Severe Bronchiolitis Research Articles

Successful treatment of severe post hematopoietic stem cell transplantation bronchiolitis obliterans syndrome with lung transplantation in a patient with multi‐organ chronic graft‐versus‐host disease

AbstractAllogeneic stem cell transplant and chronic graft‐versus‐host disease may lead to severe non‐infectious pulmonary disease in 6% of patients at 5 years. We report the case of a young patient with acute myeloid leukemia who successfully received bilateral lung transplantation for severe bronchiolitis obliterans syndrome.

Analysis of predictors of response to high-flow oxygen nasal cannula therapy in a pediatric intensive care unit.

Bronchiolitis is one of the most frequent reasons for admission to pediatric intensive care units. Medical treatment is primarily supportive. The usefulness of high-flow oxygen (HFO) nasal cannula in these patients has been described. This study evaluated the clinical and analytical variables of patients admitted to our Pediatric Intensive Care Unit (PICU) for initiation or continuation of HFO for respiratory distress and to identify any variable that may be a predictor of success or failure of this technique. We conducted a retrospective observational study that included infants aged < 24 months admitted to our PICU due to bronchiolitis between January 2015 and March 2019 for HFO. We analyzed the characteristics between responders (n = 112) and non-responders (n = 37). No statistically significant differences were observed between groups regarding sex, age, weight, comorbidities, nasopharyngeal aspirate result, hours of evolution, and respiratory and heart rate. However, a pCO2 ≥ 75 mmHg (p = 0.043) and a SCORE of bronchiolitis severity (p = 0.032) were predictors of HFNC failure. The pCO2 level and SCORE of bronchiolitis severity are predictors of this respiratory support modality.

Integrated relationship of nasopharyngeal airway host response and microbiome associates with bronchiolitis severity

Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal airway, and associate them with disease severity. We investigate individual associations with disease severity identify host response, microbial taxonomical, and microbial functional modules by network analyses. We also determine the integrated relationship of these modules with severity. Several modules are significantly associated with risks of positive pressure ventilation use, including the host-type I interferon, neutrophil/interleukin-1, T cell regulation, microbial-branched-chain amino acid metabolism, and nicotinamide adenine dinucleotide hydrogen modules. Taken together, we show complex interplays between host and microbiome, and their contribution to disease severity.

Pulmonary Fibrosis and Hypereosinophilia in TLR9-/- Mice Infected by Cryptococcus gattii

Cryptococcus gattii is a worldwide-distributed basidiomycetous yeast that can infect immunocompetent hosts. However, little is known about the mechanisms involved in the disease. The innate immune response is essential to the control of infections by microorganisms. Toll-like receptor 9 (TLR9) is an innate immune receptor, classically described as a non-methylated DNA recognizer and associated with bacteria, protozoa and opportunistic mycosis infection models. Previously, our group showed that TLR9-/- mice were more susceptible to C. gattii after 21 days of infection. However, some questions about the innate immunity involving TLR9 response against C. gattii remain unknown. In order to investigate the systemic cryptococcal infection, we evaluated C57BL/6 mice and C57BL/6 TLR9-/- after intratracheal infection with 104 C. gattii yeasts for 21 days. Our data evidenced that TLR9-/- was more susceptible to C. gattii. TLR9-/- mice had hypereosinophilia in pulmonary mixed cellular infiltrate, severe bronchiolitis and vasculitis and type 2 alveolar cell hyperplasia. In addition, TLR9-/- mice developed severe pulmonary fibrosis and areas with strongly birefringent fibers. Together, our results corroborate the hypothesis that TLR9 is important to support the Th1/Th17 response against C. gattii infection in the murine experimental model.

Long-Term Pulmonary Outcomes in Children Mechanically Ventilated for Severe Bronchiolitis.

