James H. Day

Double-blind food challenge in the diagnosis of food sensitivity in the adult

This study is an attempt to determine the role of double-blind food challenge (DBFC) in suspected food sensitivity in the adult as compared wih established tests of food allergy, including the skin test, RAST, and leukocyte histamine release (LHR) to specific food antigens. Twenty-two subjects (ages 18 to 67) with histories of reactions to foods were challenged with freeze-dried food or placebo in opaque dye-free capsules, in increasing doses over a 90 min span to a total of 13 to 15 gm. This was repeated twice at weekly intervals by similar DBFC. DBFC was preceded by skin testing and venapuncture for RAST and LHR studies. Patients were kept under observation for 2 hr, after which each was asked to maintain a detailed diary of related symptoms and food ingested over the following week. Of 46 DBFCs, 13 (21%) were positive. The correlation with positive skin tests and positive DBFC was 4/13 (30%). The correlation with positive LHR and positive DBFC was lower at 2/13 (15%), and 1/13 (7.6%) with RAST. We concluded that DBFC is an effective test of adult food sensitivity compared with tests usually performed and should be used when the diagnosis is in doubt.

Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: Effects after controlled ragweed pollen challenge in an environmental exposure unit ☆ ☆☆ ★ ★★

BACKGROUND Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a newer once-daily selective H1-antagonist. In traditional clinical trials, cetirizine has been shown to be safe and effective for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE To better characterize the efficacy and onset of action of cetirizine in a more controlled but clinically relevant setting, this agent was compared with loratadine and placebo in patients with symptomatic seasonal allergic rhinitis undergoing controlled pollen challenge in an environmental exposure unit (EEU). METHODS This was a double-blind, randomized, parallel-group study. After screening, patients were exposed to ragweed pollen (primed) in the EEU (up to six exposures), and those with qualifying symptom scores were randomized to controlled pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once-daily treatment with 10 mg cetirizine (n = 67), 10 mg loratadine (n = 67), or placebo (n = 68). The mean ragweed pollen level was 3480 +/- 350 grains/m3 (standard deviation). The primary efficacy variables were the total symptom complex (TSC) and the major symptom complex (MSC) scores. Symptoms were evaluated every half hour in the EEU throughout the study. RESULTS Cetirizine produced a 36.7% mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0% with placebo (p < or = 0.01). Cetirizine also produced a 37.4% mean reduction in MSC scores overall versus 14.7% with loratadine and 6.7% with placebo (p < or = 0.01). Onset of action as assessed by reductions in TSC and MSC scores versus placebo was evident within 1 hour with cetirizine (p < or = 0.02) and 3 hours with loratadine (p < or = 0.03). The incidence of treatment-related side effects was similar among groups, with headache reported most commonly in each group. CONCLUSION Cetirizine is well tolerated and effective in reducing symptoms of seasonal allergic rhinitis in patients undergoing controlled pollen challenge.

A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed?

The precise amount of epinephrine needed to reverse severe symptomatology due to an anaphylactic reaction is unknown. We tried to determine how frequently more than one injection of epinephrine is required to treat an anaphylactic reaction. A retrospective review of patient charts with anaphylactic reactions requiring epinephrine, in response to inhalant allergen and hymenoptera venom immunotherapy as well as live hymenoptera stings, examined type of reaction; number, doses, and timing of epinephrine administered; and ancillary treatment. A total of 105 anaphylactic reaction events of varying severity (Rings classification) were recorded (54--Grade I, 29--Grade II, 18--Grade III, 0--Grade IV, 4--unknown). The median epinephrine dose administered was 0.3 cc (range 0.1 to 0.8 cc, 1:1000). The timing of the first epinephrine injection was < or = 5 minutes in 27, 6-10 minutes in 13, 11-30 minutes in 16, < or = 30 minutes in 32, 31-60 minutes in 12, and > 60 minutes in five epinephrine treated patients. Overall, 38 patients (35.5%; CI95, 26.4-44.6%) required > 1 epinephrine injection. Of these, 11 experienced Grade I (11/54-20.3%; CI95, 9.6-31.0%), 12--Grade II (12/29-41.5%, CI95, 23.5-59.3%), and 13--Grade III (13/18-72.2%, CI95, 51.5-92.9%); reactivity was unknown in 2 patients. Forty-four patients also received an antihistamine, 10 received corticosteroids, and 30 received both medications and/or other ancillary therapy. A significant number of patients (> 35%) with anaphylactic reactions received greater than one epinephrine dose to manage events for the three classes of severity. Patients at risk for anaphylaxis and their caregivers need to recognize that more than one dose of epinephrine may be required for treatment of anaphylaxis.

