ARTICLE

Allergic Frank

Rhinitis

S. Virant,

FOCUS

MD*

QUESTIONS

1. What are the historical and clinical features of allergic rhinitis in children? 2. What chemical mediators are released in allergic rhinitis and how do they create symptoms? What are the common complications of untreated allergic rhinitis? 4. In patients who have chronic rhinitis, what is the role of nasal cytology in directing evaluation and therapy? 5. What are the roles of environmental control, pharmacotherapy, and immunotherapy in management of allergic rhinitis? 3.

Epidemiology Allergic rhinitis affects as many as 8% to 10% of children in the United States. Many of these children suffer significant morbidity, leading to mulions of lost school days annually. Morbidity is amplified when these children concurrently suffer from complications of allergic rhinitis, such as recurrent otitis media or chronic sinus disease. Typically, children who have allergic rhinitis have a family history of atopic disorders. Upper airway allergy may become manifest at any age, but the appearance of symptoms is most common during childhood or young adulthood. Clinical signs of rhinitis may be perennial, seasonal, or episodic, and the primary focus of complaints may relate to secondary problems, including ear, sinus, or lung disease.

Complications

stellation of immunomodulators directs the B-cell to produce IgE rather than the IgG response of the nonallergic patient. Clinical disease occurs when an allergen reacts with antigen-specific IgE on the patient’s nasal mast cells. When these factors combine, the mast cell is activated to release a Variety of preformed and newly produced mediators, including histamine, leukotrienes, and prostaglandins (Fig 1). Histamine is a potent vasodilator and acts directly on local receptors to induce vasodilation and edema; it acts indirectly to trigger neural reflexes, inducing mucus hypersecretion and sneezing. The vasoactive properties of histamine are amplified by several of the leukotrienes and prostaglandins. Simultaneously, a variety of chemotactic factors, such as leukotriene B4 (LTB4), platelet activating factor (PAF), and eosinophil chemotactic factor (ECF), induce an influx of eosinophils into the nasal secretions (Fig 2). Clonal expansion of the eosinophil population is enhanced by T cell-derived interleukin 5 (IL-5,). In this context, allergic rhinitis should be viewed as an inflammatory disease in which the eosinophil can chronically release multiple injurious proteins that amplify tissue edema and nonspecific nasal hyperreactivity.

Patients

who

rhinitis

have

perennial

have virtually

allergic

continuous

re-

lease of nasal mediators. Copious Secretions and tissue edema can lead to anterior nasal obstruction in the area of the sinus ostia and to posterior obstruction around the eustachian tube orifices. Unchecked, this process results in stasis of secretion within the sinuses or middle ear, creating an ideal milieu for bacterial infection.

Accordingly,

it is not surprising

that

chronic sinusitis and recurrent otitis media are the most common complications of underlying allergic rhinitis in children. From a clinical perspective, the pediatrician should be aware that young children rarely are seen with “uncomplicated” allergic rhinitis or hay fever. With this in mind, a pattern of recurrent sinus or middle ear infection should prompt consideration of predisposing factors that may need additional therapy, such as allergy, immunodeficiency, or abnormal anatomy. Evaluation should include a thorough review of the patient’s history (looking for a suggestion of an atopic component), a comprehensive airway examination, and study of nasal cytology for eosinophils. If allergy is suspected, appropriate further diagnostic tests should be initiated,

(#{231}

Pathophysiology In the allergic patient, disease is mediated by the production of antigenspecific IgE by the patient’s B lymphocytes. Current research suggests that the primary defect may be the excessive production of interleukin 4 (IL-4) or a deficient level of gamma

interferon

(y-INF)

presented

with

*Clinical

Associate

when

a T-cell

is

This

con-

an antigen. Profrssor

in Review

Vol.

HIS RELEASING FACTOR

IL-S

: INFLAMMATION

LEUKOTR1ENES

/

IEE’:EII::

-0

HISTAMINE

IgE

of Pediatrics,

University of Washington, Seattle, WA. Send request for reprints to the author: Northwest Asthma and Ailergy Center, 4540 Sand Point Way N.E., Seattle, WA 98105, (206) 5271200.

