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Allergens of the house dust mite, Dermatophagoides pteronyssinus, in patients with mite allergic rhinitis: a clinical investigation by intracutaneous skin tests and nasal provocation tests.

To determine the allergens of mite allergic rhinitis, we studied 31 patients with mite allergic rhinitis by skin tests and nasal provocation tests (15 for skin and 16 for nasal tests) using 6 fractions of Dermatophagoides pteronyssinus (Dp) extract differing in molecular weights (15, 25, 32, 53, 95 and 190 kDMW). In skin testing, patients showed intense positive reactions to the fractions of 15, 25, 32, 95 and 190 kDMW, among which the most patients showed positive reactions to the fractions of 15 and 25 kDMW. Significant differences were found in patients' positive reactivity among each fraction and between low (15 and 25 kD) and high (95 and 190 kD) molecular weight fractions as well. In nasal provocation tests, patients showed intense positive reactions to the fractions of 15, 32, 53 and 95 kDMW, especially to the fractions of 15 and 95 kDMW. Furthermore, the insidence of positive reactions to the 15 kDMW fraction was significantly higher than that to any other fraction in the skin tests (P < 0.05). From these results, the low molecular weight fraction, 15 kDMW, is considered to be the main allergen of this mite and the high molecular weight fractions, 95 and 190 kDMW, may also be considered to be allergens of this mite.

Adolescent↗

Rhino-rheo-manometric (R.R.M.) nasal provocation test.

The nasal provocation test--which has been considered till now too much time-consuming and troublesome for the patient--becomes rapid and simple by the use of the rhino-rheo-manometry. It is possible, by this method, to evaluate the conductance of a single nasal fossa and its reduction after allergen challenge. The results of test performed in patients suffering from extrinsic perennial nasal atopy by Dermatophagoides pt. have proved that the test becomes rapid and not troublesome by using the rhino-rheo-manometry. This method, giving a provocation threshold, may be used both in diagnosis and control of specific immunotherapy.

Antigen-Antibody Reactions↗

Studies on allergen and allergoid preparations from purified timothy (Phleum pratense) pollen extracts. III. Comparative investigations by skin prick tests and nasal provocation tests.

The allergenic activities of allergen (GEN) and allergoid (GOID) preparations from partially purified timothy pollen extract were investigated in quantitative skin prick tests and nasal provocation tests. In skin prick test GOID yielded significantly less activity than GEN. Approximately 90 times more protein of GOID than of GEN was necessary to elicit wheals of the same mean size as 1 mg/ml histamine control solution (1 HEP). In nasal provocation the patients seemed to react differently with respect to their nasal sensitivity to GOID. One group of patients showed equal sensitivity to GOID and GEN, whereas the second group showed higher thresholds to GOID. These differences in nasal sensitivity to GOID could be of practical value to predict the optimal dosage schedule for the treatment of patients with GOID.

Adolescent↗

Immunotherapy with partially purified and standardized tree pollen extracts. II. Results of skin prick tests and nasal provocation tests from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Patients allergic to tree pollen entered a 3-year course of immunotherapy (1980-83) with either birch pollen extracts alone (n = 26) or patient-tailored extracts of birch, alder and hazel pollen (n = 27). The clinical and immunological results of this study are published elsewhere. This paper contains an evaluation of skin prick test and nasal provocation test results. There were no significant differences between the two treatment groups concerning these two parameters. In both groups the allergen-specific sensitivity in the skin showed seasonal variations but a significant decrease. During the years of treatment there was also a significant decrease in the specific sensitivity of the nasal mucosa. With the present demands for purification and standardization of allergen extracts it is of practical and economic interest to know that tree pollen-allergic patients showing positive reactions to birch, alder and hazel extracts can be effectively treated using birch pollen extract alone.

Asthma↗

[The skin prick test and nasal provocation test with individually prepared flour extracts in patients with bakers' rhinitis and asthma].

