Aero-Allergen induced Allergy:Indian Practitioners' Review and Scope of Fexofenadine

Allergic rhinitis (AR) and asthma are the most pervasive forms of allergy diseases worldwide. (2) Aero-allergens such as pollen, fungus, insects, and dust mites are a major cause of allergic respiratory disorders. (3) Aeroallergens have a significant role in the aetiology of allergic disorders, and sensitivity to them varies among countries and geographical areas. (2)

Patterns of sensitization to Aero-allergens:

India is a diverse country with a wide range of flora, wildlife, climates, lifestyles, and dietary habits. More than 25% of Indians are reported to be allergic to one or more allergens as cited in scientific literature. (1)

Aero-allergen Induced Allergy–Indian Evidence:

A review conducted by Laha A et al. explores the field of aero-allergy in India during the last two decades, with special emphasis on patterns across various centres [such as West Bengal, Bihar (Eastern region); Delhi, Chandigarh, Uttar Pradesh (Northern re- gion); Karnataka, Telangana (Southern region); Rajasthan, Maharashtra (Western region); Madhya Pradesh (Central region)] and relevant scientific advances in this direction. The following are the key points as highlighted below: (3)

• In India, 83 pollen, 34 fungi, six forms of dust mites, and 19 insect species have been reported as relevant allergens.
• Polymorphisms in 40 genes in the Indian population indicate specific allergic pathways in predisposed individuals.
• The review noted that from the Central region, major pollen allergens are Ailanthus, Carica, Datura and Parthenium. In Western region, Parthenium hysterophorus, Cynodon dactylon, Ipomoea sp., Holoptelea integrifolia, Cassia sp., Ischaemum sp. etc are the dominant allergens. In the Eastern region Saccharum of- ficinarum (grass) is the major one. This suggests that diverse regional aeroallergen exposures in India necessitate a tailored approach to diagnosis and treatment.
• Aero-allergic diseases have a complex interplay between genetic and environmental factors. Having said that, a critical analysis of environmental allergens (such as pollens, fungal spores,dust mites, etc) would help clinicians choose relevant allergens for testing and adopt region-wise management of allergic diseases.

Pharmacotherapy in Respiratory Allergic Disorders: Brief Review

Pharmacotherapy is a widely used method of treating various allergic conditions in India. Long and short-acting β2 agonists, corticosteroids, antihistamines, leukotriene receptor antagonists, xanthine derivatives, and other medications are widely utilized for pharmacotherapy in India. Typically, these medications are recommended based on the clinical symptoms of the patient. (3)

Recent research has revealed that several antihistamines exhibit anti-inflammatory characteristics that are not receptor-mediated, indicating additional clinical advantage in the control of allergen-induced inflammation. (4)

Fexofenadine, a second-generation antihistamine, is a non-sedating, second-generation selective histamine H1-receptor antagonist. The drug is also known for its least sedating properties, fewer adverse effects, and increased H1 -receptor specificity compared with first-generation antihistamines. (5)

Fexofenadine in Aero-allergen Induced Allergic Rhinitis: Evidence from Clinical Studies

An open clinical trial assessed the anti-inflammatory effects of fexofenadine in patients with intermittent allergic rhinitis. The study enrolled 22 patients with intermittent allergic rhinitis due to birch and mugwort pollen. Fexofenadine 120 mg was administered once a day as a treatment intervention. A symptom score assessed clinical improvement, and nasal airway flows were measured by anterior rhinomanometry at baseline and after 2 weeks of treatment with fexofenadine. Fexofenadine induced a significant improvement in nasal symptoms (including airway obstruction, sneezing, itching, and rhinorrhea) and ocular symptoms (p<0.001), nasal edema and secretion (p<0.001), and nasal airway flow (p<0.001). The clinical improvement was related to a significant reduction in all inflammatory mediators such as prostaglandin D2, kinins, and leukotrienes (p<0.01 in all cases). The study demonstrated that fexofenadine is effective and able to mediate significant changes in different nasal lavage markers among patients with intermittent allergic rhinitis. (4)

