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.

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.

Construction and analysis of a nomogram prediction model for post-infectious bronchiolitis obliterans in children with adenovirus pneumonia after invasive mechanical ventilation.

BACKGROUND: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model. METHODS: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed. RESULTS: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01). CONCLUSIONS: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built.

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.

Risk Factors for the Development of Post-Infectious Bronchiolitis Obliterans in Children: A Systematic Review and Meta-Analysis.

Post-infectious bronchiolitis obliterans (PIBO), one of the major complications of respiratory tract infection, is commonly underdiagnosed. To identify the risk groups that may develop PIBO and avoid misdiagnoses, we investigated the risk factors associated with the development of PIBO. We searched PubMed, Embase, and MEDLINE databases for studies that included risk factors for the development of PIBO published from inception to 13 June 2022. We limited our search to studies that reported the estimates of odds ratio (OR), hazard ratio (HR), or relative risks for developing PIBO. A fixed-effect and a random-effect model were used. We included seven studies reporting data on the risk factors for PIBO in 344 children with PIBO and 1310 control children. Twenty-two variables, including sex, age, respiratory pathogens, symptoms, laboratory and radiologic findings, and mechanical ventilation, were mentioned in at least one study. The significant risk factors mentioned in two or more studies included elevated lactate dehydrogenase levels, pleural effusion, hypoxemia, sex, and mechanical ventilation. The significance of the duration of hospitalization and fever as risk factors for PIBO differed when the studies were classified according to the statistical method. In addition, the risk factors differed according to respiratory infection pathogens. This meta-analysis identified potential risk factors associated with the development of PIBO. The results of this study highlight the importance of avoiding misdiagnosis and help establish management strategies for patients at a high risk of developing PIBO.

Clinical Analysis and Risk Factors of Bronchiolitis Obliterans After Mycoplasma Pneumoniae Pneumonia.

Purpose: Severe mycoplasma pneumoniae (MP) pneumonia can cause bronchiolitis obliterans (BO). In order to improve the prognosis of BO, it is necessary to grasp the clinical characteristics and risk factors of BO after severe MP pneumonia and intervene as soon as possible. Patients and Methods: This study retrospectively analyzed the clinical data of 110 patients with severe MP pneumonia, and divided them into BO group (22 cases) and non-BO group (88 cases). The clinical characteristics of BO group were analyzed, and the clinical data of two groups were compared to identify the risk factors of BO. Results: At the time of diagnosis, all BO patients had symptoms of cough and wheezing, and 10 (45.45%) had decreased exercise intolerance. Lung function showed moderate to severe obstructive ventilatory dysfunction, high-resolution computed tomography (HRCT) showed mosaic perfusion patterns. Multivariate binomial regression analysis showed that higher levels of serum lactate dehydrogenase (LDH) and hypoxemia were independent risk factors for BO after severe MP pneumonia. Conclusion: Higher levels of serum LDH and hypoxemia were independent risk factors for BO after severe MP pneumonia. For patients with risk factors, clinicians should regular follow-up for early diagnosis and intervention of BO.

Caspase-1 and interleukin-18 in children with post infectious bronchiolitis obliterans: a case-control study.

The exact immunological mechanisms of post infectious bronchiolitis obliterans (PIBO) in childhood are not fully known. It has been shown that the inflammasome and IL-18 pathway play important roles in the pathogenesis of lung fibrosis. We aimed to investigate the role of caspase-1, IL-18, and IL-18 components in PIBO. From January to May 2020, children with PIBO, children with history of influenza infection without PIBO, and healthy children were asked to participate in the study in three pediatric pulmonology centers. Serum caspase-1, IL-18, IL-18BP, IL-18R, and INF-γ levels were measured by ELISA and compared between the 3 groups. There were 21 children in the PIBO group, 16 children in the influenza group, and 39 children in the healthy control group. No differences in terms of age and gender between the 3 groups were found. IL-18 and IL-18BP levels were higher in the healthy control group (p = 0.018, p = 0.005, respectively). IL-18R was higher in the PIBO group (p = 0.001) and caspase-1 was higher in the PIBO and influenza group than the healthy control group (p = 0.002). IFN-γ levels did not differ between the 3 groups. IL-18BP/IL-18 was higher in the influenza group than the PIBO group and the healthy control group (p = 0.003). CONCLUSIONS: Caspase-1 level was increased in patients with PIBO which suggests that inflammasome activation may have a role in fibrosis; however, IL-18 level was found to be low. Mediators other than IL-18 may be involved in the inflammatory pathway in PIBO. Further immunological studies investigating inflammasome pathway are needed for PIBO with chronic inflammation. WHAT IS KNOWN: • Post infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease during childhood which is associated with inflammation and fibrosis which lead to partial or complete luminal obstruction especially in small airways. • The exact immunological mechanisms of PIBO in childhood are not fully known. WHAT IS NEW: • Inflammasome activation persists even years after acute infection and may play a role in fibrosis in PIBO. • Mediators other than IL-18 may be involved in these inflammatory pathway.