Pediatrics

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PLATELET’ ACTIVATING FACTOR FIGURE

1992

1. Pathogenesis

of allergic

PROSTAGLANDINS KININS rhinitis:

Generation

of mediators.

323

ALLERGY

r

Allirgic

-

Rhinitis HISTORY

including skin testing for relevant inhalant allergens. Subsequent aggressive treatment of the patient’s allergic

rhinitis

can be critical

symptoms recurrent

Children who have allergic rhinitis may have a history of watery rhinorrhea, nasal obstruction, sneezing, or nasal pruritus. Frequently, patients will have accompanying symptoms of conjunctival erythema and pruritis, a

in alleviating

and breaking infections.

the cycle

of

A small subset of children who have allergic rhinitis may have sig-

sensation

nificant amounts of chronic middle ear fluid and negative middle ear pressure. Untreated, this can lead to poor tympanic membrane compliance

and significant studies hearing

hearing

have loss

loss.

confirmed that is most critical

overt

Several such in th

Occasionally,

of conditions

including

should

allergic

be con-

rhinitis

rhinitis,

infectious rhinitis (viral “upper respiratory tract infection” or rhinosinusi-

tis), and anatomic

abnormalities

as choanal

and

atresia

such

adenoid

hyper-

trophy. It is important to consider that several of these problems can coexist in the same child. Accordingly, even when the primary focus is on recurrent

airway

infections

Symptoms during

cough,

or

the chief

or

parental

or

“mouth breathing,” the possibility of an allergic component should be evaluated via a comprehensive history, directed physical examination, and nasal cytology study.

is suspected,

parents

con-

should

be questioned about clinical signs of related disorders, including middle ear disease, delayed speech or language development, chronic cough or wheezing, exercise intolerance, eczema, and urticaria. Frequently, the family history discloses other affected members. The child’s environmental history should be reviewed comprehensively, with emphasis on home heating sources, the bedroom environment, animals, or airway irritants such as wood or cigarette smoke. Similarly, potential allergen triggers should be explored in other

IMMEDIATE

LEUKOTRIENE

+

HISTAMINE PROSTAGLANDIN

D,

CONGESTION VASCULAR MUCOUS + NEURAL

PERMEABILITY PRODUCTION IRRITATION

+

RHINORRHEA SNEEZING

KININS

residence.

Finally, it is important to realize that children who have chronic nasal symptoms may either exaggerate or downplay their the significance

be tempered findings.

may be

the spring

cerns may not focus on symptoms of typical allergic rhinitis but rather on what are perceived to be more serious secondary problems, such as recurrent ear or sinus infections and chronic asthma. Similarly, a history of recurrent “colds” should prompt historical scrutiny. The absence of fever, sore throat, vomiting, and diarrhea or the presence of pruritus should heighten suspicion of allergy. When the diagnosis of allergic

Diagnosis

sidered,

(eg,

ears,

summer pollen periods) or perennial. In this regard, it can be useful to ask about exacerbating factors, including dust, animals, or particular pollens.

When a child is seen with a history of rhinorrhea or nasal congestion, a variety

wheezing.

seasonal

child between 1 and 4 y of age because this is a period of rapid language development. These findings provide a clinical impetus for objectively monitoring middle ear function with audiometry and tympanometry and for aggressively treating the atopic pediatric patient. Differential

of plugged

frequented environments, including day-care facilities or a relative’s

PRURITUS

LEUKOTRIENE

B4

EOSINOPHIL

ACTIVATING

CHEMOTAXIS

1

HLAYED CONGESTION

FACTOR

RHINORRHEA EOSINOPHIL CHEMOTACTIC FACTOR (ECF)

FIGURE

324

2. Pathogenesis

of allergic

I

MEDIATOR AND RELEASE

4NASAL TI

rhinitis:

The

role

of mediators

in symptom

VI TJ

physical

EXAMINATION

who

have

chronic

allergic

rhinitis frequently display dark “cirdes” or “allergic shiners” beneath the eyes; these are secondary to obstruction of normal outflow from re-

gional lymphatics and veins. If the degree of nasal obstruction is severe, the child will be a constant obligate mouth-breather. It is important to note that these findings are not specific for allergic rhinitis-any source of nasal congestion can produce them. Regardless of etiology, chronic breathing through the mouth can influence the development of the midface muscles and create a highly arched palate, overjet, and dental malocclusion.

