Authors: Adem Yaşar, Özge Yilmaz, Aynur Hasanova, Berna Cansu Aritaş, Hasan Yüksel
Categories: Research, Chronic cough, Flexible bronchoscopy, Pediatric pulmonology, Airway abnormalities, Diagnostic utility
Source: European Journal of Pediatrics
Authors: Adem Yaşar, Özge Yilmaz, Aynur Hasanova, Berna Cansu Aritaş, Hasan Yüksel
Chronic cough, defined as cough lasting more than four weeks in children, is a frequent reason for pediatric pulmonology referrals. The underlying etiology often remains unclear despite extensive non-invasive evaluations, thus necessitating flexible bronchoscopy. In this study, we aimed to evaluate if specific clinical symptoms were predictive of anatomic or functional airway abnormalities detected in bronchoscopy. We analyzed 168 pediatric patients (0–18 years) who underwent flexible bronchoscopy for chronic cough at a tertiary center for this retrospective study. Demographic and clinical data, including cough characteristics and triggering factors, were extracted from medical records. Bronchoscopic findings, including structural and functional airway abnormalities, were documented. Logistic regression and receiver operating characteristic (ROC) analysis were performed to identify predictors of anatomical abnormalities. Bronchoscopy showed that 30% of the cases had unusual structures, with airway malacia (33%), vascular compression (21%), and subglottic stenosis (17%) being the most frequent issues. Younger age (OR = 0.84; 95% CI: 0.75–0.94; p = 0.002) and dry cough phenotype (p = 0.002) were significantly associated with anatomical abnormalities, whereas second-hand smoke exposure and gastroesophageal reflux disease (GERD) were not. ROC analysis demonstrated moderate predictive power (AUC = 0.74) for identifying anatomical abnormalities based on clinical parameters.
Conclusion: Airway malacia, vascular compression and subglottic stenosis are the most common structural and functional airway abnormalities in children with chronic cough. This study has shown that detecting anatomical or functional airway abnormalities with bronchoscopy is more common in young children with prolonged cough. What is Known:• Flexible bronchoscopy is a key diagnostic tool for pediatric chronic cough when non-invasive evaluations are inconclusive, routinely identifying anomalies such as airway malacia, vascular compression, and subglottic stenosis.• Current guidelines offer limited guidance on which clinical features should prompt early bronchoscopy referral in children with chronic cough.What is New:• Younger age and a dry cough phenotype are independent predictors of anatomical airway abnormalities on flexible bronchoscopy (OR = 0.84; AUC = 0.74).• A symptom-based decision algorithm incorporating age, cough type, and gender demonstrates moderate discriminative power to guide bronchoscopy referral and may optimize diagnostic yield.
Chronic cough, defined as a cough lasting more than four weeks in children, is a prevalent symptom leading to pediatric pulmonology referrals [1]. It may lead to considerable distress for both patients and caregivers. Chronic cough often requires a more extensive evaluation to determine underlying causes, unlike acute cough, which is typically self-limiting and associated with viral infections [2].
The etiology of chronic cough in pediatric patients is multifaceted, encompassing conditions such as asthma, gastroesophageal reflux disease (GERD), protracted bacterial bronchitis, and postnasal drip associated with upper respiratory infections [3]. Also, less common but important causes like congenital airway problems, cystic fibrosis, and interstitial lung diseases should be looked at, especially when standard treatments don’t work [4]. Given this wide differential diagnosis, a systematic and evidence-based approach is critical to optimizing clinical outcomes and minimizing unnecessary interventions [5].
The initial assessment of a child presenting with chronic cough involves a comprehensive medical history, thorough physical examination, and non-invasive investigations like chest radiography and spirometry [6]. These evaluations help to distinguish between common and uncommon causes and identify red flags suggestive of serious underlying pathology. However, when these standard tests fail to clarify the etiology, the use of more advanced diagnostic methods become necessary; highlighting the critical role of flexible bronchoscopy (FB) in further assessment [7].
