Brehmer.pdf

For reprint orders, please contact:reprints@expert-reviews.com of allergic rhinitisExpert Rev. Med. Devices 7(1), 21–26 (2010) Allergic rhinitis, although not life threatening, significantly affects the quality of the patient’s daily life. The three major steps in the treatment of the condition are avoidance of allergens, treatment of symptoms (in particular, antihistaminics and topical nasal corticosteroids) and specific immunotherapy. Avoidance of the allergen is usually not possible and symptom relief is often limited, despite the availability of a number of pharmacological options. Specific immunotherapy demands a high level of cooperation on the part of the patient for at least 3 years. Endonasal phototherapy with the Rhinolight® device (Rhinolight Ltd, Szeged, Hungary) for the treatment of immunoglobulin E-mediated allergic rhinitis is a new option that utilizes the immunosuppressive effects of UV radiation. The method directs a combination of UV-B (5%), UV-A (25%) and visible light (70%) into the nasal cavity, and its effectiveness has been demonstrated in one double-blind, placebo-controlled study. The results of additional studies have been presented at various medical conferences and in abstracts. Reports in the literature confirm that phototherapy is a well-established and successful treatment of atopic dermatitis and other skin diseases.
KEYWORDS: allergic rhinitis • phototherapy • Rhinolight® • ultraviolet therapy
Allergies represent one of the greatest health The severity of the symptoms are to be defined problems in modern societies [1]. A tentative on the basis of their intensity and their effect on estimate of the prevalence of allergic rhinitis the patient’s quality of life:(AR) suggests a figure of 500 million suffer- • Mild: symptoms are present but do not impair ers worldwide [2]. This would make AR one of the most common allergic diseases in the world, with increasing prevalence and often • Moderate/severe: symptoms are present and far-reaching consequences for quality of life, since it also reduces the patient’s efficiency In the Allergic Rhinitis and its Impact on and leads to labor and productivity losses [3,4].
Asthma (ARIA) updates, a joint effort of the The condition, therefore, has a significant WHO and the Global Allergy and Asthma socioeconomic impact.
Exposure of the nasal mucosa to various aller- gic stimuli can cause rhinitis. AR is defined clini- treatment for the moderate-to-severe intermit- cally as a symptomatic disease of the nose caused tent and persistent forms of AR [2]. Apart from by a specific type of IgE-mediated inflammation allergen avoidance, SIT is the sole causal thera-of the nasal mucosa triggered by exposure to an peutic concept for the treatment of IgE-mediated allergen. It is classified into a seasonal, a peren- nial and an occupational form. The WHO has
proposed a classification based on the duration Role of immunotherapy in
of the symptoms [2]:
allergic rhinitis
• Intermittent: less than 4 days per week, or less The effectiveness of SIT, both in the sub- cutaneous (SCIT) and sublingual (SLIT) application forms for the treatment of AR, • Persistent: more than 4 days per week, or has been confirmed in double-blind, random- ized, placebo-controlled studies and in various www.expert-reviews.com
Special Report Brehmer
meta-analyses [5,6]. Such studies have shown a high degree of the risk of a serious reaction to SIT is low, the incidence of such effectiveness against tree-, grass- and cereal-pollen allergies, as reactions has increased since the introduction of standardized and well as against those caused by mugwort and ragweed. In the more potent extracts [22]. New routes of application, for exam-case of perennial allergies, a therapeutic effect has been shown ple, intralymphatic injection of allergens, are currently being against house dust mites and animal dander [7,8]. Worldwide, SIT investigated [23].
for the treatment of allergic diseases is very common outside the USA and the UK. In an official report published in 2007, it was Rhinophototherapy
stated that in Great Britain, immunotherapy was not used to its Recently, a rhinophototherapy device, Rhinolight® (Rhinolight
full potential, the reason being partly historical – when early types Ltd, Szeged, Hungary), enabling the application of radiation
of immunotherapy were administered, a number of patients had comprising a combination of UV-B (5%), UV-A (25%) and vis-
suffered anaphylactic shock [9].
