Positive Nasal Challenge Research Articles

Occupational rhinoconjunctivitis due to hops exposure in a brewery worker

Rationale Asthma and urticaria from beer has been reported in atopic patients. Barley, the basic ingredient used in brewing, has nearly always been the main allergen. Hops (Humulus lupulus) is known to cause allergy contact dermatitis but it has been rarely implicated in beer allergy. We try to prove the clinical relevance of hops as a occupational allergen in a brewery worker. Methods Case Report: An atopic 35-year-old brewery worker man, with rhinoconjunctivitis diagnosis due to grass and olea pollen, developed occupational rhinoconjunctivitis after three years of exposure to hops, staying symptom free away from his laboral environment. He was able to drink beer. We preformed skin-prick test with a common commercial inhalants battery including pollens, mites, animal dander, molds and latex. We also used hops and barley home-made extracts. Specific IgE to barley, malt, corn, wheat and hops were also carried out. In order to demonstrate the patients symptoms we made a nasal challenge with hops extract. Results Skin-prick test were positive to grass, olive pollen and also with hops. Specific IgE was positive only to hops. Nasal challenge with hops extract reproduced an immediate nasal response. Prick test with hops in 10 controls patients were negative. Conclusions We report a case of rhinoconjunctivitis after occupational exposure to hops in a brewery worker, confirmed by a positive nasal challenge. The positive results of skin-prick test and specific IgE demonstrate an IgE mediated mechanism.

Nasal provocation tests with Dermatophagoides pteronyssinus, D. farinae, Lepidoglyphus destructor, and Tyrophagus putrescentiae

Rationale The objective of this study was to perform nasal provocation tests with standardized extracts of Dermatophagoides pteronyssinus, D. farinae, Lepidoglyphus destructor and Tyrophagus putrescentiae in a group of patients sensitized to Dermatophagoides spp. Methods A total of 25 patients with allergic rhinitis with or without asthma were entered in the study. All patients had positive skin tests to Dermatophagoides spp. Three groups of patients were studied. Group A consisted of 10 patients, who underwent nasal provocation tests with standardized extracts of D. pteronyssinus and D. farinae (100 HEP/ml). Group B consisted of 10 patients, 9 of whom were skin prick test positive to L. destructor. All 10 patients underwent a nasal provocation test with L. destructor and 5 with D. pteronyssinus. Group C, consisted of 5 patients, 2 of whom were skin test positive to T. putrescentiae. All individuals underwent nasal provocation tests with T. putrescentiae and Dermatophagoides spp. Specific IgE was measured by the CAP system. Results Group A: 7 patients had a positive provocation test with D. pteronyssinus and 8 with D. farinae. Group B: 6 patients had a positive provocation test with L. destructor. Group C: 3 patients had a positive provocation test with T. putrescentiae. Conclusions We confirm a high prevalence of positive nasal challenges to L. destructor and T. putrescentiae in patients sensitized to these mites and to Dermatophagoides spp. The clinical relevance of these mites species is suggested. In general, there was a good correlation between specific IgE levels and positive provocation tests.

Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?

The pathophysiology of idiopathic rhinitis is unknown although evidence is accumulating to suggest that many patients may have a localized form of allergic rhinitis in the absence of other atopic symptoms and markers. This study compares detailed nasal challenge results obtained from patients with idiopathic rhinitis to those of atopic and normal controls. Patients with idiopathic rhinitis (n = 23), perennial allergic rhinitis (n = 8) and normal controls (n = 8) underwent a normal saline challenge to exclude hyper-reactivity and then bilateral nasal allergen challenges. Nasal patency was assessed by anterior active rhinomanometry. All of the patients with atopic rhinitis demonstrated positive bilateral allergen challenges. All normal control subjects had bilateral negative challenges. Two patients in the idiopathic group tested positively to saline and were excluded from further study with 62% of the remainder testing positive to allergens. Of the idiopathic patients testing positive, 85% were sensitive to house dust mite. A significant proportion of patients with idiopathic rhinitis have positive nasal challenges, the vast majority to house dust mite allergen. These findings add to the weight of evidence that suggests 'localized allergy' may exist in the absence of systemic atopic markers.