Risk Factors for Post-infectious Bronchiolitis Obliterans in Children: A Systematic Review and Meta-Analysis.

Background: Post-infectious bronchiolitis obliterans (PIBO) is a long-term sequela after an initial insult to the lower respiratory tract. A comprehensive understanding of the factors that contribute to a high risk of developing PIBO is important to help define therapeutic strategies and improve prognosis. Methods: We performed a systematic review of published literature available in the online databases including PubMed, Embase, Web of Science, CNKI, Wan Fang, and VIP, with the last search updated on 27 January 2022. Observational studies and case-control studies that provide sufficient data to examine associations between potential risk factors and PIBO were included. Pooled odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) and heterogeneity were calculated. Results: A total of 14 risk factors were selected from 9 studies included in the analysis. The strongest risk factors were hypoxemia, mechanical ventilation, tachypnea, and wheezing. Hypoxemia conferred the greatest risk with pooled OR of 21.54 (95% CI: 10-46.36, p < 0.001). Mechanical ventilation ranked second (pooled OR 14.61, 95% CI: 7.53-28.35, p < 0.001). Use of γ-globulin, use of glucocorticoids, co-infection of bacteria, a history of wheezing, and being male were other prominent risk factors. The effects of premature birth, allergic rhinitis, and imaging finding (pulmonary consolidation, atelectasis, pleural effusion) are less clear and require further confirmation. Cases that developing PIBO had a lower age compared with controls (MD, -8.76 months, 95% CI: -16.50 to -1.02, p = 0.03). No significant differences were observed in the duration of fever (MD, 1.74 days, 95% CI: -0.07 to 3.54, p = 0.06). Children diagnosed with PIBO had higher LDH levels (MD, 264.69 U/L, 95% CI: 67.43 to 461.74, p = 0.008) and duration of hospitalization (MD, 4.50 days, 95% CI: 2.63 to 6.37, p < 0.001). Conclusion: In this study, we found that the strongest risk factors for PIBO were hypoxemia, mechanical ventilation, tachypnea, and wheezing. Use of glucocorticoids, γ-globulin, co-infection of bacteria, a history of wheezing, and being male may also play a role. The factors discussed above can inform the generation of a clinical prediction model for the developing PIBO in children.

Effects of Inhaled Corticosteroids on Lung Function in Children With Post-infectious Bronchiolitis Obliterans in Remission.

Background: Post-infectious bronchiolitis obliterans (PIBO) is a rare and irreversible chronic obstructive pulmonary disease with no specific treatment, especially for patients with PIBO in remission. In this study, we evaluated the effects of continuous inhaled corticosteroids (ICSs) and intermittent ICSs on lung function in the remission of PIBO. Methods: This was a retrospective study, and all the subjects we included were divided into continuous ICS group and intermittent ICS group according to treatment regimens. Patients in continuous ICS group received continuous ICSs (2 times a day), and patients in intermittent ICS group received intermittent ICSs (inhaled corticosteroids after acute respiratory tract infection or wheezing). Different lung function tests were performed at different ages. Tidal breathing lung function tests were performed in patients with PIBO aged ≤ 5 years, and the lung ventilation function test and the bronchial dilation test were performed in patients with PIBO aged more than 5 years. Lung function was assessed at the beginning of follow-up and at the end of follow-up (1 year of ICSs). Results: After 1 year of ICSs, patients aged more than 5 years, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) were significantly higher than at the beginning of follow-up. After 1 year of ICSs, the difference in VT/Kg, TPTEF/TE, and VPEF/VE between the end and the beginning of follow-up in continuous ICS group shows an upward trend. But those showed a downward trend in intermittent ICS group. FVC, FEV1, and maximal mid-expiratory flow velocity 25-75% (MMEF25-75%) of continuous ICS group were significantly higher than at the beginning of follow-up. The difference in FEV1 and MMEF25-75% between the end of follow-up and the beginning of follow-up in continuous ICS group was significantly higher than that in intermittent ICS group. A total of 52.94% of patients with PIBO aged more than 5 years were positive for bronchial dilation tests. Conclusion: Inhaled corticosteroids can effectively improve lung function and relieve airway obstruction in patients aged more than 5 years in PIBO remission, especially continuous ICSs. Patients with PIBO may have reversible airflow limitations.

