Differential diagnosis and management of adult-onset laryngomalacia.

OBJECTIVE: Adult-onset laryngomalacia is a rare clinical entity that has been infrequently reported. This study aims to evaluate the clinical presentation, diagnosis, and management of adult-onset laryngomalacia through literature review and report of a case. METHODS: PubMed and Google Scholar databases were queried for articles published from 1960 to 2019 including only patients aged 18 years and older. Included keywords were: 'laryngomalacia', 'adult laryngomalacia', 'acquired laryngomalacia', 'idiopathic laryngomalacia', 'laryngeal obstruction', 'floppy epiglottis', 'floppy epiglottis', and 'epiglottis prolapse'. Data extracted from literature included clinical presentation, diagnostic workup, surgical management, and follow-up care. SOURCES: PubMed and Google Scholar. RESULTS: A total of 21 articles reported 41 cases of adult-onset laryngomalacia. Within these cases, 5 etiologies were identified: neurologic (n = 14), exercise-induced (n = 9), post-operative (n = 7), idiopathic (n = 7), and age-related (n = 4) laryngomalacia. Anterior prolapse of arytenoids and aryepiglottic folds was the most common laryngoscopic finding (n = 21), followed by posterior epiglottic prolapse (n = 20). Management included supraglottoplasty (n = 14), epiglottidectomy (n = 8) or epiglottopexy (n = 2). Neurologic etiology required tracheotomy more often than the other etiologies (n = 5, 36% vs. 15%). Three patients were managed expectantly without surgical intervention and reported symptom resolution. CONCLUSION: Adult laryngomalacia is a rare diagnosis comprising a spectrum of disease. This diagnosis may be overlooked, but association with neurologic injury or trauma should encourage consideration. In comparison to pediatric laryngomalacia, patients often require surgical intervention. Surgical decision is based on the direction of supraglottic collapse, where supraglottoplasty and partial epiglottidectomy are effective interventions. LEVEL OF EVIDENCE: N/A.

Laser supraglottoplasty for laryngomalacia; a 14 year experience of a tertiary referral center.

To review the outcomes of laser supraglottoplasty performed in children with symptomatic laryngomalacia and determine the factors influencing them. We retrospectively reviewed the medical records of patients who underwent laser supraglottoplasty for symptomatic laryngomalacia at the Lausanne University Hospital from November 2001 to November 2014. We examined the patient's demography, symptoms, comorbidities, type of laryngomalacia, synchronous airway lesions, and final outcomes. Seventy-nine patients were included in this study; median age at the time of surgery was 12.7 months. 55.7 % of the cases had comorbidities, 22.8 % of the patients were premature and synchronous airway lesions were present in 32.9 % of the cases. The different morphological types of laryngomalacia (I-III) were seen in 26.6, 62 and 11.4 % of the patients, respectively. Overall, operation specific success rate of laser supraglottoplasty was 86.1 %. Failures in 11 (13.9 %) of the 79 cases required 15 revision procedures. Success rates for patients with associated comorbidities, synchronous airway lesions, neurological disorders and prematurity were 81.8, 76.9, 69.2 and 66.7 %, respectively. Patients with type III laryngomalacia had a limited success rate (66.7 %) as compared to patients with morphological types I and II (90.5 and 87.8 %, respectively). Laser supraglottoplasty is an effective and safe treatment for symptomatic laryngomalacia. Patients with prematurity, type III LM, synchronous airway lesions and associated comorbidities are predisposed to surgical failure.

Neuropathological features of pediatric laryngomalacia.

