World Allergy Forum: Non-Allergic Rhinitis and Polyposis
Nasal Polyps and Aspirin-Intolerance
Marek L. Kowalski M.D., Ph.D.
Majority of ASA-sensitive asthmatics challenged with aspirin, in addition to bronchospasm, demonstrate nasal responses heralded by rhinorrhea, sneezing and nasal obstruction, but the nasal responses to aspirin, are superimposed on existing pathology of the upper respiratory tract. These patients suffer from chronic intractable rhinosinusitis with nasal polyposis and persistent asthma of greater than average severity, usually requiring corticosteroids.
The incidence of sinusitis by roentgenogram in ASA-sensitive asthmatics is up to 90% and the frequency of nasal polyps may be as high as 70%, as compared to about 7% in general asthmatic population. It is generally assumed, that chronic rhinosinusitis in ASA-sensitive patients is more severe, than in ASA-tolerant patients: high recurrence of nasal polyps, and frequent need for sinal endoscopic surgery is characteristic for this group of patients.
Using CT scans and scoring system we studied a group of ASA-sensitive patients with chronic rhinosinusitis and nasal polyps, and patients with chronic rhinosinusitis and nasal polyps, but without intolerance. The extend of the disease, assessed by the scoring scale, was significantly higher in ASA-sensitive patients as compared to ASA-tolerant patients.
It is not clear if the basic pathomechanism of chronic airway inflammation in ASA-sensitive patients is different from ASA-tolerant patients with chronic rhinosinusits and nasal polyps. Our recent study demonstrated that density of eosinophils, mast cells, and CD45RO+ cells in nasal polyps from ASA-sensitive patients are significantly higher, than in ASA-tolerant polyps. These data suggest that the basic pathomechanism of chronic airway inflammation may be different in ASA-sensitive and ASA-tolerant patients with hyperplastic rhinosinusitis.
In addition to enhanced inflammatory cell recruitment a delayed programmed cell death ( apoptosis) could be implicated in increased accumulation of inflammatory cells in nasal polyps tissues. Eosinophils due to their abundance in nasal polyps seem to be the primary inflammatory cells regulating and perpetuating inflammation. We have found, that although the density of eosinophils was significantly increased in nasal polyps from ASA-sensitive, the density of apoptotic cells was significantly lower in ASA-sensitive patients as compared to both atopic and non atopic ASA-tolerant patients with nasal polyps. We concluded from this study, that enhanced nasal eosinophilia as well as severity and persistence of nasal polyposis in ASA-sensitive patients might be related to impaired apoptosis in ASA-sensitive patients.
Cellular apoptosis, in addition to cytokines, may be controlled by prostaglandin E2, that is a strong survival factor for eosinophils. However, a significant role for PGE2 in controlling of apoptosis in ASA-sensitive patients seems to be unlikely since we have recently demonstrated, that PGE2 release by epithelial cells (EC) cultured from nasal polyps is significantly lower in ASA-sensitive as compared to ASA-tolerant polyps.
Accordingly, Picado et al.demonstrated, that ASA-sensitive polyps had lower expression of COX-2 as compared to AT polyps indicating, that a lower levels of PGE2 generation noticed in ASA-sensitive patients could result from a decreased expression of COX-2. On the other hand, PGE2 has a significant anti-inflammatory activity, including inhibitory effect on eosinophil chemotaxis and activation, thus an intrinsic defect in local generation of PGE2 may contribute to development of more severe eosinophilic inflammation in ASA-sensitive patients.
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