The reliability of skin prick tests (SPT) may be insufficient for the screening of occupational inhalant allergies. The influence of different flour extracts on the SPT in flour allergic subjects has not been compared previously. In this study, SPT reactions against two commercially available rye and wheat flour extracts and individually prepared extracts from flour samples were compared in 35 patients with known bakers' rhinitis. Flour sensitization was confirmed by a positive nasal provocation test (NPT) and/or serum-specific IgE. The sensitivity of NPT with a combination of rye and wheat flour extracts of individual flour samples was 94%. Wheat and/or rye flour specific IgE (RAST>/=2) was true positive in 86%. The sensitivity of the SPT was 94% for individual rye flour extracts compared to 38% and 59% for two commercially available rye flour extracts and 88% for individual wheat flour extract compared to 53% and 48% for commercially available wheat flour extracts. SPT and sIgE did not reveal a significant difference in prevalence between rye and wheat flour sensitization. Thirty healthy volunteers served as the control group. Three control subjects with histamine equivalent SPT reactions to grass pollen had a positive SPT reaction against individual flour extracts, whereas NPT with undiluted individual flour extracts was negative in all controls. SPT with individually prepared flour extracts appears to be sensitive for the demonstration of inhalant flour allergy. Our findings show that extracts of individual flour samples rather than commercially available extracts should be used for both SPT and NPT if flour allergy is suspected.

Adult↗

Nasal provocative test in patients allergic to pollen.

Nasal provocative test (NPT) can be defined as a method for recreating upper respiratory tract response to natural allergens or irritants. It can be used in solving nasal patophisiology problems: establishing whether and how the patient's nose is sensitive to antigens or irritants; quantitative evaluation of sensitivity; establishing factors influencing sensitivity. This method is employed to confirm clinical diagnosis in cases where difficulties arise in interpretation of diagnostic tests. The study based on nasal provocative tests establish an allergy to pollen in cases of pollinosis, and select appropriate components for the desensitising vaccine. Sample group included 53 patients, 29 were females and 24 were males, aged 15-42 years, selected from 1,021 patients diagnosed between 1999-2002 in the Allergology Department of the ENT Department of the MMI. The sample patients were diagnosed based on additional tests with allergic inflammation of the nasal mucosa caused by allergy to pollen of such plants as birch, grass, rye, mugwort and plantain. Research methods included: subjective physical examination, prick tests, total and specific IgE levels in serum, nasal provocative tests and rhinomanometric examination. Allergen solution was administered onto the mucosa with a calibrated atomiser. NPT solutions containing pollen of birch, grass, rye, mugwort and plantain were used. Provocative test was considered positive if, following allergen provocation, rhinomanometric examination revealed an increase in respiratory resistance by at least 40 % in comparison with the control test. On the basis of the study, 2 conclusions were drawn: 1) Nasal provocative test is an essential element in diagnostics of allergic nasal obstruction. 2) Rhinomanometry, as an objective method of examining nasal patency, is crucial for evaluating the nasal provocative test.

Adolescent↗

Basic study of nasal provocative test first report: side, site of the nose, size of site and allergen amount.

The methodology of the provocative nasal test has varied according to the investigators. In order to establish a standard method of this test quantification of the nasal challenge, including the amount of the allergen, nasal site, side and size of allergen deposition, was studied. From the results obtained it is preferable to use the end point test and to apply allergen to the anterior part of the inferior turbinate in a 7mm2 size of surface area, bilaterally. An alternative test is to use a fixed amount of allergen (500 mug house dust in house dust allergy).

Allergens↗

Do tryptase, ECP and specific IgE measurement by nasal incubation increase the specific nasal provocation test sensitivity?

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool. Fitted to reproduce natural exposure condition to pick the responsible allergen for nasal symptoms out, it is applied when prick test and RAST responses are doubtful. SNPT results have been evaluated measuring nasal resistance (anterior rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity. This study focused on the determination of allergic response markers, triggered by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal mucosa applying a new method, based on in situ incubation, before and after sNPT. The latter was performed following a standardized method. Tryptase levels increased in 13 patients (65%), were unchanged in four patients (20%), and slightly decreased in three patients (15%). The increase recorded was significant in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen allergic patients. ECP values increased in 13 patients (65%), were unchanged in two patients (10%), and highly decreased in five patients (25%). ECP increase was not significant (p> 0.05). Specific IgE levels increased in seven patients (35%), were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE increase was significant in pollen-allergic patients (p<0.05), while it was not significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE were not detected in the control group. The data obtained showed a positive sNPT response in 12 patients (60%). Comparing our results with those derived from classical-parameter employment, we gathered an improvement of 10%. On the basis of the usual parameters, in fact, we recorded 50% positivity, while the use of mediators provided an additional 10% improvement in sNPT sensitivity: taking together the usual parameters and nasal allergic mediators values, we reached an sNPT over-all sensitivity of 85%.

Adolescent↗

Nasal provocation testing: an objective assessment for nasal and eustachian tube obstruction.