Objectives:Bronchiolitis is a common indication for mechanical ventilation in the PICU. Both bronchiolitis and invasive mechanical ventilation may cause adverse long-term pulmonary outcomes. This study investigates children with a history of invasive mechanical ventilation for bronchiolitis, addressing: 1) the extent, 2) potential explanatory factors, and 3) possible impact on daily life activities of adverse long-term pulmonary outcomes.Design:Single-center cohort study.Setting:Outpatient PICU follow-up clinic.Patients:Children 6–12 years old with a history of invasive mechanical ventilation for bronchiolitis (age <2 yr).Interventions:None.Measurements and Main Results:Long-term pulmonary outcomes were assessed by a standardized questionnaire and by spirometry. Nineteen out of 74 included children (26%) had adverse long-term pulmonary outcomes, of whom the majority had asthma (14/74, 19%). By logistic regression analysis, we assessed whether background characteristics and PICU-related variables were associated with long-term pulmonary outcomes. In general, we failed to identify any explanatory factors associated with adverse long-term pulmonary outcomes. Nonetheless, atopic disease in family and longer duration of invasive mechanical ventilation (days) were associated with greater odds of having asthma at follow-up (odds ratio, 6.4 [95% CI, 1.2–36.0] and 1.3 [95% CI, 1.0–1.7], respectively). Adverse pulmonary outcome at follow-up was associated with more frequent use of pulmonary medication after PICU discharge. In comparison with those without adverse pulmonary outcomes, we did not identify any difference in frequency of sports performance or school absenteeism.Conclusions:In this single-center cohort, one-quarter of the children attending follow-up with a history of invasive mechanical ventilation for bronchiolitis had adverse, mostly previously undetected, long-term pulmonary outcomes at 6–12 years. Atopic disease in family and longer duration of invasive mechanical ventilation were associated with presence of asthma. The presence of adverse pulmonary outcomes was associated with more frequent use of pulmonary medication after PICU discharge.

Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study.

Infants hospitalized for bronchiolitis are at high risk for asthma. Glutathione-related metabolites may antagonize oxidative stress, which induces airway injuries in respiratory infection and subsequent airway remodeling. However, little is known about the relationship of glutathione-related metabolites with bronchiolitis severity and the risk of asthma. In a multicenter prospective observational cohort study of infants hospitalized for bronchiolitis, we measured nasopharyngeal and serum glutathione-related metabolites by using liquid chromatography–tandem mass spectrometry. We then examined their association with bronchiolitis severity (defined by positive pressure ventilation (PPV) use). We also identified severity-related glutathione-related metabolite signatures and examined their association with asthma at age 6 years. In 1013 infants, we identified 12 nasopharyngeal and 10 serum glutathione-related metabolites. In the multivariable models, lower relative abundances of seven metabolites, e.g., substrates of glutathione, including cysteine (adjOR 0.21, 95%CI 0.06–0.76), glycine (adjOR 0.25, 95%CI 0.07–0.85), and glutamate (adjOR 0.25, 95%CI 0.07–0.88), were significantly associated with PPV use (all FDR < 0.05). These associations were consistent with serum glutathione-related metabolites. The nasopharyngeal glutathione-related metabolite signature was also associated with a significantly higher risk of asthma (adjOR 0.90, 95%CI 0.82–0.99, p = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

Prognostic Role of Lung Ultrasound in Children with Bronchiolitis: Multicentric Prospective Study.

There is increasing recognition of the role of lung ultrasound (LUS) to assess bronchiolitis severity in children. However, available studies are limited to small, single-center cohorts. We aimed to assess a qualitative and quantitative LUS protocol to evaluate the course of bronchiolitis at diagnosis and during follow-up. This is a prospective, multicenter study. Children with bronchiolitis were stratified according to clinical severity and underwent four LUS evaluations at set intervals. LUS was classified according to four models: (1) positive/negative; (2) main LUS pattern (normal/interstitial/consolidative/mixed) (3) LUS score; (4) LUS score with cutoff. Two hundred and thirty-three children were enrolled. The baseline LUS was significantly associated with bronchiolitis severity, using both the qualitative (positive/negative LUS p < 0.001; consolidated/normal LUS pattern or mixed/normal LUS p < 0.001) and quantitative models (cutoff score > 9 p < 0.001; LUS mean score p < 0.001). During follow-up, all LUS results according to all LUS models improved (p < 0.001). Better cut off value was declared at a value of >9 points. Conclusions: Our study supports the role of a comprehensive qualitative and quantitative LUS protocol for the identification of severe cases of bronchiolitis and provides data on the evolution of lung aeration during follow-up.