Comparative clinical efficacy, onset and duration of action of levocetirizine and desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in the Environmental Exposure Unit (EEU)

The Environmental Exposure Unit, an indoor pollen challenge system to test anti‐allergic medications, was used to compare the onset and duration of action and the efficacy of levocetirizine and desloratadine, two recently developed H1‐antagonists. In this double‐blind, placebo‐controlled, parallel‐group study, qualified subjects were randomised to once‐daily levocetirizine 5 mg (n = 141), desloratadine 5 mg (n = 140) or placebo (n = 92) and exposed to ragweed pollen on two consecutive days (7 h and 6 h). Symptoms were self‐rated every 30 min. On both days, levocetirizine produced a greater improvement in the major symptom complex score (primary efficacy variable) than desloratadine (p = 0.015); both were better than placebo (p < 0.001). Levocetirizine acted earlier (1 h vs. 3 h) and produced greater symptom relief at 24 h than desloratadine (p = 0.003). Levocetirizine also alleviated nasal obstruction better than desloratadine (p = 0.007) on day 1; and better than placebo (p = 0.014) after the second dose on day 2, which was not observed with desloratadine. Levocetirizine and desloratadine were safe and well tolerated.

Onset of Action, Efficacy, and Safety of a Single Dose of Fexofenadine Hydrochloride for Ragweed Allergy Using an Environmental Exposure Unit

BACKGROUND Fexofenadine hydrochloride is the active acid metabolite of terfenadine. Fexofenadines anti-allergic properties require confirmation in a clinical setting. OBJECTIVE The purpose of this study was to characterize the time to onset of clinically important relief of symptoms of allergic rhinitis in subjects taking single doses of either 60 mg or 120 mg fexofenadine HCl, or placebo, after exposure to ragweed pollen in a controlled environment. Other objectives were to assess the efficacy and safety of single doses of fexofenadine HCl. METHODS One hundred forty-six ragweed-sensitive subjects were primed in the off-season with ragweed pollen in the environmental exposure unit. One hundred thirty-six subjects who adequately responded to priming entered a single-dose placebo phase. Placebo-responders were disqualified from the study, leaving 99 subjects with adequate symptoms to be randomized and given a single dose of either fexofenadine HCl 120 mg (33), 60 mg (33) or placebo (33), after 60 minutes of allergen exposure. Exposure continued over five hours and subjects recorded symptoms every 20 minutes. This study was of a randomized, placebo-controlled, double-blind, parallel design. RESULTS Median time to onset for relaxed criteria clinically important relief was 60 minutes for both fexofenadine treatment groups, and 100 minutes for placebo (P = .018). The proportion with relief was 82% at 60 mg, 85% at 120 mg, and 64% for placebo. Treated groups had reductions in symptom scores double that of placebo. CONCLUSIONS Fexofenadine is safe and efficacious at single doses of 60 mg and 120 mg. Average time to onset was 60 minutes using controlled pollen exposure in an environmental exposure unit.

A randomized, double-blind, placebo-controlled, controlled antigen delivery study of the onset of action of aerosolized triamcinolone acetonide nasal spray in subjects with ragweed-induced allergic rhinitis

BACKGROUND Clinically apparent relief of nasal symptoms of allergic rhinitis is generally recognized to occur within 3 days to 1 week when intranasal corticosteroids are used. OBJECTIVE A study was designed to evaluate the onset of action of triamcinolone acetonide (TA) in patients with ragweed-induced allergic rhinitis with an environmental exposure unit (EEU). METHODS Eighty-five adults with ragweed-induced allergic rhinitis were primed with ragweed allergen in the EEU. Symptoms were recorded during a baseline exposure in the EEU, and subjects were randomized with a 5:1 ratio to receive either TA 400 micrograms (n = 71) or its propellant (n = 14). Subjects received study medication for 7 days under supervision in the morning and returned to the EEU in the evening for ragweed allergen challenge and symptom assessment. Clinically apparent onset of action was defined as a 25% decrease in symptom scores from baseline. RESULTS A mean reduction in nasal congestion from baseline of greater than 25% (onset of action) was observed in the TA group, but not in the placebo group, by 10 hours. This was also observed for itching of the nose or palate and a combined measure of symptoms. In addition, the proportion of subjects with less nasal congestion after 1 day of treatment was greater in the TA group (41%) than in the placebo group (7%) (p less than 0.05). CONCLUSION The unexpected early relief of symptoms observed in the TA group and, to a lesser extent in the placebo group, has important clinical implications in the treatment of allergic rhinitis.

Suggestion and relaxation in asthmatics

inhalants. In this investigation asthma is considered as a learned response, whatever the initiating factors. In many cases exposure to certain allergens and non-specific stimuli are necessary and sufficient causes. These taken together with constitutional predisposition and the effects of respiratory infections are usually cited as being responsible for the acquisition of asthma. From a treatment point of view, factors which currently precipitate, maintain and aggravate the patient’s asthmatic condition are critical. Edge11 [l] estimated that 23 per cent of his patients with perennial asthma had no identifiable extrinsic causes, and Rees [2] found psychological factors to be of major importance in 21 per cent of those he studied. In a proportion of cases a positive correlation between skin-test reactivity to allergens and asthmatic symptoms exists, and Resh [3] observed a positive correlation of O-58 between introdermal tests and Qualitative Inhalation tests. Psychodynamic studies such as those by French and Alexander [4] and Fenichel [5] must be viewed with caution, for they were unlikely to examine a representative group of asthmatics, since their patients were composed mainly of those seeking psychiatric help. Testing concepts which present problems of measurement, such as unconscious conflicts, have been very difficult and produced questionable results. The studies of Purcell et al. [6], Dekker et al. [7] and Franks and Leigh [8] failed to isolate a specific asthmatic personality apart from a mildly neurotic one. Others like Feingold et al. [9], Freeman et al. [IO], Block et al. [l l] and Resh, [3], concluded that there is an almost inverse relationship between the degree of psychopathology and defined allergy in asthmatics. In all studies where asthmatics were dzflerentiated on the basis of skin-tests into reactors and non-reactors, personality differences were detected. Heterogeneity of asthmatics in terms of specific allergic reactivity is known and evidence that this is also true for psychological factors is mounting.