Nasal provocative testing is the introduction of a specific factor into the nose and the subsequent assessment of the pathophysiologic changes induced by the challenge. The provocative test primarily affects the nasal airway but also may affect the adjacent organs, including the eustachian tube, middle ear, sinuses, and lower respiratory tract. Recent advances in the measurement of nasal airway resistance with microcomputer-assisted rhinomanometry have improved the objective assessment of nasal airway obstruction. Eustachian tube obstruction has been shown after nasal provocation by a new procedure, sonotubometry, which can be performed in series with rhinomanometry and pulmonary spirometry. As will be described these procedures have helped elucidate the extent and pathophysiology of diseases affecting the upper airway, especially allergic rhinitis. At present, nasal provocation is primarily a clinical investigative test. It is anticipated that with further development and refinement, it can be used to a greater extent in the diagnosis and management of nasal diseases.

Allergens↗

Acoustic rhinometry, rhinomanometry and the amount of nasal secretion in the clinical monitoring of the nasal provocation test.

BACKGROUND: The reliable interpretation of the nasal provocation test in allergy diagnosis requires objective and measurable monitoring parameters for clinical practice. The clinical usefulness of the nasal provocation test has been limited by scanty knowledge of the specificity and sensitivity of the test and a lack of reference values. OBJECTIVE: To test and compare three objective monitoring parameters of a nasal provocation test in occupational allergic rhinitis. To evaluate the magnitude of the nasonasal effects in a unilateral allergen challenge. METHODS: The monitoring parameters of the nasal reaction were derived from the minimum cross-sectional area on acoustic rhinometry, the nasal resistance on active anterior rhinomanometry and the amount of nasal secretion measured at 15 min intervals for 60 min. Twenty-three bovine-allergic dairy and beef cattle farmers and 19 exposed, non-allergic control subjects were challenged first with a control solution and then with the cow allergen. RESULTS: All the three monitoring parameters showed high specificity and sensitivity in finding allergic and non-allergic subjects. The secretion parameter was found to be slightly superior to the acoustic rhinometry and rhinomanometry parameters. The side difference in the nasal response between the allergen-challenged and the contralateral diluent-challenged cavity was significant for all the parameters among the allergic subjects. The contralateral secretion amount was 1/3 of the ipsilateral secretion, indicating the magnitude of the contralateral nasonasal reflex. A nasonasal reflex was also noted in the nasal patency monitoring. The coefficient of variation was significantly lower for the acoustic rhinometry than for the rhinomanometry (P=0.0001). The optimal threshold values for a positive test were a secretion amount of 100 mg, a 15% decrease in the minimum cross-sectional area and a 50% increase in the resistance for the observation period of 30 min and correspondingly 210 mg, 30% and 100% for 60 min. CONCLUSION: The low-pressure aspiration of the nasal secretion from the anterior part of the nasal cavity was found to be a reliable and practical monitoring parameter to be used together with acoustic rhinometry or rhinomanometry in the nasal provocation test for clinical purposes. Although significant nasonasal effects took place in the unilateral allergen challenge, the response was more prominent in the allergen-challenged than in the contralateral diluent-challenged nasal cavity in most allergic subjects.

Acoustics↗

Improved diagnosis and treatment of allergic rhinitis by the use of nasal provocation tests.

A simple and safe method of nasal provocation for out-patients that requires no special equipment is described. A total of 2,645 cases were tested by nasal provocation tests. Of the total, 1,175 were tested with Dermatophagoides pteronyssinus, 825 with mixed grass pollens, 352 with plantain (Plantago lanceolata), and 125 for cats and correlating nasal tests with skin tests yielded 80%, 90%, and 85%, respectively. Immunotherapy for allergic rhinitis was only considered justifiable when the nasal provocation test was positive. The nasal provocation test was repeated at the end of the normal course of injections recommended by the manufacturer. If the nasal provocation test was still positive, further injections were given until the test became negative. This method of improving diagnostic accuracy and monitoring results of immunotherapy was used with both aqueous extracts which were used for skin testing (Australian Government Commonwealth Serum Laboratories) and with Allpyral pyridine-extracted alum-precipitated extracts (Dome Laboratories, England). The number of injections of allergen required to convert a positive nasal provocation test to negative varied from 26 to 69 for mite aqueous injections with only 12 to 19 for mite suspension and 47 to 98 for grass aqueous injections compared with 12 to 36 for grass suspension. Direct provocation tests of the nose should give a more accurate diagnosis than RAST or skin tests and are required for monitoring therapy because considerable individual variations in sensitivity and response to treatment were demonstrated. Standard dosage schedules are not suitable for individual patients, who should have their immunotherapy personalized.