Predicting the severity of viral bronchiolitis in children

Acute viral bronchiolitis is one of the common causes of hospitalization and mortality, especially among children in the first year of life who have risk factors (prematurity, congenital heart defects, bronchopulmonary dysplasia, immunosuppression). As factors associated with the severe course of bronchiolitis, along with the traditional ones, single nucleotide polymorphisms of the genes of the immune response molecules can be considered.The aim. Based on the analysis of clinical, laboratory and molecular genetic parameters, to identify prognostic criteria for the severe course of acute viral bronchiolitis in children.Materials and methods. The study included 106 children with acute viral bronchiolitis (severe course – 34, mild course – 72), the etiology of which in 67.9 % was respiratory syncytial virus. Forty-seven anamnestic, clinical, traditional laboratory and molecular genetic parameters were assessed as prognostic criteria. Determination of SNP genes of cytokines IL-4 (C-589T), IL-10 (G-1082A), IL-10 (C-592A), IL-10 (C-819T), TNF-α (G-308A), IL-17A (G197A), IL-17F (His161Arg), TLR2-753ArgGln, TLR6-Ser249Pro in venous blood was carried out by the polymerase chain reaction method.Results. An additional criterion for the risk of developing a severe course of bronchiolitis can be the mutant genotype (AA) SNP of the IL-10 gene (C-592A), which was detected exclusively in the group of patients with severe bronchiolitis, increasing the risk of developing a severe disease by 16.11 times (OR = 16.11; 95 % CI: 0.81–121.22, p = 0.02) in conjunction with already established modifying factors: the presence of congenital heart disease, bronchopulmonary dysplasia, prematurity, birth weight &lt; 1500 g. Based on a comprehensive assessment of the established risk factors, a method has been developed that allows calculate the likelihood of developing a severe course of acute viral bronchiolitis. Conclusion. The use of the developed prediction method will not only increase the likelihood of developing severe acute viral bronchiolitis in children, but also determine the priority group among children with predictors of severe viral bronchiolitis for priority immunoprophylaxis against RS-virus infection.

Total immunoglobulin E in infant bronchiolitis and risk of developing asthma

Bronchiolitis is the leading cause of infant hospitalization in the United States.1 In addition to the acute morbidity, bronchiolitis also puts patients at increased risk for subsequent morbidity. Indeed, approximately 30% of infants hospitalized with bronchiolitis (severe bronchiolitis) develop recurrent wheezing and asthma.1 Yet, the underlying mechanisms of the bronchiolitis-asthma link remain unclear.

Breath sound analyses of infants with respiratory syncytial virus acute bronchiolitis.

The reliability of a breath sound analysis using an objective method in infants has been reported. Breath sounds of infants with respiratory syncytial virus (RSV) acute bronchiolitis were analyzed via a breath sound spectrogram to evaluate their characteristics and examine their relationship with the severity. We evaluated the inspiratory and expiratory breath sound parameters of 33 infants diagnosed with RSV acute bronchiolitis. The sound powers of inspiration and expiration were evaluated at the acute phase and recovery phase of infection. Furthermore, the relationship between the breath sound parameters and the clinical severity of acute bronchiolitis was examined. Analyses of the breath sound spectrogram showed that the power of expiration as well as the expiration-to-inspiration sound ratio in the mid-frequency (E/I MF) was increased in the acute phase and decreased during the recovery phase. The E/I MF was inversely correlated with the SpO2 and positively correlated with the severity score. In infants with RSV acute bronchiolitis, the sound power of respiration was large at the acute phase, significantly decreasing in the recovery phase. In 61% of participants, nonuniform, granular bands were shown in the low-pitched region of the expiratory spectrogram.

IFN-λ Diminishes the Severity of Viral Bronchiolitis in Neonatal Mice by Limiting NADPH Oxidase-Induced PAD4-Independent NETosis.

