Allergic Rhinitis and Asthma: Role of Environmental Determinants

Approximately 56 million Americans (20% of the population) suffer from allergic rhinitis, and about 5% have asthma.¹ Recent epidemiologic studies indicate that the prevalence of allergic rhinitis and asthma is increasing in the United States and throughout the world.^1,2

Indoor environmental allergen exposure is widely believed to be a major contributing factor to the rising prevalence of these disorders. This hypothesis is supported by studies that have compared the prevalence of atopy and asthma among rural and urban populations and found that these conditions were more prevalent among rural inhabitants who moved to urban dwellings.^1,3 This striking finding highlights the importance of domestic exposures in creating susceptibility to atopy and asthma among urban dwellers.

In this article, I review the environmental determinants of allergic rhinitis and asthma. In a second article I address the importance of allergen avoidance measures in patients with these conditions and review interventions directed at reducing exposure to dust mite, pet, and cockroach allergens.

ALLERGIC DISEASE

The annual cost of treating allergic rhinitis in the United States exceeds $3 billion. The annual cost of asthma treatment is estimated at nearly $13 billion per year.^1,4 This economic burden is even more substantial if one factors in the costs of treating sinusitis and otitis media, which are common complications of inadequately treated allergic rhinitis.^1,5 The significant morbidity and rising health care costs associated with allergic rhinitis and asthma mandate that physicians become more proficient in the evaluation and treatment of these conditions. The triggers and symptoms of rhinitis and asthma are reviewed in the Table.

Allergic rhinitis. This is the most prevalent chronic illness diagnosed in children younger than 18 years and the fifth most common chronic illness diagnosed overall. Persons with allergic rhinitis are at increased risk for asthma.^1,5 Seasonal allergic rhinitis refers to the presence of allergy symptoms triggered by pollen or mold spore allergens during the spring, summer, or fall. These pollen and mold spore seasons vary geographically throughout the United States.

Symptoms may include sneezing fits (5 to 10 sneezes in succession); itchiness of the eyes, ears, nose, throat, and palate; runny nose; watery/puffy eyes; nasal congestion; postnasal drip; sinus pressure; and fatigue. Symptoms are typically worse when patients are outdoors during pollen seasons and improve when they are indoors in an air-conditioned environment.^1,6 Patients usually can distinguish whether symptoms occur seasonally, perennially, or both.

Perennial allergic rhinitis refers to year-round symptoms that are triggered by indoor allergens, such as those from dust mites, cockroaches, mold spores, feathers, and animals. Symptoms include nasal congestion, postnasal drip, sinus pressure/headaches, and ear plugging/popping and may include any or all of the above seasonal allergy symptoms.

Patients with both perennial symptoms and seasonal exacerbations are considered to have perennial allergic rhinitis with a seasonal component.^1,6 Triggers may include outdoor pollens and indoor allergens such as dust mites; mold spores; and exposures to cats, dogs, birds, and cockroaches. Perennial allergens, such as those from dust mites, molds, animals, and cockroaches, may be difficult to identify by the history alone. Skin testing is necessary to confirm sensitization to these allergens but does not indicate that the person is currently being exposed.^1,6

Conditions such as nonallergic rhinitis (vasomotor rhinitis or nonallergic rhinitis with eosinophil syndrome) can mimic allergic rhinitis. Patients with nonallergic rhinitis experience nasal congestion, postnasal drip, sinus pressure/headaches, and ear plugging. Results of skin testing for seasonal and perennial allergens are negative.

The triggers for nonallergic rhinitis include weather changes (both temperature and barometric pressure changes); postural changes; and irritants, such as smoke, potpourri, perfumes, cleaning agents, solvents, incense, and soaps or detergents.^1,6 Patients who have allergic and nonal- lergic rhinitis components are said to have mixed rhinitis, which may occur in up to 50% of patients presenting with rhinitis symptoms.

Asthma. This chronic obstructive inflammatory lung disease is characterized by airway inflammation, bronchial hyperresponsiveness, and at least partial improvement of lung function after treatment with bronchodilator medication.^1,7 Untreated asthma can lead to airway remodeling or scarring of the airways that results in permanent loss of lung function.

