Is There a Role for Leukotriene Antagonists in the Prevention of Recurrent Nasal Polyps?
Is There a Role for Leukotriene Antagonists in the Prevention of Recurrent Nasal Polyps?
Purpose of review The aim of this review is to provide the current available data for leukotriene receptor antagonists in the treatment of nasal polyps, the use in the postoperative therapy single or as an add-on to standard treatments.
Recent findings Surgical treatment of nasal polyps was refined in the last 30 years by the introduction of functional endoscopic sinus surgery and nasal endoscopy for monitoring nasal polyp patients. As the relapse is the main challenge and as nasal steroids only delay it, a more efficient treatment is needed. Leukotriene antagonists have effects on asthma and allergic rhinitis; preliminary data show some benefits in nasal polyps.
Summary In the surgery of nasal polyps, recurrence is the main problem. Steroids are the current standard therapy, but the limitations are obvious. The role of leukotrienes in the disorder of nasal polyps is well established now, and with the antagonists available, interest rose in treating nasal polyps. A total of 356 patients took part in several studies involving leukotriene antagonists in the nasal polyp population. Some studies have minor levels of evidence; the data show positive effects for patients in preoperative and postoperative studies and medical treatments. There were benefits as an add-on to steroids and data from allergic rhinitis studies also show possible synergism with antihistamines. There are hints for a positive effect on eosinophil inflammation, clinical symptom scores, nasal airflow, sneezing and postnasal drip. Although some effects are shown, more controlled studies are necessary for reliable data.
Nasal polyps are an inflammatory disease of the nasal mucosa, and due to modern techniques, local diagnosis and monitoring as well as surgical therapy are established. The focus of this paper is on leukotrienes as one of the most potent mediators of inflammation.
The first mention of leukotrienes as potent mediators in inflammation goes back to the 1930s. Due to the effects of these substances on smooth muscle cells they were named 'slow reacting substance of anaphylaxis'. Later on, they were isolated and detected to be metabolites of the 5-lipoxygenase pathway of arachidonic acid metabolism. They were characterized and because of their main characteristic of three double bonds in the carboxy backbone they were named trienes. Their leucocytic origin gave them the prefix leuko and then they were finally named the leukotrienes A4, B4, C4, D4 and E4 (LTA4, LTB4, LTC4, LTD4 and LTE4), of which the latter is the final product of the human metabolic pathway. There is another way of breaking down arachidonic acid, the so-called cyclooxygenase (COX) pathway resulting in the synthesis of prostaglandins and thromboxanes. This pathway is also of special interest in inflammation as many anti-inflammatory drugs are potent inhibitors of both forms of COX, the COX 1 and COX 2. Therefore, it is easy to understand that defects in the COX pathway or inhibition of the enzymes may result in increased levels of leukotrienes. These increased levels may lead to anaphylactic or better anaphylactoid reactions. The lack of immunoglobulin E antibodies also led to the terminus 'pseudoallergic reaction'. This is one of the main features of so-called aspirin intolerance. Asthma, sinusitis and aspirin (ASA) intolerance are common together in the so-called ASA syndrome or trias. Patients with these conditions are more likely to develop relapse of disease and are more difficult to treat anyway. Leukotrienes are potent inflammatory mediators. They are produced by a number of cell types involved in nasal mucosal inflammation, especially mast cells, basophils, eosinophils and macrophages and monocytes. There is evidence that these cells are involved in nasal airway inflammation and especially in nasal polyp pathogenesis. The pathogenesis of asthma is tightly linked with leukotriene effects. Therefore, the possible therapeutic influence on key inflammatory cells by a well characterized pathway seems possible. Positive inhibition of a long-known player in the field of inflammatory reaction seems to be of crucial interest. With the development of modern drugs to interfere with this pathway, the possibility of a new treatment is on the way.
Abstract and Introduction
Abstract
Purpose of review The aim of this review is to provide the current available data for leukotriene receptor antagonists in the treatment of nasal polyps, the use in the postoperative therapy single or as an add-on to standard treatments.
Recent findings Surgical treatment of nasal polyps was refined in the last 30 years by the introduction of functional endoscopic sinus surgery and nasal endoscopy for monitoring nasal polyp patients. As the relapse is the main challenge and as nasal steroids only delay it, a more efficient treatment is needed. Leukotriene antagonists have effects on asthma and allergic rhinitis; preliminary data show some benefits in nasal polyps.
Summary In the surgery of nasal polyps, recurrence is the main problem. Steroids are the current standard therapy, but the limitations are obvious. The role of leukotrienes in the disorder of nasal polyps is well established now, and with the antagonists available, interest rose in treating nasal polyps. A total of 356 patients took part in several studies involving leukotriene antagonists in the nasal polyp population. Some studies have minor levels of evidence; the data show positive effects for patients in preoperative and postoperative studies and medical treatments. There were benefits as an add-on to steroids and data from allergic rhinitis studies also show possible synergism with antihistamines. There are hints for a positive effect on eosinophil inflammation, clinical symptom scores, nasal airflow, sneezing and postnasal drip. Although some effects are shown, more controlled studies are necessary for reliable data.
Introduction
Nasal polyps are an inflammatory disease of the nasal mucosa, and due to modern techniques, local diagnosis and monitoring as well as surgical therapy are established. The focus of this paper is on leukotrienes as one of the most potent mediators of inflammation.
The first mention of leukotrienes as potent mediators in inflammation goes back to the 1930s. Due to the effects of these substances on smooth muscle cells they were named 'slow reacting substance of anaphylaxis'. Later on, they were isolated and detected to be metabolites of the 5-lipoxygenase pathway of arachidonic acid metabolism. They were characterized and because of their main characteristic of three double bonds in the carboxy backbone they were named trienes. Their leucocytic origin gave them the prefix leuko and then they were finally named the leukotrienes A4, B4, C4, D4 and E4 (LTA4, LTB4, LTC4, LTD4 and LTE4), of which the latter is the final product of the human metabolic pathway. There is another way of breaking down arachidonic acid, the so-called cyclooxygenase (COX) pathway resulting in the synthesis of prostaglandins and thromboxanes. This pathway is also of special interest in inflammation as many anti-inflammatory drugs are potent inhibitors of both forms of COX, the COX 1 and COX 2. Therefore, it is easy to understand that defects in the COX pathway or inhibition of the enzymes may result in increased levels of leukotrienes. These increased levels may lead to anaphylactic or better anaphylactoid reactions. The lack of immunoglobulin E antibodies also led to the terminus 'pseudoallergic reaction'. This is one of the main features of so-called aspirin intolerance. Asthma, sinusitis and aspirin (ASA) intolerance are common together in the so-called ASA syndrome or trias. Patients with these conditions are more likely to develop relapse of disease and are more difficult to treat anyway. Leukotrienes are potent inflammatory mediators. They are produced by a number of cell types involved in nasal mucosal inflammation, especially mast cells, basophils, eosinophils and macrophages and monocytes. There is evidence that these cells are involved in nasal airway inflammation and especially in nasal polyp pathogenesis. The pathogenesis of asthma is tightly linked with leukotriene effects. Therefore, the possible therapeutic influence on key inflammatory cells by a well characterized pathway seems possible. Positive inhibition of a long-known player in the field of inflammatory reaction seems to be of crucial interest. With the development of modern drugs to interfere with this pathway, the possibility of a new treatment is on the way.