Diagnostic approach to occupational rhinitis: the role of nasal provocation tests.

PURPOSE OF REVIEW: The diagnosis of occupational rhinitis is a challenge. Underdiagnosis is substantial as the clinical presentation is nonspecific and often no occupational history is taken. Detection of occupational rhinitis can be improved by including screening questions on occupational exposure in the assessment of every patient with adult-onset rhinitis. RECENT FINDINGS: Case reports, case series and epidemiological studies continuously demonstrate new sensitizers and irritants capable of inducing allergic or nonallergic (irritant-induced) occupational rhinitis. Recent reviews have focused on the value of immunological tests with specific IgE, skin prick tests or basophil activation tests in demonstrating sensitization to occupational agents. Nasal provocation tests (NPT) can establish a definite diagnosis of allergic occupational rhinitis. Several NPT guidelines have been published, however, focusing exclusively on standardized high-molecular weight allergens. When performing NPT with nonstandardized agents -- like most occupational sensitizers -- adapted protocols are needed. SUMMARY: We provide pragmatic guidance to clinicians taking care of rhinitis patients on how to diagnose occupational rhinitis, based on recent insights from the literature. We focus on the challenges in the diagnostic work-up, on how to identify suspected causes, and on the role of NPT.

[The usefulness of nasal provocation tests for respiratory physicians]. / Intérêt des tests de provocation nasale pour le pneumologue.

Rhinitis and asthma are common diseases that are strongly linked from both the epidemiological and patho-physiological point of view. A precise aetiological diagnosis is required in order to optimize treatment. Nasal provocation tests (NPT) determine precisely the role of the allergen in the initiation of the symptoms of rhinitis particularly when the history does not produce convincing evidence of the clinical relevance of an allergen. It may also have important consequences for the choice of an allergenic immunotherapy. NPT are not standardized but simple methods based on international recommendations provide us with good diagnostic accuracy. In this paper, we will discuss the practical aspects of NPT as well as the clinical or research situations where they may be useful for the respiratory physician.

EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Local allergic nasal reactions convert to classic systemic allergic reactions: a long-term follow-up.

BACKGROUND: There is poor knowledge about the evolution of the negative skin test in local allergy over time. Does the negative skin test of patients with local allergies remain negative permanently or does it become positive? METHODS: We describe our long-term observation concerning the evolution of the negative skin test over time. This is a retrospective, follow-up study using data from the medical records of a group of patients with local allergy. A total of 42 patients aged between 3 and 70 years (median age: 31.5 years) were studied. The duration of follow-up varied from 1 to 27 years. Skin tests were performed using the skin-prick test and intracutaneous techniques for pollen, molds, mites, feathers (goose and duck) and animal danders. Nasal provocation tests were conducted with the same allergens. Additionally, specific IgE in 17 patients was measured by enzyme allergosorbent test. RESULTS: During the period of observation, the negative skin test reactions converted into positive reactions in 17 patients (40%). In addition to the negative skin reactions, 55% of the patients also presented positive skin reactions. The conversion rate was higher in children and adolescents than in adults. In 4 patients, conversions occurred >7 years after the initial examination. Specific IgE was negative in all but 2 patients, in whom the conversion in the skin test was accompanied by a switch from negative to positive specific IgE. CONCLUSION: Conversions from local to classic systemic respiratory allergic reactions appear to be a common phenomenon.

Nitrite/nitrate in nasal lavage fluid reflects nasal symptoms after a single nasal allergen provocation in patients with seasonal allergic rhinitis

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Allergen-specific nasal provocation testing: review by the rhinoconjunctivitis committee of the Spanish Society of Allergy and Clinical Immunology.

Specific nasal provocation testing (NPT) consists of eliciting a response from the nasal mucosa by controlled exposure to allergens. It is indicated in the diagnostic confirmation of allergic rhinitis and when discrepancies arise or difficulties exist in the assessment of a patient's medical history and the results of skin and/or serological tests. The technique is also applied to evaluate sensitivity to the allergen, the efficacy and safety profile of treatment, and in research on the pathophysiological mechanisms of nasal response to allergens. NPT also provides information on the etiology of occupational respiratory diseases of allergic origin. Although there have been many studies and publications on the use and standardization of bronchial provocation tests with allergen, few analyze specific NPT. In this review, the Rhinoconjunctivitis Committee of the Spanish Society of Allergy and Clinical Immunology discuss the methodology, monitoring, and assessment of allergen-specific NPT in order to provide a practical and up-to-date review of the technique.

Proposed diagnostic standard using visual analogue scale and acoustic rhinometry in nasal provocation test in allergic patients.

