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Table of Contents
ORIGINAL ARTICLE
Year : 2009  |  Volume : 11  |  Issue : 1  |  Page : 21-24

Effectiveness of intranasal treatment with lysine acetylsalicylate in decreasing the relapse rate of nasal polyposis


Department of Otorhinolaryngology, Ain-Shams University, Cairo, Egypt

Date of Web Publication7-Jan-2020

Correspondence Address:
Youssef Tamer
Department of Otorhinolaryngology, Ain-Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-8491.275321

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  Abstract 


Objective: to examine the effect of long term topical (endonasal) treatment with Acetyl salicylic acid (ASA) on the recurrence rates of nasal polyps after endoscopic polypectomy in both aspirin sensitive and aspirin tolerant patients.
Mehods: In our study we divided the patients into 2 groups: First group (study group): 36 patients with nasal polyps ( 21 men, 15 women ) aged 18-59 years were enrolled in the study. According to ENT indications, all patients underwent endoscopic removal of nasal polyps. About one month after surgery patients underwent intranasal treatment with increasing doses of lysine acetylsalicylate (LAS) corresponding to 450, 900 and 1800 microgram of LAS diluted in 2 ml normal saline and used as local spray in the nose once daily six times/week. Second group (control group): 40 patients with nasal polyps (26 men , 14 women, aged 18-58) who underwent endoscopic removal of nasal polyps and used saline nasal spray only postoperatively (placebo).
Results: The difference between the 2 groups as regard the recurrence rate of the nasal polyps was statistically highly significant with (P<0.001, Fischer’s exact test). No statistical significant difference in the rates of recurrence was found between aspirin tolerant and aspirin sensitive patients (P>0.05).
Conclusion:_In conclusion, the postoperative use of local ASA spray in the nose is safe, cost effective and significantly decreases the rate of recurrence of nasal polyps after surgery in both aspirin tolerant and aspirin sensitive patients.

Keywords:  nasal polyps; recurrence; Acetyl salicylic acid; sinuscopic surgery; aspirin triad.


How to cite this article:
Tamer Y, Medhat T. Effectiveness of intranasal treatment with lysine acetylsalicylate in decreasing the relapse rate of nasal polyposis. Saudi J Otorhinolaryngol Head Neck Surg 2009;11:21-4

How to cite this URL:
Tamer Y, Medhat T. Effectiveness of intranasal treatment with lysine acetylsalicylate in decreasing the relapse rate of nasal polyposis. Saudi J Otorhinolaryngol Head Neck Surg [serial online] 2009 [cited 2022 Dec 4];11:21-4. Available from: https://www.sjohns.org/text.asp?2009/11/1/21/275321




  Introduction: Top


Nasal polyposis is a multifactorial disease with a complex and still not completely understood pathogene-sis. In more than one third of cases it is associated with intolerance to acetylsalicylic acid (aspirin, ASA) or to other non-steroidal anti-inflammatory drugs (NSAIDs)

[1] .- Asprin or acetylsalysalicylic acid is still one of the most widely sold drugs in the world and its side effects are well known. Among these, hypersensitivity reactions represent one of the most frequently described since the first report of urticaria and angio-oedema by Hirshberg

[2] .- An increasing number of reports concerning the existence of a relationship between bronchial asthma and the presence of nasal polyposis in the clinical picture of hypersensitivity reactions to aspirin has been accumulating in the literature since the late 1920s. This association is now so well established since Samter and Beers in 1967 defined the existence of the so called “aspirin disease” characterized by the association of aspirin intolerance, intrinsic bronchial asthma and nasal polyposis (the aspirin triad) [3]. The most accepted theory postulates that the cyclo-oxygenase (COX) block (COX-1 and COX-2) induced by aspirin leads to an increase in arachidonic acid metabolism by an alternative pathway represented by lipoxygenase. This in turn increases the synthesis of leukotrienes C4, D4, and E4 which induce the allergic manifestations [4],[5],[6],[7].

Nasal polyps may benefit from medical treatment (corticosteroids) and surgery, but they frequently relapse soon after surgery with significant morbidity and high social and medical costs. Unfortunately, the effect of treatment with steroids is also often temporary [8].

