REACTIONS IN THE AIRWAYS

IV. REACTIONS IN THE AIRWAYS

Asthma, rhinitis, and nasal polyposis are the main hypersensitivity symptoms of the respi- ratory tract.

A. Azo Dyes and Benzoates

In the late 1950s it was discovered that food colorants may provoke asthma (Speer, 1958; Lockey, 1959). Of them, tartrazine has been most studied, and its role in asthmatic reac- tions was established in the 1960s (Chafee and Settipane, 1967). It is still added to many pharmaceutical products as well as to foods and soft drinks in several countries. Many adverse reactions reported have been associated with medications, pills, capsules, and elixirs. Sodium benzoate and other benzoic acid derivatives can also produce respiratory symptoms. The tartrazine molecule possesses similarities to other azo compounds, benzo- ates, pyrazole compounds, and the hydroxyaromatic acids, which include salicylate and aspirin ( Figure 1 ) (Miller, 1985).

Usually the subjects examined for tartrazine and benzoate reactions have been highly selected, often asthmatics who are known to be intolerant to aspirin. Aspirin was reported to cause serious reactions in some patients with asthma as early as 1919 (Cooke, 1919). The reported figures of intolerance to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with asthma differ widely, from 1 to 44% (Vedanthan et al., 1977; Weber et al., 1979). In an unselected population an incidence of 0.5% has been reported (Schlumberger, 1980).

Often patients have rhinitis associated with nasal polyps for years before asthmatic intolerance to aspirin becomes manifest. It is possible that when intolerance to aspirin develops, it also extends to some food additives, which then cause adverse reactions via

Figure 1 Molecular similarities between azo dyes, benzoates, pyrrazole compounds, and hydro- xyaromatic acids including acetylsalicylic acid.

aspirin sensitivity (Speer et al., 1981; Rosenhall, 1977). Concomitant reactivity to tartra- zine has been reported in 8–50% of aspirin-sensitive asthmatic patients (e.g., Samter and Beers, 1968; Settipane and Pudupakkam, 1975; Stenius and Lemola, 1976; Spector et al., 1979). No correlation between aspirin and tartrazine was found by Stevenson et al. (1986).

Rosenhall (1977) tested 504 patients with asthma and rhinitis. Reaction to at least one of the substances (food colorants, preservatives, analgesics) occurred in 106 (21%) patients. In 33 patients who reacted to tartrazine, 42% were also intolerant to aspirin and 39% to sodium benzoate. Stenius and Lemola (1976) tested 140 asthmatics, of whom 17 Rosenhall (1977) tested 504 patients with asthma and rhinitis. Reaction to at least one of the substances (food colorants, preservatives, analgesics) occurred in 106 (21%) patients. In 33 patients who reacted to tartrazine, 42% were also intolerant to aspirin and 39% to sodium benzoate. Stenius and Lemola (1976) tested 140 asthmatics, of whom 17

Some of the asthmatic patients experience only rhinitis when challenged with aspi- rin, tartrazine, or benzoates. There were 104 patients with chronic rhinitis in the Rosenhall study; 4% of them had a positive reaction with nasal symptoms and 16% had a doubtful reaction when challenged.

It has been assumed that children have adverse reactions of the respiratory tract to food additives less frequently than adults. Vedanthan et al. (1977), Osterballe et al. (1979), and Weber et al. (1979) found few asthmatic children who reacted to aspirin, food color- ants, and benzoates.

Many of the studies on food colorants have been open and poorly controlled. Re- cently, Morales et al. (1985) made a placebo-controlled study and challenged 47 asthmatic patients with intolerance to aspirin. Only one patient had a respiratory reaction to tartrazine on two successive occasions. The authors stated:

The inconvenience associated with a colour-free diet and the small incidence of proven reac- tions to tartrazine, tend to invalidate the practice of recommending such diets unless evidence is available of a positive challenge test on at least two occasions. Even so, the risks induced are minimal.

Genton et al. (1985) also made a placebo-controlled study and challenged 17 asthmatics whose case histories suggested an intolerance to aspirin or additives with tartrazine and sodium benzoate. Only two patients had a mild positive reaction. Additionally, two pa- tients reacted with urticaria. Stevenson et al. (1986) made single-blind challenges with 25–50 mg of tartrazine in 150 aspirin-sensitive asthmatics and found six positive re- sponses. Double-blind rechallenge with tartrazine was negative in all five patients in whom the test was performed.

