Principles of Treatment of Allergic Disease

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Chapter 136 Principles of Treatment of Allergic Disease

The basic principles of the treatment of allergic disease include the avoidance of exposure to allergens and irritants that trigger symptoms and the pharmacologic management of symptoms caused by unavoidable acute and chronic allergen exposures. In selected patients with allergic disease refractory to avoidance measures and optimal pharmacologic management, allergen immunotherapy may be considered.

Environmental Control Measures

Children spend the majority of their time in indoor environments, including the home. In an effort to save energy, houses and buildings have been built more tightly and with more insulation with fewer air exchanges. These factors have led to an increase in indoor humidity and higher concentrations of allergens and irritants in indoor air. Examination of indoor environments suggests that house dust mite, cat, and cockroach allergens are the most common significant triggers of allergic disease in these settings; exposures to allergens from other pets, pests, fungi, and respiratory irritants such as cigarette smoke are also a problem.

More than 30,000 species of mites have been identified, but the term dust mites usually refers to the pyroglyphid mites Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei, which are the major sources of allergen in house dust. Respiration and water vapor exchange occur through the skin of dust mites, rendering them sensitive to decreases in humidity and temperature extremes. The regular use of humidifiers and swamp coolers promotes dust mite survival. Mites do not survive with relative humidity <50%. They feed on animal and human skin scales and other debris, which is why they exist in large numbers in mattresses and bedding, carpet, and upholstered furniture. They are also found in flour and mixes for baked goods. Anaphylaxis has been reported following the ingestion of baked goods such as waffles and pancakes prepared with flour infested with dust mites. Dust mite fecal pellets are a major source of allergens. They consist of partially digested food combined with digestive enzymes encased in a permeable membrane, which keeps the fecal pellets intact. These fecal pellets have been likened to pollen grains, given their similarities in size (10-40 µm), the amount of allergen they contain, and their ability to release allergens rapidly on contact with moist mucous membranes. Mites can persist in imported furnishings for at least 2 yr; mite allergens have been shown to remain stable under domestic conditions for periods of at least 4 yr. Dust mite allergens become airborne during normal household activities; a vigorous disturbance such as vacuuming without a vacuum bag or shaking a bed sheet can launch significant amounts of dust mite allergens into the air. Once airborne, dust mite allergen particles settle out of the air relatively rapidly because of their size and weight. Nonetheless, dust mite allergen exposure likely occurs during sleep on mite-infested pillows and mattresses and during normal household activities when dust mite concentrations in the home are high enough. Levels of dust mite allergens as low as 2 µg/g of house dust can lead to sensitization, whereas levels of 10 µg/g of house dust are associated with symptoms.

Appropriate environmental control measures can significantly reduce exposure to dust mite allergens (Table 136-1). Major emphasis should be placed on reducing exposure to dust mite allergens in the bedroom and the bed because of the large amount of time the child spends there. Encasements impermeable to dust mite allergens should be placed on all pillows, the mattress, and the box spring. Dust should be removed from the surfaces of these covers and the bed frame by vacuuming weekly. The sheets and mattress pad should be washed weekly in hot water at a temperature of >130°F. Minimizing the number of items in the room that collect dust, such as books, drapes, toys, stuffed animals, and any clutter, is recommended. Major reservoirs of dust mite allergen that are often more difficult to deal with include the carpet and upholstered furniture, which should be vacuumed weekly with an efficient double-thickness-bagged vacuum cleaner. Although the application of acaricides or denaturing agents to carpets and upholstered furniture has been advised, the actual benefit remains unclear, and the amount of effort required may be more than most families are willing to invest. If possible, carpet removal, at least in the bedroom, may prove a better choice for eliminating a large reservoir of dust mite allergen. Other measures for dust mite allergen control include maintaining the indoor relative humidity at <50% and keeping the air conditioning set at the lowest level during the warmer months.

Table 136-1 ENVIRONMENTAL CONTROL OF ALLERGEN EXPOSURE

ALLERGEN CONTROL MEASURES
Dust mites

Animal dander Cockroaches Mold Pollen

Modified from Leung DYM, Sampson HA, Geha RS, et al: Pediatric allergy principles and practice, St Louis, 2003, Mosby, p 294.