Flexible bronchoscopy is a well-established tool that allows for direct visualization of the airway, facilitating the detection of structural anomalies such as tracheomalacia, bronchomalacia, and airway stenosis, as well as functional abnormalities including mucosal inflammation and excessive secretions [8]. Additionally, FB enables targeted sampling for microbiological, cytological, and histopathological analyses, providing valuable insights into chronic infection, inflammation, and airway remodelling [9].
Flexible bronchoscopy has been shown to yield critical diagnostic insights in children with chronic cough, informing clinical decision-making and reducing prolonged diagnostic uncertainty [10, 11]. Even though FB is a valuable diagnostic tool, the relationship between specific clinical symptoms and bronchoscopic findings is not completely understood. Further research is needed to optimise indications for FB and enhance its clinical utility in patient care [12]. By improving our understanding of these associations, we can enhance diagnostic accuracy and optimize patient-centered management strategies [13].
Current recommendations are valuable but offer limited guidance on which young patients with chronic cough should be referred for bronchoscopy, leading to uncertainty in clinical decision-making. Especially the association between specific clinical symptoms and bronchoscopic results remains poorly defined [6, 14].
In this study, we aimed to evaluate if specific clinical symptoms were predictive of anatomic or functional airway abnormalities detected in bronchoscopy. By analyzing the association between specific clinical presentations with both structural and functional airway abnormalities, we seek to enhance the diagnostic approach and contribute to more targeted bronchoscopic evaluation strategies for this patient population.
This retrospective study was conducted at Manisa Celal Bayar University, School of Medicine, Department of Pediatric Allergy and Immunology, and Pediatric Pulmonology. The medical records of pediatric patients aged 0–18 years who underwent flexible bronchoscopy between December 29, 2017, and June 7, 2024, were reviewed.
This retrospective study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The protocol was approved by the Ethics Committee of Manisa Celal Bayar University School of Medicine (Approval Number: 23. 10.2024/20.478.486/2655). The requirement for informed consent was waived by the Ethics Committee due to the retrospective nature of the study.
During the study period, a total of 522 FB procedures were performed. Among these, patients who underwent FB due to chronic cough were identified, and 168 cases met the inclusion criteria. Patients who underwent FB for other indications, such as cystic fibrosis, primary ciliary dyskinesia (PCD), and foreign body aspiration, were excluded from the study.
Relevant clinical data were retrospectively extracted from the patients’ medical records. The demographic and clinical characteristics of the patients, including age at presentation, gender, duration of cough, and cough characteristics (dry, productive, or metallic), were recorded. Additionally, potential triggering factors, such as sleep, eating, supine position, exertion, and nasal congestion, were evaluated. Bronchoscopy findings, including structural and functional airway abnormalities such as airway malacia, vascular compression and subglottic stenosis, were obtained from procedural reports.
Flexible bronchoscopy was performed using Fujinon EB-470S (4.9 mm external diameter, 2-mm internal diameter) or Fujinon EB-470P (3.8-mm external diameter, 1.2-mm internal diameter), depending on the patient’s age and body weight. The procedure was conducted under general anesthesia, administered via mask inhalation of nitrous oxide (NO₂) and intravenous (IV) propofol. Neuromuscular blockers were used in selected cases.
Data were analyzed using Jamovi statistical software (version 2.3; The Jamovi Project, 2022). Continuous variables were presented as mean ± standard deviation (SD), and categorical variables as frequency (percentage). One-way ANOVA was used for comparisons among multiple groups, while Student’s t-test was applied for two-group comparisons of normally distributed continuous variables. A chi-square test or Fisher’s exact test was used for categorical variables. A logistic regression analysis was done to examine the relationship between clinical characteristics and anatomical abnormalities, showing results as odds ratios (OR) and 95% confidence intervals (CI). ROC curve analysis was performed to evaluate the predictive power of clinical parameters. Statistical significance was set at p < 0.05.
