Pathogen Spectrum and Lobar Distribution of Consolidation in Pediatric Post-Infectious Bronchiolitis Obliterans: A 10-Year Retrospective Study

Pathogen Spectrum and Lobar Distribution of Consolidation in Pediatric Post-Infectious Bronchiolitis Obliterans: A 10-Year Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pathogen Spectrum and Lobar Distribution of Consolidation in Pediatric Post-Infectious Bronchiolitis Obliterans: A 10-Year Retrospective Study Kuimiao Deng, Lin Lin, Jiemin Zeng, Wenyan Li, Kang Zhu, Gen Lu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8418588/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background Post-infectious bronchiolitis obliterans (PIBO) is a chronic pediatric airway disease characterized by fixed airflow limitation and recurrent infectious exacerbations. Empiric antibiotic treatment during exacerbations is often broad because rapid, actionable signals of bacterial etiology are limited. We investigated whether the lobar distribution of consolidation on high-resolution computed tomography (HRCT) is associated with bronchoalveolar lavage fluid (BALF) bacterial findings in children with established PIBO. Methods We retrospectively reviewed children with established PIBO hospitalized at Guangzhou Women and Children’s Medical Center (January 2015-June 2025) who developed HRCT-confirmed pulmonary consolidation during an acute infectious exacerbation and underwent bronchoscopy with BALF culture. Consolidation distribution by lobe was assessed independently by a pediatric radiologist and a respiratory physician blinded to microbiology, and patterns were compared between culture-positive and culture-negative episodes. Results Forty-seven children met inclusion criteria; 33 (70.2%) had positive BALF cultures. Haemophilus influenzae (39.4%), Staphylococcus aureus (27.3%), Streptococcus pneumoniae (24.2%), and Moraxella catarrhalis (21.2%) were the most frequent isolates. Middle and/or lower-lobe consolidation was more common in culture-positive than culture-negative episodes (93.9% vs 50.0%; OR 15.5, 95% CI 2.6–91.2), whereas upper-lobe consolidation was more frequent in culture-negative episodes (64.3% vs 24.2%; OR 5.6, 95% CI 1.5–21.8). S. aureus showed more diffuse lobar involvement, while other common pathogens predominantly involved the middle/lower lobes. Conclusions In pediatric PIBO exacerbations, lobar consolidation patterns on HRCT align with BALF bacterial findings and may help prioritize sampling and support more targeted empiric antibiotic choices and de-escalation within antimicrobial stewardship strategies. Post-infectious bronchiolitis obliterans Lobar consolidation Respiratory bacterial pathogens Bronchoalveolar lavage High-resolution computed tomography Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Bronchiolitis obliterans (BO) is a chronic and irreversible lung disease, with post-infectious bronchiolitis obliterans (PIBO) being the predominant form in children ( 1 ). It is usually caused by severe infection of respiratory pathogens, with adenovirus being the most common. PIBO is characterized by bronchiolar inflammation and fibrosis. These pathological changes lead to persistent airflow limitation and recurrent pulmonary consolidations, ultimately impairing lung function and reducing the quality of life in affected children ( 2 , 3 ). In clinical practice, patients with BO who develop pulmonary infections tend to have rapid and severe disease progression. Although significant advances have been made in pediatric respiratory care, PIBO remains a challenging condition. This is largely due to the limited understanding of its microbial spectrum when accompanied by bacterial infections, the heterogeneity of clinical manifestations, and the lack of effective treatment options ( 4 , 5 ). In patients with PIBO, bacterial pneumonia may further compromise lung function and exacerbate the disease ( 6 ). Rapid identification of the causative bacterial pathogen is essential for initiating targeted antibiotic therapy and preventing disease progression. Bronchoalveolar lavage fluid (BALF) culture remains a cornerstone of diagnosis, as it provides definitive evidence of microbial presence or infection in the lower respiratory tract ( 7 – 9 ). Nevertheless, the chronic course and clinical heterogeneity of PIBO make it particularly challenging to distinguish active infection from bacterial colonization or residual airway inflammation. This diagnostic complexity often leads to the adoption of empirical antibiotic strategies that may be either unnecessarily broad or insufficiently targeted ( 4 ). Previous studies have indicated that the lobar distribution of pulmonary consolidation on imaging may be associated with specific microbial etiologies or reflect distinct pathogenic mechanisms ( 10 , 11 ). However, there is currently a lack of clinical evidence specifically linking the lobar distribution of pulmonary consolidations to the pattern of bacterial pathogens in pediatric PIBO. In clinical practice, when PIBO is complicated by pulmonary consolidation, empirical antibiotic therapy is often not standardized. Clinicians frequently resort to higher-grade or broad-spectrum antibiotics due to concerns about the chronic course of PIBO and the risk of rapid clinical deterioration. The overuse of such antibiotics, however, is a growing global concern, as it contributes to the emergence of multidrug-resistant organisms ( 12 , 13 ). Therefore, rational antibiotic selection is especially critical in chronic pediatric lung diseases like PIBO. A better understanding of the association between consolidation patterns and pathogen distribution could help guide more targeted diagnostic and treatment decisions, reduce unnecessary use of advanced antibiotics, limit the development of resistance, and ultimately improve patient outcomes. Therefore, we hypothesized that distinct lobar consolidation patterns may be associated with specific bacterial pathogens, and that identifying these correlations can support more effective antibiotic stewardship in PIBO. To address these critical knowledge gaps, we conducted a rare and valuable 10-year retrospective study involving a cohort of pediatric PIBO cases collected over an extended period. This is the first study to systematically compare the lobar distribution of pulmonary consolidation on chest imaging with bacterial pathogen profiles identified from BALF cultures in this population. These data provide important evidence for guiding empirical antibiotic therapy and improving antimicrobial stewardship in pediatric respiratory care. Methods Study Design and Setting We performed a retrospective, single-center observational study at the Department of Pediatric Respiratory Medicine, Guangzhou Women and Children’s Medical Center, a tertiary care hospital in southern China, including patients managed from January 2015 to June 2025. This study was reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Study population, timing of investigations, and definitions PIBO was diagnosed by pediatric pulmonologists based on a history of severe lower respiratory tract infection followed by persistent respiratory symptoms and fixed airflow limitation, compatible HRCT features (e.g., mosaic attenuation/air trapping with or without bronchiectasis), and exclusion of alternative diagnoses, consistent with published workshop reports and national consensus recommendations ( 1 ). For the present analysis, we studied infectious exacerbation episodes occurring in children with an established PIBO diagnosis. An infectious exacerbation was defined as acute worsening of respiratory symptoms accompanied by new or worsening consolidation on HRCT and clinical suspicion of lower respiratory tract infection prompting antibiotic therapy and bronchoscopy at the treating team’s discretion. HRCT and bronchoscopy/BAL were performed during the same hospitalization; however, the exact HRCT-to-BAL interval was not uniformly captured in the retrospective records and therefore could not be analyzed as an effect modifier. Patient Selection and Enrollment The patient selection process is depicted in Fig. 1 . Between January 2015 and June 2025, a total of 668 hospitalized children with a diagnosis of PIBO at Guangzhou Women and Children’s Medical Center were screened for study eligibility. Of these, 606 patients were excluded due to the absence of pulmonary consolidation on radiological review by a senior pediatric radiologist. The remaining 62 patients with radiographically confirmed pulmonary consolidation occurring during the infectious acute phase of the disease were further assessed. Fifteen of these 62 patients were excluded because they did not undergo bronchoscopy. Additional exclusion criteria were primary immunodeficiency, congenital lung malformation, significant chronic pulmonary disease, incomplete medical records, or evidence of active pulmonary tuberculosis or fungal infection. After applying all inclusion and exclusion criteria, 47 eligible patients were included in the final analysis. All included patients met established clinical and radiological diagnostic criteria for PIBO and had available BALF culture results. These 47 patients were subsequently categorized into two groups based on their BALF culture results: 33 patients with positive cultures and 14 with negative cultures. Data Collection Demographic characteristics (age, sex), clinical information (symptom duration, presence of fever, prior antimicrobial use), and laboratory parameters—including white blood cell count (WBC), neutrophil percentage (NEU%), platelet count (PLT), C-reactive protein (CRP), and procalcitonin (PCT)—were retrospectively extracted from electronic medical records. Data on viral and Mycoplasma pneumoniae co-infection were obtained from polymerase chain reaction (PCR) assays or serological testing. Bronchoalveolar Lavage and Microbiological Analysis Flexible bronchoscopy was performed under sedation using standardized protocols. BAL fluid samples were collected from the most radiographically affected lung segment and transported promptly to the microbiology laboratory. For bacterial culture, blood agar and chocolate agar plates were used; for fungal culture, blood agar and Sabouraud agar plates were employed. Cultures