OBJECTIVE: Laryngomalacia is the most common pediatric laryngeal anomaly. The pathophysiology of laryngomalacia is not well defined; the leading hypothesis suggests weak laryngeal tone and neuromuscular discoordination. Only a few studies explored the histopathology of the laryngeal submucosal nerves, with reported nerve hypertrophy. Our study aims to describe the histopathology of submucosal nerves in specimens obtained from children with severe laryngomalacia compared to pediatric cadaveric controls. STUDY DESIGN: Prospective study. SETTINGS: Tertiary care children's hospital. METHODS: Histologic and immunohistochemical sections of supraglottic tissue from 26 children with severe laryngomalacia and six pediatric autopsies were digitally scanned and assessed with image analysis software (QuPath), resulting in the identification and measurement of 4561 peripheral nerves and over 100,000 foci of neurofilaments. RESULTS: Chronic inflammation was noted in all patients. Eosinophils were rare. The mean nerve area and perimeter were significantly smaller for patients with laryngomalacia compared to the control group (1594.0 ± 593.2 µm^2 vs. 2612.1 ± 2824.0 µm^2, p < 0.0001, and 158.8 ± 30.3 µm vs. 217.6 ± 165.0 µm, p < 0.0001). Nerve-per-area unit was significantly greater for patients with laryngomalacia compared to controls (1.39E-05 vs. 6.19 E-06, p = 0.009). The mean area and the number of neurofilaments per total nerve area were similar. Immunohistochemistry for calretinin, a marker for intestinal ganglion cells in Hirschsprung disease, was absent from all specimens. CONCLUSIONS: This series includes a comparison of all identifiable nerve fibers obtained from children with severe laryngomalacia and shows that the mucosal nerves are smaller on average than controls. These findings fail to provide support for significant morphologic peripheral nerve pathology in laryngomalacia.

Tetrasomy 13q32.2qter due to an apparent inverted duplicated neocentric marker chromosome in an infant with hemangiomas, failure to thrive, laryngomalacia, and tethered cord.

BACKGROUND: Approximately 100 small supernumerary marker chromosomes (sSMCs) with a non-α-satellite neocentromere structure have been reported in the literature. Of the few derived from chromosome 13, five have consisted of inverted duplicated segment 13q32qter. CASE REPORT: We herein describe the sixth case, characterized by genome wide SNP array, conventional cytogenetics and FISH studies. The de novo occurrence of the marker, the poor prognosis and the presence of hemangiomas are consistent with previous cases. CONCLUSION: We hereby expand the clinical spectrum of this rare cytogenetic disorder and suggest a possible mechanism for the pathogenesis of associated congenital vascular malformations.

Malacia, inflammation and bronchoalveolar lavage culture in children with persistent respiratory symptoms.

In children with persistent respiratory symptoms despite regular anti-asthma inhalation treatment, diagnostic investigations to exclude underlying disease are warranted. 124 children were prospectively enrolled, and 24-h oesophageal pH measurement and fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) were performed. BAL fluid (BALF) was processed for neutrophil counting and bacterial culture. Inflammation of the respiratory mucosa was assessed. A structural abnormality of the central airways was found in 47% of subjects (40% females). In 19% of subjects, neither anatomical anomalies nor inflamed respiratory mucosa were observed, whereas in 64%, definite macroscopic mucosal inflammation was observed. Inflammation of the respiratory mucosa was associated with a significantly higher percentage of neutrophils in the BALF: median (interquartile range) 48 (14-82)% compared with 7 (0-16)% (p<0.025). A positive BALF culture was found in 62% of the infants with mucosal inflammation compared with 25% in the group without inflammation (p<0.016). 56% of the BALF samples were positive for bacterial culture. In children with persistent respiratory symptoms, nearly half have anatomical anomalies of the central airways. In 62% of the children with mucosal inflammation, a positive BAL culture and a significantly higher percentage of BALF neutrophils were detected.

Location of airway obstruction in term and preterm infants with laryngomalacia.

OBJECTIVE: The aim of this study was to describe and compare the airway findings in term and preterm infants with laryngomalacia. METHODS: A retrospective review of 130 patients diagnosed as having laryngomalacia at a tertiary referral center between July 2004 and August 2009 was conducted. Medical records were reviewed for demographic data, supraglottic and glottic airway findings, concomitant airway lesions, and the need for intervention. RESULTS: The mean gestational age and age at diagnosis was 36 and 15 weeks, respectively. Combined posterior and anterior supraglottic collapse was the most common finding (31%). Posterior collapse alone occurred in 25%, anterior collapse in 14%, and lateral collapse in 10%. Twelve percent of patients had all 3 sites of collapse. Forty-one percent of patients had a secondary airway lesion, with tracheomalacia being the most common. Preterm infants had significantly higher rates of reflux and more sites of collapse than did term infants (P < .0001). Eight patients required an intervention for their symptoms. CONCLUSIONS: Children with laryngomalacia tend to have more than 1 area of supraglottic collapse, and more than one third have a secondary lesion. All patients who required an intervention had more than 1 area of collapse, and 63% of these patients had a secondary airway lesion. Our high incidence of secondary lesions is similar to recent reports.

