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1. Curcumin Supplementation and Vascular and Cognitive Function in Chronic Kidney Disease: A Randomized Controlled Trial

Author

Colin J. Gimblet, Nicholas T. Kruse, Katharine Geasland, Jeni Michelson, Mingyao Sun, Patrick Ten Eyck, Cari Linkenmeyer, Safur Rehman Mandukhail, Matthew J. Rossman, Meenakshi Sambharia, Michel Chonchol, Manjula Kurella Tamura, Douglas Seals, Karin F. Hoth, and Diana Jalal

Subjects
CKD, curcumin, vascular function, oxidative stress, Therapeutics. Pharmacology, RM1-950
Abstract

Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid–femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was −0.7 (−2.1, 1.1) and −0.1 (−1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.

Published
2024
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3. Examining the Effect of Genes on Depression as Mediated by Smoking and Modified by Sex

Author

Kirsten Voorhies, Julian Hecker, Sanghun Lee, Georg Hahn, Dmitry Prokopenko, Merry-Lynn McDonald, Alexander C. Wu, Ann Wu, John E. Hokanson, Michael H. Cho, Christoph Lange, Karin F. Hoth, and Sharon M. Lutz

Subjects
depression, mediation analysis, smoking, sex moderation, Genetics, QH426-470
Abstract

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [LOC105378800] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 4.0 × 10−4) among all participants and a marginally significant indirect effect among females (p = 0.02) and males (p = 4.0 × 10−3). Moreover, rs10501696 [GRM5] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 0.01) among all participants and a significant indirect effect among females (p = 2.2 × 10−3). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [GRM5] on broad depression through the log of pack-years of cigarette smoking (p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years (p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [LOC105378800, GRM5] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex.

Published
2024
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4. Factors associated with the decision to receive bivalent COVID-19 booster vaccination among health care personnel

Author

Nicholas M. Mohr, Ian D. Plumb, Eliezer Santos León, Karisa K. Harland, Anusha Krishnadasan, Utsav Nandi, Karin F. Hoth, Howard A. Smithline, and David A. Talan

Subjects
COVID-19 vaccines, vaccination hesitancy, health personnel, public health, occupational health, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

ABSTRACTCOVID-19 vaccination is effective at reducing SARS-CoV-2 complications, but uptake has been low. Our objective in this study was to compare the importance of factors reported to influence the decision to receive a bivalent COVID-19 booster vaccine among health care personnel (HCP) tested for SARS-CoV-2 between October 2022 and April 2023 in a 20-hospital vaccine effectiveness study in the United States (n = 1656). Compared with those who had not received the booster, the factors most likely to be reported to be important were concerns about contracting COVID-19 (84.0% of those who had received the bivalent booster vs. 47.5% of those who had not, difference 36.6% points (PP), 95% confidence interval [CI] 32.1 to 41.1%), spreading infection to family members (89.2% vs. 62.8%, difference 26.3 PP, 95% CI 22.3 to 30.4%), and spreading infection to colleagues at work (85.5% vs. 59.4%, difference 26.1 PP, 95% CI 21.7 to 30.5%). HCP who had received the booster more frequently cited the primary literature (61.7% vs. 31.8%, difference 29.9 PP, 95% CI 24.6 to 35.2%) and employer recommendations (48.3% vs. 29.8%, difference 18.5 PP, 95% CI 13.2 to 23.9%) as influencing their decision. This analysis provides insight into factors for targeting future vaccine messaging.

Published
2023
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6. Presence of symptoms 6 weeks after COVID-19 among vaccinated and unvaccinated US healthcare personnel: a prospective cohort study

Author

Kye E Poronsky, Katherine E Fleming-Dutra, Nicholas M Mohr, Peter C Hou, Elizabeth Krebs, Sharon H Saydah, Wei Xing, Anusha Krishnadasan, Eva González, David A Talan, Gregory J Moran, Karin F Hoth, Shannon Landers, Ian D Plumb, Kari K Harland, Tamara Pilishvili, Zachary Mankoff, John P Haran, Melissa Briggs-Hagen, Eliezer Santos León, Howard A Smithline, Lilly C Lee, Stephen C Lim, Mark T Steele, David G Beiser, Brett Faine, Utsav Nandi, Walter A Schrading, Brian Chinnock, Anne Chipman, Megan Fuentes, Frank LoVecchio, Bradley Clinansmith, Alysia Horcher, Kelli Wallace, Lisandra Uribe, Kavitha Pathmarajah, Dean M Hashimoto, Monica Bahamon, Michelle St Romain, Efrat Kean, Amy Stubbs, Sara Roy, Gregory Volturo, Amanda Higgins, James Galbraith, James C Crosby, Mary Mulrow, Ryan Gierke, Jennifer L Farrar, Yunmi Chung, Anna Yousaf, Jennifer Onukwube Okaro, Glen R Abedi, Sankan Nyanseor, and Christopher K Watts

Subjects
Medicine
Abstract

Objectives Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work.Design Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset.Setting Health systems in 12 US states.Participants HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset.Exposures Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine.Main outcome measures Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work.Results Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79).Conclusions Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work.

Published
2023
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7. Patient Experiences with a Tertiary Care Post-COVID-19 Clinic

Author

Alpana Garg MD, Maran Subramain PhD, Patrick B Barlow PhD, Lauren Garvin PhD, Karin F Hoth PhD, Kimberly Dukes PhD, Richard M Hoffman MD, MPH, and Alejandro P Comellas MD

Subjects
Medicine (General), R5-920
Abstract

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) is a complex condition with multisystem involvement. We assessed patients’ experience with a PASC clinic established at University of Iowa in June 2020. A survey was electronically mailed in June 2021 asking about (1) symptoms and their impact on functional domains using the Patient-Reported Outcomes Measurement Information System (PROMIS) measures (Global Health and Cognitive Function Abilities) (2) satisfaction with clinic services, referrals, barriers to care, and recommended support resources. Survey completion rate was 35% (97/277). Majority were women (67%), Caucasian (93%), and were not hospitalized (76%) during acute COVID-19. As many as 50% reported wait time between 1 and 3 months, 40% traveled >1 h for an appointment and referred to various subspecialities. Participants reported high symptom burden-fatigue (77%), “brain fog” (73%), exercise intolerance (73%), anxiety (63%), sleep difficulties (56%) and depression (44%). On PROMIS measures, some patients scored significantly low (≥1.5 SD below mean) in physical (22.7%), mental (15.9%), and cognitive (17.6%) domains. Approximately 61% to 93% of participants were satisfied with clinical services. Qualitative analysis added insight to their experience with healthcare. Participants suggested potential strategies for optimizing recovery, including continuity of care, a co-located multispecialty clinic, and receiving timely information from emerging research. Participants appreciated that physicians validated their symptoms and provided continuity of care and access to specialists.

Published
2023
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8. Optimism is associated with respiratory symptoms and functional status in chronic obstructive pulmonary disease

Author

Hyeon-Kyoung Koo, Karin F. Hoth, Barry J. Make, Elizabeth A. Regan, James D. Crapo, Edwin K. Silverman, and Dawn L. DeMeo

Subjects
Optimism, COPD, Exacerbation, Dyspnea, Quality of life, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Optimism is the general belief that good things will occur in the future; optimism is modifiable by cognitive behavioral therapy (CBT). Previous studies have associated higher optimism with improved health outcomes and lower all-cause mortality. Research question Investigate association between optimism and disease-related characteristics in chronic obstructive pulmonary disease (COPD). Study design and methods Current and former smokers with/without COPD and Preserved Ratio Impaired Spirometry (PRISm) from the 10-year follow-up visit for the Genetic Epidemiology of COPD (COPDGene) study were included. Optimism was assessed at the 10-year visit using the Life Orientation Test-Revised. Models of optimism as a predictor of lung function, COPD-associated phenotypes including exacerbations, and functional assessments, were adjusted for demographic confounders, smoking status, and comorbidities. Results Among 1967 subjects, higher optimism was significantly associated with older age, non-Hispanic white race, marital status, quitting smoking status, absence of COPD, and absence of depression. In multivariable analysis, higher optimism was independently associated with fewer prior exacerbations of COPD (coef = − 0.037, P

Published
2022
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9. Cognitive Difficulties and Health-Related Quality of Life in Sarcoidosis: An Analysis of the GRADS Cohort

Author

Karin F. Hoth, Jacob Simmering, Anna Croghan, and Nabeel Y. Hamzeh

Subjects
sarcoidosis, fatigue, quality of life, cognition, cognitive difficulties, health-related quality of life, Medicine
Abstract

Rationale: Subjective cognitive difficulties are common among sarcoidosis patients; however, previous studies have not modeled the link between cognitive difficulties and health-related quality of life (HRQOL). Objectives: To determine whether cognitive difficulties are associated with HRQOL in sarcoidosis patients after adjusting for demographics, fatigue, and physical disease severity measures. Methods: We performed a secondary analysis of the Genomic Research in Alpha-1 antitrypsin Deficiency and Sarcoidosis (GRADS) study data. We examined the association between self-reported cognitive difficulties (Cognitive Failures Questionnaire (CFQ)) and HRQOL (SF12v2 mental and physical component scores) while adjusting for the demographics, fatigue, and physical disease severity measures (i.e., organ involvement, forced vital capacity). Results: Approximately one-fourth of the patients with sarcoidosis endorsed cognitive difficulties. More frequent cognitive difficulties and more severe fatigue were significantly associated with worse mental HRQOL in the fully adjusted model, while older age was associated with better mental HRQOL. The association between cognitive difficulties and physical HRQOL was not significant in the final model. More severe fatigue, joint involvement, and reduced forced vital capacity (FVC) were associated with worse physical HRQOL, while higher income and higher education were associated with better physical HRQOL. Conclusions: Perceived cognitive difficulties are associated with diminished HRQOL after adjusting for demographics, organ involvement, pulmonary function, and fatigue. The association between cognitive difficulties and reduced HRQOL primarily occurs through the impact on mental components of HRQOL.

