The Current Evidence for CPAP and the Cardiovascular Benefits

Hay Fever – Everything You Need to Know

Introduction

Hay fever, known by doctors as Seasonal Allergic Rhinitis, is an extremely common condition affecting millions in the UK. Characterised by four cardinal symptoms:

• Blocked nose (nasal congestion)
• Sneezing (medically known as ‘sternutation’)
• Itchy, watery eyes (allergic conjunctivitis)
• Runny nose (rhinorrhoea)

Other symptoms that hay fever sufferers experience are:

• Itchy nose, throat, mouth, or ears: Hay fever often leads to itchiness around the upper airway. This is due to a release of histamine.
• Coughing: Persistent coughing may arise due to postnasal drip (otherwise known as catarrh), caused by a runny nose or throat irritation and itchiness.
• Fatigue: Those with hay fever may experience tiredness and low energy levels. This is likely because of nasal obstruction disturbing the sleep of the sufferer.
• Headaches: Nasal congestion may block the sinuses causing headaches and facial discomfort. Sleep deprivation itself may also cause headaches.
• Loss of smell and taste: If the nasal congestion becomes extreme, air may not be able to reach the upper parts of the nose where the olfactory nerve is found (nerve of sense of smell). If air is unable to stimulate this nerve, the person may temporarily be unable to smell or taste anything.

Hay fever can significantly affect daily life during the warmer months (spring – summer – autumn). The culprit behind this discomfort is an allergic reaction to airborne allergens like pollen from trees, grass, or weeds.

How Common is Hay Fever & is it Really a Problem?

Studies suggest that hay fever affects at least one in four people in the UK, indicating a prevalence rate of approximately 25% (Durham et al. 1997). However, another study found that hay fever affects at least one in 10 people (prevalence rate of 10%) (White et al. 2004). This discrepancy might be because of differences in the way hay fever was diagnosed between the two studies, but it's clear that hay fever is a common problem.

To highlight this, hay fever is often underdiagnosed or misdiagnosed, with some individuals not being properly recognised as having the condition, even though they meet clinical criteria (Sibbald & Rink. 1991).

Hay fever significantly affects quality of life, including sleep disturbances and reduced performance at work or school (Durham et al. 1997). De la Hoz Caballer et al. in 2012 estimated that allergy sufferers experience a 40% decrease in productivity when pollen allergy symptoms are at their worst. That equates to losing 2 full days of work each week or losing £325 million from the UK economy each year.

Despite its prevalence, many patients report inadequate advice or treatment, with two-thirds finding their condition poorly controlled. Effective treatments are not always adequately prescribed or utilised (Scadding, 2007).

Why Do People Get Hay Fever?

From an immunological standpoint, hay fever is the result of an overactive immune response to harmless substances like pollen. When exposed to these allergens, the immune system mistakenly identifies them as threats (the thought is that the immune system accidently believes pollen to be a part of parasitic worms), and releases immunoglobulin E (IgE) antibodies. These antibodies bind to allergens and trigger mast cells to release histamine and other inflammatory chemicals. This response causes the symptoms mentioned above.

Some bacterial strains have been associated with lower rates of hay fever and allergies, particularly in people exposed to farming environments or diverse microbiomes early in life. These are mainly beneficial microbes that help train the immune system. Examples include:

• Lactobacillus species: Found in fermented foods and the gut microbiome, these bacteria can help regulate immune responses and reduce inflammation linked to allergies.
• Bifidobacterium species: Commonly found in the gut microbiome, they play a role in modulating the immune system and reducing hypersensitivity to allergens.
• Acinetobacter species: Present in soil and farming environments, exposure to Acinetobacter has been linked to protective effects against allergies.
• Mycobacterium vaccae: Found in soil, this species has shown promise in reducing allergic inflammation and promoting a balanced immune response.

Although there is no direct evidence that microbes resemble pollen allergens, early life exposure to a wide range of microbes helps train the immune system to distinguish between harmful and harmless substances. In environments with limited microbial exposure (e.g. highly sanitised living conditions), the immune system may become “hyperreactive” to harmless substances like pollen.

How to Treat Hay Fever

In this section I will discuss a number of treatment options including conservative (limiting exposure to pollen), nasal sprays, steroids, antihistamines and immunotherapy.

Limiting Exposure to Pollen

Managing hay fever effectively starts with understanding when specific allergens are most active. Pollen levels can vary greatly throughout the year, with tree pollen dominating in spring, grass pollen peaking in early summer, and weed pollen extending symptoms into autumn. Awareness of these seasonal patterns is key to minimising exposure and reducing the severity of allergic reactions.

