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quality of life between monosensitised and polysensitised patients, all three studies (24-26) showed comparable decrease in RQLQ score between monosensitised and polysensitised patients. In a pooled analysis, the changes in RQLQ score were comparable in the two groups. There are some possible explanations for the comparable clinical effectiveness of HDM AIT between monosensitised and polysensitised patients. First, the difference between polysensitisation and polyallergic conditions may be related to the comparable clinical effectiveness: polysensitised patients are not necessarily polyallergic. To determine true polyallergy, medical history (e.g. the association between the sensitised allergens and the period during which the symptoms occur) may not be sufficient, and nasal challenge tests or component-based diagnostics are often needed; however, these tests are seldomly used in clinical settings (17). Hence, although patients included in this systematic review were polysensitised, some patients may have had HDM as the only clinically relevant allergen. Second, HDMs play a major role in contributing to nasal symptoms, with the effect of other allergens being minor. Despite multiple clinically relevant allergens in each patient, not every allergen triggers an equivalent allergic response. In a previous study, we reported the lack of a significant correlation between the changes in the number of sensitised allergens and the changes in nasal visual analogue scale (VAS) score in children treated for 3 years with SLIT (36), suggesting that allergens other than HDM do not have a significant effect on nasal symptoms. Therefore, single-allergen AIT with one clearly responsible allergen may have comparable clinical effectiveness. The present study has some limitations. First, the clinical effectiveness of AIT in monosensitised and polysensitised patients was evaluated without control groups. Ideally, two pairs were needed for the design of this meta-analysis: monosensitised patients treated with AIT versus monosensitised patients treated with placebo, and polysensitised patients treated with AIT versus polysensitised patients treated with placebo. Although there are several controlled studies for AIT in monosensitised patients, no controlled study for AIT in only polysensitized patients was found. Therefore, we used the changes in nasal symptoms, 358 Kim et al. medication, and quality of life scores from pre-treatment to post-treatment in monosensitised versus polysensitised patients from studies with results for both groups. Second, the clinically relevant allergen was not clearly demonstrated in several of the included studies. Among nine included studies, only four (23,24,28,29) demonstrated clinical relevance for HDM sensitization in their inclusion criteria, whereas five (21,22,25-27) merely described subjects as those with AR sensitized to HDM. As HDM plays a major role in countries where the individual studies were conducted, patients with AR sensitized to HDM may have a clinically relevant HDM allergy. However, confirming the clinical relevance is very important before starting AIT. Furthermore, only two studies demonstrated clinical relevance for allergens other than HDM, which suggests that some polysensitised patients might not be polyallergic. Therefore, patients who are not true polyallergic might contribute to the comparable clinical effectiveness of HDM AIT between monosensitised and polysensitised patients. To the best of our knowledge, this is the first systematic review and meta-analysis to compare the clinical effectiveness of single-allergen AIT with HDM extracts in monosensitised and polysensitised patients. Despite its limitations, we believe this study may provide supporting evidence and rationale for single-allergen AIT for indications other than grass pollen in
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