PUBLICATIONS
ENT Department- University of Siena Medical School
Nasal polyps are the common end-point of numerous conditions characterized by a flogistic background and a rarely curable (in its true sense) pathology; moreover many aspects of the pathogenetic processes of this disease, are yet subjects of debate among clinicians and researchers1.
Even though naso-sinusal polyposis affects only from 1% to 4% of the adult population, it represents, for physicians in general and for ENT specialists in particular, a important clinical problem, specifically for what concern the high incidence of post-surgical relapses2. We actually know that medical treatment is, in most cases, not sufficient, and the surgical approach in nasal polyposis is only partially resolutive3
When approaching this kind of pathology, major objectives of the medical management should be to eliminate or reduce the size of polyps, to re-establish a valid nasal breathing, to improve or restore the sense of smell and, of course, to prevent the relapses.
In this sense, the efficacy of systemic steroids is well known, but these drugs are of scarce utility in this local pathology for their side effects and their contraindications, such as heart diseases, hypertension, etc.
Topical steroids have rare systemic side effects, and, in spite of the fact that they can cause local side effects such as soreness, epistaxis and candidosis, some Authors consider these drugs as the treatment of choice in the prevention of relapses4. Beclomethasone was the first corticosteroid administered, obtaining a percentage of relapses of 20% after 2 years of follow-up5. Later Flunisolide6 was employed with good results but with only one year's follow up. At last, the efficacy of fluticasone in the post-operative follow up requires further investigations7.
These studies on topic steroids show a quite good rate of success in preventing relapses of polyps, but, unfortunately, they are focused only on short term results, lacking of a long follow up period.
Although we believe these preliminary results are extremely interesting, in our opinion, the correct approach to the treatment of relapses imply a real interference with the early phase of nasal polyps development. According to us, the most important element in this context is the alteration of transmembranal ionic flows leading to an oedematous infiltrate of nasal mucosa 8.
Sodium ions are major determinants in cellular fluids homeostasis. Sodium enters in normal nasal epithelium cell through the baso-lateral surface of the cells in contact with the blood vessels, combined with the entry of chlorine by a non-ATP-ase-dependent form of clearance. There is also an ATP-ase-dependent pump on the baso-lateral surface that accounts for the excretion of sodium and the absorption of potassium. Moreover sodium penetrates into cells through a selective channel following its electrochemical gradient 9.
Major causes of the deregulation of this ionic flows homeostasis are, probably, the mediators of inflammation. The damage caused by these mediators (first of all the Major Basic Protein MBP) leads to an altered regeneration of the epithelial cells and to an uncorrected production of transmembrane channels10. However imbalance of ionic flows occurs also in the absence of inflammatory phenomena as shown by studies carried out using the ultrasonic nebulized distilled water on bronchial and nasal level11; in these cases, the hypotonic solution produces an uncontrolled flow of sodium and calcium with an overactivation of all the functions related to these ions.
According to the above mentioned data, the use of a diuretic of ansa, the furosemide, to prevent the relapses of naso-sinusal polyps and to slow the rate of growing of polyps, acquires a strong rationale.
This drug, by acting (in nasal-epithelial cells), at the level of Na/Cl membrane co-clearance, is able to create a chemical gradient between the interstice and the surface of the epithelium, that leads to a ionic flow of sodium, chlorine and water12. This is the anti-edemagenic effect of furosemide. Moreover it is possible to speculate that the imbalance of sodium and chlorine transmembranal flows will lead to a deregulation of calcium homeostasis at an interstitial and intracellular level.
The depletion of calcium would result in the stabilization of the cells populating the nasal mucosa of polyps prone subjects (eosinophils, neutrophils, lymphocytes, etc) with a block in the formation of oxygen metabolites and in the release of mediators of inflammation (histamine and leukotrienes) and of mitogenic cytokines.
In order to validate this hypothesis, we undertook a study to demonstrate the long term efficacy of intranasal furosemide versus intranasal mometasone furoate and versus the therapeutic abstention in preventing relapses of rhino-sinusal polyps.
We selected 170 patients aged between 19 and 63 and affected by not yet surgically treated bilateral obstructive or sub-obstructive naso-sinusal polyposis.
All patients were surgically treated in our Department: demographical and surgical data are summarized in table 1. In the immediate post-operative period all patients received the standard medical treatment (nasal lavages with physiological solution and emollient oil).
One month after surgery patients were randomly divided into 3 groups: group I consisted of 97 patients, group II consisted of 40 subject, whereas group III included 33 patients. The groups did not differ for what concern severity of the disease before surgery and surgical procedures adopted.
Patients assigned to group I started a treatment with furosemide diluted in physiological solution (2 ml of furosemide in 2 ml of saline) administered as nasal puffs (2 puffs per nostril a day, each puff corresponding to 50 g) for 30 days. The therapy was administered for 1 month and then interrupted for 1 months and so on for the first 2 years (6 months of treatment/year); then patients followed this treatment for 1 month and interrupted it for 2 months during the third, forth and fifth years of treatment (4 months of treatment/year). After 5 years of treatment, furosemide was administered for 1 month twice a year. No specific treatment was administered to group II.
Patients assigned to group III started a treatment with mometasone furoate, a topical corticosteroid, administered as nasal puffs (2 puffs per nostril a day, corresponding to 200 g/day) for 30 days. This treatment was administered with the same therapeutic scheme of group I. Patients were visited every 6 months for a maximum follow up time of 10 years. Every control included: a complete ORL examination, an Active Anterior Rhinomanometry (AAR), an Acoustic Rhinometry (AR), and a nasal endoscopy. We stadiated, by using endoscopic and rhinometric data, relapsing nasal polyposis into 4 classes (see table 2 for details). Patients presenting a residual polyposis after surgical treatment were, obviously, excluded from the study.
Patients treated with furosemide did not have relapses in 82.5% of cases; on the contrary, in the group treated with mometasone furoate and in the not-treated group the percentage of success was 75.8% and 70% respectively.
Moreover, if we consider the severity of relapsing polyps, we found that in group I only 11.8% of relapses belonged to stage 3 of our severity scale, whereas 66.6% of group II — polyps and 12.5% of group III — ones pertained to stage 3 (Table 3).
In conclusion, according to our long term follow up data, furosemide represents undoubtedly an efficacious therapeutic aid in the prevention of nasosinusal polyposis and a valid alternative to corticosteroids, and could represent, if our data will be confirmed by further trials, the treatment of choice for this pathology.
References
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