Bronchoscopic findings in preschoolers with refractory respiratory symptoms: Analysis of bacterial colonization and comorbidities

Bronchoscopic findings in preschoolers with refractory respiratory symptoms: Analysis of bacterial colonization and comorbidities | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 27 March 2025 V1 Latest version Share on Bronchoscopic findings in preschoolers with refractory respiratory symptoms: Analysis of bacterial colonization and comorbidities Authors : H. Donath , J. Ruff , L. Heumüller , O. Eickmeier , Dressler M , RSchubert , K. Blumchen , Johannes Schulze , Stefan Zielen , and J. Trischler [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174306276.62692678/v1 253 views 175 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Preschool children with refractory respiratory symptoms often undergo diagnostic bronchoscopy. The objective of this retrospective analysis was to analyze BAL fluid findings regarding bacterial colonization, cytology and following treatment changes. Moreover, we aimed to correlate bacterial colonization of the airways to allergic sensitization status, asthma severity, vaccination titers and comorbidities like gastroesophageal reflux disease (GERD) or eosinophilic esophagitis (EoE). Methods: In a retrospective analysis, the electronic medical records of 355 children aged 1 to 5 years between 2010 and 2019 who underwent bronchoscopy and further diagnostic testing for persistent respiratory symptoms were analyzed. Results: In 214 children (61.7%) a bacterium was found by culture in the BAL fluid. Of these, 105 (49%) received antibiotic treatment. The most common bacteria were Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis (34%, 25% and 16%). There was a significant difference between neutrophil counts in bacteria positive vs. bacteria negative BAL (29.2 + 28.1 % vs. 21.2 + 25.4 %, p=0.02). Children lacking sufficient S. pneumoniae antibodies had significantly more often positive S. pneumoniae cultures in BAL (28.3% vs. 12.8%; p=0.0024). GERD was detected in a total of 115 children (32%) and 9 (2.8%) were diagnosed with EoE Conclusion: Bronchoscopy is a valuable diagnostic tool in persistent respiratory symptoms in preschoolers. Bacterial colonization of the airways is common and airway neutrophils were significantly higher in colonized airways. In many bronchoscopies, results were obtained that led to a change in therapy. Moreover, testing for adequate pneumococcal titers is reasonable in children with persistent respiratory symptoms. Bronchoscopic findings in preschoolers with refractory respiratory symptoms: Analysis of bacterial colonization and comorbidities H. Donath1, J. Ruff1, L. Heumüller1, O. Eickmeier1, M Dressler1, R.Schubert1, K. Blumchen1, J. Schulze1, S. Zielen 1,2, J. Trischler1 1 Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, University Hospital Frankfurt, Goethe University Frankfurt Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany 2 Respiratory Research Institute, Medaimun GmbH, 60596 Frankfurt am Main, Germany Corresponding author: Dr. Jordis Trischler Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology University Hospital Frankfurt Goethe University Frankfurt Theodor-Stern-Kai 7 60590 Frankfurt am Main, Germany E-Mail: [email protected] Other authors: Dr. Helena Donath, E-Mail: [email protected] Julius Ruff: E-Mail: [email protected] Laura Heumüller, E-Mail: l.heumü [email protected] Dr. Olaf Eickmeier, E-Mail: [email protected] Dr. Melanie Dressler: E-Mail: [email protected] Prof. Ralf Schubert: E-Mail: [email protected] Prof. Dr. med. S. Zielen, E-mail: [email protected] Prof. Dr. med. J. Schulze, E-mail: [email protected] PD Dr. med. K. Blümchen, E-mail: [email protected] Abstract Background: Preschool children with refractory respiratory symptoms often undergo diagnostic bronchoscopy. The objective of this retrospective analysis was to analyze BAL fluid findings regarding bacterial colonization, cytology and following treatment changes. Moreover, we aimed to correlate bacterial colonization of the airways to allergic sensitization status, asthma severity, vaccination titers and comorbidities like gastroesophageal reflux disease (GERD) or eosinophilic esophagitis (EoE). Methods: In a retrospective analysis, the electronic medical records of 355 children aged 1 to 5 years between 2010 and 2019 who underwent bronchoscopy and further diagnostic testing for persistent respiratory symptoms were analyzed.Results: In 214 children (61.7%) a bacterium was found by culture in the BAL fluid. Of these, 105 (49%) received antibiotic treatment. The most common bacteria were Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis (34%, 25% and 16%). There was a significant difference between neutrophil counts in bacteria positive vs. bacteria