Published
2022
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10. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

Author

Brigid A. Adviento, Elizabeth A. Regan, Barry J. Make, MeiLan K. Han, Marilyn G. Foreman, Anand S. Iyer, Surya P. Bhatt, Victor Kim, Jessica Bon, Xavier Soler, Gregory L. Kinney, Nicola A. Hanania, Katherine E. Lowe, Kristen E. Holm, Abebaw M. Yohannes, Gen Shinozaki, Karin F. Hoth, Jess G. Fiedorowicz, James D. Crapo, Edwin K. Silverman, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Emily S. Wan, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Matthew Strand, Jim Crooks, Katherine Pratte, Aastha Khatiwada, Erin Austin, Gregory Kinney, Kendra A. Young, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2023

11. Carotid Artery Stiffness is Associated With Cognitive Performance in Former Smokers With and Without Chronic Obstructive Pulmonary Disease

Author

Karin F. Hoth, Kerrie L. Moreau, Howard D. Weinberger, Kristen E. Holm, Kimberly Meschede, James D. Crapo, Barry J. Make, David J. Moser, Elizabeth Kozora, Russell P. Bowler, Gary L. Pierce, Patrick Ten Eyck, and Frederick S. Wamboldt

Subjects
carotid artery stiffness, chronic obstructive pulmonary disease, cognition, smoking, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Heavy smokers perform worse on neuropsychological assessment than age‐matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty‐four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild‐moderate chronic obstructive pulmonary disease (GOLD 1–2), and 23 with severe‐very severe chronic obstructive pulmonary disease (GOLD 3–4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack‐years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery β‐stiffness index was associated with reduced executive functioning‐processing speed in the fully adjusted model (β=−0.49, SE=0.14; P=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning‐processing speed. β‐Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning‐processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.

Published
2020
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12. Use of the Spirometric 'Fixed-Ratio' Underdiagnoses COPD in African-Americans in a Longitudinal Cohort Study

Author

Elizabeth A. Regan, Melissa E. Lowe, Barry J. Make, Jeffrey L. Curtis, Quan Chen, Michael H. Cho, James L. Crooks, Katherine E. Lowe, Carla Wilson, James K. O’Brien, Gabriela R. Oates, Arianne K. Baldomero, Gregory L. Kinney, Kendra A. Young, Alejandro A. Diaz, Surya P. Bhatt, Meredith C. McCormack, Nadia N. Hansel, Victor Kim, Nicole E. Richmond, Gloria E. Westney, Marilyn G. Foreman, Douglas J. Conrad, Dawn L. DeMeo, Karin F. Hoth, Hannatu Amaza, Aparna Balasubramanian, Julia Kallet, Shandi Watts, Nicola A. Hanania, John Hokanson, Terri H. Beaty, James D. Crapo, Edwin K. Silverman, Richard Casaburi, and Robert Wise

Subjects
Internal Medicine
Published
2023

13. Association of low income with pulmonary disease progression in smokers with and without chronic obstructive pulmonary disease

Author

Katherine E. Lowe, Barry J. Make, James D. Crapo, Gregory L. Kinney, John E. Hokanson, Victor Kim, Anand S. Iyer, Surya P. Bhatt, Karin F. Hoth, Kristen E. Holm, Robert Wise, Dawn DeMeo, Marilyn G. Foreman, Thomas J. Stone, and Elizabeth A. Regan

Subjects
Medicine
Abstract

Low socioeconomic status has been associated with chronic obstructive pulmonary disease (COPD) but little is known about its impact on disease progression. We assessed the association of income to symptoms, pulmonary disease severity and progression in smokers with and without COPD. The COPDGene cohort of 4826 smokers who reported annual income in phase 2 was analysed. Those who reported annual income

Published
2018
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14. Comparative Impact of Depressive Symptoms and FEV

Author

Jacqueline, O'Toole, Han, Woo, Nirupama, Putcha, Christopher B, Cooper, Prescott, Woodruff, Richard E, Kanner, Robert, Paine, Russell P, Bowler, Alejandro, Comellas, Karin F, Hoth, Jerry A, Krishnan, Meilan, Han, Mark, Dransfield, Anand S, Iyer, David, Couper, Stephen P, Peters, Gerard, Criner, Victor, Kim, R Graham, Barr, Fernando J, Martinez, Nadia N, Hansel, Michelle N, Eakin, and Prescott G, Woodruff

Subjects
Pulmonary Disease, Chronic Obstructive, Depression, Forced Expiratory Volume, Surveys and Questionnaires, Smoking, Quality of Life, Humans, Female, Respiratory Function Tests, Original Research
Abstract

RATIONALE: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. OBJECTIVES: Examine the impact of depressive symptoms compared with FEV(1)% on COPD morbidity. METHODS: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV(1)% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. RESULTS: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV(1)% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV(1)% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV(1)%, explaining 30–67% of heterogeneity. FEV(1)% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16–32% of heterogeneity. Depressive symptoms accounted for 3–17% variance in change over time in PROs. In contrast, FEV(1)% accounted for 1–4% variance over time in PROs. CONCLUSIONS: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV(1)%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.

Published
2023

15. Tobacco industry ownership of pharmaceutical companies: an international survey of people with respiratory disease

Author

Ruth Tal-Singer, Linda Walsh, Tim Deuby, Angela Shaughnessy, Karin F Hoth, Victor Gascon, Susanne Hintringer, Nicole Hass, Tonya Winders, Lucy Morgan, Byron Thomashow, and David M Mannino

Subjects
Pulmonary and Respiratory Medicine
Abstract

The 2021 purchase of the respiratory pharmaceutical company Vectura by Phillip Morris International has been criticised by the public health and medical community, as a conflict of interest, with little input to date, from the patient community or the public. To address this gap, the COPD Foundation, along with global partners, surveyed 1196 people with chronic respiratory disease. 70% were bothered by a tobacco company making an inhaler to treat lung conditions and 48% reported that they would want to switch inhalers if they knew that a tobacco company made or sold their inhaler devices. Patients care about who makes the therapies used to treat their diseases.

Published
2022

16. Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease

Author

Jacqueline O’Toole, Han Woo, Nirupama Putcha, Christopher B. Cooper, Prescott Woodruff, Richard E. Kanner, Robert Paine, Russell P. Bowler, Alejandro Comellas, Karin F. Hoth, Jerry A. Krishnan, Meilan Han, Mark Dransfield, Anand S. Iyer, David Couper, Stephen P. Peters, Gerard Criner, Victor Kim, R. Graham Barr, Fernando J. Martinez, Nadia N. Hansel, Michelle N. Eakin, Neil E. Alexis, Wayne H. Anderson, Mehrdad Arjomandi, Igor Barjaktarevic, Lori A. Bateman, Surya P. Bhatt, Eugene R. Bleecker, Richard C. Boucher, Stephanie A. Christenson, Alejandro P. Comellas, David J. Couper, Gerard J. Criner, Ronald G. Crystal, Jeffrey L. Curtis, Claire M. Doerschuk, Mark T. Dransfield, Brad Drummond, Christine M. Freeman, Craig Galban, MeiLan K. Han, Annette T. Hastie, Eric A. Hoffman, Yvonne Huang, Robert J. Kaner, Eric C. Kleerup, Lisa M. LaVange, Stephen C. Lazarus, Deborah A. Meyers, Wendy C. Moore, John D. Newell, Laura Paulin, Cheryl Pirozzi, Elizabeth C. Oelsner, Wanda K. O’Neal, Victor E. Ortega, Sanjeev Raman, Stephen I. Rennard, Donald P. Tashkin, J Michael Wells, Robert A. Wise, and Prescott G. Woodruff

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Internal medicine, medicine, Pulmonary disease, medicine.disease, business, Depressive symptoms, Depression (differential diagnoses), respiratory tract diseases
Abstract

Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives:...

Published
2022

17. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A Post Hoc Analysis of the COPDGene and SPIROMICS Cohorts

Author

Anand S. Iyer, Trisha M. Parekh, Jacqueline O’Toole, Surya P. Bhatt, Michelle N. Eakin, Jerry A. Krishnan, Abebaw M. Yohannes, Prescott G. Woodruff, Christopher B. Cooper, Richard E. Kanner, Nicola A. Hanania, Mark T. Dransfield, Elizabeth A. Regan, Karin F. Hoth, Victor Kim, James D. Crapo, Edwin K. Silverman, Barry J. Make, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Huries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San José Estépar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Los Angeles, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Comorbid anxiety, business.industry, Internal medicine, Post-hoc analysis, Medicine, Respiratory system, business, Depressive symptoms
Published
2022

19. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Divay Chandra, Aman Gupta, Gregory L. Kinney, Carl R. Fuhrman, Joseph K. Leader, Alejandro A. Diaz, Jessica Bon, R. Graham Barr, George Washko, Matthew Budoff, John Hokanson, Frank C. Sciurba, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Adel R. Boueiz, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Carla G. Wilson, Robert Jensen, Jim Crooks, Douglas Everett, Camille Moore, null Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Carlos Martinez, Susan Murray, Xavier Soler, Farnoush Banaei-Kashani, Russell P. Bowler, Katerina Kechris, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Michael E. DeBakey, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya P. Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Carlos H. Martinez, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronary Artery Disease, Critical Care and Intensive Care Medicine, COPD: Original Research, Coronary artery disease, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Functional residual capacity, Risk Factors, Internal medicine, medicine, Humans, Lung volumes, 030212 general & internal medicine, Myocardial infarction, Lung, Subclinical infection, COPD, business.industry, Smoking, Organ Size, Middle Aged, respiratory system, medicine.disease, Coronary Vessels, United States, Respiratory Function Tests, respiratory tract diseases, Airway Obstruction, Plethysmography, Biological Variation, Population, Pulmonary Emphysema, 030228 respiratory system, Asymptomatic Diseases, Cohort, Cardiology, Airway Remodeling, Female, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Published
2021

20. Association of Systemic Inflammation with Depressive Symptoms in Individuals with COPD

Author

Karin F. Hoth, Yingze Zhang, Craig M Riley, Russell P. Bowler, Hilary C Strollo, Jessica Bon, Frank C. Sciurba, Seyed Mehdi Nouraie, Nicola A. Hanania, and C. Karoleski

Subjects
Male, medicine.medical_specialty, TNF-a, Comorbidity, International Journal of Chronic Obstructive Pulmonary Disease, Systemic inflammation, Hospital Anxiety and Depression Scale, Cohort Studies, Pulmonary Disease, Chronic Obstructive, COPDGene, FEV1/FVC ratio, Internal medicine, medicine, Humans, Depression (differential diagnoses), Original Research, Inflammation, IL-6, COPD, HADS, Depression, business.industry, Beck Depression Inventory, General Medicine, medicine.disease, SCCOR, beck depression inventory, Cohort, Female, BDI, medicine.symptom, CRP, business
Abstract

