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Allergic rhinitis is currently the most common of all chronic diseases in children. However, children frequently lack the ability to verbalize their symptoms, with the result that the condition may go undiagnosed and untreated. Unfortunately, untreated allergic rhinitis not only detrimentally affects children's physical and psychosocial well-being, quality of life, and capacity to function and learn, but it is also associated with and may contribute to potentially serious sequelae, including asthma, sinusitis, and otitis media. Because children may not accurately describe their symptoms, the classic signs of allergic rhinitis in the pediatric population, including the allergic shiner, the allergic crease, and the allergic salute, are particularly important in enabling the clinician to recognize those children who may have this condition; other significant signs include mouth breathing, snoring, chronic cough, and continual throat clearing. The options for treating allergic rhinitis in the child are the same as those for the adult, and the clinician can expect the same level of efficacy. Environmental control for allergen avoidance is an important goal, but the clinician must prescribe it within the context of the family's lifestyle to obtain compliance. Complete avoidance of inhalant allergens is not always feasible, and medications are necessary. Oral antihistamines remain the mainstay of initial treatment for allergies. Given evidence of the significant deleterious effects of the sedating antihistamines on learning, the clinician should prescribe nonsedating second-generation agents whenever possible. Decongestants may be needed. Intranasal corticosteroids are a most effective option, and these agents lack the systemic side effects associated with orally administered steroids. In persistent disease, allergen immunotherapy injections may be considered. In all cases, the clinician should consider issues that are likely to influence compliance in the pediatric population.

Background: Recent studies have documented a link between respiratory viral infections and the expression of asthma and other allergic disorders. Results from other studies have suggested that diminished production of IL-10, an anti-inflammatory cytokine, may contribute to the pathophysiologic features of these diseases., Objective: The objective of this study was to determine whether diminished IL-10 production and TH2 cytokine skewing occur in allergic, as compared with nonallergic, subjects after experimental infection with the influenza A virus., Methods: PBMCs were isolated from 11 subjects with allergy and 14 subjects with no allergy before and after influenza A infection and stimulated with either mitogen (PHA) or antigen (influenza A). Supernatants were assayed for IL-10, IL-4, and IFN-gamma by ELISA., Results: PBMC IL-10 production was significantly diminished in subjects with allergy, as compared with subjects with no allergy, after experimental infection with influenza A virus. However, significant TH2 skewing and enhanced airway symptoms were not observed in these same subjects., Conclusions: These data provide further support that subjects with allergy have an intrinsic inability to upregulate IL-10 production in response to inflammatory stimuli and extend this observation to include respiratory viral infections. Future studies in this area could lead to a better understanding of the pathogenesis of asthma and other allergic disorders

Otitis media and otitis media with effusion are among the most common childhood illnesses and contribute a great deal to health care costs. The cause of otitis media is multifactorial. Eustachian tube dysfunction, bacterial or viral infection of the middle ear, and nasal inflammation resulting from allergic rhinitis or upper respiratory infection are acknowledged contributing factors. Data from epidemiology studies indicate that 25% to 40% of upper respiratory infections in children younger than 3 years are accompanied by an episode of otitis media, 40% to 50% of children older than 3 years with chronic otitis media have confirmed allergic rhinitis. Studies of the pathogenesis of otitis media have identified interactions among infection, allergic reactions, and eustachian tube dysfunction. Nasal inflammation due to allergen challenge results in classic signs and symptoms of allergic rhinitis and eustachian tube dysfunction. Eustachian tube dysfunction leads to increased negative pressure in the middle ear and improper ventilation. Both viral upper respiratory infection and nasal allergic reaction provoke nasal inflammation, eustachian tube dysfunction, and enhanced nasal protein transudation and secretion, which is likely to be sustained and modulated by inflammatory mediators and cytokines. In a study of experimental infection with influenza A virus, histamine release increased from peripheral blood basophils of patients with allergic rhinitis. These data support an interaction between viral infection and nasal allergy in enhancing certain pathophysiologic responses. Viral upper respiratory infections may promote secondary bacterial infections by altering bacterial adherence, modulating host immune and inflammatory responses, and impairing eustachian tube function. In acute otitis media, bacteria are cultured front approximately 70% of middle ear effusions with Streptococcus pneumoniae being the most common organism. Initial management of otitis media consists of appropriate antimicrobial therapy. In the presence of allergic rhinitis, antiallergic therapies may be used to augment symptom resolution and therapeutic response. Surgical insertion of tympanostomy or ventilation tubes to promote drainage of unresolved effusions has become common. Further delineation of the pathogenesis of otitis media and otitis media with effusion will guide appropriate medical management and may decrease the need and frequency of surgical procedures.

