Subglottic cysts (SGCs) are a rare cause of respiratory distress resulting from upper airway obstruction in infants and young children. Risk factors other than prematurity with a history of endotracheal intubation have not yet been well elucidated. Therefore, we aimed to describe the clinical features and analyze the risk factors of SGCs.
We conducted a retrospective review of medical records of pediatric patients who underwent marsupialization for SGCs between January 2017 and March 2022. These records were then compared with those of controls with a history of neonatal intubation, with a case-to-control ratio of 1:3.
Eleven patients (eight boys and three girls) diagnosed with SGCs and 33 control patients (26 boys and seven girls) were included. All patients had a history of premature birth and neonatal intubation. Symptoms of SGCs appeared at a mean age of 8.2 months (range, 1–14 months) after extubation. The mean duration of intubation was 21.5 days (range, 2–90 days), and the intubation period was longer in patients with SGCs than in controls (21.5±24.8 days vs. 5.3±7.1 days;
This study showed that gestational age, birth weight, and the intubation period were significantly associated with the development of SGCs. Pediatric patients presenting with progressive dyspnea who have the corresponding risk factors should undergo early laryngoscopy for the differential diagnosis of SGC.
Subglottic cysts (SGCs) are rare, benign lesions that cause upper airway narrowing in infants and young children. First reported by Wigger and Tang in 1968, these lesions occur in the subglottic space, the narrowest part of the upper airway [
As abnormal breathing sounds are the primary symptom of SGCs, some patients are incorrectly diagnosed with asthma or recurrent croup, and inadequate treatment is provided. In addition, subglottic stenosis, laryngomalacia, vocal cord paralysis, hemangioma, lymphangioma, and foreign bodies that can cause upper airway narrowing should be considered in the differential diagnosis. Although SGCs are often diagnosed using flexible laryngoscopy in outpatient clinics, microlaryngobronchoscopy under general anesthesia can be used to accurately evaluate the extent of the lesion and provide treatment simultaneously.
Marsupialization, the treatment of choice for several types of cysts, is accomplished by a variety of methods, including CO2 and thulium lasers, cold dissection, and laryngeal microdebriders [
For efficient marsupialization of SGCs, good exposure of the airway is required with an appropriate level of anesthesia and oxygenation. Apneic anesthesia is the most basic tubeless anesthetic technique for achieving a sufficient surgical field of view, but apnea can be maintained for only 3 minutes or less in children; therefore, its use for SGC treatment in children is limited [
As SGCs are a rare cause of stridor in children, only a few studies have reported its clinical features, and the risk factors for SGCs, other than premature birth and history of intubation, are still unknown. Therefore, this study aimed to describe the clinical features and analyze the risk factors of SGCs. We also report our experience of using STRIVE Hi for the marsupialization of SGCs.
The medical records of 11 pediatric patients with SGCs between January 2017 and March 2022 were retrospectively reviewed. Patients with SGC and control patients with a history of neonatal intubation were compared to determine the possible risk factors of SGC with a case to control ratio of 1:3. Controls were selected using incidence density sampling [
For every patient with SGC, three control patients were randomly selected from those who were intubated in the neonatal intensive care unit during the same period. In this study, gestational age and sex were not considered when selecting controls to match with the cases. The variables used for matching cannot be evaluated as risk factors through comparison between the two groups although age and sex have been reported as risk factors for SGC. The obstruction grade of SGCs was defined as follows: grade 1, lumen obstruction by the cyst is less than 25%; grade 2, lumen obstruction between 26% and 50%; grade 3, lumen obstruction between 51% and 75%; and grade 4, lumen obstruction between 76% and 100%.
Approval for this study was obtained from the Institutional Review Board of the Seoul National University Hospital (No. 2108-025-1241), and informed consent requirement was waived.
