Diagnosis Of Post-infectious Bronchiolitis Obliterans Research Articles

Bronchiolite obliterante post-infettiva (PIBO), chi è costei?

The paper presents the case of a 14-month-old child with a persistent respiratory distress with wheezing and diffuse crackles on chest auscultation. Symptoms appeared after a viral pneumonia caused by Adenovirus. The recent history, the clinical manifestations and the lung CT (Computed Tomography) scans, which showed a diffuse mosaic pattern, with air trapping, bronchiectasis and peribronchial inflammation, led to the diagnosis of Post-infectious Bronchiolitis Obliterans (PIBO). PIBO is a rare chronic paediatric pulmonary disease characterized by irreversible fibrotic narrowing of the small airways. It can present with a broad severity spectrum, and the evolution of this condition is not predictable in the single patient. Adenovirus is by far the most common cause of this lung pathology, and during the post Covid-19 pandemic an unprecedented rise in PIBO cases triggered by Adenovirus lower respiratory infections was observed. The treatment of PIBO is empirical, and a defined protocol does not exist yet. Therapeutic approaches range from nil to methylprednisolone pulse therapy, which would seem effective especially if performed early and if peribronchitis is found on imaging. Some studies evaluated the administration of intravenous immunoglobulins, while in more advanced cases showing fibrotic transformation of the parenchyma, the use of antifibrotic drugs (hydroxychloroquine, nintedanib) may be tried

Pulmonary Function in Post-Infectious Bronchiolitis Obliterans in Children: A Systematic Review and Meta-Analysis.

Owing to the rarity of post-infectious bronchiolitis obliterans (PIBO), pulmonary function in children with PIBO has been mainly investigated in small-sample sized studies. This systematic review and meta-analysis investigated pulmonary function in children with PIBO, regardless of age at respiratory insult and PIBO diagnosis. A systematic literature search revealed 16 studies reporting pulmonary function data in 480 children with PIBO. Levels of key pulmonary function parameters were summarized by pooled mean difference (MD) only in children with PIBO, and a random effect model was used. Pooled MDs (95% confidence interval [CI]) for FEV1, FVC, and FEF25-75% were 51.4, (44.2 to 58.5), 68.4 (64.4 to 72.3), and 26.5 (19.3 to 33.6) % predicted, respectively, with FEV1/FVC of 68.8% (62.2 to 75.4). Pooled MDs (95% CI) of the z-scores for FEV1, FVC, and FEF25-75% were -2.6 (-4.2 to -0.9), -1.9 (-3.2 to -0.5), and -2.0 (-3.6 to -0.4). Pooled MD (95% CI) for the diffusion capacity of the lungs for carbon monoxide from two studies was 64.9 (45.6 to 84.3) % predicted. The post-bronchodilator use change in the FEV1 in three studies was 6.1 (4.9 to 7.2). There was considerable heterogeneity across the studies. PIBO is associated with moderately impaired pulmonary function, and this review facilitates an understanding of PIBO pathophysiology in children.

Talaromyces marneffei infection associated with bronchiolitis obliterans in an HIV-negative child: a case report

BackgroundTalaromyces marneffei is an opportunistic pathogen that infects immunodeficient and immunocompromised patients. We presented a pediatric patient with a diagnosis of T. marneffei infection who was followed up in the Guangzhou Women and Children’s Medical Centre.Case presentationThe child was a 5-year-old girl with persistent cough and gasping over 2 months who was confirmed with T. marneffei infection by bronchoalveolar lavage fluid culture and high-throughput sequencing technology. Human immunodeficiency virus (HIV) was negative according to a serum-specific antibody test. She was treated with amphotericin B and itraconazole as antifungal agents, with good clinical response. At follow-up, high-resolution computed tomography showed a mosaic sign in the whole lung field with a diagnosis of post-infectious bronchiolitis obliterans (PIBO) as the sequela. She has a mutated COPA gene with uncertain pathogenic potential on whole-exome sequencing.ConclusionsClinicians should consider PIBO as a possible sequela in an HIV-negative paediatric patient with T. marneffei infection.

