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Is it possible to cure all forms of Acute Rhinosinusitis in 4 weeks? Evidence from the Prosinus study

MULLOL, J.
Coordinator of the Rhinology Unit.
Hospital Clínic i Provincial de Barcelona, and co-president of EP3OS. Spain

New Treatment Approaches to Rhinosinusitis: Less is more.
Crete. Greece. 15-19 June 2008
Keywords New Treatment approaches to Rhinosinusitis - PDF

ABSTRACT

The EP3OS guidelines and their 2007 update are a reference tool for Rhinosinusitis. They embody the international consensus on the definition of the disease, updates of the studies available, epidemiology, management, diagnosis and trends in all aspects of the disease.

The PROSINUS study is a pioneering observational, multicentre, prospective, epidemiological study performed in Spain to assess the diagnosis and treatment of rhinosinusitis as applied in actual clinical practice by primary care physicians and ORL specialists. The main conclusions are that acute rhinosinusitis is mostly moderate/severe; excessive use is made of diagnostic tests such as plain X-rays of the sinuses; the specialists are less prone to inappropriate use of antibiotics and mucolytics than primary care physicians; the mean treatment duration is 13.7 days and the cure rate after 4 weeks is 82.7%; treatment with cyclamen increases the cure rate both when used alone and combined with other treatments; the socioeconomic cost of acute rhinosinusitis is high: 795 euros per event (between 700 million and 1.4 billion euros a year in Spain alone).

The impact of acute rhinosinusitis in the European Union is extraordinarily high. The incidence of the common cold is 100%, while the estimated prevalence of acute rhinosinusitis is 1-2% (with 10-20 million cases/year).

Rhinosinusitis European Union

In an effort to update knowledge and recommendations in the management of this disease, the 2007 update of the EP3OS document has been recently published. Among other contributions, it has established the definition and diagnosis of acute rhinosinusitis for ORL specialists:

Regarding symptoms

Sudden onset of two or more symptoms, one of which should be either Nasal Blockage/Obstruction/Congestion or Nasal Discharge (anterior/posterior nasal drip):

Regarding examination

Regarding imaging

(Plain X-Ray not recommended)

CT Scan is also not recommended unles additional problems are present, such as:

Clinical EP3OS definition of acute rhinosinusitis

The EP3OS guidelines provide a general classification of rhinosinusitis and nasal polyps based on symptom duration and severity. Based on symptom duration, a distinction is made between acute rhinosinusitis (persistence of symptoms for more than 10 days but less than 12 weeks) and chronic rhinosinusitis (symptoms do not completely disappear after 12 weeks). Based on symptom severity (using the VAS (Visual Analogue Scale) scoring system), rhinosinusitis can be mild (VAS ≥ 3), moderate (> 3-7), or severe (VAS >7).

Three basic goals are established for the treatment of rhinosinusitis by otorhinolaryngologists: symptom relief, rapid cure of the disease, and prevention of complications. A series of potential signs of complications are mentioned which should alert the GP to the need to refer the patient to a specialist: reddened eyes, eyeball displacement, double vision, reduced vision, frontal swelling, intense unilateral frontal headache, and signs of meningitis or focal neurological signs.

The EP3OS guidelines provide a series of basic diagnostic and treatment recommendations, which vary depending on the treating physician: Primary Care physicians, non-ORL specialists and ORL specialists. The treatment recommendations for the GP include the following: if symptoms duration is less than 10 days, give symptomatic treatment; however, if symptoms persist beyond this period, the possibility of moderate or severe rhinosinusitis should be considered and, initially, treatment with topical nasal corticoids is indicated. Lastly, in the more serious cases, combined administration of antibiotics and/or topical nasal corticoids is recommended. When these treatment options do not give the expected results, the patient should be referred to the specialist.

Clinical EP3OS definition of acute rhinosinusitis

Considering the levels of scientific evidence and recommendation grades, the first-line drugs for the treatment of moderate/severe acute rhinosinusitis are: oral antibiotics (Ia), antibiotics + intranasal corticoids (Ib), intranasal corticoids alone (Ib), oral corticoids (Ib), and antihistamines (Ib; only for allergy cases). For the moment, there is insufficient consistent evidence to support the efficacy of other treatment resources such as mucolytics, phytotherapy or saline solution.