Allergens↗

Occupational allergic rhinitis from guar gum.

Three cases of allergic rhinitis from a vegetable gum, guar gum, have been detected. Two subjects were exposed to fine guar gum powder (Emco Gum 563, Meyhall Chemical AG, Switzerland), an insulator in rubber cables, when opening cables in a power cable laboratory. After 1-2 years' exposure the patients developed rhinitis. Scratch-chamber tests, nasal provocation tests, nasal eosinophilia and a RAST test proved their allergy. A third subject developed allergic rhinitis from another guar gum product (Meyproid 5306, Meyhall Chemical AG) after 2 years' exposure in a paper factory. A positive skin test and nasal provocation test confirmed the diagnosis. A fourth case of possible allergy to guar gum after exposure to Meyproid 5306 in a paper factory is also presented. No final diagnosis was reached in this case (in 1974). The present subjects, only one of whom was atopic, developed allergy within 2 years, although their exposure to guar gum was not especially heavy. Therefore, when handling guar, adequate ventilation facilities should be provided and protective clothing, including a respiratory mask, should be worn.

Adult↗

Antigen sensitivity evaluated by tear-specific and serum-specific IgE, skin tests, and conjunctival and nasal provocation tests in patients with ocular allergic disease.

The potential for ocular allergic patients to have a site-specific antigen sensitisation was investigated using various diagnostic tests of allergen sensitivity in subjects with allergic conjunctivitis (AC: n = 135), vernal keratoconjunctivitis (VK: n = 20), rhinoconjunctivitis (n = 20) or rhinitis (N = 10). In the AC and VK patients, skin tests and conjunctival provocation tests (CPT) were performed, and the levels of specific IgE in serum and in tears were identified. A subgroup of 36 patients was also challenged with a nasal-specific provocation test (NPT). Results showed a poor correlation between skin test results and tear-specific IgE, and also between serum-specific IgE and tear-specific IgE in both AC and VK patients (K < 0.3). CPT and tear IgE were significantly correlated (K = 0.5) in the ocular allergic population. In patients with rhinoconjunctivitis or rhinitis, and in 10 normal subjects, results of CPT and NPT were in 100% agreement. Conversely, in patients with only conjunctivitis, little correlation was found between the results of CPT and NPT (K = 0.3). Tear-specific IgE was the only positive diagnostic sign of antigen sensitivity in 35% of VK patients and 30% of AC patients. These results suggest that the conjunctiva can be a uniquely sensitised target organ in allergic patients.

Conjunctiva↗

[Nasal provocation tests in the diagnosis of allergic rhinitis].

Allergic rhinitis is a frequent immunological disease affecting about 10-25% of the total population. The pathogenesis of allergic rhinitis is presumed to involve an IgE-mediated mechanism. Careful patient history, together with the skin prick test or RAST, usually allows an easy diagnosis of allergic rhinitis. In other cases it may be necessary to confirm diagnosis by the nasal provocation test. Different methods of provocation and measurement of nasal responses have been used in recent years. Scoring of the severity of clinical symptoms is too subjective to be clinically useful and should therefore be supplemented by one of the objective measurement techniques, such as anterior rhinomanometry. Additional analysis of nasal cytologic findings and determination of biomarkers in nasal secretions can be a critical tool in the evaluation of pathophisiology of allergic rhinitis. We critically discuss indications and contraindications for nasal challenges and review current techniques of provocation. We also provide various methods of assessment of nasal responses. The included examples of nasal provocation tests protocols may be helpful in introducing nasal provocation tests into everyday clinical practice.

Administration, Intranasal↗

Determination of eosinophil rate after nasal provocation test in allergic rhinitis diagnosis.

After nasal provocation test in patients with allergic rhinitis, using the allergen they were sensitized to, we have observed: 1) an increase in the percentage of nasal eosinophils after 2, 3, 24 and 48 hours; 2) sneezes, mainly in the first 30 minutes; 3) nasal obstruction in the first three hours; 4) absence of rhinorrhea, but not in all the patients; and 5) no predominance of nasal, auricular and/or palatine pruritus at any time. When patients without rhinitis, or with allergic rhinitis were stimulated using a pneumoallergen they were not sensitized to, no significative increase in the nasal eosinophils percentage was found. No symptoms were observed either. So, we can conclude that nasal secretion samples, for eosinophilia percentage determination, should be taken from 2 to 48 hours after nasal provocation, and that the most frequent symptoms, which are probably related to cellular changes, are nasal obstruction and sneezes.

Adolescent↗