain in weight and BMI modestly increased the risk of RAS, adding to the list of unfavorable outcomes associated with weight gain following transplant.

Late-Onset Noninfectious Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation: Single-Center Experience.

OBJECTIVES: We aimed to reveal the incidence of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome and risk factors involved in development. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively investigated 745 patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between January 2000 and December 2020. We evaluated demographic characteristics, comorbidities, and hematopoietic stem cell transplantation characteristics to determine possible risk factors affecting development of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome. RESULTS: Of 745 patients, 8.9% (n = 66) had late-onset noninfectious pulmonary complications. Complications included 38 patients with bronchiolitis obliterans syndrome, 13 with venous thromboembolism, 8 with cryptogenic organizing pneumonia, 5 with pneumothorax, 4 with interstitial lung disease-restrictive graft-versus-host disease, 5 with bronchiectasis, 2 with pneumomediastinum, and 1 with pleural effusion. Patients with and without complications were not significantly differentin terms of smoking history, hematopoietic stem cell transplantation characteristics, and conditioning regimens. Patients with complications had higher busulfan and lower antithymocyte globulin use than those without complications (both P<.05). Patients with complications more commonly had hematopoietic stem cell transplantation from related donors and chronic graft-versus-host disease (P < .05). Patients with bronchiolitis obliterans syndrome had more frequent use of busulfan (P <.05) but less frequent use of total body irradiation (P <.05) and antithymocyte globulin (P <.05) than those without this syndrome. Rate of hematopoietic stem cell transplantation from a related donor (P < .05) and frequency of chronic graftversus-host disease (P < .001) were significantly higher in patients with bronchiolitis obliterans syndrome, presented with bronchiectasis (78.6%), air trapping (67.9%), bronchial wallthickening (53.6%), and mosaic attenuation (39.3%) in thorax computed tomography. Pretransplant spirometry did not predict bronchiolitis obliterans syndrome development. CONCLUSIONS: Determining risk factors for late-onset noninfectious pulmonary complications is needed to aid in prevention and follow-up.

Detection of Bronchiolitis Obliterans Syndrome after Pediatric Hematopoietic Stem Cell Transplantation: An Official American Thoracic Society Clinical Practice Guideline.

Background: Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. Methods: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of, post-HSCT BOS in children. A systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. Conclusions: This document provides an evidence-based approach to the detection of post-HSCT BOS in children while also highlighting considerations for the implementation of each recommendation. Further, the document describes important areas for future research.

Nuances in the interpretation and utility of donor-derived cell-free DNA in lung transplantation following allogeneic hematopoietic stem cell transplantation - Case report.

Respiratory complications following allogeneic HSCT can lead to severe morbidity and mortality. Lung transplantation (LT) is a potential treatment for select patients with late-onset non-infectious pulmonary complications post-HSCT. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for monitoring the health of allografts following LT. However, its utility in a multi-genome setting of LT after HSCT has not yet been clinically validated. Here we describe a case of a 75-year-old, male patient who underwent single-lung transplantation for BOS related to chronic GVHD and presented with persistently elevated dd-cfDNA levels. In a surveillance biopsy, the patient was diagnosed with mild acute cellular rejection at three months. The patient's lung function remained stable, and the reported dd-cfDNA levels decreased after the rejection episode but remained elevated above levels that would be considered quiescent for LT alone. In this unique setting, as 3 different genomes contributed to the dd-cfDNA% reported value, valuable insight was obtained by performing further analysis to separate the specific SNPs to identify the contribution of recipient, lung-donor, and HSCT-donor cfDNA. This study highlights the potential utility of dd-cfDNA in the multi-genome setting of lung transplant post-HSCT, nuances that need to be considered while interpreting the results, and its value in monitoring lung rejection.

The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study.

Introduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.

[Paraneoplastic pemphigus with underlying Castleman's disease in a 16-year-old girl]. / Morbus Castleman-assoziierter paraneoplastischer Pemphigus bei einer 16-jährigen Patientin.

Paraneoplastic pemphigus is a rare, life-threatening autoimmune disease that is clinically characterized by mostly extensive and refractory mucosal erosions and polymorphous skin lesions. We report here on a 16-year-old girl with isolated oral erosions, in whom mucosal pemphigoid was initially suspected and after treatment with prednisolone and dapsone marked improvement was achieved. However, a few months later the patient developed massive respiratory insufficiency as a result of bronchiolitis obliterans, so that a lung transplant was planned. As part of the preparatory diagnostic workup, unicentric, abdominally localized Castleman's disease was diagnosed, which ultimately led to the diagnosis of paraneoplastic pemphigus as evidenced by envoplakin autoantibodies. Tumor resection and subsequent lung transplantation achieved good results with sustained mucocutaneous remission.

Clinical analysis of air-leak syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.

BACKGROUND: Air-leak syndrome (ALS) is considered as an independent risk factor for poor prognosis in adult patients who had received hematopoietic stem cell transplantation (HSCT), and the 5-year overall survival (OS) of ALS is less than 30%. However, the clinical features of ALS among post-transplant pediatric patients have rarely been explored. PROCEDURES: We retrospectively reviewed 2206 pediatric patients who had received an allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in prognosis following HSCT. RESULTS: In our research, ALS was divided into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). Following treatment of the ALS, 18 patients survived (18/28, 64.3%), and 10 patients died of respiratory failure or infection (10/28, 35.7%). CONCLUSIONS: The OS of ALS in Hebei Yanda Lu Daopei Hospital is significantly higher than others, and they were cited to be related to early diagnosis and timely FAM treatment in previous reports.