negative BAL (29.2 + 28.1 % vs. 21.2 + 25.4 %, p=0.02). Children lacking sufficient S. pneumoniae antibodies had significantly more often positive S. pneumoniae cultures in BAL (28.3% vs. 12.8%; p=0.0024). GERD was detected in a total of 115 children (32%) and 9 (2.8%) were diagnosed with EoEConclusion: Bronchoscopy is a valuable diagnostic tool in persistent respiratory symptoms in preschoolers. Bacterial colonization of the airways is common and airway neutrophils were significantly higher in colonized airways. In many bronchoscopies, results were obtained that led to a change in therapy. Moreover, testing for adequate pneumococcal titers is reasonable in children with persistent respiratory symptoms. INTRODUCTION Most preschool children with chronic or recurrent bronchitis are successfully treated for preschool wheeze with inhaled bronchodilators and inhaled corticosteroids (ICS) [1]. However, there is a subgroup of children who have recurrent or persistent, severe respiratory symptoms that are therapy refractory [2, 3]. These symptoms can range from obstructive episodes to recurrent pneumonias and wet cough, such as protracted bacterial bronchitis (PBB), with a high rate of overlap [4]. According to current guidelines, these children are treated with courses of antibiotics and/or ICS [5, 6, 7]. If treatment is not successful and respiratory symptoms persist, these children often undergo bronchoscopy for diagnostic purposes. The aim is to improve treatment by detecting bacteria and viruses in bronchoalveolar lavage (BAL) fluid and to exclude rare causes of these refractory symptoms, like anatomical and functional abnormalities (e.g. trachea- and bronchomalacia, -stenosis). Additionally, by combining gastroscopy, alternate or aggravating causes for these symptoms, like gastroesophageal reflux disease (GERD) or eosinophilic esophagitis (EoE) can be assessed. There is growing evidence that children who exhibit severe persistent preschool wheeze have increased bacterial colonization [8, 9] and altered colonization profiles in BAL fluid [10]. In a recent study, children with recurrent severe wheeze and allergic sensitization had a higher percentage of Moraxella (M.) catarrhalis detection [10]. Earlier retrospective studies in children with recurrent wheeze could detect Haemophilus influenzae, M. catarrhalis and Streptococcus pneumoniae [8, 9]. In the sequence of the etiopathogenesis, colonization occurs first, with bacteria being present and multiplying without causing symptoms. Infection can follow when bacterial growth, combined with impaired defenses, leads to inflammation and clinical illness [11]. However, it is unclear if bacterial colonization in wheezing preschool children leads to infection, is a mere indicator of immunological processes that increase susceptibility to wheezing, or maybe even predicts asthma diagnosis later in life [12]. Therefore, the objective of this retrospective analysis of diagnostic bronchoscopies in preschool children with persistent respiratory symptoms was to analyze BAL fluid findings regarding bacterial colonization and cytology, and the following treatment changes. Moreover, we aimed to correlate bacterial colonization of the airways to allergic sensitization status, asthma severity, vaccination titers and comorbidities like GERD and EoE. MATERIAL AND METHODS Patients and demographics The present study was a retrospective cohort analysis of electronic patient records from a period of ten years (01.01.2010-31.12.2019) at the Department of Pediatrics, Division of Pneumology, Allergology, Infectious Diseases and Gastroenterology, University Hospital Frankfurt (Ethic commission reference number: 2022-763). All patients aged 1-5 years who underwent inpatient bronchoscopy for chronic or refractory respiratory disease (wheeze, cough, wet cough, recurrent pneumonia) were included. For the analysis, cases who underwent bronchoscopy due to foreign body aspiration, intensive care/intubation or known chronic pulmonary conditions such as cystic fibrosis, bronchopulmonary dysplasia, bronchiolitis obliterans, immunodeficiency, etc. were excluded. We also did not include children younger than one year due to the higher prevalence of airway anomalies in this group. Cases were taken from the patient software ORBIS (Dedalus Healthcare GmbH, Bonn, Germany) when the procedural code for bronchoscopy was available. Additional clinical data were added via the program Medistar (CompuGroup Medical Deutschland AG, Koblenz, Germany). Age, sex, length of stay, symptoms and medications (antibiotics, PPI and asthma medication) before and after bronchoscopy were taken from medical history. Asthma medication was grouped according to global initiative for asthma (GINA) guideline into steps 1-5 [7] and separated into groups for definition