When pollen grains become airborne, they are inhaled and come into contact with the nasal lining. For those of us who are allergic to certain types of pollen, the immune system mistakenly identifies the proteins in the pollen as a threat, and launches an immune reaction, flooding the bloodstream with chemicals including histamine as a defensive response. The resulting uncomfortable symptoms are due to histamine inflaming the lining of the nasal passages, sinuses, and eyelids by dilating the blood vessels, causing sneezing, itching, stinging, and a runny or blocked nose.

Hay fever, or allergic rhinitis, is the most common allergy affecting an estimated 400 million people worldwide. Despite its substantial adverse effects on quality of life and healthcare expenditure, the underlying causes of this immune overreaction are still not well understood, hence prevention is largely impossible. Seasonal allergies tend to be worse in the US South, with many people reporting new or worse allergies after moving to the region. This is partly because the South has longer allergy seasons, so residents are exposed to pollen for longer. With their warmer winters, Southern states contain plants that do not become dormant, also leading to increased exposure and causing longer and more severe symptoms.

The warm spring months in this area produce tree pollen from early spring, grass pollen from early May to the summer, and finally ragweed from early September. Some unfortunate allergy sufferers may also react to mountain cedar pollen from December to February. In addition, humid and wet environments mean there are more plants and fungi, which create greater amounts of pollen and spores. A rainy spring can promote faster plant growth and lead to an increase in mold.

The so-called 'Pollen Belt' stretches from the southern Midwest to the Southeast. Every year, the Asthma and Allergy Foundation of America ranks the top US cities for seasonal allergies, and these areas always make the list. For example, in 2022, McAllen, Texas was ranked 3rd on the list of most challenging places to live with allergies, with Richmond, Virginia at #4.

An added challenge for allergy patients in big cities within the Pollen Belt is pollution, which can trigger an immune response in itself, as well as causing some pollen grains to split open, making it easier for the particles to enter eyes, ears and nose. The pollen that causes hay fever varies between people and areas, but is generally the very small pollen of wind-pollinated plants such as pine, birch, and horse chestnut trees, also grasses and weeds such as ragweed and sorrel.

Individuals are more at risk of allergic rhinitis if they also have eczema or asthma, and if they were exposed to air pollution and tobacco smoke at an early age. For many years, scientists have searched for genetic factors which raise the risk of allergic rhinitis. Recently, a team in Germany provided new insights in this area.

Dr. Marie Standl of Helmholtz Zentrum Munchen, in Munich, and colleagues compared genetic information from around 60,000 patients with allergic rhinitis with more than 150,000 healthy similar individuals. This highlighted 42 significant 'risky' genetic variants, 22 of which had previously been linked to allergic rhinitis.

The importance of the 20 new genetic variants was then confirmed using genetic information from another 60,000 patients and 620,000 healthy people. Some of these variants cause changes in the chromosome region that oversees proteins which help the immune system distinguish between its own cells and foreign, harmful substances. A strong overlap was seen with risky genes for allergic rhinitis and those for other autoimmune diseases. Findings were described in the journal Nature Genetics. Dr. Standl said, "In order to improve the prevention and treatment of this disease, we first need to understand why the body defends itself against certain, actually harmless substances."

"The higher the number of study participants, the more reliable conclusions we can draw. The identified risk genes can explain about eight per cent of all cases of allergic rhinitis." Co-author Dr. Klaus Bonnelykke added, "The risky areas we have identified can help our understanding of the mechanisms causing allergic rhinitis and hopefully also to find targets for treatment and prevention. Still, the genes we identified only partly explain why so many people develop allergic rhinitis. One important next step is to understand how risk genes interact with our environment."

The first line of treatment is to limit contact with an individual's allergens. It may be possible to avoid outdoor activities and keep windows closed on days with high pollen forecasts. Air conditioners with allergy filters, and wearing sunglasses may help. However, this approach may not always be possible. As such, antihistamines are widely used, as well as nasal corticosteroid sprays. Decongestants can also be used in the short term. All are effective for many, but some individuals do not respond adequately to these treatments.

