Nasal response to allergen and hyperosmolar challenge

Rhinitis causes both clinical and social discomfort to patients, and in clinical practice is often underdiagnosed. We have examined a simple method for the assessment of a positive nasal provocation test to help in the diagnosis of rhinitis. In patients with histories suggestive of house dust mite (HDM) sensitivity and positive skin-prick tests or specific IgE to Dermatophagoides pteronyssinus , there was a fall in nasal inspiratory peak flow (NIPF) following nasal challenge with allergen. This was not seen in control subjects or in pollen-sensitive patients when challenged with house dust mite. Frequency of sneezing and degree of rhinorrhoea increased in these patients following challenge, and based on these findings we propose a simplified scoring system for the diagnosis of allergic rhinitis. We examined non-specific nasal reactivity using hyperosmolar solutions as a challenge system and found that allergic subjects responded with a fall in NIPF, although the clinical response was not identical to that seen with allergen. Control subjects did not respond to hyperosmolar challenge.     

Nasal mast cell response to natural allergen exposure

A redistribution of mast cells into the epithelium and towards the mucosal surface was previously observed during the allergy season in individuals allergic to birch pollen. We have therefore attempted to investigate in greater detail the role of mast cells in mucosal allergy by the study of the morphological and biochemical changes that occur in the nasal mucosa of allergic individuals during natural allergen exposure. An activation of the intraepithelial mast cells was indicated by the observation of ultrastructural signs of a secretory activity. We also found that the normal strong correlation between mast cell numbers and histamine content in the nasal mucosa was absent in specimens taken during allergen exposure, which was interpreted as a result of a release of histamine from the mast cells with the appearance of a transient, non-mast cell pool of tissue histamine. Furthermore, the histamine content of the nasal mucosa during the pollen season was strongly correlated to the severity of symptoms experienced by the patients. These observations provide additional evidence that mucosal mast cells have a pathogenetic role in continuous allergic airway disease.     

Nasal eosinophilia in children: its use in the nasal allergen provocation test

This pediatric cytological and clinical study aimed at assessing the value of nasal eosinophilia during nasal provocation tests for identifying an offending allergen. The population studied comprised 50 children aged from 4 to 18 yr; 39 of these had well-characterized allergic rhinitis, which in 21 cases was combined with asthma, and the remaining 11 had nonatopic chronic rhinitis. Nasal secretions, collected by nose blowing, were stained with May-Grünwald-Giemsa or Wright stain. The percentage of nasal eosinophils was obtained by examining the cells in the whole slides. Counts were carried out on secretions collected before challenge, after insufflation of saline solution (for verification), and 40 min after insufflation into each nostril of an allergen (housedust mite extract). The nasal provocation test was considered positive when insufflation of the allergen increased nasal eosinophilia by more than 10%, provided that the prechallenge proportion of eosinophils was less than 50%. No increase in specific bronchial resistance was noted. These results indicate that nasal provocation tests are safe, even in asthmatic children.     

The effect of Iodoxamide tromethamine on the immediate asthmatic response to allergen provocation

The inhibition of immediate allergen-induced airflow obstruction by lodoxamide tromethamine (LT), a new drug with properties considered to be similar to those of sodium cromoglycate, was studied in twelve young asthmatic volunteers. Single aerosolized doses of 0.01 mg LT, 0.1 mg LT or placebo were administered by inhalation 15 min prior to allergen provocation at weekly intervals, in a double-blind random order study. Following inhalation of both doses of LT a significantly greater amount of allergen had to be administered to cause a 20% fall in the forced expiratory volume in one second (FEV¹) from control levels than was the case following placebo pre-treatment (P < 0.001). After single-dose inhalation of LT only minor unwanted effects were recorded; in particular a transient feeling of heat in the upper respiratory tract after inhalation of the higher dose of drug.     