were incubated at 35°C in aerobic conditions with 5% CO₂ for 24–48 hours for bacteria and 24 hours to 7 days for fungi. Growth exceeding 10⁴ CFU/mL was considered positive for lower respiratory tract pathogens. Because PIBO is a chronic airway disease in which airway colonization can occur, we interpreted BALF culture results as evidence of bacterial isolation rather than definitive causation. To reduce misclassification, we applied a quantitative threshold (> 10^4 CFU/mL), excluded samples containing ciliated epithelial cells, and considered concordant acute clinical and radiologic features when interpreting results. When two bacterial species each exceeded the quantitative threshold in the same BALF sample, the episode was classified as a bacterial co-infection. Microbial identification and antimicrobial susceptibility were performed using MALDI-TOF mass spectrometry, automated identification systems, and standard drug sensitivity testing (Kirby-Bauer disk diffusion or MIC), with manual confirmation when needed. Selected samples underwent targeted next-generation sequencing (tNGS) at external laboratories. To ensure sample quality, direct smears were examined for ciliated epithelial cells, and only specimens without these cells were analyzed. All procedures followed strict aseptic techniques. Detection of respiratory viruses and Mycoplasma pneumoniae was performed using PCR and/or serology according to the manufacturers’ instructions. Imaging Review and Definition of Consolidation All patients underwent high-resolution computed tomography (HRCT) of the chest. The distribution of pulmonary consolidation was independently evaluated by a senior pediatric radiologist and a respiratory physician experienced in flexible bronchoscopy, both blinded to clinical and microbiological information. Discrepancies were resolved by consensus. Lung lobes were categorized as upper, middle, or lower, and the presence, extent, and anatomical location of consolidation were systematically documented. Statistical Analysis All statistical analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as median and interquartile range (IQR) and compared using the Mann–Whitney U test. Categorical variables were presented as frequencies and percentages, with group comparisons performed using the Chi-square test or Fisher’s exact test, as appropriate. A two-sided p-value of < 0.05 was considered statistically significant. Use of AI tools We used ChatGPT (GPT-5, OpenAI, San Francisco, CA, USA) to assist in improving the clarity and readability of the manuscript text. The tool was not used for study design, data collection, data analysis, interpretation of results, or drawing scientific conclusions. All contents were reviewed and verified by the authors to ensure accuracy and integrity. Results A total of 47 pediatric patients diagnosed with PIBO were included in the study, comprising 33 cases with positive BALF cultures and 14 with negative cultures. The demographic characteristics, clinical features, treatment modalities, laboratory results, co-infection profiles, and imaging findings are summarized in Tables 1 and 2 . Table 1 Demographic, Clinical, and Treatment Comparison in Culture-Positive and Culture-Negative PIBO patients. Data are presented as n (%), mean ± SD, or median, as appropriate. Culture positive Culture negative p -value Number of patients ( n ) 33 14 - Ages (months) 32.26 35.69 - Male (%) 24(72.7%) 9(64.3%) 0.73 Premature birth , n (%) 1(3.0%) 3(21.4%) 0.07 Clinical manifestations Length of hospital stay (days) 16.92 16.03 - Cough 32(97.0%) 14(100.0%) 1 Fever (> 38.0℃) 8(24.2%) 10(71.4%) 0.004 ** Wheezing, n (%) 26(78.8%) 11(78.6%) 1 Tachypnoea, n (%) 23(69.7%) 11(78.6%) 0.73 Treatment ICU admission, n (%) 9(26.5%) 3(21.4%) 1 Use of glucocorticoids, n (%) 7(21.2%) 4(28.6%) 0.71 Use of immunoglbulin, n (%) 6(18.2%) 3(21.4%) 1 This table compares demographics, clinical features, and treatment characteristics between culture-positive and culture-negative episodes among children with PIBO. WBC, white blood cell count; CRP, C-reactive protein; PCT, procalcitonin; ICU, intensive care unit. Table 2 Laboratory, Co-infection, and Imaging Features in Culture-Positive and Culture-Negative PIBO patients. Culture positive Culture negative p -value Number of patients ( n ) 33 14 - Laboratory findings WBC(×10^9/L) 9.92 10 0.61 PLT(×10^9/L) 402 418 0.96 CRP, mg/L 1.14 8.17 0.21 PCT, µg/L 0.1 0.1 0.98 AST, U/L 38 32.5 0.32 ALT, U/L 16 17 0.1 LDH, U/L 303 290 0.88 Neutrophil proportion, % 51 53.5 0.63 Lymphocytes, proportion, % 38 32.5 0.64 Co-infection , n (%) 11(33.3%) 9(64.3%) 0.05 * Adenoviridae 4(12.1%) 3(21.4%) 0.41 Mycoplsma pneomoniae 0(0.0%) 3(21.4%) 0.02 * Other viruses 7(21.2%) 3(21.4%) 1 Imaging findings , n (%) Lung consolidation-Upper lobes 8(24.2%) 9(64.3) 0.02 * Lung consolidation-Middle or lower lobes 31(93.9%) 7(50.0%) 0.01 ** Atelectasis 8(24.2%) 3(21.4%) 1 Data are presented as n (%), mean ± SD, or median, as appropriate. WBC, white blood cell count; PLT, platelet count; CRP, C-reactive protein; PCT, procalcitonin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase. Demographic and Clinical Characteristics The two groups were comparable in terms of mean age (32.3 vs. 35.7 months) and sex distribution (male: 72.7% vs. 64.3%; p = 0.73). Although the incidence of premature birth was higher in the culture-negative group (21.4% vs. 3.0%), the difference did not reach statistical significance ( p = 0.07). There were no significant differences between groups regarding length of hospital stay, cough, wheezing, or tachypnea. However, the incidence of fever (> 38.0°C) was significantly lower in the culture-positive group than in the culture-negative group (24.2% vs. 71.4%; p = 0.004). Rates of ICU admission, glucocorticoid therapy, and immunoglobulin administration were similar between groups (Table 1 ). Laboratory Findings and Co-infection Profiles No statistically significant differences were observed in laboratory parameters, including white blood cell count, platelet count, C-reactive protein (CRP), procalcitonin (PCT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), or differential leukocyte counts. The overall rate of co-infection (bacterial or viral) was higher in the culture-negative group than in the culture-positive group (64.3% vs. 33.3%; p = 0.05). Importantly, Mycoplasma pneumoniae was identified exclusively in the culture-negative group (21.4% vs. 0%; p = 0.02). The prevalence of adenovirus infection did not differ significantly between groups (21.4% vs. 12.1%; p = 0.41), nor did the occurrence of other viral pathogens (Table 2 ). Imaging Findings Radiological assessment revealed that upper-lobe consolidation was more common in the culture-negative group than in the culture-positive group (64.3% vs 24.2%; OR 5.6, 95% CI 1.5–21.8; p = 0.02). Conversely, consolidation involving the middle and/or lower lobes predominated in the culture-positive group (93.9% vs 50.0%; OR 15.5, 95% CI 2.6–91.2; p = 0.01). The frequency of atelectasis was similar between groups (Table 2 ). Pathogen Spectrum in Culture-Positive Patients Of the 33 pediatric patients with positive bronchoalveolar lavage fluid (BALF) cultures, Haemophilus influenzae ( H. influenzae ) was the most commonly isolated pathogen, identified in 39.4% of cases. Staphylococcus aureus ( S. aureus ), and Streptococcus pneumoniae ( S. pneumoniae ) were detected in 27.3% and 24.2% of patients, respectively. Moraxella catarrhalis ( M. catarrhalis ) was present in 21.2% of cases. Infrequent isolates included Escherichia coli ( E. coli ) and Pseudomonas aeruginosa ( P. aeruginosa) , each accounting for 3.0% of the culture-positive cohort. The detailed distribution of pathogens is presented in Fig. 2 . Co-infections, defined as the isolation of two bacterial species from the same BALF sample, were identified in 18 patients (54.5% of the culture-positive cohort). The highest co-infection rate was observed in S. aureus cases (66.7%), most often with H. influenzae ( n = 3), M. catarrhalis ( n = 2), or P. aeruginosa ( n = 1). H. influenzae had a co-infection rate of 46.2%, predominantly with S. aureus ( n = 3), S. pneumoniae ( n = 2), or M. catarrhalis ( n = 1). Co-infection was less common in M. catarrhalis (42.9%) and S. pneumoniae (25%), and rare in other pathogens (50% of two isolates). No cases involved three or more bacterial species. The distribution of co-infecting pathogens is summarized in Table 3 . Table 3 Pathogen distribution and co-infection patterns in culture-positive PIBO. Pathogen ( n , %) Co-infection n (%) Common Co-pathogens S. aureus (9, 27.3%) 6(66.7%) H. influenzae ( n = 3), M. catarrhalis ( n = 2), P. aeruginosa ( n = 1) S. pneumoniae (8, 24.2%) 2(25%) H. influenzae ( n = 2) H. influenzae (13, 39.4%) 6(46.2%) S. aureus ( n = 3), S. pneumoniae ( n = 2), M. catarrhalis ( n = 1) M. catarrhalis (7, 21.2%) 3(42.9%) S. aureus ( n = 2), H. influenzae ( n = 1) Others (2, 6.1%)† 1(50%) S. aureus ( n = 1) † Others include Escherichia coli and Pseudomonas aeruginosa . Data are presented as n (%). Co-infection refers to the isolation of two distinct bacterial species from the same bronchoalveolar lavage fluid sample; no cases with ≥ 3 species were found. For each primary pathogen, common co-pathogens are listed from most to least frequent. S. aureus , Staphylococcus aureus ; S. pneumoniae, Streptococcus pneumoniae ; H. influenzae, Haemophilus influenzae ; M. catarrhalis, Moraxella catarrhalis , P. aeruginosa, Pseudomonas aeruginosa . Lobar Distribution of Pulmonary Consolidation According to BALF Culture Results As shown in Fig. 3 , the distribution of pulmonary consolidation differed markedly between culture-positive and culture-negative groups. In the culture-positive cohort, middle and lower lobe consolidations were predominant, observed in 81.8% and 75.8% of cases, respectively. In contrast, upper lobe consolidation was more frequently seen in the culture-negative group (64.3%) compared to the culture-positive group (24.2%, p = 0.02). The prevalence of middle or lower lobe involvement was significantly higher in the culture-positive group than in the culture-negative group (93.9% vs. 50.0%, p = 0.01). These findings suggest that the presence of consolidation in the middle and/or lower