Decoding Complications of Allergic Rhinitis and Role of Early Interventions

The burden of this clinical entity:

AR is a global health problem with a reported incidence of up to 39.7 % in the West. In India, up to 30 % population suffers from allergic rhinitis, and 15 % develop asthma. (1)

AR occurs in childhood, with a mean onset age of 10.6 years. Prevalence rates of 10% are reported in those younger than 12 years, and 20% to 30% are reported among adolescents. The incidence is slightly higher in males. Although racial differences have been reported, migration studies suggest that environmental factors play a vital culprit. It was found that there is a 17% prevalence of AR among children born to parents without allergic rhinitis, a 26% prevalence in children with one parent having AR, and a 52% prevalence rate in children with both parents having AR. (2)

Understanding the Clinical Pathophysiology & Sequels of Allergic Rhinitis (AR):

The treatment of nasal obstruction, a major symptom of persistent AR, is often complicated. The complex network of inflammatory and neurogenic phenomena that induce mucosal accumulation of inflammatory cells, engorgement of sinusoidal capacitance vessels, increased permeability of blood vessels, and mucous production leads to reduced air passage through the nasal cavities. This sets up a vicious cycle with nasal congestion, which elicits mouth breathing, difficulties in falling asleep, night-time awakening, snoring, and nasal congestion on awakening with consequent daytime somnolence. (3)

Poorly managed AR symptoms can lead to sleep deprivation, secondary daytime fatigue, learning impairment, decreased overall cognitive functioning, decreased long-term productivity, and a decreased quality of life. Apart from these, poorly controlled AR may also contribute to the development of other related comorbidities, including acute and chronic sinusitis, recurrence of nasal polyps, otitis media/otitis media with effusion, hearing impairment, abnormal craniofacial development, sleep apnea, worsening of underlying asthma, and increased propensity to develop asthma. (4) The presence of AR significantly increases the probability of having asthma. Up to 40% of people with AR have or will have asthma. Atopic eczema precedes AR frequently, and patients may sometimes have conjunctivitis as well. (5)

Bronchial hyperresponsiveness (BHR) has been observed in children affected by AR. In the ‘Environment and Childhood Asthma’ birth cohort study, it was found that AR and asthma were associated with atopic eczema or food allergy connected with BHR and high Fractional exhaled Nitric oxide (FeNO) levels among adolescents, particularly among boys. Hence, there is a need for early diagnosis and intervention of both AR and asthma to prevent disease control and improve the quality of life. (6)

• AR usually precedes asthma, and several factors, like the common epidemiologic and pathophysiologic characteristics, genetic links, and treatment outcomes, support this concept. Early intervention of AR may prevent the subsequent development of Asthma in later life. Early pharmacologic interventions using non-sedating antihistamines (mainly oral), topical nasal glucocorticosteroids, and an oral leukotriene receptor antagonist (LTRA) help to reduce the disease burden and comorbidities. Montelukast, an LTRA developed for asthma treatment, has also found use in AR. Montelukast, combined with antihistamines, has substantially improved symptoms and quality of life. (7)
• Michelle C et al put forth the role of early intervention in AR. They mentioned that avoidance of allergen sensitization, allergen immunotherapy, inhaled corticosteroids, modification of the microbiome, and prevention of early-life viral infections might help limit the allergic progression. (8)
• Yonekura S et al conducted a randomized, double-blind crossover study to examine the efficacy of prophylactic treatment with an antihistamine for seasonal allergic rhinitis (SAR) using an environmental challenge chamber (ECC) on 50 patients with levocetirizine hydrochloride 5 mg. They found that early intervention with levocetirizine soon after the onset of symptoms may attenuate these symptoms as effectively as a prophylactic treatment before pollen dispersal and further added that it reduces the overall medical costs and is convenient to the patient. (9)

Depending on the disease severity, standard treatment algorithms are formulated based on the severity, chronicity, and associated comorbidities.

British Society of Allergy and Clinical Immunology (BSCAI) guidelines have put forth allergen avoidance, saline irrigation, carbon dioxide washing, and pharmacotherapy for managing AR. Pharmacotherapy in general management of AR includes the following (10):

• Second-generation antihistamines for Mild Intermittent AR
• Second-generation antihistamines + Intranasal steroids or Leukotriene receptor antagonists for Mild Persistent AR
• Intranasal steroids with or without intranasal antihistamines + leukotriene receptor antagonist + Immunotherapy for Moderate to severe intermittent AR
• Nasal saline irrigation, Intranasal steroids+ leukotriene receptor antagonist+ Immunotherapy, and ipratropium nasal spray in severe rhinorrhoea for moderate-to-severe persistent AR.

The recommended dosage of medications includes Levocetirizine at 2.5–10mg for >2 years.

Antihistamines are highly effective in reducing pruritis, sneezing, and watery rhinorrhoea. They are the mainstay therapy for allergic rhinitis. Among these, second-generation antihistamines have shown a favourable effect on sleep in patients with allergic rhinitis and are generally recommended for mild to moderate disease as first-line therapy. Montelukast reduces symptoms of allergic rhinitis not controlled with antihistamines alone by competitively and reversibly inhibiting cysteinyl leukotrienes (CysLTs), specifically leukotrienes D4 (LTD4), thus, theoretically decreasing congestion and nasal stuffiness associated with allergic rhinitis. Montelukast reduces both daytime and night-time symptoms in patients with allergic rhinitis. (12)

Benefits of Levocetirizine Montelukast Combination in Allergic Rhinitis

• A study by Gupta et al found that a combination of montelukast with levocetirizine is well tolerated and was found to be very effective in improving the Daytime Nasal Symptom Scores in patients with allergic rhinitis. A study performed on 102 patients who were randomly assigned to receive montelukast and levocetirizine or levocetirizine alone found that the combination of montelukast and levocetirizine has significantly improved the Night-time Nasal Symptom Score along with Composite Symptom Scores. (12)
• Bylappa et al. published that a fixed-dose combination of montelukast 10 mg and levocetirizine 5 mg was superior to monotherapy alone in patients with seasonal allergic rhinitis. This combination has improved the daytime nasal symptoms score and led to improvement in other symptoms of allergic rhinitis when compared with monotherapy. (13)
• Another investigation by Kim et al. investigated the pharmacokinetics and tolerability of the fixed-dose combination (FDC) of 10/5 mg of montelukast/levocetirizine compared to separate tablets. It was concluded that the pharmacokinetics and tolerability profiles of montelukast and levocetirizine after a single oral administration were comparable between the FDC and separate tablets; FDC of montelukast and levocetirizine could be a convenient therapeutic option. (14)

• AR is an IgE-mediated inflammatory disease of the nasal mucosa.
• AR often precede asthma
• Most of the primary preventive approaches aim at working on innate immune responses
• Management includes modifying environmental exposures, pharmacotherapy, and allergen-specific immunotherapy.
• Scientific evidence supports that a fixed-dose combination of montelukast and levocetirizine yields better clinical benefits than individual pharmacotherapy agents.

Given the disease burden, effective preventive strategies and early pharmacological interventions are needed to limit disease progression and enhance the quality of life of allergic rhinitis patients.