At present it seems that respiratory adverse reactions to food colorants and benzoates are infrequent. Asthmatic patients with aspirin intolerance may have an increased risk of experiencing these reactions. If the reaction occurs, it is usually mild. Life-threatening reactions are extremely rare.

B. Sulfites

Sulfiting agents include sulfur dioxide (SO 2 ), sodium sulfite, and the potassium and sodium salts of bisulfite and metabisulfite. Sodium and potassium bisulfite and metabisulfites are converted into sulfurous acid in solutions and sulfur dioxide itself. Sulfites are antioxidants that are used as preservatives in foods and drugs, especially in injected and inhaled medica- tions, and as antimicrobial and sanitizing agents in the production of wine (Settipane, 1984). They are used on dehydrated vegetables and dried fruits, in fruit drinks, and also in many other products (Przybilla and Ring, 1987).

Prenner and Stevens (1976) were the first to report a patient who experienced an anaphylactic reaction after ingestion of sulfites in foods. After that, several reports sug- gesting anaphylactoid reactions to sulfite agents were published (e.g., Stevenson and Si- mon, 1981). Freedman (1977a) demonstrated that asthmatics could react to the sulfur Prenner and Stevens (1976) were the first to report a patient who experienced an anaphylactic reaction after ingestion of sulfites in foods. After that, several reports sug- gesting anaphylactoid reactions to sulfite agents were published (e.g., Stevenson and Si- mon, 1981). Freedman (1977a) demonstrated that asthmatics could react to the sulfur

Bronchoconstriction after oral administration of sulfur dioxide was seen in 4 of 17 adult asthmatics by Genton et al. (1985). Towns and Mellis (1984) reported that as many as 19 children of 29 with chronic asthma reacted with bronchoconstriction when chal- lenged with metabisulfite in a solution of 0.5% citric acid. None of the children reacted to metabisulfite in capsule form. Wolf and Nicklas (1985) described a 7-year-old child who experienced cough and chest tightness immediately after ingestion of a restaurant salad. The reaction was confirmed in an oral challenge test. Schwartz and Sher reported

a patient sensitive to bisulfite in local dental anesthetics and another patient who got bron- chospasm from bisulfite in eyedrops (Schwartz and Sher, 1983, 1985). It seems that sulfites cause adverse respiratory reactions more often than food color- ants and benzoates. These reactions are obviously nonspecific in nature, similar to the response to metacholine and histamine (Bush et al., 1986). Reactions to sulfites may be severe and not readily recognized if not suspected.

C. Other Agents

‘‘Chinese restaurant asthma’’ has been suggested to be caused by monosodium l-glutamate (Schaumburg et al., 1969; Allen and Baker, 1981; Allen et al., 1983). There are, however, studies in which double-blind provocation tests have produced no asthmatic symptoms at all (Ghezzi et al., 1980; Grattini, 1982; Morselli and Grattini, 1970). Numbness of the neck, headache, facial pressure, and chest pain have also been claimed to be symptoms of Chinese restaurant syndrome in some individuals. Tarasoff and Kelly (1993) made a critical review of the glutamate literature and performed a very strict double-blind peroral challenge test with 1.5, 3.0, and 3.15 g per person. They found no difference between the responses to placebo and glutamate, and they stated the ‘‘Chinese Restaurant Syndrome’’ to be anecdotal. Just recently, Yang et al. (1997) recorded headache, muscle tightness, numbness and tingling, general weakness, and flushing from glutamate more often than from placebo, 2.5 g of monosodium glutamate being a threshold dose for positive re- sponses. The dilemma on the effects of glutamate thus seems to continue.

Occupational asthma induced by inhalation of dust from spices such as powdered coriander, curry, and paprika has been described (Toorenenberger and Dieges, 1985). Enzymes are frequent causes of IgE-mediated nasal, bronchial, and skin symptoms. α-Amylase is a usual flour additive which has been found to cause both immediate and delayed contact allergies in bakers. Morren et al. (1993) tested 32 bakers, 7 of whom reacted to α-amylase in scratch-chamber test at 20 min. RAST was positive in five of them. Two patients showed also a delayed reaction in the scratch-chamber test. Larese et al. (1993) made skin prick tests with α-amylase in 226 bakers and pastrymakers. Seventeen (7.5%) reacted to it. Rhinitis, conjunctivitis, and asthma were the most common allergic

Severe systemic allergic reaction to papain in a meat tenderizer was experienced by a male patient within 20 min after eating beefsteak (Mansfield and Bowers, 1983).