Postinfectious bronchiolitis obliterans masked by misdiagnosis as asthma.

Asthma and postinfectious bronchiolitis obliterans (PIBO) have similar clinical findings, and PIBO may be misdiagnosed with asthma. This study aimed to determine the clinical features of PIBO in children and the causes of delay in its diagnosis. We retrospectively evaluated all patients diagnosed with PIBO in four pediatric pulmonology centers between 2007 and 2018. In total, 64 PIBO patients were retrospectively reviewed. We compared the clinical and laboratory differences between PIBO patients who had initially been misdiagnosed with asthma and correctly diagnosed with PIBO. Of the 64 patients, 22 (34.4%) had initially been misdiagnosed with asthma. Adenovirus was the most common infectious agent in children. The age upon diagnosis was older, and the symptom duration was significantly longer in patients misdiagnosed with asthma (P < .05). There were no statistical differences in terms of sex, history of prematurity, duration of hospitalization, treatment, history of oxygen or mechanical ventilation support, pulmonary function test (PFT) results and asthma-predisposing findings between the two groups (P > .05). Patients with PIBO who had initially been misdiagnosed with asthma were correctly diagnosed at older ages and had longer symptom duration. Asthma may mask PIBO diagnosis by the similarity of symptoms and the clinical response to inhaled β2-agonist or steroid treatment. PFTs may not help clinicians because of the age of children. The delay in the diagnosis of PIBO is probably attributable to the fact that some clinicians fail to include PIBO in the differential diagnosis when there is no clinical response to asthma medication.

Clinical profile and course of children with postinfectious bronchiolitis obliterans from a tertiary care hospital.

Background:Postinfectious bronchiolitis obliterans (PIBO) is a chronic obstructive lung disease with scanty information in literature on etiology, clinical profile, treatment, and outcome.Objective:The objective of the study is to describe the clinical profile and course of children diagnosed with PIBO.Methods:A chart review of children below 18 years of age diagnosed as PIBO over the past 9 years was carried out. Details of clinical profile, laboratory investigations, imaging, treatment received, and outcome were recorded.Results:Eight children (boys 4) with PIBO were identified. Median (interquartile range [IQR]) age at the first episode of acute severe bronchiolitis such as illness and diagnosis of PIBO was 15 (6, 23.5) and 30 (16.5, 60) months, respectively, indicating a delay in diagnosis. The most common symptoms were recurrent episodes of cough (100%), fast breathing (100%), wheezing (87.5%), and fever (62.5%). Median (IQR) number of hospitalizations and episodes of antibiotic use prior to diagnosis were 2.5 (2, 5.5) and 2 (2, 4), respectively. Three (37.5%) children received mechanical ventilation during previous hospitalizations. Chest computed tomography revealed mosaic attenuation in 8 (100%), ground-glass opacities in 2 (25%), and bronchial wall thickening in 2 (25%). After diagnosis, 7 received oral steroids, 7 received hydroxychloroquine, 5 received azithromycin, and 2 received azathioprine. The median (IQR) duration of follow-up (n = 6) was 6 (1.5, 9.5) months. Median (IQR) number of pulmonary exacerbations in follow-up was 2 (1, 5).Conclusion:PIBO is still an under-recognized entity with substantial delay in diagnosis and unnecessary use of antibiotics. Clinical course with imaging findings may help to diagnose and manage this entity.

