The role of allergy in pediatric rhinosinusitis.

PURPOSE OF REVIEW: This review focuses on the association between allergic disease and pediatric rhinosinusitis. For this purpose, allergic rhinitis and chronic rhinosinusitis (CRS) were the areas chosen for further discussion. RECENT FINDINGS: The role of allergy as a major immunopathologic mechanism causing inflammation in pediatric rhinosinusitis is becoming better defined. However, despite the fact that allergic rhinitis and CRS are characterized by inflammation, there appears to be a distinct difference in the inflammatory response of children and adults with CRS, which may attest to a difference in the pathophysiologic pathways. Local allergic rhinitis, a recently described pathological entity, appears to affect a significant number of patients with a previous diagnosis of nonallergic rhinitis, making this a prevalent entity in patients evaluated with rhinitis. With regard to the relationships between allergy and infectious diseases, it has been reported that basophils are activated in the presence of suboptimal doses of allergens and bacteria and may explain the clinical behavior of allergy exacerbation. SUMMARY: Allergic rhinitis is frequently associated with CRS. The management of CRS should include evaluation of the pediatric patient for allergic disease and the management should be targeted at decreasing the inflammatory response, which will most likely result in better control of the CRS patient.

Food allergy in adults and children.

Food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food and is distinct from food intolerance. Clinical manifestations of food allergy are varied and involve many systems including respiratory, cutaneous, and gastrointestinal. The double-blinded placebo-controlled oral food challenge remains the gold standard for the diagnosis of IgE-mediated food allergy. Areas of ongoing research include improved understanding of determinants for the development of tolerance versus sensitization for foods, the role of diagnostic testing for specific epitopes for food allergens, and the use of oral immunotherapy for IgE-mediated food allergy.

Inhalant allergies in children.

Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted.

Neurotrophins and tonsillar hypertrophy in children with obstructive sleep apnea.

Enlarged adenotonsillar tissue (AT) is a major determinant of obstructive sleep apnea (OSA) severity in children; however, mechanisms of AT proliferation are poorly understood. We hypothesized that early exposure to respiratory syncytial virus (RSV) may modify AT proliferation through up-regulation of nerve growth factor (NGF)-neurokinin 1 (NK1) receptor dependent pathways. AT harvested from 34 children with OSA and 25 children with recurrent tonsillitis (RI) were examined for mRNA expression of multiple growth factors and their receptors. In addition, NK1 receptor expression and location, and substance P tissue concentrations were compared in AT from OSA and RI children. NGF mRNA and its high-affinity tyrosine kinase receptor (trkA) expression were selectively increased in OSA (p<0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p<0.01), and substance P concentrations in OSA patients were higher than in RI (p<0.0001). AT from OSA children exhibit distinct differences in the expression of NGF and trkA receptors, NK1 receptors, and substance P. The homology between these changes and those observed in the lower airways following RSV infection suggests that RSV may have induced neuro-immunomodulatory changes within AT, predisposing them to increased proliferation, and ultimately contribute to emergence of OSA.

Executive summary: asthma and the unified airway.

Asthma is a common comorbid disorder that will be seen by otolaryngologists in their treatment of patients with rhinitis, rhinosinusitis, and otitis media. Among otolaryngologists, however, a diagnosis of asthma is infrequently considered in this patient population. Otolaryngologists, however, may be in an important position to recognize this potential diagnosis and provide treatment or appropriate referral. To further develop this relationship among upper and lower airway inflammation, and to provide important information to otolaryngologists regarding this relationship, a multidisciplinary workgroup was impaneled by the American Academy of Otolaryngologic Allergy in August 2006. The full report of this meeting is published separately as a Supplement to Otolaryngology-Head and Neck Surgery. This Executive Summary provides a brief synopsis of that document, with a focus on comorbid respiratory inflammation for otolaryngologists. In the treatment of their patients with allergic rhinitis and rhinosinusitis, otolaryngologists must be aware of the possible presence of asthma so that appropriate treatment and/or referral can be initiated. The impact of this practice will allow more comprehensive treatment of patients with upper and lower airway disease, and will improve patient symptoms, function, and quality of life.

Asthma and the unified airway.

