Richard J. Schwab
University of Pennsylvania · Rehabilitation Medicine
Active 1951–2025
About
Richard J. Schwab, MD, is a Professor of Medicine specializing in Sleep Medicine at the Hospital of the University of Pennsylvania. He serves as the Division Chief of the Division of Sleep Medicine within the Department of Medicine at the Perelman School of Medicine. His research focuses on the pathogenesis of obstructive sleep apnea, utilizing novel upper airway imaging techniques to understand the biomechanics of airway closure. His studies examine dynamic changes in the upper airway and surrounding soft tissue structures during wakefulness and sleep, employing magnetic resonance imaging and electronic beam computed tomography. His work has led to several novel findings, including the significance of lateral pharyngeal walls in airway caliber regulation and the characterization of upper airway changes during the respiratory cycle. Dr. Schwab collaborates closely with departments of Radiology and Biomechanical and Computer Engineering to develop advanced analysis software for three-dimensional modeling of the biomechanical relationships in the upper airway.
Research topics
- Medicine
- Internal medicine
- Physical therapy
- Intensive care medicine
Selected publications
Now is the time to prioritize sleep timing for cardiovascular health
Journal of Clinical Sleep Medicine · 2025-08-14
articleOpen accessSenior authorClinical Cancer Research · 2025-06-13
articleAbstract Background: Patients (pts) with estrogen receptor-positive, HER2-negative, locally advanced/metastatic breast cancer (ER+, HER2– LA/mBC) who relapse on/after adjuvant endocrine therapy (adj ET) and have endocrine resistance have a high unmet need. For pts who relapse on/or <12 months after adj ET, fulvestrant plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is first-line (1L) standard of care. However, fulvestrant has limited efficacy in pts with ESR1-mutated tumors and requires monthly intramuscular injections that negatively impact quality of life (QoL). New treatment options, such as combinations of an oral selective ER degrader (SERD) plus a CDK4/6i (beyond palbociclib) are needed to improve survival, QoL, tolerability, and adherence. Giredestrant is a highly potent, nonsteroidal, oral SERD that achieves robust ER occupancy and is active regardless of ESR1 mutation status. Giredestrant was well tolerated with promising activity as monotherapy and in combination with any approved CDK4/6i in Phase I/II studies in ER+, HER2– BC. pionERA BC is the first study to investigate an oral SERD (giredestrant) plus investigator’s choice of CDK4/6i in pts with 1L ET-resistant ER+, HER2– LA/mBC. Methods: pionERA BC (NCT06065784) is a Phase III, global, randomized, open-label, multicenter study in pts with ER+, HER2– LA/mBC with resistance to prior adj ET. Pts will be randomized 1:1 to receive giredestrant (30 mg orally, once daily) or fulvestrant (500 mg intramuscularly on Days 1 and 15 of Cycle 1 [28-day cycles], then on Day 1 of subsequent cycles), in combination with investigator’s choice of CDK4/6i (palbociclib, abemaciclib, or ribociclib administered per local prescribing information), stratified by: prior adj CDK4/6i (yes vs. no); choice of CDK4/6i; ESR1 mutation status by central testing (ESR1 mutated vs. ESR1 no mutation detected [ESR1nmd]); disease site (visceral vs. non-visceral). Pts will receive treatment until disease progression, unacceptable toxicity, death, or withdrawal of consent. Eligibility: female/male pts with ER+, HER2– LA/mBC; relapse on prior standard adj ET on treatment after ≥12 months or off treatment within 12 months of completion (prior neoadj/adj CDK4/6i allowed); no prior systemic treatment for LA/mBC; documented ESR1 mutation status by circulating tumor DNA. Enrollment of pts with ESR1nmd tumors will be capped at 60% of the total study population. Dual primary endpoints (EPs): investigator assessed progression-free survival (PFS) in the ESR1 mutated population and in the full analysis set (per RECIST v1.1). Secondary EPs: PFS (ESR1nmd population); overall survival (OS); investigator assessed confirmed overall response rate; duration of response; clinical benefit rate (per RECIST v1.1); time to chemotherapy; safety; pt-reported outcomes (time to confirmed deterioration in pain, physical and role functioning, global health status/QoL). The dual primary EPs will be compared between treatment arms using a stratified log-rank test at an overall 0.05 significance level (two-sided). PFS will be assessed using a hierarchical fixed-sequence testing approach. An interim OS analysis is planned at the time of the primary PFS analysis; an independent data monitoring committee review the safety data. Target enrollment: 1050 pts; recruitment ongoing. © 2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 ASCO Annual Meeting. All rights reserved. Citation Format: Kevin Kalinsky, Rinath Jeselsohn, Meritxell Bellet, Peter Fasching, Gonzalo Gomez-Abuin, Kyung Hae Jung, Sandrine Lavallé, Vanesa Lopez Valverde, Yen-Shen Lu, Richard Schwab, Nicholas Turner, Vanessa Breton, Alberto Zambelli, Fabrice André. pionERA Breast Cancer: Phase 3 study of first-line giredestrant vs fulvestrant, + a CDK4/6 inhibitor, in patients with estrogen receptor+, HER2- locally advanced/metastatic breast cancer with resistance to prior adjuvant endocrine therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-08-01.
Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16
articleMotivation: Patients with obstructive sleep apnea (OSA) are at increased risk for various disorders, thought to be caused by apnea related disturbances in cerebral oxygen metabolism (CMRO2). Goal(s): To evaluate changes in CMRO2 and upper airway architecture during sleep and in response to apneas in a sample of OSA patients and healthy subjects. Approach: CMRO2 and upper airway architecture are evaluated during sleep using a custom MRI sequence, while sleep stage was evaluated by means of concurrently recorded EEG. Results: OSA-patients experienced disturbances in CMRO2 during sleep including a larger sleep-stage dependent decrease in CMRO2 over healthy controls. Impact: Seeing how the upper airway becomes obstructed during sleep may be valuable for surgical treatment planning. Further, identification of the neurometabolic consequences of OSA can enhance our basic understanding of neuro-and cardiovascular risk.
2025-09-27
article1st authorCorresponding<bold>Introduction:</bold> Obesity is the primary risk factor for obstructive sleep apnea (OSA). Patients with OSA and obesity have increased pharyngeal soft tissue and fat volumes. In SURMOUNT-OSA, tirzepatide (TZP) demonstrated robust reductions in body weight in moderate-to-severe OSA and obesity. This study investigated the effects of TZP on pharyngeal soft tissue and fat volumes with magnetic resonance imaging (MRI) on a subset of patients from SURMOUNT-OSA Study 1. <bold>Methods:</bold> SURMOUNT-OSA Study 1 evaluated TZP MTD (10mg or 15mg) versus placebo (PBO) for 52 wks in adults with moderate-to-severe OSA and obesity not treated with positive airway pressure therapy. MRI was used to measure change in soft tissue and fat volumes from baseline to 52 wks for the tongue, soft palate, pterygoid, and lateral pharyngeal walls in participants receiving TZP (n=14) or PBO (n=14). All available data points were analyzed using mixed model for repeated measures. <bold>Results:</bold> Participants had a mean age of 49 yrs and mean BMI of 39.7kg/m<sup>2</sup> at baseline. There was significantly greater reduction in absolute soft tissue volume with TZP compared to PBO at 52 wks (Fig.1) in the tongue (p=0.022), pterygoid (p=0.003), and lateral pharyngeal walls (p=0.025). <bold>Conclusions:</bold> In SURMOUNT-OSA, TZP-treated participants displayed reductions in pharyngeal soft tissue volumes compared to PBO. This may be a mechanism by which TZP improved OSA. <fig><object-id>erj;66/suppl_69/PA6031/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>
Clinical Cancer Research · 2025-06-13
articleAbstract Background: First-line (1L) standard of care for hormone receptor-positive, HER2-negative metastatic breast cancer (HR+, HER2– mBC) is endocrine therapy + a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). However, crosstalk between the estrogen receptor, CDK4/6 and PI3K oncogenic pathways may lead to treatment resistance. PIK3CA mutations are not only associated with poor prognosis but also a predictive biomarker of response to PI3K inhibitors. The INAVO120 (NCT03006172) study showed that combining 1L inavolisib (INAVO; a highly potent and selective inhibitor of the p110 catalytic subunit alpha isoform encoded by PIK3CA) with fulvestrant (FUL) and palbociclib conferred a significant and clinically meaningful progression-free survival improvement, and numerically favorable trend in overall survival, in patients (pts) with PIK3CA-mutated, HR+, HER2– locally advanced (LA)/mBC. Abemaciclib (abema) and ribociclib (ribo) are other CDK4/6is used in clinical practice, and data showing combinability with INAVO are of great interest. We present preliminary safety data from the INAVO + FUL + abema/ribo arms of the MORPHEUS-pan BC (NCT03424005) umbrella study. Methods: Eligible pts had PIK3CA-mutated, HR+, HER2– LA/mBC, prior therapy for metastatic disease, fasting glucose of &lt;126 mg/dL or &lt;7.0 mmol/L and hemoglobin A1c levels of ≤6.4%. Pts were randomized to receive INAVO (9 mg orally [PO] once daily on Days [D] 1–28 of 28-D cycles) + FUL (500 mg intramuscularly on D1 & 15 of Cycle 1, then on D1 of each cycle) + either abema (150 mg PO twice daily on D1–28 of 28-D cycles) or ribo (400 mg PO once daily on D1–21 of 28-D cycles). Results: In the INAVO + FUL + abema arm (n = 4), one pt had received one prior line of therapy, one pt had three prior lines, and two pts had more than four prior lines. In the INAVO + FUL + ribo arm (n = 6), one pt had