Another

common,

more specific facial finding is a horizontal nasal crease across the lower third of the nose due to frequent rubbing induced by nasal pruritus. The nasal mucosa in patients who have allergic rhinitis is typically pale, swollen,

and

bathed

in clear

watery

secretions. Such expected findings can be altered in the presence of concomitant sinus disease, which often induce(s)

mucosal

erythema

and

pu-

rulent secretions. The presence of nasal polyps should raise concern about the possibility of cystic fibrosis because other causes are exceedingly rare during childhood. Chronic postenor nasal drainage may induce pharyngeal follicular hypertrophy. This finding is not unique to allergic rhinitis and may be observed with infectious rhinitis or sinusitis. The

PLATELET

by objective

PHYSICAL

Children

symptoms. Therefore, of the history should

remainder

of the examination

should be comprehensive, but give special attention to excluding conjunctival erythema or discharge, serous otitis media, abnormal tonsillar tissue, forced expiratory cough or wheeze, eczema, and urticaria. The presence

of such

significant

eye,

ear,

lung, and skin findings increases the likelihood that atopy-including allergic rhinitis-may be an important

generation.

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ALLERGY Nl.rglc Rhinitis

1 source of symptoms complications.

NASAL

or cause

of EOSINOPHIUC ALLERGIC

CYFOLOGY

Clinical

In concert with a comprehensive history and physical examination, a study of nasal cytology can be helpful in assessing a child suspected of having allergies. A sample generally can be obtained readily by having the patient blow his or her nose or by using a cotton swab. The secretions then can be collected on regular plastic wrap and transferred to a glass slide. Nasal secretions may be stained with either Wright or Hansel stain. Subsequently, the secretions are examined for the presence of eosinophils, neutrophils, and other cellular components. Together, cytologic and clinical findings can help clarify the diagnosis (Table). In general, the presence of > 10% eosinophils is considered a positive test for eosinophilia. Although patients who have allergic rhinitis often demonstrate 100% nasal eosinophilia, it is important to remember that atopy and infection can coexist. When infectious rhinitis or sinusitis occurs, a finding of > 90% neutrophils does not exdude allergic rhinitis (Figs 3 and 4). Although nasal eosinophilia may reflect “nonallergic rhinitis with eosinophilia syndrome” (NARES) or polyps,

these

conditions

are rare

dur-

ing childhood. ANCILLARY

TESTS

Depending on the patient’s clinical history and examination, a variety of ancillary tests can be useful in evaluating the patient who has allergic rhinitis, including audiometry, tympanometry, pulmonary function tests, sinus radiographs, and occasionally chest radiographs. When a child has a history of recurrent otitis media or recurrent middle ear effusion, or when speech and language delay is suspected, audiometry and tympanometry are essential. Abnormal hearing in the allergic child is due to significant middle ear effusion and concomitant decreased tympanic membrane compliance. Baseline data are important in assessing clinical response to aggressive therapy. Pediatrics

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EOSINOPHIUC NONALLERGIC

NEUTROPHIUC

VASOMOTOR

findings

Typically during childhood

Adulthood, young

Sneezing,

Severe obstruction; anosmia, polyps common

Purulent secretions, sinus tenderness, nocturnal

Episodic or perennial

Perennial symptoms

Appearance most common during fall and winter

Variable presentation

Triggers are often obvious, eg, dust mites, animals, pollens

Aspirin-sensitive often; frequent asthma and sinus disease

Infection typical; can be caused by irritation (eg, cigarette or wood smoke)

Can

Eosinophils ± Basophils ± Neutrophils

Neutrophils, often with intracellular bacteria

Generally unremarkable

nasal

pruritus,

clear

rhinorrhea

Nasal

often

Any

age

Adulthood, rare in children Congestion, minimal rhinorrhea cough

be hormonal (eg, thyroid disease, pregnancy)

cytolo’

Eosinophils ± Basophils ± Neutrophils

Children with allergic rhinitis frequently have a history of episodic wheezing, intermittent cough, or simply a sensation of dyspnea. In this setting, baseline pulmonary function obtained with either a peak flow meter or a spirometer often will reveal “silent asthma.” Subsequent response to bronchodilator therapy can confirm reversibility and provide a useful guide to initial therapy. Occasionally the clinical history will suggest exercise intolerance or cough only with exercise in the face of normal baseline pulmonary function. In fact, studies suggest that 35% to 40% of children who have allergic rhinitis also have significant lower airway obstruction following exercise. An exercise tolerance test can be useful in clarifying the diagnosis when the history is atypical.

