Red light redux

Three years ago I investigated claims that were being made for a red-light phototherapy device, marketed as a hay fever treatment by Lloydspharmacy.  The claims were based on a single, small, un-replicated trial with blinding problems (Neuman and Finkelstein, 1997).  Given that this is the hay fever season, I thought I’d revisit the topic and see if things have changed much.

The only new investigation of red-light devices phototherapy treatment for hay fever I am aware of was published in 2009.  Emberlin and Lewis (2009) reported “a double-blind, placebo-controlled grass pollen challenge conducted out of the pollen season, on 101 adult male and female hay fever sufferers. Subjects were assigned to placebo or active groups by stratified random sampling using responses to a baseline questionnaire. All subjects used active or placebo devices three times a day for 14 days before pollen challenge. Subjects were monitored for 2.5 h after challenge.”

On the positive side, the authors found:

“Significant reductions in severity of symptom scores were found for sneezing, running nose, running eyes and itchy mouth/palate (p < or = 0.05).”

But, on the other hand:

“No significant differences were found in the results for itchy eyes, itchy nose, itchy throat, ECPs, PIFn and PEFn.”

The authors concluded:

“The results show that the device significantly reduced some hay fever symptoms. The study would have been improved if compliance was monitored electronically and if nasal congestion was monitored by report. The mode of action is unclear. The study does not consider long-term implications of the therapy.”

In December 2009 the ASA considered whether this study was sufficient to support the claims that Lloydspharmacy had made in a TV commercial.  (You can read the adjudication here.)  The decision went against them.  The ASA’s expert found a number of problems with using this study to support Lloydspharmacy’s claims:

• The study was conducted outside the pollen season.
• It was based on a response 2½ hours after a single dose of pollen, not a realistic simulation of what really happens.
• Only high doses of pollen were administered, providing no guide to how effective the device would be when the pollen count was in the medium to low range.
• It gave no insight into whether the effect would last the four to five months of the ‘pollen season’.
• The trail was limited to adults.
• There was no baseline assessment, so it was, “not clear what subjects responses to pollen were prior to intervention with the device and therefore it was difficult to compare any later change in response to pollen.”
• The design relied on subjective reporting of symptoms
• Compliance was measured by diary card and interview only, relying on the recollection of the participants.

The study definitely places red-light phototherapy in the “potentially interesting but needs proper trials” category.  However, the evidence just isn’t there to support the marketing claims. This is unfortunate, because Lloydspharmacy continue to make similar claims, supposedly supported by this work, on their website.  The upside is that the ASA now regulates this form of advertising on the web^*.

To be fair, other phototherapy vendors make even more speculative claims, for similar devices.  For instance:

• peak nutrition claim that a similar device, “Offers relief from hay fever, animal hair or house dust”
• Health Innovations‘ website asserts that allergic symptoms can be practically eliminated.

Other similar claims are not hard to find.  Perhaps the extension to other irritants is an attempt to keep these products selling throughout the year?

It seems that red-light phototherapy also has some competition.

A spectral shift

When I first started to look at phototherapy treatments for hay fever, I kept finding more research from the other end of the spectrum, so to speak.  There do seem to be more papers around, at least indexed in PubMed dealing with UV phototherapy.  Looking again, this trend has strengthened.

Initial enthusiasm for the shorter wavelength end of the spectrum seems to have originated in Russia^**; most of the initial crop of papers are from Eastern Europe.  For example, Csoma and colleagues from the University of Szegin Hungary (Csoma et al, 2004) reported an open study on UVB treatment of, “severe allergic rhinitis” delivered by an, “308 nm XeCl UVB excimer laser.”  This was a very small study (n=18), with ten patents in a ‘low-dose’ group, of who only 7 completed the trial, and eight in a ‘medium-dose’ group.  Only the medium-dose group showed improvement:

“the XeCl UVB irradiation significantly inhibited the rhinorrhoea, the sneezing, the nasal obstruction and the total nasal score”.  Such a small trial, with no blinding or placebo control, says very little.  The treatment might have merit, providing there’s no problem exposing the interior of the nose to UVB radiation.

Some of the same authors (Koreck et al 2005a) investigated a, ” combination of UV-B (5%), UV-A (25%), and visible light (70%), referred to as mUV/VIS”  This was, at least, a randomized double-blind trial.  However, with only 49 hay fever sufferers, it’s still a small trial.  The results appear to be mainly positive:

“… 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).”

