Although asthma management guidelines emphasize the importance of assessing HRQOL (4
), the impact of asthma genetics on HRQOL have not been described. The genetic variants examined in this study were among some of the most highly replicated within the asthma literature, demonstrating associations with PFT, asthma symptoms, and IgE (10
). We sought to extend scientific knowledge by determining whether the same association between previously implicated genes and asthma symptoms could be shown with HRQOL.
Results from this study identified key differences in child HRQOL, with the following individual SNPs evidencing significant variations: IL-4RA rs 1805010 and IL-4 rs 2243250. Specifically, children homozygous for the major variant at each of the aforementioned SNPs evidenced significantly better HRQOL than their counterparts. Moreover, when variants were combined and contrasted (i.e., children homozygous for major variants were compared with children carrying either one or two minor variant alleles), children homozygous for major variant alleles continued to demonstrate better HRQOL. Because significant associations with pulmonary function were not observed, results from this study suggest that genes can be associated with asthma HRQOL independent of pulmonary function.
The most likely explanation for these observations is that the same genes that influence pediatric asthma symptoms and severity influence HRQOL, but that HRQOL may be a more sensitive outcome for asthma genetic studies than lung function. An alternative explanation is that genes have a role in child and maternal perceptions of HRQOL. The idea that genes influence individuals’ sensitivity to and interpretation of stressful events and mood reflects a bio-behavioral approach to adjustment (26
). Even though behavioral genetic analysis of parent and child perceptions was not specifically measured here, previous studies provide support for the unique influence of genetics on childhood psychological and behavioral factors (27
Results of this study should be viewed in light of several limitations. First, some differences are statistically significant, but may be less clinically meaningful due to relatively similar mean values. Second, gene-gene interaction effects were not conducted for HRQOL or pulmonary functioning due to low sample power. Moreover, the effect of asthma therapy on HRQOL was not considered in this analysis. It may be that particular SNPs predispose children to better response to asthma treatment, thereby rendering better HRQOL. Alternatively, children not receiving the preferred treatment or those with genetic profiles that are not responsive to the preferred treatment could be expected to evidence worse HRQOL. Previous research in the area of pharmacogenetics suggests that airway symptoms for adults and children alike do respond to asthma medication treatments differently based on genotype (29
). Differential response to asthma treatment could likely mean a differential impact of asthma symptoms on quality of life.
Finally, the current study utilized parent-reported HRQOL for children. Prior research indicates parent and child reports of HRQOL may be discordant (30
) possibly owing to differences in the way that parents and children interpret events or respond to Likert scales (i.e., endorsing very high or very low scores versus moderate; (32
). Moreover, parents may be more accurate in describing behavioral or family impact of illness, and children and adolescents may be more accurate in describing effects on mood (34
). Additional research incorporating child self-report is needed to substantiate this study’s initial findings.
Maintenance of patients’ functional well-being is a primary goal for medical practitioners and one that requires on-going, comprehensive assessment (35
). Everyday, patients and families make decisions about medical treatment based on an array of factors, only some of which relate to their health status. Factors such as medication side effects, forgetfulness, peer perceptions, and family functioning can all influence decisions about treatment, and conceivably, perceptions of health status (36
). Information gained from a comprehensive assessment of how children with asthma are feeling and functioning is vital to enabling clinicians and families to better manage the clinical visit, address therapeutic options, and accurately assess treatment efficacy. To this end, HRQOL assessment, including not only a discussion of asthma symptoms but their perceived functional impact, supports clinicians in determining best course of care and outcome.
Previous research indicates that including an assessment and discussion of HRQOL in clinical care is not only feasible, but preferred by patients. Wagner et al found that the majority of patients with epilepsy who took part in a randomized controlled trial regarding the routine use of HRQOL assessment in clinical care wanted their clinician to ask about emotional and physical functioning and reported a willingness to complete a brief questionnaire at each visit to facilitate the assessment process (39
). These findings were irrespective of whether or not patients were part of the intervention. Moreover, clinicians rated the availability of health status assessment as most helpful in treating patients with poorer functioning. More recent research found that including HRQOL in regular clinic visits was associated with higher patient- reported satisfaction and resulted in improved self-reported HRQOL (40
The current study’s findings suggest that clinical efforts to improve health outcomes in pediatric asthma should target those most at-risk for poor HRQOL. Our data support that genetic biomarkers may help distinguish this group in childhood asthma. Thus, there is potential for genetic tests to inform personalized medicine not only in terms of asthma risk, but also HRQOL. Additional research is needed to help clarify the impact of genes on asthma treatment responsiveness and health functioning to better inform pediatric personalized medicine and improve children’s HRQOL.