Post-infectious Bronchiolitis Obliterans Patients Research Articles

Successful treatment of postinfectious bronchiolitis obliterans with gamma globulin in a tertiary center: 10 years of experience.

Bronchiolitis obliterans is characterized by partial or total occlusion of the bronchioles due to inflammation and fibrosis, and the most common form is postinfectious bronchiolitis obliterans (PIBO). This study aimed to retrospectively present our intravenous immunoglobulin (IVIG) treatment experience in PIBO patients with a clinically severe course despite receiving commonly used treatment protocols. The study included patients aged 0-18 with subtle immunological abnormalities who were followed up in our center for PIBO between 2010 and 2021. Clinical evaluation, body mass index (BMI), computerized tomography (CT) image scoring, and immunological parameters were recorded before and after IVIG treatment. Of the 11 patients included in the study, 90% were male, the mean age at diagnosis was 27.1 months (range: 5-68 months) and the mean current age was 81.4 months (range: 15-188 months). The number of hospital visits due to infection and the frequency of hospitalizations decreased markedly in the patients who underwent IVIG therapy. Oxygen therapy was discontinued in all patients, and improvements in radiological severity scores were observed. BMI z-scores improved over the baseline values after IVIG therapy. Corticosteroids are considered the best first-line treatment to control inflammation in PIBO. In our study group, PIBO patients showed favorable clinical and radiological responses to regular IVIG treatment, possibly due to minor immune deficiency secondary to steroids or as a result of undetected adaptive and innate immune defects involved in the etiology of severe PIBO.

The clinical presentation, etiology, and disease progression of children with post-infectious bronchiolitis obliterans in Cape Town, South Africa

Objectives: We describe the clinical spectrum, etiology, and progression of children with post-infectious bronchiolitis obliterans (PIBO) from a low- and middle-income setting for which there is limited literature. Materials and Methods: A cross-sectional, retrospective, and descriptive study between November 2019 and October 2020 of all PIBO patients aged 6 months to 15 years managed at pediatric pulmonology service in Cape Town, South Africa. Results: Fifty-one patients with PIBO were enrolled; 78% were males, median age of 60 months (IQR 33–107). Median age at disease presentation was 6 months (IQR 3–12), 80% presented with cough; 94% required hospital admission, 92% needed supplemental oxygen therapy and 75% needed ventilatory support. Reported cigarette smoke exposure was high (47%). Adenovirus infection was the most common etiology (64%). Chest radiographic findings included lung hyperinflation (43 [84.3%]) and bronchiectasis (23 [45%]). Twenty-seven patients had spirometry and showed mixed (41% [n = 8]) or obstructive (27% [n = 12]) pattern with mean (standard deviation) forced expiratory volume in 1s (FEV1) z-score −3.3 (± 1.4), forced vital capacity (FVC) z-scores −2.4 (± 1.6), and FEV1/FVC z-score −3.1 (± 2.4). Systemic corticosteroids were used during initial presentation in 47 patients (92%). Forty-four patients (86%) required two or more subsequent hospital admissions. Improvement of symptoms was reported in 82% of patients with a mean follow-up period of 5 years. Cough (43% [n = 22]) and wheeze (39% [n = 20)]) were the most common reported current symptoms. Conclusion: PIBO is a recognized cause of pediatric obstructive lung disease in South African settings, with adenovirus pneumonia being the most common preceding illness. Symptoms of airway obstruction persist over time, but improvement was observed with treatment including corticosteroids.

Follow-up on the therapeutic effects of a budesonide, azithromycin, montelukast, and acetylcysteine (BAMA) regimen in children with post-infectious bronchiolitis obliterans.

BackgroundPost-infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease without optimal treatment. Currently, treatment in children mainly relies on systemic corticosteroids, but long-term use of these drugs may lead to adverse reactions. This study aimed to evaluate the short-term efficacy of the budesonide, azithromycin, montelukast, and acetylcysteine (BAMA) regimen in paediatric PIBO patients and whether it can reduce systemic corticosteroid use.MethodsThis was a prospective study. From June 2017 to July 2020, patients diagnosed with PIBO at Yuying Children’s Hospital of Wenzhou Medical University were treated with the BAMA regimen for 3 months. Methylprednisolone was added only when the clinical manifestations did not improve or deteriorated. All patients were followed up every 2 to 4 weeks, and changes in clinical symptoms were recorded. Pulmonary function tests and high-resolution computed tomography (HRCT) were performed, and systemic corticosteroid use was recorded after the 3-month follow-up.ResultsA total of 75 patients with PIBO were included; overall, 54 patients completed the course of treatment. After treatment, the respiratory manifestations were improved in 37 patients (68.5%), but 4 patients (7.4%) showed decreased exercise tolerance, and 2 patients (3.7%) were readmitted to the hospital. Additionally, 17 (56.7%) of the 30 patients whose pulmonary function was re-examined showed improvement, and 28 (77.8%) of the 36 patients who underwent HRCT showed marked improvement. Importantly, 20 patients (54.1%) received systemic corticosteroids for 2 weeks or less, while 31.5% of patients used no corticosteroids.ConclusionsThe BAMA regimen effectively relieved clinical symptoms and signs of PIBO in children, improved pulmonary function and HRCT manifestations, and reduced the use of systemic corticosteroids.