Below is a more detailed list of pollen counts of various plants and spores:

Tree Pollen Allergens (Peak in the spring)

• Hazel – February to March
• Alder – February to April
• Ash – March to May
• Birch – Late March to early May
• Willow – April to May
• Poplar – April to May
• Oak – April to June
• Plane – Late April to June

Grass Pollen Allergens (Peak: Late Spring to Summer)

• Ryegrass – May to July
• Timothy grass – May to July
• Meadow fescue – May to July
• Orchard grass – May to July

Weed Pollen Allergens (Peak: Summer to Early Autumn)

• Plantain – May to July
• Dock – May to August
• Nettle – Late June to September
• Mugwort – July to September
• Ragweed – Late July to October

Fungal Allergens

• Fungal spores (e.g. Alternaria, Cladosporium) – Summer to early autumn, particularly humid conditions

Myth – “Avoid going outside in the morning or evening because that is when the pollen count is highest”

Research on pollen counts indicates that they are not consistently highest in the morning and evening. Instead, the timing of peak pollen concentrations varies depending on the type of pollen and environmental conditions.

Pollen levels often show a specific pattern with some studies finding peak pollen counts in the afternoon and evening, rather than the morning (Fineman et al. 2022; Calderón-Ezquerro et al. 2018; Alcázar et al. 2019; Borycka & Kasprzyk. 2018).

Specific Pollen Types

• Olea Pollen: Highest concentrations were observed between 12:00 and 14:00 during the season, with afternoon and evening peaks in the preseason (Fernández-Rodríguez et al. 2020).
• Quercus Pollen: Exhibited low morning concentrations with peaks in the evening, influenced by wind patterns (Calderón-Ezquerro et al. 2018).
• Grass Pollen: In Copenhagen, peak concentrations were noted in the evening, while in Cordoba, peaks occurred in the afternoon (Alcázar et al. 2019).
• Birch and Alder Pollen: Typically show early afternoon peaks, with some models indicating night-time peaks due to weather conditions (Borycka & Kasprzyk. 2018; Berggren et al. 1995).

Environmental Influences

Meteorological factors such as wind speed, direction, and rain significantly affect pollen distribution and peak times. For example, rain can initially increase pollen counts before washing them out (Borycka & Kasprzyk. 2018; Berggren et al. 1995). Rain causes pollen to absorb moisture, swell, and break into smaller fragments about 2.5µm in diameter. This process can temporarily worsen hay fever symptoms as these smaller fragments are more likely to be inhaled. However, as rain continues, it ‘washes’ pollen out of the air, eventually improving symptoms.

Dispelling the Myth

The evidence suggests that pollen counts do not universally peak in the morning and evening. Instead, peak times vary by pollen type and are influenced by environmental conditions. Understanding these patterns can help individuals with allergies plan their activities to minimize exposure.

Other Practical Tips to Limit Exposure to Pollen

Simple lifestyle adjustments can significantly ease symptoms, even during peak pollen seasons. Below are practical strategies to help create a pollen-free environment inside your home and take precautions when stepping outside.

Indoor Strategies

• Keep windows closed during high pollen seasons.
• Use air purifiers with HEPA filters to trap pollen and other airborne allergens.
• Regularly clean and vacuum with a HEPA-filtered vacuum to reduce allergens indoors.
• Wash bedding and curtains frequently to remove trapped allergens.
• Avoid drying laundry outdoors, as pollen can cling to fabrics.

Outdoor Precautions

• Check daily pollen forecasts and stay indoors during high pollen counts.
• Wear sunglasses and a wide-brimmed hat to shield eyes and face from pollen. No real evidence that this works, but it is widely practiced.
• Avoid grassy areas, especially freshly mown grass.
• Shower and change clothes after outdoor activities to remove pollen from skin and hair.
• Plan outdoor activities for times when pollen levels are lower, such as during or after rain.

Barriers & Balms

• Apply a barrier balm around nostrils to trap pollen before it enters the nasal passages. Evidence suggests barrier balms or ointments may alleviate allergic rhinitis symptoms (Chen et al. 2020).
• AM-301 Nasal Spray: Forms a protective barrier on the nasal mucosa, reducing symptoms of allergic rhinitis more effectively than saline sprays (Couroux et al. 2023; Becker et al. 2024; Nehrig et al. 2021).
• Hydroxypropyl Methylcellulose (HPMC) Powder: Applied nasally, it acts as a barrier against pollen allergens, reducing nasal symptoms (Popov et al. 2017).
• Nasal Ointments: Studies suggest products like Bepanthen® Eye and Nose Ointment can act as a physical pollen barrier (Metz et al. 2018).

