Competency-Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal. STUDY DESIGN: Blinded modified Delphi consensus process. SETTING: Tertiary care center. METHODS: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items. RESULTS: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus. CONCLUSIONS: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:1168-1174, 2021.

Competency-Based Assessment Tool for Pediatric Tracheotomy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric tracheotomy. STUDY DESIGN: Blinded, modified, Delphi consensus process. METHODS: Using the REDCap database, a list of 31 potential items was circulated to 65 expert surgeons who perform pediatric tracheotomy. In the first round, items were rated as "keep" or "remove," and comments were incorporated. In the second round, experts were asked to rate the importance of each item on a seven-point Likert scale. Consensus criteria were determined a priori with a goal of 7 to 25 final items. RESULTS: The first round achieved a response rate of 39/65 (60.0%), and returned questionnaires were 99.5% complete. All items were rated as "keep," and 137 comments were incorporated. In the second round, 30 task-specific and seven previously validated global rating items were distributed, and the response rate was 44/65 (67.7%), with returned questionnaires being 99.3% complete. Of the Task-Specific Items, 13 reached consensus, 10 were near consensus, and 7 did not achieve consensus. For the 7 previously validated global rating items, 5 reached consensus and two were near consensus. CONCLUSIONS: It is feasible to reach consensus on the important steps involved in pediatric tracheotomy using a modified Delphi consensus process. These items can now be considered to create a competency-based assessment tool for pediatric tracheotomy. Such a tool will hopefully allow trainees to focus on the important aspects of this procedure and help teaching programs standardize how they evaluate trainees during this procedure. LEVEL OF EVIDENCE: 5 Laryngoscope, 130:2700-2707, 2020.

Bridging the gap: Using 3D printed polycaprolactone implants to reconstruct circumferential tracheal defects in rabbits.

OBJECTIVE: 1) To assess the feasibility of reconstructing 2-cm-long circumferential tracheal defects with a 3D printed polycaprolactone (PCL) implant in rabbits. 2) To evaluate endoscopic, histologic, and functional characteristics of a PCL tracheal implant over time. METHODS: Ten New Zealand rabbits were included in this study. A 2-cm-long 3D printed PCL tracheal implant was created. All rabbits underwent surgical excision of a 2-cm-long cm segment of cervical trachea, which was reconstructed with the implant. Rabbits were sacrificed at the following time points: 0, 4, 5, 6, and 7 weeks postoperatively. At these time points, a rigid bronchoscopy was performed, and blinded evaluators calculated the percentage of airway stenosis. The tracheas were then harvested and prepared for histologic analysis. RESULTS: All rabbits survived to their date of sacrifice except for one. Rabbits were euthanized between 0 to 54 days postoperatively with a median of 30 days. All rabbits developed significant granulation tissue with an average percentage stenosis of 92.3% ± 6.1%. On histology, granulation was present with extensive neovascularization and mixed inflammatory cells. There was re-epithelialization present on the luminal surface of the PCL implant near the anastomoses but absent at the center of the implant. CONCLUSION: This study demonstrates that our 2-cm-long 3D printed PCL tracheal implant can be used to reconstruct a tracheal defect of equivalent size in a New Zealand rabbit model in the short term. However, significant granulation tissue formation limits long-term survival. Further research is warranted to limit the granulation tissue overgrowth. LEVEL OF EVIDENCE: NA Laryngoscope, 2019.

Rhinologic manifestations of Burkitt Lymphoma in a pediatric population: Case series and systematic review.