Hilary C Strollo,1 Seyed M Nouraie,1 Karin F Hoth,2 Craig M Riley,3 Chad Karoleski,1 Yingze Zhang,1 Nicola A Hanania,4 Russell P Bowler,5,6 Jessica Bon,1 Frank C Sciurba1 1University of Pittsburgh Medical Center, Department of Medicine, Department of Pulmonary Allergy and Critical Care Medicine, Pittsburgh, PA, USA; 2University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA, USA; 3Chester County Hospital, University of Pennsylvania Health System, West Chester, PA, USA; 4Baylor College of Medicine, Department of Pulmonary, Critical Care and Sleep Medicine, Houston, TX, USA; 5National Jewish Health, Department of Medicine, Denver, CO, USA; 6University of Colorado School of Medicine, Denver, CO, USACorrespondence: Hilary C StrolloUniversity of Pittsburgh Medical Center, Department of Medicine, Department of Pulmonary Allergy and Critical Care Medicine, NW 628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USATel +1 412-692-2210Fax +1 412-692-4842Email strolloh2@upmc.eduRationale: Depression is a prevalent comorbidity of chronic obstructive pulmonary disease (COPD) that, along with COPD, has been associated with inflammation. An association between inflammation and depression in COPD has not been validated in a large COPD cohort.Methods: Individuals from the University of Pittsburgh SCCOR cohort and the COPDGene cohort with tobacco use history and airway obstruction (FEV1/FVC < 0.7) were evaluated using the Beck Depression Inventory II (BDI-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Participants completed symptom-related questionnaires and plasma IL-6 measurements. T-test, Fisher’s Exact tests and logistic regression were used for statistical analysis.Results: The SCCOR cohort included 220 obstructed participants: 44% female and 21.4% with elevated depressive symptoms. GOLD staging distribution was predominantly stage I and II. The COPDGene cohort included 745 obstructed participants: 44% female and 13.0% with elevated depressive symptoms. GOLD distribution was predominantly stage II and III. In the SCCOR cohort, correlation between IL-6 and depressive symptoms trended toward significance (p= 0.08). Multivariable modeling adjusted for FEV1, age, gender and medical comorbidities showed a significant association (OR = 1.70, 95% CI = 1.08– 2.69). IL-6 was significantly associated with elevated depressive symptoms in COPDGene in both univariate (p=0.001) and multivariable modeling (OR = 1.52, 95% CI =1.13– 2.04).Conclusion: Elevated plasma IL-6 levels are associated with depressive symptoms in individuals with COPD independent of airflow limitation and comorbid risk factors for depression. Our results suggest that systemic inflammation may play a significant and possibly bidirectional role in depression associated with COPD.Keywords: IL-6, depression, beck depression inventory, BDI, HADS, TNF-a, CRP, SCCOR, COPDGene

Published
2021

21. Cognitive performance is lower among individuals with overlap syndrome than in individuals with COPD or obstructive sleep apnea alone: association with carotid artery stiffness

Author

Karin F. Hoth, Russell P. Bowler, Barry Make, Rachel E. Luehrs, Gary L. Pierce, Mark S. Aloia, James D. Crapo, Elizabeth Kozora, Kerrie L. Moreau, David J. Moser, Kimberly Meschede, Frederick S. Wamboldt, and Howard D. Weinberger

Subjects
medicine.medical_specialty, Carotid Artery, Common, Physiology, 030204 cardiovascular system & hematology, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, Cognition, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Effects of sleep deprivation on cognitive performance, Association (psychology), Sleep Apnea, Obstructive, COPD, business.industry, Stiffness, Overlap syndrome, medicine.disease, respiratory tract diseases, Obstructive sleep apnea, Carotid Arteries, Arterial stiffness, Cardiology, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article
Abstract

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack years, and postbronchodilator FEV(1)/FVC. We also examined the association between CCA stiffness and cognitive performance among each group separately. Individuals with overlap syndrome (n = 12) had greater CCA β-stiffness index (P = 0.015) and lower executive function-processing speed (P = 0.019) than individuals with COPD alone (n = 47), OSA alone (n = 9), and former smoker controls (n = 21), differences that remained significant after adjusting for age, BMI, sex, pack years, and FEV(1)/FVC. Higher CCA β-stiffness index was associated with lower executive function-processing speed in individuals with overlap syndrome (r = −0.58, P = 0.047). These data suggest that CCA stiffness is greater and cognitive performance is lower among individuals with overlap syndrome compared with individuals with COPD or OSA alone and that CCA stiffening may be an underlying mechanism contributing to the lower cognitive performance observed in patients with overlap syndrome. NEW & NOTEWORTHY Previous studies have demonstrated greater carotid artery stiffness and lower cognitive function among individuals with COPD alone and OSA alone. However, the present study is the first to demonstrate that individuals that have both COPD and OSA (i.e., overlap syndrome) have greater carotid artery stiffness and lower executive function-processing speed than individuals with either disorder alone. Furthermore, among individuals with overlap syndrome greater carotid artery stiffness is associated with lower executive function-processing speed.

Published
2021

22. Effects of Pioglitazone or Exercise in Older Adults with Mild Cognitive Impairment and Insulin Resistance: A Pilot Study

Author

Kerry L. Hildreth, Rachael E. Van Pelt, Kerrie L. Moreau, Jim Grigsby, Karin F. Hoth, Victoria Pelak, C. Alan Anderson, Bennett Parnes, John Kittelson, Pamela Wolfe, Tammie Nakamura, Sunny A. Linnebur, Jennifer M. Trujillo, Christina L. Aquilante, and Robert S. Schwartz

Subjects
Mild cognitive impairment, Insulin resistance, Pioglitazone, Exercise, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Aims: To examine the effects of pioglitazone or endurance exercise training on cognitive function in older adults with mild cognitive impairment (MCI) and insulin resistance. Methods: Seventy-eight adults (mean age ± SD: 65 ± 7 years) with central obesity and MCI were randomized to 6 months of endurance exercise, pioglitazone or control. Results: Sixty-six participants completed the study. Exercise training did not significantly increase peak oxygen uptake compared to control (p = 0.12). Compared to control, insulin resistance improved in the pioglitazone group (p = 0.002) but not in the exercise group (p = 0.25). There was no measureable effect of pioglitazone or exercise on cognitive performance compared to control. Conclusion: In this pilot study, pioglitazone improved insulin resistance but not cognitive performance in older adults with MCI and insulin resistance.

Published
2015
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23. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease

Author

Thuonghien V. Tran, Gregory L. Kinney, Alejandro Comellas, Karin F. Hoth, Arianne K. Baldomero, A. James Mamary, Jeffrey L. Curtis, Nicola Hanania, Richard Casaburi, Kendra A. Young, Victor Kim, Barry Make, Emily S. Wan, Alejandro A. Diaz, John Hokanson, James D. Crapo, Edwin K. Silverman, Surya P. Bhatt, Elizabeth Regan, Spyridon Fortis, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Marilyn G. Foreman, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Jessica Bon, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush BanaeiKashani, Perry G. Pernicano, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine
Published
2023

24. Presence of symptoms 6 weeks after COVID-19 among vaccinated and unvaccinated US healthcare personnel: a prospective cohort study

Author

Nicholas M Mohr, Ian D Plumb, Kari K Harland, Tamara Pilishvili, Katherine E Fleming-Dutra, Anusha Krishnadasan, Karin F Hoth, Sharon H Saydah, Zachary Mankoff, John P Haran, Melissa Briggs-Hagen, Eliezer Santos León, and David A Talan

Subjects
General Medicine
Abstract

ObjectivesAlthough COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work.DesignCohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset.SettingHealth systems in 12 US states.ParticipantsHCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset.ExposuresTwo doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine.Main outcome measuresPrevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work.ResultsAmong 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79).ConclusionsReceipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work.

Published
2023

25. Daily Activities: The Impact of COPD and Cognitive Dysfunction

Author

Frederick S. Wamboldt, Kristen E. Holm, Karin F. Hoth, James D. Crapo, Amanda M Brunette, Russell P. Bowler, Howard D. Weinberger, Kelsey Warner, David J. Moser, Kerrie L. Moreau, Kimberly Meschede, Elizabeth Kozora, and Barry J. Make

Subjects
medicine.medical_specialty, Activities of daily living, Psychological intervention, Neuropsychological Tests, Pulmonary function testing, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Activities of Daily Living, medicine, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Depression (differential diagnoses), COPD, business.industry, Neuropsychology, Cognition, General Medicine, medicine.disease, respiratory tract diseases, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Neuropsychology and Physiological Psychology, 030228 respiratory system, Quality of Life, Physical therapy, Anxiety, Original Empirical Article, medicine.symptom, business
Abstract

Objective Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients’ functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD. Method Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George’s Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD. Results As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p Conclusion The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients’ engagement in daily activities.

Published
2020

26. Clinical Markers Associated with Risk of Suicide or Drug Overdose Among Heavy Smokers - A Longitudinal Follow-Up Study of the COPDGene Cohort

Author

Brigid A, Adviento, Elizabeth A, Regan, Barry J, Make, MeiLan K, Han, Marilyn G, Foreman, Anand S, Iyer, Surya P, Bhatt, Victor, Kim, Jessica, Bon, Xavier, Soler, Gregory L, Kinney, Nicola A, Hanania, Katherine E, Lowe, Kristen E, Holm, Abebaw M, Yohannes, Gen, Shinozaki, Karin F, Hoth, and Jess G, Fiedorowicz

Abstract

Studies have shown that chronic obstructive pulmonary disease (COPD) and smoking are associated with increased suicide risk. To date there are no prospective studies examining suicide risk among smokers along a spectrum of pulmonary disease ranging from completely normal spirometry to severe COPD.Which clinical variables predict death by suicide or overdose of indeterminate intent in a large cohort of heavy smokers within the COPDGene study?We studied data from 9,930 participants involved in COPDGene, a multisite, prospective cohort study of current and former smokers. Primary cause of adjudicated deaths was identified using death certificates, family reports, and medical records. We examined time to death by suicide/overdose as the primary outcome in Cox regression adjusted for age, sex, race, BMI, pack-years, current smoking status, airflow limitation (%predicted FEVThe cohort was 47% female, 33% Black (67% White), had a mean (SD) age of 59.6 (9.0) years, and mean FEVIn this well-characterized cohort of current and former smokers with and without COPD, we identified risk factors for suicide/overdose that emphasize the subjective experience of illness over objective assessments of lung function.