Face Masks

Filter masks may be an option for some trying to manage their hay fever, especially during high pollen seasons. These masks are designed to block airborne particles, including pollen.

What Type of Mask is Effective?

• FFP2 Masks: Filter at least 94% of airborne particles, providing good protection for most hay fever sufferers.
• FFP3 Masks: Filter at least 99% of airborne particles, ideal for individuals with severe hay fever or sensitivity to fine allergens.

Features to Look For

• Tight Seal: Ensures the mask fits snugly over your nose and mouth.
• Comfort: Lightweight and breathable masks prevent discomfort.
• Adjustable Straps: Helps achieve a better fit for different face shapes.

While masks can effectively reduce throat and nasal symptoms, they do not help alleviate eye-related hay fever symptoms.

Air Purifiers

These devices filter pollen from indoor air. Although studies specific to hay fever are lacking, research on house dust mites suggests their potential benefits.

What the Study Involved

• Patients were divided into two groups:
• One group used real HEPA (High-Efficiency Particulate Air) purifiers.
• The other group had placebo devices that looked like purifiers but did not actively filter the air.
• Two purifiers were placed in each home (bedroom and living room) and used for six weeks.

Results of the Experiment

• Symptom Relief: Patients using active purifiers needed less medication and showed noticeable improvement compared to the placebo group.
• Air Quality: Active air purifiers significantly reduced airborne particles indoors, with bedroom particles measuring 2.5µm decreasing by up to 51.8%.

While most pollen particles are larger (around 10µm or more), the smaller 2.5µm particles are relevant as they form shortly after rain. Rain causes pollen to absorb moisture, swell, and break into smaller fragments about 2.5µm in diameter. These smaller fragments are more likely to be inhaled and can temporarily worsen hay fever symptoms. However, prolonged rain eventually washes pollen out of the air, improving symptoms.

How Nasal Saline Irrigation Can Help Hay Fever

Using a saline solution (a mixture of salt and water) to rinse the nose may help ease hay fever symptoms. It works by flushing out allergens like pollen, reducing irritation, and making breathing easier. Studies show it could help reduce the severity of symptoms in both adults and children for up to three months.

A meta-analysis study performed by the Cochrane database team examined 14 studies with 747 participants, including 499 children and 248 adults. The results are provided below:

• At up to 4 weeks: People using saline reported significantly better symptom relief compared to those who did not (this improvement was large when measured using clinical scoring methods).
• At 4 weeks to 3 months: People continued to experience relief from symptoms, with a noticeable improvement compared to no saline treatment.

Nasal saline is very safe. None of the studies reported side effects like nosebleeds or discomfort in people who used saline, making it a good option for many.

Antihistamines

Antihistamines are commonly used to treat hay fever by blocking the effects of histamine (a chemical responsible for many allergy symptoms). They are generally effective in alleviating symptoms such as itching, sneezing, and sometimes runny nose, though their effectiveness can vary.

Efficacy of Antihistamines

• Oral Antihistamines: Loratadine is effective in reducing overall allergic symptoms without causing significant sedation, unlike Clemastine (Irander et al. 1990).
• Antihistamine Sprays: These sprays help reduce hay fever symptoms, including nasal congestion (Trigg & Davies. 1996).

Safety and Side Effects

• General Safety: Antihistamines are safe, but some patients may experience drowsiness, especially with older medications (Li et al. 2022).
• Non-Sedating Antihistamines: Loratadine is preferred due to fewer sedative effects (Howarth & Holgate. 1984; Irander et al. 1990).

Comparative Effectiveness

• Oral antihistamines: These are less effective than nasal steroids but are an option for patients who cannot tolerate nasal treatments (Marko & Pawliczak, 2023; Prescrire Int. 2008).
• Nasal azelastine: It has similar efficacy to oral antihistamines (Prescrire Int. 2008).

Conclusion

Antihistamines, particularly non-sedating ones like Loratadine, are effective for treating hay fever symptoms such as itching, sneezing, and runny nose. They are generally safe, with minimal sedative effects, making them a preferred choice for many patients, though individual responses may vary.