Epigenetic regulation of inflammation by microRNAs in post-infectious bronchiolitis obliterans.

OBJECTIVES: Post-infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post-transcriptional gene regulation in order to characterise PiBO. METHODS: A total of 39 patients with well-defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next-generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein-protein interaction network analysis respectively. RESULTS: Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL-1ß, IL-6, IL-8 and TGF-ß compared to controls.Next-generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for Padj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR-335-5p, miR-186-5p, miR-30b-5p and miR-30c-5p were further validated using qRT-PCR. Interestingly, these miRNAs are functionally implicated in cytokine-cytokine receptor interaction, TGF-ß signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1). CONCLUSION: Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics.

Epidemiology of Adenovirus Pneumonia and Risk Factors for Bronchiolitis Obliterans in Children During an Outbreak in Jilin, China.

Background: Jilin Province, located in northeastern China, recently experienced a human adenovirus (HAdV) epidemic. Few studies involving hospitalized pediatric patients with pneumonia caused by HAdV in our region exist. HAdV pneumonia can lead to severe long-term respiratory sequelae, such as post-infectious bronchiolitis obliterans (PIBO), which has a poor prognosis and greatly influences the quality of life of pediatric patients. However, studies on the risk factors for PIBO are limited. Objective: To describe the HAdV pneumonia prevalence and determine potential risk factors for PIBO development among hospitalized children in Jilin Province, China. Methods: The data of 187 children with HAdV pneumonia (10 months-12 years old) admitted to the First Hospital of Jilin University during an outbreak between October 2018 and January 2020 were retrospectively studied. We analyzed the epidemiological characteristics of HAdV pneumonia, focusing on severe HAdV pneumonia (66 cases). The risk factors for BO development were determined by comparing the demographic and clinical data of the BO and non-BO groups. Results: The largest number of HAdV pneumonia cases occurred in January 2019 (severe n = 18, general n = 21), followed by December 2018 (severe n = 14, general n = 11), June 2019 (general n = 17), July 2019 (general, n = 14), and May 2019 (general, n = 13). In total, 91.98% of the children with HAdV pneumonia were <6 years old (172/187), and 50% of the pediatric patients with severe HAdV pneumonia were <2 years old (33/66). We found that 30.3% of the severe cohort developed BO (20/66), and the strongest independent risk factors for PIBO were persistent wheezing (OR 181.776, 95% CI, 3.385-9,761.543) and acute respiratory failure (OR 51.288, 95% CI, 1.858-1,415.441) during a severe pneumonia episode. Conclusions: The largest number of HAdV pneumonia cases, especially severe cases, occurred in winter in Northeast China, followed by summer. The majority of children admitted with HAdV pneumonia were <6 years old, and half of severe HAdV pneumonia patients were <2 years old. Children who had persistent wheezing or acute respiratory failure during the acute phase of severe HAdV pneumonia were prone to the development of BO.

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

BACKGROUND: Post-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. METHODS: This 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. RESULTS: A 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. CONCLUSIONS: The 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.

Post-infectious bronchiolitis obliterans in children: Clinical and radiological evaluation and long-term results.

BACKGROUND AND OBJECTIVE: This study aims to evaluate clinical and radiological findings and treatment outcomes of the patients with PIBO. METHODS: One hundred fourteen children were enrolled. Initial demographic and clinical findings were evaluated. Pre- and post-treatment clinical and radiological findings were compared. RESULTS: The median age of the patients at initial pulmonary injury was 7,2 months, the median age at diagnosis was 17.5 months. Persistent wheezing was the most common complaint. Thirty-five patients had mechanical ventilation history. 82,5% of patients had clinical improvement. Bronchiectasis, atelectasis, hyperinflation and air trapping in HRCT improved significantly with treatment. Post-treatment Bhalla scores decreased from 8.3 to 6.5 (p= 0,001). Improvement was observed in radiological and clinical findings after treatment. CONCLUSIONS: This study is one of the largest studies in the literature and one of the few studies that evaluate clinical and radiological outcomes of patients with PIBO.