Typical asthma symptoms include wheezing, coughing, chest tightness, and shortness of breath. However, many other conditions, such as gastroesophageal reflux disease, postnasal drainage from chronic sinusitis, vocal cord dysfunction, congestive heart failure, and pulmonary emboli, can present with symptoms that mimic asthma. It is always important to remember that "all that wheezes may not be asthma and all that is asthma may not wheeze."

Common triggers for patients with allergic asthma include animals, dust mites, cockroaches, mold spores, and pollen. Nonallergic triggers include viral upper respiratory tract infections, exercise, extreme temperatures, and a wide spectrum of irritants.^1,7

ENVIRONMENTAL DETERMINANTS

Asthma is a complex disease that is influenced by multiple genetic and environmental determinants.Debate continues about whether genetic or environmental factors predominate in the development of asthma. However, most studies now indicate that environmental exposures play a key role in causing and aggravating asthma. This concept is best exemplified in studies of monozygotic twins, which have identified as much as a 50% discordance for asthma among genetically identical probands.⁸ The implication is that differences in environmental exposures may be important in the phenotypic expression of asthma.

Evidence also indicates that asthma is primarily an allergy-mediated disease. In 1989, Burrows and colleagues⁹ reported a strong correlation between total IgE levels, positive allergen skin test responses, and asthma findings; this has subsequently been confirmed by other investigators. It is now well established that patients with extrinsic (allergic) and intrinsic (nonallergic) asthma both express TH2 cytokines that play a role in the development of asth- ma and a number of other allergic diseases.¹⁰

Atopy is now considered a risk factor for asthma. The critical period for allergen sensitization appears to be the first 2 to 3 years of life.¹¹ However, sensitization may begin even earlier; researchers have shown that the developing fetus can elicit IgE-mediated responses to relevant allergenic stimuli at as early as 22 weeks' gestation.¹²

Researchers are now investigating whether environmental interventions initiated during the third trimester in pregnant women with a personal or family history of allergies or asthma would prevent or delay allergen sensitization and asthma in their infants. Preliminary data indicate that specific interventions successfully reduced allergen exposures and allergen sensitization and the development of asthma in children whose homes had such interventions.¹³

Most of the longitudinal birth cohort studies indicate that avoidance measures over several years prevent allergen sensitization and the progression of asthma and allergic rhinitis when multiple interventions are implemented. For example, one study reported that strict allergen avoidance reduced the risk of dust mite sensitization and the development of some cases of childhood asthma.¹⁴ The recently published Canadian Childhood Asthma Primary Prevention Study implemented a multifaceted intervention program to prevent asthma in high-risk infants (ie, infants with an immediate family history of asthma and allergies).¹⁵ Researchers found that the prevalence of pediatric allergist-diagnosed asthma was lower in the intervention group at 7 years of age. However, studies that implemented single interventions to reduce allergen exposure (bedding encasements only) did not demonstrate prevention of dust mite sensitization or the prevention of asthma and allergic rhinitis.^16,17

Dust mite allergen. A number of studies have sought to determine the role of allergenic stimuli in the subsequent development of allergic asthma. To date, the dust mite allergen has been the most extensively studied allergen. The major allergens of house dust mites come from their fecal waste particles and glandular secretions.^18,19

Dust mite allergens are primarily enzyme proteins, which may explain why they are highly sensitizing. About 90% of persons with allergies and more than 70% of asthmatic patients are sensitized to dust mites. These organisms thrive in humid environments and feed on human skin scales. They are most commonly found in bedding (pillows, mattresses, box springs, comforters), carpets, and upholstered furniture.^18,19

Many studies have confirmed the relationship between dust mites and the development of asthma and allergic rhinitis.^17-20 Sporik and associates¹⁹ reported that exposure to house dust mites in early childhood is an important determinant in the later development of asthma. Peat and associates²¹ found that house dust mites are an important cause of childhood asthma and that reducing young children's exposure to these organisms may help prevent asthma. Subsequent studies have shown that reduction of dust mite allergen to very low levels (less than 2 µg/g of dust) can prevent dust mite sensitization and asthma.¹⁹ As mentioned, single interventions directed at reducing dust mite allergen (such as bedding encasements over the pillow and mattress) effectively reduced allergen exposure but did not reduce asthma and allergy symptoms.^17,20

