Acceptability and Feasibility of Salivary Stress Research with Adolescents and Young Adults with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) primarily impacts Black and African Americans, who often face social inequities, such as intersectional discrimination and low neighborhood resources. These stressors can “get under the skin” and influence biological stress responses that have negative downstream impacts on overall health. Nevertheless, despite the consensus that salivary cortisol is the gold standard measurement of physiological stress, only 1 published study with a small sample (n = 22) has investigated cortisol in SCD using salivary methods. The aims of the present study were to (1) determine the acceptability and feasibility of at-home saliva collection and (2) examine social-ecological and disease-related correlates of participation in salivary stress research.

Method: Adolescents and young adults (AYA) with SCD (ages 16 to 25 years) recruited from outpatient clinics completed a survey study with the option to opt into a 1-day, 4-sample, at-home saliva collection. AYA who opted into salivary study were provided with materials to complete collection and log each sample within a mobile application at (1) waking, (2) 30 minutes after waking, (3) 8 hours after waking, and (4) bedtime. AYA stored saliva in their home freezer prior to returning samples to study team in a sealed refrigerated envelope with ice pack. Samples were then assayed at the Salimetrics' SalivaLab (Carlsbad, CA). Acceptability was assessed via survey regarding: (a) likelihood to provide saliva for research, (b) barriers to and (c) facilitators of saliva collection, and (d) perceived difficulty of collecting samples at each daily timepoint. Feasibility was assessed via (a) saliva collection enrollment rate, (b) completion rate, (c) days taken to return samples to study team, and (d) proportion of samples meeting quality criteria for analysis. Social-ecological factors were assessed using AYA demographics, the Perceptions of Racism in Children and Youth (PRaCY) survey, and census tract-level neighborhood factors from the 2020 American Census Survey. Disease-related factors were obtained from the electronic health record, and self-management skills were assessed using the Transition Readiness Assessment Questionnaire, 6^th edition.

Results: Forty-nine AYA (Mean_age = 19.6, 40.8% female sex) completed acceptability surveys. Findings show that 70% reported being Likely or Very Likely provide saliva samples for research, 15% were Neutral, and 15% were Unlikely or Very Unlikely. Further AYA endorsed forgetfulness as the primary barrier to engagement in salivary research (79.6%) and text-message reminders as the primary facilitator of engagement (77.6%). Finally, 61.2% to 81.7% of AYA rated each saliva collection timepoint as Easy or Very Easy to collect, 10.2% to 20.4% rated collection timepoints as Neutral difficulty, and 14.3% to 20.4% rated collection timepoints as Difficult or Very Difficult.

Most AYA who completed surveys opted into the at-home saliva collection (75.5%; n=37). Of these, 86.5% (n = 32) completed and logged their samples at waking and 30 minutes after waking, 73.0% (n = 27) completed their sample 8 hours after waking, and 62.2% (n = 23) completed their bedtime sample. In total, 89.2% (n = 33) collected and returned at least 2 samples to study team. Of these, 81.8% (n = 27) returned their samples via clinic drop off and 18.2% (n = 6) requested a home-pickup. On average, the study team received samples 35 days after collection. Cortisol assays showed that 96.5% of total samples (110/114) met quality criteria for analysis.

Finally, findings from independent samples t-tests and chi-square tests showed that AYA with higher neighborhood poverty, more hospitalizations in the year prior to enrollment, and lower self-management skills were less likely to opt into saliva collection. Age, sex, SCD genotype, and PRaCY scores were not associated with participation in the salivary arm of the study.

Conclusion: Findings demonstrate that at-home saliva collection for stress research is both acceptable and feasible among AYA with SCD. However, lower participation rates in individuals facing higher neighborhood poverty, more hospitalizations, and lower self-management skills were identified. Findings highlight the need for tailored support strategies to enhance participation in salivary research within this population, ultimately contributing to a better understanding of stress-related biomarkers in SCD.

Crosby:Takeda: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk (Forma Therapeutics): Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Professional Resource Exchange: Patents & Royalties. Thompson:Editas: Consultancy, Research Funding; Beam Therapeutics: Consultancy, Research Funding; Novartis: Research Funding; bluebird bio: Consultancy, Research Funding; Global Blood Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; CRISPR/Vertex: Consultancy, Research Funding.