Inflammatory processes of the upper and lower airway commonly co-exist. Patients with upper respiratory illnesses such as allergic rhinitis and acute and chronic rhinosinusitis often present to both otolaryngologists and primary care physicians for treatment of their symptoms of nasal and sinus disease. These patients often have concurrent lower respiratory illnesses such as asthma that may be contributing to their overall symptoms and quality of life. Unfortunately, asthma frequently remains undiagnosed in this population. It was the objective of this paper to examine the relationship between upper respiratory illnesses such as rhinitis and rhinosinusitis and lower respiratory illnesses such as asthma, and to provide a framework for primary care and specialty physicians to approach these illnesses as a spectrum of inflammatory disease. The present manuscript was developed by a multidisciplinary workgroup sponsored by the American Academy of Otolaryngic Allergy. Health care providers in various specialties contributed to the manuscript through preparation of written materials and through participation in a panel discussion held in August 2006. Each author was tasked with reviewing a specific content area and preparing a written summary for inclusion in this final document. Respiratory inflammation commonly affects both the upper and lower respiratory tracts, often concurrently. Physicians who are treating patients with symptoms of allergic rhinitis and rhinosinusitis must be vigilant to the presence of asthma among these patients. Appropriate diagnostic methods should be used to identify individuals with concurrent respiratory illnesses, and comprehensive treatment should be instituted to reduce symptoms and improve quality of life.

Leukotriene modifier therapy for mild sleep-disordered breathing in children.

BACKGROUND: Children with mild sleep-disordered breathing (SDB), who may not be recommended for adenotonsillectomy, frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions, such as leukotriene modifier therapy. METHODS: Twenty-four children with SDB completed an open-label intervention study for 16 weeks with daily montelukast therapy. Sleep studies and adenoid size estimates from lateral X-ray films of the neck were obtained before and after treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea or recurrent throat infections were subjected to quantitative polymerase chain reaction, immunohistochemistry, and Western blotting for gene and protein expression of leukotriene receptors LT1-R and LT2-R, and for concentrations of LTB4 and LTC4/D4/E4. RESULTS: Montelukast treatment induced significant reductions in adenoid size and respiratory-related sleep disturbances, which were absent in 16 children with SDB who did not receive treatment. LT1-R and LT2-R mRNA was similarly abundant in adenoid tissues, but increased LT1-R and LT2-R protein expression and higher levels of LTB4 and LTC4/D4/E4 emerged in children with obstructive sleep apnea. CONCLUSIONS: Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep. Double-blind, placebo-controlled trials will be needed to corroborate current findings and solidly establish antiinflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for adenotonsillectomy.

Glucocorticoid receptor subunit expression in adenotonsillar tissue of children with obstructive sleep apnea.

Tonsillectomy and adenoidectomy (T&A) is a frequent surgical procedure in children with obstructive sleep apnea (OSA). Many symptomatic children who do not fulfill the currently recommended criteria for T&A may benefit from topical intranasal steroid therapy. However, the expression of glucocorticoid receptor (GCR) expression in adenoid and tonsillar tissue is currently unknown. The objective of this study was to assess and compare expression patterns of the human GCR in children who undergo T&A for either recurrent throat infections (RI) or OSA. Adenotonsillar tissues from 36 children with OSA or RI were subjected to quantitative PCR using specific primers for GCR-alpha and GCR-beta and to immunohistochemistry and Western blotting for protein expression of GCR isoforms. mRNA encoding for expression of both GCR-alpha and GCR-beta was detected in the tonsils and adenoids of all children, with markedly higher relative abundance of the GCR-alpha. Furthermore, GCR-alpha mRNA expression was increased in OSA-derived adenoid and tonsil tissues compared with RI, whereas no differences emerged for GCR-beta. Immunoblots confirmed these findings for the protein transcripts of these genes, and immunohistochemistry showed a specific topographic pattern of distribution for both receptors in tonsillar tissue. GCR-alpha and GCR-beta are expressed in pediatric adenotonsillar tissue, are more abundant in OSA patients, and demonstrate a specific topographic pattern of expression. These findings along with the high GCR-alpha:GCR-beta ratio suggest a favorable profile for topical steroid therapy in snoring children with adenotonsillar hypertrophy.