Risk factors for the development of post-infectious bronchiolitis obliterans after Mycoplasma pneumoniae pneumonia in the era of increasing macrolide resistance.

BACKGROUND: The prevalence of macrolide-resistant Mycoplasma pneumoniae (MP) pneumonia has been rapidly increased. MP pneumonia is a risk factor for the development of post-infectious bronchiolitis obliterans (PIBO). The aim of the present study was to identify the risk factors for the development of PIBO after MP pneumonia in the era of increasing macrolide resistance of MP. MATERIALS AND METHODS: This retrospective study enrolled 150 children with a mean age of 6.0 years admitted to the hospital due to MP pneumonia between May 2019 and February 2020 at a tertiary hospital. The clinical, radiologic, and laboratory data were obtained using retrospective chart review. RESULTS: Eighteen children (12%) were diagnosed with PIBO after MP pneumonia. PIBO was diagnosed after a mean duration of 100.0 days (range, 6-268 days) from symptom onset. The respiratory virus co-infection (adjusted odds ratio [aOR], 4.069; 95% confidence interval [95% CI], 1.224-13.523), adenovirus co-infection (aOR, 5.607; 95% CI, 1.801-17.454), longer duration between symptom onset and admission (aOR, 1.150; 95% CI, 1.020-1.298), higher levels of serum lactate dehydrogenase (LDH) at the time of admission (aOR, 1.001; 95% CI, 1.000-1.003), and poor response to stepwise treatment increased the risk for development of PIBO after MP pneumonia. However, macrolide resistance of MP was not associated with development of PIBO after MP pneumonia. CONCLUSION: The present study suggests that respiratory virus co-infection, including adenovirus, poor response to the treatment of MP pneumonia, and higher levels of serum LDH, but not macrolide resistance of MP, are risk factors of PIBO after MP pneumonia.

Therapeutic effect of budesonide, montelukast and azithromycin on post-infectious bronchiolitis obliterans in children.

Optimal treatment options for post-infectious bronchiolitis obliterans (PIBO) have not yet been established. The present study retrospectively analyzed the effect of budesonide, montelukast and azithromycin on treating PIBO in children <5 years old.. Based on treatment regimen, the cohort was divided into group A and group B. Group A received a combination of budesonide, montelukast and azithromycin for at least 3 months and group B received unconventional treatment (budesonide for nebulization intermittently, prednisone, montelukast and antibiotics if necessary) compared with standard treatment. Tidal pulmonary function and symptoms assessment were performed at diagnosis and after 3 months of therapy. There were no significant differences in the sex, age, pulmonary function and symptoms assessment between groups A and B at diagnosis. However, following 3 months of treatment, the time to peak tidal expiratory flow as a proportion of expiratory time, and volume to peak expiratory flow as a proportion of exhaled volume in group A were significantly higher compared with those in group B. The respiratory rate in group A was significantly lower compared with group B. The symptoms assessment score in group A was significantly higher compared with that of group B. In conclusion, the present study demonstrates that combination therapy with budesonide, montelukast and azithromycin improves pulmonary function and respiratory symptoms in PIBO children <5 years old. The present study was retrospectively registered on March 22, 2020 with register no. YY202003-008-HB03.

Post-infectious Bronchiolitis Obliterans: HRCT, DECT, Pulmonary Scintigraphy Images, and Clinical Follow-up in Eight Children.

Background: Bronchiolitis obliterans (BO), first mentioned in 1901, is a severe and rare chronic lung disease in children. BO has various etiologies and the most common in children is post-infectious BO (PIBO). High resolution CT (HRCT) is an often-used image tool for the diagnosis of BO, and pulmonary scintigraphy is an alternative tool that can functionally evaluate BO. Recently, dual-energy computed tomography (DECT) have also been applied to BO for its accuracy and safety. Here we described the characteristics of HRCT, pulmonary scintigraphy, DECT, and the clinical profiles of patients with PIBO. Methods: This is a retrospective and descriptive study. Data were collected from patients diagnosed with PIBO from 2014 to 2019 in the Pediatric Cardiopulmonary Outpatient Clinics of Kaohsiung Medical University Hospital. The diagnosis was based on clinical, chest X-ray, and HRCT findings. Clinical profile, radiological characteristics, and images of pulmonary scintigraphy were documented. Results: Eight children (4 boys and 4 girls) were diagnosed with PIBO at a mean age of 25.8 months (range 15 to 41 months). Two of our patients developed pulmonary hypertension. The most common HRCT finding is mosaic pattern, where match ventilation/perfusion (V/Q) defects is a general feature in pulmonary scintigraphy. DECT pulmonary blood vasculature images revealed various degrees of decreased perfusion and is compatible with the decreased perfusion on pulmonary scintigraphy. Conclusion: The therapeutic strategy of PIBO is still lacking of standardization. HRCT and V/Q scans are important image tools in diagnosis and follow-up of BO. DECT may be used in BO patients as it has no additional radiation exposure and add value on functional information of HRCT.