Enough to show promise, but larger trials would be needed to be sure that this treatment is really helpful.  Many of the same authors (Koreck et al, 2005b) published an article in Hungarian reporting the results of a randomized, double-blind placebo-controlled study of intranasal phototherapy in patients with a least two years history of, “ragweed-induced allergic rhinitis that was not controlled by anti-allergic drugs”.  They claimed:

“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.”

The following year, this group was back in print with another study (Csoma et al, 2006) looking at, “8-methoxypsoralen (8-MOP) plus UVA light (PUVA)” as a treatment for allergic rhinitis.  This was a very small trial, “An open study … in 17 patients with hay fever.”  Positive results were claimed, though such a small unblended trial adds little to the evidence base.

Kemény and Koreck (2007) also went into print with a review, repeating many of the same claims.

Koreck et al (2007) examined the response of the nasal mucosa to PUVA with a trial in, “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.”  They concluded that:

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

This makes me wonder whether UV damage in the nasal mucosa would continue to be repaired over successive hay fever seasons, or whether a larger study might not show the same trend.

Moving on to some more recent papers, Yaniv et al. (2009) treated fourty-eight patients with allergic rhinitis symptoms using a KTP/532 YAG laser.  The authors observed that:

“At examination after 1 year, nasal obstruction was improved in 69% and nasal discharge in 40% of cases.”

Their conclusion was that this approach:

 “…is effective for the treatment of nasal obstruction and discharge. Comparison with other techniques showed it to be the most effective in reducing nasal discharge. It can be done as an office procedure and does not damage the nasal mucous membrane. The KTP/532 YAG laser is effective as an additional treatment for patients refractory to medication.”

Also, Cingi et al (2009) have recently looked at, “The effects of phototherapy on quality of life in allergic rhinitis cases.”  This study used a quality of life questionnaire on, “100 consecutive cases.”  The authors found “significant differences … in all quality of life variables” when pre and post treatment data were compared.

Brehmer (2010) published a trial of a product called ‘Rhinolight’, which appears to offer the same type of radiation explored by Koreck et al (2005a), “a combination of UV-B (5%), UV-A (25%) and visible light (70%)”  The author claims that this device has had, “its effectiveness has been demonstrated in one double-blind, placebo-controlled study.”  They go on to say that, “The results of additional studies have been presented at various medical conferences and in abstracts.”  This suggests a number of minor publications.  In the same year, Cingi et al (2010) published a trial using similar illumination: “a prospective, randomized, single-blind, placebo-controlled study” of phototherapy for allergic rhinitis.  This is one of the largest studies that I have found, with seventy-nine patients.  They were randomized to either treatment or control (“low-intensity visible light” – a good placebo design) groups.  The assessment was based on, “total nasal symptom score before treatment and 1 month after the end of treatment.”  The results:

“Total nasal scores decreased in both groups but the decrease was highly significant in the active treatment group when compared with the placebo (p < 0.001).”

This appears to be an encouraging result, but larger trials are still needed, along with replication by other groups.  Neither does this study look at the kind of long term treatment that a hay fever sufferer needs to get through a complete season.

A paper that has just appeared in print (Garaczi et al, 2011) appears to demonstrate superiority of intranasal phototherapy (5% UVB, 25% UVA and 70% visible light – “Rhinolight”) over 180 mg fexofenadine Hydrochloride per day, over a two-week period.  Symptom severity was subjectively assessed by the thirty-one (n=31) participants and recorded in a diary.  This work comes from the same university group responsible for most of the studies I found (University of Szeged, Hungary).  Their reported results are:

“…all of the parameters the scores decreased significantly at the end of the treatment compared with day 1 for all of the parameters: sneezing (P = 0.0002), rhinorrhea (P = 0.0004), nasal itching (P = 0.0003), nasal obstruction (P = 0.0014) and palate itching (P = 0.00002) respectively. In the fexofenadine HCl group none of the symptoms improved significantly (P > 0.05) at the end of the study except sneezing (P = 0.007).  TNS was significantly decreased in the rhinophototherapy group (P < 0.0001), but no significant difference was observed in the fexofenadine HCl group after 2 weeks of treatment compared to the baseline (P = 0.35) …”

This study has limitations that appear to be fairly typical in this field: it’s small (pilot study), of short duration and relies on subjective data recorded by the trial subjects.  I also wonder if the more dramatic nature of nasal illumination, compared to taking a tablet, is significant in the outcome as well; particularly as the fexofenadine Hydrochloride seems to have performed so poorly.  For instance, Bernstein et al (1997) reported favourable performance for this drug against placebo in a double blind five hundred and seventy patient, 14 day, multicentre trial.  A similar impression of efficacy is provided in a review by Bachert (2009).

