Health & Medical Immune System Disorders

Early Intervention for Infantile and Childhood Asthma

´╗┐Early Intervention for Infantile and Childhood Asthma

Abstract and Introduction

Abstract


Asthma is a chronic airway inflammatory disease and it is accepted that early initiation of anti-inflammatory medication is beneficial for adult asthma. Pathological and epidemiological studies suggested that early intervention with anti-inflammatory drugs such as inhaled corticosteroids (ICS) should take place before preschool age, possibly between 1 and 3 years of age. However, the effect of early intervention using ICS in young children is considered controversial as several clinical studies have suggested that ICS does not alter the natural history of asthma in young children. Although there is limited and some negative evidence for the effect of ICS in young children, ICS remains the most effective medication for controlling asthma of the currently available drugs for all ages. Therefore, pediatricians should prescribe ICS to control the active symptoms of asthma, owing to the well-known, beneficial effects of ICS on decreasing the symptom burden of young children with asthma.

Introduction


Asthma is a disease characterized by chronic airway inflammation. The inflammation leads to hyper-responsiveness in the airway, with recurrent episodes of wheezing, coughing and shortness of breath. Anti-inflammatory drugs are mainly used for asthma therapy since airway inflammation has become the main target of therapy. Almost all reports and guidelines agree that inhaled corticosteroids (ICS) are the most effective anti-inflammatory drugs. The idea of 'early intervention' in asthma treatment studies the concept that earlier therapeutic intervention using anti-inflammatory drugs from the onset of asthma results in subsequently better control of symptoms and improved prognoses. Owing to the fact that asthma is a chronic disorder and the long duration of the disease induces pathologic changes in terms of airway remodeling, it is reasonable to assume that earlier therapeutic intervention is important for the improvement of long-term outcomes. Many reports have extrapolated that early intervention improves long-term outcomes; however, some reports concluded that the late-intervention group will catch up with the early-intervention group so that, after an adequate period of time, there are no differences in most of the outcomes between the two groups. One problem of these studies is the limited availability of validated clinical outcomes. For example, there are still no readily available methods that measure airway inflammation, and most of the studies used lung function indices or patient questionnaires as study outcomes. Another problem encountered is that, by their nature, early intervention studies demand prolonged and, in some cases, lifelong follow-up. To date, clinical trials of early intervention in adult asthma have tended to conclude with positive results; however, the efficacy of early intervention in infants and young children is still controversial as this young age group has additional concerns compared with older age groups.

First, the mechanism responsible for remodeling and its stimuli are still unclear, particularly in younger children. Because remodeling may lead to thickening of the airway wall and may play an important role in the pathophysiology of the disease, it is important to know, for the discussion of early intervention, how early this pathologic change starts in the natural history of asthma. Second, preschool-aged patients with symptoms of wheezing include several different phenotypes. Martinez et al. reported that, in their community-based cohort, 51.5% of children had never wheezed until 6 years of age and 19.9, 15.0 and 13.7% were classified as having transient early wheezing, wheezing of late onset and persistent wheezing, respectively. Based on their cohort study, they suggested three different wheezing/asthma phenotypes, namely transient early wheezing, nonatopic wheezing and IgE-mediated wheezing/asthma. Most of the transient early wheezing in children resolves by 3 years of age, and nonatopic wheezing in toddlers and early school-aged children resolves by 13 years of age. Thus, children who are affected by chronic asthma later in life seem to be a minority among young wheezing children. If there is a method that can identify children at high risk (IgE-mediated wheezing/asthma), it may allow us to treat them before the critical time; however, there is currently no clear method to identify these children. Third, early intervention of asthma is broadly perceived by many pediatricians to include secondary prevention of asthma and improve most of its natural history. Therefore, clinical trials in infants and young children sometimes use an end point such as improvements in natural history, prevention of asthma development or long-term prognosis instead of control of active symptoms. This makes it more difficult to evaluate the early therapeutic intervention trial because the treatment of young children is already difficult for the reasons mentioned above. Thus, early intervention in younger children is more controversial than for adult-onset asthma.

The aim of this article is to review the studies of early intervention in asthma therapy, with a focus on young children, including trials of secondary prevention of asthma development, and to discuss when treatment should be started, which children should be treated and how to start early intervention in young children.

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