Effects of intranasal phototherapy on nasal mucosa in patients with allergic rhinitis

https://doi.org/10.1016/j.jphotobiol.2007.09.013Get rights and content

Abstract

Rationale

Rhinophototherapy has been shown to be effective in the treatment of allergic rhinitis. Considering that phototherapy with ultraviolet light (UV) induces DNA damage, it is of outstanding importance to evaluate the damage and repair process in human nasal mucosa.

Methods

We have investigated eight patients undergoing intranasal phototherapy using a modified Comet assay technique and by staining nasal cytology samples for cyclobutane pyrimidine dimers (CPDs), which are UV specific photoproducts.

Results

Immediately after last treatment Comet assay of nasal cytology samples showed a significant increase in DNA damage compared to baseline. Ten days after the last irradiation a significant decrease in DNA damage was observed compared to data obtained immediately after finishing the treatment protocol. Difference between baseline and 10 days after last treatment was not statistically significant. Two months after ending therapy, DNA damage detected by Comet assay in patients treated with intranasal phototherapy was similar with that of healthy individuals. None of the samples collected before starting intranasal phototherapy stained positive for CPDs. In all samples collected immediately after last treatment strong positive staining for CPDs was detected. The number of positive cells significantly decreased 10 days after last treatment, but residual positive staining was present in all the examined samples. This finding is consistent with data reported in skin samples after UV irradiation. Cytology samples examined two months after ending therapy contained no CPD positive cells.

Conclusion

Our results suggest that UV damage induced by intranasal phototherapy is efficiently repaired in nasal mucosa.

Introduction

Phototherapy is widely used for the treatment of several immune-mediated skin diseases like atopic dermatitis and psoriasis [1]. In the last decade new applications have been developed and ultraviolet (UV) light has been applied with good results in the treatment of oral mucosal diseases, such as lichen planus and graft versus host disease [2], [3]. Recently, intranasal phototherapy with mixed UVA–UVB–visible light (mUV/vis) has been reported to be successful for the treatment of seasonal allergic rhinitis [4].

One of the main mechanisms of action of UV light is induction of DNA damage in the irradiated cells. This mechanism is responsible in part for the biological effects of UV light and consequently its therapeutic use. However, DNA damage is also implicated in the mutagenic and carcinogenic potential of UV light. Knowledge of the mutagenic risk of DNA photodamage has stimulated interest to determine the wavelengths dependent distribution of different DNA photodamage types [5], [6]. UV light is able to cause DNA damage by direct mechanisms (absorption of photons by the DNA) or by indirect mechanisms such as generation of reactive oxygen species [6]. UVC (100–280 nm) has been shown to induce direct DNA damage, mirrored by the preponderant production of promutagenic photoproducts, mainly cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6-4 PPs). UVB (280–320 nm) radiation is also acting mostly on DNA through direct excitation processes and results in the formation of CPDs and to a lesser extent of 6-4 PPs. It has been reported that UVC and UVB induced photodamage is more complex including also induction of strand breaks and oxidative DNA modifications [6], [7]. Until recently, the formation of single-strand breaks, alkali-labile lesions and oxidative DNA modifications has been considered to be the main mechanism of UVA (320–400 nm) damage. Recent data showed that UVA induces in bacteria, cultured cells and human skin the formation of CPDs but not 6-4 PPs [8].

Cells possess repair mechanism in response to UV induced DNA damage. The primary process that removes DNA damage is the nucleotide excision repair (NER) pathway. The removal of DNA base modifications via NER requires DNA damage recognition, lesion demarcation, dual asymmetrical incisions at the 5′ and 3′ sites flanking the lesion, excision of nucleotides from the single-stranded loop, containing the lesion, and gap-filling by DNA synthesis and ligation [9]. Alternatively, highly damaged cells undergo cell cycle arrest, activation of the caspase cascade and finally apoptotic cell death [10].

Although, skin diseases are successfully treated with phototherapy and data from the literature support that no significant increase in skin cancer risk is present in patients treated for decades with UVB light, no data are available regarding the effect of UV light on nasal mucosa.

In the present study we have evaluated the in vivo effect of intranasal phototherapy, by assessing DNA damage and repair in nasal mucosa.

