Update on gastroesophageal reflux disease in pediatric airway disorders.

In this article, the literature regarding the effects of gastroesophageal reflux disease (GERD) on otolaryngologic disorders in infants and children is reviewed. We specifically focus on studies that suggest how GERD may be associated with sinusitis, cough, laryngitis, airway obstruction, apnea, recurrent croup, laryngomalacia, stridor, and subglottic stenosis in children.

Esophageal biopsy for the diagnosis of gastroesophageal reflux-associated otolaryngologic problems in children.

Recently, gastroesophageal reflux (GER) has been found to contribute to many types of otolaryngologic pathology in infants and children. The complaints may be intermittent and unresponsive to usual therapies, such as antimicrobial treatments. A high index of suspicion for GER and for the concept of "silent" GER (GER without overt symptoms) is necessary for accurate diagnosis and treatment of otolaryngologic manifestations of GER in these patients. In this prospective historical cohort study, the records were reviewed from 101 children who underwent esophagoscopy and biopsy as a diagnostic test for GER at the time of other otolaryngologic procedures. Significant associations were found between the presence of histologic esophagitis and asthma, recurrent croup, cough, apnea, sinusitis, stridor, laryngomalacia, subglottic stenosis, posterior glottic erythema, and posterior glottic edema. There were no complications. Esophageal biopsy is a rapid, safe and effective diagnostic test for GER that should be considered at the time of other procedures in children with selected GER-associated problems.

Subglottic injury, gastric juice, corticosteroids, and peptide growth factors in a porcine model.

OBJECTIVES: To study the effects of mucosal injury, gastric juice, and corticosteroids and to determine the presence of peptide growth factors in the subglottic mucosa in a porcine model. STUDY DESIGN: Prospective cohort animal study. METHODS: In this model of subglottic injury, five groups (n = 5 each) of piglets were used. Injury was induced by electrocautery (acute), electrocautery plus repeated saline application (chronic), electrocautery plus repeated gastric juice application (chronic plus gastric juice), or repeated gastric juice application (gastric). Control piglets had normal saline applied repeatedly. RESULTS: Histopathologic findings for the gastric juice group included basal cell hyperplasia (80%), squamous metaplasia (80%), and mucosal ulceration (40%). Control piglets showed squamous metaplasia (80%) but no basilar hyperplasia or ulceration. Immunohistochemistry detected peptide growth factors and epidermal growth factor receptor (EGFR) in all groups. Decreased staining was most frequent in the acute injury group. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) documented lower expression of EGFR in the gastric juice group (P = .01). CONCLUSIONS: These findings suggest that peptide growth factors and EGFR are part of normal subglottic mucosal turnover. Noxious stimuli decrease production of these factors. Gastric juice had adverse effects documented by histopathology and molecular techniques.

Characterization of cytokines present in middle ear effusions.

Retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion (COME), results in ongoing inflammation with the potential for pathologic changes and hearing loss. Cytokines are glycoproteins produced by macrophages and other cells. Activities of cytokines include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell activation, regulation of antibody formation, and inhibition of cartilage, bone and endothelial cell growth. Using enzyme-linked immunospecific assays we measured levels of six cytokines in middle ear effusions (MEE) from children with COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50 pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth cytokine, interleukin-4, were undetectable. Age was observed to have a significant effect on the levels of specific cytokines. Interleukin-1 (IL-1) correlated inversely (P less than .02) with age such that the younger the child, the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated directly (P less than .005) with age such that the older the child, the higher the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly 14 times higher (P less than .005) than those from children undergoing their first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with the early stages of COME, while TNF correlated with persistence of disease. The presence of these cytokines in MEE may be responsible for the mucosal damage, bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME.

Sensorineural hearing loss from quinolinic acid: a neurotoxin in middle ear effusions.

Quinolinic acid (QUIN) is an endogenous metabolite that exerts a neurotoxic effect by binding to specific neuronal receptors. Studies involving a broad spectrum of infectious and inflammatory central nervous system diseases have suggested a role for QUIN in causing neuronal injury. Since there is evidence for presence of the QUIN receptor in mammalian cochleas, QUIN was measured in middle ear effusions (MEEs). Gas chromatography/mass spectrometry detected QUIN in each of 65 diluted human MEEs, with a mean of 482 +/- 75 (SEM) nmol/L and a range from 15 to 2667 nmol/L. QUIN was also detected in each of 197 chinchilla MEEs from five different models of otitis media, with a mean of 10.6 +/- 1.3 (SEM) mumol/L and a range from 0.23 to 146.0 mumol/L (corrected for dilution). To determine whether QUIN causes sensorineural hearing loss (SNHL), QUIN solutions were placed on round window membranes (RWM) for 20 to 240 minutes, in 20 chinchillas. SNHL was detected by electrocochleography in QUIN-exposed animals, but not in saline controls. We conclude that QUIN is present in MEEs and that QUIN in the middle ear has the potential to cross the RWM and cause sensorineural hearing loss, possibly by binding to specific neuronal receptors in mammalian cochleas.