lobes is closely associated with positive BALF cultures, while upper lobe consolidation is more characteristic of culture-negative cases. Association Between Pathogen Type and Lobar Distribution of Consolidation Representative HRCT images illustrating typical patterns of lobar consolidation associated with different bacterial pathogens—as well as examples from culture-negative cases—are presented in Fig. 4 . These images demonstrate the spectrum of radiological manifestations observed in PIBO patients, including upper, middle, lower lobe, and multifocal consolidations. As shown in Fig. 5 , the lobar distribution of pulmonary consolidation varied by pathogen among culture-positive patients. Consolidations associated with S. aureus demonstrated a diffuse pattern, involving the upper, middle, and lower lobes in 42.4%, 42.4%, and 60.6% of cases, respectively. In contrast, consolidations due to S. pneumoniae and H. influenzae were more frequently localized to the lower lobes (63.6% and 69.7%, respectively), with middle lobe involvement in 33.4% and 39.4%, and relatively infrequent upper lobe involvement (12.3% and 15.1%). For M. catarrhalis , consolidation predominantly affected the lower (57.6%) and middle (44.4%) lobes, with minimal upper lobe involvement (14.3%). Notably, the few cases of E. coli and P. aeruginosa both exhibited consolidation exclusively in the middle lobe (100%). Collectively, these findings indicate that, while S. aureus infection tends to involve all lung regions, other common bacterial pathogens are more frequently associated with consolidation of the middle and lower lobes. Discussion Main findings and interpretation Our main observation is that the anatomical distribution of consolidation on HRCT was associated with BALF culture yield and pathogen profile in paediatric PIBO exacerbations. Middle- and/or lower-lobe consolidation coincided with culture positivity, whereas upper-lobe consolidation was more frequent when cultures were negative. In addition, co-infection (bacterial or viral) occurred more often in culture-negative episodes, and Mycoplasma pneumoniae appeared only in the culture-negative group. Read together, these signals suggest that in PIBO, where consolidation is located may carry clinically useful information about the likelihood of a bacterial aetiology and the expected pathogen spectrum, although prospective validation is needed before translating this association into decision tools. Pathogen spectrum and lobe-dependent patterns Among culture-positive episodes with consolidation, H. influenzae , S. aureus , and S. pneumoniae predominated. A lobe-dependent pattern was evident: H. influenzae and S. pneumoniae aligned more often with middle/lower-lobe disease, while S. aureus tended to be more diffuse. This distribution is biologically plausible. Dependent lung segments are preferentially affected by gravity, airway branching angles, regional ventilation–perfusion relationships, and mucus stasis—factors that can amplify bacterial burden in children with chronic small-airway injury and impaired mucociliary clearance, as in PIBO ( 14 – 18 ). Although our retrospective design limits causal inference, the repeated pairing of HRCT distribution with BALF-identified organisms lends clinical credibility to the signal and supports the concept of integrating imaging anatomy with microbiological evidence when characterising PIBO exacerbations. Culture-negative consolidation: beyond “no bacteria” Our findings also caution against equating culture negativity with the absence of infection. Culture yield is influenced by fastidious organisms, polymicrobial interactions, and critically prior antibiotic exposure. The higher frequency of co-infection and the exclusive detection of M. pneumoniae in culture-negative episodes are consistent with the notion that culture-based methods may miss atypical or partially treated infections, and that mixed bacterial–viral illness may present with consolidation but lower bacterial recoverability ( 19 – 22 ). Moreover, upper-lobe consolidation being common in culture-negative episodes may reflect a broader differential diagnosis in PIBO, including non-bacterial inflammatory activity, mucus plugging with atelectasis-like density, or aspiration-related patterns depending on positioning and clinical context ( 23 ). These considerations strengthen the argument for interpreting HRCT and BALF results together rather than in isolation, and for exercising antimicrobial restraint when culture-negative episodes lack additional indicators of bacterial infection. Clinical implications and antimicrobial stewardship At the bedside, combining lobe-specific HRCT with BALF results can help clinicians “set” pre-test probabilities, prioritise sampling, and support judicious empiric therapy rather than reflexive escalation to broad-spectrum antibiotics( 24 ). This approach is compatible with international and Chinese paediatric respiratory guidance regarding the roles of HRCT and bronchoscopy/BAL in complex diffuse lung disease and difficult to characterise infections ( 1 , 3 , 25 ). In paediatric CAP, major guidelines likewise emphasise targeted therapy and reassessment based on microbiology and clinical course, with opportunities for narrowing or discontinuation when bacterial infection is unlikely ( 17 ). In PIBO, where chronic airway injury and frequent antibiotic exposure may increase the risk of antimicrobial resistance, a stewardship-minded approach that combines targeted BALF sampling with early review of microbiology results and timely narrowing or de-escalation when findings are concordant may be particularly valuable, but requires prospective evaluation to confirm safety and clinical benefit ( 26 ). Explaining the higher proportion of Moraxella catarrhalis We observed a relatively higher proportion of M. catarrhalis (21.2%) than many prior series ( 15 , 27 – 32 ). Several non-mutually exclusive factors could contribute: regional epidemiology; outpatient prescribing patterns that select β-lactamase–producing organisms; vaccine-era ecological shifts affecting S. pneumoniae/H. influenzae niches; and differences in laboratory workflows. In addition, chronic airway colonisation in PIBO may blur the boundary between carriage and infection during acute worsening ( 33 , 34 ). Contemporary studies suggest that pneumococcal conjugate vaccine (PCV) programs can alter nasopharyngeal community dynamics and associations among common respiratory bacteria, including M. catarrhalis ( 35 , 36 ). These attributions remain provisional; multicentre longitudinal sampling—ideally integrating quantitative culture and molecular testing—will be required to distinguish colonisation from true infection more robustly and to map how local vaccine and antibiotic landscapes shape pathogen spectra in PIBO. Limitations and Implications This single-centre, retrospective study may over-represent severe or complex PIBO; several pathogen strata were small. Culture-based methods under-detect fastidious or mixed infections, and the cross-sectional sampling frame limits temporal inference. Prior antimicrobial exposure, which we captured, could depress culture yield or shift spectra. Targeting BALF to the most affected segment may bias detection toward the radiographically dominant lobe, and HRCT–bronchoscopy timing varied within clinical constraints, introducing a margin of misclassification. Even so, a pragmatic take-away emerges: in paediatric PIBO, middle/lower-lobe consolidation should prompt careful microbiological evaluation and thoughtful empiric narrowing/de-escalation when results agree with BALF, whereas isolated upper-lobe consolidation with negative cultures argues against unnecessary broad-spectrum therapy—subject to prospective confirmation ( 37 , 38 ). Future studies should validate these patterns in multicentre cohorts, incorporate molecular diagnostics to improve pathogen ascertainment, and link stewardship-guided empiric strategies to clinical endpoints such as time to defervescence, treatment failure, and adverse events. Declarations Clinical trial number: not applicable. Ethics approval and consent to participate The study was reviewed and approved by the Ethics Committee of Guangzhou Women and Children’s Medical Center (approval No. 批字[2025]第228A01). Given the retrospective study design and the use of anonymised (de-identified) data extracted from the hospital electronic medical record system, the requirement for informed consent to participate was waived by the Ethics Committee. The study was conducted in accordance with the principles of the Declaration of Helsinki. Conflict of interest All authors have nothing to disclose. Funding This work was supported by the Research Foundation of Guangzhou Women and Children’s Medical Center for Clinical Doctor (No. 2020BS005). The funder had no role in the study design; data collection, analysis, or interpretation; manuscript preparation; or the decision to submit for publication. Author Contribution Kuimiao Deng: investigation, writing – original draft, data curation, methodology, project administration, formal analysis, writing – review and editing. Lin Lin: conceptualization, writing –review and editing, methodology. Jiemin Zeng: writing – review and editing, conceptualization. Wenyan Li: writing – review and editing, conceptualization. Kang Zhu: writing – review and editing, conceptualization, data curation, investigation. Gen Lu: conceptualization, funding acquisition, methodology, supervision, resources, writing – review and editing, investigation. Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request. References Flanagan F, Casey A, Reyes-Múgica M, Kurland G. Post-infectious bronchiolitis obliterans in children. Paediatr Respir Rev. 2022;42:69–78. Mazenq J, Dubus J-C, Chanez P, Gras D. 