OBJECTIVE: The authors aimed to analyze symptom change after nasal provocation and acoustic rhinometry results of a larger number of allergic rhinitis patients and also aimed to propose a new diagnostic threshold by investigating the difference between patients with allergic and non-allergic perennial rhinitis. METHODS: The authors checked symptom change and performed acoustic rhinometry before and after nasal provocation in 208 patients (114 males and 94 females, 19-58 years old) with allergic rhinitis and 222 patients (116 males and 106 females, 20-74 years old) clinically diagnosed with non-allergic perennial rhinitis (control group). Then the authors compared VAS (visual analogue scale), TNV (total nasal volume), MCA (minimal cross-sectional area), length of MCA and change of these values between allergic patients group and control group, to propose the new diagnostic standard. RESULTS: The change of symptom score and number of sneezing after nasal provocation were significantly different between allergic patient and control group. The basal TNV, MCA, length of MCA, and changes of these values were also significantly different. By drawing the ROC (receiver operator characteristic) curve and evaluating the sensitivity and specificity for each criteria, we could set the diagnostic criteria as follows: (1) symptom change: more than 2 points in the case of nasal obstruction and more than 1 point for the case of rhinorrhea or itching, (2) more than 24.5% change of the TNV, and (3) more than 20% change of the MCA. CONCLUSION: VAS change and acoustic rhinometry in nasal provocation test could be a valuable tool in diagnosing allergic rhinitis with high sensitivity and specificity.

EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed.

[Specific nasal provocative test in allergic rhinitis diagnosis: reliability and standardization]. / Il test di provocazione nasale specifico nella diagnosi di rinite allergica: attendibilità e standardizzazione.

Specific vasomotorial rhinopathy, or allergic rhinitis is to be seen as a systemic pathology characterized by a condition of hyperactivity, the target organ of which is the nose. Particular attention, among the diagnostic tests, should be reserved to the specific nasal provocative test (sNPT), which has been part of the clinical routine for years but has nonetheless failed to achieve a suitable level of standardization. With this intent, we have devoted the present work to the assay of several phlogosis mediators (tryptase, specific IgE and ECP) before and after performing the sNPT. We have studied 20 patients affected by allergic rhinitis, aged between 13 and 61, with single or multiple allergen sensitivities, but in any case with a predominant sensitization, who underwent sNPT between October 2000 and July 2001. In every patients we performed ECP, tryptase and specific IgE assay via direct incubation in the nasal mucosa, before and after specific nasal provocation. The results of the sNPT (rhinomanometry and symptoms score) were compared with the variations in the phlogosis mediators assayed at nasal level. On the basis of the variations in the rhinomanometric resistance and symptoms score, the sNPT was positive in 10 patients (50%). Tryptase and specific IgE increased to a statistically significant degree (respectively, p = 0.01 and p < 0.05) in all of the patients; the ECP variations, instead, were not significant (p > 0.05). Overall, the simultaneous assay of ECP, tryptase and specific IgE, increasing the sensibility of the sNPT, enabled a positive result to be ascertained in 60% of the subjects examined. The method is furthermore based on the principle of local reactivity in that it assays the phlogosis mediators not at systemic level, but directly in the target organ, showing itself to be more specific than level I and II tests.

Skin test results but not serology reflect immediate type respiratory sensitivity: a study performed with recombinant allergen molecules.

The diagnosis of type I allergy, an IgE-antibody-mediated hypersensitivity disease affecting more than 25% of the population, is based on the measurement of allergen-specific serum IgE levels and provocation testing. Whether the determination of allergen- specific serum IgE levels can replace in vivo provocation testing for allergy diagnosis is a controversial issue. We used purified recombinant timothy grass and birch pollen allergens to compare by skin prick and nasal provocation testing as well as by serology in vivo sensitivity with antibody-binding capacity in 24 pollen allergic patients and eight control individuals. Results from biologic tests were correlated with each other and with allergen-specific IgE and IgG1-4 levels. IgE-reactive allergens induced immediate skin and nasal reactions, but the intensity of the allergic tissue reactions was not correlated with either the levels of allergen-specific IgE or the levels of allergen-specific IgG antibodies. Less frequently detected allergens with low IgE-binding capacity were able to induce strong allergic reactions comparable to those caused by major allergens with high IgE-binding capacity. In contrast, skin test and nasal provocation results were significantly correlated (r = 0.63, p < 0.01). Our study thus demonstrates on a molecular level that skin testing provides a better reflection of immediate type respiratory sensitivity than serologic measurements. These results have implications for allergy diagnosis and, in particular, for the selection of relevant allergen components for specific immunotherapy.

Specific and non-specific nasal provocation tests in children with perennial allergic rhinitis.