Infants with attenuated type III IFN (IFN-λ) responses are at increased risk of severe lower respiratory tract infection (sLRI). The IL-28Rα-chain and IL-10Rβ-chain form a heterodimeric receptor complex, necessary for IFN-λ signaling. Therefore, to better understand the immunopathogenic mechanisms through which an IFN-λlo microenvironment predisposes to a sLRI, we inoculated neonatal wild-type and IL-28R-deficient (IL-28R -/-) mice with pneumonia virus of mice, a rodent-specific pneumovirus. Infected IL-28R -/- neonates displayed an early, pronounced, and persistent neutrophilia that was associated with enhanced reactive oxygen species (ROS) production, NETosis, and mucus hypersecretion. Targeted deletion of the IL-28R in neutrophils was sufficient to increase neutrophil activation, ROS production, NET formation, and mucus production in the airways. Inhibition of protein-arginine deiminase type 4 (PAD4), a regulator of NETosis, had no effect on myeloperoxidase expression, citrullinated histones, and the magnitude of the inflammatory response in the lungs of infected IL-28R -/- mice. In contrast, inhibition of ROS production decreased NET formation, cellular inflammation, and mucus hypersecretion. These data suggest that IFN-λ signaling in neutrophils dampens ROS-induced NETosis, limiting the magnitude of the inflammatory response and mucus production. Therapeutics that promote IFN-λ signaling may confer protection against sLRI.

The effect of environmental noise isolation on bronchiolitis severity in hospitalised children.

Bronchiolitis is an infectious disease, with no effective treatment. Music and Mozart's works specifically are known to have a positive effect on physiological parameters, while noise is considered harmful. We aim to evaluate the short-term effect of environmental noise detachment and/or music listening on the course of bronchiolitis in hospitalised children. This is a prospective, double-blinded randomised controlled trial. Patients were divided into three intervention groups: 1-Mozart's Sonata, 2-instrumental music, 3-silence. Music was heard via media players and soundproof headphones. Disease severity was evaluated before and after intervention using the Modified Tal score. Seventy music sessions were included in the analysis (Mozart n=23, instrumental n=22, silence n=25). A one-point drop in the average bronchiolitis severity score was observed in all three groups from 7.1 (CI 95%, 5 to 9.2) to 6.1 (CI 95%, 4.3 to 7.9), p < 0.001. No significant difference was found between the three groups with respect to change in the severity score before and after the intervention. Isolation from disturbing sounds heard in paediatric departments could be considered a simple non-invasive intervention in children hospitalised with bronchiolitis. Further studies are warranted to evaluate long-term effects of this intervention and the specific effect of music.

MLKL Regulates Rapid Cell Death-independent HMGB1 Release in RSV Infected Airway Epithelial Cells.

Respiratory syncytial virus (RSV)-induced bronchiolitis is a significant contributor to infant morbidity and mortality. Previously, we identified that necroptosis, a pro-inflammatory form of cell death mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3, and mixed lineage kinase domain like protein (MLKL), occurs in RSV-infected human airway epithelial cells (hAECs), mediating the release of the alarmin high mobility group box 1 (HMGB1). Here, we show that RSV infection of hAECs induces the biphasic release of HMGB1 at 6 (“early”) and 24 (“late”) hours post infection (hpi). The early phase of HMGB1 release at 6 hpi is cell death-independent, however, this release is nonetheless attenuated by inhibition of MLKL (primarily associated with necroptosis). The early release of HMGB1 promotes the late phase of HMGB1 release via the activation of RAGE (receptor for advanced glycation endproducts) and occurs with cell death. Treatment of hAECS with exogenous HMGB1 combined with a pan-caspase inhibitor induces hAEC necroptosis, and is attenuated by the RAGE antagonist, FPS-ZM1. Together, these findings demonstrate that RSV infection of hAECs leads to the early release of HMGB1, followed by a paracrine feed-forward amplification loop that further increases HMGB1 levels and promotes cell death. As the inhibition of MLKL or targeting of HMGB1/RAGE pathway attenuates the release of pro-inflammatory HMGB1 and decreases viral load, this suggests that the pharmacological targeting of these pathways may be of benefit for the treatment of severe RSV bronchiolitis.