Published
2022

27. Depressive and anxiety symptoms in patients with COPD: A network analysis

Author

Abebaw M. Yohannes, Martino Belvederi Murri, Nicola A. Hanania, Elizabeth A. Regan, Anand Iyer, Surya P. Bhatt, Victor Kim, Gregory L. Kinney, Robert A. Wise, Michelle N. Eakin, and Karin F. Hoth

Subjects
Pulmonary and Respiratory Medicine, Pulmonary Disease, Chronic Obstructive, Depression, Health Status, Humans, Bayes Theorem, Anxiety
Abstract

Individuals with Chronic Obstructive Pulmonary Disease (COPD) often develop anxiety and depression, which worsen illness management and prognosis. Physical and psychological symptoms, contextual and illness-related factors display complex reciprocal interactions, which give rise to heterogeneous presentations. Examining the patterns of association between specific physical and psychological symptoms in patients with COPD may help to focus on the precision of the patient-centred care.We used network analyses to examine the links between symptoms of COPD, depression and anxiety.Data from 1587 individuals with COPD from the COPDGene study were included. We estimated a Bayesian Gaussian Graphical Model to highlight the unique associations between symptoms of COPD (assessed with the COPD Assessment Test), depression and anxiety (assessed with the Hospital Anxiety and Depression Scale (HADS), while examining the role of sociodemographic characteristics, lung function tests, and health status.Unique Variable Analysis reduced 14 HADS items to Tension/worry (chronic anxiety), Fear/panic (acute anxiety), Restlessness, Anhedonia, Sadness and Slowing. In network analyses, chest-tightness was related to acute anxiety, while cough and weakness were connected with core depressive symptoms (sadness and lack of pleasure). Chronic anxiety was linked with acute anxiety and depressive symptoms. Findings were confirmed accounting for the role of confounders, including lung function, sex, ethnicity and lifestyle factors. A simulation based on our model yielded distinct predictions about anxiety and depression in two participants with similar COPD severity, but different symptom profiles.Network analyses highlighted specific associations between symptoms of COPD, depression and anxiety. Accounting for symptom-level interactions may help to promote personalized treatment approaches.

Published
2022

28. Reduced Attention in Former Smokers with and without COPD

Author

Kerrie L. Moreau, Russell P. Bowler, Elizabeth Kozora, Karin F. Hoth, Howard D. Weinberger, James D. Crapo, David J. Moser, Anna Croghan, Amanda M Brunette, Barry J. Make, Kimberly Meschede, Frederick S. Wamboldt, and Kristen E. Holm

Subjects
Male, Perseveration, media_common.quotation_subject, Population, Impulsivity, Severity of Illness Index, Article, Pulmonary function testing, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Attention, 030212 general & internal medicine, education, Lung, Applied Psychology, Aged, media_common, COPD, education.field_of_study, Smokers, 030505 public health, business.industry, Smoking, Age Factors, Middle Aged, medicine.disease, Respiratory Function Tests, respiratory tract diseases, Objective test, Anxiety, Female, medicine.symptom, 0305 other medical science, business, Clinical psychology, Vigilance (psychology)
Abstract

BACKGROUND: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to: 1) identify specific attention deficits in COPD, and 2) determine which demographic/clinical characteristics are associated with reduced attention. METHODS: 84 former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner’s Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable. RESULTS: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model. CONCLUSION: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.

Published
2019

29. Patient experience with healthcare: Feedback for a ‘Post COVID-19 clinic’ at a tertiary care center in rural area

Author

Maran Subramain, Kimberly Dukes, Alpana Garg, Lauren Garvin, Alejandro P. Comellas, Richard M. Hoffman, Patrick B. Barlow, and Karin F. Hoth

Subjects
Response rate (survey), medicine.medical_specialty, Ambulatory care, business.industry, Family medicine, Patient experience, Health care, Medicine, Context (language use), business, Mental health, Depression (differential diagnoses), Integrated care
Abstract

PurposePost-acute sequelae of SARS-CoV-2 (PASC) is a complex condition with multisystem involvement. We assessed patients’ perspectives and experience with a PASC clinic established at University of Iowa in June 2020.MethodsWe conducted a mixed-method survey in June 2021 to ask PASC clinic patients about 1) PASC symptoms and their impact on physical and mental health, and cognition using the PROMIS Global Health and Cognitive Function abilities items, and 2) satisfaction with clinic services and referrals, barriers to care, and recommended support resources.FindingsNinety-seven patients (97/277, 35% response rate) completed the survey. Most were women (67%, n=65/97), Caucasian (93%, n=90/97) and received outpatient care during acute COVID-19 illness (79%). Fifty percent reported wait time of 1-3 months and 40% traveled >1 hour for appointment. The most common symptoms >3 months from initial infection were fatigue (77%), “brain fog” (73%), exercise intolerance (73%), anxiety (63%), sleep difficulties (56%) and depression (44%). Qualitative analysis of open-ended answers added valuable context to quantitative results. A minority of patients reported significantly reduced functioning (≥1.5 SD below mean) of their physical health (22.5%), mental health (15.9%) and cognitive abilities (17.6%). Satisfaction with clinical services was high though participants identified barriers to care including scheduling delays and financial concerns. Respondents suggested potential strategies for optimizing recovery including continuity of care, a co-located multispecialty clinic and being provided with timely information from emerging research.ConclusionOur study reports high PASC symptom burden, its impact on health and patient experience with healthcare. It is important that primary healthcare professionals listen to patients with empathy and support them during recovery. Healthcare systems and policymakers should focus on accessible, comprehensive, and patient-centered integrated care.

Published
2021

30. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

Author

Auyon J. Ghosh, Brian D. Hobbs, Matthew Moll, Aabida Saferali, Adel Boueiz, Jeong H. Yun, Frank Sciurba, Lucas Barwick, Andrew H. Limper, Kevin Flaherty, Gerard Criner, Kevin K. Brown, Robert Wise, Fernando J. Martinez, David Lomas, Peter J. Castaldi, Vincent J. Carey, Dawn L. DeMeo, Michael H. Cho, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Adel El-Boueiz, Marilyn G. Foreman, Lystra P. Hayden, Jacqueline Hetmanski, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Jarrett Morrow, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Richard Rosiello, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Male, Endotype, Respiratory System, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Gastroenterology, Loss of heterozygosity, Pulmonary Disease, Chronic Obstructive, Genotype, 80 and over, 2.1 Biological and endogenous factors, Medicine, Longitudinal Studies, Aetiology, Lung, Aged, 80 and over, COPD, RNA sequencing, Middle Aged, Respiratory Function Tests, medicine.anatomical_structure, Phenotype, Meta-analysis, Respiratory, Female, alpha-1 antitrypsin, Genetic Markers, Adult, Pulmonary and Respiratory Medicine, Chronic Obstructive, Heterozygote, medicine.medical_specialty, Chronic Obstructive Pulmonary Disease, Pulmonary disease, Pulmonary Disease, Clinical Research, Internal medicine, alpha 1-Antitrypsin Deficiency, Humans, Allele, Aged, Emphysema, COPDGene Investigators, Whole Genome Sequencing, business.industry, Original Articles, medicine.disease, Survival Analysis, respiratory tract diseases, meta-analysis, alpha 1-Antitrypsin, Case-Control Studies, business
Abstract

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Published
2021

31. Effects of cardiac resynchronization therapy on health-related quality of life in older adults with heart failure

Author

Karin F Hoth, Justin Nash, Athena Poppas, Kristin E Ellison, Robert H Paul, and Ronald A Cohen

Subjects
Geriatrics, RC952-954.6
Abstract

Karin F Hoth1,2, Justin Nash3, Athena Poppas4, Kristin E Ellison4, Robert H Paul5, Ronald A Cohen31Division of Psychosocial Medicine, National Jewish Medical and Research Center, Denver, CO, USA; 2Department of Psychiatry, University of Colorado, Denver, CO, USA; 3Department of Psychiatry and Human Behavior; 4Department of Cardiology, Warren Alpert Medical School of Brown University, Providence, RI, USA; 5Department of Psychology, Division of Behavioral Neuroscience, University of Missouri St. Louis, St. Louis, MO, USAAbstract: The aim of the study was to examine changes in health-related quality of life among older adults undergoing cardiac resynchronization therapy (CRT), a pacemaker based intervention for heart failure. Twenty-one patients (mean age = 68; SD = 8) completed measures of cardiovascular health and quality of life prior to and 3-months post-CRT. Following the intervention, patients reported improvements in their perception of their physical functioning (t = 2.8, p < 0.01) and feelings of vitality (t = 2.9, p < 0.01) on the MOS SF-36 Health Survey. Patients improved on objective clinical measures of exercise capacity, cardiac ejection fraction, and ventricular dyssynchrony. Younger patients reported greater improvements in physical functioning and decreases in pain. Higher baseline body mass index was associated with less improvement in physical functioning. Finally, patients with nonischemic heart failure reported greater improvements on multiple subscales of the SF-36 than patients with ischemic heart failure. This preliminary study documented improvements in health-related quality of life following CRT. The findings highlight that specific patient characteristics may be associated with quality of life changes. Future studies will benefit from including quality of life measures that assess multiple health-related domains.Keywords: cardiac resynchronization therapy, heart failure, quality of life

Published
2008

32. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A

Author

Anand S, Iyer, Trisha M, Parekh, Jacqueline, O'Toole, Surya P, Bhatt, Michelle N, Eakin, Jerry A, Krishnan, Abebaw M, Yohannes, Prescott G, Woodruff, Christopher B, Cooper, Richard E, Kanner, Nicola A, Hanania, Mark T, Dransfield, Elizabeth A, Regan, Karin F, Hoth, Victor, Kim, and Harjinder, Singh

Subjects
Pulmonary Disease, Chronic Obstructive, Smokers, Depression, Humans, Letters, Anxiety, Anxiety Disorders
Published
2021

33. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author

Stefanie E. Mason, Rafael Moreta-Martinez, Wassim W. Labaki, Matthew J. Strand, Elizabeth A. Regan, Jessica Bon, Ruben San Jose Estepar, Richard Casaburi, Merry-Lynn McDonald, Harry B. Rossiter, Barry Make, Mark T. Dransfield, MeiLan K. Han, Kendra Young, Jeffrey L. Curtis, Kathleen Stringer, Greg Kinney, John E. Hokanson, Raul San Jose Estepar, George R. Washko, James D. Crapo, Edwin K. Silverman, Sara Cummings, Kelley Madden, Barry J. Make, Juliet Nabbosa, Emily Port, Serine Rashdi, Lori Stepp, Shandi Watts, Michael Weaver, Terri Beaty, Russell P. Bowler, David A. Lynch, Gary Anderson, Eugene R. Bleecker, Harvey O. Coxson, Ronald G. Crystal, James C. Hogg, Michael A. Province, Stephen I. Rennard, Thomas Croxton, Weiniu Gan, Lisa A. Postow, Lisa M. Viviano, Corinne Costa-Davis, Elisha Malanga, Delia Prieto, Ruth Tal-Singer, Homayoon Farzadegan, Akila Hadji, Leena Sathe, David Baraghoshi, Grace Chen, James Crooks, Ruthie Knowles, Katherine Pratte, Carla Wilson, Pearlanne T. Zelarney, Katerina J. Kechris, Sonia Leach, Erin E. Austin, Annika Czizik, Gregory Kinney, Yisha Li, Sharon M. Lutz, Margaret F. Ragland, Nicole Richmond, Kendra A. Young, Michael Cho, Peter J. Castaldi, Kimberly Glass, Craig Hersh, Wonji Kim, Yang-Yu Liu, Craig P. Hersh, Jacqueline Bidinger, Michael H. Cho, Douglas Conrad, Dawn L. DeMeo, Adel R. El-Boueiz, Marilyn G. Foreman, Auyon Ghosh, Georg Hahn, Nadia N. Hansel, Lystra P. Hayden, Brian Hobbs, Woori Kim, Christoph Lange, Merry- Lynn McDonald, Michael McGeachie, Matthew Moll, Melody Morris, Nikolaos A. Patsopoulos, Dandi Qiao, Ingo Ruczinski, Emily S. Wan, Jennifer G. Dy, Sean B. Fain, Shoshana Ginsburg, Eric A. Hoffman, Stephen Humphries, Philip F. Judy, Alex Kluiber Stefanie Mason, Andrea Oh, Clare Poynton, Joseph M. Reinhardt, James Ross, Joyce D. Schroeder, Arkadiusz Sitek, Robert M. Steiner, Edwin van Beek, Bram van Ginneken, Eva van Rikxoort, Robert Jensen, Co-Chair: John E. Hokanson, Surya P. Bhatt, Victor Kim, Nirupama Putcha, MeiLan Han, Alejandro A. Diaz, Elizabeth Regan, Antonio Anzueto, William C. Bailey, Gerard J. Criner, Kim Sprenger, Takis Benos, Nicola A. Hanania, Karin F. Hoth, Allison Lambert, Katherine Lowe, Gabriela Oates, Trisha Parekh, Gloria Westney, Aparna Balasubramanian, Aladin Boriek, Ashraf Fawzy, Francine Jacobson, David C. LaFon, Neil MacIntyre, Diego Maselli-Caceres, Meredith C. McCormack, Frank Sciurba, Xavier Soler, Vickram Tejwani, Edwin JR. van Beek, Raymond C. Wade, Mike Wells, Chris H. Wendt, Jeong H. Yun, Jingzhou Zhang, Lucas Gillenwater, Katherine E. Lowe, Katherine A. Pratte, Margaret Ragland, Amy Attaway, Stefanie Mason, Punam Kumar Saha, Ava Wilson, Hannatu Amaza, Adrienne Baldomero, A. James Mamary, James O’Brien, Robert A. Wise, Michelle Eakin, Jess G. Fiedorowicz, Ben Henkle, Kristen Holm, Anand Iyer, Ken M. Kunisaki, Charlene McEvoy, Takudzwa Mkorombindo, Gen Shinozaki, Abebaw Yohannes, Brian D. Hobbs, Bruce E. Miller, Tara Retson, Lisa McCloskey, Perry G. Pernicano, Mustafa Atik, Laura Bertrand, Thomas Monaco, Dharani Narendra, Veronica V. Lenge de Rosen, Kwame Badu-Danso, Francine L. Jacobson, Laura Kaufman, Cherie Maguire, Sophie Struble, Seth Wilson, R. Graham Barr, Casandra Almonte, John H.M. Austin, Maria Lorena Gomez Blum, Belinda M. D’Souza, Emilay Florez, Rodney Martinez, Wendy Curry, H. Page McAdams, Charlotte V. Reikofski, Lacey Washington, Robert Brown, Cheryl Clare, Marie Daniel, Karen Horton, Cheng Ting 'Tony' Lin, Tahira Mirza, Meagan Scott, Becky Shade, Matt Budoff, Robert Calmelat, Deborah Cavanaugh, Chris Dailing, Leticia Diaz, Hans Fischer, Renee Love Indelicato, Janos Porszasz, April Soriano, William Stringer, Miriam Urrutia, Arianne Baldomero, Brian Bell, Miranda Deconcini, Linda Loes, Jonathan Phelan, Camille Robichaux, Cheryl Sasse, Joseph H. Tashjian, Eric L. Flenaugh, Kema Abson, Hirut Gebrekristos, Priscilla Johnson, Jessica Jordan, Mario Ponce, Silanath Terpenning, Derrick Wilson, Grace Broadhurst, Debra Dyer, Elena Engel, Jay Finigan, Andrew Hill, Alex Jones, Ryan Jones, Jordan Owen, Richard Rosiello, Nicole Andries, Mary Charpentier, Diane Kirk, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Valena Davis, Parag Desai, Dee Fehrle, Carla Grabianowski, Michael Jacobs, Laurie Jameson, Gayle M. Jones, Steven Kelsen, Nathaniel Marchetti, Francine McGonagle, Aditi Satti, Kartik Shenoy, Regina Sheridan, Maria Vega-Sanchez, Samantha Wallace, Samuel Akinseye-kolapo, Matthew Baker, Arnissa Goggins, Anny McClain, Hrudaya Nath, Satinder P. Singh, Sushil K. Sonavane, Elizabeth Westfall, Marissa Gil, Tarek El Hajjaoui, Albert Hsiao, Amber Martineau, Jenna Mielke, Karl Perez, Gabriel Querido, Tara Reston, Andrew Yen, Alejandro Comellas, Spyridon Fortis, Mauricio Galizia, Eric Garcia, Janet Keating, Archana Laroia, Changhyun Lee, Amber Meyer, Brian Mullan, Prashant Nagpal, Oloigbe Ofori, and Sierra Suiter

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chronic Obstructive, Clinical Sciences, Respiratory System, Critical Care and Intensive Care Medicine, COPD: Original Research, Body Mass Index, Pectoralis Muscles, Pulmonary Disease, sarcopenia, Pulmonary Disease, Chronic Obstructive, Interquartile range, Clinical Research, Internal medicine, medicine, Tobacco Smoking, COPD, 2.1 Biological and endogenous factors, Humans, Longitudinal Studies, Aetiology, Pectoralis Muscle, Lung, Nutrition, Smokers, COPDGene Investigators, Proportional hazards model, business.industry, Prevention, Smoking, muscle wasting, medicine.disease, mortality, Confidence interval, Good Health and Well Being, Sarcopenia, Cardiology, Body Composition, Cardiology and Cardiovascular Medicine, business, Body mass index, Bioelectrical impedance analysis, Biomarkers
Abstract

BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Published
2021

35. Optimism is associated with respiratory symptoms and functional status in chronic obstructive pulmonary disease

Author

Hyeon-Kyoung Koo, Karin F. Hoth, Barry J. Make, Elizabeth A. Regan, James D. Crapo, Edwin K. Silverman, and Dawn L. DeMeo

Subjects
Male, Quality of life, Comorbidity, Severity of Illness Index, Diseases of the respiratory system, Pulmonary Disease, Chronic Obstructive, Forced Expiratory Volume, Surveys and Questionnaires, Humans, COPD, Lung, Aged, Retrospective Studies, Aged, 80 and over, Optimism, RC705-779, Research, Smoking, Exacerbation, Middle Aged, respiratory tract diseases, Cross-Sectional Studies, Functional Status, Dyspnea, Spirometry, Disease Progression, Female, Follow-Up Studies, Forecasting
Abstract

Background Optimism is the general belief that good things will occur in the future; optimism is modifiable by cognitive behavioral therapy (CBT). Previous studies have associated higher optimism with improved health outcomes and lower all-cause mortality. Research question Investigate association between optimism and disease-related characteristics in chronic obstructive pulmonary disease (COPD). Study design and methods Current and former smokers with/without COPD and Preserved Ratio Impaired Spirometry (PRISm) from the 10-year follow-up visit for the Genetic Epidemiology of COPD (COPDGene) study were included. Optimism was assessed at the 10-year visit using the Life Orientation Test-Revised. Models of optimism as a predictor of lung function, COPD-associated phenotypes including exacerbations, and functional assessments, were adjusted for demographic confounders, smoking status, and comorbidities. Results Among 1967 subjects, higher optimism was significantly associated with older age, non-Hispanic white race, marital status, quitting smoking status, absence of COPD, and absence of depression. In multivariable analysis, higher optimism was independently associated with fewer prior exacerbations of COPD (coef = − 0.037, P 1 (%) or FVC (%) with optimism score. Interpretation Fewer exacerbations and less severe respiratory symptoms and higher functional capacity were associated with higher optimism, which may impact health outcomes in current and former smokers with and without COPD. Optimism is a modifiable trait and these results may further support a role for CBT to improve outcomes in COPD.

Published
2021

36. Symptoms of Depression and Anxiety in Patients with COPD: A Network Analysis

Author

G.L. Kinney, M. Belvederi Murri, Robert A. Wise, Anand S Iyer, Surya P. Bhatt, Karin F. Hoth, E.A. Regan, Michelle N. Eakin, Victor Kim, Nicola A. Hanania, and Abebaw Mengistu Yohannes

Subjects
medicine.medical_specialty, COPD, business.industry, medicine, Anxiety, In patient, medicine.symptom, Psychiatry, medicine.disease, business, Depression (differential diagnoses)
Published
2021

37. Development of a Multidimensional Smoking Index Group Measure

Author

G.L. Kinney, Erin Austin, Y. Li, Karin F. Hoth, Dawn L. DeMeo, Kendra A. Young, N. Richmond, A. Czizik, and John E. Hokanson

Subjects
Index (economics), Group (mathematics), Statistics, Measure (physics), Psychology
Published
2021

38. Symptoms of anxiety and depression and use of anxiolytic-hypnotics and antidepressants in current and former smokers with and without COPD - A cross sectional analysis of the COPDGene cohort

Author

Barry J. Make, Anand S Iyer, Katherine E Lowe, Frederick S. Wamboldt, Elizabeth A. Regan, Carlos H. Martinez, Kristen E. Holm, Mark T. Dransfield, Karin F. Hoth, Gregory L. Kinney, Marilyn G. Foreman, Gen Shinozaki, Michael R. Jacobs, Surya P. Bhatt, Victor Kim, COPDGene Investigators, Robert A. Wise, Hilary F. Armstrong, and Nicola A. Hanania