Complications following airway surgery in Noonan syndrome.

Two children with Noonan syndrome underwent airway surgery and both experienced spontaneous chylothorax after surgery. The Noonan syndrome phenotype may include defects that significantly increase the risk of complications associated with surgery. Manifestations of Noonan syndrome may include congenital heart disease; coagulation factor deficiency; pterygium colli; and lymphangiomatosis of the pleura, lungs, and chest wall that can lead to life-threatening chylothorax. In this article, the 2 cases are presented and the relevant literature is reviewed to increase awareness of the potential problems that may be encountered in patients with Noonan syndrome. Recommendations are made regarding preoperative investigations and perioperative management to prevent complications.

Efficacy of a stepwise protocol that includes intravenous antibiotic therapy for the management of chronic sinusitis in children and adolescents.

BACKGROUND: Recent concern regarding interference with facial skeletal growth and the risk of complications after endoscopic sinus surgery (ESS) has led to interest in exploring other treatment options for the management of chronic sinusitis in children. OBJECTIVE: To present the use of a stepwise protocol that includes intravenous (IV) antibiotic therapy as a therapeutic alternative to pediatric ESS. DESIGN: Retrospective analysis of pediatric patients with chronic sinusitis treated from January 1, 1993, to July 1, 1998, with a stepwise protocol that includes the use of IV antibiotics. SETTING: Academic tertiary care children's hospital. PATIENTS: Seventy patients, aged 10 months to 15 years, with the diagnosis of chronic sinusitis as defined by symptomatic disease for at least 12 weeks. All patients had persistent symptoms and radiographic evidence of sinus disease by computed tomographic scan after a minimum 3- to 4-week course of oral antibiotics. INTERVENTIONS: Patients were treated with maxillary sinus aspiration and irrigation with selective adenoidectomy, followed by a 1- to 4-week course of a culture-directed IV antibiotic. Most patients also underwent placement of a long-arm IV catheter. OUTCOME MEASURES: Medical charts were reviewed for clinical response to IV antibiotics, complications from IV antibiotic therapy, need for ESS, and recurrent episodes of sinusitis. RESULTS: Of the 70 patients studied, 62 (89%) had complete resolution of symptoms following IV therapy with selective adenoidectomy. Eight patients (11%) failed IV therapy and required ESS. Thirty-seven patients (53%) underwent concurrent adenoidectomy. Patients treated with concurrent adenoidectomy had equivocal response rates compared with patients treated with IV antibiotic therapy alone. Follow-up data were available for 52 patients (range, 6-62 months; mean, 25 months). All recurrent episodes resolved with oral antibiotic therapy. Complications from IV therapy included superficial thrombophlebitis in 6 patients (9%) and dislodgement of a catheter guidewire during placement in 1 patient (1%), requiring venotomy. Antibiotic-related complications also occurred in 3 patients (4%) and included serum sickness, pseudomembranous colitis, and drug fevers. CONCLUSION: A stepwise protocol that includes IV antibiotic therapy is a safe and efficacious mode of therapy for the management of chronic sinusitis in children and adolescents and may be a reasonable alternative to pediatric ESS.

Demonstration of interleukin 6 in middle ear effusions.

In response to infection in the middle ear, inflammatory cells produce cytokines--potent regulators and mediators of the immune response. In an earlier study, we demonstrated that levels of the cytokine interleukin 1 were higher in middle-ear effusions from younger children, while levels of the cytokine tumor necrosis factor were higher in middle-ear effusions from older children and in those requiring tympanostomy on multiple occasions. In this study, we evaluated middle-ear effusions for levels of the cytokine interleukin 6. Activities of interleukin 6 include stimulation of bone erosion and production of antibodies and fever. Using an enzyme-linked immunosorbent assay system, significant levels of interleukin 6 (greater than 0.2 pg/mL) were found in 14 (36%) of 39 middle-ear effusions from 25 children with otitis media with effusion. The mean (+/- SE) level of interleukin 6 in middle-ear effusions was 173.9 +/- 74.7 pg/mg of total protein. Like interleukin 1, levels of interleukin 6 were higher in younger children. Tumor necrosis factor may be an important regulator of the local immune response in the middle-ear cleft during persistence of otitis media with effusion, while interleukin 1 and interleukin 6 may be important regulators during the early stages of otitis media with effusion.

Cytokines, immunoglobulins, and bacterial pathogens in middle ear effusions.

