Niels Mygind

A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force.

This report has been prepared by an EAACI task force representing the five EAACI Sections and the EAACI Executive Committee composed of specialists that reflect the broad opinion on allergy expressed by various clinical and basic specialties dealing with allergy. The aim of this report is to propose a revised nomenclature for allergic and related reactions that can be used independently of target organ or patient age group. The nomenclature is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. However, the intention has not been to revise the nomenclature of nonallergic hypersensitivity.

Consensus statement on the treatment of allergic rhinitis.

Allergic rhinitis (AR) is a high-prevalence disease in many developed countries, affecting about 10±20% of the general population (1±5). Several studies based on questionnaire and objective testing or medical examination indicate an increasing prevalence of AR in European countries over the last decades (6, 7). AR is characterized by nasal itching, sneezing, watery rhinorrhoea, and nasal obstruction. Additional symptoms such as headache, impaired smell, and conjunctival symptoms can be associated. According to the time of exposure, AR can be subdivided into perennial, seasonal, and occupational disease. Perennial AR (PAR) is most frequently caused by dust mites and animal dander. Seasonal AR (SAR) is related to a wide variety of pollen allergens including grasses, Parietaria, Ambrosia, Artemisia, birch, olive, hazelnut, and cypress. The morbidity of SAR obviously depends on the geographic region, the pollen season of the plants, and the local climate. Several other conditions can cause similar symptoms and are referred to as nonallergic (noninfectious) rhinitis: NARES (nonallergic rhinitis with eosinophilia syndrome); aspirin sensitivity; endocrine, occupational, postinfectious, and side-effects of systemic drugs; abuse of topical decongestants (rhinitis medicamentosa); and idiopathic rhinitis. Furthermore, diseases such as nasal polyposis, chronic sinusitis, cystic ®brosis, Wegeners disease, benign or malignant tumours, etc. have to be excluded carefully. Therefore, current guidelines (4) emphasize the importance of an accurate diagnosis of patients presenting with rhinitis symptoms. In fact, several causes may commonly coexist in the same *European Academy of Allergology and Clinical Immunology. Allergy 2000: 55: 116±134 Printed in UK. All rights reserved Copyright # Munksgaard 2000

Anatomy, physiology and function of the nasal cavities in health and disease

In studying drug absorption from the nasal mucous membrane, it is essential to have a clear understanding of anatomy and physiology of the nose, and how it relates to the characteristics of the delivery system used. The human nose is characterized by an individually varying shape and caliber, which might interfere with standard recommendations of intranasal medication. It is also of significance that there is a tendency for reflex- induced and profuse watery hypersecretion from glands, and for quick and considerable changes of mucosal thickness due to the presence of large venous sinusoids. These are factors which can interfere with pharmacokinetics. Also mucociliary transport rate has to be taken into consideration, as the drug is removed from the absorptive mucous membrane within 30 min. Intranasal drug distribution has been poorly studied in relation to nasal anatomy and pathology. In contrast to common believe, nasal inflammation does not seem to increase drug absorption. On the contrary, blockage, sneezing and rhinorrhoea might preclude the absorption.

Local effect of intranasal beclomethasone dipropionate aerosol in hay fever.

The effect of a daily dose of 400 μg beclomethasone dipropionate aerosol intranasally has been investigated in a double-blind cross-over trial in 29 patients with hay fever. The effect on the nasal symptoms was so pronounced in 25 patients that further symptomatic treatment was unnecessary. Beclomethasone dipropionate aerosol had, on the other hand, no direct effect on itching in the eyes, which is in accordance with the fact that biochemical investigations did not show any sign of suppression of the adrenal function. It is concluded that beclomethasone dipropionate aerosol intranasally is an effective and apparently harmless way of controlling the nasal symptoms in hay fever.

Significance of H1 and H2 receptors in the human nose: rationale for topical use of combined antihistamine preparations

The aim of this experiment was to study the importance of histamine H1 and H2 receptors in the human nose. We therefore provoked 25 healthy human subjects with histamine after local pretreatment with the H1 receptor antagonist, chlorpheniramine maleate, the H2 receptor antagonist, ranitidine hydrochloride, and a combination of these two antihistamines. The histamine-induced increase in nasal airway resistance was 52% inhibited by combined use of the two antihistamine sprays (p less than 0.05), 22% by chlorpheniramine alone (p less than 0.05), and 29% by ranitidine. The two sprays together were significantly better than the H1 antagonists alone (p less than 0.05). These results suggest an equal importance of H1 and H2 receptors in nasal blood vessels, and an additive effect of H1 and H2 antihistamines. Although chlorpheniramine effectively blocked tickling and the reflex-mediated symptoms, sneezing and hypersecretion, ranitidine had no effect, which suggests an H1 and not an H2 effect on sensory nerve endings in the airway epithelium.