Flexible Endoscopic Evaluation of Swallowing in Breastfeeding Infants With Laryngomalacia: Observed Clinical and Endoscopic Changes With Alteration of Infant Positioning at the Breast.

OBJECTIVES: This retrospective cohort study uses endoscopic assessment of the pharyngeal phase of swallowing in infants with laryngomalacia, to ascertain the impact of infant positioning on airway compromise and fluid dynamics during breastfeeding. The study aims to identify whether modification of infant positioning at the breast may improve the possibility of safe, successful breastfeeding in infants with laryngomalacia and concurrent breastfeeding difficulty. METHODS: Twenty-three infants referred for noisy breathing and difficulty feeding were assessed with flexible endoscopic evaluation of swallowing (FEES) during breastfeeding. All had endoscopically confirmed laryngomalacia. During FEES, observations were made of clinical signs of airway compromise as well as endoscopically observable anatomical features and swallowing dynamics during breastfeeding, including tongue base position, view of laryngeal inlet and vocal folds, dynamic supraglottic soft tissue collapse, timing of milk flow into pyriform fossae/hypopharynx relative to sucking, and presence of penetration and/or aspiration. If airway and/or swallowing compromise was present, the infant's initial position at the breast was altered from supine or semi lateral decubitus position to semi-prone, with a description of the clinical and endoscopically observable changes that subsequently occurred. RESULTS: Signs of dynamic airway obstruction and/or compromised airway protection with swallowing were present in 20 of the 23 infants (87%) in their initial supine or semi lateral decubitus position. These 20 infants were repositioned to semi-prone, with improvement and/or resolution of stridor and an improved ability to maintain latch in all infants. Continued endoscopic evaluation following positional change was possible in 16 infants, identifying anterior positioning of the tongue base, reduced dynamic supraglottic tissue collapse, reduced volume of milk flow into pyriform fossae during pauses in sucking and resolution of penetration and aspiration. CONCLUSION: This study has shown how alteration of breastfeeding position to semi-prone may improve dynamic airway obstruction and reduce aspiration risk in infants with laryngomalacia.

Histopathology of laryngomalacia.

BACKGROUND: Laryngomalacia is the commonest laryngeal anomaly and cause of stridor in children. Although most cases are self-limiting, failure to thrive, hypoxaemia or significant apnoeic episodes may warrant surgical intervention in the form of aryepiglottoplasty. Opinion is divided as to the pathophysiological mechanisms involved in the disease process. AIMS AND OBJECTIVES: This study explores the aetiology of laryngomalacia by reviewing the histology of aryepiglottoplasty resection specimens. MATERIAL AND METHODS: The histology reports of 61 aryepiglottoplasty specimens resected between 1 October 2014 and 31 October 2018 were reviewed. RESULTS: Age of patients ranged from 3 weeks to 36 months. 36 patients were male and 25 female. 43 of 61 (70.5%) cases had inflammation, most of which were mild. 3 (4.9%) cases had histological specimens with detectable eosinophils. None of the specimens had signs of granulomatous change, ulceration or calcification. Cartilage was present in the resected specimen in 47 (77%) cases. Over half of these (59.6%) were immature cartilage. CONCLUSION AND SIGNIFICANCE: The results suggest a mild concurrent laryngitis/supraglottitis in most cases. Eosinophilia is rare and does not support eosinophilic oesophageal reflux as part of the aetiology. The high proportion of immature cartilage in the specimens supports the theory of chondropathic aetiology.

A case of Michelin tire baby syndrome with a thickened epiglottis.

Multiple circumferential skin folds have been reported as part of the Michelin tire baby syndrome (MTBS). There has been a wide spectrum of associated clinical findings reported in children with MTBS. We report a case of MTBS associated with a thickened epiglottis.

Correlation between the clinical severity of laryngomalacia and endoscopic findings.