In the last two decades it has been observed that, in aspirin sensitive patients, oral aspirin desensitization (followed by long term aspirin treatment) often results in an improvement in the clinical course of nasal polyposis [9]. Moreover, Lysine acetyl salicylate (LAS) has been found to have an in vitro non-specific antipro-liferative, dose dependent effect on the growth of fibroblasts of both nasal polyps from aspirin tolerant and aspirin intolerant patients [10].

In this paper we tried to examine the effect of long term topical (endonasal) treatment with ASA on the recurrence of nasal polyps after polypectomy in both aspirin sensitive and aspirin tolerant patients.


  2. Material and Methods: Top


2.1. Subjects: Seventy six patients were included in this study, all diagnosed to have nasal polyposis by means of clinical criteria (ENT examination including rhinoscopy and nasal endoscopy) and CT-scan of the nasal and paranasal cavities. The severity of symptoms (impaired quality of life despite appropriate medical treatment, recurrent infections, mucoceles or other complications) and size of polyps by examination indicated surgery in all patients ( all were grade 3 polyp). Exclusion criteria: Patients not completing the intranasal treatment course or didn’t come for follow up were excluded from the study. Patients with recurrent nasal polyps after previous surgery were also excluded.

According to principles of the Helsinki declaration, informed consent to the entire protocol was obtained from each patient.

This study was conducted from March 2005 till February 2008 in Saudi German hospital and Elite Hospital in Riyadh (Saudi Arabia).

Methods: Complete ENT examination and CT scan of the sinuses were performed every 6-12 months in all patients admitted to the follow up. A nasal provocation test (NPT) with LAS was performed in all subjects. NPT measured by means of anterior rhinomanometry . After measuring basal nasal airflow, non specific hyper reactivity of the nasal mucosa was excluded by measuring nasal airflow before and 10 and 20 minutes after inhaling saline (2ml,09%). We used Aspegic 0.5 gm vial (contains 900mg LAS). We diluted it in 10 ml saline then took one ml of the diluted solution and put it on 100 ml saline so each ml contains 900 microgram LAS. Thereafter, an initial dose of 450 microgram LAS in 2 ml saline was administered (0.5 ml of diluted LAS added to 1.5 ml saline). Nasal airflow was evaluated 10 and 20 minutes after the allergen challenge. Where the NPT response was negative, 900 microgram LAS in 2 ml saline and if further negative 1800 micrograms LAS in 2 ml saline were administered, with an interval of 20 minutes, recording nasal air flow 10 and 20 minutes after inhalation. Nasal air flow was also determined 60 and 360 minutes after the positive response to identify any delayed response.

We divided the patients into 2 groups:

First group (study group): 36 patients with nasal polyps ( 21 men, 15 women ) aged 18-59 years were enrolled in this group. According to ENT indications, all patients underwent endoscopic removal of nasal polyps. About one month after surgery patients underwent intranasal treatment with increasing doses of lysine acetylsalicylate (LAS) corresponding to 450, 900 and 1800 microgram of LAS diluted in 2 ml normal saline and used as local spray in the nose once daily six times/week.

Second group (control group): 40 patients with nasal polyps (26 men , 14 women) aged 18-58 who underwent endoscopic removal of nasal polyps and used saline nasal spray only postoperatively (placebo).

Follow up : Patients were examined every 3 months in the outpatient clinic and radiographs of the paranasal sinuses were obtained every 6 months to detect relapse of the polyps.

Statistical analysis: was done using SPSS version 11 for windows and the difference between the 2 groups regarding relapse, sex and ASA sensitivity were tested using non parametric test (Fisher’s exact test). All statistical tests were 2-tailed and a P value <0.05 was considered statistically significant.


  3. Results Top


Study group:15 patients (41.7%) of the 36 enrolled patients had aspirin sensitivity detected by NPT and in 10 subjects (27.8%) the complete aspirin triad was diagnosed patients were followed up for two years after surgery and continued on LAS spray as local treatment. LAS treatment was well tolerated by all patients and no adverse reactions were observed. Ten patients (27.8%) of this group had relapse of the nasal polyps over the 2 years period [Table 1] ,[Figure 1]. Four patients relapsed in the first year (11.1%) and 6 in the second year (16.7%) [Figure 2]. Four patients of the 10 with the recurrent polyp had ASA intolerance and 6 were ASA tolerant.{Figure 1}

Control group: Eighteen patients (45%) of the 40 patients had aspirin sensitivity detected by NPT and in six (15%) the complete aspirin triad was diagnosed. All patients received saline nasal spray postoperatively as placebo and were followed up for two years after surgery. Twenty nine patients (72.5%) of this group had relapse of the nasal polyps over the two years period . Eighteen patients relapsed in the first year (45%) and 11 in the second year (27.5%) [Figure 1].Twelve patients of the 29 with the recurrent polyp had ASA intolerance and 17 were ASA tolerant.