Maybe the drug trials have overstated the benefits of fexofenadine, or maybe this small study shows UV phototherapy in an overly positive light. Only larger, well-designed trials will tell.

Finally, Brehmer and Schön (2011) aimed to, “correlate clinical symptom scores with possible changes in the LC of the nasal mucosa induced by” the same kind of phototherapy.  The study took nasal biopsies from, “ten birch pollen-sensitive patients with seasonal rhinitis before and after endonasal phototherapy.”  They reported:

“All patients showed a significant clinical benefit post-treatment … including total nasal symptom score, nasal congestion score, nasal itching score, sneezing score, nasal secretion score and impairment-to-health score. However, we found no significant morphological changes, to, or quantitative differences in, the CD1a+, CD4, CD8 or CD31 cells before and 14 days after treatment. Despite the positive clinical effect, the study revealed no effect of UV irradiation on the LC and other analysed cells of the nasal mucosa immune system.”

Although a small study that sheds little light on the effectiveness of UV phototherapy, it poses interesting questions about the mechanism that might be at work.

What to make of it all?

Clearly, there is insufficient robust evidence to support marketing claims being made for products like Medinose/Bionase and the Lloydspharmacy Hayfever reliever.  They might work, but no one can be sure.  The companies selling them should refrain from making claims that cannot be supported.

It’s also my overall impression is that there is much more research interest in UV phototherapy.  Generally, it seems to be a story of small trials, not all of them placebo controlled.  I’m always wary when a large chunk of the published evidence seems to be the work of a relatively small group of authors.  Larger, well-designed trials and the involvement of other research groups are needed to show whether this approach works or not.

The comments of Leimgruber (2006) seem appropriate here.  Talking about, “laser rhinophototherapy” (along with a drug-therapy) this author concluded that, “long-term studies involving large cohorts of patients are needed if we want to prescribe these treatments without restrictions.”

It might be that UV or red-light phototherapy can help people with hay fever.  Perhaps only one of these approaches works.  It may even be that neither of them do.  Given the available evidence, I’ll certainly be treating any claims with considerable caution.

Related posts

Blind to the Rudolph Effect
Operation Rudolph
Stuck at a Red Light

Disclaimer

I try to make sure that what I write is both accurate and fair.  If you think that I have got anything wrong please let me know.  If you are right I will happily change what I have written.

This is not medical advice.  If you need that see a properly qualified and registered doctor.

Notes

* … and I’ve let them know.

 **The first reference that I found refers to a Russian language publication called, “Use of long-wave ultraviolet radiation in the treatment of vasomotor rhinitis” (Daĭniak et al, 1977).  Unfortunately I cannot find out any of the details, but it at least shows some research interest in the topic.

References

Bachert C. A review of the efficacy of desloratadine, fexofenadine, and levocetirizine in the treatment of nasal congestion in patients with allergic rhinitis. Clinical therapeutics. 2009 May;31(5):921–944. Available from: http://dx.doi.org/10.1016/j.clinthera.2009.05.017.

Bernstein DI, Schoenwetter WF, Nathan RA, Storms W, Ahlbrandt R, Mason J. Efficacy and safety of fexofenadine hydrochloride for treatment of seasonal allergic rhinitis. Annals of allergy, asthma & immunology. 1997 Nov;79(5):443–448. Available from: http://dx.doi.org/10.1016/S1081-1206(10)63041-4.

Brehmer D, Schön MP. Endonasal phototherapy significantly alleviates symptoms of allergic rhinitis, but has a limited impact on the nasal mucosal immune cells. European archives of oto-rhino-laryngology. 2011 Mar;268(3):393–399. Available from: http://dx.doi.org/10.1007/s00405-010-1375-z.

Brehmer D. Endonasal phototherapy with Rhinolight for the treatment of allergic rhinitis. Expert review of medical devices. 2010 Jan;7(1):21–26. Available from: http://dx.doi.org/10.1586/erd.09.56.

Cingi C, Yaz A, Cakli H, Ozudogru E, Kecik C, Bal C. The effects of phototherapy on quality of life in allergic rhinitis cases. European archives of oto-rhino-laryngology. 2009 Dec;266(12):1903–1908. Available from: http://dx.doi.org/10.1007/s00405-009-1048-y.