The in vivo absorption potential of ipratropium bromide nasal spray was evaluated in studies involving healthy volunteers (0.03%, 0.06%, and 0.12% dosage strengths) and patients with perennial rhinitis (0.03% and 0.06%) and the common cold (0.06%). The dose used was two sprays per nostril, corresponding to a total dose of 84 micrograms, 168 micrograms, and 336 micrograms for the three dosage strengths. These studies indicate that 10% or less of active drug is absorbed systemically after nasal administration based on the amount of unchanged drug excreted in urine in a 24-hour interval. In most instances, the plasma drug concentrations were undetectable. In none of these studies did plasma ipratropium concentrations reach a level where systemic anticholinergic effects are known to occur.

To determine whether a viral upper respiratory tract infection can alter the responsiveness of the nasal mucosa, paired intranasal histamine and cold air challenge sessions were performed before and after (8 to 13 days) experimental rhinovirus infection in 18 nonallergic subjects and 20 subjects with seasonal allergic rhinitis. The nasal response to the challenges was measured as symptom scores for rhinorrhea and congestion, counts for sneezing, weight for expelled secretions, and inspiratory conductance for nasal patency. For both sessions, a greater response was observed in allergic subjects for sneezing, symptoms of rhinorrhea and congestion, secretion weights provoked by histamine challenge, and secretion weights provoked by cold air challenge when compared with the nonallergic subjects. A comparison of the responses to the paired challenge sessions showed greater responses for sneezing, secretion weight and rhinorrhea to histamine and for secretion weight to cold air challenges performed after rhinovirus infection. No differences were observed between allergic and nonallergic subjects with respect to the degree of enhanced responsiveness secondary to viral infection. These results document an increased responsiveness of the nose to these stimuli during the postsymptomatic period of a rhinovirus infection in both allergic and nonallergic subjects.

Background: To determine the underlying mechanisms for rhinovirus-induced nasal secretions, nasal lavage fluids were analyzed during experimental rhinovirus infections., Methods: Twenty patients with allergic rhinitis and 18 nonallergic control subjects were inoculated with rhinovirus type 39. Nasal lavage was performed before and on days 2 through 7 after viral inoculation, and the lavage fluids were assayed for proteins and mast cell mediators., Results: The secretion of total protein and both plasma proteins (albumin and IgG) and glandular proteins (lactoferrin, lysozyme, and secretory IgA) increased after rhinovirus inoculation. Analysis of the specific protein constituents revealed that nasal secretions during the initial response to the rhinovirus infection were predominantly due to increased vascular permeability. Allergic subjects tended to have fewer symptoms and more vascular permeability than control subjects, and increased histamine secretion after rhinovirus inoculation was more frequently seen in the allergy group., Conclusion: Nasal secretions found early in the course of a viral upper respiratory infection are due to increased vascular permeability, whereas glandular secretions predominate later in the infection.