The difference between the 2 groups as regard the recurrence rate of the nasal polyps was statistically highly significant with (P<0.001, Fischer’s exact test). No statistical significant difference in the rates of recurrence was found between aspirin tolerant and aspirin sensitive patients (P>0.05). No statistical significant difference between the 2 groups was found regarding ASA sensitivity and sex (P>0.05).


  4. Discussion: Top
:

Nasal polyps are the most common benign intranasal tumor. They are associated with other disease states, and their exact etiology is unknown. They frequently relapse soon after surgery with significant morbidity and high social and medical costs. The significant incidence of relapse of nasal polyps highlights the need for a maintenance treatment postoperatively to prevent the recurrence of nasal polypi. Continued topical steroid therapy, anti-histamines and deconges- tants may improve a patient’s symptoms, but they do not prevent recurrence and unfortunately, the effect of treatment with steroids is also often temporary. A study by Hartwig et al from 1998, showed that in first time surgical patients, there was no significant effect in recurrence using nasal steroid spray vs. placebo. They did confirm the benefit of post-operative topical steroids vs. placebo in those patients with recurrent nasal polyposis. However, those who had prior polypectomies had worse polyp scores with placebo than those maintained on nasal steroids [14].

An approach to the treatment of aspirin intolerance, intrinsic bronchial asthma and nasal polyposis (the aspirin triad) is to give aspirin orally after desensitisation since these patients can be desensitized by repeated challenges with aspirin and can then take the drug with impunity [9].)In a subgroup of patients ingestion of aspirin after desensitisation may result in alleviation of nasal symptoms and decreased recurrence of nasal polyps [12].)Desensitisation can be also achieved after repeated intranasal application of lysine aspirin. It has been reported that intranasal desensitisation and prolonged treatment with soluble intranasal aspirin has a beneficial effect on the symptoms of chronic rhinosinusitis and on the recurrence rate of nasal polyps.

However, the studies are limited in number, and their design is open to criticisms. Thus, we conducted a controlled trial to study the clinical effectiveness of topical lysine-aspirin on recurrence of nasal polyps in patients with aspirin-sensitive nasal polyposis and also studied the effect of topical LAS on recurrence of nasal polyps in aspirin resistant patients depending on the fact that the favourable effect of LAS in nasal polyposis is probably due to its non-specific anti-inflammatory properties rather than to desensitization. These findings are confirmed by a previous report [10] of the inhibitory effect of LAS on the growth of cultures of nasal polyps on normal skin fibroblasts from aspirin tolerant and aspirin sensitive patients. It was dose dependent, non-specific, and “cytostatic” since cell viability was always as high as 85%. Patriarca et al [13] reported that the weekly use of intranasal aspirin after desensitisation in patients with aspirin sensitivity significantly reduced the recurrence rate of nasal polyps compared with placebo but in this study they mentioned that patient underwent polypectomy only without mentioning of sinuscopic surgery and they didn’t study the effect of intranasal aspirin on recurrence of nasal polyps in patients having no aspirin sensitivity and the control group received no postoperative treatment and only follow up. In the most recent study in 2005 conducted by Parikh et al [15] they enrolled aspirin-sensitive patients confirmed by intranasal challenge and randomized to receive 16 mg of topical lysine-aspirin every 48 hours or placebo for 6 months. Twenty-two patients were enrolled. After withdrawals and drop outs, data were available on 11 patients for analysis. Statistical analysis of measured parameters did not reveal a significant clinical benefit to patients receiving topical lysine- aspirin compared with placebo. Deterioration was similar while on lysine-aspirin or placebo. They studied the effect of aspirin spray on growth of nasal polyps in aspirin sensitive patients only and the study was limited in patients numbers and the duration of follow up. They did not study the effect on recurrence of nasal polyps after surgery and their conclusion was that their study wass the first controlled clinical trial of topical desensitization in aspirin-sensitive nasal polyp patients and despite the failure to demonstrate clinical benefit, tissue studies have shown a significant improvement at the microscopic level and further works with larger numbers of patients along with conventional treatment may show a clinical improvement in these patients.