Corticosteroid Nasal Sprays

Intranasal corticosteroids are a well-established treatment for hay fever, known for their effectiveness in reducing symptoms and improving quality of life.

How Effective are Steroid Nasal Sprays?

• Steroid nasal sprays are considered the most effective treatment for hay fever, as supported by medical research (Scadding. 2007; Sousa‐Pinto et al. 2023; Sousa-Pinto et al. 2024). They significantly improve nasal and eye symptoms and enhance the quality of life for patients (Sousa‐Pinto et al. 2023; Sousa-Pinto et al. 2024; Turkeltaub et al. 1982).
• Fluticasone (Flixonase or Avamys) and Mometasone Furoate (Nasonex) are known for treating hay fever well (Soe et al. 2023; Turkeltaub et al. 1982). Azelastine-Fluticasone combinations (commonly known as Dymista nasal spray, which combines a steroid and antihistamine) show even better symptom improvement (Sousa-Pinto et al. 2024; Sousa‐Pinto et al. 2024). The only issue is that antihistamine sprays tend not to taste very nice.

How Safe are Steroid Nasal Sprays?

• General Safety: Nasal steroids are generally safe with minimal systemic side effects due to their local administration (Salib & Howarth, 2003).
• Minor Adverse Effects: They may cause mild side effects such as nosebleeds, though these are rare. Those with a deviated septum, individuals on blood thinners, or the elderly may be more susceptible (Salib & Howarth, 2003).
• Long-Term Use: While effective, there is some concern about potential olfactory damage with prolonged use, as seen in experimental studies on mice (Li et al. 2023). However, this is not a common finding in human studies.

Guidelines and Recommendations

• Clinical Guidelines: Intranasal corticosteroids (INCS) are recommended as the first-line treatment for anything more than mild intermittent rhinitis. They should be used regularly throughout the allergy season (Scadding, 2007).
• Combination Therapy: INCS can be combined with antihistamines for enhanced relief (Scadding, 2007; Sousa-Pinto et al. 2024).

Conclusion

Intranasal corticosteroids are a cornerstone in the management of hay fever, offering significant symptom relief and a favorable safety profile. They are recommended as a first-line treatment, especially for moderate to severe cases, and can be effectively combined with other medications such as antihistamines for even better control of symptoms.

Leukotriene Receptor Antagonists

Leukotriene receptor antagonists are considered as an alternative option for hay fever sufferers, but their effectiveness compared to other treatments varies.

How Good are Leukotriene Receptor Antagonists for Hay Fever?

• Comparison with Placebo and Other Treatments: Leukotriene receptor antagonists are sometimes more effective than placebo in treating hay fever symptoms. However, they are generally no more effective than nonsedating antihistamines and are less effective than intranasal corticosteroids (Nathan, 2003).
• Symptom Relief: While leukotriene receptor antagonists are expected to improve nasal congestion due to their mechanism of action, clinical studies show they are not superior to antihistamines in this regard. Some studies indicate leukotriene receptor antagonists may improve symptoms like sneezing, nasal itching, and drainage, although these effects are not consistently observed (Nathan, 2003).
• Safety: Meltzer (2002) found that leukotriene receptor antagonists are generally quite safe to use.

Conclusion

While leukotriene receptor antagonists can be effective in managing hay fever symptoms, they are generally less effective than intranasal corticosteroids and comparable to antihistamines. They are safe and well-tolerated, but their role in treatment may not be unique or superior to other available options.

Immunotherapy

Allergen immunotherapy, also known as desensitisation therapy, is a long-term treatment aimed at reducing hay fever symptoms by training the immune system to tolerate specific allergens.

What Is Allergen Immunotherapy?

It involves exposing the patient to gradually increasing amounts of the specific allergen(s) responsible for their hay fever, such as grass, tree, or weed pollen. The goal is to help the immune system become less reactive to the allergen over time, thereby reducing symptoms. Immunotherapy reduces IgE levels and increases IgG levels, which help block allergic responses (Evans et al. 1976; Lichtenstein et al. 1968).

How Do You Take This Medication?

• Subcutaneous Immunotherapy (SCIT): This involves allergy injections given under the skin, typically in a medical setting. Treatments are administered regularly (e.g. weekly) during the initial phase and then less frequently (e.g. monthly) during the maintenance phase. In the early days of this therapy, it was given once a year.
• Sublingual Immunotherapy (SLIT): This method uses tablets or drops placed under the tongue, which can be taken at home after the first dose is monitored by a healthcare provider. SLIT is commonly used for grass pollen and dust mite allergies.