INTRODUCTION: Burkitt lymphoma (BL), an aggressive form of B-cell non-Hodgkin's lymphoma, arising from the nose and paranasal sinuses is relatively rare. It can present with various symptoms leading to potential misdiagnosis and delayed treatment. BL is fatal if left untreated, while early identification and treatment can improve prognosis. OBJECTIVES: 1) To review clinical presentations and sites of involvement of six cases of pediatric BL with rhinologic manifestations and compare these with the current literature. 2) To raise awareness on the variety of presentations of BL in this particular anatomic location. METHODS: A series of six cases of pediatric (0-18 years) BL with rhinologic manifestations is presented. Age, sex, ethnicity, symptoms, imaging, staging, treatment and outcome were recorded. A systematic review of literature was also conducted using PRISMA guidelines. The search strategy used keywords related to rhinologic manifestations of BL (nasal cavity, nasopharynx, paranasal sinus etc.; Burkitt etc.) and included studies published in English and French describing patients 0-18 years of age. RESULTS: 42 patients were included (six from case series and 36 from current literature). Most common presenting symptoms were: nasal obstruction (29%), facial swelling (24%), headache (21%) and proptosis (19%). Most frequent sites of presentation were: nasopharynx (40%), maxilla (40%) and sphenoid (33%). More than half (60%) had systemic involvement, of which the most common locations were: kidney (19%), pancreas (17%) and liver (17%). Mortality from BL in children from this study population was correlated with a longer duration of symptoms prior to presentation, as well as a misdiagnosis preceding the final diagnosis of BL. CONCLUSIONS: This study brings understanding to the numerous presentations of the same aggressive disease, promotes high clinical suspicion when evaluating common otolaryngologic symptoms and can guide healthcare providers in diagnosing pediatric BL with rhinologic manifestations.

Concha bullosa mucocele: A case series and review of the literature.

BACKGROUND: Concha bullosa mucocele is a rare diagnosis that presents as a nasal mass. It impinges on surrounding structures and can easily be mistaken for a neoplasm. OBJECTIVE: The objective of this study was to shed light on this rare entity and report its diagnostic features and treatment outcomes. METHODS: A case series conducted in a tertiary health care center. Demographic data, clinical presentation, imaging, cultures, and treatments were recorded. Operative video illustration and key images were obtained. A review of the literature was also performed. RESULTS: A total of five cases were reviewed, four of which were concha bullosa mucoceles and one was a mucopyocele. Three of the patients had some form of previous nasal trauma. Headache and nasal obstruction were the most common symptoms with a nasal mass finding on physical examination. Computed tomography was used in all the patients, and magnetic resonance imaging was used in four of the five patients. Four patients had coexistent chronic rhinosinusitis, and three had positive bacterial cultures. All these patients were treated endoscopically either with middle turbinate marsupialization or subtotal resection. No recurrence has been noted thus far. CONCLUSION: Concha bullosa mucocele is a rare diagnosis. Imaging characteristics are helpful in considering the diagnosis, although surgical intervention is often necessary to confirm the diagnosis and treat concha bullosa mucocele.

Lund-Mackay and modified Lund-Mackay score for sinus surgery in children with cystic fibrosis.

OBJECTIVE: Patients with cystic fibrosis (CF) frequently present with severe sinonasal disease often requiring radiologic imaging and surgical intervention. Few studies have focused on the relationship between radiologic scoring systems and the need for sinus surgery in this population. The objective of this study is to evaluate the Lund-Mackay (LM) and modified Lund-Mackay (m-LM) scoring systems in predicting the need for sinus surgery or revision surgery in patients with CF. METHODS: We performed a retrospective chart review of CF patients undergoing computed tomography (CT) sinus imaging at a tertiary care pediatric hospital from 1995 to 2008. Patient scans were scored using both the LM and m-LM systems and compared to the rate of sinus surgery or revision surgery. Receiver-operator characteristics curves (ROC) were used to analyze the radiological scoring systems. RESULTS: A total of 41 children with CF were included in the study. The mean LM score for patients undergoing surgery was 17.3 (±3.1) compared to 11.5 (±6.2) for those treated medically (p<0.01). For the m-LM, the mean score of patients undergoing surgery was 20.3 (±3.5) and 13.5 (±7.3) for those medically treated (p<0.01). Using a ROC curve with a threshold score of 13 for the LM, the sensitivity was 89.3% (95% CI of 72-98) and specificity of 69.2% (95% CI of 39-91). At an optimal score of 19, the m-LM system produced a sensitivity of 67.7% (95% CI of 48-84) and specificity of 84.6% (95% CI of 55-98). CONCLUSION: The modified Lund-Mackay score provides a high specificity while the Lund-Mackay score a high sensitivity for CF patients who required sinus surgery. The combination of both radiologic scoring systems can potentially predict the need for surgery in this population.

Congenital intra-oral adhesions: a surgical approach to cleft palate lateral synechia syndrome.