Cat and dog allergens. Animal allergens are also an important cause of and exacerbating factor in asthma and allergic rhinitis. It is estimated that more than a third of Americans have 1 or more cats in their home. Cat allergen is a very light allergen (3 µm in diameter) that is primarily released from the sebaceous glands in the skin. Cat allergen can stay suspended in the air for 5 to 6 hours at a time and become airborne with minimal disturbance in the room.²² It sticks to walls, clothing, shoes, carpets, bedding, and furniture, and it is difficult to get rid of completely. Even after the cat has been removed from the home, measurable amounts of cat allergen can be detected for several months.²³

Lindfors and colleagues²⁴ found a strong relationship between cat exposure and sensitization. A combination of dampness, passive smoke exposure, and cat exposure with cat sensitization was strongly associated with subsequent development of asthma. Studies have also reported significant levels of cat allergen in homes where there are no cats, which suggests that cat allergen can be brought in from outside sources on shoes and clothing.²⁵ Siebers and associates²⁵ measured cat and dust mite allergen levels in the Antarctic, where there are no cats and the relative humidity seldom rises above 20%. Surprisingly, they found dust mite allergen and even greater levels of cat allergen in the living environments sampled. This study confirmed the fact that allergens can be passively transferred to local environments that would be unlikely to support their accumulation.

Ingram and associates²⁶ found high levels of cat and dog allergens in homes with cats and/or dogs. Cat and dog allergen sensitization was strongly associated with the development of asthma. Sarpong and Karrison²⁷ found that children with combined sensitivity to cat, dog, dust mite, and cockroach allergens were at increased risk for a more severe form of asthma. In addition, sensitization to cat allergen alone constituted a risk factor for more severe asthma in children.²⁸

Several studies have reported that early exposure to cat allergen may decrease the risk of sensitization and asthma.^29-32 This observation raises important questions about the dose-response relationship between allergen exposure and sensitization. Further investigation will be required in order to understand whether this finding represents immunologic tolerance or merely an interesting epidemiologic association.^29-31 Brussee and colleagues³² recently reported that early cat and dog exposure leads to sensitization and wheezing in children, especially if they have a maternal history of asthma.

Cockroach allergen. Cockroaches are present in most homes even though they usually cannot be readily observed. The sighting of a cockroach during the daytime often suggests that there is major overcrowding of cockroach populations and significant infestation in the home. The 2 major species of cockroaches in the United States are German and American.³³ A significant amount of evidence supports a relationship between cockroach sensitization and asthma.

Rosenstreich and associates³⁴ found that inner-city children with asthma are allergic to dust mites, cockroaches, and cats. However, they found that cockroach allergen levels in the bedrooms of these children were approximately 5 times higher than dust mite and cat allergen levels. Children with cockroach allergy and high cockroach bedroom exposure levels were at much greater risk for hospitalization and unscheduled medical visits for asthma and had more asthma symptoms overall compared with other children with asthma not sensitized to cockroach allergen.

The combination of cockroach sensitization and high levels of cockroach exposure may explain the increased frequency of asthma reported among inner-city children. Sarpong and colleagues³⁵ reported that African American race and low socioeconomic status were significant independent risk factors for cockroach allergen sensitization in children with atopic asthma.

Other risk factors. Many other factors have been found to be potentially important for the later development of asthma and allergies. These include a maternal history of asthma, maternal smoking during pregnancy, lack of prenatal care, low birth weight, long durationof breast-feeding, firstborn status, moldy or humid living environments, passive smoke exposure, and recurrent viral infections or bronchiolitis in the first few years of life.³⁶

References:

