Wednesday, April 24, 2013

Prosinus study goals

PROSINUS study goals (II extract)

PROSINUS is an prospective, observational, epidemiological study of health outcome in which the exposure factor is not a medicine but a disease. “it is not drug efficacy and/or tolerance that is being assessed but the evolution of a disease from initial diagnosis to final cure.” Before the first visit, information was obtained on the treatment received by the patient in the non-ENT primary care system, while the management approach applied during specialist care was examined after the first visit.
The study’s primary goal is to assess the diagnostic, treatment and clinical monitoring procedures available for acute rhinosinusitis in usual practice. The secondary goals include the following: describe the bio-demographic and clinical profile of the patient with acute rhinosinusitis, assess the degree to which the European position papers (EP3OS) are applied in the Spanish health system, determine the prevalence of complications of acute rhinosinusitis, analyse the health-related quality of life of patients with acute rhinosinusitis, and assess their treatment compliance.

Certain pharmacoeconomic goals have also been set: study the socioeconomic impact of acute rhinosinusitis, evaluating the ratio-optimization of the resources used to control the disease, and the impact on work life.
The primary study variables are: disease duration, diagnostic resources used or number of visits; the secondary variables are concerned with epidemiological data, treatment compliance (Morisky-Green test), and degree of satisfaction.

Joan Montserrat,

Wednesday, April 17, 2013

PROSINUS study results in Spain (I extract)

PROSINUS study results in Spain

The PROSINUS study has been designed in response to the shortage of epidemiological data in Spain on the diagnosis and treatment of acute rhinosinusitis (ARS). The name PROSINUS refers to a prospective epidemiological study whose purpose is to analyse the diagnosis and treatment of this disease in ENT offices in Spain and also to assess its socioeconomic impact.

However, 550 were subsequently excluded because they had chronic rhinosinusitis and a further 77 had a probable diagnosis of chronic rhinosinusitis. Of the 1,233 patients with a confirmed diagnosis of ARS, 1,172 have completed visit 1 of the study and 788 have also reached visit 2. Most of the patients (approx. 90%) initially had a moderate or severe disease, according to the VAS.
The definition of acute rhinosinusitis given in the 2005 EP3OS guidelines has been used for the study. At present, the diagnosis of rhinosinusitis is basically clinical; the main symptoms are nasal obstruction/congestion, impaired sense of smell, anterior or posterior rhinorrhoea, and facial pain/pressure; at least two symptoms are required to determine the presence of rhinosinusitis.
However, a further condition has been added in that the symptoms must be associated with suggestive endoscopic findings (polyps, rhinorrhoea and oedema) or changes in the sinonasal mucosa that can be identified by computerised tomography (CT).
In the review of the EP3OS position paper performed this year (Fokkens et al., 2007), it was proposed to reclassify the severity of rhinosinusitis by quantifying it on a visual analogue scale graded from 0 to 10. Under this new classification, a patient is considered to have mild disease when the score on the visual analogue scale does not exceed 4 and moderate/severe disease when at least one symptom attains a score between 4 and 10. As regards the duration of the rhinosinusitis, it is defined as acute or intermittent when disease duration is less than 12 weeks and chronic or persistent if it continues beyond 12 weeks. Acute rhinosinusitis is further subdivided into two clinical conditions: acute viral rhinosinusitis or common coldand acute/intermittent non-viral rhinosinusitis.
In viral rhinosinusitis, symptom duration is less than 10 days, while acute/intermittent non-viral rhinosinusitis is defined as an increase in symptom severity after 5 days or persistence of symptoms beyond 10 days after symptoms began. In both cases, symptom remission is complete within 12 weeks.

Dr. Joan Montserrat

Monday, April 8, 2013



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.

Take it from: 

Joaquim Mullol, M.D.