An array of genetic syndromes has been associated with intra-oral adhesions in neonates. The primary medical issues arise from airway obstruction, feeding difficulties and poor oral development, specifically with cleft palate lateral synechia syndrome (CPLSS). Despite this, a paucity of data exists for the clinical management of intra-oral adhesions in this population. We report the cases of a father and daughter diagnosed with CPLSS who presented with respiratory and feeding difficulties at birth undergoing surgical correction. Early surgical ligation of intra-oral bands allows for a stabilization of the airway, improved feeding and oral development with a good long-term outcome.

Synchronous airway lesions in children: an analysis of characteristics and comorbidities.

OBJECTIVES: To analyze the characteristics and the associated medical co-morbidities in children with synchronous airway lesions (SALs) found during rigid bronchoscopy. METHODS: Retrospective case series and chart review of patients who were found to have more than one airway lesion after undergoing airway evaluation via rigid endoscopy at a tertiary care pediatric hospital between 2001 and 2011. Patient demographics, presence of associated non-airway pathologies, and the number and types of airway lesions were collected. For analysis, airway lesions were classified based on the anatomical subsites involved (supraglottic, glottic, subglottic, tracheal and bronchial). RESULTS: Out of 592 rigid bronchoscopies performed, there were 73 cases with SALs (12.3%). Of these, only 20% of patients were term infants without associated congenital anomalies. Over 70% of patients with SALs have combinations of lesions involving the trachea, subglottis and supraglottis. Neurological anomalies and GERD were both independently associated with a three-time increase in the odds of having synchronous involvement of these three anatomical subsites (OR 3.15, 95% CI 1.06-9.41; OR 3.0, 95% CI 1.05-8.50, respectively). Glottic lesions were present in 28.7% of patients. Prematurity and cardiac anomalies were both associated with tendency of doubling the odds of glottic lesions (OR 2.34, 95% CI 0.84-6.52; OR 2.0, 95% CI 0.76-5.60, respectively). Overall, almost 10% of newly diagnosed lesions in context of SALs required an additional intervention. CONCLUSIONS: The majority of patients with SALs are either born prematurely or have associated congenital anomalies. In SAL patients with associated neurological anomalies or GERD, the lesions are more likely to be localized to the supraglottis, subglottis and trachea whereas prematurity and cardiac anomalies could both be increasing the odds of a glottic lesion. High suspicious index should be kept in mind when rigid bronchoscopy is performed to not miss an associated lesion.

Effect of the F508del genotype on outcomes of endoscopic sinus surgery in children with cystic fibrosis.

OBJECTIVE: Numerous authors have sought to describe genotype-phenotype correlations in cystic fibrosis (CF), notably to pancreatic insufficiency and lung disease. However, few studies have focused on the association between the F508del genotype and response to sinus surgery. The objective of this study is to assess the effect of the F508del genotype on sinonasal disease severity and outcomes following functional endoscopic sinus surgery (FESS) in a pediatric population. METHODS: A retrospective chart review of 153 children with CF seen at a tertiary care pediatric hospital from 1995 to 2008 was performed. Patients were classified into one of three groups according to F508del genotype, either as homozygous, heterozygous or not carrying a F508del mutation. The sinonasal disease phenotype of the three groups was compared based on clinical and radiological findings, extent of endoscopic sinus surgery and rate of revision surgery. RESULTS: The relationship between the F508del genotype and pancreatic insufficiency was confirmed (p<0.05). There was no association between the F508del genotype and increased need for FESS (p=0.75). Moreover, no association was established between F508del homozygosity and presence of nasal polyps, Lund-Mackay score, extent of surgery or length of postoperative hospitalization. The rates of revision surgery did not differ significantly among the three genotypes analyzed (p=0.59). CONCLUSION: There is no clear association between the F508del genotype and an increased need for FESS, extent of surgery, or revision surgery. Given the phenotypic variability of sinonasal disease in patients with CF, a prospective study is needed to better understand outcomes following FESS and the contribution of gene modifiers to this effect.

Testing for pediatric obstructive sleep apnea when health care resources are rationed.