The evaluation of suspected sinus disease should be made with a Waters view radiograph. In conjunction with the history, an initial sinus radiograph can be useful in guiding duration and intensity of therapy as well as providing a useful comparison with posttreatment radiographs. Chest radiographs are not warranted routinely in children who have asthma. Exceptions include patients who have chronic or recurrent bronchopneumonia or who are refractory to standard asthmatic therapy. SKIN

TESTS

If the history, results of suggestive of puncture skin and

physical examination, nasal cytology are allergic rhinitis, prick testing should be per-

-1 . ..

,#{149}

‘

.,s. FIGURE patients

1992

3. Nasal who have

cytology: allergic

Eosinophils rhinitis.

in

FIGURE 4. Nasal cytology: NeutrophiLc, bacteria, and eosinophils in patient who has concurrent allergic and infectious rhinitLc.

325

ALLERGY AII.rgic Rhlnltls formed for relevant inhalant allergens, including dust mites, animal danders, molds, and pollens. In the older child or adolescent, sensitivity can be enhanced by subsequently performing intradermal tests for allergens that test negative by prick puncture. Positive skin tests verify the presence of specific IgE; clinical relevance must be supported by appropriate history. In the absence of a suggestive clinical history or dermal signs of atopy, such as eczema or urticaria, the routine performance of skin tests for foods should be discouraged. RADIOALLERGOSORBENT

TESTS

Radioallergosorbent (RAST) testing should be reserved for the child who has significant dermatographism or eczema and in whom skin testing is likely to be unreliable or difficult to

creasing

symptoms. presentation, the prognosis is most difficult to predict for children who have recurrent ear and sinus disease. Although the initial treatment of these children focuses on therapy for infection and atopy, the long-term prognosis can be influenced by other factors, including immunodeficiency or abnormal anatomy. As a group, young children who have allergic rhinitis tend to improve during adolescence regardless of initial severity, perhaps due to hormonal factors. Although greatly influenced by aggressive treatment, allergic rhinitis tends to be a problem that exists well into the fifth or sixth decade of life. After that time, in concert with a general decline of the immune system, the clinical appearance of atopy is rare. Upon

seasonal

initial

Children who have allergic rhinitis frequently have “silent asthma” 35% to 40% have lower airway obstruction following exercise. ...

interpret. Although RAST results performed by a reliable laboratory can be just as clinically useful as prick puncture tests, they offer no real advantage and often are nearly 10 times as expensive as skin tests per test. In the case of an extremely allergic child who has an elevated serum IgE level, RAST tests can produce significant false-positive results due to nonspecific matrix binding. Prognosis As might be expected from the variable presentation of allergic rhinitis, the long-term prognosis can be difficult to predict. Generally, children who have uncomplicated rhinitis respond well to environmental control and appropriate pharmacotherapy. When pollens are a significant allergen, the trend is often toward in326

Management AVOIDANCE

After identifying allergens that are likely precipitants of symptoms, the primary approach in treatment should be an attempt at decreasing allergen exposure. Although complete elimination is rarely possible, significant reduction in allergen exposure often can be achieved. House dust mites are among the most important and common perennial allergens. Because these organisms thrive in a humid environment, it is not surprising that they are found virtually throughout the United States with the exception of the drier areas, such as the desert Southwest. Although the entire home can be a significant source for mites, patients and their parents should be advised Pediatrics