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13. Custovic A, Simpson BM, Simpson A, et al. Manchester asthma and allergy study: low-allergen environment can be achieved and maintained during pregnancy and in early life. J Allergy Clin Immunol. 2000;105:252-258.
14. Arshad SH, Bateman B, Matthews SM. Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomized controlled study. Thorax. 2003;58:489-493.
15. Chan-Yeung M, Ferguson A, Watson W, et al. The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age. J Allergy Clin Immunol. 2005;116:49-55.
16. Horak F Jr, Matthews S, Ihorst G, et al. Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study--24 months results of the Study of Prevention of Allergy in Children in Europe. Clin Exp Allergy. 2004;34:1220-1225.
17. Woodcock A, Forster L, Matthews E, et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med. 2003;349:225-236.
18. Marks GB, Tovey ER, Toelle BG, et al. Mite allergen (Der p 1) concentration in houses and its relation to the presence and severity of asthma in a population of Sydney schoolchildren. J Allergy Clin Immunol. 1995;96:441-448.
19. Sporik R, Holgate ST, Platts-Mills TAE, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in child-hood. N Engl J Med. 1990;323:502-507.
20. Terreehorst I, Hak E, Oosting AJ, et al. Evalua-tion of impermeable covers for bedding in patients with allergic rhinitis. N Engl J Med. 2003;349:237-246.
21. Peat JK, Tovey E, Toelle BG, et al. House dust mite allergens: a major risk factor for childhood asthma in Australia. Am J Respir Crit Care Med. 1996;153:141-146.
22. Luczynska CM, Li Y, Chapman MD, Platts-Mills TA. Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Measurements using cascade impactor, liquid impinger, and a two-site monoclonal antibody assay for Fel d I. Am Rev Respir Dis. 1990;141:361-367.
23. Carswell F, Oliver J, Weeks J. Do mite avoidance measures affect mite and cat airborne allergens? Clin Exp Allergy. 1999;29:193-200.
24. Lindfors A, van Hage-Hamsten M, Rietz H, et al. Influence of interaction of environmental risk factors and sensitization in young asthmatic children. J Allergy Clin Immunol. 1999;104:755-762.
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26. Ingram JM, Sporik R, Rose G, et al. Quantitative assessment of exposure to dog (Can f 1) and cat (Fel d 1) allergens: relation to sensitization and asthma among children living in Los Alamos, New Mexico. J Allergy Clin Immunol. 1995;96:449-456.
27. Sarpong SB, Karrison T. Skin test reactivity to indoor allergens as a marker of asthma severity in children with asthma. Ann Allergy Asthma Immunol. 1998;80:303-308.
28. Roost HP, Kunzli N, Schindler C, et al. Role of current and childhood exposure to cat and atopic sensitization. J Allergy Clin Immunol. 1999;104:941-947.
29. Henriksen AH, Holmen TL, Bjermer L. Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis. Respir Med. 2001;95:122-129.
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31. Platts-Mills TA, Vaughan JW, Blumenthal K, et al. Serum IgG and IgG4 antibodies to Fel d 1 among children exposed to 20 microg Fel d 1 at home: relevance of a nonallergic modified Th2 response. Int Arch Allergy Immunol. 2001;124:126-129.
32. Brussee JE, Smit HA, van Strien RT, et al. Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at 4 years. J Allergy Clin Immunol. 2005;115:946-952.
33. Chapman M. Cockroach allergens: a common cause of asthma in North American cities. Insights Allergy. 1993;8:1-8.
34. Rosenstreich DL, Eggleston P, Kattan M, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med. 1997; 336:1356-1363.
35. Sarpong SB, Hamilton RG, Eggleston PA, Adkinson NF. Socioeconomic status and race as risk factors for cockroach allergen exposure and sensitization in children with asthma. J Allergy Clin Immunol. 1996;97:1393-1401.
36.Holgate ST. The epidemic of allergy and asthma. Nature. 1999;402(suppl):B2-B4.

EVIDENCE-BASED MEDICINE:

• Eggleston PA. Improving indoor environments: reducing allergen exposures. J Allergy Clin Immunol. 2005;116:122-126.

• Prescott SL, Tang ML. The Australasian Society of Clinical Immunology and Allergy position statement: summary of allergy prevention in children. Med J Aust. 2005;182:464-467.

RELEVANT GUIDELINES:

• Diagnosis and Management of Rhinitis: Parameter Documents of the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology. Available at: www.jcaai.org/Param/Rhinitis/index.htm. Accessed May 24, 2006.