Cingi C, Cakli H, Yaz A, Songu M, Bal C. Phototherapy for allergic rhinitis: a prospective, randomized, single-blind, placebo-controlled study. Therapeutic advances in respiratory disease. 2010 Aug;4(4):209–213. Available from: http://dx.doi.org/10.1177/1753465810374610.

Csoma Z, Ignacz F, Bor Z, Szabo G, Bodai L, Dobozy A, et al. Intranasal irradiation with the xenon chloride ultraviolet B laser improves allergic rhinitis. Journal of photochemistry and photobiology B, Biology. 2004 Sep;75(3):137–144. Available from: http://dx.doi.org/10.1016/j.jphotobiol.2004.05.001.

Csoma Z, Koreck A, Ignacz F, Bor Z, Szabo G, Bodai L, et al. PUVA treatment of the nasal cavity improves the clinical symptoms of allergic rhinitis and inhibits the immediate-type hypersensitivity reaction in the skin. Journal of photochemistry and photobiology B, Biology. 2006 Apr;83(1):21–26. Available from: http://dx.doi.org/10.1016/j.jphotobiol.2005.11.009.

Daĭniak LB, Nikolaevskaia VP, Polubutkin PV, Skurikhina LA, Kamenetskaia TM. [Use of long-wave ultraviolet radiation in the treatment of vasomotor rhinitis]. Vestnik otorinolaringologii. 1977;(3):48–52. Available from: http://view.ncbi.nlm.nih.gov/pubmed/878155

Emberlin JC, Lewis RA. Pollen challenge study of a phototherapy device for reducing the symptoms of hay fever. Current medical research and opinion. 2009 Jul;25(7):1635–1644. Available from: http://dx.doi.org/10.1185/03007990903024699.

Garaczi E, Boros-Gyevi M, Bella Z, Csoma Z, Kemény L, Koreck A. Intranasal Phototherapy Is More Effective Than Fexofenadine Hydrochloride in the Treatment of Seasonal Allergic Rhinitis: Results of a Pilot Study. Photochemistry and Photobiology. 2011;87(2):474–477. Available from: http://dx.doi.org/10.1111/j.1751-1097.2010.00882.x.

Kemény L, Koreck A. Ultraviolet light phototherapy for allergic rhinitis. Journal of photochemistry and photobiology B, Biology. 2007 Apr;87(1):58–65. Available from: http://dx.doi.org/10.1016/j.jphotobiol.2007.01.001.

Koreck AI, Csoma Z, Bodai L, Ignacz F, Kenderessy AS, Kadocsa E, et al. Rhinophototherapy: a new therapeutic tool for the management of allergic rhinitis. The Journal of allergy and clinical immunology. 2005 Mar;115(3):541–547. Available from: http://dx.doi.org/10.1016/j.jaci.2004.11.005.

Koreck A, Csoma Z, Ignácz F, Bodai L, Kadocsa E, Szabó G, et al. [Intranasal phototherapy for the treatment of allergic rhinitis]. Orvosi hetilap. 2005 May;146(19):965–969. Available from: http://view.ncbi.nlm.nih.gov/pubmed/15969309.

Koreck A, Szechenyi A, Morocz M, Cimpean A, Bella Z, Garaczi E, et al. Effects of intranasal phototherapy on nasal mucosa in patients with allergic rhinitis. Journal of photochemistry and photobiology B, Biology. 2007 Dec;89(2-3):163–169. Available from: http://dx.doi.org/10.1016/j.jphotobiol.2007.09.013.

Koreck A, Bella Z, Kadocsa E, Perenyi A, Tiszlavicz L, Nemeth I, et al. Intranasal PUVA phototherapy in nasal polyposis–a pilot study. Roumanian archives of microbiology and immunology. 2010;69(1):20–23. Available from: http://view.ncbi.nlm.nih.gov/pubmed/21053780.

Leimgruber A. [Allergo-immunology]. Revue médicale suisse. 2006 Jan;2(48):89–92. Available from: http://view.ncbi.nlm.nih.gov/pubmed/16463791.

Neuman I, Finkelstein Y. Narrow-band red light phototherapy in perennial allergic rhinitis and nasal polyposis. Annals of allergy, asthma & immunology. 1997 Apr;78(4):399–406. Available from: http://dx.doi.org/10.1016/S1081-1206(10)63202-4.

Yaniv E, Hadar T, Shvero J, Tamir R, Nageris B. KTP/532 YAG laser treatment for allergic rhinitis. American journal of rhinology & allergy. 2009;23(5):527–530. Available from: http://dx.doi.org/10.2500/ajra.2009.23.3346.

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