Patients with allergic rhinitis (AR), compared with nonallergic persons, have been reported to respond differently to a variety of stimuli, some of which are immunologic in nature. This study compared the systemic cellular immune responses to experimental rhinovirus (RV) 39 challenge in RV-39-seronegative AR (n = 20) and nonallergic (n = 18) subjects. Peripheral blood was obtained before, 4 or 7 days after, and 23 days after RV-39 intranasal challenge and assayed for the number and function of various white blood cells. All subjects were infected, as manifested by viral shedding in nasal secretions or seroconversion. RV-39 induced marked changes from baseline values in both immune cell number and functions. Compared with nonallergic subjects, AR subjects manifested different responses for the following parameters: (1) numbers of total white blood cells and lymphocytes (smaller increases on day 4), (2) helper/suppressor T cell ratio (absence of an increase on day 7 and presence of an increase on day 23), (3) number of IL-2 receptor-positive suppressor T cells (presence of a decrease on day 7), (4) natural killer (NK) cell numbers (absence of an increase on day 4 and presence of increases on days 7 and 23), (5) NK/T cell ratio (absence of an increase on day 4 and a decrease on day 7), (6) NK cell activity (a blunted decrease on day 7 and absence of a decrease on day 23), and (7) RV-39-induced lymphocyte proliferation (exaggerated increase on day 4). The results show that intranasal challenge with RV-39 induced RV-39-specific and nonspecific systemic cellular immune responses and a unique immunologic response pattern in AR subjects.

Sinusitis can occur as an acute, subacute, recurrent acute, or chronic clinical disease process in children. Sinusitis most often manifests as a prolongation or complication of a viral upper respiratory tract infection. Because children average six to eight upper respiratory tract infections per year, sinusitis is probably a more frequent diagnosis in the pediatric age group compared with adults who average two to three upper respiratory infections per year. Upward of 5 to 13% of children may experience sinusitis, but precise incidence data are not available because many imaging techniques currently available are inappropriate procedures for a prospective pediatric survey. Symptoms of acute sinusitis in children can vary from the more common persistent, purulent rhinorrhea and cough to the less common symptoms of fever, headache, facial pain, and swelling. Recurrent acute and chronic sinusitis may be associated with another condition such as a host-defense defect, cystic fibrosis, asthma, or a local condition that predisposes to obstruction of the sinus ostia such as nasal polyps, deviated septum, foreign body, or allergic inflammation. Diagnosis of sinusitis can be made on the basis of a careful history and physical examination with radiography reserved for confirmation of clinical impression or documentation of disease. Although fiberoptic rhinoscopy is used more frequently as an adjunct in adults for the evaluation and management of sinusitis, more studies need to be performed to document its clinical usefulness in children.

To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.

Chronic and recurrent otitis media can manifest as otitis media with effusion. Both infection and eustachian tube obstruction (ETO) have been found to play an important role in its pathogenesis. ETO can be demonstrated during both early- and late-phase reactions in patients with allergic rhinitis after intranasal challenge with an allergen. Intranasal challenge with either histamine or prostaglandin D2 also provokes ETO, with the latter mediator perhaps more potent than the former. Middle ear effusions from patients with chronic or recurrent otitis media have been found to contain dramatically increased concentrations of histamine relative to the concentrations in their plasma. The development of nasal and eustachian tube obstruction in allergic rhinitis patients has been prevented by pretreatment with an antihistamine plus decongestant before intranasal challenge with pollen allergen. Investigations are currently under way to assess the effect of antihistamine pretreatment on nasal and eustachian tube obstruction in patients undergoing intranasal histamine challenge.

Specific reaginic (IgE) and hemagglutinating (IgG) antibodies were quantified after immunization with ovalbumin aluminum hydroxide gel in BN and ACI inbred rats, as well as their F1, F1 X BN backcross, F2, and F3, and F3 progeny. The dissimilarity of these immune responses indicated that reaginic (IgE) antibody synthesis was influenced by polygenic factors, but not sex, and was controlled by loci different from that governing hemagglutinating (IgG) antibody synthesis. In addition, tissue typing of the BN, ACI, F1, and F3 hybrids suggested that reaginic antibody synthesis was not linked to the major rat histocompatibility locus.

