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uabmedicine.org/learnmd
FOR FREE CME CREDIT
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 [email protected].
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.