In many countries, more than half of the households have pets, the most common of which are cats and dogs. The major sources of allergens from cats, dogs, horses, and cattle are hair, dander, and saliva, whereas the major source of allergens from rodents is urine. Studies of airborne cat allergen have shown that a significant portion is found on small particles that behave aerodynamically like spheres <7 µm in diameter. As much as 30% of airborne cat allergen may reside on particles <5 µm. Particles this small may not be adequately filtered by the nose and could potentially be deposited in the airways. Their small size enables these particles to remain airborne for longer periods and to be suspended repeatedly by air currents from heating and ventilation systems or just by walking across the carpet or sitting in an upholstered chair. Fel d 1, the major cat allergen, is a highly charged protein that readily sticks to a variety of surfaces, including walls, carpeting, and upholstered furniture. Owing to this adhesiveness, cat allergens bind to the cat owner’s clothing and are routinely transported to public buildings, including schools, where they have been measured in moderately high amounts. From these sites, significant amounts of cat allergen can subsequently be carried into homes without cats. Analysis of house dust from homes with cats reveals levels of Fel d 1 ranging from 8 µg to 1.5 mg/g of house dust. Levels of Fel d 1 in homes without cats vary from 0.2 to 80 µg/g of house dust. Sensitization to cat allergen has been associated with levels ranging from 1 to 8 µg/g of house dust. Carpets, upholstered furniture, and bedding serve as reservoirs of cat allergens, resulting in the persistence of significant amounts in the home for months after a cat has been removed. Complete avoidance of cat allergen is virtually impossible, although significant reduction in exposure to cat allergens is achievable.

Removing the pet from the home is obviously the most effective means of reducing exposure to animal allergens, although it has been demonstrated that without other interventions, such as removing carpeting and upholstered furniture and wiping down walls, it takes 6 months or more for the levels of cat allergen to drop to a level found in houses without a cat. As a result, cat owners who remove their pets from their homes should be informed not to expect immediate results. Unfortunately, advice to remove a pet from the home or keep it outdoors is often ignored. In contrast to dust mite allergens, cat allergen is light and remains suspended in the air for long periods. As a result, air cleaners with high-efficiency particulate air (HEPA) filters are helpful in reducing the amount of airborne cat allergen. Other suggested methods include washing the cat regularly and maintaining a cat allergen–free bedroom from which the cat is excluded and where mattress covers and air-filtering devices are used. The cat should also be restricted from other living areas where the sensitized child spends large amounts of time, such as the family room and other play areas (see Table 136-1). Regular vacuuming with a HEPA-filtered and double–thickness bag vacuum cleaner is also encouraged. Similar measures are suggested for the control of exposure to other animal allergens, although whether these measures reduce exposure to levels resulting in clinical improvement as demonstrated by decreased symptoms, improved peak flows, or decreases in bronchial hyperreactivity remains to be documented by appropriately controlled studies.

Infestation of the home by insects and other pests such as mice and rats is another potential source of significant allergen exposure in the indoor environment. Studies have identified the importance of exposure to cockroach allergens as a major risk factor for the development of asthma in inner-city children. Once sensitized, inner-city cockroach-sensitive asthmatic children with continued exposure to high levels of cockroach allergens in their bedrooms are at higher risk for urgent care visits and hospitalization than inner-city asthmatic children who are not allergic to cockroaches. Recommended methods to decrease cockroach allergen exposure include reducing cockroaches’ access to the home by sealing cracks in the flooring and walls and removing sources of food and water by repairing leaky pipes, putting away food, and frequent cleaning (see Table 136-1). Regular extermination using baits or chemical treatment of infested areas is also advised.

Efforts to improve indoor air quality should also encompass reducing exposure to respiratory irritants. Passive exposure to environmental tobacco smoke worsens asthma and increases nasal symptoms in patients with allergic nasal disease. Smoking cessation should be repeatedly encouraged, and smoking indoors should never be permitted. The use of wood-burning stoves and fireplaces and of kerosene heaters should be discouraged.

Although exposure to pollens and fungi occurs primarily outdoors, these allergens are detectable indoors during the warmer months, when their indoor levels often reflect their prevalence in the outdoor environment. During the winter, when the outdoor levels of other fungi are lowest, the indoor fungi Aspergillus and Penicillium are the most prevalent. Fungi are often found in damp basements and thrive in conditions associated with increased moisture in the home, such as water leaks, flooding, and increased humidity promoted by the excessive use of humidifiers or swamp coolers. Exposure to indoor fungal allergens can be reduced by maintaining the indoor relative humidity at < 50%, removing contaminated carpets, and wiping down washable surfaces prone to fungal growth, such as shower stalls, shower curtains, sinks, drip trays, and garbage pails, with the use of solutions of detergent and 5% bleach (see Table 136-1). Dehumidifiers should be placed in damp basements. Standing water at any site in the home should be eliminated, and the cause addressed. Removing all items from the home that are prone to fungal contamination and growth is also encouraged. Keeping the windows and doors closed and using air conditioning to filter outdoor air can keep both indoor pollen and fungi levels to a minimum during the warmer months, when outdoor levels of these allergens are at their peak. The use of window or attic fans is to be avoided. Laundry should be dried in a dryer rather than on a clothesline. Measures to avoid pollens and fungal spores when out of the house include closing the windows and using the air conditioner when traveling in the car, avoiding moldy vegetation, and wearing a mask when these materials cannot be avoided. Outdoor activities during periods of high pollen counts should be kept to a minimum. Someone other than the sensitized patient should mow the lawn and rake leaves. Frequent handwashing after outdoor play is suggested to avoid transferring pollens from the hands to the eyes and nose. At the end of the day, showering and shampooing are suggested to avoid contamination of the bed with allergens. During the day, the bed should remain covered with a bedspread.