In our study, we enrolled 76 patients with nasal polyps all indicated for surgery and all underwent functional endoscopic sinus surgery for removal of nasal polyps by expert surgeons. All patients were tested for salicylate sensitivity using LAS spray and rhinomanometric examination to group patients into aspirin sensitive and aspirin resistant patients. Thirty six patients received postoperative LAS spray and 40 patients received saline spray as control. All patients followed up for 2 years with clinical examination and CT scan to detect polyp recurrence.In contrast to other studies we explained a simple cost effective way to prepare LAS spray from commercial vials available in the market and we detected the recurrence in aspirin sensitive and aspirin tolerant patients.

In conclusion, the postoperative use of local ASA spray in the nose is safe, cost effective and significantly decreases the rate of recurrence of nasal polyps after surgery in both aspirin tolerant and aspirin sensitive patients. In the future we need to compare the ASA topical spray with steroid nasal spray as regard the tolerability, side effects and cost effectiveness.



 
  References Top

1.
Slavin RG, Linford P and Friedman WH: Sinusitis and bronchial asthma. J Allergy Clin Immunol. 1982; 96:102-109.  Back to cited text no. 1
    
2.
D Schiavino, E Nucera, A Milani, M Del Ninno, A Buonomo, J Sun, G Patriarca : The aspirin disease. Thorax. 2000;55(Suppl 2):S66-S69.  Back to cited text no. 2
    
3.
Samter M, Beers RF. Concerning the nature of intolerance to aspirin. J Allergy. 1967; 40:281-286.  Back to cited text no. 3
    
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Szezcklik A. The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J. 1990;3:588-593.  Back to cited text no. 4
    
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Szezcklik A, Stevenson DD. Aspirin-induced asthma: advances in pathogenesis and management.J Allergy Clin Immunol. 1999;104:5-13.  Back to cited text no. 5
    
6.
Sladek K, Szezcklik A. Cysteinyl leukotriene overproduction and mast-cell activation in aspirin-provoked bronchospasm in asthma. Eur Respir J. 1993;6:391-399.  Back to cited text no. 6
    
7.
Knapp HR, Sladek K, Fitzgerald GA. Increased excretion of leukotriene E4 during aspirin-induced asthma. J Lab Clin Med. 1992;119:48-51.  Back to cited text no. 7
    
8.
Holmberg K, Karlsson G. Nasal polyps and medical or surgical management. Clin Experim Allergy. 2000; 26 (suppl 3):23-30.  Back to cited text no. 8
    
9.
Stevenson DD, Hankammer MA, Mathison DA, et al. Aspirin-desensitization treatment of aspirin-sensitive rhinosi nusitic-asthmatic patients: long term outcomes. J Allergy Clin Immunol.1996;98:751-758.  Back to cited text no. 9
    
10.
Bruzzese N, Sica G, Iacopino F, et al. Growth inhibition of fibroblasts from nasal polyps and normal skin by lysine acetyl-salicylate. Allergy. 1998;53:431-434.  Back to cited text no. 10
    
11.
Szezcklik A, Gryglewski RJ, Czirniawska-Mysik G. : Clinical patterns of hypersensitivity to non steroidal antiin-flam matory drugs and their pathogenesis. J Allergy Clin Immunol. 1977;60:276-281.  Back to cited text no. 11
    
12.
Kowalski ML. Management of aspirin-sensitive rhinosinusitis-asthma syndrome: what role for aspirin desensitization? Allergy Proc. 1992;13:175-184.  Back to cited text no. 12
    
13.
Patriarca G, Bellioni P, Bucera E, et al. Intranasal treatment with lysine acetylsalicylate in patients with nasal polyposis. Ann Allergy. 1991;67:588-592.  Back to cited text no. 13
    
14.
Hartwig S, Linden M, Laurent C, Vargo AK, Lindqvist N. Budesonide nasal spray as prophylactic treatment after polypectomy. J Laryngol Otol. 1998;102:148-151.  Back to cited text no. 14
    
15.
Parikh, Abhi A. MS, FRCS(ORL-HNS); Scadding, Glenis K. MD, FRCP: Intranasal Lysine-Aspirin in Aspirin Sensitive Nasal Polyposis: A Controlled Trial. Laryngoscope. 115(8):1385-1390, August 2005.  Back to cited text no. 15
    


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