BACKGROUND: nasal provocation tests (NPT) have been extensively used in clinical practice to evaluate chronic rhinopathies, mainly allergic rhinitis (AR). METHODS: we submitted 10 perennial AR children (aged from six to 15 years) to histamine (H), Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) NPT. All children were sensitized (positive skin prick test, mean wheal > 3 mm) to both mites. Dp and Bt specific NPT were realized in two occasions, apart one week, always preceeded 24 hours by H challenge. Increased concentrations were applied to the nasal mucosa during each NPT: H (0,03 to 16 mg/ml), Dp (1/100,000 to 1 /2.5) and Bt (1/125,000 to 1/10). NPT were evaluated by clinical and rhinomanometric parameters (total score, TS), and by lung function tests. NPT was considered positive, when total nasal resistance (TNR) doubled in relation to basal value. RESULTS: H NPT was positive twice in 8/10 patients. Concordance between H concentration that induces a positive NPT measured by TNR or TS was observed. Regarding to specific NPT, 90 % of patients were positive to Dp and 60 % to Bt. There was no concordance between the allergen concentration that induces a positive SPT and a positive NPT, considering the different concentrations. There were no modification in lung function tests during both specific and non-specific provocation tests. CONCLUSIONS: NPT with H is an objective and reproducible method which allow evaluate nasal reactivity. Specific NPT have restricted indications, mainly when there where doubts about AR's etiology.

Challenge tests in nose and bronchi: pharmacological modulation of rhinitis and asthma.

In order to study the pathophysiology of allergic airway disease and its response to pharmacotherapy, allergic and non-allergic provocation challenge techniques can be employed. Lower airway challenge has been used widely, but the use of nasal challenge is becoming more widespread as its advantages are realized. New measurement techniques are also being used (e.g. acoustic rhinometry), along with more classical methods such as spirometry, peak airflow rate and symptom scores, to determine the response to challenge. In the lungs, allergen challenge produces a biphasic response, which is less clearly defined in the nose. Topical histamine challenge closely resembles the effects of an allergic reaction and acts by stimulating sensory nerve endings. Methacholine is also often used for nasal challenge (often in addition to histamine), due to its effects on glandular sensitivity. Exercise induces bronchoconstriction in asthmatics and can be imitated by inhalation of cold, dry air. Cold air induces glandular hypersecretion and nasal discharge in normal subjects, which is increased in severity in rhinitic patients. Drug effect investigations using antihistamines have shown that histamine is important in producing the symptom of sneezing, whereas nasal blockage is due to vasodilatation rather than plasma exudation and oedema. Beta 2-agonists reduce allergen-induced symptoms by stabilizing mast cells, whereas cholinoceptor antagonists reduce watery nasal secretion. Increased responsiveness of sensory nerves and nasal glands is a characteristic clinical feature of asthma and rhinitis, which is responsible for the symptomatology. These effects can be reduced by topical corticosteroids.

Reproducibility of the effects of intranasal ragweed challenges in allergic subjects.

BACKGROUND: Intranasal allergen challenges have been used to study the pathogenesis of disease expression, to evaluate the efficacy of therapies and to make diagnosis of allergic status. Few data, however, are available regarding the reproducibility of the responses to such provocative challenges. OBJECTIVE: The purpose of this study was to evaluate the reproducibility of selected responses of allergic subjects to intranasal pollen challenge. METHODS: Eighteen adults with ragweed allergy completed three dose-response challenge sessions at a minimum interval of 1 week. Sessions were single blinded and randomized to include two intranasal ragweed challenges (doses 10, 100, and 1000 PNU) and one placebo challenge conducted out of the ragweed season. Additionally, 12 of these subjects completed a third ragweed challenge session conducted during the ragweed season. Following administration of each dose, symptoms were scored, sneezes counted, and nasal patency measured by active posterior rhinomanometry. Total nasal secretion weight for each session was measured. RESULTS: For all measures, average dose response curves were identical for the two extra-seasonal ragweed challenges and these were significantly different from those of the placebo challenge session. Intra-individual responses to the two ragweed challenges were highly correlated between sneeze count and secretion weight, and were moderately correlated for objective and subjective measures of rhinorrhea and congestion. No significant increases in these responses were observed for the intra-seasonal ragweed challenge session. CONCLUSIONS: These results document a reproducible symptomatic and physiologic response to intranasal ragweed challenge.

Histamine nasal provocation test. An evaluation of active anterior rhinomanometry and of threshold criteria of provocative dose.

This study is a methodological approach to histamine nasal provocation. The test uses active anterior rhinomanometry and a histamine titration method, challenging both nasal cavities with a metered dose pump. It has been confirmed that the histamine nasal provocation test can differentiate between controls and non-allergic rhinitis patients. This study shows, moreover, that the method is more sensitive in assessing response to histamine provocation when a 25% increase of post-saline nasal airway resistance (PD25) is considered than a PD50 or PD100 criterion. The histamine response, was found to be independent of the baseline nasal airway resistance value. Pronounced unilateral responsiveness was frequently noticed. Both nasal cavities should be challenged and the most reactive side considered.