Section snippets

Intranasal phototherapy of ragweed allergic patients

The examinations were performed during the 2005 ragweed season in Szeged, Hungary in eight ragweed allergic patients undergoing intranasal phototherapy. Positive skin prick tests and/or an elevated level of ragweed-specific IgE antibody confirmed the diagnosis. We excluded potential subjects from the study if they had any significant nasal structural abnormalities, or had had asthma, perennial rhinitis or upper or lower respiratory infection within 4 weeks prior to the beginning of the study,

Kinetics of DNA damage detected by Comet assay in patients undergoing intranasal phototherapy

Comet assay was performed on nasal cytology samples of eight allergic rhinitis patients before starting the treatment protocol, immediately after last irradiation and 10 days after last treatment. Four of the eight patients returned for the 2 month follow-up visit when nasal cytology samples were collected.

DNA damage was significantly higher in nasal cytology samples collected immediately after completing the 2 weeks treatment regimen than before starting therapy (p = 0.02 in conventional Comet

Discussion

Although, UV light has been previously successfully applied for the treatment of diseases of the oral and nasal mucosa, no data exist regarding DNA damage and repair of oral and/or nasal mucosal epithelial cells. Fornace et al have reported that bronchial fibroblasts and epithelial cells show similar DNA damage and repair as human skin fibroblasts, suggesting that DNA repair mechanism are equally efficient in all cell types [12]. The study conducted in allergic rhinitis patients undergoing

References (28)

  • D.L. Mitchell et al.

    Repair of pyrimidine(6-4)pyrimidone photoproducts in mouse skin

    J. Invest. Dermatol.

    (1990)
  • A.R. Young et al.

    The in situ repair kinetics of epidermal thymine dimers and 6-4 photoproducts in human skin types I and II

    J. Invest. Dermatol.

    (1996)
  • D.L. Mitchell et al.

    Identification of a non-dividing subpopulation of mouse and human epidermal cells exhibiting high levels of persistent ultraviolet photodamage

    J. Invest. Dermatol.

    (2001)
  • M. Trehan et al.

    Low-dose excimer 308-nm laser for the treatment of oral lichen planus

    Arch. Dermatol.

    (2004)
  • Cited by (40)

    • Rhinophototherapy, an alternative treatment of allergic rhinitis: Systematic review and meta-analysis

      2021, Brazilian Journal of Otorhinolaryngology
      Citation Excerpt :

      However, considering the lack of medium and long-term references regarding the effects of endonasal phototherapy, it is not possible to make such assertion. A decrease in nasal mucosa moisture was observed in some studies as an adverse effect during therapy.8 The evaluated studies were carried out in Europe, the Middle East and Asia.

    • Prospective, multicenter, randomized clinical study to evaluate the clinical efficacy and tolerability of long term mixed ultraviolet and visible light phototherapy in eosinophil nasal polyps

      2017, Journal of Photochemistry and Photobiology B: Biology
      Citation Excerpt :

      The authors' previous publication revealed that mixed ultraviolet light/visible light (mUV/VIS) intranasal phototherapy was safe and effective in intermittent allergic rhinitis. UV phototherapy induced a dose-dependent increase of eosinophil and T-cell apoptosis [4–6]. In persistent allergic rhinitis, mUV/VIS improved significantly all nasal symptom scores and nasal inspiratory peak flow results [7].

    • Novel, Alternative, and Controversial Therapies of Rhinitis

      2016, Immunology and Allergy Clinics of North America
    • Comparative study in the management of allergic rhinitis in children using LED phototherapy and laser acupuncture

      2013, International Journal of Pediatric Otorhinolaryngology
      Citation Excerpt :

      SLIT is of great appeal to the pediatrician because of its ease of delivery and the potential to avoid frequent injections and serious side effects including the risk of fatal anaphylaxis, which are associated with the subcutaneous route [14,15]. Intranasal phototherapy with a combination of ultraviolet light (UV-B, UV-A) and visible light was effectively used in treating allergic rhinitis as it reduced the number of inflammatory cells and level of mediators [16–19]. Light emitting diode (LED) was also shown to be of therapeutic potential.

    View all citing articles on Scopus
    View full text