of asthma severity, with GINA steps 4 and 5 marking the most severe asthmatics. Laboratory parameters and allergic sensitization The following laboratory parameters were recorded: c-reactive protein (CRP), eosinophil granulocytes, immunoglobulin G (IgG) and its subclasses, pneumococcal antibody titers. Eosinophil granulocytes (blood) were considered pathological at values > 300/µl. High vaccination protection against pneumococcus was defined as detection of titers >1.0 μg/mL against at least three out of four serotypes (PNC6B, 7F, 19F, 23F) in enzyme-linked immunosorbent assay (ELISA) [13]. Allergic sensitization was either documented as skin prick test (SPT) and/or specific immunoglobulin E (sIgE) against birch, grass, house dust mite, chicken egg protein, and cat). Sensitization was defined as positive reaction in SPT (defined by wheal size > 3mm) and/or detection of sIgE (defined as > 0.35 kU/L). Bronchoalveolar lavage (differential cytology, virology and microbiology) Differential cell counts on BAL were recorded and percentage of neutrophil granulocytes in BAL fluid > 20% were defined as pathological. Bacterial detection was performed by culture based testing of BAL fluid with detection of any bacteria was considered positive (detection cut-off > 10³ CFU/mL). Virus detection was done by polymerase chain reaction (PCR) with cycle threshold (CT) < 30 considered as positive. Gastroscopy, pH monitoring and esophageal biopsies Gastroscopic findings were categorized into macroscopic esophagitis according to visual classification and microscopic esophagitis according to the pathological findings of biopsies from the esophagus. Reflux in pH monitoring was divided into the following three categories: pH monitoring was considered pathological if the reflux index (percentage of time with pH 5%. pH monitoring was considered as borderline with reflux index < 5%, but pathological DeMeester score or positive correlation with symptoms. pH monitoring was considered negative in case of reflux index < 5% and absence of symptoms. [14] GERD was defined as pathological pH monitoring or borderline pH monitoring and macroscopic and/or microscopic esophagitis. Eosinophilic esophagitis was defined as more 15 Eosinophils/high power field (HPF) as by international guidelines [15] Statistical analysis For this retrospective study GraphPad Prism Version 10 (GraphPad Software Inc., La Jolla, CA, USA) was used for statistical analyses. Data is presented as mean and standard deviation (SD) or as median and range respectively, according to the Kolmogorov-Smirnov test for normal distribution. Inter-group comparisons were calculated by unpaired t-test or Mann-Whitney test. P<0.05 was considered as statistically significant. Statistical analysis on categorial values were only performed on ordinal data that were treated as ranks (ordinal data) and therefore Mann-Whitney test was performed. Patient characteristics A total of 355 patients were included in this retrospective study. The flowchart with regard to the patient selection is shown in Fig. 1. 213 (60%) were boys and 142 (40%) were girls. The median age at admission was 32 months. The median length of stay was 3 days. Blood eosinophil count was obtained in 343 patients (96.6%). A pathological value > 300/µl was present in 128/343 (37.3%) of patients. Allergy testing was performed in 254 patients (71.5%) by sIgE and 311 patients (87.6%) by SPT. Sensitization was detected in 78 patients (22%) by SPT or sIgE. Total IgE was significantly higher in the group with high sensitization than in the group without sensitization (84 U/mL (IQR 45.5 -169.25 U/mL) vs. 21 U/mL (IQR 7 -55 U/mL), p<0.0001, Mann-Whitney U). Patients with sensitization (SPT or sIgE) had an median eosinophil count of 260/µl (IQR 158 -460/µl), patients without sensitization 210/µl (IQR 133 -390/µl) (p=0.147). Pneumococcal antibodies were determined in 254 patients (71.5%), of whom 141 (55.5%) had sufficient vaccination protection. Overview of patient characteristics is shown in table 1. BAL findings, antibiotic and asthmatic treatment 347 cultures of BAL fluid were performed. Of these, 133 (38.3 %) remained without bacterial growth, a bacterium was detected in 214 (61.7%). The distribution of the detected bacteria is shown in Fig. 2A. H. influenzae was the most common bacterium in 34% (n=98) of children, followed by S. pneumoniae (25%, n=70) and M. catarrhalis (16%, n=46). Eosinophils were not elevated in case of detection of M. catarrhalis (240/µl (IQR 150 -340/µL) vs. 240/µl (IQR 140 -430/µL), p=0.43). Of all positive cultures for M. catarrhalis, it was detected in 37/46 (80.4%) of children receiving asthma therapy at GINA steps 4 and 5. Among patients with sufficiently high antibodies against S. pneumoniae, S. pneumoniae grew in 18 (12.8%) of the BAL