Dyspnea and Quality of Life Improvements with Management of Comorbid Obstructive Sleep Apnea in Chronic Lung Disease.

Obstructive sleep apnea (OSA) has emerged as a significant and prevalent comorbidity associated with chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and interstitial lung diseases. These overlap syndromes are associated with worse patient-reported outcomes (sleep quality, quality of life measures, mental health) than each condition independently. Observational studies suggest that patients with overlap syndrome who are adherent to positive airway pressure therapy report improved quality of life, sleep quality, depression, and daytime symptoms. Screening for and management of OSA in patients with overlap syndrome should emphasize the interconnected nature of these 2 conditions and the positive impact that OSA management can have on patients' well-being and overall health.

Circulating metabolic profile in idiopathic pulmonary fibrosis: data from the IPF-PRO Registry.

BACKGROUND: The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF. METHODS: We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules. Linear regression was used to compare metabolite and clinical analyte levels between patients with IPF and controls and to determine associations between metabolite levels and measures of disease severity in patients with IPF. Unadjusted and adjusted univariable Cox regression models were used to evaluate associations between circulating metabolites and the risk of mortality or disease progression among patients with IPF. RESULTS: Levels of 64 metabolites and 5 clinical analytes were significantly different between patients with IPF and controls. Among analytes with greatest differences were non-esterified fatty acids, multiple long-chain acylcarnitines, and select ceramides, levels of which were higher among patients with IPF versus controls. Levels of the branched-chain amino acids valine and leucine/isoleucine were inversely correlated with measures of disease severity. After adjusting for clinical factors known to influence outcomes, higher levels of the acylcarnitine C:16-OH/C:14-DC were associated with all-cause mortality, lower levels of the acylcarnitine C16:1-OH/C14:1DC were associated with all-cause mortality, respiratory death, and respiratory death or lung transplant, and higher levels of the sphingomyelin d43:2 were associated with the risk of respiratory death or lung transplantation. CONCLUSIONS: IPF has a distinct circulating metabolic profile characterized by increased levels of non-esterified fatty acids, long-chain acylcarnitines, and ceramides, which may suggest a more catabolic environment that enhances lipid mobilization and metabolism. We identified select metabolites that were highly correlated with measures of disease severity or the risk of disease progression and that may be developed further as biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov; No: NCT01915511; URL: www. CLINICALTRIALS: gov .

Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma.

BACKGROUND: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD. METHODS: QUEST (NCT02414854) data were used in this post hoc analysis. A composite endpoint from validated patient-reported outcomes was developed to identify patients with HSD using sleep-related items from the ACQ-5, Asthma-Related Quality-of-Life Questionnaire, Rhino-Conjunctivitis Quality-of-Life Questionnaire, and Sino-Nasal Outcome Test-22. Impairment in at least 1 item was considered an indication of HSD. Change from baseline to Week 52 in nighttime symptoms, ACQ-5 score, lung function, annualized severe exacerbation rates (AER), and short-acting ß-agonists use during treatment was used to assess dupilumab efficacy. RESULTS: In type 2 asthma patients, 64% had HSD at baseline; of those with ACQ-5 ≥2.5 at baseline, 82% had HSD. In this population, dupilumab reduced nighttime symptoms and ACQ-5 score by 0.31 and 0.56 points, respectively, by Week 52 versus placebo, and led to a 66% reduction in AER during QUEST and 0.34 L improvement in pre-bronchodilator (pre-BD) forced expiratory volume in 1 s (FEV1) at Week 52. CONCLUSION: A majority of patients with moderate-to-severe type 2 asthma with ACQ-5 ≥2.5 at baseline had HSD. Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life. Further studies are needed to confirm the association between ACQ-5 score ≥2.5 and higher sleep disturbance rates.

Early career outcomes of a large four-year MD/ MPH program: Results of a cross sectional survey of three cohorts of graduates.

