Insects were recognized as inhalant allergens long before mites (which are arachnids, not insects) came to the foreground. Cockroaches have been described as allergens based on skin test data in allergic persons ( 217). Kang and associates (218) extended this work to include RASTs and bronchoprovocation studies to further implicate cockroach-associated materials as asthmagenic. Asthmatics with positive skin-prick test results to cockroach extracts have been reported to have higher total serum IgE levels than their allergic counterparts with negative skin test results. Bronchoprovocation caused a transient peripheral eosinophilia in those who reacted positively.

Of the over 50 species of cockroaches described, only 8 are regarded as "indoor" pests. Allergens from the two most common species, Blattella germanica and Periplanta americana, have been the most studied. Immunoelectrophoretic studies of roach allergens have disclosed multiple antigens, with most allergens residing in the whole-body and cast-skin fractions. Feces and egg casings were less allergenic ( 219). Roach hemolymph also may be allergenic (220). Recombinant clones have been developed for many of the allergens, and their function has been defined. Per a 1 and Bla g 1 are cross-reactive and have sequence homology with a mosquito digestive protein (221). Bla g 2 shows sequence homology to an aspartic protease (222). Per a 3 has been defined and may have some cross-reactivity with a German cockroach allergen (223). Bla g 4 is a lipocalin (224). Bla g 5 is a glutathione-S-transferase (225). In addition, a tropomyosin has been identified as an allergen from Periplanta americana, with sequence homology to dust mite and shrimp tropomyosins (226).

Outdoor insects such as mayfly and caddis fly have been studied clinically and immunologically ( 227). These insects have an aquatic larval stage and therefore are found around large bodies of water such as the Great Lakes, particularly Lake Erie. These flies were reported to cause significant respiratory allergy in the summer months, but their numbers have declined, probably because of pollution of the lakes. Japanese investigators reported that 50% of asthmatics show sensitivity to the silkworm moth (Bombyx mori) caused by antigens found in the wings. These wing allergens cross-react almost completely on RAST inhibition with butterfly allergens, but not at all with mites (228). Finished silk products are not thought to be allergenic, but contamination of some products, such as silk-filled bed quilts, with waste products of B. mori and the Antheraea pernyi can cause asthma and rhinitis.

In the Sudan, during certain seasons, respiratory allergy has been reported from inhalation of allergens of the "green nimmiti midge." These are chironomids, nonbiting members of the order Diptera (229). Studies of these chironomid antigens by RAST show the allergenic activity of the larvae to be in the hemoglobin molecule (230). Studies on this allergen from Chironomus thummi have identified regions of IgE binding and T-cell epitopes ( 231).

Outdoor air sampling in Minnesota has disclosed allergens for the moth Pseudaletia unipuncta (Haworth). The levels of this moth antigen peaked in June and again in August to September, and the allergen levels were comparable with those of pollen and mold allergens. Furthermore, 45% of patients with positive skin test results to common aeroallergens had positive reactions to whole-body insect extracts. Of 120 patients with ragweed sensitivity, 5% had elevated specific IgE to moths. Hence, Lepidoptera may be considered seasonal allergens (232).

Occupational exposure to insects may cause respiratory allergy. Chironomid larvae are used as fish food, resulting in symptoms among workers in their production, laboratory personnel, and hobbyists (231). Similar symptoms, all documented with RAST and inhalation challenge, have been reported in workers handling crickets used for frog food (233) and mealworms (Tenebrio molitor) used as fishing bait (234). Asthma and rhinitis occur in some bee keepers and in workers involved in honey production because of inhalation of honeybee body components. In these individuals, RAST inhibition is not achieved with venom extract ( 235). Occupational allergy has been reported in laboratory workers dealing with locusts (236). In these workers, as in the case of murine allergen-sensitive laboratory workers, atopy was not a prerequisite for sensitization. The primary locust allergen is the peritrophic membrane that surrounds food particles when they pass through the midgut and eventually become feces. The common housefly (Musca domestica) also has been reported as a cause of occupational allergy in laboratory workers ( 237), as has the grain beetle (Alphitobius diaperinus). Larval, pupal, and adult stages of the life cycle of this beetle all are capable of inducing allergy, but pupal extract contains the most significant allergens (238).