ible light (VIS; 70%) to the nasal mucosa in AR patients has The immunological mechanisms of SIT are not fully known. been developed. The utilization of UV radiation in medicine SIT induces clinical and immunological tolerance to the allergens is nothing new and was first employed at the beginning of the employed, with a long-term effect that persists beyond the dura- 19th Century, when Finsen successfully applied phototherapy to tion of treatment. The development of immunological tolerance is heal lupus vulgaris [24]. Since then, phototherapy has been used an active response on the part of the immune system, and involves in various modalities (broadband UV-B [290–320 nm], narrow-a complex interaction between the allergen administered and the band UV-B [311 ± 2 nm], 308 nm UV-B excimer laser, UV-A immune system. The success of the treatment is dependent on the [320–400 nm], photosensitizer and UV-A [PUVA], combined quality of the allergen vaccine (immunological activity) and the UV-A/UV-B, high-dose UV-A1 [340–400 nm] and high-dose duration of its application (the total dose of the allergen extract, VIS [400–800 nm]) in the field of dermatology, for example, to administered for at least 3 years). Since the allergen extracts dif- successfully treat atopic dermatitis and numerous skin diseases [25]. fer in terms of the manufacturing process, each manufacturer UV radiation has a range of biological effects – including local has its own in-house reference preparation (IHRP) to determine and systemic immunosuppression and immunomodulation – but the immunological activity; they cannot be compared directly. also undesired effects, such as induction of premature ageing of According to the present state of our knowledge, the major the skin and skin cancer [26]. The immunosuppressive effect of target cells of SCIT are T lymphocytes. Their function is inhib- UV light is due to the induction of apoptosis [27,28], its influence ited by the activation of regulatory CD4+ T cells, which produce on antigen presentation [29] and the suppression of surface mol-IL-10, TGF-E and mediate tolerance, and by the induction of ecules [30] that play a major role in antigen presentation, and the anergia-reduced responsiveness with decreasing cytokine pro- induction of immunosuppressive mediators [31,32].
duction, and proliferation after stimulation via the T-cell recep- The working group headed by Kemeny showed that application tor [10–12]. The result, over the long term, is a shift in the immune of the 308-nm UV-B excimer laser in the treatment of AR leads response: a dominant TH2 response (e.g., IL-4, IL-5 and IL-13) to a significant improvement in total nasal symptom score (TNS), is replaced by an enhanced TH1 response (IFN-J) [12,13]. but the wheal induced by the skin prick test was inhibited only Secondarily, the immunoglobulin production of the B lympho- at erythematous doses [33]. A study by the same working group cytes changes with induction of the allergen-specific IgG and, in demonstrated that irradiation with a combination of UV-B (5%),
particular, IgG4 production, and possibly a slower reduction in UV-A (25%) and VIS (70%) at suberythematous doses achieved
allergen-specific IgE production. The function of effector cells, a similar inhibitory effect on immediate-type skin reaction, as
such as mast cells, and basophilic leukocytes or eosinophilic with higher erythematous doses of UVB alone [34]. These find-
granulocytes, is inhibited [14]. The immunological mechanisms ings prompted a randomized, double-blind study in 49 patients
of SLIT seem to be similar to those of SCIT – with induction of with hay fever [35]. By comparison with baseline, the individual
tolerance via antigen-presenting cells (APCs) of the oral mucosa scores decreased significantly for sneezing, rhinorrhea and nasal
playing a central role [14,15]. Preserving contact of the allergen itching, but not for nasal obstruction.
with the oral mucosa would appear to be critical for the efficacy
of SLIT [16]. In comparison with SCIT, administration of an at Technique
least 50- to 100-fold subcutaneous dose is recommended for Treatment is applied for 2–3 min, three times a week for 2 con-
SLIT [17]. However, for SIT to be effective, cooperation on the secutive weeks in the seated patient during the pollen season.
