Documents

Inflammation as the Underlying Cause of
Sinonasal Disease

MULLOL J.
ENT Departament. Moscow. Russia

Present and Future of the Management of Sinonasal Disesase.
Madrid, 11 November 2007.
Keywords Present and Future of the Management of Sinonasal Disesase - PDF

INTRODUCTION

Inflammation plays an essential role in the occurrence and development of sinonasal disease. In recent years, a growing number of experimental and clinical studies have been performed on conditions such as nasal polyposis, chronic rhinosinusitis or acute rhinosinusitis that show the predominant role played by the inflammatory process, leading to the identification of inflammatory markers or precursors that have become veritable treatment targets.

This inflammation, which underlies a considerable proportion of sinonasal conditions, manifests clinically in the appearance of certain characteristic symptoms. Of these, the most significant is nasal obstruction, and it is also, as Dr. Mullol reported, “the symptom that shows the clearest correlation with the inflammatory cascade.”


ALLERGIC INFLAMMATION

To illustrate this point, the speaker described the pathophysiology of various conditions, starting with allergic rhinitis. The vehiculization of allergens, their processing and subsequent presentation of antigens to Th2 lymphocytes is the first step towards the allergic reaction. After this stage, the B lymphocytes specialise to plasma cells and produce IgE, which sensitises the mastocytes so that, in a following allergic phase, contact with new allergens initiates a renewed inflammatory cascade, mediated mainly by histamine, causing symptoms such as the sneezing and water rhinorrhoea that are typical of allergic conditions.

This situation leads to a significant increase in eosinophils, forming a vicious circle of inflammation, which is the cause of all of the typical symptoms of this type of condition (rhinorrhoea, nasal itching, sneezing, nasal obstruction, hyposmia).

Numerous studies have examined the role of a multitude of inflammatory mediators, identifying molecules that are responsible for the appearance of specific symptoms such as nasal obstruction. Of the chemical mediators that have been studied, histamine, tryptase, the kinins, neurokinin A or substance P hold particular interest. Manipulation of mediators causes allergic reactions in animal models.

The identification of inflammatory cells in the nose, either by biopsy or smear, enables a presumptive diagnosis (although not a firm diagnosis) to be established. Thus, as Dr. Mullol explained, the presence of eosinophils may suggest a possible diagnosis of allergy, NSAID intolerance or eosinophilic rhinitis; likewise, the existence of basophils/ mastocytes may suggest a possible diagnosis of allergy, NSAID intolerance, basophilic rhinitis or nasal mastocytosis.

A particularly high neutrophil count would suggest a possible diagnosis of rhinosinusitis, irritant rhinitis, viral infection or nasopharyngitis; lastly, the existence of a large number of goblet cells in the nasal cavity may suggest a possible diagnosis of allergy, infection or vasomotor rhinitis.

A key concept, particularly in allergic inflammation, is that of minimal persistent inflammation. Described by Ciprandi et al., this is to be found in all patients with allergic rhinitis; in this case, it has been found that the patients experience increased inflammation with the accompanying symptoms only during periods of peak exposure to allergens.

Consequently, the speaker inferred, “we should not assume that an asymptomatic patient has no nasal inflammation and, in fact, it is highly likely that this minimal persistent inflammation could be the cause of the hyperreactivity.”


INFLAMMATION IN ACUTE (ARS) AND CHRONIC RHINOSINUSITIS (CRS)

To date, there is little published data on inflammation in acute rhinosinusitis (ARS). However, what information there is helps us understand how this condition is not always equivalent to the presence of a bacterial infection.

In ARS, it is common to find high IL-8 (which is the neutrophils’ main chemotactic agent), TNF-alpha and total protein levels. Neutrophil and T lymphocyte levels are also usually increased (both in the epithelium and in the lamina propria).

There is more information available on the existence of inflammation in chronic rhinosinusitis (CRS) with nasal polyposis. Among other findings, there is one that is particularly interesting: the persistence of high eosinophil levels. Numerous inflammation mediators have been found in the sinonasal mucosa of subjects with CRS and nasal polyposis which may play an important role and may be caused both by specific substances and by other non-specific factors (cold, pollution,…).

Glandular secretion is an important component of inflammation, manifesting as rhinorrhoea, and is regulated not only by inflammatory regulators but also by the epithelial and inflammatory cells themselves and by classic neurotransmitters. A landmark study performed by Roca Ferrer et al. shows that the application of metacholine on the nasal mucosa induces a significant increase in glandular secretion markers (in both the nasal and bronchial mucosa) and that this effect can be blocked by the administration of an anticholinergic agent. In addition, there is a dose-dependent relationship between metacholine and glandular secretion. Identical results are obtained with the application of interleukins.

In this context, it has been shown that the administration of glucocorticoids interacts with all the stages of the inflammatory cascade. Martínez-Antón et al. have shown its ability to act on the mucins (one of the main markers of glandular secretion).

In his studies, Dr. Mullol has provided significant information on the activity of glucocorticoids as inhibitors of COX-2 expression and activity, negative regulators of the NFB receptor and modulators of the activity of other components of the inflammatory cascade, such as eosinophils, cytokins and GMCSF activity in the epithelium.

In addition, it has been recently documented that the corticoid receptor alpha (which is the active receptor for corticoids) is decreased in nasal polyps. It is therefore to be expected that nasal polyps would be less responsive to treatment with these drugs (i.e., there would be a certain amount of resistance).

It has also been seen that treatment with high doses of corticoids quickly induces a marked decrease in the expression of the corticoid receptor. Consequently, it would be expected that the treatment would progressively become less effective. However, these results are not confirmed in in vivo experiments; on the contrary, expression of the corticoid receptor increases with continued administration of glucocorticoids.

These findings about inflammation are significant; an improved understanding of the pathophysiology of sinonasal conditions will enable a more targeted management, facilitating diagnostic and treatment decisions and offering greater benefit to our patients.


Present and Future of the Management of Sinonasal Disesase - Index

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