Of the 168 pediatric patients undergoing flexible bronchoscopy for chronic cough, 54% (n = 91) were male, with a mean age of 5.9 ± 4.45 years. The mean cough duration was 9.9 ± 5.23 weeks, and the most common cough type was dry cough (63%). The most frequently reported triggering factor was nighttime sleep (31%), followed by nasal congestion (27%). Exposure to secondhand smoke was reported in 30% of patients. Among patients who underwent pulmonary function testing, no significant abnormalities were detected, whereas aeroallergen sensitivity was identified in 45% of cases (Table 1). Table 1Sociodemographic and clinical characteristics of pediatric patients undergoing flexible bronchoscopy for chronic coughn = 168Age (years)5.9 (4.45)Sex (male)91 (54.1)Cough duration (weeks)9.92 (9.00)Cough phenotypeProductive51 (31)Dry103 (62)Metallic11 (7)Triggering factorSleeping54 (32)Eating11 (6.5)Supine position33 (19.5)Exercises25 (15)Nasal congestion45 (27)Secondhand smoke (yes)49 (29)Skin prick test (positive)75 (45)()-%
Bronchoscopy revealed anatomical and functional abnormalities in 30% (n = 48) of cases. The most frequently observed anomalies included airway malacia (n = 16), vascular compression (n = 10), and subglottic stenosis (n = 8) (Fig. 1). Among these, airway malacia was the most common finding and was predominantly observed in younger children. Vascular compression was frequently associated with stridor and respiratory distress, while subglottic stenosis was more prevalent in patients with a history of prolonged cough and recurrent respiratory infections. Patients with airway abnormalities were significantly younger than those without anomalies (4.04 ± 3.18 years, p = 0.001). However, cough duration did not differ significantly between these groups (p = 0.1). Airway abnormalities were significantly associated with male gender (p = 0.016) and the dry cough phenotype (p = 0.002). In contrast, no significant associations were found regarding secondhand smoke exposure (p = 0.45), aeroallergen sensitivity (p = 0.28), GERD history (p = 0.15), or the presence of protracted bacterial bronchitis (p = 0.55) (Table 2). Fig. 1Bronchoscopic findings in pediatric patients with chronic coughTable 2Comparison of clinical and demographic factors between patients with and without anatomical airway abnormalitiesPresent (n = 48)Absent (n = 120)95% CIORp = Age4.04 ± 3.26.6 ± 4.71.164.060.001Sex**Male33 (36.3)58 (63.7)0.210.860.420.01Female15 (19.5)62 (80.5)Cough Productive9 (16.7)45 (83.3)0.05Dry37 (35.9)66 (64.1)Metallic2 (18.2)9 (81.8)Cough durationWeek8.9 ± 3.910.3 ± 5.6−0.283.220.10Triggering factorsSleeping11 (20.8)42 (79.2)0.34Eating2 (18.2)9 (81.8)Supine position17 (51.5)16 (48.5)Exercises2 (8)23 (92)Nasal congestion15 (33.3)30 (66.7)Skin prick testPresent18 (24)57 (76)0.28Absent26 (34.7)49 (65.3)Secondhand smokePresent12(24.5)37 (75.5)0.351.600.780.45Absent36 (30.3)83 (69.7)GERDPresent10 (20.4)39 (79.6)0.15Absent38 (31.9)81 (68.1)0.241.210.54PBBPresent3 (7.9)35 (92.1)0.120.550.160.55Absent10 (12.1)120(87.9)^^Student’s t test^^ Chi square test^^ One way Anova() %GERD Gastroesophageal reflux disease, PBB Protracted bacterial bronchitis
To assess the predictive factors for anatomical abnormalities, a logistic regression analysis was performed, including age, cough duration, cough phenotype, secondhand smoke exposure, and GERD history as independent variables. Younger age was the strongest independent predictor of anatomical abnormalities (p = 0.002, OR = 0.84), while GERD history was associated with a lower likelihood of airway anomalies (p = 0.034, OR = 0.39). Neither cough duration (p = 0.87) nor secondhand smoke exposure (p = 0.48) were significant predictors.