POST İNFECTİOUS BRONCHİOLİTİS OBLİTERANS İN CHİLDREN: LONG TERM FOLLOW-UP

Objective: Post infectious bronchiolitis obliterans (PIBO) is a chronic lung disease which is caused by lower respiratory tract infections (LRTI) especially in children who are under 3 years of age. Adenovirus is the major pathogen in the etiology. There are no clinical controlled trials for treatment. Long term follow up varies. We aimed to investigate long term follow-up results of PIBO patients.&#x0D; Material and methods: We analyzed the long term follow up results of PIBO patients in three pediatric pulmonology centers. Demographic fetaures, clinical, laboratory findings, treatments, treatment results were evaluated.&#x0D; Results: In ten-year period 70 patients were followed with diagnosis of PIBO in three pediatric pulmonology centers. Mean age of patients was 9.24 ± 5.76 years and51 (72%) of them were male. Mean age of patients at the diagnosis was 3.96 ± 3.85 years and 23 (32%) of them had family consangunity. Pathogen was detected in 19 patients and adenovirus was the major pathogen which was detected in 9 patients. Oxygen supplementation was present in 26 patients at the time of LTRI.&#x0D; Pulse steroid was given only in 5 patients, oral prednisolone in 30 patients, azithromycin in 10 patients, inhaled steroid in 36 patients and IVIG in 8 patients who had accompanying immunodeficiency.&#x0D; Mean FEV1 was 56.99 ± 21.73 before treatment and 69.26 ± 21.45 after treatment. Mean FVC was 61.60 ± 21.47 before treatment and 71.61 ± 20.40 was after treatment. Mean MEF25-75 was 46.39 ± 24.47 and 59.11 ± 23.92 after treatment. There were statistically significant differences in FEV1, FVC, MEF25-75 between before and after treatments (p&lt;0.05).&#x0D; Mean body mass index (BMI) was 16.67 ± 3.55 before treatment and 16.87 ±3.44 after treatment and there was no statistically significant difference (p&gt;0.05).&#x0D; FEV1, FVC, MEF25-75 and BMI had statistically significant differences before and after treatments in patients who was given oral and/or inhaled steroid treatments (p&lt;0.05).&#x0D; Conclusion: Although there is no definitive treatment recommendations for PIBO, steroid seems to be useful in children. Clinical controlled trials are needed for definitive treatment recommendations.

Health-related quality of life in patients with bronchiolitis obliterans

ObjectiveTo evaluate the overall health-related quality of life in patients with bronchiolitis obliterans. MethodsParticipants with a diagnosis of post-infectious bronchiolitis obliterans, who were being followed-up at two specialized outpatient clinics of Pediatric Pulmonology in Porto Alegre, Brazil, and controls aged between 8 and 17 years, of both genders, were included in the study. Controls were paired by gender, age, and socioeconomic level in relation to the group of participants with post-infectious bronchiolitis obliterans. The version of the Pediatric Quality of Life Inventory (PedsQ) tool validated for Brazil was applied for the assessment of Health-related Quality of Life, through an interview. The comparison of the Health-related Quality of Life means between the groups was performed using Student's t-test for independent samples and the chi-squared test, for categorical variables. Results34 patients diagnosed with post-infectious bronchiolitis obliterans and 34 controls participated in the study. The mean age of the children included in the study was 11.2±2.5 years, and 49 (72%) of them were males. The groups showed no significant differences in relation to these variables. The quality of life score was significantly and clinically lower in the post-infectious bronchiolitis obliterans group when compared with controls in the health (72.36±15.6, 81.06±16.4, p=0.031) and school domains (62.34±20.7, 72.94±21.3, p=0.043), as well as in the total score (69.53±14.9, 78.02±14.8, p=0.024), respectively. ConclusionPatients with post-infectious bronchiolitis obliterans presented lower health-related quality of life scores when compared with healthy individuals in the total score and in the health and school domains.

Serum YKL-40 levels may help distinguish exacerbation of post-infectious bronchiolitis obliterans from acute bronchiolitis in young children.