Eight subjects with seasonal allergic rhinitis confirmed by positive skin tests and serum radioallergosorbent test to ragweed or timothy grass pollen were identified. A double-blind provocative antigen challenge was performed with intranasal insufflation of 50 mg of dry pollen to which the subject was either sensitive (ragweed or timothy) or not sensitive (pine). Before and after pollen insufflation, measurements of nasal function by nasal rhinomanometry and eustachian tube (ET) function by the nine-step tympanometry test were performed for up to 14 days. The ability to dilate the ET was documented in 14 of the 16 ears of the eight subjects before challenge. Within 30 min after antigen challenge transient obstruction of the ET associated with inability to dilate upon swallowing was observed in all 14 ears. Clinical symptoms of allergic rhinitis, including rhinorrhea and nasal obstruction, were produced in all subjects. ET function changes were reversible in three of 14 ears within 2 hr but persisted for more than 3 days in six of the ears. As a control, insufflation of pine pollen did not alter ET function or rhinomanometric values or produce clinical symptoms in the eight subjects. These findings suggest an allergic basis for ET obstruction and possibly for the development of otitis media with effusion.

ETO and symptoms of AR have been demonstrated to develop after an intranasal provocative antigen-challenge test. To determine the antigen dose required to produce ETO, intranasal insufflations of increasing amounts of pollen (ragweed or timothy) from 0.1 to 100 mg were delivered to 29 patients, ages 20 to 31 yr with AR who were skin test positive or had elevated serum-IgE antibodies to ragweed or timothy but not pine pollen. Our results demonstrated ETO developed in four ears at 0.05 mg of pollen, in one at 0.5 mg, in four at 1 mg, in 28 at 10 mg, in 15 at 50 mg, and in two at 100 mg of pollen. ETO persisted from 2 to 120 hr. Dose responses and duration of ETO were compared to patients' serum-IgE antibodies that ranged from 3% to 36% B/T (median 26.4%). The patients with the highest serum-IgE antibody values (greater than or equal to 26.4%) required lower antigen-dose challenges (less than or equal to 10 mg) to develop ETO (p less than or equal to 0.01) that also persisted longer (less than or equal to 48 hr) p less than or equal to 0.05. Symptoms of AR developed with an antigen dose that was less than the antigen dose that resulted in the development of ETO in 22 patients and at the same antigen dose in the other seven subjects. At a later date, these same subjects were also challenged intranasally with 50 mg of pine pollen after which no symptoms of AR or development of ETO were noted. In summary, the expression of ETO after provocative intranasal pollen challenge in AR patients is an immune-mediated reaction that is antigen-dose dependent and related to serum-IgE antibody titer.

Otitis media with effusion (OME) is common in children, although it can occur at any age. Allergies probably contribute to the development of OME, with other major risk factors being bacterial infection and eustachian tube obstruction (ETO). We have demonstrated that patients with allergic rhinitis often develop ETO when challenged with allergens; therefore, ETO could be a link between OME and allergies. Nasal obstruction and ETO in allergic rhinitis can be alleviated or attenuated by pretreatment with intranasal corticosteroids. Therapy for allergic rhinitis complicated by OME includes treatment of the ear infection with antibiotics and the relief of allergic symptoms with antiallergy medications, including antihistamines, intranasal cromolyn, and intranasal corticosteroids, as well as environmental control and appropriate immunotherapy.

Eustachian tube (ET) function was evaluated bilaterally by use of the inflation-deflation and forced-response test before and after nasal challenge with various doses of histamine in five adult and 10 infant rhesus monkeys (Macaca mulatta). Of the 20 experiments conducted on the infant and juvenile monkeys, functional ET obstruction resulted in six ears after a dose of 0.5 mg of histamine, in 10 ears after a dose of 1 mg, and in four ears after a dose of 2 mg. In contrast, of the 10 experiments conducted on the adult monkeys, functional ET obstruction developed in two ears after a dose of 1 mg of histamine and in two ears after a dose of 4 mg. Six ears failed to respond at doses of 8 mg of histamine. The ET obstruction was characterized by increases in the values of the passive function parameters and an abolition of the ability to equilibrate applied middle ear pressures by muscular activity. ET obstruction was not observed in any ears after challenge with a saline control. The severity of the induced ET obstruction was lessened within 60 minutes after challenge. These data are similar to those reported for intranasal pollen challenges in sensitized rhesus monkeys and human volunteers and suggest that type I allergic reactions at the site of the nasopharyngeal mucosa disrupts the normal functioning of the ET by a mechanism potentially mediated by histamine release.