Air pollution, bronchiolitis, and asthma: the role of nasal microRNAs

Severe bronchiolitis (ie, bronchiolitis that requires hospitalisation) imposes a substantial acute care burden on infants and leads to chronic respiratory sequelae, such as recurrent wheeze and asthma.1 An increasing number of studies show that, in infants with severe bronchiolitis, environmental exposures play an essential role in the development of asthma. Data from observational studies show that infants with severe bronchiolitis who are exposed to higher levels of air pollution (for example, if their birth residence is located close to a main road) have a 1·2–1·6 times higher risk of developing asthma than those exposed to lower levels of air pollution.

Lung function, allergic sensitization and asthma in school-aged children after viral-coinfection bronchiolitis

Our main objective was to compare the lung function, the rate of allergic sensitization and the prevalence of asthma at 7–9 years in children hospitalized for bronchiolitis with viral coinfection versus single viral infection. Observational study in children with previous bronchiolitis and current age 7–9 years. Clinical data were collected. Fraction of exhaled nitric oxide (FeNO) determination, spirometry and skin prick test for common aeroallergens were performed. A total of 181 children hospitalized for bronchiolitis (40 coinfections and 141 single infections), with median age of 8.3 years (IQR:7.5–9.1) were included. Single-HRV-infections showed lower basal FEV1(%) than coinfections (p = 0.04) and lower z-score FEV1 than single-RSV-infections (p = 0.04) or coinfections (p = 0.02). Also, single-HRV-infections had lower post-bronchodilator FEV1(%) and z-score FEV1 values than coinfections (p = 0.03 and p = 0.03). Single-HRV-bronchiolitis was an independent risk factor for FEV1 < 80% (p = 0.007). FeNO value > 25 ppb was detected in 21(12.5%) cases, without differences between viral groups (p = 0.768). The prevalence of allergic sensitization was similar in coinfections (31.4%) versus single infections (38.7%), (p = 0.428). The highest frequency of allergic rhinitis was observed in single-HRV patients (p = 0.004). The respiratory morbidity at 7–9 years of coinfected patients was similar to the single-HRV ones. In contrast, the likelihood of current asthma was up to 5 times higher in RSV/HRV coinfections than in the single-RSV-infections ones (p = 0.012). The respiratory morbidity at 7–9 years of age after severe bronchiolitis is significantly higher in single-HRV or viral coinfection patients that in single-RSV ones. Single-HRV-bronchiolitis is independently associated with lower lung function at school-age.

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a seasonal pathogen responsible for the highest percentage of viral bronchiolitis in pediatric patients. There are currently no vaccine available and therapeutic methods to mitigate the severity of RSV bronchiolitis are limited. OM-85, an oral standardized bacterial lysate isolated from human respiratory strains and widely used to prevent recurrent infections and/or exacerbations in populations at risk, has been shown to be effective and safe in children and adults. Here, we demonstrate that airway administration of OM-85 in Balb/c mice prior to infection prevents RSV-induced disease, resulting in inhibition of viral replication associated with less perivascular and peribronchial inflammation in the lungs. These protective effects are dose and time-dependent with complete protection using 1mg dose of OM-85 only four times intranasally. Mechanistic insights using this topical route in the airways revealed increased alveolar macrophages, a selective set of tolerogenic DCs, Treg and Th1 expansion in the lung, even in the absence of infection, contributing to a better Th1/Th2 balance and preventing ILC2 recruitment in the airways and associated inflammatory sequelae. OM-85 preventive treatment also improved antiviral response by increasing IFNβ and its responsive genes in the lung. In vitro, OM-85 protects against RSV infection in a type I interferon pathway. Our animal model data suggest that intranasal use of OM-85 should be considered as a potential prophylactic product to prevent RSV bronchiolitis once human studies confirm these findings.