part of the patient is necessary – he/she must undergo regu-
During treatment, the patient experiences neither a sensation of lar, usually monthly, injections in the case of SCIT, and daily heat nor pain. A total of six treatments are applied during the 2 administration of the allergen extract when SLIT is employed weeks but not more than four in 1 week. During a session, both – and this regimen is generally maintained for a minimum of the patient and the physician must wear glasses that protect their 3 years. The literature reports compliance figures of between eyes against UV light. The first treatment is frequently followed 44 and 88% for SCIT, and between 76 and 97% for SLIT [18,19].
by deterioration in symptoms. Prior to each session, the patient is The risk of an anaphylactic reaction to SIT is feared by both required to clear his nose. Before phototherapy is begun, the endo- physicians and patients alike. Fatalities and serious side effects nasal mucosa is treated with decongestant nose drops to ensure have been reported both for SCIT and SLIT [20,21]. Although that the maximal surface area of the mucosa is irradiated. A nasal Expert Rev. Med. Devices 7(1), (2010) Endonasal phototherapy with Rhinolight® in allergic rhinitis Special Report
adapter screwed to a special device is introduced into the nasal group comprising 34 patients was formed. The parameters inves-vestibule. This device is connected to the equipment by a light- tigated were the TNS and the Rhinoconjunctivitis Quality of Life conducting cable. During irradiation, the physician gently rotates Questionnaire (RQLQ) [43]. The results showed a statistically the device in order to avoid the radiation being concentrated on a significant improvement in all the variables in the phototherapy single point. For the duration of the treatment, the nasal mucosa group. In all cases, endonasal phototherapy was well tolerated, is treated with emollients.
the sole side effect being dryness of the nasal mucosa during the treatment, which, however, responded well to emollients. Not a Efficacy & safety
single case of serious side effects occurred.
The effectiveness of endonasal phototherapy has been investi- It has been shown in vivo and in vitro that endonasal gated in seven studies involving 537 patients. In a randomized, photo therapy actively suppresses the effector phase of AR at controlled, double-blind study, 49 patients with ragweed-induced multiple points:hay fever who were unresponsive to anti-allergy drugs were evalu- • Reduction of the antigen-presenting capacity of APCs ated [35]. The two groups did not differ in terms of their anthro-pometric data, disease duration or symptoms score. In compari- • Induction of apoptosis of immune cells (dendritic cells, T-cells, son with baseline, this study showed a significant improvement in the clinical symptoms of sneezing (p < 0.016), rhinorrhea • Inhibition of synthesis and release of proinflammatory (p < 0.007), nasal itching (p < 0.014) and TNS (p < 0.004) mediators from eosinophils, mast cells, basophils and T-cells in the treatment group. None of the scores improved signifi-cantly in the control group. Examination of nasal lavage samples The major molecular target for UV-induced immuno- showed effects on eosinophils and inflammatory mediators. The suppression is UV-induced DNA damage [22]. It is this very point authors found significantly lower concentrations of eosinophils, that prompts criticism of endonasal phototherapy, expressed as a eosinophilic cationic protein and IL-5 in the treatment group. fear that endonasal phototherapy might have a carcinogenic effect In a smaller, double-blind, placebo-controlled study, 67% of the on the nasal mucosa. A study has investigated the extent of DNA treated patients experienced a significant improvement in symp- damage prior to and following a 2-week endonasal phototherapy toms [36]. In an open, multicentric study of 70 ragweed patients, session [44]. The chemical evaluation was performed in the labo-the overall efficacy assessment showed a significant inhibition of ratory and immunohistochemical investigations conducted on the clinical symptoms in 90% of the patients [37]. Another study the nasal cytology samples prior to the initiation of treatment, involving 37 patients (15 with intermittent and 22 with persistent and immediately after the final session, 10 days thereafter and AR) provided similar results [38].
then 2 months after the last application. A significant increase in In a study including 59 patients with a history of at least 2 years DNA damage was found in the mucosa immediately following the of ragweed-induced AR treated with endonasal phototherapy, 38 last therapeutic session. The damage had decreased significantly (64%) patients experienced a decrease of more than 50% in the 10 days later and was comparable with baseline: 2 months later, average change in the TNS [39].