We performed a Receiver Operating Characteristic (ROC) curve analysis to assess the model’s ability to predict anatomical abnormalities. The AUC was 0.74, indicating moderate discriminative power. The optimal cutoff value was 0.34, determined using Youden’s Index. At this threshold, the model achieved 72.9% sensitivity and 70.0% specificity, balancing the ability to detect true positive cases while minimizing false positives. Scenario-based risk estimation showed that younger children (≤ 2 years) with prolonged cough (> 12 weeks) had the highest predicted risk (55.5%), while older children (> 8 years) had a lower probability (31.1%). The dry cough phenotype was also linked to a higher likelihood of anatomical abnormalities. These findings suggest that clinicians should consider early bronchoscopy evaluation in younger children with persistent dry cough, especially when no other clear cause is identified (Fig. 2). Fig. 2Receiver Operating Characteristic (ROC) curve analysis for predicting anatomical abnormalities
This study has shown that detecting anatomical or functional airway abnormalities with bronchoscopy is more common in young children with prolonged cough. The most commonly detected abnormalities were airway malacia, vascular compression, and subglottic stenosis. Flexible bronchoscopy is an essential component in evaluating chronic cough in pediatric patients, and these results emphasize the need to use its diagnostic utility earlier in younger children.
We found airway malacia, vascular compression, and subglottic stenosis in a significant proportion of the cases in which we performed a flexible bronchoscopy for chronic cough. This emphasizes the importance of FB in cases where conventional diagnostic methods fail to determine the underlying etiology. Previous studies have reported similar rates of structural abnormalities in children undergoing bronchoscopy for chronic respiratory symptoms and support our findings [15, 16]. Our results highlighted the link between being young and having airway problems, which aligns with what we know about how birth or growth issues can significantly affect chronic cough in young children [17].
Flexible bronchoscopy remains a cornerstone in the diagnostic approach to chronic cough because it provides a direct visualization of the airway that cannot be assessed by non-invasive diagnostic methods such as spirometry or radiographic imaging [18]. The ability to assess dynamic airway changes, identify subtle mucosal abnormalities, and perform bronchoalveolar lavage (BAL) for microbiological and cytological evaluation makes FB an indispensable tool in pediatric pulmonology [19, 20]. In accordance with this, one-third of patients in our study had previously undiagnosed structural abnormalities.
The significant correlation between structural abnormalities in the airway and the male gender, as well as the presence of dry coughs in our population, highlights the need for individualized assessment strategies in diagnosis. This result is consistent with previous research suggesting that tracheomalacia and bronchomalacia are more frequently diagnosed in male infants and young children [21, 22]. Furthermore, the lack of a significant relationship between secondhand smoke exposure, aeroallergen sensitivity, and gastroesophageal reflux disease with anatomical findings suggests that while these factors may contribute to chronic cough, they do not appear to directly influence the presence of structural abnormalities [23]. This highlights the need for a direct airway check using bronchoscopy when a cough continues even without other factors like smoke exposure and allergies [24].
Based on our findings, we propose a decision tree for bronchoscopy referral guided by symptom profiles and clinical risk factors (Fig. 3). This algorithm includes important factors such as being under 5 years of age, having a dry or metallic cough, being male, having frequent respiratory infections, having stridor or worsening symptoms at night, and having an inadequate response to appropriate medical treatment. Including these clinical characteristics in a structured way provides a practical tool for pediatricians performing the initial assessment and following the patient to stratify risk and prioritize bronchoscopy referrals more efficiently. Implementation of such an approach in clinical practice may improve diagnostic yields, shorten diagnosis times, and prevent unnecessary investigations and treatment approaches for low-risk patients. Fig. 3Clinical decision algorithm for bronchoscopy referral in pediatric chronic cough (study-based)
This study has several limitations. First, its retrospective design inherently limits causal inferences and is subject to potential selection bias. Second, as a single-center study, the generalizability of our findings to broader pediatric populations may be limited. Future multicenter prospective studies with extended follow-up periods are needed to validate these findings and provide stronger evidence for the role of FB in the diagnostic algorithm of pediatric chronic cough.
In conclusion, younger age and persistent dry cough are important predictors of functional and anatomical airway abnormalities detected in flexible bronchoscopy. Therefore, earlier consideration for bronchoscopy in these children may facilitate targeted management strategies, ultimately improving clinical outcomes and reducing diagnostic uncertainty.