Environmental exposure unit: a system to test anti-allergic treatment

LEARNING OBJECTIVES Reading this article will enable readers to recognize the Environmental Exposure Unit (EEU), its historic development and its current role as a system to test anti-allergic treatment; to recognize clinical relevance of this test system and its relationship with other pollen challenge methods of evaluation of anti-allergic medication; and, to recognize variables associated with standard clinical studies of anti-allergic medication. Readers will review four studies of antihistamines tested in the Environmental Exposure Unit, three studies on nasal corticosteroids, one on topical eye drops and one on immunotherapy conducted in the EEU. DATA SOURCES The EEU has been in operation since 1985 preceded by a prototype challenge system to assess respiratory effects of urea formaldehyde foam insulation. A number of studies on the onset of action and efficacy of different antihistamines and nasal corticosteroids as well as other treatments have been completed producing accurate and consistent results influenced to some extent by study designs. STUDY SELECTION Studies of commonly used antihistamines and nasal corticosteroids are discussed in detail and represent several of the studies undertaken to date in the EEU. RESULTS Controlled ragweed pollen exposure using the EEU has shown that some antihistamines demonstrate an onset of action within 30 minutes while others have taken up to 3 hours to produce significant effect. Nasal corticosteroids evidenced the onset of clinical improvement at 5 to 6 hours with significance over placebo between 6 and 12 hours depending on dose. CONCLUSION The EEU is an effective pollen delivery system that accurately and consistently determines the onset of action and efficacy of anti-allergic treatment in large groups of subjects. It eliminates variables associated with various other methods of evaluation of these medications but does not supplant the need for such evaluations.

Intranasal fluticasone propionate versus loratadine in the treatment of adolescent patients with seasonal allergic rhinitis

Fluticasone propionate (FP) is a topical corticosteroid with minimal systemic activity. We examined safety and compared the efficacy of FP aqueous nasal spray, 200 micrograms every day with loratadine tablets, 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a randomized, double-blind, parallel-group study. Nasal and eye symptoms were recorded daily on a 4-point (0 to 3) scale. A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP (p < 0.0001). Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores. No differences were found for eye irritation symptoms (p = 0.14). Morning and evening nasal peak inspiratory flow (PIF) was recorded daily by 57 subjects. FP treatment was associated wit significantly higher PIF values than loratadine both morning (p = 0.0051) and evening (p = 0.0036). A greater improvement over 4 weeks was observed for PIF morning values in the FP group (p = 0.008) but not for evening values (p = 0.358). Statistically significant correlations were found for nasal blockage and PIF in the morning (r = -0.54, p = 0.0001) and in the evening (r = -0.46, p = 0.008).

Efficacy of Immunotherapy to Ragweed Antigen Tested by Controlled Antigen Exposure

BACKGROUND Immunotherapy is a recognized component in the management of allergic rhinitis. Its efficacy has been evaluated in a number of clinical field trials. These methods of evaluation are limited by control of antigen exposure. OBJECTIVE A study was designed to evaluate the efficacy of immunotherapy in ragweed-induced rhinoconjunctivitis using an environmental exposure unit. METHODS Forty-three subjects were grouped into (1) immunotherapy group: ragweed-allergic subjects on maintenance ragweed immunotherapy for at least 2 years (N = 16), (2) positive control group: ragweed-allergic subjects who had never received immunotherapy (n = 16), and (3) negative control group: ragweed-nonallergic subjects (N = 11). Ragweed specific skin tests and ragweed IgE levels were obtained prior to exposure. The study was done in a room where levels of 2,500 to 3,000 grains m3 of ragweed were maintained over three hours. Symptoms were recorded every 15 minutes. RESULTS Nasal symptoms in the immunotherapy group were significantly less than in the positive control group after 45 minutes (P = .025). Significant differences were not observed for ocular symptoms. Combined nasal and ocular scores were 50% less in the immunotherapy group than in the positive control group by 75 minutes (P = .039). Ragweed-specific skin tests and IgE were significantly less in the immunotherapy group than in the positive control group. Rhinoconjunctivitis symptoms in the negative control group were absent throughout. CONCLUSIONS Controlled ragweed pollen exposure in this setting demonstrated that ragweed immunotherapy significantly reduced symptoms of ragweed-allergic rhinitis but had no significant effect on ocular symptoms. This system presents opportunities for additional studies on immunotherapy for allergic respiratory conditions.