Early Predictors of Asthma : Comparing Absolute Eosinophilic Count with IL-4 and IL-5

Abstract

Asthma is a chronic inflammatory disorder characterized by hyperresponsiveness and inflammation of conducting airways. It is a heterogeneous disease with different phenotypes based on clinical, functional or inflammatory parameters [1]. The disease presents with recurrent episodes of wheezing, tightness of chest and shortness of breath, with cough particularly in early morning.[2] Prevalence of the disease varies between 1-18 % of population in different countries with 300 million people affected worldwide [3,4]. It occurs at all ages and its prevalence has been increasing in developing countries. The disease increases health burden in the population, decreases productivity and causes considerable morbidity and mortality [5]. The clinical severity of asthma ranges from mild to severe. The common symptoms are usually due to variable bronchoconstriction causing limitation of airflow [6]. The disease is episodic in nature with increase in frequency and intensity over time. It can be triggered by viral infections, allergens, tobacco smoke, exercise, stress and drugs like aspirin, beta blockers and NSAIDS. Asthma is now hypothesized to be a T helper type 2 (Th2) inflammatory disorder with increase in the number of Immunoglobulin E (IgE) producing cells. The Th2-type cytokines, such as interleukin 4 (IL-4) and interleukin 5 (IL-5) are responsible for numerous effects important in bronchial asthma. IL4 has been implicated as the main cytokine involved and causes stimulation of mucus producing cells and fibroblasts, leading to airway remodeling [7-10]. Eosinophil is the main effector cell in allergic inflammation. IL-5 is the primary cytokine involved in in-vivo production, differentiation, maturation and activation of the eosinophils. Expression of IL-5 mRNA correlates with clinical indices of disease severity in asthma and the expression of IL 5 receptor in bronchial biopsies is more than 90% restricted to eosinophils.[11] Short-term treatment mainly consists of oral or inhaled corticosteroids (ICS). Long term medications include Anti-IgE and anticholinergic drugs which are useful in patients with severe asthma. Anti-IL5 (mepolizumab) and anti IL5R (benralizumab) medications are being offered to patients with severe uncontrolled eosinophilic asthma on high dose ICS. Anti-IL4R (Dupilumab) is also an option for these patients.