Subjects
Male, medicine.medical_specialty, Exacerbation, Cross-sectional study, Anxiety, Hospital Anxiety and Depression Scale, Article, Cohort Studies, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Hypnotics and Sedatives, Medicine, 030212 general & internal medicine, Depression (differential diagnoses), Aged, COPD, Smokers, Depression, business.industry, medicine.disease, Antidepressive Agents, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Anti-Anxiety Agents, Cohort, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Objectives To compare the frequency of anxiety/depressive symptoms and use of anxiolytic-hypnotics/antidepressants in smokers with and without COPD and to identify characteristics associated with having unmedicated symptoms. Methods Cross-sectional analysis of ambulatory, current/former smokers ≥10 pack years enrolled in the COPDGene study. We measured anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (subscales ≥8), recorded anxiolytic-hypnotic/antidepressant use, and defined unmedicated symptoms as elevated anxiety/depressive symptoms and not on medications. Regression analysis identified characteristics associated with having unmedicated symptoms. Key results Of 5331 current/former smokers (45% with and 55% without COPD), 1332 (25.0%) had anxiety/depressive symptoms. Anxiety symptoms were similar in frequency in smokers with and without COPD (19.7% overall), while depressive symptoms were most frequent in severe-very severe COPD at 20.7% (13.1% overall). In the entire cohort, 1135 (21.2%) were on medications. Anxiolytic-hypnotic use was highest in severe-very severe COPD (range 7.6%–12.0%), while antidepressant use showed no significant variation in smokers with and without COPD (range 14.7%–17.1%). Overall, 881 (66% of those with symptoms) had unmedicated symptoms, which was associated with African American race (adjusted OR 2.95, 95% CI 2.25–3.87), male gender (adjusted OR 1.93, 95% CI 1.57–2.36), no health insurance (adjusted OR 2.38, 95% CI 1.30–4.35), severe-very severe COPD (adjusted OR 1.48, 95% CI 1.04–2.11), and higher respiratory symptoms/exacerbation history (adjusted OR 2.21, 95% CI 1.62–3.02). Conclusions Significant unmet mental health care needs exist in current and former smokers with and without COPD. One in five have unmedicated symptoms, identified by key demographic and clinical characteristics. Primary funding source National Institutes of Health and The COPD Foundation .

Published
2019

39. CT-measured lung air-trapping is associated with higher carotid artery stiffness in individuals with chronic obstructive pulmonary disease

Author

V. Magnotta, John D. Newell, Gary L. Pierce, Karin F. Hoth, Kelsey Warner, Eric A. Hoffman, Alejandro P. Comellas, Peggy Nopoulos, Stephan Arndt, Lyndsey E. DuBose, Rachel E. Luehrs, and Anna Croghan

Subjects
medicine.medical_specialty, Physiology, Pulmonary disease, 030204 cardiovascular system & hematology, Air trapping, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Pulse wave velocity, COPD, Lung, business.industry, Stiffness, respiratory system, Elastic artery, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Cardiology, Dilation (morphology), medicine.symptom, business, Research Article
Abstract

Early stages of chronic obstructive pulmonary disease (COPD) are characterized by the loss and narrowing of terminal bronchioles in the lung, resulting in “air-trapping,” often occurring before overt emphysema manifests. Individuals with an airway-predominant phenotype of COPD display extensive lung air-trapping and are at greater cardiovascular disease (CVD) risk than COPD patients with an emphysema-predominant phenotype. We hypothesized that the degree of computed tomography (CT)-quantified lung air-trapping would be associated with greater aortic and carotid artery stiffness and lower endothelial function, known biomarkers of CVD risk. Lung air-trapping was associated with greater aortic stiffness (carotid femoral pulse wave velocity, CFPWV) ( r = 0.60, P = 0.007) and carotid β-stiffness ( r = 0.75, P = 0.0001) among adults with ( n = 10) and without ( n = 9) a clinical diagnosis of COPD and remained significant after adjusting for blood pressure (BP) and smoking history (pack-years) (carotid β-stiffness: r = 0.68, P < 0.01; CFPWV r = 0.53, P = 0.03). The association between lung air-trapping and carotid β-stiffness remained significant after additionally adjusting for age and forced expiratory volume 1(FEV1) ( r = 0.64, P = 0.01). In the COPD group only ( n = 10), lung air-trapping remained associated with carotid β-stiffness ( r = 0.82, P = 0.05) after adjustment for age, pack-years, and FEV1. In contrast, no association was observed between CFPWV and lung air-trapping after adjustment for BP, pack-years, age, and FEV1 ( r = 0.12, P = 0.83). Lung air-trapping was not associated with endothelial function (brachial artery flow-mediated dilation) in the entire cohort ( P = 0.80) or in patients with COPD only ( P = 0.71). These data suggest that carotid artery stiffness may be a mechanism explaining the link between airway-predominant phenotypes of COPD and high CVD risk. NEW & NOTEWORTHY Previous cross-sectional studies have demonstrated greater large elastic artery stiffness and lower endothelium-dependent dilation in chronic obstructive pulmonary disease (COPD) patients compared with controls. Furthermore, COPD patients with emphysema have greater aortic stiffness than non-COPD controls, and the degree of stiffness is associated with emphysema severity. The present study is the first to demonstrate that even before overt emphysema manifests, lung air-trapping is associated with carotid artery stiffness in COPD patients independent of blood pressure, age, or smoking history.

Published
2018

40. Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Author

Emily S. Wan, Spyridon Fortis, Elizabeth A. Regan, John Hokanson, MeiLan K. Han, Richard Casaburi, Barry J. Make, James D. Crapo, Dawn L. DeMeo, Edwin K. Silverman, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Sungho Won, Phuwanat Sakornsakolpat, Dmitry Prokopenko, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Jessica Bon, Barry Make, Carlos Martinez, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Follow up studies, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Cardiology, medicine, 030212 general & internal medicine, Prism, business
Abstract

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lu...

Published
2018

41. Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Author

Vickram Tejwani, Ashraf Fawzy, Nirupama Putcha, Peter J. Castaldi, Michael H. Cho, Katherine A. Pratte, Surya P. Bhatt, David A. Lynch, Stephen M. Humphries, Gregory L. Kinney, Franco R. D’Alessio, Nadia N. Hansel, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bramvan Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, KenM. Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, and Joel Weissfeld

Subjects
Pulmonary and Respiratory Medicine, Male, Angiotensin receptor, medicine.medical_specialty, Population, Vital Capacity, Angiotensin-Converting Enzyme Inhibitors, Walk Test, Critical Care and Intensive Care Medicine, Cohort Studies, 03 medical and health sciences, Angiotensin Receptor Antagonists, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Forced Expiratory Volume, Medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Prospective Studies, education, Aged, COPD, education.field_of_study, Lung, biology, business.industry, Angiotensin-converting enzyme, respiratory system, Middle Aged, Protective Factors, medicine.disease, Angiotensin II, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Genetic epidemiology, Pulmonary Emphysema, Spirometry, Cohort, biology.protein, Cardiology, Disease Progression, Female, Cardiology and Cardiovascular Medicine, business, Lung Volume Measurements, Tomography, X-Ray Computed
Abstract

Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov

Published
2020

42. Symptoms of Anxiety, Burnout, and PTSD and the Mitigation Effect of Serologic Testing in Emergency Department Personnel During the COVID-19 Pandemic

Author

Robert M. Rodriguez, Juan Carlos C. Montoy, Karin F. Hoth, David A. Talan, Karisa K. Harland, Patrick Ten Eyck, William Mower, Anusha Krishnadasan, Scott Santibanez, Nicholas Mohr, Monica Bahamon, Jestin N. Carlson, Makini Chisolm-Straker, Brian Driver, Brett Faine, Pharm D, James Galbraith, Philip A. Giordano, John P. Haran, Amanda Higgins, Jeremiah Hinson, Stacey House, Ahamed H. Idris, Efrat Kean, Elizabeth Krebs, Michael C. Kurz, Lilly Lee, Stephen Y. Liang, Stephen C. Lim, Gregory Moran, Utsav Nandi, Kavitha Pathmarajah, James H. Paxton, Yesenia Perez, Richard Rothman, Walter A. Schrading, Jessica Shuck, Patricia Slev, Howard A. Smithline, Kimberly Souffront, Mark Steele, Michelle St. Romain, Amy Stubbs, Morgan Swanson, Josh Tiao, Jesus R. Torres, Stacy Trent, Lisandra Uribe, Arvind Venkat, Gregory Volturo, Kelli Wallace, and Kurt D. Weber

Subjects
Male, Frontline providers, medicine.medical_specialty, Health Personnel, Burnout, Anxiety, Stress, Article, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, COVID-19 Testing, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Psychiatry, Emotional exhaustion, Burnout, Professional, Pandemics, business.industry, SARS-CoV-2, Serologic testing, Stressor, COVID-19, 030208 emergency & critical care medicine, Emergency Department, Odds ratio, Emergency department, Confidence interval, United States, Emergency Medicine, Female, medicine.symptom, business, Emergency Service, Hospital
Abstract

Study Objective Among a comprehensive range of frontline emergency department health care personnel, we assessed symptoms of anxiety and burnout, specific coronavirus disease 2019 (COVID-19) work-related stressors, and risk for post-traumatic stress disorder (PTSD). We also determined whether COVID-19 serologic testing of HCP decreased their self-reported anxiety. Methods In a prospective cohort study from May 13, 2020, to July 8, 2020, we used electronic surveys to capture participant self-reported symptoms before and after serologic testing for anti-SARS-CoV-2 immunoglobulin G antibodies. Participants were physicians, nurses, advanced practice providers, and nonclinical ED personnel at 20 geographically diverse United States EDs. We evaluated these domains: 1) the effects of the COVID-19 pandemic on overall stress and anxiety; 2) COVID-19-related work stressors; 3) burnout; and 4) PTSD risk (measured using the Primary Care-PTSD Screen for DSM-5, a 5-item screening instrument in which a score of ≥3 signifies high risk for PTSD). We also assessed perceptions of whether results of COVID-19 antibody testing decreased participants’ self-reported anxiety. Results Of 1,606 participants, 100% and 88% responded to the baseline and follow-up surveys, respectively. At baseline, approximately half (46%) reported symptoms of emotional exhaustion and burnout from their work, and 308 (19.2%, 95% confidence interval [CI] 17.3% to 21.1%) respondents screened positive for increased PTSD risk. Female respondents were more likely than males to screen positive (odds ratio [OR] 2.03, 95% CI 1.49 to 2.78). Common concerns included exposing their family and the health of coworkers diagnosed with COVID-19. After receiving antibody test results, 54% (95% CI 51.8 to 56.7) somewhat agreed, agreed, or strongly agreed that knowledge of their immune status had decreased their anxiety. A positive serology result indicating prior SARS-CoV-2 infection was associated with a higher likelihood of reporting decreased anxiety (2.83, 95% CI 1.37 to 5.83). Conclusion Symptoms of anxiety and burnout were prevalent across the spectrum of ED staff during the COVID-19 pandemic. One-fifth of ED personnel appeared to be at risk for PTSD. Increased provision of serologic testing may help to mitigate anxiety.