A meta-analysis of randomized controlled trials evaluated the efficacy and safety of fexofenadine in the treatment of allergic rhinitis. Eight studies met the inclusion criteria and were included in the meta-analysis. Among 1,833 patients receiving fexofenadine and 1,699 patients receiving placebo, a significant reduction of the daily reflective total symptom scores (TSS) which include the sum of sneezing, rhinorrhea, itchy nose/palate, and itchy/watery/red eyes, (standardized mean differences –0.42; 95% CI –0.49 to –0.35, p < 0.00001) was demonstrated in the study. Positive results were also found for morning instantaneous TSS and individual nasal symptom scores (sneezing, rhinorrhea, itching, and congestion). The safety analysis did not show a significant difference in reported adverse events (AE) between the active and placebo treatment groups (OR = 1.03; 95% CI 0.87–1.22, p=0.75). The study concluded that fexofenadine is efficacious in treating pollen-induced AR. (6)

An early double-blind, randomized, 2-way cross-over study (n=25) compared the efficacy of fexofenadine and terfenadine (120 mg) for the treatment of seasonal AR to grass pollen. The finding revealed that fexofenadine appeared more effective in limiting nasal secretions than terfenadine (chi-square trend, fexofenadine vs terfenadine: p=0.008). Fexofenadine provided better protection against sneezing than terfenadine. Fexofenadine has a rapid onset of action and appears to be even quicker than terfenadine in controlling sneezing and nasal secretion. The study concluded that fexofenadine provided better protection than terfenadine against immediate allergic reactions. (7)

Take Home Clinical Pointers

• The prevalence of allergic diseases is on the rise in India.
• Aeroallergens such as pollens, fungi, insects, and dust mites are critical causative factors in the pathogenesis of allergic diseases.
• Indian literature has listed 83 pollen, 34 fungi, six dust mites, and 19 insect species as relevant allergens in the context of Indian patients.
• Antihistamines are known to have additional benefits in managing allergic diseases due to their non-receptor-mediated anti-inflammatory properties, suggesting additional effects in the management of allergen-induced inflammation.
• Second-generation antihistamines like Fexofenadine are preferred over other agents due to their less sedative properties and better safety profile.
• Several clinical trials have demonstrated the clinical efficacy and safety of Fexofenadine in aero-allergen-induced allergies.

References:

Adapted from:

1. Mahesh PA, Moitra S, Mabalirajan U, et al. Allergic diseases in India – Prevalence, risk factors, and current challenges. Clin Exp Allergy. 2023;53:276-294.
doi 10.1111/cea.14239

2. Ediger D, Günaydin FE, Erbay M, Şeker Ü. Trends of sensitization to aeroallergens in patients with allergic rhinitis and asthma in the city of Bursa, South Marmara Sea Region of Turkey. Turk J Med Sci. 2020;50(2):330-336. Published 2020 Apr 9. doi:10.3906/sag-1908-139

3. Laha A, Moitra S, Podder S. A review on aero-allergen induced allergy in India. Clin Exp Allergy. 2022;00:1-28. doi:10.1111/cea.14266

4. Schäper C, Gustavus B, Koch B, et al. Effects of fexofenadine on inflammatory mediators in nasal lavage fluid in intermittent allergic rhinitis. J Investig Allergol Clin Immunol. 2009;19(6):459-464.

5. Scadding GK, Kariyawasam HH, Scadding G, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007). Clin Exp Allergy. 2017;47(7):856-889.

6. Compalati E, Baena-Cagnani R, Penagos M, et al. Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Int Arch Allergy Immunol. 2011;156(1):1-15. doi:10.1159/000321896

7. Terrien MH, Rahm F, Fellrath JM, Spertini F. Comparison of the effects of terfenadine with fexofenadine on nasal provocation tests with allergen. J Allergy Clin Immunol. 1999;103(6):1025-1030. doi:10.1016/s0091-6749(99)70174-0