Nationwide investigation of insect allergy in patients with allergic rhinitis

To clarify the role of insects as allergens in allergic rhinitis (AR), specific IgE antibodies (sIgE) to the moth, midge, and cockroach together with 10 other allergens were measured using sera from 560 AR patients, who visited 20 otolaryngological clinics nationwide from Hokkaido to Kyushu. Nasal challenge tests were also conducted with allergen disks of these 3 insects in 65 AR patients. Frequencies of sIgE positive to the moth, midge, and cockroach were 32.5%, 16.1%, and 13.4%. Frequencies of sIgE positive to these insects were not affected by patients' residential location, age, medication, or association with bronchial asthma. The prevalence of patients with positive nasal challenge increased depending on the RAST class to the insects. Among the patients whose RAST class were 3 and 4, nasal challenges with cockroach or moth extracts were positive in 55.6% or 61.5%. A strong correlation of sIgE titers was observed between the moth and midge, but the correlation between the cockroach and moth, and between the cockroach and midge were weak. No correlation of sIgE titers was found between house dust mites and these 3 insects. These results show that the moth, midge, and cockroach are inhalant allergens causing allergic rhinitis in Japan.

In vitro diagnosis of cypress pollen allergy by using cytofluorimetric analysis of basophils (Basotest)

Background: Cupressaceae pollen allergy is a worldwide pollinosis, but its in vitro diagnosis is notoriously difficult. The Basotest is a newly available in vitro test for the detection of allergen-specific IgE based on the level of cellular activation of basophils by using flow cytometry. Objectives: The Basotest was compared with the measurement of cypress pollen–specific IgE in highly selected patients. Methods: We analyzed 34 patients allergic to cypress pollen selected on the basis of a suggestive clinical history and positive skin test and nasal challenge responses to cypress pollen extract. We also analyzed 8 patients with positive skin test responses to cypress pollen extract who did not present symptoms during the pollen season (intermediate group) and 33 control subjects. Sensitivity, specificity, and efficiency of the Basotest and serum-specific IgE levels measured by using the CAP System were determined in patients allergic to cypress pollen. Histamine release was studied in a selected group of patients. Results: The Basotest was more sensitive (91.2%) than the CAP System (76%) for the in vitro diagnosis of cypress pollen allergy. A dose-response curve was observed in basophils obtained from patients allergic to cypress pollen. There were no false-positive results with either test (specificity 100%). The results of the Basotest or those of the CAP System did not correlate with the patients’ in vivo threshold sensitivity assessed by skin tests and nasal challenge. Conclusions: The Basotest was found to be an effective diagnostic test in patients allergic to cypress pollen. (J Allergy Clin Immunol 2000;105:339-45.)

Comparison between nasal provocation tests and skin tests in patients treated with loratadine and cetirizine

Background: The effect of H1-blockers may differ depending on the target organ. Objective: A double-blind, placebo-controlled study was carried out to compare the effect of a 7-day treatment with loratadine (10 mg daily) or cetirizine (10 mg daily) on nasal challenge with grass pollen grains and skin tests with allergen or histamine. Methods: Twenty-four patients were enrolled, but the analysis was carried out on 23. Nasal challenge was carried out by using 5-fold increasing numbers of pollen grains. Skin prick tests were done with serial concentrations of allergens and 1 concentration of histamine. Patients were tested in a cross-over design, with each treatment being administered for the previous 7 days and with a 2-week washout period. Results: By comparison with placebo, loratadine and cetirizine increased significantly the threshold number of pollen grains required to induce a positive nasal challenge ( P < .001). There was no difference between loratadine and cetirizine. Skin test responses to allergen were significantly reduced by loratadine and cetirizine by comparison with placebo. Skin test responses to histamine were significantly decreased by the 2 H1-blockers, but they were more profoundly decreased by cetirizine than by loratadine. Conclusions: Both H1-blockers reduced similarly allergen-induced skin test and nasal challenge responses. Cetirizine was more effective on histamine skin test responses. (J Allergy Clin Immunol 1999;103:591-4.)