What Are the Benefits?

• Reduced severity of symptoms during pollen season.
• Lower dependence on medications like antihistamines.
• Long-lasting effects, even after stopping the treatment.
• Improved quality of life for people severely affected by hay fever.
• Prevention of new allergies.
• May prevent hay fever from progressing into asthma (James & Durham, 2008).

(Senti et al. 2015; Tang et al. 2024; Varney et al. 1991; Frew et al. 2006).

How Long Do You Need To Take The Medication?

The therapy typically lasts 3 to 5 years. Improvements may be noticeable within the first year, but full benefits are usually seen after completing the course.

How Safe Is It?

Immunotherapy is generally a safe treatment when carried out under medical supervision. Mild side effects, such as localised swelling or itching at the injection site or under the tongue, are fairly common.

However, in rare cases, serious allergic reactions like anaphylaxis can occur. To manage this risk, initial treatments are performed in a controlled medical setting, ensuring healthcare professionals can act swiftly if a severe reaction occurs, potentially saving the patient’s life.

Once a patient has undergone several doses without complications, the risk of a reaction decreases. At this point, doctors often permit the treatment to be administered at home, as it becomes a safer option. (Varney et al. 1991; Frew et al. 2006).

The Use of Probiotics in Hay Fever

At the start of this blog, I talk about how early life exposure to certain gut bacteria may reduce the chance of getting hay fever. There have been studies which found that exposure to certain bacterial strains, such as Lactobacillus acidophilus and Bifidobacterium lactis Bl-04, may reduce hay fever symptoms.

In a 12-week study, researchers tested how well the probiotic formula "NC-Seasonal-Biotic" worked to reduce hay fever symptoms, improve quality of life, and affect immune and gut health. The trial was randomised, double-blind (neither participants nor researchers knew who received the probiotic), and placebo-controlled (some participants received a harmless placebo instead of the probiotic).

Results of Study

• When looking at all participants, there were no major differences in hay fever symptoms between the probiotic and placebo groups. However, the probiotic group showed a trend toward better quality of life.
• For those who completed the entire trial (40 participants), the probiotic group had a significant reduction in symptoms like runny nose (p = 0.04) and itchy eyes (p = 0.01) compared to the placebo group.
• The probiotic group also reported better quality of life, including:
  • Improved daily functioning (p = 0.05)
  • Better sleep (p = 0.005)
  • Less fatigue (p = 0.04)
  • Reduced thirst (p = 0.007)
  • Less irritability (p = 0.007)
• The immune system of the probiotic group improved significantly, with a healthier balance in T-cell activity (Th1/Th2 ratio).
• There were no major differences in gut bacteria between the groups.
• The probiotic was generally well tolerated with minimal side effects.

Taking the "NC-Seasonal-Biotic" probiotic for 10–12 weeks appeared to reduce hay fever symptoms like runny nose and itchy eyes, improve quality of life, and boost immune system function. It was also safe and well tolerated.

So using these probiotics might be a good way to get some relief from your hay fever, but we are in the early stages of this research.

Conclusion

While hay fever can be a challenging condition to live with, understanding its causes, symptoms, and available treatments can make a significant difference in managing it effectively. From practical measures like reducing exposure to pollen, using air purifiers, and wearing protective masks, to more advanced options such as immunotherapy and exploring the potential of probiotics, there are many strategies available to ease its impact.

By tailoring your approach to your individual needs and seeking professional guidance where necessary, it is possible to enjoy better control over symptoms and improve your overall quality of life during hay fever seasons. Let this blog serve as a resource for informed decision-making and proactive management, helping you breathe easier, see clearer, and feel more comfortable even when pollen levels are high.