Nasal endothelial interleukin-10 expression is negatively correlated with nasal symptoms after allergen provocation

Background:  Despite major efforts, factors that predict or correspond to the level of allergic symptoms remain elusive. Given our previous observations of mucosal interleukin-10 (IL-10) expression by local tissue cells and its described role as immune modulator, we hypothesized that, in allergic rhinitis, nasal mucosal IL-10 expression could influence the severity of symptoms.
Methods:  In this study, we investigated endothelial IL-10 expression in nasal mucosa of healthy- and house dust mite allergic patients, both before and after provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken from healthy individuals as well as from house dust mite allergic patients, both before and after provocation. Allergic patients received fluticasone proprionate aqueous nasal spray or control treatment. In the allergic patients, endothelial IL-10 scores based on immunohistochemical stainings were correlated with allergic symptoms, measured by visual analog scores.
Results:  At baseline, variable levels of endothelial IL-10 were detected in nasal biopsies. After nasal provocation, but not at baseline, endothelial IL-10 expression corresponded very closely to the allergic symptoms after allergen provocation. Low symptom scores were correlated with high endothelial IL-10 scores. This correlation disappeared after fluticason propionate treatment.
Conclusions:  There is a large variation in the level of endothelial IL-10 expression both in healthy individuals and in house dust mite allergic patients. Endothelial IL-10 expression may affect local immune reactions resulting in reduced levels of allergic symptoms.     

Nasal allergen provocation with Dermatophagoides pteronyssinus in patients with chronic rhinitis referred to a rhinologic surgical center.

BACKGROUND: Skin tests and specific immunoglobulin (Ig)E determinations identify the presence of some immune response to allergens, but frequently do not correlate to allergic disease in vivo. OBJECTIVE: To compare clinical history, skin tests and specific IgE determinations with the results of nasal provocation tests (NPT) to confirm clinically relevant allergy to Dermatophagoides pteronyssinus (DP) in patients with chronic rhinitis referred to a rhinologic surgical center. METHODS: Clinical data of 2,194 patients with chronic nasal disorders treated at two rhinologic referral centers between 1992 and 1998 were evaluated. Clinical allergy work-up was routinely performed corresponding to German and European guidelines providing consistent data in both centers. RESULTS: Of chronic rhinitis patients, 752 of 2,194 (34%) had at least one positive skin reaction to a perennial allergen common in Central Europe. Three hundred seventy-three patients had a positive skin test to DP and were paradigmatically evaluated in detail. In 235 patients, a complete dataset including structured allergic history, skin test, specific IgE determinations, and NPT was available. Quality and severity of symptoms, clinical history, skin tests, and allergen-specific IgE-determinations were unreliable predictors of the outcome of NPT with DP. CONCLUSION: In patients referred for surgical treatment of chronic rhinitis, diagnosis of perennial allergy is unreliable unless confirmed with NPT.     

Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways

BACKGROUND: Allergic rhinitis (AR) and asthma are characterized by means of a similar inflammatory process in which eosinophils are important effector cells. The migration of eosinophils from the blood into the tissues is dependent on adhesion molecules. OBJECTIVE: To analyze the aspects of nasobronchial cross-talk, we studied the expression of adhesion molecules in nasal and bronchial mucosa after nasal allergen provocation (NP). METHODS: Nine nonasthmatic subjects with seasonal AR and 9 healthy control subjects underwent NP out of season. Bronchial and nasal biopsy specimens were taken before (T(0)) and 24 hours after NP (T(24)). Mucosal sections were analyzed for the presence of eosinophils, IL-5, eotaxin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and human endothelium (CD31). RESULTS: At T(24), an influx of eosinophils was detected in nasal epithelium (P =.01) and lamina propria (P <.01), as well as in bronchial epithelium (P =.05) and lamina propria (P <.05), of the patients with AR. At T(24), increased expression of ICAM-1, as well as increased percentages of ICAM-1+, VCAM-1+, and E-selectin+ vessels, were seen in nasal and bronchial tissue of patients with AR. The number of mucosal eosinophils correlated with the local expression of ICAM-1, E-selectin, and VCAM-1 in patients with AR. CONCLUSION: This study shows that NP in patients with AR results in generalized airway inflammation through upregulation of adhesion molecules.     