The University of Miami Miller School of Medicine started a four-year MD/ MPH program in 2011 with a mission to graduate public health physician leaders to address the public health needs of the 21st century, with emphasis on three areas: leadership, research, and public health. A prospective cross-sectional survey of early graduates was conducted to understand how they incorporate public health training into their careers. There were two study questions: What are the self-described early career activities of the graduates of the first three cohorts in the areas of leadership, research, and public health and what are the perceptions regarding the influence of the public health training on their careers? In the summer of 2020, a survey was sent to graduates from the classes of 2015, 2016, and 2017. In addition to several multiple-choice questions, the survey included an open-ended question on the impact of public health training in their careers. Inductive content analysis was used to analyze the responses to the open-ended question. Eighty-two of the 141 eligible graduates (63%) completed the survey; 80 of whom had participated or was currently participating in residency training. Forty-nine joined a residency in a primary care field. Many graduates had leadership roles in their early careers, including 35 who were selected as chief residents. Fifty-seven participated in research, most commonly in quality improvement (40), clinical (34) and community based (19). Over one third (30) chose to do work in public health during residency. Themes that emerged regarding the influence of public health training on their careers were: 1) Shifts in perspective, 2) Value of specific skills related to public health, 3) Steppingstone for professional opportunities 4) Focus on health disparities, social determinants, and inadequacies of the healthcare system, 5) Perception as leaders and mentors for peers, and 6) Preparedness for the pandemic. Graduates self-reported involvement in leadership, research, and public health activities as well as a commitment towards addressing some of our most pressing public health needs. Although long-term career outcomes need to be determined over time, graduates currently report considerable benefits of their public health training for their professional outcomes.

Vaccination in pregnancy: Healthcare provider attitudes and practices.

OBJECTIVE: To assess provider attitudes and practices regarding vaccination in pregnancy to discern strategies to increase vaccination rates in pregnancy, given that in the USA, various healthcare organizations recommend that pregnant individuals be vaccinated against influenza, pertussis, and SARS-CoV-2, but vaccination rates among gravidas remain suboptimal across these vaccines. METHODS: An Institutional Review Board-approved survey was disseminated to obstetric healthcare providers by email from June through October 2021. Questions assessed provider demographics, attitudes, and practices surrounding vaccination in pregnancy. A total of 192 providers consented, 179 initiated the survey, and 153 completed it entirely. Statistical software (SAS) was used to perform descriptive statistics. RESULTS: All providers strongly agreed/agreed that all pregnant individuals should receive vaccines in pregnancy. Following patient vaccination consent, 13% reported needing to refer patients to alternative sites for vaccine administration. Following patient vaccination decline, 13% did not determine reasons for refusal, 30% did not re-counsel at subsequent visits, and 92% did not ask another staff member to counsel the patient. CONCLUSION: Despite provider support for maternal immunization, uptake of vaccines in gravidas remains suboptimal, demonstrating a gap between provider recommendations and patient uptake. These data highlight opportunities for intervention regarding counseling and vaccine availability to increase vaccine uptake in pregnancy.

Sleep Latency and Post-Traumatic Stress Disorder Among Retired Career Florida Firefighters: Evidence From the Advancing Epidemiology of Retired Firefighters Aging Longitudinally Cohort.

OBJECTIVE: Our objective was to estimate the association of post-traumatic stress disorder (PTSD) and sleep latency among retired firefighters. METHODS: Baseline health survey data collected from retried career Florida firefighters participating in an ongoing prospective cohort study from 2017 to 2021 were analyzed. Risk for PTSD was assessed using a four-item primary care PTSD screening construct, and sleep onset latency was assessed by self-reported length of time to fall asleep. RESULTS: Among the 500 participants, 8.0% screened positive for PTSD risk and 37.6% had prolonged sleep onset latency (≥20 minutes to fall asleep). Retired firefighters with PTSD risk were 2.7 times more likely (adjusted odds ratio, 2.70; 95% confidence interval, 1.27-5.75) to have prolonged sleep latency compared with those without PTSD risk while controlling for covariates. CONCLUSIONS: Retired firefighters who screen positive for PTSD risk are three times more likely to report delayed sleep onset latency.

ATS Core Curriculum 2021. Adult Sleep Medicine: Sleep Apnea.