the findings were comparable with those seen in healthy control In an open study, the effectiveness of endonasal photo therapy persons. Mitchell et al. investigated DNA damage and repair after was compared with the effect of the antihistamine fexo fenadine a single UV irradiation (combination of UV-C, UV-B, UV-A hydrogen chloride (120 mg) in patients with ragweed AR. TNS and some VIS) of human nasal mucosa in 30 adults [45]. Nasal was decreased significantly in the endonasal phototherapy group cytology samples were taken prior to, and immediately after, treat-(p = 0.00003) but no significant change was seen in the fexo- ment, and 24, 48 and 72 h later. DNA damage in samples taken fenadine hydrogen chloride group [40]. Bella et al. investigated the immediately after UV irradiation was measured in all subjects and effect of endonasal phototherapy in 243 patients with grass-pollen was significantly greater than that at baseline. The DNA damage AR [41]. One group received endonasal phototherapy alone, while at 24, 48, and 72 h showed no significant difference compared the other group received, in addition to endonasal phototherapy, a with baseline. In a second investigation in the same study, DNA once-daily oral dose of an antihistamine or a nasal steroid (maxi- damage to, and repair of, nasal epithelium was evaluated in nasal mum: 400 μg/day). However, only 75 patients were evaluated. cytology samples before and after nine treatments applied over Nasal symptoms were improved significantly in each group. In 3 consecutive weeks. At 1 and 4 weeks after the final treatment, the group receiving endonasal phototherapy alone, 6% of the DNA damage had returned to the original baseline level. The patients experienced a worsening of their symptoms compared authors conclude that human nasal mucosa is capable of efficiently with 5% in the group receiving phytotherapy and medication. repairing UV-induced DNA damage. Earlier studies performed No change in symptoms was seen in 19% of the phototherapy on bronchial fibroblasts and epithelial cells established DNA versus 8% of the phototherapy plus medication groups. On a repair similar to that seen in human skin fibroblasts, suggesting visual analog scale, 75% of the patients receiving monotherapy that there is no difference in DNA repair mechanisms among indicated an improvement, in comparison with 87% of the group different cell types [46]. Lee et al. evaluated all prospective and receiving combined treatment. Cingi et al. prospectively investi- retrospective studies identified in Medline between 1966 and June gated the action of the endonasal phototherapy and its effect on 2002 with a view to estimate the risk of skin cancer associated quality of life in 100 patients with intermittent AR [42]. A control with UV-B phototherapy, but found no increased skin cancer risk Special Report Brehmer
associated with UV-B phototherapy [47]. In another, more recent, septal deviation or massive nasal polyposis. Phototherapy is also study involving 3867 patients treated with narrow-band UVB contraindicated in acute rhinosinusitis, in the presence of tumors phototherapy, no association was found between narrow band of the nasal mucosa, sinuses or nasopharynx. Prior to the applica-UV-B exposure alone and any skin cancer [48].
tion of endonasal phototherapy, it is most important to ensure that The surface area of each nasal cavity per nostril is 20 cm2, and the patient is not taking photosensitizing drugs. Advantages of UV-A accounts for 25% and UV-B for 5% of the total emission this form of treatment are its good tolerability and repeatability. energy. Using the treatment protocol for seasonal AR, comprising The application is simple and painless, and possible side effects six sessions, the total treatment time is 930 s. For six treatments, the such as dryness of the nasal mucosa or crusting can readily be cumulated dose of UV-B is 4185 J/m2 and of UV-A, 20925 J/m2. treated by appropriate nasal care.