fluid-culture based sterility tests whereas S. pneumoniae was detected in 32 patients without vaccination protection (28.3%) (p=0.0024, Mann-Whitney U). No protection against pneumococcal antigen was present in 31.8% (n=113) of the cohort. A total of 146 (41.1%) patients received antibiotic treatment after bronchoscopy. This contains the 105 with bacterial detection but also 41 of the 133 children with no bacterial detection. The mean length of stay of antibiotic-treated patients was 3.58 days, for the majority, antibiotic treatment was continued orally after their stay. In 71.9% of antibiotic-treated patients (n=105), bacteria were detected in the BAL fluid. The most common antibiotics prescribed after bronchoscopy were beta-lactam antibiotics (87%). Before bronchoscopy, 124 (34.9%) patients were treated with antibiotics. The most prescribed antibiotic was azithromycin in 101 (81,5%) cases. Bacteria were still detected in the BAL fluid of n=71/124 (57.3%) pretreated patients. Figure 2B shows the distribution of antibiotic therapy after bronchoscopy. A total of 300 patients (84.5%) received asthma therapy before bronchoscopy (GINA step 1: n=11, step 2+3 n= 75, step 4+5 n= 214). After bronchoscopy, 328 (92.4%) received asthma therapy (GINA step 1: n=2, step 2+3 n= 70, step 4+5 n= 256). 256 patients had asthma therapy step 4 or more according to GINA guidelines. Of these patients, 37 (14%) had M. catarrhalis and 6 (2.3%) rhinovirus in BAL fluid, whereas 4 (1.6%) had both. A total of 215/355 samples (60.5%) were examined by virus PCR. 181 (84.2%) were negative, in 34 (18.8%) a virus was detected. The distribution is shown in Fig. 2C. The most frequently detected virus was adenovirus with 65% (n=24). Airway neutrophil count was available from 248/ 347 patients (71.5%) (151 (60.9%) with bacterial detection, 97 (39.1%) without bacterial detection). There was a significant difference between airway neutrophil counts in bacteria positive vs. bacteria negative BAL fluid (Fig. 3, (18 % (IQR 3,5 -51%) vs. 9 % (IQR 2 -34 %), p=0.023). Neutrophilic airway inflammation (>20% neutrophils in the BAL fluid) was not indicative of the type of bacteria detected. No difference between peripheral eosinophil and leucocyte counts in patients with neutrophilic airway inflammation was observed. GERD, EoE and PPI therapy In 229/355 of patients (64.5 %) pH monitorings were performed. Sixty-nine (30.1%) exhibited pathological findings, 57 (24.9%) were borderline pathological, and 103 (45 %) had negative results. Patients with pathological pH monitoring had confirmatory positive histology in 52.2% and exhibited an abnormal macroscopic finding in 59.4%. Of the patients with borderline pH monitoring, the biopsy showed histologically abnormal results in 47.4% and pathological macroscopic findings in 64.9%. In 45.6% of the negative pH monitoring, the microscopic and macroscopic findings were considered positive. PPI therapy was given to 91.3%, 70.2%, and 48.6% of patients with pathological, borderline, and normal pH monitoring, respectively. In total a biopsy during their gastroscopy was taken at 324 patients. Of these 9 (2.8%) patients suffered from histologically confirmed eosinophilic esophagitis (EoE). Prior to endoscopy, all EoE patients had asthma therapy (n=2 with GINA stage 2+3, n=7 with GINA stage 4+5). Bronchoscopy revealed a bacterium in 5 patients, pH monitoring was pathological in 5/9 EoE patients. After endoscopy, 7/9 patients (77.8%) were treated with PPI, none was pre-treated with PPI. Allergic sensitization was present in three EoE patients. Laboratory chemistry showed a median peripheral eosinophil count at 0.93/nL (IQR 0.59 – 1.15/nL) and an increased IgE of 55 kU/L (IQR: 30 – 83 kU/L). DISCUSSION In the present study, bacterial colonization of the airways was detected in approximately 60% of BAL fluids. This finding is relevant, as the BAL fluids were not collected from children with acute pulmonary infections but from preschool children with recurrent respiratory symptoms. The increasing importance of the airway colonization in the pathogenesis of cough and asthma is reflected in several studies that have shown an association between the colonization of the lower airways with pathogens such as M. catarrhalis, H. influenzae, or S. pneumoniae in children and disease severity [8, 9]. Therefore, the large cohort of preschool children presented here adds to existing data and challenges treating physicians to rethink antibiotic treatment in these cases. Only few studies of bacterial cultures from BAL of healthy children have been published, with varying results, generally showing less bacterial growth and different species [16, 8]. Due to ethical reasons, BAL in completely healthy children is rare, and children often undergo bronchoscopy for different indications. The