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].

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.