Children with post-infectious bronchiolitis obliterans (PIBO) are frequently hospitalized with acute exacerbation, but clinical differentiation of PIBO exacerbation from acute bronchiolitis is often challenging, which may result in treatment delay and chronic lung function impairment. We aimed to examine whether serum YKL-40 and growth factors could be markers for PIBO exacerbation. Thirty-seven children admitted with acute exacerbation of PIBO were enrolled and studied retrospectively. Diagnosis of PIBO was based on clinical history of acute respiratory infection followed by persistent airway obstruction and characteristic findings in high-resolution computed tomography. Serum levels of YKL-40, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and platelet-derived growth factor (PDGF)-BB were measured on admission. The biomarkers were also examined in children admitted with acute bronchiolitis serving as positive controls (N = 30) and in age-matched controls (N = 20). Only YKL-40 levels were found to be significantly higher in PIBO patients with exacerbation compared with that in bronchiolitis patients and showed a positive correlation with the severity of disease before diagnosis of PIBO. Conclusion: Our results suggest that measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from acute bronchiolitis in young children. What is Known: • The children with post-infectious BO (PIBO) usually have recurrent wheezing and need frequent hospitalization due to acute exacerbation during the first disease years. • Clinical differentiation of PIBO exacerbation from acute bronchiolitis in young children is often challenging, which may result in treatment delay and chronic lung function impairment. What is New: • Measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from acute bronchiolitis in young children.

P244 Serum YKL-40 levels may help distinguish exacerbation of post-infectious bronchiolitis obliterans from acute bronchiolitis in young children

Introduction: The children with post-infectious bronchiolitis obliterans (PIBO) are frequently hospitalized with acute exacerbation, but clinical differentiation of PIBO exacerbation from ordinary bronchiolitis is often challenging, which may result in treatment delay and chronic lung function impairment. We aimed to examine whether serum YKL-40 and growth factors could be markers for PIBO exacerbation. Methods: Thirty-seven children admitted with acute exacerbation of PIBO were enrolled. Diagnosis of PIBO was based on clinical history of acute respiratory infection followed by persistent airway obstruction and characteristic findings in high-resolution computed tomography. Serum levels of YKL-40, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1 and platelet derived growth factor (PDGF)-BB were measured. The mediators were also examined in the children admitted with acute bronchiolitis serving as positive controls (N=30) and in age-matched controls (N=20). Results: Only YKL-40 levels were found to be significantly higher in PIBO patients with exacerbation compared with bronchiolitis patients and showed a positive correlation with the severity of disease before diagnosis of PIBO. Conclusion: Our results suggest that YKL-40 might be involved in the pathogenesis of PIBO and measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from ordinary acute bronchiolitis in young children.

Post-Infectious Bronchiolitis Obliterans in Children: Long-Term Outcome, Prognostic Factors, and Relation with Serum KL-6 Levels

Background: Post-infectious bronchiolitis obliterans (PIBO) is a rare form of chronic obstructive lung disease in children, with insufficient data on the factors that predict the prognosis of PIBO. Objectives: The aims of this study were to assess the long-term outcome of PIBO patients, evaluate prognostic factors, and investigate the relation between serum Krebs von den Lungen 6 (KL-6) level and disease severity. Methods: Thirty-eight children with a clinical and radiological diagnosis of PIBO were enrolled on this study. Information was obtained from medical records regarding the clinical characteristics related to the first severe lung infection, the patient's clinical presentation at PIBO diagnosis, treatment, and overall outcome. The clinical conditions of the patients at the time of their PIBO diagnosis and at their last follow-up admission were evaluated using the clinical severity score (CSS). Samples for serum KL-6 level were obtained in 36 PIBO and 42 control group patients. The association of K...

Post-infectious bronchiolitis obliterans and mannose-binding lectin insufficiency in Argentinean children.

