Unfolding Allergic Rhinitis and Asthma Link: Reviewing Role of Intranasal Spray in Pediatric Patients

symptom complex comprising nasal itching, sneezing, rhinorrhea, and nasal blockage, AR represents a global health issue that contributes to significant morbidity. (1)

AR in childhood & the Burden of Lifelong Consequences-

AR can have a negative impact on a child's quality of life through symptoms alone. Still, it can also affect nearby organs like the sinuses, ears, and chest and lead to sleep issues. Research reveals that the percentage of new cases with seasonal AR increases between the ages of 3 and 12 years, at a rate of ~2% per year. (2,3)

• Left untreated, AR can have a negative impact on academic and occupational performance, and reduce participation in outdoor activities. (1)
• AR predisposes to asthma and interferes with the control of concurrent childhood asthma.
• AR increases the risk of hospitalization, physician visits, asthma drug costs, use of short-acting beta-agonists, and use of oral corticosteroids. (1)
• By the time they reach the age of 20, more than 60% of children with AR have comorbid ocular symptoms too. Studies further highlight that one-third of them experience severe chronic symptoms that significantly interfere with their everyday lives. (1)
• Studies have consistently highlighted that rhinitis in childhood strongly predicts adolescent- and adult-onset asthma. (1)

Such scientific evidence calls for a need of optimizing care and early aggressive management of pediatric AR and concurrent asthma symptoms.

Managing the pediatric AR-asthma comorbid-Is there a solution?

Current key therapeutic modalities for pediatric AR include allergen avoidance and pharmacotherapy. (4)

• Allergen avoidance- While avoidance of allergens and pollutants both inside and outside the home is crucial; recent research has put forth that indoor air pollution is linked to eczema, dermatitis, conjunctivitis, AR, and asthma. Smoke, dampness, burning wood, fossil fuels, dust, chemicals in furniture and construction supplies, aerosol sprays, and cleaning supplies are all sources of indoor air pollution; and should be avoided.
• Role of Intranasal Antihistamines: Given the fact that the first-generation anti-histamines are not recommended in the pediatric population due to their well-known adverse effects, including psychomotor retardation and behavior disturbances, the focus has shifted to their second-generation successors, specifically for controlling mild AR. (1,5) Topical intranasal antihistamines (INAH) work faster (within 15 minutes) and are more effective than oral antihistamines. Studies further confirm that the patient should be shifted to an intranasal antihistamine if an oral antihistamine fails to control the symptoms. Among the available options, Azelastine has been demonstrated to be effective and safe in children with AR. (1)
• Role of Intranasal corticosteroids - Intranasal corticosteroids (INCS) are helpful as first-line treatment for moderate to severe AR. (1) Intranasal corticosteroids exhibit strong anti-inflammatory effects on the pathophysiologic components of both early and late-phase allergic reactions. (6,7). Fluticasone furoate is among the INCS with the least systemic bioavailability, exhibits good safety data, and is preferred for long-term pediatric use. (1)

Along these lines, The International Academy of Pediatrics (IAP) has recently formulated recommendations on drug therapy of AR in children (8), as summarised below:

• The choice of medications may be influenced mainly by the child's prominent symptoms.
• The controller drug is inhaled nasal steroids (INS), preferably an INCS with poor systemic bioavailability, such as Fluticasone Furoate, with continuous professional monitoring. A minimal dosage is recommended to achieve symptom management.
• Fluticasone furoate is indicated for children aged 2 to 11 years. The recommended dose for 2-11 years is 27.5 mcg/nostril OD. For children aged >12 years, it is 55 mcg/nostril OD.

The INCS in focus: Study testimonials on Fluticasone furoate nasal spray:

Efficacy & Safety:

• According to another research conducted to test the safety and efficacy of once-daily fluticasone furoate (FF) nasal spray in children with perennial allergic rhinitis (PAR), FF 55 µg led to substantial improvement in nasal symptom scores for nasal congestion, rhinorrhea, nasal itching, and sneezing (p = 0.003) compared to placebo. (9)
• Fluticasone furoate nasal spray was tested in multi-center research on children with perennial allergic rhinitis to determine its safety and effectiveness. 61 Japanese children between the ages of 2 and 15 were included in the trial and received treatment for 12 weeks with fluticasone furoate nasal spray, 55 mcg once daily. According to the results, fluticasone furoate nasal spray 55 mcg significantly reduced nasal symptoms, including sneezing, rhinorrhea, and nasal congestion, when compared to the baseline, with a mean difference from the baseline over the course of the entire treatment period. According to the study, fluticasone furoate nasal spray is safe for children ages 2 to 15 and effective with negligible systemic exposure. (7)
• The same author conducted a second multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III study with 261 children aged 6 to 15 years who were treated with fluticasone furoate nasal spray 55 mcg once daily or a placebo for two weeks. Mean changes in sneezing, rhinorrhea, and nasal congestion from baseline for the entire treatment period were higher in the FFNS 55mcg group compared to the placebo group, and the difference was statistically significant (p < 0.001). FFNS (55mcg, once daily is effective and tolerable in children (aged 6-11 years). (10)