spectrum of pathogens in the presented cohort was mainly consistent with the current literature, with H. influenzae, S. pneumoniae, and M. catarrhalis being the most common. A recent study by Robinson et al. has proposed a characterization of wheeze endotypes in a prospective workup of bronchoscopies [10]. This group has singled out M. catarrhalis as a risk factor for severe courses in preschool wheeze. This hypothesis is supported by researchers who have demonstrated a possible co-infection with M. catarrhalis and H. influenzae during severe respiratory syncytial virus (RSV) infection in the first six months of life as a risk factor for subsequent preschool asthma [17]. In the present cohort of preschool children, the majority had asthma therapy. However, there was no specific endotype as defined by blood eosinophilia that was associated with an obvious pattern of colonization. Yet, M. catarrhalis detection was more likely in preschool wheeze with high asthma therapy intensity (GINA step 4 and 5), indicating more severe asthma. We demonstrated that S. pneumoniae was detected significantly more often in the lower airways of children who had low pneumococcal vaccination titers, meaning they were either not vaccinated or did not respond adequately. Increased pneumococcal carriage in the nasopharynx of asthmatic children has been demonstrated before, but a correlation with vaccination status has not been shown so far [8]. This supports the protective effect of a vaccination also against colonization, and the presented results may indicate that risk groups in particular might potentially benefit from an additional booster vaccine. This has been suggested in a recent study, which demonstrated that a booster vaccine was able to reduce exacerbations in asthmatic preschool children who did not have sufficient vaccination titers [19]. Similar to previous studies, we also demonstrated that positive bacterial BAL fluid cultures are associated with airway neutrophilia [8, 9]. Neutrophilic inflammation is a risk factor for the development of bronchiectasis [20]. In addition, airway neutrophilia is found more frequently in patients with refractory asthma [8, 9]. Before bronchoscopy, 84.5% of children were already receiving asthma therapy. After bronchoscopy, this proportion increased to 92.4%. In particular, the proportion of patients receiving therapy according to GINA Guidelines steps 4 and 5 increased. This increase is most likely due to the patients who did not have alternating or aggravating findings on bronchoscopy and gastroscopy that would lead to alternative therapies. In the current study, 34.9% of children with chronic symptoms received antibiotic therapy before bronchoscopy. However, despite antibiotic pre-therapy, a bacterium was detected in 57.3% of pretreated patients. The most frequently prescribed antibiotic was azithromycin. Although this is not in accordance with most guidelines for PBB [6], it is still common practice in pediatric pulmonology despite ongoing efforts by antibiotic stewardship programs. Apart from its microbial effect, azithromycin also has anti-inflammatory properties, and few studies showed a positive effect on infection-triggered wheeze in preschoolers [21]. Nevertheless, this must be critically evaluated considering the increased incidence of macrolide resistance in common respiratory pathogens. Moreover, in light of the presented microbiological findings, azithromycin does not seem to be the right antimicrobial agent. GERD is known to have a higher prevalence in children with persistent asthma [22]. Overall, though, the incidence of GERD seems to decrease during infancy [23]. Typical symptoms can be absent, and the diagnosis is therefore challenging. The current diagnostic recommendation is esophageal multichannel intraluminal impedance testing [24]. Nevertheless, pH monitoring, as well as histological examination of biopsies are still a diagnostic pillar [24]. While in the present study only 32.4% were found to have GERD on pH monitoring and/or biopsy, 60.6% received PPI therapy based on macroscopic impression after bronchoscopy. In infancy there is little to no evidence about when and how to treat [25]. The only consensus is that PPI should be used critically in this vulnerable age group, as side effects are considerable including frequent pulmonary infections due to lowered acid barrier. Unfortunately, the authors cannot provide data on Helicobacter pylori infections in the present cohort. Finally, the high rate of EoE detections should be emphasized. The stated incidence in Europe and North America of 6.6/100,000 children [26] was exceeded in the present investigation with 2.5% of the total cohort. A combined gastroscopy and bronchoscopy appears to be reasonable in refractory respiratory symptoms despite