UAB MEDICINE PULMONARY SERVICES FEATURE STORIES
FALL 2019
To read this and previous issues online, please visit uabmedicine.org/pulmupdate
NEW RESEARCH HOPES TO IDENTIFY INDIVIDUALS AT RISK OF CLINICALLY SIGNIFICANT COPD In an article published in the Journal of the American Medical Association, Surya Bhatt, MD, associate professor in the UAB Division of Pulmonary, Allergy, and Critical Care Medicine and medical director of the UAB Pulmonary Function and Exercise Physiology Lab, says there is much confusion and debate in the medical community on what are the best spirometry criteria to use for diagnosing chronic obstructive pulmonary disease (COPD). Currently, major respiratory society guidelines recommend diagnosing airflow obstruction when the ratio of the forced expiratory volume in one second (FEV1) to the forced vital capacity (FVC) is less than a fixed threshold of 0.70. This means that during a forced exhalation following a maximal inhalation, normal individuals should be able to blow out at least 70% of their lung size or vital capacity in the first second. However, there is no rigorous, population-based evidence to support the threshold of 0.70, which was set by expert opinion as the optimal FEV1/FVC threshold for defining clinically significant airflow obstruction, according to the published research. “A diagnosis of COPD needs confirmation by demonstrating obstruction to airflow using spirometry,” Dr. Bhatt says. “The currently used criteria are based on expert opinion, and until these results were published, there was not enough evidence to support their use.”
The multisite team, led by researchers from UAB and the University of Columbia, analyzed data from a large, multiethnic sample of 24,207 adults in the United States. They found that the currently used threshold of 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different from – or was more accurate than – other fixed thresholds. The 0.70 threshold also was more accurate than other thresholds that define normal lung function and are derived from reference populations. These results support the continued use of FEV1/FVC <0.70 to identify individuals at risk of clinically significant COPD. Cigarette smoking is the primary cause of COPD in the United States, but air pollutants at home and work also can cause it. COPD makes breathing difficult for the estimated 14 million Americans who have this disease. Millions more suffer from COPD but have not been diagnosed. Although there is no cure, it can be treated. “The ongoing disagreement between experts on the best spirometry criteria to diagnose airflow obstruction has resulted in a lack of clarity for clinicians,” Dr. Bhatt said. “Using a simple, standard threshold has the potential to improve the diagnosis and treatment of this common disease.”
CURRENT AND FORMER SMOKERS HAVE SIGNIFICANT UNMET MENTAL HEALTH CARE NEEDS Physician scientists from the UAB Division of Pulmonary, Allergy, and Critical Care Medicine – in partnership with researchers across the country – found that smokers with and without chronic obstructive pulmonary disease (COPD) have significant unmet mental health care needs, particularly anxiety and depressive symptoms. The findings were published in the Journal of Psychosomatic Research. “In the group of more than 5,000 smokers – with and without COPD – from the multisite, longitudinal genetic epidemiology of COPD (COPDGene) study, one in four had clinically elevated anxiety/depressive symptoms,” says study lead author and UAB assistant professor Anand S. Iyer, MD. “Of those with elevated symptoms, two-thirds were not receiving any type of medication to treat these symptoms, such as an anti-anxiety or antidepressant medication.” “While depressive symptoms were most frequent in those with the most severe cases of COPD,” Dr. Iyer adds, “anxiety symptoms were similar in frequency between smokers with and without COPD, so the problem seems to start a lot earlier in the disease.” According to Dr. Iyer, untreated emotional symptoms leave a major gap in COPD care that warrants early palliative care or primary palliative care. He says emotional symptoms have
been shown to impact many COPD-related outcomes. “We have previously found that depression predicts hospital readmissions in COPD, and others have found associations with exacerbations and poor adherence to medications,” Dr. Iyer says. “Clinically, we treat many COPD patients and smokers who have borderline COPD and also have clinically important emotional symptoms that would warrant treatment.” Dr. Iyer adds that pulmonary and primary care clinicians do not assess these symptoms often enough, which leaves many patients potentially untreated for elevated emotional symptoms – a major gap in comprehensive COPD care. It is not clear who is in charge of managing those symptoms. “Since the elevated emotional symptoms we discovered were also present in smokers who had milder COPD, earlier assessment and triage in the primary care setting is needed, potentially even early palliative care,” he says. “There are similar receptors in the brain functioning in smokers addicted to cigarettes and who have anxiety and depression,” Dr. Iyer says. “In fact, most of the smoking cessation medications frequently used to help patients quit are antidepressants, too.”