Nasal provocative testing is the introduction of a specific factor into the nose and the subsequent assessment of the pathophysiologic changes induced by the challenge. The provocative test primarily affects the nasal airway but also may affect the adjacent organs, including the eustachian tube, middle ear, sinuses, and lower respiratory tract. Recent advances in the measurement of nasal airway resistance with microcomputer-assisted rhinomanometry have improved the objective assessment of nasal airway obstruction. Eustachian tube obstruction has been shown after nasal provocation by a new procedure, sonotubometry, which can be performed in series with rhinomanometry and pulmonary spirometry. As will be described these procedures have helped elucidate the extent and pathophysiology of diseases affecting the upper airway, especially allergic rhinitis. At present, nasal provocation is primarily a clinical investigative test. It is anticipated that with further development and refinement, it can be used to a greater extent in the diagnosis and management of nasal diseases.

Radial immunodiffusion was used to measure the concentrations of IgG, IgA, and IgM in the sera of 224 asthmatic children, ages 6 months to 14 years. IgM was greater than two standard deviations above age-matched normal values in 51% of these asthmatic subjects. Immunoglobulin profiles were repeated up to four years later in 29 individuals with elevated IgM and increased IgM synthesis was sustained in 14 of these asthmatic subjects. Serum IgE concentrations were elevated in 23 of 35 asthmatic patients. There was no statistical difference in mean IgE between asthmatic children with normal or increased IgM. The distribution of IgE in each group was similar. Only 10 of 224 subjects had an IgA concentration less than 2 SD below age-matched control subjects. The significance and possible mechanisms of hyper-M-immunoglobulinemia are discussed.

Eustachian tube obstruction (ETO) has been reported to develop more frequently in subjects with allergic rhinitis (AR) than in subjects without AR after a single intranasal histamine challenge. The present double-blind crossover study was designed to confirm and extend this observation. In a pilot study, nebulization was demonstrated to be superior to insufflation in provoking ETO. Five subjects with AR and five subjects without AR were repeatedly challenged intranasally with nebulized normal saline or increasing doses of histamine (0.01, 0.1, 0.5, 1.0, 5, and 10 mg per nostril). Subjects with AR were selected on the basis of AR symptoms and IgE antibodies to allergens and were challenged in their nonallergy seasons. ETO was assessed by nine-step tympanometry and nasal airway resistance by anterior rhinomanometry before and after each challenge. Of nine ears in subjects with AR, ETO developed in five ears at 0.1 mg and in four ears at 0.5 mg. In contrast, in 10 ears of subjects without AR, ETO developed in two ears at 5 mg but did not develop in eight ears at doses as large as 10 mg. This test effectively discriminated subjects with AR from subjects without AR, groups that could not be similarly differentiated by nasal or skin responsiveness to histamine challenge. Saline challenges provoked ETO in three of nine ears of subjects with AR and in one of 10 ears of subjects without AR. These data suggest a hyperresponsiveness of the nasopharyngeal and/or tubal mucosa to histamine in subjects with AR that may predispose these patients to otitis media with effusion.

Signs, symptoms, and radiographic abnormalities of sinusitis are frequent in children with asthma; it is not known whether sinus inflammation is associated with bacterial infection or other mechanisms. Eight asthmatic patients with exacerbation of asthma despite bronchodilator therapy were studied after maxillary sinusitis was confirmed by radiographs. All had cough, wheezing, nasal stuffiness, rhinorrhea and were afebrile. Four patients had headaches, and two had facial pain. Maxillary sinus aspirates were obtained, and bacterial cultures were positive in five: Branhamella catarrhalis (2), nontypeable Hemophilus influenzae (2), Streptococcus pneumoniae (1). Nose and throat cultures did not correlate with sinus cultures. All patients received bronchodilators, and four of eight patients received steroids. All were treated for 14 to 28 days with antibiotics during which seven of the eight patients improved clinically including all with positive sinus cultures. Asthma-symptoms diary scores were kept by five; all demonstrated improvement. Pulmonary-function tests improved in five of seven patients after the antibiotic and asthma therapy including the four patients with positive cultures. Sinus radiographs cleared in three, improved in three, and were unchanged in two patients after antibiotic therapy.