Dosage Regime of Fluticasone Furoate Nasal Spray

For children (2 to 11 years of age)- The recommended starting dosage is one spray (27.5 mcg) in each nostril once daily (total daily dose, 55 mcg). Patients not adequately responding to one spray in each nostril once daily (total daily dose, 55 mcg) may use two sprays in each nostril once daily (total daily dose, 110 mcg). Once adequate control of symptoms is achieved, dose reduction to one spray in each nostril once daily (total daily dose, 55 mcg) is recommended. (11)

Fluticasone Furoate Nasal Spray -Patient Benefit of Superior Sensory Attributes:

• When comparing the sensory features of FFNS to those of other INCs, patients preferred FFNS. Patients preferred FFNS over fluticasone propionate nasal spray (FPNS) when deciding between similar sensory perceptions as scent, aftertaste, and mist gentleness. Also, patients preferred FFNS to mometasone furoate nasal spray (MFNS) due to fewer unfavorable sensory experiences with FFNS compared to MFNS, suggesting that FFNS is associated with higher patient adherence and better treatment results. (12)

Benefits of Combination Therapy-

• Studies indicate that 56% of AR patients continue to rely on two or more prescription drugs to control AR. Integrating two medications into a single system reduces costs while significantly enhancing patient compliance. The addition of an antihistamine is advised for children whose AR remains uncontrolled despite regular use of an INS. (1)

Key pointers-

• Childhood allergic rhinitis frequently goes undiagnosed, untreated, and misunderstood. It can advance to asthma or slow down the management of pre-existing asthma, has significant comorbidities, and has negative consequences on quality of life and academic performance.
• Correct diagnosis and successful treatment are crucial to prevent chronic complications.
• Intranasal antihistamines and intranasal corticosteroids show promise in managing pediatric AR-asthma comorbid effectively.
• Combining these two drug classes into a single system has led to increased efficacy, patient compliance, and better clinical outcomes.
• FFNS is an appealing treatment option for controlling pediatric AR since it is both safe and effective, and practically advantageous based on the patient's preferences.

References

1. Scadding, G. K., Smith, P. K., Blaiss, M., Roberts, G., Hellings, P. W., Gevaert, P., Mc Donald, M., Sih, T., Halken, S., Zieglmayer, P. U., Valovirta, E., Pawankar, R., & Wahn, U. (2021). Allergic Rhinitis in Childhood and the New EUFOREA Algorithm. Frontiers in Allergy. https://doi.org/10.3389/falgy.2021.706589

2. Gough H, Grabenhenrich L, Reich A, Eckers N, Nitsche O, Schramm D, et al. Allergic multimorbidity of asthma, rhinitis, and eczema over 20 years in the German birth cohort MAS. Pediatr Allergy Immunol. (2015) 26:431–7. doi: 10.1111/pai.12410 PubMed Abstract | CrossRef Full Text | Google Scholar

3. Grabenhenrich LB, Keil T, Reich A, Gough H, Beschorner J, Hoffmann U, et al. Prediction and prevention of allergic rhinitis: a birth cohort study of 20 years. J Allergy Clin Immunol. (2015) 136:932–40. doi: 10.1016/j.jaci.2015.03.040

4. Roberts G, Xatzipsalti M, Borrego LM, Custovic A, Halken S, Hellings PW, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy. (2013) 68:1102–16. doi: 10.1111/all.12235

5. Scadding G K. Optimal management of allergic rhinitis. Arch Dis Child. (2015) 100:576–82. doi: 10.1136/archdischild-2014-306300

6. Anolik, R. (2010). Fluticasone furoate nasal spray: Profile of an enhanced-affinity corticosteroid in the treatment of seasonal allergic rhinitis. Journal of asthma and allergy, 3, 87.

7. Okubo, K., Okamasa, A., Honma, G., & Komatsubara, M. (2015). Safety and efficacy of fluticasone furoate nasal spray in Japanese children 2 to< 15 years of age with perennial allergic rhinitis: a multicentre, open-label trial. Allergology international, 64(1), 60-65.

8. https://iapindia.org/pdf/Ch-014-Allergic-Rhinitis.pdf

9. Máspero JF, Rosenblut A, Finn A Jr, Lim J, Wu W, Philpot E. Safety and efficacy of fluticasone furoate in pediatric patients with perennial allergic rhinitis. Otolaryngol Head Neck Surg. 2008;138(1):30-37. doi:10.1016/j.otohns.2007.10.023

10. Okubo K, Okamasa A, Honma G, Komatsubara M. Efficacy and safety of fluticasone furoate nasal spray in Japanese children with perennial allergic rhinitis: a multicentre, randomized, double-blind, placebo-controlled trial. Allergol Int. 2014;63(4):543-551. doi:10.2332/allergolint.14-OA-0688

11. https://www.sanofi.in/dam/jcr:bf814355-32d8-43cc-8fda-9276a8734f1d/Allegra%20Nasal%20%20Spray%20-%20PI.pdf

12. May, J. R., & Dolen, W. K. (2019). Evaluation of intranasal corticosteroid sensory attributes and patient preference for fluticasone furoate for the treatment of allergic rhinitis. Clinical Therapeutics, 41(8), 1589-1596.