IMPORTANCE: Evaluation of pediatric obstructive sleep apnea in resource-limited health care systems necessitates testing modalities that are accurate and more cost-effective than polysomnography. OBJECTIVE: To trace the clinical pathway of children referred to our sleep laboratory for possible obstructive sleep apnea who were evaluated using nocturnal pulse oximetry and the McGill Oximetry Score. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of children 2 to 17 years old with suspected obstructive sleep apnea due to adenotonsillar hypertrophy, conducted at a Canadian pediatric tertiary care center. INTERVENTIONS: Nocturnal pulse oximetry studies scored using the McGill Oximetry Score. MAIN OUTCOMES AND MEASURES: For children who underwent adenotonsillectomy we determined the length of time from oximetry to surgery, postoperative length of stay, postoperative readmissions, and emergency department visits in the month following surgery and major surgical complications. We analyzed these outcomes by oximetry result. We compared the cost savings of our diagnostic approach with those of other diagnostic models. RESULTS: Among 362 children, the median age was 4.8 years (interquartile range, 3.3-6.7), and 61% were male. Two-hundred-sixty-six (73%) and 96 (27%), respectively, had inconclusive and abnormal oximetry results. Eighty of 96 of children with abnormal oximetry results (83%) and 81 of 266 children with inconclusive oximetry results (30%) underwent adenotonsillectomy. Thirty-three of 266 children (12%) underwent further evaluation with polysomnography; of 14 diagnosed as having OSA, 12 underwent adenotonsillectomy. Children with abnormal oximetry results were operated on soonest after testing and triaged based on oximetry results. No child with an inconclusive oximetry result required hospitalization for more than 1 night postoperatively; 14% of children (11 of 80) with an abnormal oximetry result required hospitalization for 2 or 3 nights (χ2 = 12.0; P = .001). Rates of readmissions and emergency department visits were low, irrespective of oximetry results (whether inconclusive or abnormal). We show that our oximetry-based diagnostic approach results in considerable cost savings compared with a polysomnography-for-all approach. CONCLUSIONS AND RELEVANCE: Oximetry studies evaluated with the McGill Oximetry Score expedite diagnosis and treatment of children with adenotonsillar hypertrophy referred for suspected sleep-disordered breathing. When resources for testing for sleep-disordered breathing are rationed or severely limited, our proposed diagnostic approach can help maximize cost-savings and allows sleep laboratories to focus resources on medically complex children requiring polysomnographic evaluation of suspected sleep disorders.

Thyroid gland rupture: a rare finding after a blunt neck trauma.

This is a case report of a 13 years old boy with a thyroid rupture secondary to a hockey stick blunt trauma to his neck and a literature review focused on diagnosis and management. There are 14 other cases in the literature, 7 of which required surgical intervention mainly to evacuate a hematoma. The case in this review did not develop any complications. This is the first reported case in the literature of thyroid gland rupture due to a blunt trauma in a child. Patients with thyroid gland rupture should be monitored closely for developing a hematoma or thyroid storm.

Series of congenital vallecular cysts: a rare yet potentially fatal cause of upper airway obstruction and failure to thrive in the newborn.

OBJECTIVES: Stridor is a relatively common symptom during the neonatal period. The most probable cause of inspiratory stridor and supralaryngeal airway obstruction in infancy is laryngomalacia. Laryngeal cysts are known to be found in association with supraglottic prolapse and are a rare yet potentially lethal cause of respiratory distress in the newborn. In the absence of more alarming presenting signs, the vallecular cyst, a form of laryngeal cyst, frequently defies diagnosis. We present a series of illustrative cases to raise awareness of vallecular cyst to help reduce the therapeutic delays that are currently encountered clinically. METHODS: A retrospective case series of four patients was reviewed. Each patient presented initially with stridor and additional signs of upper airway obstruction shortly after birth and was later diagnosed with vallecular cyst. RESULTS: The predominant presenting signs were stridor (four cases), signs of respiratory distress (three cases), failure to thrive (three cases), poor feeding (two cases), and cyanotic spells (one case). Age at presentation ranged from 16 days to 8 months. A definitive diagnosis was achieved by flexible laryngoscopy in all four cases. Coexistent laryngomalacia was found in three of the four cases. Primary outcomes at 1 month following marsupialization were complete remission in all four cases. CONCLUSIONS: The challenge in making an early diagnosis of vallecular cyst, especially when laryngomalacia is comorbid, has been reaffirmed in our case series. Diagnosis requires a high index of clinical suspicion in combination with careful inspection of the tongue base with direct examination and/or appropriate imaging modalities.

Linking laryngopharyngeal reflux to otitis media with effusion: pepsinogen study of adenoid tissue and middle ear fluid.

