Parents of wheezy infants and toddlers often ask, "When will my child ever grow out of his or her asthmatic symptoms?" This is a question that many physicians involved would like to be able to answer. Wheezing is one of the most common symptoms in preschoolers. Previous studies done in Singapore showed that 25% of toddlers had wheezing before the age of two years [1]. Other population studies have also demonstrated that approximately one in three children have at least one episode of wheezing before the age of 3 years, and that the cumulative prevalence of wheeze is almost 50% at the age of 6 years [2]. However, in spite of the high prevalence, there is little evidence regarding the pathophysiology and treatment of preschool wheezing [3].

In preschool children, not only are there different phenotypes of wheezing, the etiology of wheeze is also heterogeneous. Two major distinct phenotypes have been distinguished in previous studies: virus-induced wheezing (i.e. non-atopic), and multi-trigger (i.e. atopic) wheezing. Virus-induced wheezing, which makes up about two-thirds of all preschool wheezing, is an intermittent form of recurrent airway obstruction with normal pre-morbid lung function and asymptomatic periods between attacks. These children have a favorable prognosis, and usually only need supportive treatment. On the other hand, multi-trigger wheezing is associated with an underlying allergic constitution, and is less prevalent in preschool children. This form of wheezing tends to occur during and between episodes and is more likely to persist beyond early childhood, with associated significant deficits in lung growth up to 11 years of age [3, 4].

There is great value in being able to distinguish the persistent wheezers from the transient ones amongst preschool children for the sake of better disease management. This is because a longer duration of wheeze is associated with an increase in disease severity and more troublesome disease [5].

Studies that have been done so far have given a clinical profile of preschool children who were at increased risk of developing persistent wheeze. These factors include gender (male>female), positive atopic status, previous respiratory syncytial virus infection and the lack of anti-inflammatory treatment, especially inhaled corticosteroids. However, these factors still require further investigation and are still insufficient in helping us predict the prognosis of the disease in this age group [6].

There is general consensus among various studies that other atopic conditions, such as allergic rhinitis, atopic eczema and food allergy; and family history of atopy are factors associated with persistent wheeze [7-10]. Furthermore, in a large cohort study performed in Germany, it was demonstrated that any allergic sensitization in early life significantly increased the risk of becoming asthmatic at an older age [11]. Clinical and objective measurement of allergic sensitization can be achieved via two methods - skin prick test (SPT) or serum immunoglobulin E (IgE) testing. Although there is concordance among various studies that increased serum IgE is associated with persistence of asthma [12, 13], a clear relationship between positive SPT and asthma persistence is difficult to establish [10, 14, 15].

Thus, the objective of this study is to determine the association of a positive SPT to house dust mites (HDMs) on wheezing preschool children in Singapore and persistent wheezing at age of 8 to 14 years old.

Of the 78 children who participated in the study, 42 (53.8%) out of the 78 children had a positive SPT to at least one HDM and 36 (46.2%) of them had a negative SPT.

The study shows that HDM sensitization, demonstrated by a positive SPT to HDM at an early age in Singaporean children, is associated with persistence of wheeze at age 8 to 14 years old. This suggests that children who have a positive SPT to at least one of the three HDM have an increased risk of maintaining their asthma after 4 to 9 years, than those with a negative test for HDM. Thus, the findings propose the use of SPT as an objective tool to prognosticate the persistence of wheeze in toddlers, age two to five years old, presenting with recurrent wheeze.

At present, there are several theories explaining the pathogenesis of atopic wheeze, which usually results in persistent wheeze. For decades, the primary assumption is that allergy is caused by overactive immunological responses against allergens, driven by activated Th2 cells and due to aberrant T-regulatory cells [18, 19]. Recently, Turi et al postulated that the impaired epithelial barrier function that allows aeroallergens to trigger the overactive immunological responses could be a direct result of proteolytic activities of aeroallergens, including HDM [20]. The current hypothesis is that Der p1 m, the major allergen in HDM, causes injury to the epithelium and enters the tissue to induce inflammation via Toll-like receptor 4 [21, 22]. Another allergen found in HDM, Der p 2 also activates respiratory epithelial cells aggravating and resulting in a more prolonged and persistent wheeze [23].

However, as to whether HDM is causal in its relationship with atopic wheeze, resulting in persistent wheeze, it is still a common consensus that HDM sensitization is one of the strongest and most consistent associations with persistence of wheeze in various types of studies from different populations across different time periods and age groups [24-27]. Holt et al. [24], in a population where HDM was the dominant allergen, had similar findings and found that specific IgE to HDM at age two years to be a strong predictive factor of persistent wheeze by age five years (12.7% risk). The Manchester Asthma and Allergy Study group, which studied the sensitization to HDM at age 1, 3, 5, and 8 years, also established that early sensitization to HDM carries the greatest risk of persistent wheeze [27]. Similarly, the Multi-Centre Allergy Study group concluded that those with early (1 year) inhalant sensitization to be a high-risk group for asthma at age 7 years [28].

This makes a positive SPT to HDM, which demonstrates HDM sensitization, an important marker of potentially difficult and persistent wheeze in children, as it is the most common allergy in children in Singapore.

In this study, however, the association between HDM sensitization and current eczema or rhinitis was not demonstrated. Further studies, with larger population are suggested.

The differences in baseline demographics between the SPT positive and SPT negative groups were found to be statistically insignificant (p < 0.05) (Table 1). Thus, there are no potential confounding factors that may affect the results.

In conclusion, our findings have clinical implications. In areas of high HDM prevalence such as Singapore, HDM sensitization status demonstrated by a positive SPT could be used as an objective marker to identify toddlers at risk of persistent wheeze. Therefore, a positive SPT to HDM demonstrating HDM sensitization in young children with early wheeze would allow for more informed discussions between physicians and parents about subsequent risk of persistent wheeze, allowing for better management.

The limitation of this study is that all the participants were recruited from a high-risk group and therefore may differ from the general population in the prevalence of atopic and allergic disease. Further exploration can be done in populations who are not at similar risk.