For those who still have symptoms, or prefer not to use these medications, there is the option of desensitisation, or immunotherapy, which aims to impact on the underlying allergy itself. Traditionally it involves multiple injections, but sublingual - under the tongue - immunotherapy has been developed, using highly concentrated extracts of the pollen which causes the allergy. If started in the months prior to the pollen season, it can have a clinically significant effect on symptoms and reduce the amount of medication required.

Recent findings have suggested that two years' worth of treatment with grass pollen immunotherapy is not sufficient to reduce symptoms of allergic rhinitis one year after the end of treatment. In this study, continuous treatment for three years was needed for long-term remission of symptoms lasting several years after stopping treatment. Dr. Stephen Durham of Imperial College London, UK, and colleagues investigated the long-term benefits of a two-year treatment approach.

“Hay fever causes major impairment of sleep, work and school performance and leisure activities during what for most of us is the best time of the year,” said Professor Durham. His team carried out a randomised clinical trial of 106 adults who received this therapy. Participants had moderate to severe hay fever and were administered either the daily oral treatment, weekly injections for 15 weeks followed by monthly boosters, or a placebo. A total of 92 patients completed the study. Nasal symptoms were tested and found to be no better than those who received a placebo. This was the case for those who received the immunotherapy via a sublingual or subcutaneous route.

In the Journal of the American Medical Association, the researchers write, "International guidelines regarding immunotherapy recommend a minimum of three years of treatment with both delivery methods [subcutaneous and sublingual].

"If a two-year regimen had demonstrated long-term benefits in addition to efficacy, this could have represented cost savings in terms of clinical resources and improved convenience for the patient. Because this was not observed, clinicians should be advised to follow established guidelines that recommend at least three years treatment."

Professor Durham added, "This study shows that whereas both immunotherapy treatments were highly effective, two years of treatment was insufficient for long-term benefits. You treat patients for three years and then they have a big improvement in their hay fever for several years afterwards. Exposing people to grass pollen in this way is a very effective treatment for people who really have debilitating hay fever." The research was funded by the Immune Tolerance Network, supported by the US National Institute of Allergy and Infectious Diseases, National Institutes of Health.

An investigation was carried out last year into the future of treatment for allergic rhinitis. Anne K. Ellis, MD, of Queen's University, Kingston, Ontario, Canada and colleagues reviewed the published literature on expert perspectives of allergic rhinitis management. They concluded that telemedicine, social media, and mHealth - medical provision using mobile devices - can facilitate integrated healthcare for allergic rhinitis management. "Pharmacotherapy remains the standard of care for allergic rhinitis management," they write, "however treatment combinations are recommended."

The review outlines the promising technique of 'intralymphatic immunotherapy', in which immunotherapeutic agents are injected directly into a lymph node with the aim of boosting the body's response. This method has already been shown to improve the efficacy of various vaccines, such as BCG vaccines in dogs and mice, and protein based vaccines in cows, as well as tumor cell-based cancer vaccines.

A further method which is raising hopes for allergic rhinitis treatment is 'peptide immunotherapy' which may offer the potential to restore normal immune reactions by expanding the numbers of regulatory T-cells and reducing the number of symptom-producing T-cells in the immune system.

"Studies of targeted biologics for allergic rhinitis are ongoing," the review authors write. For example, they add, "probiotics may be beneficial for allergic rhinitis management, particularly Bifidobacterium, and as an add-on to allergen immunotherapy."

In summary, allergic rhinitis is a chronic condition that is optimally managed with integrated care including a number of therapies. Progress is underway into the development of new formulations and combinations of existing therapies, in addition to novel approaches for treating the condition.

 

References

Waage, J. et al. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nature Genetics, 16 July 2018, doi: 10.1038/s41588-018-0157-1
https://www.nature.com/articles/s41588-018-0157-1

Linton, S. et al. Future of allergic rhinitis management. The Annals of Allergy, Asthma, & Immunology, 7 May 2021, doi: 10.1016/j.anai.2021.04.029
https://pubmed.ncbi.nlm.nih.gov/33971355/

Asthma and Allergy Foundation of America, (2022). [2022 Allergy Capitals: The Most Challenging Places to Live With Allergies]
https://www.aafa.org/allergy-capitals/