HYPOTHESIS/OBJECTIVES: Laryngopharyngeal reflux (LPR) was recently implicated in the etiology of otitis media with effusion (OME). To study the hypothesis that gastric juice reaches the middle ear through the nasopharynx and eustachian tube, we evaluated the presence of pepsinogen in the adenoid tissues of children with otitis media with effusion (OME) and compared them with the tissues of a control group of children without OME. METHODS: In the study group, middle ear effusions (MEEs) and adenoidal tissue biopsies were obtained from patients undergoing simultaneous tympanostomy tube placement and adenoidectomy. In the control group, adenoid specimens were taken during adenoidectomy (+/- tonsillectomy) from children with no history of OME. The adenoid tissues were analyzed immunohistochemically to confirm the presence of pepsinogen. Normal gastric tissue was used as a positive control and lymphatic tissue as a negative control. Total pepsinogen levels of MEE were measured with enzyme-linked immunosorbent assay. RESULTS: Adenoid tissue of the OME group (n = 25) demonstrated significantly higher pepsinogen immunoreactivity when compared with the adenoid tissue of the control group (n = 29), specifically in staining of both the epithelia (p < .0001) and the subepithelia, (p < .001). The presence of pepsinogen was detected in 84% of MEEs from the OME group, at concentrations 1.86 to 12.5 times higher than that of serum. Pepsinogen messenger ribonucleic acid was not demonstrated in any of the adenoid tissues of the OME group. CONCLUSION: LPR plays an important role in the pathogenesis of OME as gastric reflux reaches the middle ear through the nasopharynx and eustachian tube to cause OME.

Complications of adenotonsillectomy revisited in a large pediatric case series.

OBJECTIVE: To document the most important postoperative adenotonsillectomy morbidities, with an emphasis on prolonged hospitalization and readmissions. DESIGN: Retrospective chart analysis. METHODS: We reviewed 2067 cases of adenotonsillectomies performed at our institution over a period of 6 years. RESULTS: Of these cases, 1927 patients had undergone tonsillectomy by electrocautery and adenoidectomy by suction-coagulator, of whom 9.3% required admission. The incidence of admissions owing to bleeding was 1.7%, whereas admissions owing to respiratory and gastrointestinal complications represented 3.7% and 5.2%, respectively. Compared with the literature and our institution's previous results, these morbidity values were found to be either comparable or significantly lower (p < .05). CONCLUSION: We attribute this improvement to our use of electrocautery-based techniques not only for tonsillectomy but also for adenoidectomy.

Hydrogen peroxide mouth rinse: an analgesic post-tonsillectomy.

OBJECTIVE: To compare the analgesic efficacy of hydrogen peroxide (H2O2) mouth rinse with control for post-tonsillectomy pain management. DESIGN: Double-blinded, prospective, randomized, controlled clinical trial. PATIENTS AND METHODS: Thirty-seven patients from 5 to 14 years old undergoing electrocautery tonsillectomy were randomized to either the H2O2 mouth rinse or the water rinse (control) group. For 14 days, patients recorded pain levels twice daily using a visual analogue scale. Analgesic uses, as well as any complications, were also noted by the patients. RESULTS: Thirty-seven patients completed the study, 21 in the treatment group and 16 in the control group. Mean postoperative days of pain were 10.3 and 8.3, respectively, and differed significantly (p = .008). Mean postoperative days of analgesic use were 9.0 and 6.7, respectively, and differed significantly (p = .005). Only one incidence of postoperative hemorrhage occurred in the study group. CONCLUSION: In our study, the H2O2 mouth rinse does not provide a better analgesic effect than the water rinse for post-tonsillectomy pain relief.

Similar allergic inflammation in the middle ear and the upper airway: evidence linking otitis media with effusion to the united airways concept.

