Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species.
Idiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown. Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens.



Utilizing 30 human iSGS, 20 intubation-related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger-sequencing techniques.



With unbiased culture-independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens.



These studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.



NA Laryngoscope, 127:179-185, 2017.
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
Alexander
A
Gelbard
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
Nicolas-George
NG
Katsantonis
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
Masanobu
M
Mizuta
Department of Medicine, Division of Pulmonary and Critical Care, Vanderbilt University, Nashville, Tennessee.
Dawn
D
Newcomb
Department of Medicine, Division of Infectious Disease, Vanderbilt University, Nashville, Tennessee.
Joseph
J
Rotsinger
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
Bernard
B
Rousseau
Department of Otolaryngology, University of Virginia Health System, Charlottesville, Virginia.
James J
JJ
Daniero
Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.
Eric S
ES
Edell
Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota.
Dale C
DC
Ekbom
Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota.
Jan L
JL
Kasperbauer
Department of Otolaryngology, Johns Hopkins, Baltimore, Maryland.
Alexander T
AT
Hillel
Department of Medicine, New York University School of Medicine, New York, New York, U.S.A.
Liying
L
Yang
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
C Gaelyn
CG
Garrett
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
James L
JL
Netterville
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
Christopher T
CT
Wootten
Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee.
David O
DO
Francis
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee.
Charles
C
Stratton
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee.
Kevin
K
Jenkins
Department of Pediatrics, Division of Medical Genetics, Vanderbilt University, Nashville, Tennessee.
Tracy L
TL
McGregor
Department of Medicine, Division of Infectious Disease, Vanderbilt University, Nashville, Tennessee.|Veterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee.
Jennifer A
JA
Gaddy
Department of Medicine, Division of Pulmonary and Critical Care, Vanderbilt University, Nashville, Tennessee.|Veterans Affairs Tennessee Valley Healthcare Services, Nashville, Tennessee.
Timothy S
TS
Blackwell
Department of Medicine, Division of Infectious Disease, Vanderbilt University, Nashville, Tennessee.
Wonder P
WP
Drake
D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007442:Intubation, Intratracheal / Q000009:adverse effects; D007829:Laryngostenosis / Q000209:etiology / Q000382:microbiology*; D064307:Microbiota; D008854:Microscopy, Electron; D009161:Mycobacterium / Q000302:isolation & purification*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D014135:Tracheal Stenosis / Q000209:etiology / Q000382:microbiology*
ISS; Mtb; Mycobacterium; iSGS; idiopathic subglottis stenosis; laryngotracheal stenosis; tracheal stenosis