UAB MEDICINE PULMONARY SERVICES
RANKED NATIONALLY BY U.S. News & World Report NEW PHYSICIANS Gretchen Winter, MD Assistant Professor Dr. Winter earned her medical degree from Baylor College of Medicine in 2012, completed residency training at Indiana University in 2016, and finished her fellowship at the Cleveland Clinic in 2019. Her research and clinical interests include physician burnout, patient-physician communication, and medical education.
Ravi Virdi, MD Assistant Professor Dr. Virdi attended medical school at India’s Government Medical College and completed his residency at Nassau University Medical Center. After a pulmonary fellowship at the University of Southern California, he joined UAB Medicine in 2019. Dr. Virdi’s clinical and research interests focus on airway management, interstitial lung disease, and critical care medicine.
Aline Zouk, MD Assistant Professor After completing her initial medical training at American University of Beirut, Dr. Zouk completed a residency at Indiana University, followed by a pulmonary medicine fellowship at UAB. She then completed an interventional pulmonology fellowship at New York University before returning to UAB. Dr. Zouk’s clinical and research interests include ventilation and intubation, pulmonary hypertension, cystic fibrosis, and idiopathic pulmonary fibrosis.
FALL 2019
To read this and previous issues online, please visit uabmedicine.org/pulmupdate
COHORT WILL STUDY HOW VAPING, ENVIRONMENT, AND LIFESTYLE IMPACT LONG-TERM LUNG HEALTH IN MILLENNIALS Physicians in the UAB Division of Pulmonary, Allergy, and Critical Care Medicine say there is little information on the long-term respiratory impact of vaping, just as there is little information on whether poor air quality where people grow up increases their risk for respiratory conditions later in life. These issues will be examined in a large, first-of-its-kind longitudinal study of lung health funded by the National Institutes of Health. The study, titled “The American Lung Association Lung Health Cohort,” is supported by a $24.8 million grant awarded by the National Heart, Lung, and Blood Institute (NHLBI) to Northwestern University. UAB will serve as a major study site. Researchers will capture baseline lung health measurements of 4,000 healthy adults age 25-35 to identify an ideal picture of respiratory health and understand the key risk factors and biomarkers associated with impaired lung health. Scientists will follow these individuals for six years to track how their environment, lifestyle, and physical activity habits affect their respiratory health. Participants will be measured on their exposure to smoking, drinking, and vaping; have a nutritional assessment; wear physical activity monitors; and self-report symptoms such as fatigue and sleep disturbances. “The long-term impact of e-cigarettes and vaping is not known, and it is possible that these habits are as harmful as smoking,” says Mark Dransfield, MD, medical director for the UAB Lung Health Center. “It is critically important that we understand the health effects, as millions of young people are now using these products.” “We know that smoking and air pollution contribute to lung disease,” Dr. Dransfield continues. “But our understanding of other risk factors, particularly in youth and young adulthood, is limited, and this has hampered preventive efforts.” Researchers will leverage the national infrastructure of the American Lung Association’s Airways Clinical Research Centers to recruit study participants from its 17 metropolitan centers across the country, including UAB, Northwestern University, Johns Hopkins Medicine, Brigham and Women’s Hospital, the University of Michigan, and Beth Israel Deaconess Medical Center. The long-term goal of the study is to identify who is at risk for developing chronic lung diseases such as chronic obstructive pulmonary disease (COPD), emphysema, and pulmonary fibrosis.