BACKGROUND: Otitis media with effusion (OME) is a chronic inflammatory disease of the middle ear space characterized by the accumulation of fluid. Previous investigations have suggested that the immunopathologic mechanism underlying the development of middle ear effusion in patients with allergy is largely due to the effects of T(H)2 mediators. The composition of the inflammatory substrate in the effusions of allergic otitis media is similar to the late-phase allergic response seen elsewhere in the respiratory tract, such as in asthma and in allergic rhinitis. OBJECTIVE: To determine whether the middle ear compartment may be a component of the united airways in allergic disease by comparing the inflammatory profiles of the middle ear to the upper airway. METHODS: Middle ear effusions, torus tubaris (Eustachian tube mucosa at the nasopharyngeal orifice), and adenoidal tissue biopsies were obtained from 45 patients undergoing simultaneous tympanostomy tube placement for OME and adenoidectomy for adenoid hypertrophy. The cellular and cytokine profiles of each site were investigated by using immunocytochemistry (elastase, CD3, major basic protein) and in situ hybridization (IL-4, IL-5, IFN-gamma mRNA). Atopic status was determined for each patient by using skin prick testing. RESULTS: Eleven of the 45 patients with OME (24%) were atopic. The middle ear effusions of atopic patients had significantly higher levels of eosinophils, T lymphocytes, and IL-4 mRNA + cells ( P < .01) and significantly lower levels of neutrophils and IFN-gamma mRNA + cells ( P < .01) compared with nonatopic patients. The nasopharyngeal tissue biopsies revealed similar cellular and cytokine profiles. CONCLUSION: In atopic patients with OME, the allergic inflammation occurs on both sides of the Eustachian tube, both in the middle ear and in the nasopharynx. The results of this study support the concept that the middle ear may be part of the united airway in atopic individuals.

Intraoral drainage: recommended as the initial approach for the treatment of parapharyngeal abscesses.

OBJECTIVE: We sought to compare the efficacy, safety, and cost of intraoral drainage (IOD) of parapharyngeal abscesses (PPAs) in the pediatric population with those of the more commonly used external neck drainage (END). PATIENTS AND STUDY DESIGN AND SETTING: An 11-year retrospective review was conducted of all patients admitted to a tertiary-care, university-affiliated, pediatric hospital with a diagnosis of PPA. Patients were divided into 2 groups according to the treatment received (IOD or END) and were followed to 1 month postoperatively. All children referred to our institution with a final diagnosis of PPA were included in the study. OUTCOME: Outcome measures were duration of anesthesia, duration of postoperative intravenous antibiotics (DPOIA), length of postoperative hospital stay (LPOHS), and occurrence of complications. RESULTS: Fifteen patients underwent IOD, and 10 patients, END. IOD shortened anesthesia time by 31.7 minutes compared with END (P = 0.0003). IOD was associated with a decrease in DPOIA and LPOHS by 1.1 days (P = 0.1931) and 1.6 days (P = 0.0649), respectively. The cost of treatment was thereby reduced. No complications were encountered in either group. CONCLUSIONS: IOD is a safe and effective treatment for PPA in the pediatric population. It leads to decreased morbidity, shortened anesthesia time, and reduced economic burden.

Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults.

BACKGROUND: Exposure to bacterial products in early life could protect against development of atopy. We examined the effect of bacterial lipopolysaccharide on allergic inflammation and expression of cytokines and lipopolysaccharide receptor (toll-like receptor 4 TLR4) in nasal mucosa of 15 atopic children and ten atopic adults. METHODS: Explanted mucosa was cultured with allergen with or without lipopolysaccharide (0.1 mg/L) for 24 h. Immunocytochemistry and in-situ hybridisation were used to phenotype the cells and cytokines. FINDINGS: In explants from atopic children, lipopolysaccharide prevented allergen-induced T-helper type 2 (Th2) inflammation and upregulated Th1 cytokine reactivity and expression. These effects were blocked by antibody to interleukin 10. In children but not in adults, lipopolysaccharide caused increases of three times in T-cell reactivity, five times in T-cell proliferation, and four times in expression of interleukin 10 compared with mucosa stimulated with allergen alone. This difference in response was mirrored by lipopolysaccharide-induced increases in TLR4 reactivity in children but not adults. TLR4 receptor was expressed by CD3-positive T cells, and TLR4-positive cells contained interleukin 10. Lipopolysaccharide increased expression of cells positive for both CD3 and TLR4; both TLR4 and interleukin 10; and both CD4 and CD25. INTERPRETATION: Lipopolysaccharide inhibits allergic inflammation in nasal mucosa of atopic children by skewing local immune responses from Th2 to Th1 and upregulating production of interleukin 10. These effects are mediated by TLR4. Our results emphasise an important difference between adults and children in their ability to respond to bacterial products. These differences could have a role in normal maturation of the immune system.