All procedures were performed by a single surgeon (SKK) using the STRIVE Hi anesthesia technique. Microlaryngobronchoscopy was performed to accurately evaluate SGC before marsupialization. A Benjamin-Lindholm laryngoscope (Karl Storz) was used for airway suspension to visualize the cyst. Marsupialization was performed using the CO2 laser or cold steel microinstruments (
The STRIVE Hi technique was used as previously described [
Fisher’s exact test and Pearson’s chi-square test were used to analyze the categorical variables such as sex, premature birth, and delivery methods. Student
Of the 11 children, eight (72.7%) were male and 3 (27.3%) were female. All the patients were preterm infants with a history of endotracheal intubation during the neonatal period. The mean duration of intubation was 21.5 days (range, 2–90 days). The average interval from extubation to the onset of symptoms due to SGC was 8.2 months (range, 1–14 months). All patients, except for one who had an abnormal radiologic finding, presented with stridor as a symptom. Seven patients (63.6%) had multiple cysts, and the occurrence rates on the left (54.5%) and right sides (45.5%) of the glottis were similar. All patients were diagnosed as having SGC by transnasal flexible laryngoscopy in the clinic. Under general anesthesia using the STRIVE Hi technique, marsupialization of the cysts was performed. During the follow-up period, which ranged from 3 months to 4 years, no recurrence was observed in any of the patients. Six patients (54.5%) showed coexistence of subglottic stenosis and SGC (
Gestational age (28.3±4.2 weeks vs. 33.8±4.4 weeks;
Univariate analysis revealed that gestational age (odds ratio [OR], 0.763;
SGCs are a rare cause of upper airway narrowing or obstruction in children that has been reported to a limited extent in the literature. However, as the survival rate of preterm infants with a history of endotracheal intubation improves, the incidence of SGCs is likely to increase [
Children with SGCs usually show symptoms caused by upper airway narrowing, such as stridor, dyspnea, and hoarseness. Because of these symptoms and the low prevalence of SGCs, they are commonly misdiagnosed as bronchitis, asthma, and croup, resulting in inaccurate and unnecessary treatment [
There are several causes of upper airway narrowing or obstruction. Therefore, laryngomalacia, vocal cord paralysis, subglottic hemangioma or lymphangioma, and foreign bodies obstructing the upper airway, must also be considered in the differential diagnosis [
Laryngomalacia is marked by symptoms such as inspiratory stridor and choking while feeding, while vocal fold paralysis can lead to aspiration. SGCs do not exhibit any distinctive or specific symptoms except stridor. It is crucial to thoroughly examine the patient’s medical records for a diagnosis of SGC. Similar to previous reports, all of the children diagnosed with SGC in this study were born prematurely and had been intubated at birth [
Marsupialization is the primary treatment of choice for SGC. Previous studies have reported that marsupialization can be performed using various techniques, including cold microinstruments, CO2 and thulium lasers, microdebriders, and Bugbee fulgurating electrode devices [
The insufficient marsupialization of SGCs increases the probability of recurrence [
According to studies published to date, temporary tracheostomy was performed in 14%–33% of patients with SGCs [
It has been recently reported that the prognosis may differ depending on the depth of the SGC location. Unsaler et al. [
In this study, all patients with SGCs had a history of premature birth. We showed that low gestational age at birth, low birth weight, and a long intubation period were significant risk factors for SGCs. SGCs are retention cysts formed due to the blockage of the ducts of the mucous gland by subepithelial fibrosis, which results from the mucosal damage caused by endotracheal intubation and subsequent healing [
Unfortunately, the authors cannot guarantee that no SGC occurred in the children in the control group, as laryngoscopy was not performed after extubation in all cases, especially if no symptoms or only mild symptoms related to airway obstruction were present. It is possible that some SGCs may have gone unnoticed in these cases.
Our study has several limitations. First, this was a retrospective review with only 11 pediatric patients and a relatively short follow-up period at a single center. Further studies with a larger sample size, patients with various severities of SGC, and a longer follow-up period are needed to confirm our results. Patients who underwent neonatal endotracheal intubation during the same period as patients with SGCs were included in the control group. This process might have introduced selection bias, as the controls selected might not have been representative of their population. In addition, there have been reports of patients with SGCs without a history of tracheal intubation; therefore, other risk factors may exist in addition to the factors described in this study.
▪ Risk factors for subglottic cysts (SGCs), other than premature birth and a history of intubation, were previously unknown.
▪ Gestational age, birth weight, and the intubation period were associated with SGCs.
▪ Infants and children with progressive dyspnea and risk factors require screening for SGCs.
No potential conflict of interest relevant to this article was reported.
Conceptualization: SHH, SKK. Data curation: SHH, JYJ, MK. Formal analysis: SHH, MK. Methodology: SHH, SKK. Writing–original draft: SHH. Writing–review & editing: all authors.
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2019M 3A9H1103617), by Korean Fund for Regenerative Medicine funded by Ministry of Science and ICT, and Ministry of Health and Welfare (grant number: 22A0103L1-11), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI14C1277). Also, this work was supported by the Technology Innovation Program (or Industrial Strategic Technology Development Program-Bio-industrial technology development-customized diagnostic treatment products) (20014955, Development of Intelligent Automation System for mass production of cell therapy products) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea).