received one prior line, three pts had two prior lines, one pt had four prior lines, and one pt had more than four prior lines. The most common metastatic sites (occurring in &gt;1 pt in either arm) in the INAVO + FUL + abema arm were bone (n = 3) and liver (n = 2); in the INAVO + FUL + ribo arm, bone (n = 5), liver (n = 3), and lymph nodes (n = 2). At clinical cutoff (May 1, 2024) all pts were on study and receiving treatment. Median duration of safety follow-up was 2.9 months in the INAVO + FUL + abema arm and 2.5 months in the INAVO + FUL + ribo arm. All pts had at least one adverse event (AE). The most common AEs, occurring in &gt;1 pt in either arm (INAVO + FUL + abema vs ribo), included hyperglycemia (4 vs 5 pts), diarrhea (3 vs 4), vomiting (2 vs 4), increased blood creatinine (2 each), nausea (2 each), cough (1 vs 2), fatigue (1 vs 2), musculoskeletal pain (1 vs 2), erythema (0 vs 2), headache (0 vs 2), and decreased platelet count (2 vs 0). Two pts in the INAVO + FUL + abema arm and one pt in the INAVO + FUL + ribo arm had grade 3 AEs. There were no grade 4 or 5 AEs, and no AEs leading to withdrawal of any treatment in either arm. All pts in the INAVO + FUL + abema arm and two pts in the INAVO + FUL + ribo arm had AEs leading to dose modification/interruption; the most common (&gt;1 pt in either arm) were diarrhea (n = 2 in the INAVO + FUL + abema arm; n = 1 in the INAVO + FUL + ribo arm) and hyperglycemia (n = 2 in each arm). Two AEs of special interest were reported in the INAVO + FUL + abema arm (grade 2 pneumonitis, grade 3 stomatitis) and one in the INAVO + FUL + ribo arm (grade 3 hyperglycemia) per CTCAE 4.0. Conclusions: No unexpected safety findings were observed at this early timepoint in either arm; pts remain on-study and follow-up is ongoing. Treatment-related AEs for each combination were driven by the known safety profiles of INAVO and each individual CDK4/6i. Updated data, including pharmacokinetics and data from additional participants, will be presented. Citation Format: Sherene Loi, Hilary Martin, Mafalda Oliveira, Janelle Soong, Fiona Young, Clélia Cahuzac, Colby Shemesh, Chunyan Song, Kristin Kallapur, Richard Schwab, Einav Nili Gal-Yam. Preliminary safety in the inavolisib + fulvestrant + ribociclib/abemaciclib arms of MORPHEUS-pan breast cancer: A Phase 1b/2 study of efficacy & safety of multiple treatment combinations in patients with metastatic/locally advanced breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-07-23.
Effect of Neck-Bending on Upper Airway Caliber and Surrounding Soft Tissues in Controls and Apneics
medRxiv · 2025-06-06 · 1 citations
preprintOpen access1st authorCorrespondingRationale: Head and neck flexion/extension affect upper airway size. The mechanisms that contribute to these effects are unclear. Objectives: To investigate the changes in airway caliber and movement of the surrounding soft-tissues in apneics and controls during head/neck flexion and extension. Methods: Upper airway MRI was obtained in 24 controls (AHI<5; 1.5±1.5 events/hour) and 33 apneics (AHI≥5; 33.2±28.7 events/hour) with the neck in flexion, extension, and neutral positions. Differences in airway measures and soft-tissue movement were assessed. Results: During extension, controls and apneics showed increased minimum cross-sectional area (CSA) and lateral dimensions in the retropalatal airway (p≤0.007) and increases in all retroglossal airway measures (p≤0.018) compared to neutral position; controls also had increased retropalatal anteroposterior (AP) dimension (p=0.015). During flexion, both groups showed reduced retropalatal lateral dimensions (p≤0.016); controls also had reduced retroglossal CSA (p=0.007). When examining associations with degree of head/neck bending, moving from flexion to extension resulted in increased retropalatal and retroglossal airway sizes (p<0.0001), less lateral wall narrowing (p≤0.002), and more anterosuperior movement of the soft palate and tongue (p≤0.0001). Results were generally consistent in controls and apneics, although each 1° change from flexion to extension resulted in greater increases in retropalatal airway size in controls (interaction p≤0.005). Conclusion: Controls and apneics showed reductions in retropalatal and retroglossal airway caliber during neck flexion and increases during extension, primarily due to movement of the soft palate, tongue, and lateral pharyngeal walls. These data provide important insights into the role of head and neck position on upper airway caliber.
