PMID- 32369195
OWN - NLM
STAT- MEDLINE
DCOM- 20210118
LR  - 20221005
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 131
IP  - 2
DP  - 2021 Feb
TI  - Laryngotracheal Mucosal Surface Expression of Candidate Biomarkers in Idiopathic 
      Subglottic Stenosis.
PG  - 342-349
LID - 10.1002/lary.28712 [doi]
AB  - OBJECTIVES: Idiopathic subglottic stenosis (iSGS) is an inflammatory process 
      leading to fibrosis and narrowing of the laryngotracheal airway. There is 
      variability in patient response to surgical intervention, but the mechanisms 
      underlying this variability are unknown. In this pilot study, we measure 
      expression of candidate targets at the mucosal surface of the subglottis in iSGS 
      patients. We aim to identify putative biomarkers for iSGS that provide insights 
      into the molecular basis of disease progression, yield a gene signature for the 
      disease, and/or predict a response to therapy. STUDY DESIGN: In vitro comparative 
      study of human cells. METHODS: Levels of candidate transcripts and proteins were 
      measured in healthy and stenotic laryngotracheal tissue specimens taken from the 
      mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre- 
      and post-operative pulmonary function test and patient reported voice and 
      breathing outcomes were also assessed. Unsupervised clustering was used to define 
      patient subgroups based on expression profile. RESULTS: Pulmonary function and 
      voice and breathing outcome metrics demonstrated significant post-operative 
      improvement. Transcript levels of alphaSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and 
      TGFB1 and protein levels of CCL2, IFNG, and IL-6 were significantly upregulated 
      in stenotic as compared to healthy tissues. Marked heterogeneity was observed in 
      the patterns of expression of candidate markers across individuals and tissue 
      types. Patient subgroups defined by expression profile did not show a 
      statistically significant difference in dilation interval. CONCLUSION: 
      Pro-inflammatory and pro-fibrotic pathways are significantly upregulated along 
      the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit 
      further investigation as potential iSGS biomarkers. LEVEL OF EVIDENCE: 4 
      Laryngoscope, 131:342-349, 2021.
CI  - (c) 2020 The American Laryngological, Rhinological and Otological Society, Inc.
FAU - Liu, Melissa M
AU  - Liu MM
AUID- ORCID: 0000-0002-4385-9507
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, U.S.A.
FAU - Motz, Kevin M
AU  - Motz KM
AUID- ORCID: 0000-0002-9255-7265
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, U.S.A.
FAU - Murphy, Michael K
AU  - Murphy MK
AD  - Department of Otolaryngology & Communication, State University of New York 
      Upstate Medical University, Syracuse, New York, U.S.A.
FAU - Yin, Linda X
AU  - Yin LX
AUID- ORCID: 0000-0001-8515-2051
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, 
      Minnesota, U.S.A.
FAU - Ding, Dacheng
AU  - Ding D
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, U.S.A.
FAU - Gelbard, Alexander
AU  - Gelbard A
AD  - Department of Otolaryngology, Vanderbilt University School of Medicine, 
      Nashville, Tennessee, U.S.A.
AD  - The North American Airway Collaborative, U.S.A.
FAU - Hillel, Alexander T
AU  - Hillel AT
AUID- ORCID: 0000-0001-8471-5449
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland, U.S.A.
AD  - The North American Airway Collaborative, U.S.A.
LA  - eng
GR  - R01 DC018567/DC/NIDCD NIH HHS/United States
GR  - R21 DC017225/DC/NIDCD NIH HHS/United States
GR  - American College of Surgeons/International
GR  - 1R21DC01722501/DC/NIDCD NIH HHS/United States
GR  - Triological Society/International
GR  - 1409-22214/Patient Centered Outcomes Research Institute/International
GR  - 1K23DC014082/DC/NIDCD NIH HHS/United States
GR  - R01 HL146401/HL/NHLBI NIH HHS/United States
GR  - K23 DC014082/DC/NIDCD NIH HHS/United States
GR  - 1K23DC014082/DC/NIDCD NIH HHS/United States
GR  - 1R21DC01722501/DC/NIDCD NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200505
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Biomarkers)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/analysis
MH  - Dilatation
MH  - Disease Progression
MH  - Endoscopy
MH  - Female
MH  - Fibrosis
MH  - Humans
MH  - Laryngeal Mucosa/*pathology
MH  - Laryngostenosis/*genetics/pathology
MH  - Larynx/*pathology
MH  - Male
MH  - Membrane Proteins/*analysis
MH  - Middle Aged
MH  - Pilot Projects
MH  - Predictive Value of Tests
MH  - Respiratory Function Tests
MH  - Trachea/*pathology
MH  - Transcriptome
PMC - PMC7641987
MID - NIHMS1593552
OTO - NOTNLM
OT  - Idiopathic subglottic stenosis
OT  - dilation
OT  - gene expression
OT  - protein expression
EDAT- 2020/05/06 06:00
MHDA- 2021/01/20 06:00
PMCR- 2022/02/01
CRDT- 2020/05/06 06:00
PHST- 2020/01/11 00:00 [received]
PHST- 2020/03/11 00:00 [revised]
PHST- 2020/04/10 00:00 [accepted]
PHST- 2020/05/06 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/05/06 06:00 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - 10.1002/lary.28712 [doi]
PST - ppublish
SO  - Laryngoscope. 2021 Feb;131(2):342-349. doi: 10.1002/lary.28712. Epub 2020 May 5.