to intensify their efforts at environmental control in the bedroom. Encasing the mattress and box spring in a plastic airtight enclosure and doing subsequent weekly cleaning with a damp cloth provide an excellent means of reducing exposure near the airway at night. Dust collectors, such as stuffed toys, stuffed furniture, book shelves, or open stereo or television cabinets, should be removed from the bedroom. Bedding and linens should be cleaned weekly in hot water to reduce dust mite concentrations. In homes equipped with central forced air systems, consideration should be given to installing a good mechanical electrostatic type filter or even an electrostatic air cleaner. Patients should be counseled that, unless their vacuum cleaner contains an adequate HEPA filter, excessive vacuuming actually can be deleterious by aerosolizing dust mites antigens into the home environment. For children who have marked dust mite sensitivity, antigen denaturing or miticidal solutions (such as tannic acid or benzyl benzoate) may be useful for periodic treatment of furniture and carpets. When practical, carpet removal can reduce allergen exposure markedly. Animal danders provide a second common source of perennial allergen exposure. Complete avoidance of animal danders is possible by getting rid of pets, but often a family can find it emotionally difficult to make such a change. A reasonable compromise involves total exclusion of the pet from the patient’s bedroom and limiting animal access to a home area that the patient seldom frequents, ideally with less furniture and carpeting. Tannic acid solutions also can be used to denature the animal allergen(s). When mold allergy is evident, children should be told to avoid any outdoor areas with decaying vegetation, including piles of dead leaves or compost bins. Indoors, an attempt should be made to reduce mold growth by decreasing excessive moisture. This can be accomplished, for example, by installing better fans in the bathroom or kitchen. If problems persist, a dehumidifier should be considered. When extremely dry indoor environments require the use of a humidifier, these devices should be in Review

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ALLERGY All.rglc Rhlnftls cleaned growth

regularly to discourage mold and subsequent aerosolization

of spores. When attempts at prevention are inadequate, exposure can be diminished by treating obvious mold growth areas with mild acidic solutions. Seasonal pollen-induced allergy is difficult to control environmentally. Nonetheless, parents should be reminded to keep the child’s bedroom windows closed during the day in the pollen season and to use air-conditioning systems in their automobiles if possible. Children who are sensitive to grass pollen should try to minimize periods of work or play in the yard, especially during June or July and when the grass is being mowed. The family should try to avoid outdoor travel, including camping during late summer and early fall, if the child is sensitive to ragweed.

absorption data, neither agent is appropriate for rapid blockade of allergic events. All antihistamines are competitive receptor antagonists and, accordingly, should be taken on a regular basis rather than “as needed” for the relief of preexisting symptoms. Often, regular treatment with antihistamines also will allow the patient to achieve tolerance to many of the undesirable side effects of traditional antihistamines. Used correctly, antihistamines often will prevent sneezing, rhinorrhea, and typical pruritus induced by allergen exposure. If nasal congestion persists as a significant symptom (often owing to the presence of other vasoactive mediators), an adrenergic decongestant frequently is effective. Such medications (including phenyl-

use of decongestants appears to be safe. When allergen avoidance and the use of antihistamines and decongestants does not control symptoms, consideration should be given to the use of topical agents that control airway inflammation, such as cromolyn sodium or corticosteroids. Cromolyn sodium is available in a topical solution that inhibits the release of mediators from mast cells. Nasal use of cromolyn sodium appears to be virtually free of side effects with routine chronic prophylactic use. Drawbacks include the need for administration 4 to 6 times per day, absence of systemic efficacy, and expense. With all of these considerations, cromolyn sodium should be considered an adjunct to antihistamine therapy and probably

PHARMACOTHERAPY

Most children who have an inhalant allergy cannot control their symptoms totally by allergen avoidance. Accordingly, a variety of medications, including antihistamines, decongestants, cromolyn, and topical corticosteroids, are useful to help diminish the effect of various chemical and cellular

mediators

involved

in the al-

lergic process. Initial medical therapy often involves the use of antihistamines, which include a variety of agents that compete with histamine for binding to H1 receptors on endothelium and smooth muscle. Because histamine is a central vasoactive mediator in allergic rhinitis, the prophylactic use of antihistamines typically provides significant control of symptoms. Dosage (and efficacy) of traditional antihistamine classes frequently is limited by the appearance of undesirable side effects, including sedation or restlessness, dry mouth, urinary retention, constipation, and even blurred vision. When such side effects are apparent in the child older than 6 y, a trial of the newer nonsedating antihistamines (terfenadine or astemizole) is warranted. Although sedation is unusual, daily dosages above 120 mg terfenadine or 10 mg astemizole should be avoided because safety

has

Given

their metabolic

Pediatrics

not been

in Review

demonstrated.

half-life VoL

A variety of medications, including antihistamines, decongestants, cromolyn, and topical corticosteroids, are useful to diminish mediators of the allergic process.