Clinical analysis of adenovirus postinfectious bronchiolitis obliterans and nonadenovirus postinfectious bronchiolitis obliterans in children.

Background and Objective:Postinfectious bronchiolitis obliterans (PIBO) is an uncommon and severe form of chronic obstructive lung disease in children. Adenovirus (ADV) is the main pathogen of PIBO in children. However, the risk factors of ADV-PIBO are not fully understood. This study aims to analyze the clinical characteristics of PIBO caused by ADV and compared with non-ADV-PIBO.Materials and Methods:A retrospective study of children under the age of 14 years diagnosed PIBO was performed in 56 ADV-PIBO cases, 29 non-ADV-PIBO, and 39 healthy controls to determine clinical characteristics of PIBO.Results:There was no difference between ADV-PIBO and non-ADV-PIBO cases in gender, age, individual and family atopy or history of asthma, and previous history of wheezing and no difference in the clinical manifestations and signs between the two groups. However, the hospital stay, duration of ventilator use, and multifocal pneumonia incidence of ADV-PIBO group have a significant differences compared with non-ADV-PIBO. Notably, inflammatory markers lactic dehydrogenase (LDH), interleukin 8 (IL-8), and interferon-gamma (IFN-γ) were significantly increased in PIBO patients, and those expressed in ADV-PIBO patients were higher than those in non-ADV-PIBO patients. In addition, ADV-PIBO children required a longer duration of oral prednisone and azithromycin than non-ADV-PIBO cases.Conclusions:Compared with non-ADV-PIBO, ADV-PIBO has a longer hospital stay, longer duration of ventilator use, increased LDH, IL-8, and IFN-γ expressions, and longer duration of oral prednisone and azithromycin treatment. Further research is needed to determine why PIBO caused by ADVs are more severe than those caused by other pathogens.

Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China

Primary ciliary dyskinesia (PCD) is a heterogeneous disease with a diverse clinical and genetic spectrum among populations worldwide. Few cases of pediatric PCD have been reported from China. What are the clinical and genotypic characteristics of children with PCD in China? Clinical characteristics, laboratory findings, and genetic results obtained for 75 patients with PCD were reviewed retrospectively at a single center in China. Genetic sequencing was conducted using whole-exome screening. Patient median age at diagnosis was 7.0 years (range, 2 months-14 years). Of 75 patients, 88%(66/75) had chronic wet cough, 77%(58/75) had recurrent sinusitis, 76%(57/75) had bronchiectasis, 40%(30/75) had neonatal respiratory distress, and 28%(21/75) had coexistent asthma. Notably, postinfectious bronchiolitis obliterans (PIBO) as first presentation was found in 8%of children (6/75). Genes with the highest incidence of mutations were DNAH11 (15/51), followed by DNAH5 (9/51), CCDC39 (5/51), DNAH1 (4/51), and CCNO (3/51). Four genes (DNAI1, HEATR2, RSPH9, and DNAAF3) each were respectively found in two patients, and seven genes (CCDC40, LRRC6, SPAG1, RSPH4A, ARMC4, CCDC114, and DNAH14, a novel gene) each were mutated once. No differences in classical clinical features were observed among patients with commonly observed PCD-associated genotypes. However, three of six PIBO patients carried DNAH1 mutations. Besides typical clinical features, PIBO was observed as the first presentation of pediatric PCD in China. An association of the novel gene DNAH14 with PCD was observed, expanding the PCD genotypic spectrum.

Prediction of postinfectious bronchiolitis obliterans prognosis in children.

The prognosis of postinfectious bronchiolitis obliterans (PIBO) has many implications, ranging between reduced quality of life and life-threatening complications. We evaluated the prognostic factors for PIBO using the baseline clinical characteristics of patients and built a prediction model for determining the prognoses of PIBO patients using the identified parameters. We included 47 PIBO patients who underwent spirometry and impulse oscillometry and followed them up for at least 1 year. A patient's prognosis was classified as poor if the patient experienced at least one of the following: persistent respiratory symptoms for more than 1 year, two or more instances of hospitalizations due to respiratory symptoms, or more than one intensive care unit admission. The prognoses of 32/47 (68.1%) patients was good, while that of 15/47 (31.9%) was poor. Spirometry results showed significantly lower forced vital capacity (FVC), forced expiratory volume in the first second (FEV1 ), forced expiratory flow at 25%-75% of FVC, and post-bronchodilator (BD) FEV1 values in the poor prognosis group; chest computed tomography (CT) demonstrated more inflammatory bronchiolitis findings. We created a nomogram for predicting prognoses using post-BD FEV1 and inflammatory bronchiolitis on chest CT. The area under the curve for the nomogram was 84.6% (95% confidence interval: 72.8%-96.4%). PIBO patients with lower pulmonary function values and more findings of inflammatory bronchiolitis on initial examination have poor prognoses. The nomogram for predicting PIBO prognosis is easy to use and can be applied at the time of diagnosis.

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.

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.

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.

Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility.

ABSTRACTObjective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications.

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.