Open, prospective, multicenter study on postoperative intranasal phototherapy in nasal polyposis.

BACKGROUND: The therapeutic effect of ultraviolet (UV) light is generally attributed to its immunosuppressive and immunomodulatory effects. Since chronic inflammation is the major factor in the development of nasal polyposis, we have previously used mixed ultraviolet-visible light (mUV-VIS, Rhinolight®) phototherapy for the treatment of nasal polyps. AIMS: In the present open, multicenter study, our aim was to delineate whether mUV-VIS applied postoperatively in vivo together with intranasal steroid treatment could reduce the recurrence of nasal polyps. METHODS: After functional endoscopic sinus surgery, one group of patients received mUV-VIS light together with standard intranasal steroid (mometason furoate 2 × 200 µg) application for a 12-week treatment period, whereas the other patient group obtained only intranasal steroid for the same duration. We recorded nasal endoscopy images and obtained demographical and clinical data, total nasal score (TNS), and nasal obstruction symptom evaluation (NOSE). We performed acoustic rhinometry and measured nasal inspiratory peak flow. Follow-up was 12 months. RESULTS: We found that the recurrence of nasal polyps was significantly diminished, and based on video-endoscopic measurements, the size and grade of recurrent polyps were significantly smaller in the phototherapy-receiving group. Nasal obstruction values and NOSE were significantly better throughout the follow-up period in the mUV-VIS light-treated group than in the intranasal steroid monotreatment group. CONCLUSIONS: Rhinophototherapy together with standard nasal steroid application may have a supportive role in the treatment of recurrent bilateral nasal polyps.

Rhinophototherapy in persistent allergic rhinitis.

Previous published results have revealed that Rhinolight® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight® group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight® treatment is safe and effective in persistent allergic rhinitis.

Different activations of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis.

Both up- and down-regulation of the Toll-like receptors (TLRs) and antimicrobial peptides (AMPs) of the sinonasal mucosa have already been associated with the pathogenesis of chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps. The objective of this study was to determine the expression of all known TLR and several AMP genes and some selected proteins in association with allergy, asthma and aspirin intolerance (ASA) in CRS subgroups. RT-PCR was applied to measure the mRNA expressions of 10 TLRs, four defensins, lysozyme, cathelicidin and lactoferrin (LTF) in sinonasal samples from patients with CRSsNP (n = 19), CRSwNP [ASA(-): 17; ASA(+): 7] and in control subjects (n = 12). Protein expressions were detected with immunohistochemistry (n = 10). Statistical analysis was done with the Kruskal-Wallis ANOVA, Mann-Whitney U, and Student t test. TLR2, TLR5, TLR6, TLR7, TLR8, TLR9, ß-defensins 1 and 4, cathelicidin and LTF mRNA expressions were significantly (p < 0.05) increased in CRSwNP, whereas only TLR2 and LTF were up-regulated in CRSsNP compared to controls. There was no statistical difference in respect of allergy, aspirin intolerance and smoking between CRSsNP, ASA(-) and ASA(+) CRSwNP patients. TLR2, TLR3, TLR4, LTF, ß defensin 2 and lysozyme protein expressions were found to be elevated in macrophages of CRSwNP samples (p < 0.05). Gene expression analysis showed markedly different expressions in CRSwNP (6 out of 10 TLR and 4 out of 7 AMP genes were up-regulated) compared to CRSsNP (1/10, 1/7). The distinct activation of the innate immunity may support the concept that CRSsNP and CRSwNP are different subtypes of CRS. These findings were found to be independent from allergy, asthma, smoking, aspirin intolerance and systemic steroid application.

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.

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.

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.

Intranasal PUVA phototherapy in nasal polyposis--a pilot study.

Nasal polyposis (NP) affects 4% of the general population, representing a major health problem. In spite of complex (surgical and medical) treatment, the relapse rate is high and it has a negative impact on the quality of life. Recently we found that intranasal photochemotherapy with ultraviolet A light (PUVA) is effective in allergic rhinitis. In the present study PUVA was administered for 6 weeks in 7 patients with NP. Nasal lavages were performed in all patients before and at the end of the treatment; from four patients a biopsy specimen was also collected. Eosinophils significantly decreased in patients with NP and slightly in a patient who had associated aspirin sensitivity. IL-5 and eosinophil cationic protein (ECP) levels showed a decreasing trend in patients with NP and an increasing trend in patients with associated aspirin sensitivity. Our results suggest that intranasal PUVA might represent a future therapeutic method in a subset of patients with NP.

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.

[Intranasal phototherapy for the treatment of allergic rhinitis]. / Intranasalis fototerápia az allergiãs rhinitis kezelésében.

INTRODUCTION: Allergic rhinitis is a frequent disease, accompanied by significant social-economic costs and a negative impact on the quality of life. Phototherapy has a profound immunosuppressive effect and is effectively used in the treatment of several immune mediated skin diseases such as atopic dermatitis. AIMS: The authors investigated the efficacy of intranasal phototherapy with a combination of low doses of ultraviolet-B, ultraviolet-A and visible light in allergic rhinitis. METHODS: A randomized, double-blind, placebo-controlled study was conducted in patients with a history of at least 2 years of moderate to severe ragweed-induced allergic rhinitis that was not controlled by anti-allergic drugs. Intranasal phototherapy was performed 3 times a week for 3 weeks. As placebo low intensity visible light was used. RESULTS: Phototherapy resulted in a significant improvement of clinical symptoms for nasal itching, rhinorrhea, sneezing and total nasal score. Scores for nasal obstruction slightly improved during phototherapy while a significant increased was found in the placebo group. In the overall efficacy assessment, both patients and investigators found phototherapy significantly more efficient than placebo. Phototherapy was well tolerated, the only side effect was the slight dryness of the nasal mucosa. CONCLUSIONS: These results suggest that intranasal phototherapy is effective for the treatment of allergic rhinitis, and opens up new opportunities for the treatment of immune-mediated mucosal diseases.

Rhinophototherapy: a new therapeutic tool for the management of allergic rhinitis.

BACKGROUND: Phototherapy has a profound immunosuppressive effect and is able to inhibit hypersensibility reactions in the skin. OBJECTIVE: We evaluated whether phototherapy using a combination of UV-B (5%), UV-A (25%), and visible light (70%), referred to as mUV/VIS, is effective in treating allergic rhinitis. METHODS: We conducted a randomized, double-blind study, in 49 patients with hay fever. The study was performed during the ragweed season. Each intranasal cavity was illuminated 3 times a week for 3 weeks with mUV/VIS or with low-intensity visible light. Symptom scores, inflammatory cells, and their mediators were assessed in nasal lavages. In vitro effects of mUV/VIS irradiation on T-cell and eosinophil apoptosis and its inhibitory effect on mediator release from basophils were examined. RESULTS: Rhinophototherapy was tolerated well and resulted in a significant improvement of clinical symptoms for sneezing (P < .016), rhinorrhea (P < .007), nasal itching (P < .014), and total nasal score (P < .004). None of the scores improved significantly in the control group. Scores for nasal obstruction slightly improved after mUV/VIS treatment and significantly increased in the control group (P < .017). In the nasal lavage, phototherapy significantly reduced the number of eosinophils and the level of eosinophil cationic protein and IL-5. In vitro irradiation of T cells and eosinophils with mUV/VIS light dose-dependently induced apoptosis. Furthermore, mUV/VIS irradiation inhibited the mediator release from RBL-2H3 basophils. CONCLUSION: These results suggest that phototherapy is an effective modality to treat allergic rhinitis and offer new options for the treatment of immune-mediated mucosal diseases.