Quarterly Pulmonary Update Spring 2020 | Page 2

UAB MEDICINE PULMONARY SERVICES SPRING 2020 NEW PHYSICIANS Chao He, MD, PhD Assistant Professor Dr. He received his medical degree from Soochow University in China and his PhD in free radical and radiation biology from the University of Iowa. He joined the ABIM Pathway in 2015 and completed his residency and clinical fellowship in Pulmonary and Critical Care Medicine in June 2019. He currently is a T32 postdoctoral research fellow working in Dr. A. Brent Carter’s lab. Dr. He’s research is focused on defining the role of alveolar macrophages in lung fibrosis. Previously he has shown that macrophages undergo a different polarization process during fibrosis development, and the process is regulated by redox signaling. His current work investigates NOX4 and its role in mediating lung macrophage polarization. Daval Rhaval, MD Assistant Professor Dr. Rhaval’s clinical interests include critical care, with special interest in ICU delirium, early ambulation and sepsis management. He has had robust exposure to various endobronchial and pleural procedures, including indwelling pleural catheter, percutaneous tracheotomy, bronchothermoplasty. Dr. Rhaval is also interested in sleep medicine, ICU ultrasonography, and hemodynamic management. His training in public health and epidemiology gave him great insight in evidence-based medicine. Dr. Raval also has experience as an independent hospitalist. He has been involved in quality improvement and resource utilization projects. His interest in resident and medical student education has grown over his career, indicated by his teaching of medical students and residents throughout his training. Megan Kiedrowski, PhD Assistant Professor Dr. Kiedrowski is a microbiologist interested in host-pathogen interactions during polymicrobial infections. Her current work focuses on interactions between the host airway epithelium, bacterial pathogens, and viruses during cystic fibrosis respiratory infections. Previously, Dr. Kiedrowski worked as a postdoctoral fellow in Jennifer Bomberger’s laboratory in the Department of Microbiology and Molecular Genetics at the University of Pittsburgh. She investigated polymicrobial infections in the CF lung and the impact of the host environment on microbe-microbe interactions in polymicrobial infections. She also worked as a postdoctoral fellow in the laboratory of Jo Handelsman in the Department of Molecular, Cellular and Developmental Biology at Yale University. There, she conducted research on microbial communities and examined microbe-microbe interactions in the gut environment and in biofilms. Dr. Kiedrowski received her doctoral degree in microbiology from the University of Iowa. She carried out her graduate research in the laboratory of Alex Horswill, where she studied Staphylococcus aureus biofilm formation and presented her work at many national and international conferences. RANKED NATIONALLY BY U.S. News & World Report To read these and past stories online, please visit uabmedicine.org/referpulm. RESEARCH POINTS TO POSSIBLE TARGET FOR TREATING IPF A. Brent Carter, MD, and colleagues report that the recruited monocyte-derived macrophages, which have an increased flux in the mevalonate metabolic pathway — without any experimental injury — can induce lung fibrosis in a mouse model. Their study, “Increased flux through the mevalonate pathway mediates fibrotic repair without injury,” is published in the Journal of Clinical Investigation. “Here, we show a paradigm shift that indicates a critical and essential role for monocyte-derived macrophage/fibroblast crosstalk in the development and progression of fibrosis in the absence of epithelial injury,” Dr. Carter says. Research has shown that three hallmarks of the mechanism that leads to lung fibrosis in the absence of injury in mice also are found in bronchoalveolar (BAL) cells. The three hallmarks are: 1. Activation of the small GTPase protein Rac1 and its localization into the intermembrane space of mitochondria in the BAL cells 2. Increased production of mitochondrial reactive oxygen species by BAL cells in patients with IPF 3. Evidence of increased flux through the non-sterol arm of the mevalonate pathway in the BAL cells that results in the augmented activation of Rac1. In macrophages, an increased flux through the non-sterol arm of the mevalonate pathway increases the production of geranylgeranyl diphosphate, or GGDP. This increased flux is secondary to greater levels of acetyl-CoA from metabolic reprogramming of the macrophages to β oxidation. Using GGDP, an enzyme then adds geranylgeranyl (a lipophilic membrane anchor) to Rac1, a Rho GTPase, and the geranylgeranylated Rac1 translocates from the cytosol to the intermembrane space of mitochondria. There, it induces production of reactive oxygen species. The reactive oxygen species cause a phenotypic shift of the macrophage to a profibrotic state, acting through key transcription factors. The profibrotic macrophages then produce TGF-β1, which transforms fibroblasts into pathogenic myofibroblasts. “We propose that monocyte-derived macrophage/fibroblast crosstalk can induce fibrosis without epithelial