Prednisone and Nebulized Epinephrine for Severe Bronchiolitis

Prednisone and Nebulized Epinephrine for Severe Bronchiolitis

TLR4 Gene Polymorphisms Interaction With Ascaris Infection in Severe RSV Bronchiolitis.

IntroductionThe identification of gene-environment interactions allows the recognition of groups with higher risk of morbidity. This study evaluated the interaction between the presence of TLR4 gene polymorphisms and Ascaris infection with severe bronchiolitis in a tropical Colombian region.MethodsWe included all infants younger than 24 months hospitalized due to bronchiolitis in Hospital centers in the county of Rionegro, Colombia. To identify interaction between severe bronchiolitis and presence of TLR4 polymorphisms and Ascaris infection, we used log-binomial regression.ResultsFour hundred and seventeen infants were hospitalized due to bronchiolitis, of which 115 (27%) had severe bronchiolitis. In infants with respiratory syncytial virus (RSV) acute infection and positive anti-Ascaris IgE, TLR4 Asp299Gly was associated to low risk of severe bronchiolitis (OR 0.09, CI 95% 0.01–0.48). Conversely, in infants RSV negative with negative anti-Ascaris IgE, TLR4 Asp299Gly was associated with an increased risk of severe bronchiolitis (OR 14.5, CI 95% 2.2–96).ConclusionIn our population there is an interaction between the presence of severe bronchiolitis, TLR4 Asp299Gly and Ile399Thr polymorphisms, anti-Ascaris IgE levels and RSV. This association should be evaluated in other populations to elucidate its role in the pathogenesis of severe bronchiolitis.

Nasopharyngeal airway dual-transcriptome of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study

Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. This study sought to examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population. This multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months) examined the infants' nasopharyngeal metatranscriptomes (microbiomes) and transcriptomes (hosts), as well as metabolomes at hospitalization. The longitudinal relationships investigated include (1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), (2) microbial function, and (3) host response with risks of developing asthma by age 6 years. First, the abundance of S pneumoniae was associated with greater risks of asthma (P= .01), particularly in infants with nonrhinovirus infection (Pinteraction= .04). Second, of 328 microbial functional pathways that are differentially enriched by asthma development, the top pathways (eg, fatty acid and glycolysis pathways; false discovery rate [FDR]< 1×10-12) were driven by these 3 major species (eg, positive association of S pneumoniae with glycolysis; FDR< 0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially enriched (FDR< .05)-for example, downregulated interferon-α and -γ and upregulated T-cell activation pathways. S pneumoniae was associated with most differentially expressed transcripts (eg, DAGLB; FDR< 0.05). By applying metatranscriptomic, transcriptomic, and metabolomic approaches to a multicenter cohort of infants with bronchiolitis, this study found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development.

The importance of immature granulocyte and immature reticulocyte fraction for the severity of acute bronchiolitis

The immature granulocyte (IG) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Here, our aim is to determine the effectiveness of IG and IRF percentages for the severity of acute bronchiolitis (AB). A single-center, prospective study was performed in patients who were hospitalized for acute bronchiolitis and healthy children were included as a control group. The demographic characteristics, white blood cell (WBC) count, platelet (PLT) count, eosinophil%, IG%, and IRF% values were analysed. Receiver operating characteristics (ROC) analysis was used to compare the diagnostic accuracies and predictive performances. We enrolled 168 infants in the acute bronchiolitis group and 80 in the control group. The Clinical Severity Score (CSS) showed that 48, 93, and 27 patients had mild, moderate, and severe bronchiolitis, respectively. The WBC, PLT, and IRF value were significantly higher in patients (p &lt; 0.001). There was no difference between the patients and control group in terms of IG and eosinophil percentage. Only a positive correlation was observed between the clinical severity of the AB and IRF (p=0.003).The ROC curve analysis indicated that the IRF% cut-off point for predicting severity AB was &gt;12.4, with a sensitivity of 53% and specificity of 88% (Areas under the curves (AUC):0.701,p&lt;0.001). The WBC count, PLT count, and IRF value increased in the AB group. The IRF percentage can be used to predict the clinical severity of AB in children.