OBJECTIVE: To correlate the clinical severity of laryngomalacia (LM) with endoscopic findings, swallowing evaluations and polysomnography in a cohort of patients. Method: We conducted a retrospective analysis between 2017-2018 on a cohort of patients diagnosed with upper airway obstruction (UAO), stridor, noisy breathing or laryngomalacia. This study took place at the Pediatric Pulmonology Department, Riley Children's Hospital, Indianapolis, United States of America. RESULTS:   There were 157 patients with laryngomalacia included in the study. Patients with severe LM were significantly younger than those with mild LM (p=0.0214) and moderate LM (p=0.0220). Subjects with type I of LM were significantly older than type III (p=0.0051). When associations were tested between polysomnogram (PSG) variables and clinical severity, there were significant associations with age at PSG. The overall apnea-hypopnea index (AHI) in mild (p=0.0103) and moderate (p=0.0242) were significantly lower than the severe group. The rapid eye movement (REM) AHI was significantly lower in moderate cases than severe (p=0.0134). The end-tidal carbon dioxide (EtCO2) peak was significantly lower in mild cases than severe (p=0.0141). The total sleep time (TST) peripheral capillary oxygen saturation (SpO2) 90% occurs in both mild (p=0.0197) and moderate (p=0.0498) were significantly lower than the severe group. CONCLUSIONS: The severity of the clinical manifestations of LM did not correlate with the different endoscopic types in our study. The presence of cyanosis was associated with type III LM. Rapid eye movement AHI and EtCO2 in polysomnogram were remained significantly associated with clinical severity.

Three-dimensional finite element modeling for evaluation of laryngomalacia severity in infants and children.

This study was performed to investigate the feasibility of using a three-dimensional (3D) finite element model for laryngomalacia severity assessment. We analyzed laryngeal computed tomography images of seven children with laryngomalacia using Mimics software. The gray threshold of different tissues was distinguishable, and a 3D visualization model and finite element model were constructed. The laryngeal structure parameters were defined. The peak von Mises stress (PVMS) value was obtained through laryngeal mechanical analysis. The PVMS values of the laryngeal soft tissue and cartilage scaffolds were independently correlated with disease severity. After stress loading the model, the relationship between laryngomalacia severity and the PVMS value was apparent. However, the PVMS value of laryngeal soft tissue was not correlated with laryngomalacia severity. This study established the efficacy of a finite element model to illustrate the morphological features of the laryngeal cavity in infants with laryngomalacia. However, further study is required before widespread application of 3D finite element modeling of laryngomalacia. PVMS values of the laryngeal cartilage scaffold might be useful for assessment of laryngomalacia severity. These findings support the notion that structural abnormalities of the laryngeal cartilage may manifest as quantifiable changes in stress variants of the supraglottic larynx.

Microdebrider-assisted supraglottoplasty for laryngomalacia.

OBJECTIVES: We describe our series in the surgical treatment of laryngomalacia using a microdebrider. METHODS: We performed a retrospective review of patients who underwent microdebrider-assisted supraglottoplasty for laryngomalacia between October 2004 and February 2008. Patients with neurologic conditions and secondary airway lesions were excluded. The main outcome measures included complications, pain, resolution of stridor, presence of aspiration, and need for revision surgery. RESULTS: Twenty-eight patients underwent microdebrider-assisted supraglottoplasty. The mean age at diagnosis was 109 days, and the mean age at the time of the procedure was 182 days. Nineteen patients (68%) had gastroesophageal reflux at diagnosis. The average operative time was 35.7 minutes (range, 11 to 65 minutes). No intraoperative complications or device problems occurred. Two patients remained intubated after the procedure. One patient required a tracheotomy, and 1 patient underwent revision supraglottoplasty. Three patients had aspiration that resolved. There was negligible pain from the procedure, as all patients immediately resumed a diet. All patients had immediate or eventual resolution of stridor. CONCLUSIONS: This is the largest series of patients who underwent microdebrider-assisted supraglottoplasty for laryngomalacia. This procedure is relatively safe, with minimal pain, and effective in patients with laryngomalacia. Microdebrider-assisted supraglottoplasty is the method of choice for supraglottoplasty in our institution.

General anesthesia for a patient with deletion 6q syndrome in addition to laryngomalacia undergoing dental treatment.

Chromosome 6 deletions are very rare (1,2), and deletion 6q syndrome is clinically characterized by mental and/or neuromotor retardation and microcephaly (3). Other alterations frequently observed are decreased biparietal diameter, hypertelorism, hypotelorism, absent eyebrows, prominent eyes with ptosis, receding chin, dysmorphic ears, large extremities, prominent nasal bridge, long philtrum, epicthus, strabismus, and micrognathia (3-5). Laryngomalacia is the most common congenital laryngeal anomaly and the most frequent cause of stridor in infants (6-11). We report the case of a 14-year-old male patient with both deletion 6q syndrome and laryngomalacia, who we treated for multiple dental caries. He had a medical history of tracheotomy at age 11 years for laryngomalacia, and has suffered from epileptic attacks and aspiration pneumonia over the last 2 and 6 years, respectively. Since he was mentally retarded and in a poor respiratory state, dental treatment under general anesthesia was scheduled in our hospital. General anesthesia was induced and maintained using 30% nitrous oxide and 1-3% sevoflurane in oxygen through the tracheotomy tube. Pre- and intraoperative endotracheal suction improved the condition of both lungs markedly and the procedures were uneventful and completed in 2 h and 58 min.