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Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 Apr, 2026 Reviews received at journal 31 Mar, 2026 Reviewers agreed at journal 21 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviews received at journal 02 Mar, 2026 Reviewers agreed at journal 09 Feb, 2026 Reviewers invited by journal 06 Jan, 2026 Editor invited by journal 26 Dec, 2025 Editor assigned by journal 26 Dec, 2025 Submission checks completed at journal 26 Dec, 2025 First submitted to journal 21 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8418588","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":572042689,"identity":"f1ceb4ed-91bb-4264-849f-f33f472ccc47","order_by":0,"name":"Kuimiao Deng","email":"","orcid":"","institution":"Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kuimiao","middleName":"","lastName":"Deng","suffix":""},{"id":572042690,"identity":"6c76a53b-3c18-4a6c-a90a-931787b53996","order_by":1,"name":"Lin Lin","email":"","orcid":"","institution":"Guangzhou Women and 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09:10:02","extension":"html","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":127972,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/65910fc0fb4d421ceabe489b.html"},{"id":100124147,"identity":"58c2ef8f-db22-4842-879e-c85a103aa6db","added_by":"auto","created_at":"2026-01-13 09:10:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":325338,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient selection and classification according to BALF culture results. The diagram outlines the screening, inclusion, and exclusion process for children diagnosed with post-infectious bronchiolitis obliterans (PIBO) between January 2015 and June 2025. Patients meeting the clinical and radiological criteria for PIBO and with available BALF culture results were included; exclusion criteria are detailed in the Methods section.\u003c/p\u003e","description":"","filename":"Figure1.PatientSelectionFlowchart.png","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/c214d8745e96a9aefe03c1d4.png"},{"id":100366680,"identity":"80d986d3-f37a-4d53-9ef4-2b44c760d8bf","added_by":"auto","created_at":"2026-01-16 07:56:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":303149,"visible":true,"origin":"","legend":"\u003cp\u003eBacterial pathogen distribution in BALF cultures from pediatric PIBO patients (\u003cem\u003en\u003c/em\u003e = 33). The relative frequencies of culture-positive isolates are shown: \u003cem\u003eHaemophilus influenzae\u003c/em\u003e 39.4 %, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e 27.3 %, \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e 24.2 %, \u003cem\u003eMoraxella catarrhalis\u003c/em\u003e 21.2 %. Less common pathogens include \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, each at 3.0 %.\u003c/p\u003e","description":"","filename":"Figure2.BALFCulturePathogenDistribution.png","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/58806cb136ef3c99f4a6a207.png"},{"id":100124160,"identity":"521a6512-3d18-4d81-a78b-174d03ed1a0c","added_by":"auto","created_at":"2026-01-13 09:10:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":146429,"visible":true,"origin":"","legend":"\u003cp\u003eLobar distribution of pulmonary consolidation in pediatric PIBO according to BALF culture results. (A) Percentage of upper, middle, and lower lobe consolidation in culture-positive cases (\u003cem\u003en\u003c/em\u003e = 33). (B) Percentage of consolidation by lobe in the culture-negative group (\u003cem\u003en\u003c/em\u003e = 14). Middle and lower lobe involvement was more frequent in the culture-positive group, whereas upper lobe consolidation predominated in the culture-negative group.\u003c/p\u003e","description":"","filename":"Figure3.LobarConsolidationbyCulture.png","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/d428ae663056f8511576b2d9.png"},{"id":100124172,"identity":"4217f62f-5010-4644-89e3-00ef4ba4cead","added_by":"auto","created_at":"2026-01-13 09:10:06","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1941036,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative HRCT images of pulmonary consolidation in pediatric PIBO patients. (A) Upper lobe consolidation in a culture-negative case. (B) Middle lobe consolidation with \u003cem\u003eHaemophilus influenzae\u003c/em\u003e. (C) Lower lobe consolidation with \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e. (D) Multifocal consolidation with \u003cem\u003eStaphylococcus aureus\u003c/em\u003e. Black arrows indicate areas of consolidation.\u003c/p\u003e","description":"","filename":"Figure4.HRCTExamplesofConsolidation.png","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/956ce46707a9b335fd7641da.png"},{"id":100124145,"identity":"b4144272-4730-49d6-a4e4-36630ec834db","added_by":"auto","created_at":"2026-01-13 09:10:02","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003eLobar distribution of pulmonary consolidation by bacterial pathogen in pediatric PIBO (n = 33). (A) Staphylococcus aureus: Consolidation in upper, middle, and lower lobes. (B) Haemophilus influenzae: Predominantly middle and lower lobes. (C) Streptococcus pneumoniae: Mainly middle and lower lobes. (D) Moraxella catarrhalis: Most often middle and lower lobes. (E) Escherichia coli: Middle lobes. (F) Pseudomonas aeruginosa: Lower lobes.\t\u003c/p\u003e","description":"","filename":"Figure5.LobarConsolidationbyPathogens.png","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/223ff36ad06ac71092359c69.png"},{"id":100382094,"identity":"6c889ea5-646b-43c2-9053-250a537f59b3","added_by":"auto","created_at":"2026-01-16 10:40:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4006527,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8418588/v1/31bdfbf9-3ede-43ed-a59d-1b6e9aafd6a1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pathogen Spectrum and Lobar Distribution of Consolidation in Pediatric Post-Infectious Bronchiolitis Obliterans: A 10-Year Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBronchiolitis obliterans (BO) is a chronic and irreversible lung disease, with post-infectious bronchiolitis obliterans (PIBO) being the predominant form in children (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is usually caused by severe infection of respiratory pathogens, with adenovirus being the most common. PIBO is characterized by bronchiolar inflammation and fibrosis. These pathological changes lead to persistent airflow limitation and recurrent pulmonary consolidations, ultimately impairing lung function and reducing the quality of life in affected children (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In clinical practice, patients with BO who develop pulmonary infections tend to have rapid and severe disease progression. Although significant advances have been made in pediatric respiratory care, PIBO remains a challenging condition. This is largely due to the limited understanding of its microbial spectrum when accompanied by bacterial infections, the heterogeneity of clinical manifestations, and the lack of effective treatment options (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn patients with PIBO, bacterial pneumonia may further compromise lung function and exacerbate the disease (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Rapid identification of the causative bacterial pathogen is essential for initiating targeted antibiotic therapy and preventing disease progression. Bronchoalveolar lavage fluid (BALF) culture remains a cornerstone of diagnosis, as it provides definitive evidence of microbial presence or infection in the lower respiratory tract (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Nevertheless, the chronic course and clinical heterogeneity of PIBO make it particularly challenging to distinguish active infection from bacterial colonization or residual airway inflammation. This diagnostic complexity often leads to the adoption of empirical antibiotic strategies that may be either unnecessarily broad or insufficiently targeted (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePrevious studies have indicated that the lobar distribution of pulmonary consolidation on imaging may be associated with specific microbial etiologies or reflect distinct pathogenic mechanisms (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, there is currently a lack of clinical evidence specifically linking the lobar distribution of pulmonary consolidations to the pattern of bacterial pathogens in pediatric PIBO. In clinical practice, when PIBO is complicated by pulmonary consolidation, empirical antibiotic therapy is often not standardized. Clinicians frequently resort to higher-grade or broad-spectrum antibiotics due to concerns about the chronic course of PIBO and the risk of rapid clinical deterioration. The overuse of such antibiotics, however, is a growing global concern, as it contributes to the emergence of multidrug-resistant organisms (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Therefore, rational antibiotic selection is especially critical in chronic pediatric lung diseases like PIBO. A better understanding of the association between consolidation patterns and pathogen distribution could help guide more targeted diagnostic and treatment decisions, reduce unnecessary use of advanced antibiotics, limit the development of resistance, and ultimately improve patient outcomes.\u003c/p\u003e \u003cp\u003eTherefore, we hypothesized that distinct lobar consolidation patterns may be associated with specific bacterial pathogens, and that identifying these correlations can support more effective antibiotic stewardship in PIBO. To address these critical knowledge gaps, we conducted a rare and valuable 10-year retrospective study involving a cohort of pediatric PIBO cases collected over an extended period. This is the first study to systematically compare the lobar distribution of pulmonary consolidation on chest imaging with bacterial pathogen profiles identified from BALF cultures in this population. These data provide important evidence for guiding empirical antibiotic therapy and improving antimicrobial stewardship in pediatric respiratory care.