Nasal provocation testing: a review.

OBJECTIVE: This review focuses on the uses of nasal provocation testing (NPT) for scientific investigations of the mechanisms of allergic and nonallergic rhinitis. It also describes the use of NPT as a diagnostic tool in clinical practice. The indications, contraindications, advantages, and limitations of different techniques for evaluation of nasal responses are reviewed. The paper familiarizes investigators with particulars of different nasal delivery systems, provocation agents, nasal patency measurements, secretion collection, and nasal lavage techniques. DATA SOURCES: Relevant publications obtained from a literature review. STUDY SELECTION: Relevant publications on the topics of NPT, allergic, and nonallergic rhinitis were critically evaluated. RESULTS AND CONCLUSIONS: To date, NPT has been used primarily as a research tool for the investigation of allergic and nonallergic rhinitis with a wide variety of techniques depending on the specific scientific purposes. NPT will continue to provide useful information about the pathogenesis of airway diseases. Standardized nasal provocation testing has the potential to become a more frequently used clinical test in the diagnosis of allergic and occupational rhinitis and for determination of the appropriate and focused therapy.     

The effect of single and multiple dose therapy with azelastine on the immediate asthmatic response to allergen provocation testing

The effect of 2.2 or 4.4 mg of azelastine administered orally on immediate allergen-induced airflow obstruction was studied in 20 young patients with asthma. Provocation testing was performed after a single oral dose of azelastine or placebo and repeated after 3 weeks of twice daily therapy with azelastine or placebo. After multiple dose therapy with 4.4 mg of azelastine for 21 days, significantly more allergen was required to produce a 35% fall in specific airways conductance than after placebo therapy (p less than 0.008). Apart from a "bitter, metallic" taste in the mouth reported by 41.2% of the patients while they were receiving azelastine, no other unwanted effects were encountered.     

Conjunctival allergen provocation test : guidelines for daily practice

Conjunctival allergen provocation test (CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)‐triggering symptoms in IgE‐mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half‐life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum‐specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information.     

Nasal provocation and passive anterior rhinomanometry (PAR)

A rapid and convenient method of nasal provocation (aerosol provocation combined with passive anterior rhinomanometry) is described. A comparative study between skin tests, bronchial provocations and nasal provocations highlights the usefulness of this method.     

Nasal provocation test with lysine acetylsalicylate in aspirin-sensitive patients

The authors have studied nasal provocation testing (NPT) with aspirin in 45 aspirin-sensitive patients (40 affected by nasal polyposis) and in 38 aspirin-tolerant patients (27 affected by nasal polyposis). The test was positive in 37.7% of aspirin-intolerant subjects, but only in 7.9% of subjects in the control group (P less than .01).     

Facial thermography during nasal provocation tests with histamine and allergen

Changes of skin temperature (T°) of the nose area during nasal provocation tests with histamine and allergen were followed by means of an infrared thermography camera. By a colimator system in which temperatures measured on a given surface can be integrated and averaged, thermography allows the continuous and quantitative recording of the temperature during the whole procedure in a completely noninvasive way. In 10 normal subjects, increasing doses of histamine induced a dose-dependent rise of the nose external temperature. No significant change was observed with the vehicle solution. In six subjects allergic to grass pollen, the nebulization of increasing concentrations of a pollen extract induced a dose-dependent rise in T°. The T° rise observed after histamine or allergen corresponded to a marked nasal obstruction. The nebulization of the highest dose of the pollen extract did not induce any T° rise in six nonallergic subjects. The continuous recording of the skin temperature by a noninvasive method might yield additional information on the vascular changes rapidly occurring during nasal challenges.