1348 Exploratory Analysis of Patient Opinions, Preferences, and Experiences with Insomnia Treatment
SLEEP · 2025-05-01
articleOpen accessAbstract Introduction Little is known about patient beliefs and preferences regarding treatment approaches for insomnia. Understanding of such inclinations will allow clinicians to better address these perspectives, and in so doing improve treatment adherence. In the present study, patient beliefs about the relevance of evidence-based treatment and preferences for and experiences with over-the-counter (OTCs), prescriptive medications (RXs), and behavioral treatments (BTs), were surveyed. Methods Four items were added to the Penn Behavioral Sleep Medicine online screener (sleeplessinphilly.com), which profiles sleep and general health of individuals seeking to participate in research. Two questions asked about the importance of safety and effectiveness information for OTCs and RXs (on a 0-5 scale, 0=not important, 5=very important). One question asked respondents to rank which of the treatment approaches (OTCs, RXs, BTs) were most and least preferable. One question asked respondents to indicate which of these treatments they had tried, and in what order. Examples were given for each treatment (e.g., BT was parenthetically defined as “4-10 week cognitive behavioral therapy for insomnia”). Results 181 patients completed the survey (82.3% female, mean±SD age of 48.2±12.2 years). The mean Insomnia Severity Index (ISI) for the group was 16.8±5.1. Roughly 80% of respondents scored evidence and safety information as important (responses of 4 or 5) for both OTCs (82.3%, 4.3±1.2) and RXs (80.7%, 4.3±1.2). The most frequently preferred first, second, and third choices were BTs (45.9%), OTCs (43.6%), and RXs (50.3%), respectively. Despite this stated preference, 71.8% of respondents tried OTCs first, 33.7% tried RXs second and 8.3% tried BTs third. Overall, just 8.8% tried BTs first, and 25.4% ever tried BTs. Conclusion Survey findings highlight that patients consider information on safety and effectiveness of insomnia treatment as important (equally so for Rx and OTC treatments), that they prefer behavioral and OTC care as compared to prescriptive medications. Interestingly, although the most patients stated a preference for behavioral therapies first, most reported trying OTCs first and only 8.8% had tried BTs first. This likely reflects the limited availability of BTs, particularly compared to the ease at which patients can access OTC therapies. Support (if any)
Respiratory Inductance Plethysmography to Quantify Changes in Ventilation in Obstructive Sleep Apnea
IEEE Transactions on Biomedical Engineering · 2025-10-07 · 3 citations
articleOpen accessBackground and objective: The study aims to determine whether respiratory inductance plethysmography (RIP) signals can be used to quantify changes in ventilation and provide advanced obstructive sleep apnea (OSA) severity metrics. This approach seeks to address limitations in current airflow-based OSA measures, particularly those relying on nasal pressure, which may be compromised by oral breathing. Methods: Adult patients with OSA (N = 89, 68Male:21Female) completed in-laboratory polysomnography (PSG) allowing for RIP-based ventilation estimates to be compared against a gold standard oronasal-pneumotach (normalized ventilation %eupnea). Concordance was assessed on three levels: 1) individual breath ventilation, 2) individual respiratory event depth (percentage reduction in ventilation from local average), and 3) patient-specific OSA severity in terms of average event depth and ventilatory burden (average event depth x average event duration x event rate). To address overestimation of RIP ventilation during obstruction, we developed and applied a calibration and linearization method (“RIP correction”). Concordance analysis evaluated median bias for both small (130%eupnea), along with bias and intraclass correlation coefficient (ICC) calculation for events and patient-specific measures. Results: For individual breaths (N = 495,631), RIP correction reduced overestimation bias for small breaths from 12 to 2%eupnea. For individual events (N = 34,497), RIP correction reduced mean bias for event depth estimates from 9 to 1%eupnea. For patient-specific analysis underestimation of average event depth was attenuated from 9 to 4%eupnea and for ventilatory burden, from 275 to 116%eupnea min/hr. Additionally, RIP correction improved ICC for event depth and patient-level traits. Conclusion: RIP signals, with appropriate processing, enable quantification of advanced ventilation-based OSA metrics, addressing concerns that airflow-based measures may be affected by breathing route.
