Inspired by Gellrich et al 2022.[1]
SAR – Seasonal Allergic Rhinitis (aka hay fever)
key to acronyms
aka – also known as
AR – allergic rhinitis
RCT – randomised controlled trial
MA – manual acupuncture
ARC – Acupuncture in Routine Care (acronym for a set of pragmatic trials within the
Modellvorhaben Akupunktur)
ICER – incremental cost-effectiveness ratio
QALY – quality adjusted life year (used to calculate ICER)
Th1 – pro-inflammatory T helper cells leading to an increased cell-mediated response
Th2 – pro-inflammatory T helper cells leading to a humoral immune response
Treg – regulatory T cells
TNFα – tumour necrosis factor alpha
IL – interleukin
When I trained with and joined the BMAS in the early 90’s I met Lyn Williamson, a very bright and academic GP, who was also an enthusiastic medical acupuncturist. She published a couple of papers of acupuncture in SAR (hayfever) and presented the first of these at the BMAS Spring Scientific meeting in Cheltenham in 1994 – my first BMAS meeting after initial training.[2]
A few years later I was still finding my feet outside military practice and being drawn in to treating non pain conditions. I remember being hugely sceptical of the potential for needles alone to treat allergy, principally because at the time we had no concept for any potential mechanism. Having taken over Adrian White’s practice, I inherited several patients who appeared to respond really well, so I was lucky, because I would have been very unlikely to try it otherwise.
Lyn’s research was also illuminating in terms of methodology. In her sham controlled RCT of acupuncture for SAR (n=102) no difference was found between a standard MA protocol of 3 bilateral points (BL2, LI20, LI4) and the same number of points placed subcutaneously in the middle of the patella.[3]
the special knee acupuncture
Lyn went on to become a consultant rheumatologist and got involved in the medical school at Oxford. Some years later we met after a module I ran for some of her students, and she mentioned that patients were still going back to her former practice every year and asking for the special knee acupuncture for their hay fever.
A few years later we saw the first of the papers from Benno Brinkhaus in Berlin. This included both acupuncture and Chinese herbal medicine in a sham controlled trial (n=52) and the results were reasonably positive.
Next came the huge ARC trial on AR (n=981 randomised, n=5237 total cohort).[4] This was part of the Modellvorhaben Akupunktur – a set of large research projects on acupuncture funded by the health insurance companies in Germany.[5] This trial demonstrated that the addition of acupuncture to usual care resulted in clinically relevant and persistent benefits, and that the effects were not different between the randomised and non-randomised groups who received acupuncture.
There was a health economic assessment performed on the randomised groups that demonstrated cost-effectiveness of acupuncture using a (willingness to pay) threshold of €50,000 per QALY gained.[6] Interestingly, the results were 4 times better for women than men in terms of cost-effectiveness. A similar result was found in osteoarthritis too, although the sex difference was even more dramatic and for OA knee the ICER was considerably over threshold in men.[7]
The next paper out of the Berlin stable was the ACUSAR trial.[8,9] This was a large 3-arm sham controlled trial (n=422) that demonstrated superiority over sham, as well as a significant effect in the following season, a year after the course of treatment. The latter result challenged me to come up with a physiological explanation.
In the cost effectiveness analysis of the ACUSAR trial, whilst MA showed a clear benefit over rescue medication in terms of QALYs, it was also more expensive, so the ICER range was not entirely within the threshold of €50,000 per QALY gained.[10]
So, now we can jump nearly ten years to the current episode in the SAR story, a sub-study from the ACUSAR trial examining nasal secretions and plasma for inflammatory biomarkers. Of the original 422 SAR patients, 16 of 212 were recruited to this sub-study from the acupuncture group, 6 of 102 from the sham group and 8 of 108 from the rescue medication group.
eotaxin was lower in nasal secretions
No significant changes were noted in the biomarkers related to Th1-, Th2-, or Treg-cluster in those patients who received acupuncture, in either nasal fluid or plasma; however, lower nasal concentrations of eotaxin were seen compared with the sham group sample, and general trends in some non-specific inflammatory markers. Eotaxins are a CC chemokine subfamily of eosinophil chemotactic proteins, ie they wind up eosinophils.
This is a small preliminary study looking into mechanisms of acupuncture in SAR and the indications are that the effect is likely to be general rather than specific. I think these fits well with the research on vagal anti-inflammatory reflexes, which appears to indicate a general dampening down of inflammation via key components in the pro-inflammatory cascade, such as TNFα, along with increases in anti-inflammatory cytokines such as IL-10.
This brings me back to how a course of acupuncture in one season might still have measurable effects in the following year. A general reduction in inflammation during the course of treatment in the first year may reduce the formation of immune memory by limiting contact between the specialised immune cells and the antigen (pollen) in the nasal mucosa. A reduced immune memory would be compatible with reduced symptoms in the following year.
References
1 Gellrich D, Pfab F, Ortiz M, et al. Acupuncture and its effect on cytokine and chemokine profiles in seasonal allergic rhinitis: a preliminary three-armed, randomized, controlled trial. Eur Arch Oto-Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol – Head Neck Surg Published Online First: 17 March 2022. doi:10.1007/s00405-022-07335-5
2 Williamson L. Hay Fever Prophylaxis Using Single Point Acupuncture: A Pilot Study. Acupunct Med 1994;12:84–7. doi:10.1136/aim.12.2.84
3 Williamson L, Yudkin P, Livingstone R, et al. Hay Fever Treatment in General Practice: A Randomised Controlled Trial Comparing Standardised Western Acupuncture with Sham Acupuncture. Acupunct Med 1996;14:6–10. doi:10.1136/aim.14.1.6
4 Brinkhaus B, Witt CM, Jena S, et al. Acupuncture in patients with allergic rhinitis: a pragmatic randomized trial. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol 2008;101:535–43. doi:10.1016/S1081-1206(10)60294-3
5 Cummings M. Modellvorhaben Akupunktur–a summary of the ART, ARC and GERAC trials. Acupunct Med 2009;27:26–30. doi:10.1136/aim.2008.000281
6 Witt CM, Reinhold T, Jena S, et al. Cost-effectiveness of acupuncture in women and men with allergic rhinitis: a randomized controlled study in usual care. Am J Epidemiol 2009;169:562–71. doi:10.1093/aje/kwn370
7 Reinhold T, Witt CM, Jena S, et al. Quality of life and cost-effectiveness of acupuncture treatment in patients with osteoarthritis pain. Eur J Health Econ 2008;9:209–19. doi:10.1007/s10198-007-0062-5
8 Brinkhaus B, Witt CM, Ortiz M, et al. Acupuncture in seasonal allergic rhinitis (ACUSAR)–design and protocol of a randomised controlled multi-centre trial. Forsch Komplementarmed 2010;17:95–102. doi:10.1159/000303012
9 Brinkhaus B, Ortiz M, Witt CM, et al. Acupuncture in Patients With Seasonal Allergic Rhinitis. Ann Intern Med 2013;158:225. doi:10.7326/0003-4819-158-4-201302190-00002
10 Reinhold T, Roll S, Willich SN, et al. Cost-effectiveness for acupuncture in seasonal allergic rhinitis: economic results of the ACUSAR trial. Ann Allergy Asthma Immunol 2013;111:56–63. doi:10.1016/j.anai.2013.04.008
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