The average UV exposure of males and females in the southern Although investigations into the safety of endonasal photo- hemisphere (e.g., 34° South) varies between 29,000 J/m2 for indoor therapy suggest that UV-induced damage to nasal mucosa is workers and 95,000 J/m2 per year for outdoor workers [49]. efficiently repaired [44–46], a degree of uncertainty remains with regard to the possibility of cancerogenicity, since long-term inves- Expert commentary & five-year view
tigations are still lacking. The author is, therefore, of the opinion Research into the development of endonasal phototherapy of AR that the number of treatment regimes per patient should be lim-was begun in 1999 by researchers at the dermatological clinic ited to a single regime per year. The equipment has been awarded and the Faculty of Science at the University in Szeged, Hungary.
a Conformité Européene (CE) mark and thus meets the require- In the meantime, according to the manufacturer of the device, ments of the EU guidelines on health and safety. Since endonasal endonasal phototherapy is employed in the following 19 coun- phototherapy is, at present, not performed in the UK, Rhinolight tries: Hungary, Slovakia, Romania, Serbia, Croatia, Poland, has not been recognized by NICE. Bulgaria, Greece, Austria, Switzerland, the Ukraine, Russia, Owing to its novelty and some as yet unresolved questions, Germany, Italy, Portugal, Turkey, Hong Kong, South Korea and endonasal phototherapy should be considered an effective alterna-Japan. Over the last 5 years, approximately 10,000 patients have tive, but not be promoted to, first-line therapy for AR. Allergies been treated with this modality worldwide, with half of the treat- are on the increase worldwide, and there is a need to develop ments being carried out in Hungary. Endonasal phototherapy treatments that work rapidly on symptoms and do not lose their can readily be performed during the pollen season, does not take effectiveness over time. When long-term studies have confirmed long and relieves the patient of their symptoms. Endonasal photo- the safety of this form of treatment and the persistence of its therapy represents an alternative form of treatment in patients effect, endonasal phototherapy will play an important role in the
who refuse medication (e.g., drugs, SCIT or SLIT), who have treatment of AR – as it already does in the field of dermatology.
experienced a severe side effect with SCIT or SLIT, in whom
drug treatment produced no, or only inadequate, effects, or who Financial & competing interests disclosure
were unable to undergo SIT owing to contraindications (inad-
The author has no relevant affiliations or financial involvement with any equately treated asthma and/or irreversible airway obstruction, organization or entity with a financial interest in or financial conflict with severe cardiovascular disease, local or systemic treatment with the subject matter or materials discussed in the manuscript. This includes E-blockers, inadequate compliance, pregnancy, nursing, or they employment, consultancies, honoraria, stock ownership or options, expert were a competitive athlete). Contraindications for endonasal testimony, grants or patents received or pending, or royalties.
photo therapy include anatomical variations, such as a pronounced No writing assistance was utilized in the production of this manuscript. Key issues
• Allergic rhinitis (AR) is an increasing global health problem, and the costs it incurs are substantial. In the UK, direct NHS costs for the management of allergic problems are estimated at more than GB£1 billion per annum.
• Untreated AR has a major influence on a patient’s ability to sleep, their quality of life and cognitive function, and on • According to the WHO, AR must be considered a risk factor for the development of asthma.
• AR is a symptomatic disorder of the nose induced by IgE-mediated inflammation after allergen exposure of the membranes lining • The backbone of its treatment is avoidance of allergens, use of drugs and specific immunotherapy.
• The radiotherapy device Rhinolight® is effective agaist AR.
• The application of endonasal phototherapy has, to date, been free from serious side effects.
• Endonasal phototherapy is an effective alternative when specific immunotherapy is contraindicated or when when antiallergic medication is not tolerated, associated with side effects or is inadequate. • Data on long-term efficacy and safety are mandatory. Efforts should be undertaken to re-evaluate those patients who have • Provided that long-term studies confirm the effectiveness and safety of endonasal phototherapy, it will have an important role to play Expert Rev. Med. Devices 7(1), (2010) Endonasal phototherapy with Rhinolight® in allergic rhinitis Special Report
References
12 Jutel M, Pichler WJ, Skrbic D, Urwyler A, Papers of special note have been highlighted as: immunotherapy results in decrease of IL-4 sun? J. Am. Acad. Dermatol. 46(6), and IL-5 and increase of IFN-J-secretion in specific allergen-stimulated T cell cultures. Meltzer EO, Nathan R, Derebery J et al. Sleep, quality of life, and productivity J. Immunol. 154(8), 4187–4194 (1995).