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003e We performed a retrospective, single-center observational study at the Department of Pediatric Respiratory Medicine, Guangzhou Women and Children\u0026rsquo;s Medical Center, a tertiary care hospital in southern China, including patients managed from January 2015 to June 2025. This study was reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy population, timing of investigations, and definitions\u003c/h3\u003e\n\u003cp\u003ePIBO was diagnosed by pediatric pulmonologists based on a history of severe lower respiratory tract infection followed by persistent respiratory symptoms and fixed airflow limitation, compatible HRCT features (e.g., mosaic attenuation/air trapping with or without bronchiectasis), and exclusion of alternative diagnoses, consistent with published workshop reports and national consensus recommendations (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). For the present analysis, we studied infectious exacerbation episodes occurring in children with an established PIBO diagnosis. An infectious exacerbation was defined as acute worsening of respiratory symptoms accompanied by new or worsening consolidation on HRCT and clinical suspicion of lower respiratory tract infection prompting antibiotic therapy and bronchoscopy at the treating team\u0026rsquo;s discretion. HRCT and bronchoscopy/BAL were performed during the same hospitalization; however, the exact HRCT-to-BAL interval was not uniformly captured in the retrospective records and therefore could not be analyzed as an effect modifier.\u003c/p\u003e\n\u003ch3\u003ePatient Selection and Enrollment\u003c/h3\u003e\n\u003cp\u003eThe patient selection process is depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Between January 2015 and June 2025, a total of 668 hospitalized children with a diagnosis of PIBO at Guangzhou Women and Children\u0026rsquo;s Medical Center were screened for study eligibility. Of these, 606 patients were excluded due to the absence of pulmonary consolidation on radiological review by a senior pediatric radiologist. The remaining 62 patients with radiographically confirmed pulmonary consolidation occurring during the infectious acute phase of the disease were further assessed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFifteen of these 62 patients were excluded because they did not undergo bronchoscopy. Additional exclusion criteria were primary immunodeficiency, congenital lung malformation, significant chronic pulmonary disease, incomplete medical records, or evidence of active pulmonary tuberculosis or fungal infection. After applying all inclusion and exclusion criteria, 47 eligible patients were included in the final analysis.\u003c/p\u003e \u003cp\u003eAll included patients met established clinical and radiological diagnostic criteria for PIBO and had available BALF culture results. These 47 patients were subsequently categorized into two groups based on their BALF culture results: 33 patients with positive cultures and 14 with negative cultures.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eDemographic characteristics (age, sex), clinical information (symptom duration, presence of fever, prior antimicrobial use), and laboratory parameters\u0026mdash;including white blood cell count (WBC), neutrophil percentage (NEU%), platelet count (PLT), C-reactive protein (CRP), and procalcitonin (PCT)\u0026mdash;were retrospectively extracted from electronic medical records. Data on viral and \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e co-infection were obtained from polymerase chain reaction (PCR) assays or serological testing.\u003c/p\u003e\n\u003ch3\u003eBronchoalveolar Lavage and Microbiological Analysis\u003c/h3\u003e\n\u003cp\u003eFlexible bronchoscopy was performed under sedation using standardized protocols. BAL fluid samples were collected from the most radiographically affected lung segment and transported promptly to the microbiology laboratory.\u003c/p\u003e \u003cp\u003eFor bacterial culture, blood agar and chocolate agar plates were used; for fungal culture, blood agar and Sabouraud agar plates were employed. Cultures were incubated at 35\u0026deg;C in aerobic conditions with 5% CO₂ for 24\u0026ndash;48 hours for bacteria and 24 hours to 7 days for fungi. Growth exceeding 10⁴ CFU/mL was considered positive for lower respiratory tract pathogens.\u003c/p\u003e \u003cp\u003eBecause PIBO is a chronic airway disease in which airway colonization can occur, we interpreted BALF culture results as evidence of bacterial isolation rather than definitive causation. To reduce misclassification, we applied a quantitative threshold (\u0026gt;\u0026thinsp;10^4 CFU/mL), excluded samples containing ciliated epithelial cells, and considered concordant acute clinical and radiologic features when interpreting results. When two bacterial species each exceeded the quantitative threshold in the same BALF sample, the episode was classified as a bacterial co-infection.\u003c/p\u003e \u003cp\u003eMicrobial identification and antimicrobial susceptibility were performed using MALDI-TOF mass spectrometry, automated identification systems, and standard drug sensitivity testing (Kirby-Bauer disk diffusion or MIC), with manual confirmation when needed. Selected samples underwent targeted next-generation sequencing (tNGS) at external laboratories.\u003c/p\u003e \u003cp\u003eTo ensure sample quality, direct smears were examined for ciliated epithelial cells, and only specimens without these cells were analyzed. All procedures followed strict aseptic techniques. Detection of respiratory viruses and \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e was performed using PCR and/or serology according to the manufacturers\u0026rsquo; instructions.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eImaging Review and Definition of Consolidation\u003c/h2\u003e \u003cp\u003eAll patients underwent high-resolution computed tomography (HRCT) of the chest. The distribution of pulmonary consolidation was independently evaluated by a senior pediatric radiologist and a respiratory physician experienced in flexible bronchoscopy, both blinded to clinical and microbiological information. Discrepancies were resolved by consensus. Lung lobes were categorized as upper, middle, or lower, and the presence, extent, and anatomical location of consolidation were systematically documented.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as median and interquartile range (IQR) and compared using the Mann\u0026ndash;Whitney U test. Categorical variables were presented as frequencies and percentages, with group comparisons performed using the Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. A two-sided p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eUse of AI tools\u003c/h3\u003e\n\u003cp\u003eWe used ChatGPT (GPT-5, OpenAI, San Francisco, CA, USA) to assist in improving the clarity and readability of the manuscript text. The tool was not used for study design, data collection, data analysis, interpretation of results, or drawing scientific conclusions. All contents were reviewed and verified by the authors to ensure accuracy and integrity.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 47 pediatric patients diagnosed with PIBO were included in the study, comprising 33 cases with positive BALF cultures and 14 with negative cultures. The demographic characteristics, clinical features, treatment modalities, laboratory results, co-infection profiles, and imaging findings are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic, Clinical, and Treatment Comparison in Culture-Positive and Culture-Negative PIBO patients. \u003cb\u003eData are presented as n (%), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or median, as appropriate.\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCulture positive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCulture negative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of patients (\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAges (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(72.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePremature birth\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical manifestations\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(97.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever (\u0026gt;\u0026thinsp;38.0℃)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWheezing, \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(78.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(78.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTachypnoea, \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(69.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(78.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU admission, \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of glucocorticoids, \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of immunoglbulin, \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThis table compares demographics, clinical features, and treatment characteristics between culture-positive and culture-negative episodes among children with PIBO. WBC, white blood cell count; CRP, C-reactive protein; PCT, procalcitonin; ICU, intensive care unit.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory, Co-infection, and Imaging Features in Culture-Positive and Culture-Negative PIBO patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCulture positive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCulture negative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of patients (\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory findings\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC(\u0026times;10^9/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT(\u0026times;10^9/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCT, \u0026micro;g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST, U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT, U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH, U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil proportion, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes, proportion, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCo-infection\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenoviridae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycoplsma pneomoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther viruses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImaging findings\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung consolidation-Upper lobes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003csup\u003e\u003cb\u003e*\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung consolidation-Middle or lower lobes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(93.