American Journal of Respiratory and Critical Care Medicine · 2025-07-30 · 21 citations
articleOpen accessAbstract Background Obstructive sleep apnea (OSA) pathogenesis, clinical manifestations, and consequences vary markedly among patients. Yet OSA heterogeneity goes largely unaddressed in current management pathways, which are characterized by high treatment failure rates of ∼50%. Growing knowledge of OSA pathogenesis has stimulated new lines of investigation for therapies targeted to specific underlying mechanisms or “endotypes.” OSA endotypes include the primary anatomic predisposition to pharyngeal collapse, as well as “nonanatomic” mechanisms of low arousal threshold, unstable control of breathing (high loop gain), and impaired pharyngeal dilator muscle function. Identification of interindividual differences in OSA endotypes and disease expression, or “OSA phenotypes,” offers promise for a more targeted approach to OSA management in which appropriate treatments are tailored to individual needs. However, these concepts have largely been limited to the research setting, and more evidence is needed to support clinical translation. Goals To outline the rationale for clinical use, challenges, and key research priorities required to translate OSA endophenotyping for delivery of a more tailored approach to improve patient care and outcomes. Methods An international multidisciplinary working group with expertise in OSA epidemiology, pathophysiology, diagnostics, and treatments was convened. The group met at the American Thoracic Society 2024 International Conference to discuss the current state of OSA endophenotyping and required research objectives. This research statement, authored with input from all members, summarizes the group discussion, identified key areas, and research priorities. Results The working group identified research priorities that cover the spectrum from discovery to translation/implementation, including technical standards, validation, establishment of clinical cutoffs and minimal clinically important differences, generalizability across diverse populations, stability and reproducibility of measurement, prospective study design and conduct, clinical utility, and impact analysis. Conclusions This research statement provides a road map of the opportunities and key steps required to generate the evidence necessary to translate OSA endophenotyping concepts into clinical care at scale.
Quantifying Sleep-Wake Rhythms in the Hospital Environment with Digital Technologies
npj Digital Medicine · 2025-11-22
preprintOpen accessPostoperative clinical care is prone to circadian desynchronization that may influence health outcomes. In an exploratory, feasibility-oriented and signal-exploration effort, we collected 1.8 million data points using 11 remote sensors during preoperative, in-hospital and post-discharge settings in 13 elective cardiac surgery patients (5.2% enrolled from 252 screened). We found that room traffic continued during nighttime with ≥1 visit/h. Sound levels exceeded the recommended 45 dBA threshold (51.9 ± 3.3 vs. 48.3 ± 4.2 dBA during nighttime). Brightness dropped at night (89.9 ± 87.7 to 3.7 ± 9.8 lux), but bright light exposures occurred. Ambient room temperature lacked sleep-inducing diurnal variability. Behavioral-physiological rhythms were disrupted and phase-shifted during hospitalization. Time awake during night hours increased from 10.7 ± 7.9% preoperatively to 34.8 ± 29.1% in-hospital. Cognitive function scores decreased (26.8 ± 2.8 points preoperatively to 24.7 ± 3.9 points in-hospital) with 31% of patients developing transient mild impairment. These data will inform the design of a controlled trial seeking to modify circadian/diurnal disruptors to enhance patient outcomes. Clinicaltrials.gov NCT05828680, November 21, 2022.
Recent grants
NIH · $2.4M · 2013
NIH · $437k · 2000
NIH · $863k · 2002
Core E: Biostatistical and Data Management Core
NIH · $46.8M · 2022
NIH · $7.2M · 2007
Frequent coauthors
- 89 shared
Allan I Pack
California University of Pennsylvania
- 65 shared
Brendan T Keenan
University of Pennsylvania
- 62 shared
Þórarinn Gíslason
National University Hospital of Iceland
- 61 shared
Greg Maislin
- 44 shared
Peter A. Cistulli
University of Sydney
- 38 shared
Bryndís Benediktsdóttir
- 36 shared
Erna Sif Arnardóttir
Reykjavík University
- 35 shared
Patrick J. Strollo
University of Pittsburgh
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