Pharmacologic Therapy

Adrenergic Agents

Adrenergic agents exert their effects through the stimulation of cell surface α- and β-adrenergic receptors in a variety of target tissues. These receptors belong to the G protein–coupled superfamily of receptors. In general, α-adrenergic receptor stimulation results in excitatory responses such as vasoconstriction, whereas β-adrenergic stimulation leads to inhibitory responses such as bronchodilation. The α-adrenergic receptors have been classified into α1– and α2-adrenergic receptors. Further studies of these receptors in humans have identified 3 subtypes of α1-adrenergic receptors and 3 subtypes of α2-adrenergic receptors. The β-adrenergic receptors are further divided into 3 subtypes: β1, β2, and β3. Each of these adrenergic receptors exhibits a distinctive tissue distribution. The physiologic response in a given tissue to the administration of an adrenergic agent depends on the specific receptor-binding characteristics of the drug as well as the numbers and distribution of the various types of adrenergic receptors in the tissue. Epinephrine remains the drug of choice for the treatment of anaphylaxis because of its combined α- and β-adrenergic effects.

The α-adrenergic agents are effective in the treatment of allergic nasal disease because of their decongestant effects (see Tables 137-2 and 137-4). In the nose, stimulation of α1-adrenergic receptors on postcapillary venules and of α2-adrenergic receptors on precapillary arterioles leads to vasoconstriction, resulting in a reduction in nasal congestion. The oral decongestants currently in clinical use include pseudoephedrine and phenylephrine. These medications are available individually or in combination with antihistamines in liquid and tablet forms, including sustained-release preparations. Phenylpropanolamine and all combination products containing this sympathomimetic amine similar in structure to pseudoephedrine have been taken off the market in the USA by the U.S. Food and Drug Administration (FDA) because of concerns about the risk of hemorrhagic stroke and the inability to predict who is at risk. Pseudoephedrine is rapidly and thoroughly absorbed, whereas phenylephrine, the less effective of the two drugs, is incompletely absorbed, resulting in a significantly lower bioavailability of ≈ 38%. Peak plasma concentrations of these drugs are reached between 30 min and 2 hr of administration, but the decongestant effect has not been directly correlated to the plasma concentration. Pseudoephedrine is excreted essentially unchanged by the kidney. The use of oral decongestants should be avoided in patients with hypertension, coronary artery disease, glaucoma, or metabolic disorders such as diabetes and hyperthyroidism. Reported adverse effects of oral decongestants include excitability, headache, nervousness, palpitations, tachycardia, arrhythmias, hypertension, nausea, vomiting, and urinary retention. Decongestants available as topical nasal sprays include phenylephrine, oxymetazoline, naphthazoline, tetrahydrozoline, and xylometazoline. Given their efficacy and rapid onset of action, the potential for excessive use of topical nasal decongestants resulting in rebound nasal congestion is high. When this occurs, refraining from the use of these sprays for 2-3 days is necessary for recovery.

Drugs that stimulate β-adrenergic receptors have been used for years in the treatment of asthma because of their potent bronchodilator effects (see Table 138-11). The subclassification of β-adrenergic receptors into β1 and β2 subtypes led to the development of drugs selective for the β2-adrenergic receptor, such as albuterol, that have the advantage of producing significant bronchodilation with less cardiac stimulation. The long-acting inhaled β2-adrenergic agonists (LABAs) salmeterol and formoterol, with a 12-hr duration of action, are approved for use in children ≥ 4 yr of age. LABAs are not recommended for the treatment of acute asthma exacerbations because of their relatively slow onset of action. Concern about an apparent increased risk of asthma-related adverse events is why LABAs are not recommended as monotherapy for the long-term control of persistent asthma but are promoted as best used in conjunction with an inhaled steroid. Dry powder inhaled and metered-dose inhaler preparations combining a LABA with an inhaled corticosteroid have had significant impact on the treatment of children with moderate persistent asthma. In addition to their bronchodilating effects, β2

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