The American Thoracic Society Sleep Core Curriculum updates clinicians on important sleep topics, presented during the annual meeting, and appearing in summary here. This year's sleep core theme is sleep-disordered breathing and its management. Topics range from pathophysiological mechanisms for the association of obstructive sleep apnea (OSA) and metabolic syndrome, surgical modalities of OSA treatment, comorbid insomnia and OSA, central sleep apnea, and sleep practices during a pandemic. OSA has been associated with metabolic syndrome, independent of the role of obesity, and the pathophysiology suggests a role for sleep fragmentation and intermittent hypoxia in observed metabolic outcomes. In specific patient populations, surgical treatment modalities for OSA have demonstrated large reductions in objective disease severity compared with no treatment and may facilitate adherence to positive airway pressure treatment. Patient-centered approaches to comorbid insomnia and sleep apnea include evaluating for both OSA and insomnia simultaneously and using shared-decision making to determine the order and timing of positive airway pressure therapy and cognitive behavioral therapy for insomnia. The pathophysiology of central sleep apnea is complex and may be due to the loss of drive to breathe or instability in the regulatory pathways that control ventilation. Pandemic-era sleep practices have evolved rapidly to balance safety and sustainability of care for patients with sleep-disordered breathing.

ATS Core Curriculum 2020. Adult Sleep Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3-4-year recurring cycle of topics. These topics will be presented at the 2020 Virtual Conference. Below is the adult sleep medicine core that includes topics pertinent to sleep-disordered breathing and insomnia.

Sleep Complaints and Sleep Quality in Spinal Cord Injury: A Web-Based Survey.

STUDY OBJECTIVES: The purpose of this study was to determine sleep quality and presence of sleep disorders in participants with spinal cord injury (SCI). METHODS: A web-based survey, available online from February 2011 to July 2013, using validated sleep questionnaires, advertised via the internet and locally through SCI consumer organizations in the United States, Australia, New Zealand, and Canada, was designed to evaluate sleep in adults with self-reported SCI. Demographic characteristics and medical history were obtained from participant self-report. RESULTS: In our study population, 70% of the 304 participants were male with a mean age of 45 ± 13 years. The mean duration of injury was 16 ± 12 years. Cervical injuries were reported by 49% and thoracic injuries noted in 40% of participants. Increased sleep apnea risk was noted in 31% of participants, with 66% reporting snoring. Insomnia symptoms were reported by 54% of the respondents. Almost 40% of participants ranked their sleep quality as "fairly bad" to "very bad" in the previous month, 29% reported "often" or "almost always" waking up because of pain, and 22% had difficulty falling asleep because of leg cramps. In the past year, 27% of the respondents reported daily uncomfortable leg sensations and 28% found these leg symptoms to be "moderately to extremely distressing." CONCLUSIONS: This study increases the awareness that insomnia, sleep apnea, and poor sleep quality are common in individuals with chronic SCI; often coexisting. There is a need for increased screening for sleep problems by healthcare providers taking care of individuals living with SCI.

White donor, younger donor and double lung transplant are associated with better survival in sarcoidosis patients.

Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005-2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p < 0.001, Log-rank test). In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.

Diagnostic accuracy of a two-stage model for detecting obstructive sleep apnoea in chronic tetraplegia.

BACKGROUND: Obstructive sleep apnoea (OSA) is highly prevalent in people with spinal cord injury (SCI). Polysomnography (PSG) is the gold-standard diagnostic test for OSA, however PSG is expensive and frequently inaccessible, especially in SCI. A two-stage model, incorporating a questionnaire followed by oximetry, has been found to accurately detect moderate to severe OSA (MS-OSA) in a non-disabled primary care population. This study investigated the accuracy of the two-stage model in chronic tetraplegia using both the original model and a modified version for tetraplegia. METHODS: An existing data set of 78 people with tetraplegia was used to modify the original two-stage model. Multivariable analysis identified significant risk factors for inclusion in a new tetraplegia-specific questionnaire. Receiver operating characteristic (ROC) curve analyses of the questionnaires and oximetry established thresholds for diagnosing MS-OSA. The accuracy of both models in diagnosing MS-OSA was prospectively evaluated in 100 participants with chronic tetraplegia across four international SCI units. RESULTS: Injury completeness, sleepiness, self-reported snoring and apnoeas were included in the modified questionnaire, which was highly predictive of MS-OSA (ROC area under the curve 0.87 (95% CI 0.79 to 0.95)). The 3% oxygen desaturation index was also highly predictive (0.93 (0.87-0.98)). The two-stage model with modified questionnaire had a sensitivity and specificity of 83% (66-93) and 88% (75-94) in the development group, and 77% (65-87) and 81% (68-90) in the validation group. Similar results were demonstrated with the original model. CONCLUSION: Implementation of this simple alternative to full PSG could substantially increase the detection of OSA in patients with tetraplegia and improve access to treatments. TRIAL REGISTRATION NUMBER: Results, ACTRN12615000896572 (The Australian and New Zealand Clinical Trials Registry) and pre-results, NCT02176928 (clinicaltrials.gov).