[Anesthetic management for laryngoscopic evaluation of upper airway stenosis using our modified endoscopic mask].

Young children are at increased risk for hypoxaemia and hypercapnea during flexible laryngoscopy due to the small size and increased collapsibility of their airways. To evaluate upper airway stenosis of a 5-year-old girl presenting with retractive inspiratory breathing, we developed a modified endoscopy mask consisting of a regular face mask where the original port for endoscope was replaced by a disposable rubber dam. This setting allows a leak-free passage of both nasal and oral endoscopy and enables emergent endoscopic intubation through a small hole of a rubber dam. Using this airtightly sealed modified mask, we successfully managed diagnostic endoscopy of laryngomalacia and evaluated infolding of arytenoids under spontaneous ventilation with 100% oxygen.

Laryngomalacia: is there an evidence base for management?

BACKGROUND: The advent of supraglottoplasty clearly has transformed the surgical management of severe laryngomalacia. The condition, however, generally runs a milder course, with spontaneous resolution the norm. OBJECTIVES: To identify gaps in the knowledge and identify topics for future study. METHOD: Systematic review of the literature. RESULTS: The literature suggests that there is a range of abnormalities leading to the typical collapsing upper airway, and that neurological disease, other airway abnormalities, syndromes and gastroesophageal reflux all contribute to disease severity and influence outcomes. The procedures involved in supraglottoplasty are rarely specified, the indications for surgery are vaguely defined and the role of medical therapy is unclear. CONCLUSION: Every review article or survey of opinion suggests that there is still a marked variation in individual practice and a lack of consensus.

Neurological manifestations of 2q31 microdeletion syndrome.

Microdeletion of 2q31 involving the HOXD gene cluster is a rare syndrome. The deletion of the HOXD gene cluster is thought to result in skeletal anomalies in these patients. HOX genes encode highly conserved transcription factors that control cell fate and the regional identities along the primary body and limb axes. We experienced a new patient with 2q31 microdeletion encompassing the HOXD gene cluster and some neighboring genes including the ZNF385B. The patient showed digital anomalies, growth failure, epileptic seizures, and intellectual disability. Magnetic resonance imaging showed delayed myelination and low signal intensity in the basal ganglia. The ZNF385B is a zinc finger protein expressed in brain. Disruption of ZNF385B was suspected to be responsible for the neurological features of this syndrome.

The groningen laryngomalacia classification system--based on systematic review and dynamic airway changes.

OBJECTIVE: Laryngomalacia is the most common cause of dyspnea and stridor in newborn infants. Laryngomalacia is a dynamic change of the upper airway based on abnormally pliable supraglottic structures, which causes upper airway obstruction. In the past, different classification systems have been introduced. Until now no classification system is widely accepted and applied. Our goal is to provide a simple and complete classification system based on systematic literature search and our experiences. STUDY DESIGN: Retrospective cohort study with literature review. METHODS: All patients with laryngomalacia under the age of 5 at time of diagnosis were included. Photo and video documentation was used to confirm diagnosis and characteristics of dynamic airway change. Outcome was compared with available classification systems in literature. RESULTS: Eighty-five patients were included. In contrast to other classification systems, only three typical different dynamic changes have been identified in our series. Two existing classification systems covered 100% of our findings, but there was an unnecessary overlap between different types in most of the systems. Based on our finding, we propose a new a classification system for laryngomalacia, which is purely based on dynamic airway changes. CONCLUSION: The groningen laryngomalacia classification is a new, simplified classification system with three types, based on purely dynamic laryngeal changes, tested in a tertiary referral center: Type 1: inward collapse of arytenoids cartilages, Type 2: medial displacement of aryepiglottic folds, and Type 3: posterocaudal displacement of epiglottis against the posterior pharyngeal wall.