cell injury and is the primary driver in mediating disease progression,” Dr. Carter says. “These observations suggest that targeting the mevalonate pathway may abrogate the role of macrophages in dysregulated fibrotic repair.” ABOUT OUR SERVICES UAB Medicine recently launched a new webpage for medical professionals devoted to many of our key service areas, including the Division of Pulmonary, Allergy, and Critical Care Medicine. Located at uabmedicine.org/referpulm, the page features details about conditions we treat and many important therapies and clinical programs offered by the Division, such as: • Asthma and COPD Clinic • Critical care medicine, including extracorporeal membrane oxygenation (ECMO) • Sleep/Wake Disorders Center FEATURE STORIES DRS. IYER AND DRANSFIELD STUDY END-OF- LIFE SPENDING AND HEALTH CARE UTILIZATION AMONG OLDER ADULTS WITH COPD In the American Journal of Medicine, UAB Medicine pulmonary physicians Anand Iyer, MD, and Mark Dransfield, MD, recently published their findings related to spending and care utilization among older patients with COPD. As end-of-life spending and health care utilization in older adults with COPD have not been previously described, Drs. Iyer, Dransfield, and collaborators examined data from Medicare beneficiaries age 65 and up who had COPD and died between 2013 and 2014. End-of-life measures were retrospectively reviewed for two years prior to death. Hospital referral regions, or HRRs, were categorized into quintiles of age-sex-raceadjusted overall spending during the last two years of life. The research examined geographic and spending quintile variation in spending and health care utilization across the continuum. The investigators analyzed data from 146,240 decedents with COPD from 306 HRRs. Age-sex-race-adjusted overall spending per decedent during the last two years of life varied significantly nationwide, from roughly $48,000 to $79,000. Inpatient care accounted for 40.2% of spending. Overall, approximately 82% of decedents were admitted to the hospital for nearly two weeks, with 55% of those in an intensive care unit for about five days. Compared to HRRs in the lowest spending quintile, HRRs in the highest spending quintile had hospital lengths of stay that were 1.5-fold longer. Skilled nursing facilities accounted for 11.6% of spending (approximately $7,000 per decedent) and were used by nearly 40% of decedents for nearly 20 days. Hospice accounted for 10.3% of spending (about $6,307 per decedent) and was used by approximately 47% of decedents for roughly 40 days. There was significant geographic variation in hospice use nationwide. After completing its analysis, the research team discovered that end-of-life spending and health care utilization in older adults with COPD varied substantially nationwide. Decedents with COPD frequently used acute and post-acute care near the end of life. Hospice use was higher than expected, with significant geographic disparities. • Pulmonary fibrosis and interstitial lung disease • Primary Ciliary Dyskinesia and Bronchiectasis Clinic • Cystic fibrosis • Interventional pulmonology To read these and past stories online, please visit uabmedicine.org/referpulm. UAB EMPLOYEE WELLNESS HOSTS SECOND ANNUAL ‘LOVE YOUR LUNGS’ EXPO On Dec. 5, 2019, the UAB Division of Pulmonary, Allergy, and Critical Care Medicine collaborated with the UAB Lung Health Center and UAB Employee Wellness to host the second annual “Love Your Lungs” Health Expo. UAB employees, students and members of the community were invited to learn about healthy lung resources, win prizes, discuss lung health with UAB Medicine faculty, take part in educational contests, and, of course, snap a selfie with 17-foot inflatable lungs. Participating organizations provided resources and opportunities to help employees live well — from a dynamic schedule of wellness programs and initiatives to on-campus tools, classes, and screenings that make it easy to make healthy choices in the workplace. “The whole reason we’re doing this event is to remind employees about how important it is to take care of your lungs by living tobacco-free and by paying attention to the risk factors for lung cancer,” says Anna Threadcraft, previous UAB Employee Wellness director and the event’s coordinator. Love Your Lungs also was designed to communicate with the local community, alerting residents about important lung health information they may have not known. “Lung cancer is the number one cause of death in Alabama, and 80% of those who have lung cancer are either current or former smokers,” says Monica Baskin, PhD, professor of Preventive Medicine and associate director for Community Outreach and Engagement at the O’Neal Comprehensive Cancer Center at UAB. This event also served to remind UAB Medicine physicians to encourage their patients to quit smoking, emphasizing the impact that a simple suggestion can have coming from a health care provider. “One of the most effective interventions you can do is to advise your patients to quit smoking,” says John I. Kennedy Jr., MD, senior advisor and director of Wellness at UAB. Healthy lung resources are available online at uab.edu/ loveyourlungs.