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• Soe, K., Krikeerati, T., Pheerapanyawaranun, C., Niyomnaitham, S., Phinyo, P., & Thongngarm, T. (2023). Comparative efficacy and acceptability of licensed dose intranasal corticosteroids for moderate-to-severe allergic rhinitis: a systematic review and network meta-analysis. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1184552
• Turkeltaub, P., Norman, P., Johnson, J., & Crepea, S. (1982). Treatment of seasonal and perennial rhinitis with intranasal flunisolide. Allergy, 37. https://doi.org/10.1111/j.1398-9995.1982.tb01916.x
• Sousa‐Pinto, B., Vieira, R., Brozek, J., Cardoso-Fernandes, A., Lourenço-Silva, N., Ferreira-Da-Silva, R., Ferreira, A., Gil-Mata, S., Bedbrook, A., Klimek, L., Fonseca, J., Zuberbier, T., Schünemann, H., & Bousquet, J. (2024). Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis. The Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2024.04.016
• Li, P., Wang, N., Kai, L., Si, J., & Wang, Z. (2023). Chronic intranasal corticosteroid treatment induces degeneration of olfactory sensory neurons in normal and allergic rhinitis mice. International Forum of Allergy & Rhinology, 13, 1889-1905. https://doi.org/10.1002/alr.23142
• Nathan, R. (2003). Pharmacotherapy for allergic rhinitis: A critical review of leukotriene receptor antagonists compared with other treatments. Annals of Allergy, Asthma & Immunology, 90(2), 182-190; quiz 190-1, 232. https://doi.org/10.1016/S1081-1206(10)62138-2
• Meltzer, E. (2002). Clinical evidence for antileukotriene therapy in the management of allergic rhinitis. Annals of Allergy, Asthma & Immunology, 88(4 Suppl 1), 23-29. https://doi.org/10.1016/S1081-1206(10)62025-X
• Zissler, U., Jakwerth, C., Guerth, F., Pechtold, L., Aguilar-Pimentel, J., Dietz, K., Suttner, K., Piontek, G., Haller, B., Hajdu, Z., Schiemann, M., Schmidt‐Weber, C., & Chaker, A. (2018). Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three-year grass-pollen AIT. EBioMedicine, 36, 475-488. https://doi.org/10.1016/j.ebiom.2018.09.016
• Evans, R., Pence, H., Kaplan, H., & Rocklin, R. (1976). The effect of immunotherapy on humoral and cellular responses in ragweed hayfever. The Journal of Clinical Investigation, 57(5), 1378-1385. https://doi.org/10.1172/JCI108406
• Wachholz, P., Nouri-Aria, K., Wilson, D., Walker, S., Verhoef, A., Till, S., & Durham, S. (2002). Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1 : Th2 cytokine ratios. Immunology, 105. https://doi.org/10.1046/j.1365-2567.2002.01338.x
• Sousa‐Pinto, B., Vieira, R., Brozek, J., Cardoso-Fernandes, A., Lourenço-Silva, N., Ferreira-Da-Silva, R., Ferreira, A., Gil-Mata, S., Bedbrook, A., Klimek, L., Fonseca, J., Zuberbier, T., Schünemann, H., & Bousquet, J. (2024). Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis. The Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2024.04.016
• Li, P., Wang, N., Kai, L., Si, J., & Wang, Z. (2023). Chronic intranasal corticosteroid treatment induces degeneration of olfactory sensory neurons in normal and allergic rhinitis mice. International Forum of Allergy & Rhinology, 13, 1889-1905. https://doi.org/10.1002/alr.23142
• Nathan, R. (2003). Pharmacotherapy for allergic rhinitis: A critical review of leukotriene receptor antagonists compared with other treatments. Annals of Allergy, Asthma & Immunology, 90(2), 182-190; quiz 190-1, 232. https://doi.org/10.1016/S1081-1206(10)62138-2
• Meltzer, E. (2002). Clinical evidence for antileukotriene therapy in the management of allergic rhinitis. Annals of Allergy, Asthma & Immunology, 88(4 Suppl 1), 23-29. https://doi.org/10.1016/S1081-1206(10)62025-X
• Zissler, U., Jakwerth, C., Guerth, F., Pechtold, L., Aguilar-Pimentel, J., Dietz, K., Suttner, K., Piontek, G., Haller, B., Hajdu, Z., Schiemann, M., Schmidt‐Weber, C., & Chaker, A. (2018). Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three-year grass-pollen AIT. EBioMedicine, 36, 475-488. https://doi.org/10.1016/j.ebiom.2018.09.016
• Evans, R., Pence, H., Kaplan, H., & Rocklin, R. (1976). The effect of immunotherapy on humoral and cellular responses in ragweed hayfever. The Journal of Clinical Investigation, 57(5), 1378-1385. https://doi.org/10.1172/JCI108406
• Wachholz, P., Nouri-Aria, K., Wilson, D., Walker, S., Verhoef, A., Till, S., & Durham, S. (2002). Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1 : Th2 cytokine ratios. Immunology, 105. https://doi.org/10.1046/j.1365-2567.2002.01338.x

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