(A) A bilateral subglottic cyst with transparent, thin capsules that obstruct more than 75% of the subglottis. (B) Marsupialization of subglottic cysts using a CO2 laser with the STRIVE Hi anesthesia technique. (C) Postoperative view after complete marsupialization. STRIVE Hi, SponTaneous Respiration using IntraVEnous anesthesia and Hi-flow nasal oxygen.
Summary of the clinical features of 11 children with SGCs
No. | Sex | Gestational age at birth (wk) | Duration of previous intubation (day) | Presentation interval (mo) | Obstruction grade of the subglottic cyst | Presenting symptom | Site | Management | Other airway lesion |
---|---|---|---|---|---|---|---|---|---|
1 | M | 34 | 15 | 10 | 1 | Stridor | Left 2, right 1 | L, MMC | SGS Gr II |
2 | M | 33 | 7 | 5 | 3 | Stridor, hoarseness | Right 1 | L, MMC, B | SGS Gr II |
3 | M | 32 | 2 | 12 | 2 | Abnormal radiologic finding | Left 1 | C | SGS Gr I |
4 | M | 24 | 23 | 13 | 2 | Stridor, dyspnea hoarseness | Left 2, right 1 | L, MMC | - |
5 | M | 33 | 10 | 14 | 3 | Stridor | Right 1 | L | SGS Gr II |
6 | M | 24 | 37 | 1 | 2 | Stridor | Left 1 | L | - |
7 | M | 27 | 10 | 3 | 2 | Stridor, dyspnea, hoarseness | Left 4, right 3 | L | - |
8 | M | 30 | 17 | 9 | 2 | Stridor | Left 3, right 3 | L, MMC, B | SGS Gr II |
9 | F | 24 | 90 | 4 | 4 | Stridor, dyspnea, hoarseness | Left 2, right 2 | L, MMC, B | Tracheomalacia |
10 | F | 26 | 5 | 7 | 3 | Stridor, dyspnea, | Left 2, right 2 | L | SGS Gr I |
11 | F | 24 | 20 | 12 | 4 | Stridor | Left 1, right 1 | L, MMC | Tracheomalacia |
Obstruction grade of SGC Gr I, lumen obstruction ≤25%; Gr II, 25%<lumen obstruction≤50%; Gr III, 50%<lumen obstruction≤75%; and Gr IV, 75%<lumen obstruction≤100%.
SGC, subglottic cyst; L, laser (CO2); MMC, mitomycin-C; SGS, subglottic stenosis; Gr, grade; B, balloon dilatation; C, cold microinstrument.
Comparison of the risk factors between SGC patients and the control group
Variable | SGC patient | Control | |
---|---|---|---|
Sex | 0.692 | ||
Male | 8 (72.7) | 26 (78.8) | |
Female | 3 (27.3) | 7 (21.2) | |
Prematurity | 0.311 | ||
Term | 0 | 6 (18.2) | |
Preterm | 11 (100) | 27 (81.8) | |
Gestational age at birth (wk) | 28.3±4.2 | 33.8±4.4 | 0.001 |
Birth weight (g) | 1,134.1±515.1 | 2,178.2±910.1 | 0.001 |
Delivery method | 0.461 | ||
Vaginal delivery | 2 (18.2) | 11 (33.3) | |
Cesarean delivery | 9 (81.8) | 22 (66.7) | |
Duration of intubation (day) | 21.5±24.8 | 5.3±7.1 | <0.001 |
Frequency of intubation | 1.6±0.8 | 1.3±0.8 | 0.118 |
Values are presented as number (%) or mean±standard deviation.
SGC, subglottic cyst.
Statistically significant (
Univariate and multivariate analyses of risk factors for SGCs
Variable | Univariate analysis |
Multivariate analysis |
||||
---|---|---|---|---|---|---|
OR | 95% CI | OR | 95% CI | |||
Sex | ||||||
Male | 1.393 | 0.290–6.679 | 0.679 | |||
Female | 1 (Reference) | |||||
Gestational age at birth (wk) | 0.763 | 0.636–0.915 | 0.003 |
|||
Birth weight | 0.998 | 0.997–0.999 | 0.005 |
|||
Delivery method | ||||||
Vaginal delivery | 0.444 | 0.082–2.420 | 0.348 | |||
Cesarean delivery | 1 (Reference) | |||||
Duration of intubation (day) | 1.127 | 1.018–1.248 | 0.021 |
1.168 | 1.005–1.357 | 0.043 |
Frequency of intubation | 1.506 | 0.691–3.281 | 0.303 |
SGC, subglottic cyst; OR, odds ratio; CI, confidence interval.
Statistically significant (