SAVE THE DATE
FRIDAY & SATURDAY APRIL 3-4, 2020
UAB 2020 PULMONARY UPDATE
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FEATURE STORIES
To read this and previous issues online, please visit uabmedicine.org/pulmupdate
FEASIBILITY OF A NEW MODEL FOR EXERCISE PRESCRIPTION IN CYSTIC FIBROSIS
FDA APPROVES PHASE 2 TRIAL OF POTENTIAL IPF THERAPY GKT831
In a REACT Center pilot study, UAB pulmonologist Stefanie Krick, MD, and physical therapist John Lowman, PT, PhD, will examine the feasibility of a new, comprehensive exercise and behavior intervention for patients suffering from cystic fibrosis (CF). Pulmonary exacerbations are the main cause for progressive lung function decline, hospitalization, and mortality in patients with CF. Current studies on the role of exercise in CF show that physical exercise training has a positive effect on aerobic exercise capacity, pulmonary function, and health-related quality of life. However, almost all of these studies were conducted in outpatient settings and were focused on shortterm outcomes. The overarching hypothesis of this study is that providing both a comprehensive exercise program and a behavioral intervention during a two-week hospitalization for a pulmonary exacerbation will be a long-term solution that enhances adherence to an exercise program – and that adherence to this program will result in improved, patient-centered outcomes. The proposed study will enroll 20 hospitalized patients admitted to UAB Hospital for an acute pulmonary exacerbation, with a planned admission of 10-14 days, who do not have a structured exercise regimen. Standard care includes antibiotic and airway clearance therapies for 10-14 days. Participants also will receive an exercise program and a behavioral intervention that includes a heart rate/activity monitor, exercise log, and exercise training manual. Clinical outcomes will be assessed at admission and discharge and again at 2 weeks and 16 weeks after discharge. The comprehensive exercise program will include aerobic and resistance exercise as well as addressing any individual musculoskeletal/postural impairments. The exercise intervention will be 30 minutes a day, 6 days a week, at moderate intensity, alternating aerobic and resistance exercise. The behavioral intervention, based on social-cognitive theory, will include one-on-one coaching. In addition to the “inhospital intervention” period, participants will return to the UAB Outpatient CF Clinic and receive a “booster” intervention 2-4 weeks after discharge, at which point the program is reviewed. Results from this study will inform clinicians about the potential costs, barriers, development needs, and scientific promise of this proposed practice. If the planned intervention is found to be effective in larger trials, then this model also could be applied to other chronic medical conditions for which acute exacerbations requiring hospitalization are common.
Victor Thannickal, MD
The U.S. Food and Drug Administration (FDA) has approved the start of a phase 2 clinical trial of treatment candidate GKT831 for idiopathic pulmonary fibrosis (IPF). GKT831 is an orally available inhibitor of the NOX1 and NOX4 enzymes. NOX enzymes are known to help generate reactive oxygen species (ROS), high levels of which have been associated with tissue damage.
In July 2018, the National Institutes of Health awarded an $8.9 million grant to Victor Thannickal, MD, director of the UAB Division of Pulmonary, Allergy, and Critical Care Medicine, to fund a multi-year research program focusing on the effect of NOX enzymes in IPF. Dr. Thannickal’s research will assess the safety and effectiveness of GKT831 in 60 patients on standard of care treatment, comparing the potential therapy to placebo. Participants will receive 400 mg of GKT831 twice a day, a dose that showed anti-fibrotic and anti-inflammatory activity and had an excellent safety profile in a phase 2 trial (NCT03226067) in patients with the liver disease primary biliary cholangitis, according to GKT831 maker Genkyotex. The primary goal of the 24-week trial will be to assess the change in plasma levels of o,o’-dityrosine, which can be a marker of pulmonary oxidative stress and often is increased in patients with interstitial lung disease. Researchers also will evaluate changes in exercise capacity and lung function through the 6-minute walk distance test and forced vital capacity assessment. Preclinical studies conducted on mice by Dr. Thannickal and his team identified NOX4 as a key driver of lung fibrosis, as it triggered the differentiation of fibroblasts into myofibroblasts and was involved in the production of extracellular matrix, which accumulates in patients with IPF. Researchers also demonstrated that levels of NOX4 are increased in people with IPF and that suppressing NOX1/4 with GKT831 had anti-fibrotic effects and extended the survival of aged mice with lung fibrosis. In turn, several models of lung disease identified NOX1 as a driver of vascular remodeling, which was reduced after treatment with GKT831. “This is an important step forward in translating seminal preclinical discoveries to patients with fibrotic lung disease,” Dr. Thannickal says. “NOX1/4 inhibition may have profound diseasemodifying effects on the fibrotic and vascular remodeling, which drives disease progression in IPF. We believe GKT831 has the potential to be an effective IPF treatment.”