Post-infectious bronchiolitis obliterans (PIBO) is a severe disorder following acute lower pulmonary infection in young children, especially caused by adenovirus. Mannose-binding lectin (MBL) deficiency arising from polymorphisms in the coding and non-coding region on the MBL2 gene has been associated with more frequent and severe respiratory infections. Our aim was to evaluate the influence of MBL variants in the susceptibility and evolution of children with PIBO. One hundred eleven children with PIBO diagnosis were studied. The coding A, B, D and X promoter variants of MBL2 gene were assessed by PCR-RFLP. B and D alleles were pooled as O. The combined genotypes A/A and YA/O were grouped as sufficient MBL (sMBL), and O/O and XA/O as insufficient MBL (iMBL) groups. To evaluate the frequency of MBL2 polymorphisms in the general population, we studied DNA samples from 127 healthy donors from the blood bank of the hospital (control group). iMBL variants were significantly more frequent in PIBO children compared with controls (21.6% vs 10.2%, P = 0.01). PIBO patients with iMBL required intensive care unit (P = 0.001) and mechanical assistance at the moment of viral injury (P = 0.001) more frequently than those with sMBL. Insufficiency of MBL was more common in PIBO children than in healthy controls. This genetic condition was significantly associated with more severe initial disease, illustrating the relevance of innate immune defence factors prior to the maturation of the adaptative immune system.

Postinfectious bronchiolitis obliterans in children: lessons from bronchiolitis obliterans after lung transplantation and hematopoietic stem cell transplantation

Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease.

Post-infectious bronchiolitis obliterans in children: a review of 42 cases

BackgroundThis study aimed to describe the clinical characteristics, radiological features and outcomes of 42 children with post-infectious bronchiolitis obliterans (PIBO).MethodsForty-two children diagnosed with PIBO were prospectively studied at the First Hospital of Jilin University in northern China between January, 2008 and January, 2013. Their clinical characteristics, lung high resolution computed tomography (HRCT) findings and pulmonary function tests were reported.ResultsIn children with PIBO, adenovirus was the most common etiologic agent (21/42), followed by Mycoplasma pneumoniae (M. pneumoniae). All of the patients presented with repeated wheezing and tachypnea. In addition, 22 patients required intensive management, while six patients required home oxygen therapy. HRCT findings were consistent with the PIBO diagnosis in all of the patients. Pulmonary function testing was useful in evaluating therapeutic responses. Systemic steroids combined with azithromycin were effective for PIBO treatment.ConclusionsSevere adenovirus bronchiolitis and M. pneumoniae infections have a higher risk of development for PIBO. HRCT and pulmonary function testing are useful in the diagnosis of PIBO. The degree of airway obstruction did not differ significantly between adenovirus and M. pneumoniae. A combination of steroids and azithromycin offers some benefit in treating these patients.

Clinical prediction rule to diagnose post‐infectious bronchiolitis obliterans in children

Infant pulmonary function testing has a great value in the diagnosis of post-infectious bronchiolitis obliterans (BOs), because of characteristic patterns of severe and fixed airway obstruction. Unfortunately, infant pulmonary function testing is not available in most pediatric pulmonary centers. To develop and validate a clinical prediction rule (BO-Score) to diagnose children under 2 years of age with BOs, using multiple objectively measured parameters readily available in most medical centers. Study subjects, children under 2 years old with a chronic pulmonary disease assisted at R. Gutierrez Children's Hospital of Buenos Aires. Patients were randomly divided into a derivation (66%) and a validation (34%) set. ROC analyses and multivariable logistic regression included significant clinical, radiological, and laboratory predictors. The main outcome measure was a diagnosis of BOs. The performance of the BO-Score was tested on the validation set. Hundred twenty-five patients were included, 83 in the derivation set and 42 in the validation set. The BO-Score (area under ROC curve = 0.96; 95% CI, 0.9-1.0%) was developed by assigning points to the following variables: typical clinical history (four points), adenovirus infection (three points), and high-resolution computed tomography with mosaic perfusion (four points). A Score > or =7 predicted the diagnosis of BOs with a specificity of 100% (95% CI, 79-100%) and a sensitivity of 67% (95% CI, 47-80%). The BO-Score is a simple-to-use clinical prediction rule, based on variables that are readily available. A BO-Score of 7 or more predicts a diagnosis of post-infectious BOs with high accuracy.