OBJECTIVE: To elucidate the role of cytokines, immunoglobulins, and bacterial pathogens in the middle ear effusions (MEEs) of children with otitis media (OM). DESIGN: Paired MEEs and serum samples collected from consecutive patients were assayed for immunoglobulins. Middle ear effusions were cultured for bacterial pathogens and assayed for interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and interferon gamma. The medical charts of the patients were retrospectively reviewed to define the history of OM. SUBJECTS: Seventy-five patients with a history of recurrent acute OM, persistent OM with effusion, or both. Exclusion criteria included the presence of a major coexisting condition, or an unclear or atypical history of OM. SETTING: A private practice at a tertiary care children's hospital. INTERVENTIONS: At the time of tympanostomy tube placement, with the patient under general anesthesia, one MEE and a serum sample were collected. RESULTS: Interleukin-1 beta was detected in 58% (44/75) MEEs; interleukin-6, 83% (60/72); tumor necrosis factor alpha, 37% (28/75) [corrected]; and interferon gamma, 61% (45/74). Concentrations of interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha in MEEs were highly correlated with each other (P < .01 for each association) suggesting increased local production and the expected effects of cytokines stimulating their own production during OM. High concentrations of tumor necrosis factor alpha in MEEs were also associated with a history of multiple placements of tympanostomy tubes (r = .63). CONCLUSIONS: These data suggest a regulatory role for cytokines in inflammation during OM, and suggest that high concentrations of tumor necrosis factor alpha in MEEs may be a marker for OM chronicity.

Alternative to endoscopic sinus surgery in the management of pediatric chronic rhinosinusitis refractory to oral antimicrobial therapy.

We determined the safety, feasibility, and efficacy of a treatment regimen consisting of maxillary sinus aspiration and irrigation with or without adenoidectomy, followed by culture-directed intravenous antibiotics and oral prophylaxis, for children with chronic rhinosinusitis refractory to oral antimicrobial therapy. Twenty-seven children (age 1-12 years, mean 6.7 years) with symptomatic (mean duration 16 months) and computed tomography-proven sinus disease, which persisted despite at least 1 month of oral antibiotics, were treated. Twenty-four patients (89%) had complete resolution of their presenting symptoms after intravenous therapy; in 3 (11%), intravenous therapy failed and endoscopic sinus surgery was required. Follow-up data were available for 26 of the children (96%); 23 of them had initial complete resolution. At last follow-up (mean 282 days, range 26-1095 days), 10 of these 23 patients (44%) remained asymptomatic, and 13 (57%) had had at least one other episode of sinusitis (mean 1.0, range 1-3) treated with oral antibiotics, with resolution. Treatment-related complications included superficial thrombophlebitis (7%), diarrhea (7%), intravenous catheter guide-wire kink requiring venotomy (4%), and serum sickness-like syndrome (4%). These preliminary results suggest that this treatment plan is relatively safe and feasible and that it may be a reasonable alternative to endoscopic sinus surgery in children with chronic rhinosinusitis unresponsive to orally administered antimicrobial therapy.

Head and neck space infections in infants and children.

A retrospective study was performed in 117 children with head and neck space infections treated at the Children's Hospital of Pittsburgh from January 1986 through June 1992. Peritonsillar space infections were the most common (49%), followed by retropharyngeal (22%), submandibular (14%), buccal (11%), parapharyngeal (2%), and canine (2%) space infections. The most common pathogens isolated (N = 78) were the aerobes beta-hemolytic streptococcus (18%) and Staphylococcus aureus (18%), the anaerobes Bacteroides melaninogenicus (17%) and Veillonella (14%), and the gram-negative organism Haemophilus parainfluenzae (14%). beta-Lactamase production by aerobic pathogens was detected in 22% of cultures. Computed tomography scans (N = 16) were reviewed in blinded fashion and compared with operative findings. The sensitivity of computed tomography scan in detecting the presence of an abscess vs. cellulitis was high (91%), whereas the specificity was rather low (60%). Treatment of head and neck space infections in children should consist of accurate physical diagnosis aided by imaging studies, empiric antibiotic therapy that covers gram-negative and beta-lactamase--producing organisms as well as gram-positive organisms and anaerobes, and timely surgical intervention, when indicated.

Totally obstructing tracheotomy-associated suprastomal granulation tissue.

Although tracheotomy-associated suprastomal granulation tissue is quite common, suprastomal granulation tissue that totally obstructs the airway is relatively rare and can be associated with serious complications. In this report the complications and management of six cases of totally obstructing suprastomal granulation tissue (TOSGT) are presented. Complications associated with the presence or management of TOSGT included progression of subglottic stenosis, development of posterior laryngeal stenosis, development of supraglottic stenosis following CO(2) laser supraglottoplasty, and dislodgement of the TOSGT with distal tracheal obstruction resulting in anoxic brain injury. It is recommended that the tracheotomy tube remains in position at all times during attempted removal, and that if endoscopic removal is not possible, that open tracheoplasty is the safest method for removal. Measures that may decrease the chances of recurrence include diligent diagnosis and treatment of gastroesophageal reflux disease (GERD) and bacterial infection. TOSGT may be a marker for some patients with abnormal wound healing.