UAB MEDICINE PULMONARY SERVICES
RANKED NATIONALLY BY U.S. News & World Report NEW PHYSICIANS Gretchen Winter, MD Assistant Professor Dr. Winter earned her medical degree from Baylor College of Medicine in 2012, completed residency training at Indiana University in 2016, and finished her fellowship at the Cleveland Clinic in 2019. Her research and clinical interests include physician burnout, patient-physician communication, and medical education.
Ravi Virdi, MD Assistant Professor Dr. Virdi attended medical school at India’s Government Medical College and completed his residency at Nassau University Medical Center. After a pulmonary fellowship at the University of Southern California, he joined UAB Medicine in 2019. Dr. Virdi’s clinical and research interests focus on airway management, interstitial lung disease, and critical care medicine.
Aline Zouk, MD Assistant Professor After completing her initial medical training at American University of Beirut, Dr. Zouk completed a residency at Indiana University, followed by a pulmonary medicine fellowship at UAB. She then completed an interventional pulmonology fellowship at New York University before returning to UAB. Dr. Zouk’s clinical and research interests include ventilation and intubation, pulmonary hypertension, cystic fibrosis, and idiopathic pulmonary fibrosis.
FALL 2019
To read this and previous issues online, please visit uabmedicine.org/pulmupdate
COHORT WILL STUDY HOW VAPING, ENVIRONMENT, AND LIFESTYLE IMPACT LONG-TERM LUNG HEALTH IN MILLENNIALS Physicians in the UAB Division of Pulmonary, Allergy, and Critical Care Medicine say there is little information on the long-term respiratory impact of vaping, just as there is little information on whether poor air quality where people grow up increases their risk for respiratory conditions later in life. These issues will be examined in a large, first-of-its-kind longitudinal study of lung health funded by the National Institutes of Health. The study, titled “The American Lung Association Lung Health Cohort,” is supported by a $24.8 million grant awarded by the National Heart, Lung, and Blood Institute (NHLBI) to Northwestern University. UAB will serve as a major study site. Researchers will capture baseline lung health measurements of 4,000 healthy adults age 25-35 to identify an ideal picture of respiratory health and understand the key risk factors and biomarkers associated with impaired lung health. Scientists will follow these individuals for six years to track how their environment, lifestyle, and physical activity habits affect their respiratory health. Participants will be measured on their exposure to smoking, drinking, and vaping; have a nutritional assessment; wear physical activity monitors; and self-report symptoms such as fatigue and sleep disturbances. “The long-term impact of e-cigarettes and vaping is not known, and it is possible that these habits are as harmful as smoking,” says Mark Dransfield, MD, medical director for the UAB Lung Health Center. “It is critically important that we understand the health effects, as millions of young people are now using these products.” “We know that smoking and air pollution contribute to lung disease,” Dr. Dransfield continues. “But our understanding of other risk factors, particularly in youth and young adulthood, is limited, and this has hampered preventive efforts.” Researchers will leverage the national infrastructure of the American Lung Association’s Airways Clinical Research Centers to recruit study participants from its 17 metropolitan centers across the country, including UAB, Northwestern University, Johns Hopkins Medicine, Brigham and Women’s Hospital, the University of Michigan, and Beth Israel Deaconess Medical Center. The long-term goal of the study is to identify who is at risk for developing chronic lung diseases such as chronic obstructive pulmonary disease (COPD), emphysema, and pulmonary fibrosis.
