Data from this prospective cohort study showed that pollen SCIT improved HRQoL, and reduced symptoms after 1 year of treatment and the improvements were maintained during the study period. The proportion of children with severe and/or very severe symptoms decreased significantly after 1 year of pollen SCIT. Moreover, there was an association between symptoms and the different domains of HRQoL: more symptoms were associated with decreased HRQoL. As expected, we could also see a decrease in IgE levels and an increase in IgG4 levels after 3 years of pollen SCIT.
The present study is one of few studies that has assessed long-term effects on symptoms and HRQoL of pollen SCIT in children. However, a recently published study examined children (5–15 years, n = 163) and adults (n = 236) treated with SLIT for grass pollen allergy. The results showed a good effect on both HRQoL and symptoms during the 3-year study period , which is in line with our study. Another long-term study, which compared the effects on HRQoL between SCIT and SLIT for children allergic to pollen or house dust mites, showed similar results after 3 years of immunotherapy . In a study observing the effects of 1 year of pollen SCIT in children from age 12 years and adults with allergic rhinitis, HRQoL improved significantly, and asthmatic symptoms were reduced .
Changes in HRQoL may depend on age and maturity. Our study shows extensive improvement in HRQoL after 1 year, but it can be discussed if the aging process could play a role in this. However, we measured the effect of pollen SCIT in three different ways (HRQoL, symptoms and immunological factors), all of which showed an effect, which may indicate that neither age nor maturity affected the outcome, despite a long treatment period.
Our results with reduced symptoms after pollen SCIT are in line with the findings of a review study  that summarized data from 160 pollen SCIT and SLIT studies in children and adults (most adult participants) with allergic rhinoconjunctivitis and examined the symptom effects of pollen SCIT. Allergen-specific immunotherapy was found to be effective in decreasing symptoms and reducing medication needs in patients with allergic rhinoconjunctivitis during the treatment period .
In the present study, more boys than girls received pollen SCIT, and the girls were older when they started with the treatment, something seen in previous studies. Further, it has been reported that girls with allergic rhinitis are underdiagnosed and undertreated [17, 23]. This indicates that there is a need to investigate why there are gender differences in diagnosis and treatment.
In our study, having more symptoms affected HRQoL negatively. It is difficult to make a direct comparison with published literature, as there are no previously published reports on factors influencing HRQoL in connection with SCIT. A Swedish study examined how different allergic conditions affected HRQoL in children, showing that asthma significantly affected HRQoL and that allergic comorbidities also impacted HRQoL .
Allergen-specific immunotherapy requires commitment from the child and their family. This can be compared with treatment of other chronic diseases, such as oral immunotherapy in children with peanut allergy. In our study, HRQoL improved after pollen SCIT. In a randomized placebo-controlled study  which assessed, among other things, how quality of life was affected after oral immunotherapy with peanuts, a significant improvement in HRQoL was found after treatment completion .
The strengths of the present study include that it was performed in a clinical setting, evaluating effects of pollen SCIT over time and with a relatively large number of participants. The children started the treatment in different years, which decreased the impact of different pollen counts in different years. All children and adolescents received the same treatment, which was given in accordance with guidelines. In the present study, we used DISABKIDS, a validated instrument for assessing HRQoL in children with chronic diseases. It is considered suitable for capturing the emotional impact of the allergic disease, which can be difficult to do with disease-specific questionnaires [26,27,28].
A limitation of our study was the lack of a placebo control group; use of such a group was impossible for ethical reasons. Measurements of HRQoL based on life situations are difficult to evaluate as both subjective and objective circumstances must be considered. Measuring the effect of pollen SCIT in three different ways (HRQoL, symptoms, allergen-specific IgE and IgG4 antibodies) decreased the risk that the results depended on other circumstances.
DISABKIDS consists of 37 items, which may have affected the tendency to complete the questionnaire . The younger children answered the questions with help of their parents when required, which may have affected the answers. To register symptoms from eyes, nose and/or lungs, we used symptom scores, which are not a validated instrument. Also, a limitation could be that we have no data on medication use during the time of immunotherapy.