Retinoic Acid: A Silver Bullet In The Adjunctive Management Of Tracheal Stenosis

Faiz Y. Bhora, MD1 Russell Seth Martins, MD1 Kostantinos Poulikidis, MD1 Syed Shahzad Razi, MD1  M. Jawad Latif, MD1  Killol Patel, MD1 Robert S. Lebovics, MD1 Jeffrey Luo, PhD1
1 JFK University Medical Center, 65 James Street, Edison, NJ, 08820

 

BACKGROUND

• Tracheal stenosis (TS) is progressive occlusion of the airway
 • Standard of care revolves around endoscopic interventions
  • Carbon dioxide laser, cryoablation, balloon dilation [1]
 • Significant (~15%) of patients exhibit recalcitrant disease course and need repeated procedures

• Need to develop pharmacological adjunct to consolidate interventional management
 • TS known to involve epithelial hyperkeratinization, hyperproliferation, and granulation tissue accumulation [2]
  • Retinoic acid known to favorably regulate these pathways

• Utilize next-gen sequencing to elucidate nature of retinoid dysfunction in TS

 

METHODS

• Design: adult patients with severe, recalcitrant TS (IRB approval ID: 2019-19, Nuvance Health)

• Setting: single center, JFK University Medical Center outpatient facility

• Intervention: tracheal granulation tissue biopsies collected at time of endoscopic intervention

• Main outcome measures: next-gen sequencing (RNAseq)

• Analysis: differential gene expression between diseased tissue and normal control data (from public databases), functional interaction networK

 

RESULTS

• Dysregulated Retinoid Metabolism Pathway

• Dysregulated Retinoid Metabolism Gene Expression

• Genes Affected by Retinoid Deficiency (Retinoic Acid Receptor-γ, RARG)

 

LIMITATIONS

• Limited number of patients (n = 11)

• Complementary proteomics and histopathological analysis ideal to support transcriptomic data

• In vitro/in vivo experiments necessary to confirm biological efficacy of retinoic acid/retinoid therapy

CONCLUSIONS

• Severe, recalcitrant TS associated with decreased RA synthesis, increased RA degradation, and reduced RA activity in the cell

• Administration of pre-formed RA may alleviate key genetic dysregulations in TS

 

NEXT STEPS

• Examine differences between recalcitrant vs non-recalcitrant TS gene expression

• Verify local RA depletion in TS granulation tissue biopsies

• Pre-clinical animal models: RA administration as prophylactic and curative treatment

 

REFERENCES

• [1] Almanzar A, Danckers M. Laryngotracheal Stenosis.  StatPearls [Internet]: StatPearls Publishing; 2022

• [2] Carpenter DJ, Hamdi OA, Finberg AM, Daniero JJ. Laryngotracheal stenosis: Mechanistic review. Head Neck. 2022 Aug;44(8):1948-1960. doi: 10.1002/hed.27079. Epub 2022 Apr 30. PMCID: PMC9543412.