phototherapy. Clin. Dermatol. 21(5), States: findings from the Burden of Rhinitis treatment of allergic disease in the big picture in America survey. Allergy Asthma Proc. of regulatory T cells. J. Allergy Clin. Immunol. 123(4), 735–746 (2009).
to phototherapy. Methods 28(1), 138–144 Bousquet J, Khaltaev N, Cruz AA et al. Allergic Rhinitis and its Impact on Asthma allergen-specific immunotherapy. J. Allergy Demonstrates the mechanisms
(ARIA) 2008 update (in collaboration with Clin. Immunol. 119(4), 780–791 (2007).
underlying phototherapy.
Novak N, Haberstok J, Bieber T, Allam JP. and AllerGEN. Allergy 63(Suppl. 86), 27 Novák Z, Bérces A, Rontó G, Pállinger E, The immune privilege of the oral mucosa. Trends Mol. Med. 14(5), 191–198 (2008).
different UV-emitting light sources in the Gupta R, Sheikh A, Strachan DP, Anderson Pfaar O, Klimek L. Efficacy and safety of induction of T-cell apoptosis. Photochem. HR. Burden of allergic disease in the UK: specific immunotherapy with a high-dose Photobiol. 79(5), 434–439 (2004).
secondary analyses of national databases. sublingual grass pollen preparation: a double- Clin. Exp. Allergy 34(4), 520–526 (2004).
28 Matz H. UV light and its interaction with blind, placebo-controlled trial. Ann. Allergy cutaneous receptors. Dermatol. Clin. Bunnag C, Jareoncharsri P, Tantilipikorn P, Asthma Immunol. 100(3), 256–263 (2008).
and current status of allergic rhinitis and 29 Toews GB, Bergstresser PR, Streilein JW. asthma in Thailand – ARIA Asia–Pacific rhinitis and its impact on asthma. J. Allergy Workshop report. Asian Pac. J. Allergy Clin. Immunol. 108(5 Suppl.), 147–343 Immunol. 27(1), 79–86 (2009).
J. Immunol. 124(1), 445–453 (1980).
completion of optimal dose, multiple allergen 30 Weiss JM, Renkl AC, Denfeld RW et al. immunotherapy. Ann. Allergy Asthma analysis. Allergy 60(1), 4–12 (2005). Immunol. 82(3), 281–286 (1999).
Passalacqua G, Musarra A, Pecora S et al. Quantitative assessment of the compliance Langerhans cells. Eur. J. Immunol. with a once-daily sublingual immunotherapy allergic rhinitis. Cochrane Database Syst. Luger TA. Inhibition of the induction of During a Year). J. Allergy Clin. Immunol. AJ. Usefulness of specific immunotherapy in mediated epidermal cytokine. J. Invest. patients with severe perennial allergic rhinitis 20 Blazowski L. Anaphylactic shock because of Dermatol. 87(2), 289–291 (1986).
induced by house dust mite: a double-blind, sublingual immunotherapy overdose during randomized, placebo-controlled trial. Clin. 32 Shreedhar V, Giese T, Sung V W, Ullrich third year of maintenance dose. Allergy Exp. Allergy 33(8), 1076–1082 (2003).
immune suppression. J. Immunol. 160(8), academy of allergy, asthma and immunology. twelve-year survey of fatal reactions to standardized cat extract. J. Allergy Clin. Highlights the mechanisms by which
Immunol. 111(1), 155–161 (2003).
UV radiation causes systemic
1990–2001. J. Allergy Clin. Immunol. immune response.