Positive nasal challenge responses to Blomia tropicalis

BACKGROUND: Blomia tropicalis, a dust mite commonly found in subtropical and tropical environments, is the fourth most common mite in the United States. Thirty-eight percent of 167 consecutive subjects evaluated for allergic respiratory symptoms in the Tampa Bay area had positive skin test responses to B. tropicalis. METHODS: Nasal challenges were performed in 19 subjects with allergic rhinitis; 12 had positive skin test responses to B. tropicalis (group I), and seven had negative skin test responses to B. tropicalis but positive skin test responses to Dermatophagoides pteronyssinus and D. farinae (group II). Subjects were challenged with a normal saline control solution and increasing concentrations of a 1 mg/ml in-house extract of B. tropicalis (1:125,000 vol/vol, 1:25,000 vol/vol, 1:5000 vol/vol, 1:1000 vol/vol, and 1:200 vol/vol). Inspiratory nasal airway resistance was measured every 5 minutes for 15 minutes by posterior rhinomanometry at 50 Pa after each nasal challenge. RESULTS: Nasal challenge response was considered positive and stopped when the mean inspiratory nasal airway resistance was greater than twice the mean inspiratory nasal airway resistance after the normal saline challenge. Ten of 12 (83%) subjects in group I and none of seven (0%) subjects in group II had positive nasal challenge responses to B. tropicalis ( p = 0.0024). CONCLUSION: B. tropicalis is allergenic and should be considered as a cause of allergic rhinitis when evaluating a patient who lives in an area where it is endemic. (J A LLERGY C LIN I MMUNOL 1996;97:1045-9.)

Nasal and bronchial provocation challenges with Bayberry ( Myrica cerifera) pollen extract

Southern bayberry, distributed throughout the southeastern United States, is the source of the fifth most common windborne tree pollen in Tampa, Fla. Fifteen percent of 400 consecutive subjects evaluated for allergic respiratory symptoms in the Tampa Bay area had positive skin tests to bayberry pollen extract. Bayberry pollen extract was obtained commercially and used to perform 25 nasal and 22 bronchial challenges on 45 subjects. Twelve of 13 (92%) study subjects with allergic rhinitis and positive skin tests to bayberry pollen extract and two of 12 (17%) control subjects with negative skin tests had positive nasal challenges (p = 0.0001). Four of seven (57%) study subjects with extrinsic asthma and positive skin tests to bayberry pollen extract and none of the 15 (0%) control subjects with negative skin tests had positive bronchial challenges (p = 0.001). Sera from 30 subjects who underwent 31 challenges were assayed for bayberry pollen extract-specific IgE by plate radioimmunoassay. Specific IgE antibodies were present in the sera of 8 of 13 (62%) subjects with positive challenges and absent in 15 of 18 (83%) subjects with negative challenges (p = 0.01). Intradermal skin tests with bayberry pollen extract were more predictive of provocation challenge results than plate radioimmunoassay (positive predictive value of 80%, 95% CI 62% to 98%; versus 73%, 95% CI 47% to 99%). Bayberry pollen extract is allergenic, and the Southern bayberry tree fulfills Thommen's criteria defining aeroallergen-producing plants.

Trichophyton tonsurans allergen. I. Characterization of a protein that causes immediate but not delayed hypersensitivity.

Fungal infections of skin or nails are extremely common and often caused by dermatophyte fungi of the genus Trichophyton. These fungi are unusual in that they can give rise to delayed hypersensitivity (DH) or immediate hypersensitivity (IH) responses. Recently, IH to Trichophyton tonsurans has been demonstrated in patients by skin tests, serum IgE antibody test (RAST), and positive nasal and bronchial challenges. To further investigate the immunology of Trichophyton, a 30-kDa T. tonsurans allergen was isolated by gel filtration and hydrophobic interaction chromatography. This protein, Tri t I, gave a single band on SDS-PAGE, and the 30 amino-terminal amino acids have been determined. Among patients with positive IH skin tests, 34 of 48 (71%) had IgG antibody and 26 of 48 (54%) had IgE antibody to Tri t I. Among those who had positive responses to both skin tests and RAST, 22 of 30 (73%) had IgE antibodies to Tri t I; thus, this protein represents a major allergen. Twelve clones of murine IgG mAb antibodies were produced. Two clones, 2F2-F7 and 6B11-C2, were found to define separate epitopes on Tri t I and were used to develop an immunometric assay for the quantitation of Tri t I. Twenty-three of 38 volunteers with a history of athlete's foot were found to have either IH and/or DH to Trichophyton mix and underwent further testing with purified Tri t I. Of the nine found to have IH to the mix, eight were sensitive to Tri t I. Seven of these eight had IgG and IgE antibodies to Tri t I, by Ag-binding RIA, and all were RAST positive to the unpurified extract. An additional 14 had either DH alone (n = 7) or a wheal and flare response followed by DH at 48 h (n = 7). Of these 14 who had DH responses to Trichophyton mix, only one showed DH to an equivalent quantity of purified Tri t I; among this group, none showed IH or serum IgE antibodies and only one had detectable IgG antibody to Tri t I. The results suggest that the majority of subjects with DH to Trichophyton are responding to a protein other than Tri t I and that the wheal that precedes DH reactions is some patients is not associated with IgE antibodies.

Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains

Nasal challenges with pollen grains represent one of the techniques of provocation. However, the clinical criteria of positivity are not clearly established. Nasal challenges with increasing numbers of orchard-grass pollen grains were performed in 60 patients allergic to grass pollens and 20 normal subjects. Before any challenge, the nose was washed three times with saline and then lactose, and 50, 150, 450, 1350, and 4050 orchard-grass pollen grains were insufflated into the nostrils until a symptom score of 5 was reached. This score was mainly based on major symptoms of allergic rhinitis, for example, rhinorrhea, nasal obstruction, sneezes, and to a lesser extent, on minor symptoms, such as pruritus, conjunctivitis, and pharyngitis. Nasal secretions were obtained after each challenge by lavage. Histamine was titrated by a radioimmunoassay with a monoclonal antibody against acylated histamine. Prostaglandin D 2 (PGD 2) was assayed with an enzyme immunoassay with a polyclonal antibody against PGD 2 methoxamine. None of the normal subjects had a symptom score >2; 55 60 patients had a positive challenge. The release of PGD 2 was significantly ( p < 0.001, Kruskal-Wallis test) correlated with a symptom score of 5; 74.5% of patients had a significant release of PGD 2 in nasal secretions. In contrast, although 58.2% of patients had a release of histamine in nasal secretions when the challenge was positive, the correlation with symptom scores was not significant. PGD 2 in nasal secretions increased 3.7-fold after a positive nasal challenge. In a second experiment series, the number of grains required to elicit a positive challenge was tested in 40 patients who were challenged twice, and a significant ( p < 0.001, Kruskal-Wallis test) correlation was observed between the number of pollen grains required in both tests. The correlation between the threshold release of PGD 2 or histamine in nasal secretions was tested in 24 patients who were challenged twice, and there was a significant correlation between the numbers of pollen grains required in both tests. This study confirms the value of PGD 2 as a marker of nasal allergy and demonstrates that symptom scores can be used to assess the positivity of nasal challenges with pollen grains.

A new approach to immunotherapy for house dust mite (D. pteronyssinus) allergy with high dosage of an aluminium adsorbed extract.

A group of 50 patients with inhalant sensitivity to the house dust mite (D. pteronyssinus) was selected on a basis of positive history and prick tests or raised total IgE estimation together with positive nasal challenge. D. pteronyssinus was the sole or major allergen for each patient. Prior to the trial, a wider group of patients was given domestic dust avoidance regimens to follow, which produced an adequate symptomatic response in 36.8% of cases. The non-responders to this procedure were offered hyposensitization using standard aluminium adsorbed extracts, together with maintenance therapy, for a total of 12 months, and 89% of them made a good response. The study group in this trial was thus drawn from 7.69% of total attenders, who had failed on all previous treatments. This group was then given a course of an aluminium adsorbed extract ('Norisen', Merck) in a dosage which attained 10,000 PNU on the final dose, and maintenance therapy was given at this level. Thirty-eight (77.5%) of the 49 patients completing the course of treatment showed an excellent or good response and 74% experienced no side-effects. Side-effects which were reported were of similar incidence and severity to those noted on previous allergen treatments. It is suggested, therefore, that higher dosages of extract than that previously recommended should be used in D. pteronyssinus hyposensitivity therapy whenever the diagnosis is well established and there has been an inadequate response to standard measures.

When is a positive nasal challenge test clinically relevant?

339 subjects with a clinically manifest or latent allergy to different allergens were tested intranasally: 163 with grass pollens, 19 with tree pollens, 46 with cat fur, 23 with dog hair, 79 with mites and 9 with horse hair. Two thirds of the patients with a latent allergy towards pollens either reacted to a pollen concentration of 1% w/v or not at all, one third responded to 0.1% w/v. Two thirds of the pollinosis patients reacted at 0.01% w/v, one third at 0.1% w/v. Threshold dosages were also found for animal fur: The limits are at 1.5% w/v (manifest allergy) and 150% w/v (latent allergy) and the transitional range at 15% w/v. No threshold was found for mites. The study shows that for certain allergens there exist threshold concentrations which should not be exceeded. Where there is no threshold dose, as e.g. with mites, the nasal test is no more informative than the skin test.