Nasal polyposis, eosinophil dominated inflammation, and allergy

A polyp is an oedematous mucous membrane which forms a pedunculating process with a slim or broad stalk or base. Nasal polyps originate in the upper part of the nose around the openings to the ethmoidal sinuses. The polyps extend into the nasal cavity from the middle meatus, resulting in nasal blockage and restricted airflow to the olfactory region. The polyp stroma is highly oedematous with a varying density of inflammatory cells. Nasal polyposis, consisting of recurrent, multiple polyps, is part of an inflammatory reaction involving the mucous membrane of the nose, paranasal sinuses, and often the lower airways. The polyps are easily accessible for immunological and histological studies and an increasing number of publications have appeared in recent years, including two monographs.1 2 Nasal polyps have long been associated with rhinitis and asthma. However, the role of allergy in the aetiology and pathogenesis of nasal polyps is a controversial issue. It has been postulated that allergy is an aetiological factor for nasal polyposis. If this is so, then it can be expected that allergic patients will have polyps more often than a control population and that patients with polyps have an increased occurrence of positive allergy testing. In this paper we will describe the possible connection between nasal polyposis and allergy, based on an analysis of (1) the occurrence of polyps and of allergy, (2) the anatomy and histology of nasal polyps, (3) the inflammation in nasal polyps, (4) the occurrence of positive allergy tests in patients with polyps, (5) the effect of allergen exposure on nasal symptoms in patients with polyps, and (6) the response to treatment. While the aetiology of nasal polyposis is unknown in many patients, in a few cases it is well defined. Polyps occur in most patients with allergic fungal sinusitis. In this …

Histopathologic Examination and Enumeration of Polymorphonuclear Leukocytes in the Nasal Mucosa during Experimental Rhinovirus Colds

The histology of the nasal mucosa was examined by serial scrape and punch biopsies in 20 rhinovirus infected volunteers and 10 sham inoculated controls. No morphologic changes could be detected in the epithelial or subepithelial portions in the mucosa of specimens from infected volunteers. There was a significant increase in the number of polymorphonuclear leukocytes (PMNs) in the nasal epithelium of the infected subjects early in the course of the cold compared to their pre-infection baseline. However, trauma to the nasal mucosa from repeated sampling led to an outpouring of PMNs into nasal mucus, making evaluation of the results difficult. The number of mast cells seen in the mucosal specimens of the infected subjects did not differ from that seen in controls.

Allergen-induced increase of eosinophil cationic protein in nasal lavage fluid: Effect of the glucocorticoid budesonide

It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days after pretreatment for 2 weeks with the glucocorticoid, budesonide, as a nasal spray (400 micrograms/day) and with placebo with a double-blind, crossover design. Nasal lavage fluid was repeatedly collected during a 10-hour period to study both early and late-phase responses. 99mTechnetium-albumin was added to the lavage fluid, making it possible to calculate the amount of secretion and the degree of dilution. The results were as follows: (1) There was no correlation between ECP concentration and dilution factor in the individual samples. (2) The mean concentration of ECP in lavage fluid from untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic molecule.

Inhibition of the immediate allergic reaction in the nose by the beta-2 adrenostimulant fenoterol

Abstract Sympathomimetic agents inhibit antigen-induced release of histamine in animal experiments and in in vitro studies of human tissue, but the significance of this effect for treatment of allergic airway diseases has not been established. It was the aim of our study to investigate the protective effect of the beta-2 adrenostimulant fenoterol on allergen-induced nasal symptoms and to relate the efficacy to dose and time. In a double-blind crossover design 16 patients with hay fever were challenged with grass pollen extract in the nose after pretreatment with intranasal placebo and fenoterol in different doses, delivered as a micronized powder from a pressurized canister and as a watery solution from a pump spray. Sneezing was recorded, and rhinorrhea and changes in nasal airway resistance were measured for 15 min after the provocation. Fenoterol, micronized powder as well as solution, had a marked inhibitory effect on all three nasal symptoms (p

3. Advances in the medical treatment of nasal polyps

The objectives of the medical management of nasal polyposis are to eliminate or reduce the size of polyps, re‐establish nasal breathing, reduce symptoms of rhinitis, restore the sense of smell and prevent the recurrence of nasal polyps. Corticosteroids have a proven therapeutic effect on the symptoms of nasal polyposis and may reduce one of the underlying causes of polyps, inflammation. The efficacy of topical corticosteroids such as beclomethasone dipropionate nasal spray and betamethasone nasal drops in reducing polyp size and rhinitis symptoms has been demonstrated in several randomized, placebo‐controlled trials. Flunisolide and budesonide have also been shown to delay the recurrence of polyps after surgery. Topical corticosteroids can be used as long‐term therapy either alone in mild cases, or combined with systemic corticosteroids and/or surgery in severe cases. Most patients will respond well to topical corticosteroid treatment of their nasal polyposis; consequently, the requirement for repetitive nasal surgery will be reduced.