Allergy, Volume 1: Report. The Stationary 33 Csoma Z, Ignacz F, Bor Z et al. Intranasal 22 Applegate LA, Ley RD, Alcalay J, Kripke ML. Identification of the molecular target Francis JN, Till SJ, Durham SR. Induction for the suppression of contact hypersensitivity rhinitis. J. Photochem. Photobiol. B. 75(3), by ultraviolet radiation. J. Exp. Med. 170(4), pollen immunotherapy. J. Allergy Clin. Immunol. 111(6), 1255–1261 (2003).
34 Koreck A, Csoma Z, Boros-Gyevi M et al. 23 Martínez-Gómez JM, Johansen P, Erdmann Akdis CA, Blaser K. IL-10-induced anergy in peripheral T cell and reactivation by irradiation with ultraviolet and visible administration route for allergen-specific light. J. Photochem. Photobiol. B. 77(1–3), steps in specific immunotherapy. FASEB J. immunotherapy. Int. Arch. Allergy Immunol. Special Report Brehmer
Koreck AI, Csoma Z, Bodai L et al. •• Identifies similar DNA repair in bronchial
Rhinophototherapy: a new therapeutic tool Rhinophototherapy in grass pollen induced fibroblasts and epithelial cells as in
for the management of allergic rhinitis. allergic rhinitis. WAO J. DOI: 10.1097/01.
human skin fibroblasts. The authors
J. Allergy Clin. Immunol. 115(3), 541–547 conclude that DNA repair mechanisms
are equally efficient in all cell types.
•• Describes the efficacy of phototherapy in
Lee E, Koo J, Berger T. UVB phototherapy allergic rhinitis.
phototherapy on quality of life in allergic 36 Robert F. Shine on allergic rhinitis with literature. Int. J. Dermatol. 44(5), 355–360 rhinophototherapy. Family Prac. News rhinitis cases. Eur. Arch. Otorhinolaryngol. 48 Hearn RM, Kerr AC, Rahim KF, Ferguson 43 Juniper EF, Guyatt GH. Development and 37 Koreck A, Csoma Zs, Kenderessy Szabó A J, Dawe RS. Incidence of skin cancers in et al. Rhinophototherapy improves allergic testing of a new measure of health status rhinitis by inducing apoptosis in T cells for clinical trials in rhinoconjunctivitis. ultraviolet B phototherapy. Br. J. Dermatol. and eosinophils and inhibiting histamine Clin. Exp. Allergy 21(1), 77–83 (1991).
release from mast cells. Presented at: XXIII. 44 Koreck A, Szechenyi A, Morocz M et al. •• Summarizes the association between
Effects of intranasal phototherapy on nasal narrow band UV-B treatment and basal
mucosa in patients with allergic rhinitis. cell carcinomas, squamous cell carcinomas
J. Photochem. Photobiol. B. 89(2–3), and melanomas.
Phototherapy for allergic rhinitis – our •• Found that nasal mucosa exposed to UV
Photochem. Photobiol. 81(4), 736–749 Otorhinolaryngol. Head Neck Surg. light posses the capacity to repair
UV-induced DNA damage.
Mitchell D, Paniker L, Sanchez G et al. Affiliation
39 Boros-Gyevi M, Garaczi E, Koreck A, Széll M, Kemény L. Studies on the role of tumor ultraviolet radiation. J. Cell. Mol. Med. the therapeutic response to intranasal UV phototherapy. WAO J. DOI: 10.1097/01.
University of Witten/Herdecke, Faculty of •• Demonstrates the capacity of airway
mucosa to repair after UV-induced DNA
damage and compare it with the
Kemény L. Intranasal phototherapy is more biological response of a tissue that is not
effective than fexofenadine hydrochloride normally exposed to UV-radiation.
in the treatment of seasonal allergic rhinitis. Clin. Immunol. 115(Suppl. 1), 50 46 Fornace AJ Jr, Lechner JF, Grafstrom RC, Harris CC. DNA repair in human bronchial epithelial cells. Carcinogenesis 3(12), 1373–1377(1982).
Expert Rev. Med. Devices 7(1), (2010)

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