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003csup\u003e\u003cb\u003e**\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtelectasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eData are presented as n (%), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or median, as appropriate. WBC, white blood cell count; PLT, platelet count; CRP, C-reactive protein; PCT, procalcitonin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase.\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eThe two groups were comparable in terms of mean age (32.3 vs. 35.7 months) and sex distribution (male: 72.7% vs. 64.3%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.73). Although the incidence of premature birth was higher in the culture-negative group (21.4% vs. 3.0%), the difference did not reach statistical significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.07). There were no significant differences between groups regarding length of hospital stay, cough, wheezing, or tachypnea. However, the incidence of fever (\u0026gt;\u0026thinsp;38.0\u0026deg;C) was significantly lower in the culture-positive group than in the culture-negative group (24.2% vs. 71.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). Rates of ICU admission, glucocorticoid therapy, and immunoglobulin administration were similar between groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory Findings and Co-infection Profiles\u003c/h2\u003e \u003cp\u003eNo statistically significant differences were observed in laboratory parameters, including white blood cell count, platelet count, C-reactive protein (CRP), procalcitonin (PCT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), or differential leukocyte counts.\u003c/p\u003e \u003cp\u003eThe overall rate of co-infection (bacterial or viral) was higher in the culture-negative group than in the culture-positive group (64.3% vs. 33.3%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05). Importantly, \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e was identified exclusively in the culture-negative group (21.4% vs. 0%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). The prevalence of adenovirus infection did not differ significantly between groups (21.4% vs. 12.1%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.41), nor did the occurrence of other viral pathogens (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eImaging Findings\u003c/h2\u003e \u003cp\u003eRadiological assessment revealed that upper-lobe consolidation was more common in the culture-negative group than in the culture-positive group (64.3% vs 24.2%; OR 5.6, 95% CI 1.5\u0026ndash;21.8; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). Conversely, consolidation involving the middle and/or lower lobes predominated in the culture-positive group (93.9% vs 50.0%; OR 15.5, 95% CI 2.6\u0026ndash;91.2; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). The frequency of atelectasis was similar between groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePathogen Spectrum in Culture-Positive Patients\u003c/h2\u003e \u003cp\u003eOf the 33 pediatric patients with positive bronchoalveolar lavage fluid (BALF) cultures, \u003cem\u003eHaemophilus influenzae\u003c/em\u003e (\u003cem\u003eH. influenzae\u003c/em\u003e) was the most commonly isolated pathogen, identified in 39.4% of cases. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (\u003cem\u003eS. aureus\u003c/em\u003e), and \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e (\u003cem\u003eS. pneumoniae\u003c/em\u003e) were detected in 27.3% and 24.2% of patients, respectively. \u003cem\u003eMoraxella catarrhalis\u003c/em\u003e (\u003cem\u003eM. catarrhalis\u003c/em\u003e) was present in 21.2% of cases. Infrequent isolates included \u003cem\u003eEscherichia coli\u003c/em\u003e (\u003cem\u003eE. coli\u003c/em\u003e) and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (\u003cem\u003eP. aeruginosa)\u003c/em\u003e, each accounting for 3.0% of the culture-positive cohort. The detailed distribution of pathogens is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCo-infections, defined as the isolation of two bacterial species from the same BALF sample, were identified in 18 patients (54.5% of the culture-positive cohort). The highest co-infection rate was observed in \u003cem\u003eS. aureus\u003c/em\u003e cases (66.7%), most often with \u003cem\u003eH. influenzae\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3), \u003cem\u003eM. catarrhalis\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), or \u003cem\u003eP. aeruginosa\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1). \u003cem\u003eH. influenzae\u003c/em\u003e had a co-infection rate of 46.2%, predominantly with \u003cem\u003eS. aureus\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3), \u003cem\u003eS. pneumoniae\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), or \u003cem\u003eM. catarrhalis\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1). Co-infection was less common in \u003cem\u003eM. catarrhalis\u003c/em\u003e (42.9%) and \u003cem\u003eS. pneumoniae\u003c/em\u003e (25%), and rare in other pathogens (50% of two isolates). No cases involved three or more bacterial species. The distribution of co-infecting pathogens is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePathogen distribution and co-infection patterns in culture-positive PIBO.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathogen (\u003cem\u003en\u003c/em\u003e, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCo-infection \u003cem\u003en\u003c/em\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCommon Co-pathogens\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e (9, 27.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eH. influenzae\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3), \u003cem\u003eM. catarrhalis\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), \u003cem\u003eP. aeruginosa\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS. pneumoniae\u003c/em\u003e (8, 24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eH. influenzae\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eH. influenzae\u003c/em\u003e (13, 39.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3), \u003cem\u003eS. pneumoniae\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), \u003cem\u003eM. catarrhalis\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eM. catarrhalis\u003c/em\u003e (7, 21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), \u003cem\u003eH. influenzae\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers (2, 6.1%)\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u0026dagger; Others include \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eData are presented as n (%).\u003c/b\u003e Co-infection refers to the isolation of two distinct bacterial species from the same bronchoalveolar lavage fluid sample; no cases with \u0026ge;\u0026thinsp;3 species were found. For each primary pathogen, common co-pathogens are listed from most to least frequent. \u003cem\u003eS. aureus\u003c/em\u003e, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e; \u003cem\u003eS. pneumoniae, Streptococcus pneumoniae\u003c/em\u003e; \u003cem\u003eH. influenzae, Haemophilus influenzae\u003c/em\u003e; \u003cem\u003eM. catarrhalis, Moraxella catarrhalis\u003c/em\u003e, \u003cem\u003eP. aeruginosa, Pseudomonas aeruginosa\u003c/em\u003e.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLobar Distribution of Pulmonary Consolidation According to BALF Culture Results\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the distribution of pulmonary consolidation differed markedly between culture-positive and culture-negative groups. In the culture-positive cohort, middle and lower lobe consolidations were predominant, observed in 81.8% and 75.8% of cases, respectively. In contrast, upper lobe consolidation was more frequently seen in the culture-negative group (64.3%) compared to the culture-positive group (24.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). The prevalence of middle or lower lobe involvement was significantly higher in the culture-positive group than in the culture-negative group (93.9% vs. 50.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). These findings suggest that the presence of consolidation in the middle and/or lower lobes is closely associated with positive BALF cultures, while upper lobe consolidation is more characteristic of culture-negative cases.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eAssociation Between Pathogen Type and Lobar Distribution of Consolidation\u003c/h2\u003e \u003cp\u003eRepresentative HRCT images illustrating typical patterns of lobar consolidation associated with different bacterial pathogens\u0026mdash;as well as examples from culture-negative cases\u0026mdash;are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. These images demonstrate the spectrum of radiological manifestations observed in PIBO patients, including upper, middle, lower lobe, and multifocal consolidations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the lobar distribution of pulmonary consolidation varied by pathogen among culture-positive patients. Consolidations associated with \u003cem\u003eS. aureus\u003c/em\u003e demonstrated a diffuse pattern, involving the upper, middle, and lower lobes in 42.4%, 42.4%, and 60.6% of cases, respectively. In contrast, consolidations due to \u003cem\u003eS. pneumoniae\u003c/em\u003e and \u003cem\u003eH. influenzae\u003c/em\u003e were more frequently localized to the lower lobes (63.6% and 69.7%, respectively), with middle lobe involvement in 33.4% and 39.4%, and relatively infrequent upper lobe involvement (12.3% and 15.1%). For \u003cem\u003eM. catarrhalis\u003c/em\u003e, consolidation predominantly affected the lower (57.6%) and middle (44.4%) lobes, with minimal upper lobe involvement (14.3%). Notably, the few cases of \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eP. aeruginosa\u003c/em\u003e both exhibited consolidation exclusively in the middle lobe (100%). Collectively, these findings indicate that, while S. aureus infection tends to involve all lung regions, other common bacterial pathogens are more frequently associated with consolidation of the middle and lower lobes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eMain findings and interpretation\u003c/h2\u003e \u003cp\u003eOur main observation is that the anatomical distribution of consolidation on HRCT was associated with BALF culture yield and pathogen profile in paediatric PIBO exacerbations. Middle- and/or lower-lobe consolidation coincided with culture positivity, whereas upper-lobe consolidation was more frequent when cultures were negative. In addition, co-infection (bacterial or viral) occurred more often in culture-negative episodes, and \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e appeared only in the culture-negative group. Read together, these signals suggest that in PIBO, where consolidation is located may carry clinically useful information about the likelihood of a bacterial aetiology and the expected pathogen spectrum, although prospective validation is needed before translating this association into decision tools.