Published
2020

44. Optimism Is Associated with Symptoms and Functional Status in COPD

Author

Karin F. Hoth, E.K. Silverman, B.J. Make, E.A. Regan, D.L. DeMeo, J.D. Crapo, and H.-K. Koo

Subjects
COPD, Optimism, business.industry, media_common.quotation_subject, Medicine, Functional status, business, medicine.disease, Clinical psychology, media_common
Published
2020

45. Mortality, Chronic Pain, and Opiate Use in the COPDGene Cohort

Author

G.L. Kinney, John E. Hokanson, Karin F. Hoth, B.J. Make, J.D. Crapo, D.L. DeMeo, Kendra A. Young, E.A. Regan, M.F. Ragland, and Katherine E Lowe

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Cohort, medicine, Chronic pain, Opiate, business, medicine.disease
Published
2020

46. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

Author

Barry J. Make, Venkata Bandi, Douglas Stinson, Ella A. Kazerooni, Harry B. Rossiter, Farnoush Banaei-Kashani, Xavier Soler, Arun C. Nachiappan, Paul J. Friedman, Karen M. Horton, Terri H. Beaty, Christine H. Wendt, Andrew Yen, Philip F. Judy, Ferdouse Begum, Jeffrey L. Curtis, Lystra P. Hayden, Joe W. Ramsdell, Peter J. Castaldi, Alejandro P. Comellas, Emily S. Wan, Susan Murray, Aladin M. Boriek, David Pace, Jessica Bon, Nadia N. Hansel, Chandra Dass, Marilyn G. Foreman, Neil R. MacIntyre, Kartik Shenoy, David A. Lynch, Brian D. Hobbs, Raúl San José Estépar, John D. Newell, Philip Alapat, Karin F. Hoth, Stephen M. Humphries, Robert M. Steiner, Alessandra Adami, R.P. Bowler, Parag Desai, Mustafa Al Qaisi, Anna Rozenshtein, Joel L. Weissfeld, Robert A. Wise, Nan M. Laird, Margaret M. Parker, Felix J. S. Bragman, Camille M. Moore, Abbie Begnaud, Allison A. Lambert, Elizabeth Guy, Michael R. Jacobs, Mario E. Ruiz, Dawn L. DeMeo, Sungho Won, Alex Kluiber, Amit D. Parulekar, John H. M. Austin, Nathaniel Marchetti, Dandi Qiao, Douglas Everett, Joseph H. Tashjian, Juerg Tschirren, Kendra A. Young, Adel Boueiz, James D. Crapo, Gregory L. Kinney, Richard Casaburi, Russell P. Bowler, Daniel C. Alexander, Francis Cordova, Craig P. Hersh, George R. Washko, H. Page McAdams, Amir Sharafkhaneh, A. James Mamary, J. Michael Wells, Lacey Washington, MeiLan K. Han, Mark T. Dransfield, Nirupama Putcha, Craig J. Galbán, Dmitry Prokopenko, Eric A. Hoffman, Gloria Westney, Katerina Kechris, Bojidar Rangelov, Carla Wilson, Charlene McEvoy, Divay Chandra, Edwin J R van Beek, Carlos H. Martinez, Kalpatha Guntupalli, Gregory D.N. Pearson, Diego Maselli-Caceres, James C. Ross, Katherine A. Pratte, Christoph Lange, David Ciccolella, Charlie Lan, R. Graham Barr, Phuwanat Sakornsakolpat, Aditi Satti, Irene Swift, Robert H. Brown, Hans Fischer, Victor Kim, Maria Elena Vega-Sanchez, Sandra G. Adams, Belinda D’Souza, Perry G. Pernicano, Bram van Ginneken, Hrudaya Nath, Byron Thomashow, Jim Crooks, Joanne Billings, Jered Sieren, Eitan Halper-Stromberg, Matthew J. Budoff, William C. Bailey, Eva M. van Rikxoort, Merry-Lynn McDonald, Francine L. Jacobson, Edwin K. Silverman, John E. Hokanson, Robert L. Jensen, John Hughes, Michael H. Cho, Alexandra L. Young, Steven G. Kelsen, Janos Porszasz, Jacqueline B. Hetmanski, Alex Swift, John R. Hurst, Elizabeth A. Regan, Anand S Iyer, Frank C. Sciurba, Mustafa A. Atik, Gerard J. Criner, Antonio Anzueto, Sharon M. Lutz, David J. Hawkes, Carl R. Fuhrman, William W. Stringer, Harvey O. Coxson, Berend C. Stoel, Eugene Berkowitz, Joyce D. Schroeder, Tadashi Allen, Surya P. Bhatt, Matthew Strand, Brad H. Thompson, Nicola A. Hanania, Brian Bell, Teresa Gray, Gilbert E. D'Alonzo, and Richard Rosiello

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Pulmonary disease, Critical Care and Intensive Care Medicine, Machine Learning, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, COPD, business.industry, Disease progression, Editorials, Original Articles, Middle Aged, Models, Theoretical, respiratory system, medicine.disease, respiratory tract diseases, 030228 respiratory system, Disease Progression, Bronchitis, Female, Ct imaging, business, Tomography, X-Ray Computed, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

Published
2020

47. COPDGene

Author

Katherine E, Lowe, Elizabeth A, Regan, Antonio, Anzueto, Erin, Austin, John H M, Austin, Terri H, Beaty, Panayiotis V, Benos, Christopher J, Benway, Surya P, Bhatt, Eugene R, Bleecker, Sandeep, Bodduluri, Jessica, Bon, Aladin M, Boriek, Adel Re, Boueiz, Russell P, Bowler, Matthew, Budoff, Richard, Casaburi, Peter J, Castaldi, Jean-Paul, Charbonnier, Michael H, Cho, Alejandro, Comellas, Douglas, Conrad, Corinne, Costa Davis, Gerard J, Criner, Douglas, Curran-Everett, Jeffrey L, Curtis, Dawn L, DeMeo, Alejandro A, Diaz, Mark T, Dransfield, Jennifer G, Dy, Ashraf, Fawzy, Margaret, Fleming, Eric L, Flenaugh, Marilyn G, Foreman, Spyridon, Fortis, Hirut, Gebrekristos, Sarah, Grant, Philippe A, Grenier, Tian, Gu, Abhya, Gupta, MeiLan K, Han, Nicola A, Hanania, Nadia N, Hansel, Lystra P, Hayden, Craig P, Hersh, Brian D, Hobbs, Eric A, Hoffman, James C, Hogg, John E, Hokanson, Karin F, Hoth, Albert, Hsiao, Stephen, Humphries, Kathleen, Jacobs, Francine L, Jacobson, Ella A, Kazerooni, Victor, Kim, Woo Jin, Kim, Gregory L, Kinney, Harald, Koegler, Sharon M, Lutz, David A, Lynch, Neil R, MacIntye, Barry J, Make, Nathaniel, Marchetti, Fernando J, Martinez, Diego J, Maselli, Anne M, Mathews, Meredith C, McCormack, Merry-Lynn N, McDonald, Charlene E, McEvoy, Matthew, Moll, Sarah S, Molye, Susan, Murray, Hrudaya, Nath, John D, Newell, Mariaelena, Occhipinti, Matteo, Paoletti, Trisha, Parekh, Massimo, Pistolesi, Katherine A, Pratte, Nirupama, Putcha, Margaret, Ragland, Joseph M, Reinhardt, Stephen I, Rennard, Richard A, Rosiello, James C, Ross, Harry B, Rossiter, Ingo, Ruczinski, Raul, San Jose Estepar, Frank C, Sciurba, Jessica C, Sieren, Harjinder, Singh, Xavier, Soler, Robert M, Steiner, Matthew J, Strand, William W, Stringer, Ruth, Tal-Singer, Byron, Thomashow, Gonzalo, Vegas Sánchez-Ferrero, John W, Walsh, Emily S, Wan, George R, Washko, J, Michael Wells, Chris H, Wendt, Gloria, Westney, Ava, Wilson, Robert A, Wise, Andrew, Yen, Kendra, Young, Jeong, Yun, Edwin K, Silverman, and James D, Crapo

Subjects
respiratory tract diseases, Original Research
Abstract

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene(®)), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics – environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry – were evaluated in a group of 8784 current and former smokers who were participants in COPDGene(®) Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV(1) > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene(®) 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15–6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

