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.

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.

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.

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.

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.

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.

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.

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.

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.

Upper airway abnormalities detected in children using flexible bronchoscopy.

OBJECTIVES: Rapid anatomical evaluation is essential to establish the severity of cases with upper respiratory obstruction and to define the degree of respiratory distress. Detailed airway endoscopy is required in most patients, not only for diagnosis, but also to treat the condition. In this study, as two of the largest paediatric pulmonology centres in Turkey, we reviewed the data of our bronchoscopy patients, and aimed to document the upper airway abnormalities that we detected during these procedures. PATIENTS AND METHODS: A retrospective analysis was made of the records of 1076 paediatric cases with pulmonary/airway disease who had undergone flexible bronchoscopy between 2007 and 2011. RESULTS: Upper airway malacia disorders were the most common (79.6%, n=259) bronchoscopic findings detected in the patients. The other most common pathologies were laryngeal edema (12.9%, n=42), external tracheal compression (12.3%, n=40), subglottic stenosis (4.0%, n=13), tracheal stenosis (2.8%, n=9), and vocal cord paralysis/irregularity (2.8%, n=9). The mean duration of symptoms was shortest in patients with vocal cord paralysis, and longest in patients with tracheal nodules (p<0.001). CONCLUSION: Paediatricians should keep in mind the possibility of malacia disorders and other congenital and acquired upper airway abnormalities in children with chronic respiratory problems. Diagnosis of underlying diseases, as soon as possible, permits the withdrawal of antibiotics or antiasthmatic drugs often used unnecessarily for long periods to treat these children.

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.

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.

Comparison between rigid and flexible laser supraglottoplasty in the treatment of severe laryngomalacia in infants.

OBJECTIVE: Traditionally, laser supraglottoplasty for the treatment of severe laryngomalacia (SLM) is via rigid endoscopy (RE). Potassium-titanyl-phosphate (KTP) laser fiber can pass through a flexible endoscopy (FE) and cauterize tissue. This study is designed to evaluate and compare clinical variables between these two techniques in the treatment of SLM in infants. METHODS: A retrospective study includes four-year period of consecutive infants who received laser supraglottoplasty. In the first two years (2006-2007), conventional RE CO(2)-laser with general anesthesia and endotracheal intubation were used. In the latter two years (2008-2009), a novel technique of FE KTP-laser with intravenous sedation, nasopharyngeal oxygen and a noninvasive respiratory support (if indicated), without any artificial airway was used immediately after the diagnostic FE. After laser surgery, infants were followed for three months. Clinical variables were analyzed and compared. RESULTS: A total of 57 infants (27 in RE group, 30 in FE group) were enrolled. Basic variables were similar between both groups. Clinical improvement was comparable with 88.9% and 93.3% in the RE and FE groups, respectively. There are no significant differences in mean number of laser surgery, major complications, duration of post-laser respiratory support and hospitalization days, body weight percentile between the two groups. However, the durations of waiting time, operation, ET intubation and total hospital days were significantly less in the FE group. CONCLUSIONS: FE technique has similar success rate but more convenient and cost-effective than the RE technique. It may to be a practical alternative therapy for infants with SLM.

Submucosal nerve hypertrophy in congenital laryngomalacia.

OBJECTIVES/HYPOTHESIS: To determine the neuropathologic findings in tissue obtained from children with laryngomalacia at a tertiary-care pediatric hospital. STUDY DESIGN: Retrospective review of consecutive cohort compared with a control group. METHODS: We reviewed supra-arytenoid pathology specimens from 43 children with severe laryngomalacia and 13 age-matched pediatric autopsy controls. Histopathologic comparison was made of nerve hypertrophy (including nerve perimeter and surface area) among experimental and control pathologic specimens. RESULTS: There exists a statistically significant increase in nerve perimeter (P = .001) and nerve surface area (P = .02) in supra-arytenoid specimens in patients with severe laryngomalacia compared with age-matched autopsy supra-arytenoid tissue. CONCLUSIONS: The pathologic finding of nerve hypertrophy in children with laryngomalacia provides new evidence to support neurologic dysfunction as the etiologic theory of laryngomalacia.

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.

Supraglottoplasty outcomes in relation to age and comorbid conditions.

OBJECTIVE: To determine if age and comorbid conditions effect outcomes in children undergoing supraglottoplasty for severe laryngomalacia. DESIGN: Retrospective study. SETTING: Urban tertiary-care children's hospital. PATIENTS: Children undergoing supraglottoplasty for severe laryngomalacia between February 2004 and July 2008. 56 patients were identified. OUTCOME MEASURES: Persistence of upper airway obstruction, revision surgery (supraglottoplasty), and additional surgery (tracheostomy). RESULTS: 33/56 (58.9%) patients had no comorbid conditions and 23/56 (41.1%) patients had comorbid conditions. In noncomorbid patients, 36.4% of those less than 2 months of age at the time of surgery required revision supraglottoplasty, compared to 5.3% of patients between 2 and 10 months (p<0.05). Compared to the 2-10-month age group, there was a significantly higher percentage of patients with comorbid conditions in the >10-month group (32.1% vs. 79%, p<0.01). Patients with comorbid conditions were diagnosed at a significantly later age than those without (6 mo vs. 2 mo, respectively), and had significantly higher rates of revision supraglottoplasty (47.8% vs. 18.2%) and tracheostomy (39.1% vs. 0.0%). 70% of children with neurological conditions required revision surgery, with 60% requiring tracheostomy. The revision surgery and tracheostomy rates were significantly higher compared to the noncomorbid group (p<0.01 and p<0.0001). Children with cardiac conditions had a higher rate of tracheostomy than noncomorbid children (30% vs. 0%, p<0.01). 16.7% of children with genetic conditions required supraglottoplasty, and none required tracheostomy. CONCLUSIONS: In noncomorbid patients, those undergoing supraglottoplasty less than 2 months of age had a significantly higher rate of revision supraglottoplasty. Patients with neurologic and cardiac comorbidities require tracheostomy at a significantly higher rate than noncomorbid patients.