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003ePathogen spectrum and lobe-dependent patterns\u003c/h2\u003e \u003cp\u003eAmong culture-positive episodes with consolidation, \u003cem\u003eH. influenzae\u003c/em\u003e, \u003cem\u003eS. aureus\u003c/em\u003e, and \u003cem\u003eS. pneumoniae\u003c/em\u003e predominated. A lobe-dependent pattern was evident: \u003cem\u003eH. influenzae\u003c/em\u003e and \u003cem\u003eS. pneumoniae\u003c/em\u003e aligned more often with middle/lower-lobe disease, while S. aureus tended to be more diffuse. This distribution is biologically plausible. Dependent lung segments are preferentially affected by gravity, airway branching angles, regional ventilation\u0026ndash;perfusion relationships, and mucus stasis\u0026mdash;factors that can amplify bacterial burden in children with chronic small-airway injury and impaired mucociliary clearance, as in PIBO (\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Although our retrospective design limits causal inference, the repeated pairing of HRCT distribution with BALF-identified organisms lends clinical credibility to the signal and supports the concept of integrating imaging anatomy with microbiological evidence when characterising PIBO exacerbations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eCulture-negative consolidation: beyond \u0026ldquo;no bacteria\u0026rdquo;\u003c/h2\u003e \u003cp\u003eOur findings also caution against equating culture negativity with the absence of infection. Culture yield is influenced by fastidious organisms, polymicrobial interactions, and critically prior antibiotic exposure. The higher frequency of co-infection and the exclusive detection of \u003cem\u003eM. pneumoniae\u003c/em\u003e in culture-negative episodes are consistent with the notion that culture-based methods may miss atypical or partially treated infections, and that mixed bacterial\u0026ndash;viral illness may present with consolidation but lower bacterial recoverability (\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Moreover, upper-lobe consolidation being common in culture-negative episodes may reflect a broader differential diagnosis in PIBO, including non-bacterial inflammatory activity, mucus plugging with atelectasis-like density, or aspiration-related patterns depending on positioning and clinical context (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These considerations strengthen the argument for interpreting HRCT and BALF results together rather than in isolation, and for exercising antimicrobial restraint when culture-negative episodes lack additional indicators of bacterial infection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eClinical implications and antimicrobial stewardship\u003c/h2\u003e \u003cp\u003eAt the bedside, combining lobe-specific HRCT with BALF results can help clinicians \u0026ldquo;set\u0026rdquo; pre-test probabilities, prioritise sampling, and support judicious empiric therapy rather than reflexive escalation to broad-spectrum antibiotics(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). This approach is compatible with international and Chinese paediatric respiratory guidance regarding the roles of HRCT and bronchoscopy/BAL in complex diffuse lung disease and difficult to characterise infections (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In paediatric CAP, major guidelines likewise emphasise targeted therapy and reassessment based on microbiology and clinical course, with opportunities for narrowing or discontinuation when bacterial infection is unlikely (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In PIBO, where chronic airway injury and frequent antibiotic exposure may increase the risk of antimicrobial resistance, a stewardship-minded approach that combines targeted BALF sampling with early review of microbiology results and timely narrowing or de-escalation when findings are concordant may be particularly valuable, but requires prospective evaluation to confirm safety and clinical benefit (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eExplaining the higher proportion of Moraxella catarrhalis\u003c/h2\u003e \u003cp\u003eWe observed a relatively higher proportion of \u003cem\u003eM. catarrhalis\u003c/em\u003e (21.2%) than many prior series (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28 CR29 CR30 CR31\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Several non-mutually exclusive factors could contribute: regional epidemiology; outpatient prescribing patterns that select β-lactamase\u0026ndash;producing organisms; vaccine-era ecological shifts affecting \u003cem\u003eS. pneumoniae/H. influenzae\u003c/em\u003e niches; and differences in laboratory workflows. In addition, chronic airway colonisation in PIBO may blur the boundary between carriage and infection during acute worsening (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Contemporary studies suggest that pneumococcal conjugate vaccine (PCV) programs can alter nasopharyngeal community dynamics and associations among common respiratory bacteria, including \u003cem\u003eM. catarrhalis\u003c/em\u003e (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). These attributions remain provisional; multicentre longitudinal sampling\u0026mdash;ideally integrating quantitative culture and molecular testing\u0026mdash;will be required to distinguish colonisation from true infection more robustly and to map how local vaccine and antibiotic landscapes shape pathogen spectra in PIBO.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and Implications\u003c/h2\u003e \u003cp\u003eThis single-centre, retrospective study may over-represent severe or complex PIBO; several pathogen strata were small. Culture-based methods under-detect fastidious or mixed infections, and the cross-sectional sampling frame limits temporal inference. Prior antimicrobial exposure, which we captured, could depress culture yield or shift spectra. Targeting BALF to the most affected segment may bias detection toward the radiographically dominant lobe, and HRCT\u0026ndash;bronchoscopy timing varied within clinical constraints, introducing a margin of misclassification. Even so, a pragmatic take-away emerges: in paediatric PIBO, middle/lower-lobe consolidation should prompt careful microbiological evaluation and thoughtful empiric narrowing/de-escalation when results agree with BALF, whereas isolated upper-lobe consolidation with negative cultures argues against unnecessary broad-spectrum therapy\u0026mdash;subject to prospective confirmation (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Future studies should validate these patterns in multicentre cohorts, incorporate molecular diagnostics to improve pathogen ascertainment, and link stewardship-guided empiric strategies to clinical endpoints such as time to defervescence, treatment failure, and adverse events.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e The study was reviewed and approved by the Ethics Committee of Guangzhou Women and Children\u0026rsquo;s Medical Center (approval No. 批字[2025]第228A01). Given the retrospective study design and the use of anonymised (de-identified) data extracted from the hospital electronic medical record system, the requirement for informed consent to participate was waived by the Ethics Committee. The study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflict of interest\u003c/strong\u003e \u003cp\u003eAll authors have nothing to disclose.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by the Research Foundation of Guangzhou Women and Children\u0026rsquo;s Medical Center for Clinical Doctor (No. 2020BS005). The funder had no role in the study design; data collection, analysis, or interpretation; manuscript preparation; or the decision to submit for publication.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKuimiao Deng: investigation, writing \u0026ndash; original draft, data curation, methodology, project administration, formal analysis, writing \u0026ndash; review and editing. Lin Lin: conceptualization, writing \u0026ndash;review and editing, methodology. Jiemin Zeng: writing \u0026ndash; review and editing, conceptualization. Wenyan Li: writing \u0026ndash; review and editing, conceptualization. Kang Zhu: writing \u0026ndash; review and editing, conceptualization, data curation, investigation. Gen Lu: conceptualization, funding acquisition, methodology, supervision, resources, writing \u0026ndash; review and editing, investigation.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFlanagan F, Casey A, Reyes-M\u0026uacute;gica M, Kurland G. Post-infectious bronchiolitis obliterans in children. Paediatr Respir Rev. 2022;42:69\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMazenq J, Dubus J-C, Chanez P, Gras D. 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Rev Mal Respir. 2025;42(3):148\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu D, Liu J, Zhang L, Chen Y, Zhang Q. Risk Factors for Post-infectious Bronchiolitis Obliterans in Children: A Systematic Review and Meta-Analysis. Front Pediatr. 2022;10:881908.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah SN, Bachur RG, Simel DL, Neuman MI. Does This Child Have Pneumonia? The Rational Clinical Examination Systematic Review. JAMA. 2017;318(5):462\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDas S, Dunbar S, Tang YW. Laboratory Diagnosis of Respiratory Tract Infections in Children - the State of the Art. Front Microbiol. 