Published
2019

48. Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

Author

Cashell E. Jaquish, Craig P. Hersh, Emily Barron-Casella, Larry Phillips, James S. Pankow, JoAnn E. Manson, Mariza de Andrade, Vivien A. Sheehan, Norann A. Zaghloul, Yongmei Liu, Sergei Nekhai, Russell P. Tracy, Bruce S. Weir, Pankaj Qasba, Adrienne M. Stilp, Tasha E. Fingerlin, Heather M. Ochs-Balcom, L. Adrienne Cupples, Rongze Yang, David A. Schwartz, Shannon Kelly, Scott E. Devine, Tanja Smith, G.L. Kinney, Beverly Snively, Kent D. Taylor, Manolis Kellis, Ruth J. F. Loos, Seth A. Ament, Kathleen C. Barnes, Robert C. Kaplan, Ulrich Broeckel, Hemant K. Tiwari, Karin F. Hoth, Peter Durda, Julie L. Mikulla, Charles B. Eaton, Cotton Seed, Merry Lynn McDonald, Eric Boerwinkle, Josh Smith, Honghuang Lin, Ingrid B. Borecki, Jeffrey L. Curtis, Emelia J. Benjamin, Kenneth Rice, Sharon L.R. Kardia, Nicholas L. Smith, Coleen M. Damcott, Jeffrey Haessler, Kimberly L. Jones, Elaine Cornell, Nona Sotoodehnia, Adolfo Correa, Rich Johnston, C. Charles Gu, Chii Min Hwu, Peter C. Anderson, Lesley F. Tinker, Colleen Davis, R. Graham Barr, Scott T. Weiss, Leanna Farnam, Chao Hsiung, Brian Silver, Patrick F. McArdle, Lisa W. Martin, Yii-Der Ida Chen, John Barnard, Holly Kramer, Sekar Kathiresan, Gonçalo R. Abecasis, Barry Make, Michael C. Mahaney, Marco V Perez, Donna K. Arnett, Mark Chaffin, Xiuqing Guo, Joshua C. Bis, Pamela Russell, Paul L. Auer, James G. Wilson, Marilyn J. Telen, David K. Levine, Jennifer A. Smith, Christopher Scheller, Meher Preethi Boorgula, Aakrosh Ratan, Kari E. North, Dan E. Arking, Elizabeth A. Regan, Margaret G. Parker, Andres Metspalu, Jai G. Broome, Daniel Taliun, Lynette Ekunwe, Alyna T. Khan, Hao Mei, Dhananjay Vaidya, Ellen M. Schmidt, Stanford Mwasongwe, Joshua P. Lewis, Stacey Gabriel, Christine E. Seidman, Margery Gass, Deborah A. Nickerson, Nicola L. Hawley, Rebecca L. Beer, Afshin Parsa, Steven L. Salzberg, Terri H. Beaty, Stella Aslibekyan, Girish N. Nadkarni, Wei Zhao, David L. Tirschwell, Karen Bunting, Dawn L. DeMeo, Laura J. Rasmussen-Torvik, Julia Powers Becker, Dmitry Prokopenko, Karen Schwander, Bruce D. Gelb, Stephanie Krauter, Laura M. Raffield, Michael E. Hall, Frank C. Sciurba, Lauren Margolin, Nora Franceschini, Daniel N. Harris, Seyedeh M. Zekavat, Dawood Darbar, Keng-Han Lin, Haley Huston, Steven A. Lubitz, Andrea Ganna, Carole Sztalryd, Cathy C. Laurie, Christy Chang, James E. Hixson, Steven A. McCarroll, Barbara A. Konkle, Michael D. Kessler, Scott I. Vrieze, Yingze Zhang, Sarah Ruuska, George J. Papanicolaou, Weiniu Gan, Maris Alver, Elizabeth A. Streeten, Fei Fei Wang, Lu-Chen Weng, Braxton D. Mitchell, Lee-Ming Chuang, Sean P. David, Wei-Min Chen, Susan R. Heckbert, Ryan D. Hernandez, Andrew D. Johnson, Cristen J. Willer, Ani Manichaikul, Jonathan M. Bloom, Timothy D. O’Connor, Sylvia Smoller, Marguerite R. Irvin, Seung Hoan Choi, Ida Surakka, Veikko Salomaa, Diane M. Becker, Ron Do, W. Craig Johnson, Cecelia A. Laurie, Meryl S. LeBoff, Aniket Shetty, Tõnu Esko, Michael C. Zody, Xiaoqi Geng, Da Wei Gong, Snow Xueyan Zhao, Esteban G. Burchard, Xiuwen Zheng, Cara L. Carty, Alexander P. Reiner, Tim Assimes, Deborah A. Meyers, Mina K. Chung, Harald H H Göring, Benjamin M. Neale, Pradeep Natarajan, Yan Gao, Stephen S. Rich, Yun Ju Sung, Susan K. Dutcher, Ferdouse Begum, Stephanie M. Gogarten, John Blangero, Jonathan Cardwell, Kayleen Williams, Rakhi P. Naik, Amol C. Shetty, Sayantan Das, Myriam Fornage, May E. Montasser, Michelle Daya, Edwin K. Silverman, Daniel E. Weeks, Laura J. Kaufman, Dimitrios Avramopoulos, Michael Y. Tsai, Christine M. Albert, Vijay G. Sankaran, Jeffrey R. O'Connell, Thomas W. Blackwell, Stephen T. McGarvey, Robert M. Reed, Leslie A. Lange, Qing Duan, Bruce M. Psaty, Leslie S. Emery, Bertha Hidalgo, Jennifer A. Brody, L. Keoki Williams, Soren Germer, Zhaohui S. Qin, Deepti Jain, Deborah Applebaum-Bowden, Carla Wilson, Degui Zhi, Christoph Lange, Elliott Hong, L.F. Bielak, Wen Jane Lee, Yue Guan, Tarik Walker, Rebecca D. Jackson, Charles R. Farber, Mark J. Daly, Stephanie M. Fullerton, John E. Hokanson, Karol E. Watson, James Luo, Richard Casaburi, Seunggeun Lee, Jill M. Johnsen, Margaret A. Taub, Ryan L. Minster, Ravi Duggirala, Susan K. Mathai, Yun Li, Quenna Wong, Matthew Flickinger, Huichun Xu, Susan Redline, Ulrike Peters, Ivana V. Yang, Jesse M. Engreitz, Sanni Ruotsalainen, Sean K. McFarland, Avram D Walts, Patricia A. Peyser, Allison E. Ashley-Koch, Lewis C. Becker, Nicholette Palmer Allred, James A. Perry, Jody S. Sylvia, Tamar Sofer, Vasan S. Ramachandran, Laura Almasy, Matthew J. Budoff, Ranjan Deka, David M. Herrington, Simeon I. Taylor, Daniel Levy, Chaojie Yang, Sameer Chavan, Kathleen A. Ryan, Josyf C. Mychaleckyj, Ingo Ruczinski, Sebastian Zoellner, Michael Preuss, Tim Poterba, Wendy S. Post, Amber L. Beitelshees, Ben Heavner, Carolina Roselli, Namiko Abe, Jonathon LeFaive, Mark T. Gladwin, Brian Custer, Robert B. Wallace, Simin Liu, Michael H. Cho, Robert E. Handsaker, Dabeeru C. Rao, Bo Juen Chen, Wayne Hui Heng Sheu, Xiang Zhou, Marcos Bezerra, Solomon K. Musani, Eimear E. Kenny, James F. Casella, Kathryn L. Lunetta, Nancy Min, Nicholas Rafaels, Lisa R. Yanek, Min A. Jhun, David C. Glahn, Rasika A. Mathias, Mollie A. Minear, Russell P. Bowler, Jason Ernst, Carolyn J. Crandall, Sara Penchev, Alvaro Alonso, Timothy A. Thornton, Toni I. Pollin, Charles Kooperberg, Ethan M. Lange, Juan M. Peralta, Pramod Anugu, Lucinda Fulton, Adam A. Szpiro, Michael R. DeBaun, M. Benjamin Shoemaker, Sam Phillips, Dan M. Roden, Mao Fu, Daniel I. Chasman, James D. Crapo, Hua Tang, Gina M. Peloso, Hyun Min Kang, Samuli Ripatti, Phuwanat Sakornsakolpat, Christopher R. Gignoux, Peter VandeHaar, Jerome I. Rotter, Dandi Qiao, Emily S. Wan, Shabnam Salimi, Kevin Sandow, Jiang He, Patrick T. Ellinor, Joanne E. Curran, Institute for Molecular Medicine Finland, Samuli Olli Ripatti / Principal Investigator, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Clinicum, Doctoral Programme in Population Health, Department of Public Health, and Complex Disease Genetics

Subjects
0301 basic medicine, Apolipoprotein B, General Physics and Astronomy, Gene Expression, Genome-wide association study, 030204 cardiovascular system & hematology, Cardiovascular, Lipoprotein particle, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, GENETIC-VARIANTS, 2.1 Biological and endogenous factors, WIDE ASSOCIATION, Aetiology, lcsh:Science, African Continental Ancestry Group, Genetics, Multidisciplinary, Genome, biology, CHOLESTEROL, Adaptor Proteins, Lipoprotein(a), Single Nucleotide, NHLBI TOPMed Lipids Working Group, 3142 Public health care science, environmental and occupational health, 3. Good health, Cholesterol, Heart Disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, RARE VARIANTS, lipids (amino acids, peptides, and proteins), LOW-FREQUENCY, Human, DNA Copy Number Variations, Science, Quantitative Trait Loci, European Continental Ancestry Group, Black People, POPULATION-SCALE, Quantitative trait locus, Article, White People, General Biochemistry, Genetics and Molecular Biology, LDL, Structural variation, 03 medical and health sciences, COMPONENTS-ANALYSIS, RISK-FACTOR, Humans, CORONARY-HEART-DISEASE, Polymorphism, Whole Genome Sequencing, Prevention, Human Genome, General Chemistry, Atherosclerosis, Vesicular Transport, Good Health and Well Being, 030104 developmental biology, chemistry, biology.protein, lcsh:Q, 3111 Biomedicine, Lipoprotein, Genome-Wide Association Study
Abstract

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans., Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Published
2018

49. Vascular health and cognitive function in older adults with cardiovascular disease

Author

Daniel E. Forman, Ronald A. Cohen, Karin F. Hoth, Andreana P. Haley, Athena Poppas, David J. Moser, John Gunstad, Robert H. Paul, Angela L. Jefferson, David F. Tate, Makoto Ono, Nicole Wake, and Marie Gerhard-Herman

Subjects
Cardiovascular disease, Vascular function, Age, Endothelium, Neurocognitive performance, Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated with the vascular responses. Methods: Eighty-eight independent, community-dwelling older adults (70.02 ± 7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-D ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function. Results: Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning. Conclusions: Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.

Published
2008
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50. Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial

Author

Warren G. Darling, Patrick Ten Eyck, Terry L. Wahls, Linda Snetselaar, Tyler J. Titcomb, Babita Bisht, Karin F. Hoth, Lucas J. Carr, Linda M. Rubenstein, and John Kamholz

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.disease_cause, Multiple sclerosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Dietary interventions, 0302 clinical medicine, Quality of life, Internal medicine, low-saturated fat diet, medicine, Paleolithic diet, 6-minute walk test, Original Research Article, Low saturated fat diet, business.industry, medicine.disease, Clinical trial, 030104 developmental biology, quality of life, Relapsing remitting, paleolithic diet, fatigue, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective To compare the effect of the modified Paleolithic elimination (Wahls) and low-saturated fat (Swank) diets in relapsing-remitting MS (RRMS). Methods Individuals (n = 87) with RRMS were randomized to the Swank or Wahls diets in a parallel group clinical trial consisting of four timepoints: 1) run-in, 2) baseline, 3) 12-weeks, and 4) 24-weeks. Results 77 participants completed 12 weeks and 72 completed 24 weeks. The 12-week change from baseline in fatigue was -0.94 ± 0.18 (FSS) and -9.87 ± 1.93 (MFIS; both p Conclusions Both diets were associated with clinically meaningful within-group reductions in fatigue and improvements in QoL. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964

Published
2021

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