SAVE THE DATE
FRIDAY & SATURDAY APRIL 3-4, 2020
UAB 2020 PULMONARY UPDATE
The Hilton Birmingham at UAB Mark your calendar now to attend this upcoming CME and CEU event.
FEATURE STORIES
To read this and previous issues online, please visit uabmedicine.org/pulmupdate
FEASIBILITY OF A NEW MODEL FOR EXERCISE PRESCRIPTION IN CYSTIC FIBROSIS
FDA APPROVES PHASE 2 TRIAL OF POTENTIAL IPF THERAPY GKT831
In a REACT Center pilot study, UAB pulmonologist Stefanie Krick, MD, and physical therapist John Lowman, PT, PhD, will examine the feasibility of a new, comprehensive exercise and behavior intervention for patients suffering from cystic fibrosis (CF). Pulmonary exacerbations are the main cause for progressive lung function decline, hospitalization, and mortality in patients with CF. Current studies on the role of exercise in CF show that physical exercise training has a positive effect on aerobic exercise capacity, pulmonary function, and health-related quality of life. However, almost all of these studies were conducted in outpatient settings and were focused on shortterm outcomes. The overarching hypothesis of this study is that providing both a comprehensive exercise program and a behavioral intervention during a two-week hospitalization for a pulmonary exacerbation will be a long-term solution that enhances adherence to an exercise program – and that adherence to this program will result in improved, patient-centered outcomes. The proposed study will enroll 20 hospitalized patients admitted to UAB Hospital for an acute pulmonary exacerbation, with a planned admission of 10-14 days, who do not have a structured exercise regimen. Standard care includes antibiotic and airway clearance therapies for 10-14 days. Participants also will receive an exercise program and a behavioral intervention that includes a heart rate/activity monitor, exercise log, and exercise training manual. Clinical outcomes will be assessed at admission and discharge and again at 2 weeks and 16 weeks after discharge. The comprehensive exercise program will include aerobic and resistance exercise as well as addressing any individual musculoskeletal/postural impairments. The exercise intervention will be 30 minutes a day, 6 days a week, at moderate intensity, alternating aerobic and resistance exercise. The behavioral intervention, based on social-cognitive theory, will include one-on-one coaching. In addition to the “inhospital intervention” period, participants will return to the UAB Outpatient CF Clinic and receive a “booster” intervention 2-4 weeks after discharge, at which point the program is reviewed. Results from this study will inform clinicians about the potential costs, barriers, development needs, and scientific promise of this proposed practice. If the planned intervention is found to be effective in larger trials, then this model also could be applied to other chronic medical conditions for which acute exacerbations requiring hospitalization are common.
Victor Thannickal, MD
The U.S. Food and Drug Administration (FDA) has approved the start of a phase 2 clinical trial of treatment candidate GKT831 for idiopathic pulmonary fibrosis (IPF). GKT831 is an orally available inhibitor of the NOX1 and NOX4 enzymes. NOX enzymes are known to help generate reactive oxygen species (ROS), high levels of which have been associated with tissue damage.