The recommendations given in the EP3OS guidelines for ORL specialists for the management of acute rhinosinusitis do not vary substantially from those given to GPs. Attention is drawn to the main symptoms of this disease (nasal obstruction and rhinorrhea). If suspected, it is recommended to perform a nasal (endoscopic) and oral examination to rule out the presence of an infection. Plain X-rays of the sinuses are not recommended and CT scans are only indicated for very specific situations (very ill or immunodepressed patients, signs of complications). These patients normally see the specialist because they have been referred by their Primary Care physicians. Consequently, it is considered that in the vast majority of cases, these will be patients with moderate/severe disease. If disease severity is moderate (no improvement after 14 days), the diagnosis should be reconsidered, performing a more thorough examination and starting treatment with corticoids and/or antibiotics. In severe cases (no improvement observed after 48 hours of treatment), the possibility of hospitalising the patient and/or giving a more aggressive treatment (IV antibiotics, oral corticoids and even surgery) should be considered. If complications appear, the EP3OS guidelines suggest referring the patient to a hospital where more exhaustive examinations should be performed (nasal endoscopy, cultures, imaging techniques) and a more powerful treatment can be given (IV antibiotics and/or surgery).

These recommendations are similar for children and there are no major differences from adults in the diagnostic and therapeutic management of acute rhinosinusitis. As treatment resources, there are levels of evidence for oral antibiotics (Ia), topical nasal corticoids alone (IV), topical corticoids + oral antibiotics (Ib), and saline solution douches (IV). For the moment, there are no published data on the efficacy of topical decongestants, among others.

As regards general recommendations, it is advised to give symptomatic treatment for cases of common cold, adding nasal corticoids and/or oral antibiotics when the clear presence of an acute rhinosinusitis is diagnosed.

The Prosinus study

THE PROSINUS STUDY

The pioneering PROSINUS study has been carried out in an attempt to determine the epidemiological impact of rhinosinusitis among Primary Care physicians and Otorhinolaryngology specialists in Spain. This is a multicentre, observational, epidemiological, prospective study evaluating the diagnosis, treatment and monitoring of acute rhinosinusitis by the GP and the specialist in normal clinical practice.

Objectives

1. Primary Objective

2. Secondary objective

The primary goal was to evaluate the diagnostic, treatment and clinical monitoring procedures for acute rhinosinusitis in usual clinical practice. The secondary goals were to describe the biodemographic and clinical profile of the patient with acute rhinosinusitis, evaluate the prevalence of acute rhinosinusitis, assess the degree of application of the European consensus guidelines in the Spanish health system, determine the prevalence of complications of acute rhinosinusitis, evaluate the health-related quality of life of patients with acute rhinosinusitis and analyse patients’ treatment compliance in the management of their disease. In addition, a pharmacoeconomic goal was proposed, studying the socioeconomic impact of acute rhinosinusitis (evaluate the relationship between the resources used and the diagnosis, treatment and evolution of acute rhinosinusitis).

About 300 specialists took part in this study, evaluating more than 1500 patients. The recruitment period ran from November 2006 to July 2007. Patients of either sex, aged over 18, diagnosed with acute rhinosinusitis according to the EP3OS 2005 definition were eligible for inclusion. Patients diagnosed with chronic rhinosinusitis, patients with an intercurrent disease requiring medication that could interfere with the sinonasal disease, and patients with monitoring difficulties or with a high risk of withdrawing prematurely from the study were excluded.

The primary endpoints were disease duration, diagnostic resources, number of visits, medication used and impact of the disease on the patient’s work activity. Other secondary endpoints were also analysed, such as the patients’ epidemiological features, treatment compliance, occurrence of complications and the patients’ degree of satisfaction. The Morisky-Green test was used to determine the patients’ treatment compliance. Visits with the specialist were programmed at baseline and 4 weeks after starting treatment.

The severity of the acute rhinosinusitis was established on the basis of the EP3OS criteria.

The most commonly reported symptoms were the following: nasal obstruction, rhinorrhea, facial pressure/pain, and impaired or lost sense of smell. Most of the symptoms reported by the patients were moderate/severe.

Among the diagnostic tests performed as a result of the current acute rhinosinusitis event and described at the first visit in the PROSINUS study (i.e., those performed before referral to the specialist), the most common were plain sinus X-rays (49%), rhinoscopy or nasal endoscopy (29%), and allergy tests (5%). In General Medicine, the average number of tests performed was 1.2.

The diagnostic tests most commonly performed by the otorhinolaryngologists were rhinoscopy or nasal endoscopy (70%), plain sinus X-rays (34%) and sinus CT scans (14%); the average number of tests performed was 1.3.

Antibiotics were the treatment most frequently prescribed by the GPs for acute rhinosinusitis at the first visit of the PROSINUS study (56%), followed by mucolytics (47%), nasal decongestants (35%), saline solutions (34%), topical nasal corticoids (27%), antihistamines (26%), and phytotherapy products (20%). The mean duration of the treatment for the acute rhinosinusitis before the first visit was 8.7 days. The mean duration of the medication received varied depending on the type of drug administered; the topical nasal corticoids and the antihistamines were the treatments continued for longest.