13

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ephrine, phenylpropanolamine, or pseudoephedrine) can be used topically or orally. Although topical vasoconstrictors prompt relief

provide excellent of symptoms, parents

should be cautioned about prolonged usage because of “rebound effects” and habituation. Prolonged treatment with oral aadrenergic decongestants does not seem to create rebound. However, some

patients

experience

tremors,

agitation, insomnia, or even hypertension. In adults, it has been observed that hypertension is more common with chronic use of phenylpropanolamine and less evident with pseudoephedrine. Although long-term safety studies in children have not been conducted, the extended oral 1992

should be considered as primary treatment only if antihistamines are ineffective or intolerable, or if the child has very confined seasonal pollenosis. Topical nasal corticosteroids are a safe, effective alternative to the use of cromolyn sodium. Unlike cromolyn sodium, current formulations of nasal corticosteroids, such as beclomethasone and flunisolide, exert their influence by directly reducing airway inflammation. Accordingly, topical nasal corticosteroids can be effective when used on a short-term basis during periods of exacerbation, and have the advantage of only twice-daily administration. Although local irritation or epistaxis can occur, side effects of these medications typically 327

ALLERGY AII#{149}rglcRhInitle are few. Systemic steroid side effects appear to present minimal risk, although this could occur if the child is taking extremely high doses and concomitant steroid dermal or pulmonary treatment. It should be emphasized that optimal efficacy for topical steroids is achieved only after 3 to 7 d. IMMUNOTHERAPY If optimal environmental control and medical management, including the topical use of corticosteroids, does not result in adequate symptom relief, or if year-round intensive daily use of medication is required, immunotherapy should be considered. The process of immunotherapy typically involves a series of injections with extracts of the specific allergens that cause symptoms for the patient. Initially, treatment is given weekly with very dilute exposure to antigen, followed by a gradual increase in tolerated dosage. With this approach, most children can achieve top dose “maintenance immunotherapy” within 4 to 8 mo. Once this level is reached, maintenance treatment is continued every 3 to 4 wk for 3 to 5 y. Immunotherapy appears to be most effective in reducing symptoms caused by seasonal pollen-related allergy. Significant relief of symptoms also has been demonstrated after immunotherapy for dust mites, animal danders (especially cat), and molds. Controlled studies have failed to demonstrate any efficacy for “immunotherapy” to foods or mixed bacterial vaccines. In addition to alleviating symptoms, immunotherapy produces a number of serologic changes, including a rise in serum antigen-specific IgG “blocking antibodies,” suppression of antigen-specific IgE, and a general reduction in basophil reactivity. Because most of these changes are allergen-specific, comprehensive initial evaluation is critical to ensure a good clinical response to allergy desensitization. With this in mind, a child who demonstrates suboptimal immunotherapy response after 2 y should be reassessed and treatment altered appropriately. SURGICAL

Aggressive

328

INTERVENTION

treatment

for allergic

rhinitis with avoidance, medication, and immunotherapy generally results in a marked reduction in secondary bouts of otitis media or sinusitis. When this trend is not observed, consultation with an otorhinolaryngologist is warranted. Often, appropriate tympanotomy tube placement, antral lavage, or even endoscopic sinus surgery can resolve chronic problems and create a milieu in which prophylactic medical therapy can be effective.

Allergic Adulthood.