multimodal therapy and with indications of reflux, especially in males with peripheral eosinophilia and elevated IgE, particularly since symptoms of EoE in preschool children can be diverse and include chronic cough. The current study has limitations, primarily due to its retrospective design, resulting in a heterogeneous cohort. Therefore, in this cohort, specific information on the respiratory symptoms that led to the indication for bronchoscopy cannot be precisely obtained. However, this heterogeneity is also partly inherent to these diseases; this is illustrated by the increased likelihood of having antibiotics prescribed for PBB or pneumonia in asthmatics [27]. Conversely, children with PBB are about twice as likely to suffer from asthma than healthy children [6]. The authors chose to define any positive bacterial culture (> 10³ CFU/mL) as bacterial colonization of the lower airways. The definition of a positive BAL culture yield is heterogenous, varying from 10³ CFU/mL to 10 5 CFU/mL [28]. It must be emphasized that a detection threshold of bacterial infection [29, 30]. It is therefore neither possible nor the intention of this study to discriminate between bacterial infection and colonization. PCR for the detection of various viral and bacterial pathogens were not available for the complete dataset. Conclusion Bronchoscopy is a valuable diagnostic tool in persistent respiratory symptoms in preschoolers. Bacterial colonization of the airways is common, and airway neutrophils were significantly higher in colonized airways. In many bronchoscopies, results were obtained that led to a change in therapy, like targeted antibiotic treatment and increased asthma medication. Moreover, testing for adequate pneumococcal titers is reasonable in cases of persistent respiratory symptoms in children, and combined gastroscopy and pH monitoring are able to find comorbidities like GERD and EoE more often in this cohort than in the general population. List of Abbreviations BAL Bronchoalveolar lavage CRP C-reactive protein CT Cycle threshold ELISA Enzyme-linked Immunosorbent Assay EoE Eosinophilic esophagitis GERD Gastro eosophageal reflux disease GINA Global initative for asthma H. Haemophilus ICS Inhaled corticosteroids IgE Immunoglobulin E IgG Immunoglobulin G M. Moraxella PBB Protacted bacterial bronchitis PCR polymerase chain reaction PPI Proton pump inhibitors RSV Respiratory syncytial virus S. Streptococcus SD Standard deviation sIgE Specific immunoglobulin E SPT Skin prick test IQR Interquartile range REFERENCES Murphy KR, Hong JG, Wandalsen G, Larenas-Linnemann D, El Beleidy A, Zaytseva OV, Pedersen SE. 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PMID: 22707884; PMCID: PMC3372796. de Blic J, Midulla F, Barbato A, Clement A, Dab I, Eber E, Green C, Grigg J, Kotecha S, Kurland G, Pohunek P, Ratjen F, Rossi G. Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory Society. Eur Respir J. 2000 Jan;15(1):217-31. doi: 10.1183/09031936.00.15121700. PMID: 10678650. Hare KM, Pizzutto SJ, Chang AB, Smith-Vaughan HC, McCallum GB, Beissbarth J, Versteegh L, Grimwood K. Defining lower airway bacterial infection in children with chronic endobronchial disorders. Pediatr Pulmonol. 2018 Feb;53(2):224-232. doi: 10.1002/ppul.23931. Epub 2017 Dec 19. PMID: 29265639; PMCID: PMC7167837. Supplementary Material File (table1-final.docx) Download 15.66 KB Information & Authors Information Version history V1 Version 1 27 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keyword preschool asthma bronchoscopy bal bacterial Authors Affiliations H. Donath Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author J. Ruff Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author L. Heumüller Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author O. Eickmeier Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author Dressler M Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author RSchubert Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author K. Blumchen Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author Johannes Schulze Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author Stefan Zielen Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author J. Trischler [email protected] Goethe-Universitat Frankfurt am Main Universitatsklinikum Frankfurt View all articles by this author Metrics & Citations Metrics Article Usage 253 views 175 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation H. Donath, J. Ruff, L. Heumüller, et al. Bronchoscopic findings in preschoolers with refractory respiratory symptoms: Analysis of bacterial colonization and comorbidities. Authorea . 27 March 2025. DOI: https://doi.org/10.22541/au.174306276.62692678/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. 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