Therapeutic Options for treat acute sinusitis: Antibiotics, mucolytics, decongestants, saline solutions, corticosteroids, antihistamines, phytoteraphy

DRUG PRESCRIPTION FOR ARS TREAMENT BY GPS AND ENT SPECIALISTS

Antibiotics and mucolytics, or its combinatio,n were mainly used in primary care setting whereas ENT specialists mainly used antibiotics, corticosteroids (oral or topics), antihistamines and, in nearly a half of the cases, phytotherapy (sinus inhalation by GP and cyclamen europaeum by ENT) or its combination.

As regards the treatments given by the otorhinolaryngologist, it was observed that 42% of the patients were prescribed antibiotics, 29% were prescribed topical nasal corticoids and 23% were prescribed antihistamines. A decrease was also documented in the level of use of other drugs, such as nasal decongestants, mucolytics, saline solutions and natural products. A phytotherapy treatment (cyclamen extract) was included in more than half of the cases. The mean duration of the treatment for the acute rhinosinusitis at the second visit was 11.5 days. The time during which topical nasal corticoids and antibiotics were given was particularly long.

The SNOT-16 quality of life test showed the deterioration suffered by these patients in the main health-related quality of life parameters, with a mean score per patient of 2.4 in this test (0-5). More than half of the patients reported having to blow their nose, with continuous and abundant nasal secretion. 44% of the patients reported headache and 37% reported facial pain or pressure. The patients also reported other symptoms that prevented them from leading a normal life (waking up at night, impaired concentration, tiredness). By the second visit, the patients’ quality of life had clearly improved (compared with the first visit), with an average score of 1 (scale, 0-5 points).

TREATMENT IMPLICATIONS

From the treatment viewpoint, the PROSINUS study provides results that invite reflection. 83% of the patients treated by the otorhinolaryngologists are cured (symptom-free) after 4 weeks. This percentage falls to 81% when the cyclamen extract is not included among the treatment resources used and increases to 86% when it is used. As Dr. Mullol stressed, “the cure rate increases 5% with the cyclamen extract, giving statistically significant differences.” The mean treatment duration is 13.7 days.

Addition of cyclamen extract to any other treatment provides, in all cases, an added benefit in terms of cure. Thus, as the Catalan expert explained, “inclusion of this product in an antibiotic treatment regimen increases the cure rate by 15% (72% with antibiotics alone vs. 87% when the cyclamen extract is added, p=NS). Addition of cyclamen extract to treatment with antibiotics + topical nasal corticoids increases the cure rate by 26% (64 vs. 90%; p=0.005). The combined use of decongestants and other drugs also benefits from inclusion of the cyclamen extract, increasing the cure rate by 19% (70% vs. 89%; p<0.04).”

Cure rate (no symptoms) after 4 weeks of ENT treatment

Group with Cyclamen Europaeum showed a significant higher cure rate

Cure rate after 4 weeks versus decongestants

Cure rate after 4 weeks withouth other therapy

The addition of antibiotics to a therapy based on the use of cyclamen extract does not provide any added benefit and the cure rate is not increased after 4 weeks in patients with acute rhinosinusitis. With antibiotic therapy, 76% of the patients are cured after 4 weeks. This percentage increases to 87% when cyclamen extract is used and remains at this percentage (87%) when antibiotics and cyclamen extract are combined. Therefore, in most cases of acute rhinosinusitis, antibiotics do not provide any added benefit if cyclamen extract is given.

COSTS

During the PROSINUS study, a socioeconomic evaluation of the treatment of acute rhinosinusitis was also performed, calculating the direct and indirect costs. This is the first study performed in Spain and Europe that specifically analyses these items.

The direct cost of a rhinosinusitis event (including doctors’ appointments, diagnostic procedures and the cost of medicines) is 261 euros. The indirect cost of a rhinosinusitis event (which includes the cost of days off work) is 534 euros. Thus, the approximate cost of an acute rhinosinusitis event is 795 euros.

It is estimated that each year there are more than 90 million cases of common cold in Spain and between 0.9 and 1.8 million cases of acute rhinosinusitis. On the basis of these figures, it is calculated that the approximate cost of acute rhinosinusitis in Spain ranges between 700 million and 1.4 billion euros a year.

Therefore, the PROSINUS study shows that acute rhinosinusitis is a very common disease condition that affects both men and women. The disease’s symptoms are predominantly moderate or severe and have a substantial impact on the patients’ quality of life. It also shows that plain X-rays of the nasal sinuses are overused both by GPs and by ORL specialists to diagnose acute rhinosinusitis. The specialists are less likely to use antibiotics and mucolytics to treat this disease than GPs. 82.8% of the patients with acute rhinosinusitis are cured during the first four weeks of treatment. This percentage is increased significantly when cyclamen extract is used, either alone or added to any other standard therapy. Lastly, it confirms the substantial socioeconomic impact of acute rhinosinusitis in Spain; the average cost of each case is 795 euros, giving a total annual cost between 700 million and 1.4 billion euros.


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