Obstructive Sleep Apnea Phenotypes and Markers of Vascular Disease: A Review.

Obstructive sleep apnea (OSA) is a chronic and heterogeneous disorder that leads to early mortality, stroke, and cardiovascular disease (CVD). OSA is defined by the apnea-hypopnea index, which is an index of OSA severity that combines apneas (pauses in breathing) and hypopneas (partial obstructions in breathing) associated with hypoxemia. Yet, other sleep metrics (i.e., oxygen nadir, arousal frequency), along with clinical symptoms and molecular markers could be better predictors of stroke and CVD outcomes in OSA. The recent focus on personalized medical care introduces the possibility of a unique approach to the treatment of OSA based on its phenotypes, defined by pathophysiological mechanisms and/or clinical presentation. We summarized what is known about OSA and its phenotypes, and review the literature on factors or intermediate markers that could increase stroke risk and CVD in patients with OSA. The OSA phenotypes where divided across three different domains (1) clinical symptoms (i.e., daytime sleepiness), (2) genetic/molecular markers, and (3) experimental data-driven approach (e.g., cluster analysis). Finally, we further highlight gaps in the literature framing a research agenda.

Insomnia, Sleep Quality, and Quality of Life in Mild to Moderate Parkinson's Disease.

RATIONALE: Sleep disorders are prevalent in Parkinson's disease but underreported in clinical settings. The contribution of sleep disorders to health-related quality of life (HRQOL) for patients with this degenerative neurological disease are not well known. OBJECTIVES: To evaluate the impact of insomnia symptoms, obstructive sleep apnea (OSA), and poor sleep quality on HRQOL in a cohort of patients with idiopathic Parkinson's disease. METHODS: We enrolled a convenience sample of 66 adults seen in the University of Miami Movement Disorders Clinic between July 2011 and June 2013. Participants completed validated questionnaires to determine insomnia symptoms, OSA risk, depression, anxiety, and HRQOL. All patients underwent unattended polysomnography to confirm OSA. Results were compared for those with and without insomnia symptoms. Principal component and regression analyses were performed to evaluate determinants of HRQOL. MEASUREMENTS AND MAIN RESULTS: Participants were predominately Hispanic males with mild to moderate Parkinson's disease. Insomnia symptoms were reported for 46% of the study subjects. OSA (apnea-hypopnea index, ≥5) was noted in 47%, with a mean apnea-hypopnea index of 8.3 ± 11.0. Fairly bad to very bad sleep quality was reported by 21% of the participants. Insomnia (r = 0.71; P < 0.001), daytime sleepiness (r = 0.36; P = 0.003), depression symptoms (r = 0.44; P < 0.001), and anxiety symptoms (r = 0.33; P = 0.006) were significant correlates of poor sleep quality. OSA, severity of Parkinson's disease, and dopaminergic therapy were not. In the principal component analysis, sleep quality was a significant component of the "psychological factor" that in turn was a significant determinant of overall HRQOL. CONCLUSIONS: Insomnia symptoms, OSA, and subsequent poor sleep quality are prevalent in Parkinson's disease. In this single-center, exploratory study, we found that insomnia and poor sleep quality, but not OSA, play important roles in determining overall quality of life for patients with this disease. Clinical trial registered with www.clinicaltrials.gov (NCT02034357).

Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial.

BACKGROUND: Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis. METHODS: Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 106 human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression. RESULTS: No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide. CONCLUSIONS: Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.