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The -308 G>A SNP of TNFA is a factor predisposing to chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarian individuals: Conclusions of a genetic study with multiple stratifications

Single nucleotide polymorphisms (SNPs) of the tumour necrosis factor alpha (TNFα) gene (TNFA) have been extensively studied and shown to be associated with an increased risk of the development of various chronic inflammatory diseases. Inflammation has been demonstrated to play a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNFα is a key pro-inflammatory cytokine with important functions in these processes. In order to determine whether the well-known TNFA -308 G>A SNP has a role in a genetic predisposition to CRS in the Hungarian population, we analyzed our genomic collection containing control and CRS patient samples in a case-control study, and compared the genotype and allele frequencies. There was no significant difference in the observed genotype or allele frequencies between the controls and the total CRS group. However, after careful stratification of the patient group on the basis of the observed clinical symptoms, we found a significantly higher carriage rate of the rare A allele-containing genotypes among the CRS patients with nasal polyposis (NP) who also exhibited sensitivity to aspirin (acetylsalicylic acid, ASA(+)). It is concluded that genetic variants of the TNFA gene may affect the risk of CRS in a clinically well-defined group of CRSNP(+)ASA(+) patients in the Hungarian population. Our results also emphasize that the group of CRS patients is not homogenous in that patients exhibiting different clinical symptoms exist. Their carried genetic predisposing factors, and as a result, the exact molecular events leading to the development of various forms of CRS, may also differ.

Narrow-band UVB phototherapy of nasal polyps: results of a pilot study.

Nasal polyposis (NP) is characterized by high recurrence rate despite medical and/or surgical treatment. The major mechanism of action of ultraviolet B light (UVB) is induction of apoptosis in inflammatory cells. Therefore phototherapy may represent a new therapeutic approach in NP. A pilot feasibility study was performed to assess the tolerability and clinical efficacy of UVB phototherapy in NP. Thirteen subjects with bilateral grade 1-3 NP were enrolled in an open-labeled prospective pilot study. Patients were exposed to gradually increasing doses of UVB light over a 12 week period (3 exposures/week). Subjects rated their nasal obstruction symptom scores weekly on a visual analogue scale from 0 to 6. The NOSE quality of life questionnaire was used at baseline and end of treatment period. Adverse events were monitored by endoscopy. Ten subjects completed the study. Nasal obstruction symptom scores and quality of life (NOSE) improved at end of treatment compared to baseline. Treatments were well tolerated and no device related adverse events were reported. The results suggest that phototherapy may represent a potential new treatment option in nasal polyps.

Ultraviolet light and photodynamic therapy induce apoptosis in nasal polyps

Intranasal phototherapy has been found to be effective for the treatment of nasal polyposis (NP) therefore the aim was to investigate the apoptosis inducing effect of phototherapy in NP. In this ex vivo study nasal polyp tissue was surgically collected from 21 consecutive patients with chronic rhinosinusitis (CRS) associated with NP. The removed polyps were cut into pieces and tissue samples were irradiated in vitro by different doses of combined ultraviolet and visible light (UV/VIS: 280-650 nm) and by selective ultraviolet and visible light (sUV/VIS: 295-650 nm). Photodynamic therapy (PDT) was performed by presensitizing tissue samples with 5-delta-aminolevulinic acid (DALA) then irradiated with visible light (VIS: 395-650 nm). Tunel assay was applied to detect apoptosis of epithelial and inflammatory cells in irradiated and control nasal polyp tissue samples. UV/VIS light significantly increased epithelial cell and subepithelial leukocyte apoptosis compared to control groups. PDT treatment showed the highest surface epithelial cell as well as subepithelial leukocyte apoptosis compared to all other groups. Intranasal phototherapy may serve as a new potential therapeutical method in treatment of NP.

A conserved linkage group on chromosome 6, the 8.1 ancestral haplotype, is a predisposing factor of chronic rhinosinusitis associated with nasal polyposis in aspirin-sensitive Hungarians

Inflammation plays a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNFα is a key pro-inflammatory cytokine in the pathogenesis of this disease. In our previous studies, we showed that the TNFA -308A allele is a genetic predisposition factor in a subgroup of aspirin-sensitive (ASA+) CRS patients suffering from nasal polyps (NP) in the Hungarian population. To determine whether the TNF -308A allele or the presence of a complex, extended ancestral haplotype (8.1AH) located on chromosome 6 is responsible for the previously observed genetic effect, we performed a case-control study for examining the frequency of 8.1AH carriers in controls and in subgroups of CRS patients. Our novel observations demonstrate that the presence of the 8.1AH may be responsible for the development of severe forms of CRS (CRSwNP, ASA+) and strengthen the clinical observation that CRS patients can be classified into clinically and genetically different subgroups.

S286 – UV Phototherapy of Nasal Polyps: Results of a Pilot Study

Objectives Nasal polyps (NPs) are characterized by high recurrence rates despite medical and\or surgical treatment. Recently, it has been shown that exposure of NPs to ultraviolet light (UV) results in induction of apoptosis of inflammatory cells. Therefore phototherapy may represent a new therapeutic approach in NPs. A pilot feasibility study was performed to assess the clinical efficacy and tolerability of phototherapy and to identify the clinical effective UV dose range in NPs. Methods A dose-titration study was conducted in 13 subjects with bilateral grade 1–3 NPs. Patients were exposed to gradually increasing doses of UV light over a 12-week period (3 exposures/week). Subjects rated their nasal obstruction symptom scores weekly on a visual analogue scale from 0 to 6. The NOSE quality of life questionnaire was used at baseline and end of treatment period. Adverse events were monitored by endoscopy. Results 10 subjects completed the study. Nasal obstruction symptom scores improved at end of treatment compared to baseline. Improvement of quality of life (NOSE) at end of treatment compared to baseline was also noted. Treatments were well tolerated and no device-related adverse events were reported. In most subjects, symptom improvement was observed after a certain threshold UV dose was reached. Therefore, the study was also informative about the clinically effective doses which will be tested in future studies of much shorter duration. Conclusions The results suggest that phototherapy may represent a potential new treatment option in NPs.