In July 2018, the National Institutes of Health awarded an $8.9 million grant to Victor Thannickal, MD, director of the UAB Division of Pulmonary, Allergy, and Critical Care Medicine, to fund a multi-year research program focusing on the effect of NOX enzymes in IPF. Dr. Thannickal’s research will assess the safety and effectiveness of GKT831 in 60 patients on standard of care treatment, comparing the potential therapy to placebo. Participants will receive 400 mg of GKT831 twice a day, a dose that showed anti-fibrotic and anti-inflammatory activity and had an excellent safety profile in a phase 2 trial (NCT03226067) in patients with the liver disease primary biliary cholangitis, according to GKT831 maker Genkyotex. The primary goal of the 24-week trial will be to assess the change in plasma levels of o,o’-dityrosine, which can be a marker of pulmonary oxidative stress and often is increased in patients with interstitial lung disease. Researchers also will evaluate changes in exercise capacity and lung function through the 6-minute walk distance test and forced vital capacity assessment. Preclinical studies conducted on mice by Dr. Thannickal and his team identified NOX4 as a key driver of lung fibrosis, as it triggered the differentiation of fibroblasts into myofibroblasts and was involved in the production of extracellular matrix, which accumulates in patients with IPF. Researchers also demonstrated that levels of NOX4 are increased in people with IPF and that suppressing NOX1/4 with GKT831 had anti-fibrotic effects and extended the survival of aged mice with lung fibrosis. In turn, several models of lung disease identified NOX1 as a driver of vascular remodeling, which was reduced after treatment with GKT831. “This is an important step forward in translating seminal preclinical discoveries to patients with fibrotic lung disease,” Dr. Thannickal says. “NOX1/4 inhibition may have profound diseasemodifying effects on the fibrotic and vascular remodeling, which drives disease progression in IPF. We believe GKT831 has the potential to be an effective IPF treatment.”
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UAB MEDICINE PULMONARY SERVICES FALL 2019 INSIDE THIS ISSUE: • New Research Hopes to Identify Individuals at Risk of Clinically Significant COPD • Current and Former Smokers Have Significant Unmet Mental Health Care Needs • Cohort Will Study How Vaping, Environment, and Lifestyle Impact Long-term Lung Health in Millennials • Feasibility of a New Model for Exercise Prescription in Cystic Fibrosis • FDA Approves Phase 2 Trial of Potential IPF Therapy GKT831
Contact UAB Medicine’s 24-hour consultation and referral service at 800.UAB.MIST or mist@uabmc.edu.
CLINICAL TRIALS
SELECTED PUBLICATIONS
• Diastolic Dysfunction and Pauci-Inflammatory Acute Exacerbations of COPD – PI: Surya P. Bhatt, MD This is a prospective study to determine the relationships between pauci-inflammatory exacerbations and diastolic dysfunction, and their implications in hospitalized patients with acute exacerbations of COPD. To assess changes within subjects from stable to acute phase, a number of comparisons will be made in subjects enrolled during acute exacerbation, with similar measurements made in the stable phase after recovery from exacerbation after at least 35 days from index hospitalization or prior exacerbation.
Parker MM, Hao Y, Guo F, Pham B, Chase R, Platig J, Cho MH, Hersh CP, Thannickal VJ, Crapo J, Washko G, Randell SH, Silverman EK, San José Estépar R, Zhou X, Castaldi PJ. Identification of an emphysema-associated genetic variant near TGFB2 with regulatory effects in lung fibroblasts. Elife. 2019 Jul 25;8.
• Autoantibody Reduction for Acute Exacerbations of Idiopathic Pulmonary Fibrosis (STRIVE-IPF) – PI: Steven R. Duncan, MD Acute exacerbations (AE) are a dreaded manifestation of idiopathic pulmonary fibrosis (IPF) that present with rapidly worsening respiratory function over days to weeks. AEs account for about half of the deaths in patients with IPF and are refractory to all medical therapies attempted to date. Considerable preliminary data show pathological B-cell abnormalities and autoantibodies are present in AE-IPF and associated with disease severity. The experimental therapy here (therapeutic plasma exchange plus rituximab plus intravenous immunoglobulin) is mechanistically targeted to ameliorate autoantibody-mediated pulmonary injury. Anecdotal pilot studies indicate these treatments have significant benefit for a disease syndrome that has, until now, been almost invariably inexorable. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF. • Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations – PI: Steven M. Rowe, MD Based on previous clinical findings, the investigators hypothesize that ivacaftor will have synergistic effects with drugs that facilitate truncated but partially active W1282X CFTR protein processing (tezacaftor) in patients with W1282X CFTR. In the current study, the investigators propose to directly test the efficacy of tezacaftor/ivacaftor (TEZ/IVA) for W1282X CFTR therapy in the clinic in comparison to ivacaftor alone. • Alvelestat (MPH996) for the Treatment of ALpha-1 ANTitrypsin Deficiency (ATALANTa) – PI: Mark Dransfield, MD This is a phase 2, multicenter, double-blind, randomized (1:1), placebo-controlled, 12-week, proof-of-concept study to evaluate the safety and tolerability as well as the mechanistic effect of oral administration of alvelestat (MPH996) in subjects with confirmed alpha-1 (Alpha-1 ZZ genotype (Pi*ZZ), Alpha-1 SZ genotype (Pi*SZ), or Alpha -1 Null phenotype (Pi*Null phenotype)) antitrypsin deficiency (AATD)-related emphysema.