Decreasing morbidity following laryngotracheal reconstruction in children.

Our objectives are to report (1) methods for decreasing infectious complications and excessive weakness associated with the period of sedation and neuromuscular blockade (NMB) following single-stage laryngotracheal reconstruction (SSLTR); (2) an association between gastroesophageal reflux (GER) and subglottic stenosis (SGS); (3) results of 21 SSLTRs and 15 two-stage LTRs (TSLTRs). A retrospective chart review was performed for the period January, 1990-August, 1995, including 36 patients who had 38 LTRs for SGS and/or posterior glottic stenosis at a tertiary care center. Our most recent post-SSLTR protocol included: (1) prophylactic antimicrobials (clindamycin plus antipseudomonal agents = C + A); (2) GER treatment; (3) titrated infusion NMB with daily recovery of neuromuscular function; (4) avoidance of prolonged simultaneous administration of NMB and corticosteroids. Patients who had prophylactic antimicrobials (C + A) during intubation following SSLTR had fewer (1/13, 8%) postoperative infectious complications than patients who received other/no antibiotics (4/8, 50%) (P < 0.05). Avoidance of prolonged simultaneous administration of NMB and corticosteroids and use of titrated infusion of NMB with daily recovery of neuromuscular function was associated with less weakness following extubation (0/11, 0% vs. 4/6, 66%) (P < 0.002). Of 26 patients tested for GER, 21 (81%) had at least one positive test, suggesting a significant association between GER and SGS (P < 0.05). The overall success rate for LTR was 33/36 or 92%. SSLTR had a 95% success rate while two-stage LTR had an 87% success rate, although two revisions were required. Prophylactic antimicrobials, improved postoperative management and GER treatment allowed successful LTRs with decreased infectious complications and less weakness.

Teratoid cyst of the floor of the mouth.

Because the term 'dermoid' is frequently used in the literature, some authors believe that this term should be used for all congenital cysts of the floor of the mouth. Three subclasses of congenital floor of the mouth cysts are described in the literature: (1) epidermoid (simple) cysts, (2) dermoid (complex) cysts and (3) teratoid (complex) cysts. The teratoid cyst is the least common. Most of these cases present during the second and third decades of life, thus presentation during infancy is extremely rare. Surgical excision is the treatment of choice. We present a 2-month old male who underwent expedient surgical excision for progressive airway compromise secondary to a teratoid cyst of the floor of the mouth. Radiographic and histopathologic evidence, as well as a review of the literature is presented.

Unmasked residual neuromuscular block after administration of vecuronium for days.

IMPLICATIONS: Significant neuromuscular block may be present in patients who have received vecuronium for days.

Effect of blood microfilters on complement activity in human plasma.

While many devices that come into direct contact with patients' blood have been shown to be safe with respect to their effects on the cellular components and coagulation system of blood, many have not been examined with respect to their potential to activate the complement system. We present evidence that suggests that a combination of nylon plus polypropylene, and a combination of polyester plus polypropylene, found in blood microfilters used to protect patients from gaseous and particulate embolism during cardiopulmonary bypass, produce significant (p less than 0.01, p less than 0.05, respectively) C3a generation during incubation in heparinized plasma. Filter mesh composed of nylon plus polypropylene produced significantly more (p less than 0.01) C3a than the polyester plus polypropylene combination.

Recovery from doxacurium infusion administered to produce immobility for more than four days in pediatric patients in the intensive care unit.

Doxacurium was administered by titrated infusion to 14 pediatric patients for 4.7-12.3 days after laryngotracheal reconstruction to produce minimum spontaneous movement and less than five posttetanic movements of the first toe after stimulation of the posterior tibial nerve. Recovery was documented by stimulation of the ulnar nerve with 2 Hz for 2 s (train-of-four [TOF]) at intervals of 1 min and measurement of the ratio of the fourth to the first response (TOF ratio) at the adductor pollicis. During spontaneous recovery, the TOF ratio was between 0.4 and 0.7 for 0.6-3.3 h, mean (SEM) 2.2 (0.31) h. The TOF ratio equaled 1 between 4.7 and 23.0 h, mean (SEM) 11.0 (2.1) h after termination of doxacurium infusion. In six of the patients, weakness and decreased coordination were noted for a few days to weeks postoperatively. There were no complications related to impairment of upper airway function or ventilation in those patients who had recovery of neuromuscular transmission to the extent of TOF ratio equal to 1 prior to extubation or in those patients in whom weakness or lack of coordination was noted after tracheal extubation.