Clinical features of postinfectious bronchiolitis obliterans in children undergoing long-term nebulization treatment.

BACKGROUND: Limited data are available in relation to the clinical features of PIBO undergoing prolonged nebulization treatment with budesonide, terbutaline and ipratropium bromide. This retrospective study aimed to outline the features of clinical, high-resolution computed tomography (HRCT) and pulmonary function test (PFT) of PIBO, undergoing maintenance therapy utilizing a triple nebulization treatment and to determine the factors associated with prognosis. METHODS: Children diagnosed with PIBO were followed up between April 2014 and March 2017. The clinical features after maintenance nebulization treatment for 12 months were thereafter summarized. RESULTS: Thirty patients, 21 boys and 9 girls, were enrolled in the study. The median age of patients was 17.4 months, with a range between 3.0 and 33 months. Persistent coughing and wheezing were detected whilst wheezing and crackles were the common manifestations presented. HRCT scans revealed patchy ground and glass opacity, while PFT showed fixed airway obstruction in all patients. Four patients were lost during follow-up. After treatment, the clinical symptoms were improved greatly in all patients (P < 0.01). The mean increase in the percentage of TPEF%TE and VPEF%VE were improved greatly (P < 0.01). Images of the HRCT scan indicated marked improvements in 18 patients (81.8%) in comparison with scans obtained pre-treatment. CONCLUSIONS: Our data suggest a potential role of long-term nebulization treatment of budesonide, terbutaline, ipratropium bromide on PIBO, due to its efficacy as indicated in the improved clinical symptoms, pulmonary functions and CT manifestations identified in the children. New prospective and controlled studies are required to confirm this proposition.

Rehabilitación respiratoria en niños y adolescentes con bronquiolitis obliterante post infecciosa / Pulmonary rehabilitation in children and adolescents with post-infectious bronchiolitis obliterans

Post-infectious bronchiolitis obliterans (PIBO) is a lung disease characterized by chronic airflow limitation associated with small airway fibrosis and obliteration, caused by viral infection in the first years of life. According to the current clinical guidelines in our country, the bases of its treatment involve pharmacological and non-pharmacological strategies. Among non-pharmacological strategies, pulmonary rehabilitation (PR) is the standout, which consists of diagnostic and therapeutic management designed to evaluate and reverse function deterioration, and aimed at improving the quality of life and the prognosis of these patients.The objective of this review is to describe and discuss the components associated with pulmonary rehabilitation of PIBO patients, emphasizing the properties and attributes of the evaluation methods and the main treatment strategies that contribute to improving these patients' functionality

La bronquiolitis obliterante post infecciosa (BOPI) es una enfermedad pulmonar caracterizada por limitación crónica al flujo de aire asociado a fibrosis y obliteración de la vía aérea pequeña, que se produce como consecuencia de un cuadro infeccioso de origen viral durante los primeros años de vida. De acuerdo a la guía clínica vigente en nuestro país, las bases de su tratamiento se sustentan en estrategias farmacológicas y no farmacológicas. Entre las estrategias no farmacológicas destaca la rehabilitación respiratoria (RR), que se estructura a partir de la ejecución de protocolos de intervención con fines diagnósticos y terapéuticos, dirigidos a evaluar y revertir el deterioro funcional, teniendo como propósito central el mejorar la calidad de vida y el pronóstico de estos pacientes. El objetivo de la presente revisión es describir y discutir los componentes asociados a la rehabilitación pulmonar de los pacientes con BOPI, haciendo énfasis en las propiedades y atributos de los métodos de evaluación y en las principales estrategias de tratamiento que contribuyen a mejorar la funcionalidad de estos pacientes

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)-ß1, 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.