Follow-up Once the initial evaluation is cornplete, a follow-up visit within 2 to 4 wk is appropriate. This visit is useful for detailing appropriate environmental control measures, assessing initial response to pharrnacotherapy, and assuring resolution of ear or sinus disease. Assuming the patient has done well, a subsequent reevaluation visit should be performed after another 4 to 6 rno (or sooner if necessary). When the child returns for reevaluation, the history should be reviewed carefully. In addition to current symptoms, the response to environmental controls and medications and the frequency of infections should be documented. Long-term follow-up, particularly in the case of a child receiving irnmunotherapy, should be maintained every 6 to 12 mo. Therapeutic failures should be scrutinized for adequate adherence to environmental control suggestions, medication cornpliance, or occult sinus disease. Assuming the patient has complied with initial suggestions, decisions regarding alternative pharmacotherapy, higher-dose immunotherapy, or consultation with an otorhinolaiyngologist should be based on the history and current clinical findings. SUGGESTED

Rosenblatt CD, Smith U, Summers Ri. Late and immediate systemic-allergic reactions to inhalant allergen immunotherapy. I Alletgy Cliii Immunol. 1986;77:865-870 Meltzer EO, Zeiger RS, Schmatz M, Jalowayski AA. Chronic rhinitis in infants and children: Etiologic, diagnostic, and therapeutic considerations. Pediatr Clin North Am. 1983;30:847-871 Murray AB, Ferguson AC. Dust-free bedrooms in the treatment of asthmatic children with house dust or house dust mite allergy: A controlled trial. Pediatrics. 1983;71 :418-422 Mygind N, Bisgaard H. Diseases of the nose. In: Bierman CW, Pearlman DS, eds.

READING

Bluestone

CD. Otitis media and sinusitis: Management and when to refer to the otolaryngologist. Pediatr Infect Dis. 1987;6:100-106 Bluestone CD, Klein JO, Paradise JL, et al. Workshop on effects of otitis media on the child. Pediatrics. 1983;71:639-652 Goldenhersh MJ, Rachelefsky OS, Dudley J, et al. The microbiology of chronic sinus disease in children with respiratory allergy. I Allergy Clin Immunol. 1990;85:1030-1039 Greenberg MA, Kaufman CR, Gonzalez GE,

Pediatrics

Diseases

from

Infancy

to

2nd ed. Philadelphia, PA: W.B. Saunders Co; 1988 Naclerio RM, Proud D, Togias AG, et al. Inflammatory mediators in late antigeninduced rhinitis. N Engi I Med. 1985; 313:65-70

Norman Imnusnol.

PS. Allergic

rhinitis.

I Allergy

Clin

1985 ;75 :531-545

Norman PS. Modulation of the mast cell and inhibition of its mediators. I Allergy Clin ImmunoL 1985;76:366-368 Patterson R, Grammer LC, Shaughnessy MA. Immunotherapy: Parameters of assessment. I Allergy

Clin

Immunol.

1985;76:394.-397

Pipkorn U, Proud D, Lichtenstein LM, KageySobotka A, Norman PS, Naclerio RM. Inhibition of mediator release in allergic rhinitis by pretreatment with topical glucocorticosteroids. N Engi I Med. 1987;316:

1506-1510

Roberts JE, Sanyal MA, Burchinal MR. Collier AM, Ramey CT, Henderson FW. Otitis media in early childhood and its relationship to later verbal and academic performance. Pediatrics. 1986;78:423-430 Schwartz Hi. The effect of cromolyn on nasal disease. Ear Nose Throat I. 1986 ;65:449456

Sundin B, Lilja 0, Graff-Lonnevig V. et al. Immunotherapy with partially purified standardized animal dander extracts. I Allergy Clin Iminunol. 1986;77:478-487 Teele DW, Klein JO, Rosner BA. Otitis media with effusion during the first three years of life and development of speech and language. Pediatrics. 1984;74:282-287 Tinkelman DO, Silk Hi. Clinical and bacteriologic features of chronic sinusitis in children. Am I Dis Child. 1989;143:938941 Virant FS. Chronic sinus disease in children. Pediatr

Asthma

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1988;

2:185-190 Virant FS. Medical management of allergic rhinitis. Insights in Allergy. 1990;5:27-31 Walker SB, Shapiro GO, Bierman CW, et al. Induction of eustachian tube dysfunction with histamine nasal provocation. I Allergy Chin Immunol. 1985;76:158-162

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