Hypersensitivity to the salivary secretions of biting insects exists. Local immediate and delayed allergy to the bites of mosquitoes, fleas (papular urticaria), sand flies, deer flies, horse flies, and tsetse flies has been reported. Other case reports have described generalized reactions to multiple bites (deer fly) consisting of fever, malaise, and hypotension associated with antibodies to the offending insect. Experimental sensitization in humans with flea bites results first in the induction of delayed, and then in immediate, wheal-and-flare hypersensitivity on skin testing.

Hypersensitivity to the venom of stinging insects (Hymenoptera) is the subject of another chapter and is not discussed here. Seeds

Seeds may be important causes of asthma and rhinitis. Cottonseed and flaxseed are exceptionally potent antigens and should be used for skin testing only by the epicutaneous method. Deaths have been reported from intradermal tests of both substances. Extreme caution should be used in skin testing.

Cottonseed is the seed of the cotton plant. After extracting the oil, which is not allergenic, the seed is ground into meal, which may be used for animal feeds or fertilizer. Cottonseed meal and flour also are used in the baking industry for certain cakes, cookies, and pan-greasing compounds. Cotton linters are the short cotton fibers that adhere to the seeds after the cotton is ginned. These are separated and used for stuffing mattresses and furniture. Enough of the water-soluble cottonseed allergen adheres to these linters to render them allergenic (239). Several cases of angioedema, urticaria, or anaphylaxis have been reported in individuals who have eaten whole-grain bread or candy containing cottonseed meal (240,241).

Flaxseed (linseed) has the same properties as cottonseed and has many of the same general uses in industry and agriculture. Additional uses are in hair preparations, poultices, electric wire insulation, and the tough backing material used in the manufacture of rugs. Linseed oil is a common household product and is found in furniture polish and printer's ink. In these forms, it produces contact rather than inhalant allergy.

Coffee bean allergy is largely confined to those who handle the green beans commercially, including longshoremen who unload the sacks of beans from ships. Chlorogenic acid has been considered an allergen in green coffee beans, castor beans, and oranges. It is a simple chemical that was thought to act as a hapten. Its importance is questionable, however, because it is destroyed by roasting and thus cannot account for allergy from drinking coffee. Castor bean ( Ricinus communis) allergy is mainly from the pulp and hull that remain after castor oil is pressed from the bean. This castor pomace is ground into a meal that is used for fertilizer. Thus, castor bean allergy also is largely occupational. Low-molecular-weight protein fractions have been isolated, as well as a toxic substance, ricin, which is not allergenic. Castor bean allergy also may occur in neighborhoods adjacent to processing plants. Asthma and rhinitis have been reported from the protein residual in the ambient air. A study from Marseilles, France, reports the incidence of castor bean allergy to be the same in atopic and nonatopic individuals ( 242). Three allergenic castor bean proteins have been identified by protein electrophoresis. One of these three, Ric c 1, one of the "2S albumins" or storage proteins of the castor bean, has homology to both rice allergens and mustard seed allergens (243,244). The 2S albumins represent one of two common storage proteins found in a variety of seeds, including sunflower seeds, Brazil nuts, and rapeseeds. Like other sensitizing allergenic proteins, these have low molecular weights, are highly soluble in water, and generally have no toxicity for nonallergic persons (245).

Soybean allergy may be more generalized and prevalent because of the increased use of soy flour and meal in commonly encountered products. In addition to use as animal feed, soy products are used for infant formula, bakery goods, Chinese cooking, cereals, fillers in meat and candy products, and in certain topical dermatologic preparations. Occupational asthma caused by soybean flour used as a protein expander in frozen meat patties has been reported. Soybean protein consists of a globulin fraction (85%) and a whey fraction. Nine proteins bound to IgE by immunoblotting have been recognized by an allergic patient's serum ( 246). Asthma epidemics have occurred in Barcelona, Spain, in association with unloading soybeans from ships. Case studies of those affected show a high incidence of IgE antibodies to soybean allergens. Subsequent investigations have shown that the major allergens are glycoproteins found in the hulls and dust, with molecular sizes less than 14 kDa (247,248 and 249).

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