2018;9:2478.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Blic JF, - Midulla F, Midulla F, Fau - Barbato A, Barbato A, Fau - Clement A, Clement A, Fau - Dab I, Dab I, Fau - Eber E, Eber E, Fau - Green C, et al. Bronchoalveolar lavage in children. 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Healthc (Basel). 2023;11(13).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntimicrobial Resistance C. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Wang Y, Zheng Y, Zhao Y, Dai H, Li G, et al. Epidemiological Characteristics of Pathogens in Bronchoalveolar Lavage Fluid in Children With Lower Respiratory Tract Infections: A Retrospective Analysis. Pediatr Pulmonol. 2025;60:e27469. (1099\u0026thinsp;\u0026ndash;\u0026thinsp;0496 (Electronic)).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372(9):835\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma S, Maycher B, Eschun G. Radiological imaging in pneumonia: recent innovations. Curr Opin Pulm Med. 2007;13(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGharib AM, Stern EJ. RADIOLOGY OF PNEUMONIA. Med Clin. 2001;85(6):1461\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYazan H, Khalif F, Shadfaan LA, Bilgin S, Nursoy M, Cakir FB, et al. Post-infectious bronchiolitis obliterans in children: Clinical and radiological evaluation and long-term results. Heart Lung. 2021;50(5):660\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen IC, Hsu JS, Chen YW, Liu YC, Wu YH, Hsu JH, et al. Post-infectious Bronchiolitis Obliterans: HRCT, DECT, Pulmonary Scintigraphy Images, and Clinical Follow-up in Eight Children. Front Pediatr. 2020;8:622065.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, He L, Zhang G, Tian X, Wang H, Wang F, et al. Computed tomography-based radiomic features combined with clinical parameters for predicting post-infectious bronchiolitis obliterans in children with adenovirus pneumonia: a retrospective study. PeerJ. 2025;13:e19145.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, du Bois RM, et al. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med. 2012;185(9):1004\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuonsenso D, De Rose C, Morello R, Lazzareschi I, Valentini P. Aspiration pneumonia in children with neurological disorders: a new indication for lung ultrasound? A case series. J Ultrasound. 2022;25(2):325\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Antimicrobial Resistance C. The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis. Lancet Public Health. 2022;7(11):e897\u0026ndash;913.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAssociation TRGPSCM. Expert Consensus on Diagnosis and Treatment of Post-Infection Bronchial Occlusion in Children (2022 Edition). Chin J Practical Pediatr. 2022;37(2):81\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWan L, Wang Z. Postinfectious Bronchiolitis Obliterans in Children. Can Respir J. 2025;2025:7790381.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePneumonia Etiology Research for Child Health Study G. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet. 2019;394(10200):757\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Mollendorf C, Berger D, Gwee A, Duke T, Graham SM, Russell FM, et al. Aetiology of childhood pneumonia in low- and middle-income countries in the era of vaccination: a systematic review. J Glob Health. 2022;12:10009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Zhang F, Wang H, Zhao C, Wang Z, Cao B, et al. Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated from community-acquired respiratory tract infections in China: Results from the CARTIPS Antimicrobial Surveillance Program. J Global Antimicrob Resist. 2016;5:36\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu P, Xu M, He L, Su L, Wang A, Fu P, et al. Epidemiology of Respiratory Pathogens in Children with Lower Respiratory Tract Infections in Shanghai, China, from 2013 to 2015. Jpn J Infect Dis. 2018;71(1):39\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao C, Yang S, Zhang F, Wang Z, Zhang Y, Wang X, et al. Antimicrobial Resistance Trends of the Most Common Causative Pathogens Associated with Community-acquired Respiratory Infections in China: 2009\u0026ndash;2018. Infect Drug Resist. 2022;15:5069\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAi L, Zhou C, Liu B, Fang L, Gong F. Changes in the Antimicrobial Resistance and Bacterial Epidemiology of Moraxella catarrhalis from Pediatric Community-Acquired Pneumonia Patients During the COVID-19 Pandemic: A 5-Year Study at a Tertiary Hospital of Southwest China. Microb Drug Resist. 2024;30(10):415\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaur R, Pichichero M, Colonization. Density, and Antibiotic Resistance of Streptococcus pneumoniae, Haemophilus Influenzae, and Moraxella catarrhalis among PCV13-Vaccinated Infants in the First Six Months of Life in Rochester, New York: A Cohort Study. J Pediatr Infect Dis Soc. 2023;12(3):135\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKantar A, Chang AB, Shields MD, Marchant JM, Grimwood K, Grigg J et al. ERS statement on protracted bacterial bronchitis in children. Eur Respir J. 2017;50(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLittorin N, Runow E, Ahl J, Resman F, Riesbeck K. Decreased prevalence of Moraxella catarrhalis in addition to Streptococcus pneumoniae in children with upper respiratory tract infection after introduction of conjugated pneumococcal vaccine: a retrospective cohort study. Clin Microbiol Infect. 2021;27(4):630. e1- e6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBernhard S, Spaniol V, Aebi C. Molecular pathogenesis of infections caused by Moraxella catarrhalis in children. Swiss Med Wkly. 2012;142:w13694.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoussard P, Pohunek P, Eber E, Midulla F, Di Mattia G, Merven M, et al. Pediatric bronchoscopy: recent advances and clinical challenges. Expert Rev Respir Med. 2021;15(4):453\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, et al. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections. JAMA. 2017;318(23):2325\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Post-infectious bronchiolitis obliterans, Lobar consolidation, Respiratory bacterial pathogens, Bronchoalveolar lavage, High-resolution computed tomography","lastPublishedDoi":"10.21203/rs.3.rs-8418588/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8418588/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePost-infectious bronchiolitis obliterans (PIBO) is a chronic pediatric airway disease characterized by fixed airflow limitation and recurrent infectious exacerbations. Empiric antibiotic treatment during exacerbations is often broad because rapid, actionable signals of bacterial etiology are limited. We investigated whether the lobar distribution of consolidation on high-resolution computed tomography (HRCT) is associated with bronchoalveolar lavage fluid (BALF) bacterial findings in children with established PIBO.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We retrospectively reviewed children with established PIBO hospitalized at Guangzhou Women and Children\u0026rsquo;s Medical Center (January 2015-June 2025) who developed HRCT-confirmed pulmonary consolidation during an acute infectious exacerbation and underwent bronchoscopy with BALF culture. Consolidation distribution by lobe was assessed independently by a pediatric radiologist and a respiratory physician blinded to microbiology, and patterns were compared between culture-positive and culture-negative episodes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eForty-seven children met inclusion criteria; 33 (70.2%) had positive BALF cultures. Haemophilus influenzae (39.4%), Staphylococcus aureus (27.3%), Streptococcus pneumoniae (24.2%), and Moraxella catarrhalis (21.2%) were the most frequent isolates. Middle and/or lower-lobe consolidation was more common in culture-positive than culture-negative episodes (93.9% vs 50.0%; OR 15.5, 95% CI 2.6\u0026ndash;91.2), whereas upper-lobe consolidation was more frequent in culture-negative episodes (64.3% vs 24.2%; OR 5.6, 95% CI 1.5\u0026ndash;21.8). S. aureus showed more diffuse lobar involvement, while other common pathogens predominantly involved the middle/lower lobes.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn pediatric PIBO exacerbations, lobar consolidation patterns on HRCT align with BALF bacterial findings and may help prioritize sampling and support more targeted empiric antibiotic choices and de-escalation within antimicrobial stewardship strategies.\u003c/p\u003e","manuscriptTitle":"Pathogen Spectrum and Lobar Distribution of Consolidation in Pediatric Post-Infectious Bronchiolitis Obliterans: A 10-Year Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-13 09:09:32","doi":"10.21203/rs.3.rs-8418588/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-01T09:05:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-31T15:04:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116670782654286466647607738787247422779","date":"2026-03-21T09:01:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321671390186346219890598052614268305156","date":"2026-03-18T17:17:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-02T19:19:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99857898463089048018879542103693281357","date":"2026-02-09T15:04:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-06T12:10:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-26T14:51:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-26T07:44:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-26T07:44:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-12-21T16:24:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"be1eb4ba-c752-4a47-8afa-00912e0a9c49","owner":[],"postedDate":"January 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-05T04:38:54+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-13 09:09:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8418588","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8418588","identity":"rs-8418588","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}