For more information or to contact a clinical trial team, visit xpertdox.com/uab-trial.
Bhatt SP, Balte PP, Schwartz JE, Cassano PA, Couper D, Jacobs DR Jr, Kalhan R, O’Connor GT, Yende S, Sanders JL, Umans JG, Dransfield MT, Chaves PH, White WB, Oelsner EC.Discriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality. JAMA. 2019 Jun 25;321(24):2438-2447 Yuan T, Volckaert T, Redente EF, Hopkins S, Klinkhammer K, Wasnick R, Chao CM, Yuan J, Zhang JS, Yao C, Majka S, Stripp BR, Günther A, Riches DWH, Bellusci S, Thannickal VJ, De Langhe SP. FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury. Stem Cell Reports. 2019 May 14;12(5):1041-1055. Oudkerk SF, Mohamed Hoesein FAA, Öner FC, Verlaan JJ, de Jong PA, Kuperus JS, Cho M, McDonald ML, Lynch DA, Silverman EK, Crapo JD, Make BJ, Lowe KE, Regan EA. Diffuse Idiopathic Skeletal Hyperostosis in Smokers is Associated with Restrictive Spirometry Pattern: An Analysis in the COPDGene Cohort. J Rheumatol. 2019 May 1 Admon AJ, Donnelly JP, Casey JD, Janz DR, Russell DW, Joffe AM, Vonderhaar DJ, Dischert KM, Stempek SB, Dargin JM, Rice TW, Iwashyna TJ, Semler MW. Emulating a Novel Clinical Trial Using Existing Observational Data. Predicting Results of the PreVent Study. Ann Am Thorac Soc. 2019 Aug;16(8):998-1007 Oelsner EC, Ortega VE, Smith BM, Nguyen JN, Manichaikul AW, Hoffman EA, Guo X, Taylor KD, Woodruff PG, Couper DJ, Hansel NN, Martinez FJ, Paine Iii R, Han MK, Cooper C, Dransfield MT, Criner G, Krishnan JA, Bowler R, Bleecker ER, Peters S, Rich SS, Meyers DA, Rotter JI, Barr RG. A Genetic Risk Score Associated with COPD Susceptibility and Lung Structure on Computed Tomography. Am J Respir Crit Care Med. 2019 Mar 29 Fortis S, Comellas A, Make BJ, Hersh CP, Bodduluri S, Georgopoulos D, Kim V, Criner GJ, Dransfield MT, Bhatt SP; COPDGene Investigators–Core Units: Administrative Center, COPDGene Investigators–Clinical Centers: Ann Arbor VaA. Combined Forced Expiratory Volume in 1 Second and Forced Vital Capacity Bronchodilator Response, Exacerbations, and Mortality in Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2019 Jul;16(7):826-835. doi: 10.1513/AnnalsATS.201809-601OC. PMID: 30908927 Casey JD, Janz DR, Russell DW, Vonderhaar DJ, Joffe AM, Dischert KM, Brown RM, Zouk AN, Gulati S, Heideman BE, Lester MG, Toporek AH, Bentov I, Self WH, Rice TW, Semler MW; PreVent Investigators and the Pragmatic Critical Care Research Group. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2019 Feb 28;380(9):811-821. doi: 10.1056/NEJMoa1812405. Epub 2019 Feb 18.