Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species

Abstract

Rationale 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. Objectives Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens. Methods Utilizing 20 human iSGS, 20 intubation-related tracheal stenosis (iLTS) and 10 healthy control specimens we applied molecular, immunohistochemical, electron microscopic, immunologic and Sanger™ sequencing techniques. Main Results 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 (Mtb), a variant member of the Mycobacterium Tuberculosis Complex (MtbC), or a closely related novel mycobacterium is present in iSGS specimens. Conclusions These studies identify a novel pathogenic role for established large airway bacteria, and provide new targets for future therapeutic intervention. Level of Evidence NA.

Outcomes after cricotracheal resection for idiopathic subglottic stenosis

“…Given our single institution cohort, risk factors for recurrence remain elusive. Further work with the NoAAC may prove fruitful in elucidating risk factors …”

“…The disorder primarily affects otherwise healthy females aged 30 to 50 years. Recent data suggests that both activation of inflammatory pathways and possible pathogenic bacteria may be contributing to the disease process . It is also theorized that hormones may play a role in disease; however, there is no clear link aside from a predilection toward females .…”

Quantification of Inflammatory Markers in Laryngotracheal Stenosis

“…16,17 Another potential explanation for the increase in INF-Υ expression in iSGS is the propensity for bacterial colonization by mycobacterium species in iSGS. 8 Previous studies have demonstrated that Mycobacteriums antigenicity invokes a robust release of INF-Υ from T-cells, natural killer cells, and macrophages. 18,19 Like IL-4, the role of this increased INF-Υ expression in iSGS is also unclear.…”

Targeting metabolic abnormalities to reverse fibrosis in iatrogenic laryngotracheal stenosis

“…The most predominant etiology of LTS is iatrogenic (iLTS), in which intubation injury to the epithelium promotes prolonged subepithelial inflammation and subsequently fibroblast proliferation and collagen deposition . This dysregulated wound‐healing response is driven by complex signaling between epithelial cells, immune mediators, and fibroblasts, which stimulates deposition of excessive collagen, leading to airway narrowing . Mild airway restriction secondary to this narrowing impacts quality of life, and in severe cases requires surgical intervention to relieve the resultant dyspnea.…”