A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study.

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8-15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < -1.645; n = 12), restrictive defects (TLC < 80% predicted, FEV1 and FVC z-scores < -1.645; n = 7) and non-specific pattern (FEV1 and FVC z-score< -1.645, FEV1/FVC z-score > -1.645, and TLC > 80% predicted; n = 8). HCT for malignant disease was the only factor associated with LONIPC (P = 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

Ventilatory capacity in CLAD is driven by dysfunctional airway structure.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. METHODS: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung µCT and tissue-core µCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. FINDINGS: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. INTERPRETATION: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. FUNDING: This research was funded with the National research fund Flanders (G060322N), received by R.V.

Detection of Bronchiolitis Obliterans Syndrome Using Nitrogen Multiple Breath Washout in Children Posthemopoietic Stem Cell Transplant.

Bronchiolitis obliterans syndrome (BOS) is a severe complication following hemopoietic stem cell transplantation (HSCT) and is often undetected until there is significant deterioration in pulmonary function. Lung clearance index (LCI2.5) derived from the nitrogen multiple breath washout (N2MBW) test may be more feasible and sensitive than spirometry, which is currently used for surveillance and detection of BOS. We aimed to examine the feasibility of performing surveillance N2MBW in children post-HSCT, and in an exploratory analysis, determine if LCI2.5 led to earlier detection of BOS when compared to spirometric indices. Participants aged 5 to 17 years were recruited prior to receiving HSCT into a prospective, single-center, feasibility study at the Royal Children's Hospital, Melbourne. N2MBW and spirometry were performed within the month prior to transplant and repeated at 3, 6, 9, and 12 months post-transplant. Data were also collected on the presence of graft-versus-host (GVHD) disease in any organ, including the lungs. Twenty-one (12 male) children with a mean age of 13.4 (range 9.2 to 17.1) years at recruitment participated in this study. Prior to HSCT, all participants had normal LCI2.5, while 16 (76%) demonstrated normal forced expiratory volume in 1 second (FEV1). Ninety-nine percent of N2MBW tests were technically acceptable, compared with 66% of spirometry tests. Three participants developed BOS, while 2 participants died of other respiratory complications. At 6 and 12 months post-transplant, the BOS group had increases in LCI2.5 ranging from 3 to 5 units and mean reductions in FEV1 % predicted of 40% to 53% relative to pre HSCT values, respectively. In those who developed BOS, post-HSCT LCI2.5 values were significantly worse when compared with the no BOS group (P < .001). Relative changes in LCI2.5 and FEV1 were both predictive of BOS at 6 months post HSCT. This study demonstrates that N2MBW is a more feasible test compared with spirometry in children post HSCT. However, in an exploratory analysis, LCI2.5 did not lead to earlier detection of BOS, when compared to spirometry.

IL-27 Levels in Bronchoalveolar Lavage Fluid in Children with Post-infectious Bronchiolitis Obliterans.

Background: Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils. Objective: To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions. Methods: A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test. Results: The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05). Conclusion: The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO.

Restrictive allograft dysfunction rather than bronchiolitis obliterans syndrome had a major impact on the overall survival after living-donor lobar lung transplantation.

PURPOSE: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT). METHODS: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed. RESULTS: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001). CONCLUSIONS: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT.

Impulse Oscillometry Versus Spirometry to Detect Bronchiolitis Obliterans Syndrome in Bilateral Lung Transplant Recipients: A Prospective Diagnostic Study.

BACKGROUND: Chronic lung allograft dysfunction (CLAD), and especially bronchiolitis obliterans syndrome (BOS), remain dominant causes of morbidity and mortality after lung transplantation. Interest is growing in the forced oscillation technique, of which impulse oscillometry (IOS) is a form, as a tool to improve our understanding of these disorders. However, data remain limited and no longitudinal studies have been published, meaning there is no information regarding any capacity IOS may have for the early detection of CLAD. METHODS: We conducted a prospective longitudinal study enrolling a consecutive sample of adult bilateral lung transplant recipients with healthy lung allografts or CLAD and performed ongoing paired IOS and spirometry tests on a clinically determined basis. We assessed for correlations between IOS and spirometry and examined any predictive value either modality may hold for the early detection of BOS. RESULTS: We enrolled 91 patients and conducted testing for 43 mo, collecting 558 analyzable paired IOS and spirometry tests, with a median of 9 tests per subject (interquartile range, 5-12) and a median testing interval of 92 d (interquartile range, 62-161). Statistically significant moderate-to-strong correlations were demonstrated between all IOS parameters and spirometry, except resistance at 20 Hz, which is a proximal airway measure. No predictive value for the early detection of BOS was found for IOS or spirometry. CONCLUSIONS: This study presents the first longitudinal data from IOS after lung transplantation and adds considerably to the growing literature, showing unequivocal correlations with spirometry but failing to demonstrate a predictive value for BOS.

Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia.

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.