Dissertation
Incidence, transcriptomic, and clinical consequences of sleep apnea: snoring is not boring for blood cancer patients
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2024
DOI: 10.25820/etd.007783
Abstract
Sleep apnea is a common but underdiagnosed condition. The central objective of this thesis is to investigate sleep apnea incidence in clinical patient populations, explore the gene transcription alterations it introduces, and consider the clinical implications of importance to treating sleep apnea patients.
We prospectively assessed respiratory distress in multiple myeloma patients and cancer-free patients recruited from Iowa Healthcare clinics via overnight oximetry. Bone marrow samples were collected via biopsy from multiple myeloma patients and sequenced at the Iowa Institute of Human Genetics.
Respiratory distress levels in both multiple myeloma and cancer-free patients were three times higher than in the general population in published prospective investigations. Respiratory distress was associated with worsened induction chemotherapy response in multiple myeloma patients, an indicator of poor prognosis. There were myeloma-related gene expression differences associated with respiratory distress in a suspected macrophage-monocyte lineage cluster.
The high incidence of respiratory distress coupled with the impact of respiratory distress on multiple myeloma prognostic indicators may justify sleep apnea screening for all newly diagnosed patients with multiple myeloma. The differential gene expression data support our hypothesis that there are myeloma-relevant genetic changes associated with respiratory distress. We expanded this investigation to two studies aimed at improving clinical practice for patients with sleep apnea.
We sought to test the hypothesis that shared medical appointments (SMA) can alleviate demand for sleep apnea referrals without significantly affecting adherence to treatment protocols. We quantitatively evaluated: 1) wait time between apnea testing and initiation of treatment; 2) care delivery measured by billing productivity; 3) patient adherence to positive airway pressure (PAP) therapy after implementation of SMA; and 4) value of services provided and the associated relative value units (RVUs). With SMA, there was a significant reduction in the mean number of days between the home sleep apnea test and initiation of treatment. There was a significant reduction in per-patient reimbursements following the implementation of SMA. On the other hand, there was not a significant difference in the number of patients seen in the clinic in total nor a significant difference in the generation of RVUs. There was no significant difference in maintenance of PAP compliance between patients who received initial treatment during a shared appointment when compared to an individual appointment. SMA reduced time to treatment and did not negatively affect PAP adherence, suggesting improved clinical care.
Opioids continue to be the leading cause of US drug overdose deaths. Evidence from clinical and basic science studies suggests a feedforward mechanism between sleep apnea and opioid use. We used data obtained from TriNetX electronic health records network to retrospectively assess opioid prescription patterns in adult patients diagnosed with sleep apnea. Sleep apnea patients were more likely to receive an opioid prescription, had a shorter record duration between their sleep test and the first subsequent opioid prescription, and these patients had more recorded visits with an opioid prescription than patients with negative sleep tests. These results confirm that the basic science suspicions of a feedforward relationship between sleep apnea and opioids are borne out in the medical record.
Taken together, our findings serve as a call for increased screening for sleep apnea. Locally, sleep apnea occurs at a much higher incidence rate than in the general population. Respiratory distress impacts an indicator of multiple myeloma prognosis and is associated with transcriptomic changes in the bone marrow. Shared medical appointments can improve our healthcare systems ability to screen more sleep apnea patients by reducing barriers without compromising care. Finally, sleep apnea may be contributing to the ongoing opioid epidemic as patient medical records show sleep apnea patients are more likely to receive an opioid prescription despite Centers for Disease Control recommendations against opioids for that population.
Details
- Title: Subtitle
- Incidence, transcriptomic, and clinical consequences of sleep apnea: snoring is not boring for blood cancer patients
- Creators
- Charles R Jedlicka
- Contributors
- Melissa L Bates (Advisor)Michael H Tomasson (Committee Member)Merry L Lindsey (Committee Member)Anna E Stanhewicz (Committee Member)Erin E Talbert (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Health and Human Physiology
- Date degree season
- Summer 2024
- DOI
- 10.25820/etd.007783
- Publisher
- University of Iowa
- Number of pages
- xviii, 167 pages
- Copyright
- Copyright 2024 Charles R Jedlicka
- Grant note
- [Grants applied for included in IRB form, 135.]
- Language
- English
- Date submitted
- 07/17/2024
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 98-113).
- Public Abstract (ETD)
- Sleep apnea is diagnosed in 3-5 percent of US adults. However, when the general population are screened for sleep apnea, 15-30% of US adults meet the criteria for sleep apnea diagnosis. Who are these undiagnosed patients? What medical conditions do they face? Is our healthcare system prepared to meet their needs if these folks seek diagnosis and treatment? These questions are the impetus for our investigations. Sleep apnea is linked to several health conditions including high blood pressure, stroke, heart failure, type 2 diabetes, and cognitive impairment. Additionally, sleep apnea is associated with cancer incidence and mortality. We investigated the incidence, clinical, and transcriptomic consequences of sleep apnea in a multiple myeloma cohort. In this thesis, our data demonstrate the critical need for blood cancer patients to be screened for sleep apnea. Our patients were three times more likely to meet the diagnostic criteria for sleep apnea than the general population. Multiple myeloma patients with sleep apnea were less likely to respond to their first round of chemotherapy. They also had myeloma-related transcriptomic changes in their bone marrow. We also demonstrated that shared medical appointments can improve our healthcare system’s capacity to screen and treat patients with sleep apnea by decreasing barriers without compromising care. Lastly, we reviewed medical records of sleep apnea patients in the context of the opioid epidemic. Contrary to Centers for Disease Control recommendations, sleep apnea patients are more likely to be prescribed opioids compared to patients without sleep apnea.
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984698250002771
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