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independently confirmed by the two investigators. For each article, information on the following aspects was noted: the name of the first author, publication year, study design, form of AIT, age group (children or/and adults), treatment duration and maintenance dose, assessed outcome, total sample size, and the number of monosensitised and polysensitised patients. As we evaluated the clinical effectiveness of AIT through the changes in clinical outcomes, the mean and standard deviation (SD) values of each of the baseline and post-treatment clinical outcome were obtained from articles included in the meta-analysis. We sent an e-mail message to the corresponding author of articles in which the mean and SD of clinical outcome scores of the study were not reported to acquire these values. The risk of bias was evaluated according to the Newcastle-OttawaScale (31). Study quality was evaluated on three domains independently by the two investigators: selection of study groups, comparability of groups, and ascertainment of exposure/outcome. Statistical analysis The primary outcome was nasal symptom score, and the secondary outcomes were medication score and quality of life score. The standardised mean difference (SMD) was the measure of effect because the included studied used different scoring systems and measures. The clinical effectiveness of AIT was evaluated by the change in nasal symptom score from baseline. For studies presenting the means and SDs only in figures, means and SDs were drawn from figures. For studies reporting median and interquartile, mean and SD were estimated using an equation (32). For studies without SDs of score change from baseline to post-treatment but with SDs of score at each time, the SDs of score change were imputed by using SDs of score at each time and a within-subject correlation of 0.5 (33,34). A random-effects model was used to calculate pooled effect estimates with 95% confidence intervals (CI). Statistical heterogeneity between the studies was assessed with the Cochran Q statistic test and the I 2 statistics. I2 values of 25%, 50%, and 75% have been suggested to be indicators of low, moderate, and high heterogeneity, respectively (33). The difference in the clinical effectiveness of AIT between monosensitised and polysensitised groups was evaluated in a subgroup analysis. A sensitivity analysis was conducted to assess the influence of an individual study on the results by omitting one study in each turn. A funnel plot and Egger’s test based on SMD and sample size-based precision estimate (the inverse of the square root of sample size) (35) were used to assess the possibility of publication bias within each group for the primary outcome and not for the secondary outcomes because 354 Kim et al. Results Briefly, of the 563 citations identified initially through the search strategy, we finally included nine for the systematic review (Figure 1). Study characteristics The characteristics of the nine included studies are summarised in Table 1. The total sample size of the nine studies was 823 patients, including 411 monosensitised and 412 polysensitised patients. All were observational studies, of which four used SCIT and five used SLIT. In the included studies, patients sensitised to HDM with or without other allergens were treated with singleallergen AIT with HDM extracts. There were seven prospective cohort studies and two retrospective cohort studies. The duration of AIT ranged from 5 months to 3 years. The risk of bias for all studies was assessed using the Newcastle-Ottawa Scale. of the small number of studies included (n< 0.01 in both monosensitised and polysensitised patients). The change in nasal symptom score was not significantly different between the two groups (p = 0.944). In three (24,25,28) out of nine studies, the baseline nasal symptom score in
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