Subglottic and Glottic Stenosis

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Subglottic and Glottic Stenosis

Laryngology, Voice and Swallowing
Author Credentials 

Alexander Gelbard, MD
Vanderbilt University Medical Center
Department of Otolaryngology
Center for Complex Airway Reconstruction
1215 21st Ave S.
Medical Center East (MCE) 7324
Nashville TN 37232
Email: alexander.gelbard@vanderbilt.edu

Module Summary

Glottic, Subglottic and Tracheal Stenosis are a group of obstructive fibrotic diseases in the larynx and trachea (collectively termed laryngotracheal stenosis, i.e. LTS). LTS can occur without known antecedent injury (idiopathic subglottic stenosis, iSGS). It also can accompany collagen vascular disease (e.g. Wegener’s Granulomatosis: GPA, Relapsing Polychondritis: RPC), follow iatrogenic injury (e.g., endotracheal intubation), or result from myriad less-frequent causes. Although different mechanisms of airway injury physiologically affect the patient in similar ways, they occur in unique populations and have divergent responses to therapy.

Module Learning Objectives 
  1. Recognize the different diseases implicated in the pathogenesis of Laryngotracheal Stenosis.
  2. Summarize the anatomic relationships between the affected laryngotracheal subsite and the findings on physical examination.
  3. Recognize the divergent natural histories of the different diseases leading to LTS.
  4. Cite the goals of initial patient evaluation and staging.
  5. Give examples of the adjuvant medical therapies in LTS.
  6. Explain the risks and benefits of endoscopic and open surgical management of LTS.
  7. Summarize the major complications associated with open surgical management of LTS.

Embryology

Learning Objectives 

Not applicable to Adult LTS. However, embryology plays a critical role in understanding the pathogenesis of pediatric LTS.

Anatomy

Learning Objectives 
  1. Be familiar with the contrasts between endoscopic and open laryngotracheal anatomy
  2. Be familiar with the relationship between the cricoarytenoid joint, intrinsic laryngeal musculature, and laryngeal cartilages.
  3. Be familiar with the neural innervation of the intrinsic laryngeal musculature
  4. Be familiar with the blood supply to the trachea
  5. Understand the relationship between tracheal diameter and patient height
References 
  1. Tarrazona V, Deslauriers J. Glottis and subglottis: a thoracic surgeon's perspective. Thorac Surg Clin. 2007;17:561-70.
  2. Thurnher D, Moukarbel RV, Novak CB, Gullane PJ. The glottis and subglottis: an otolaryngologist's perspective. Thorac Surg Clin. 2007;17:549-60.
  3. Schweizer V, Dorfl J. The anatomy of the inferior laryngeal nerve. Clin Otolaryngol Allied Sci. 1997;22:362-9.
  4. Chen T, Chodara AM, Sprecher AJ, et al. A new method of reconstructing the human laryngeal architecture using micro-MRI. J Voice. 2012;26:555-62.
  5. Grillo HC. Tracheal blood supply. Ann Thorac Surg. 1977;24:99.
  6. Coordes A, Rademacher G, Knopke S, et al. Selection and placement of oral ventilation tubes based on tracheal morphometry. Laryngoscope. 2011;121:1225-30.

Basic Science

Learning Objectives 
  1. Understand basic mathematical models describing airflow through the larynx and trachea
    1. The Venturi effect (velocity of a fluid flowing through a pipe increases as the cross sectional area decreases).
    2. Bernoulli's principle: (an increase in the speed of the fluid flowing through a pipe occurs simultaneously with a decrease in the pressure)
    3. Poiseuille’s law: (resistance is inversely related to the radius of the airway to the fourth power)
  2. Describe The pathophysiology of airway injury in endotracheal intubation
  3. Describe the Inflammatory pathways implicated in local tissue remodeling in LTS
  4. Describe the role of host immunity in mucosal airway fibrosis
  5. Describe the association of pathogenic bacteria and LTS
  6. Describe phenotypic alterations in fibroblasts in LTS airway scar
References 
  1. Sandhu GS. Management of Adult Benign Laryngotracheal Stenosis [Doctoral thesis]. UCL Discovery Press: University College London; 2011.
  2. Seegobin RD, van Hasselt GL. Endotracheal cuff pressure and tracheal mucosal blood flow: endoscopic study of effects of four large volume cuffs. Br Med J (Clin Res Ed). 1984;288:965-8.
  3. Su Z, Li S, Zhou Z, et al. A canine model of tracheal stenosis induced by cuffed endotracheal intubation. Sci Rep. 2017;7:45357.
  4. Puyo CA, Dahms TE. Innate immunity mediating inflammation secondary to endotracheal intubation. Arch Otolaryngol Head Neck Surg. 2012;138:854-8.
  5. Gelbard A, Donovan DT, Ongkasuwan J, et al. Disease homogeneity and treatment heterogeneity in idiopathic subglottic stenosis. Laryngoscope. 2016;126:1390-6.
  6. Ghosh A, Malaisrie N, Leahy KP, et al. Cellular adaptive inflammation mediates airway granulation in a murine model of subglottic stenosis. Otolaryngol Head Neck Surg. 2011;144:927-33.
  7. Mazhar K, Gunawardana M, Webster P, et al. Bacterial biofilms and increased bacterial counts are associated with airway stenosis. Otolaryngol Head Neck Surg. 2014;150:834-40.
  8. Gelbard A, Katsantonis NG, Mizuta M, et al. Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species. Laryngoscope. 2017;127:179-85.
  9. Namba DR, Ma G, Samad I, et al. Rapamycin inhibits human laryngotracheal stenosis-derived fibroblast proliferation, metabolism, and function in vitro. Otolaryngol Head Neck Surg. 2015;152:881-8.

Incidence

Learning Objectives 
  1. Know the incidence of iSGS, iatrogenic (post-intubation) LTS, GPA, and RPC
  2. Recognize groups at increased risk for iatrogenic (post-intubation) LTS
References 
  1. Maldonado F, Loiselle A, Depew ZS, et al. Idiopathic subglottic stenosis: an evolving therapeutic algorithm. Laryngoscope. 2014;124:498-503.
  2. Nouraei SA, Ma E, Patel A, Howard DJ, Sandhu GS. Estimating the population incidence of adult post-intubation laryngotracheal stenosis. Clin otolaryngol. 2007;32:411-2.
  3. Lebovics RS, Hoffman GS, Leavitt RY, et al. The management of subglottic stenosis in patients with Wegener's granulomatosis. Laryngoscope. 1992 Dec;102(12 Pt 1):1341-5.
  4. Ernst A, Rafeq S, Boiselle P, et al. Relapsing polychondritis and airway involvement. Chest. 2009;135:1024-30.
  5. Hillel AT, Karatayli-Ozgursoy S, Samad I, et al. Predictors of Posterior Glottic Stenosis: A Multi-Institutional Case-Control Study. Ann Otol Rhinol Laryngol. 2016;125:257-63.

Patient Evaluation

Learning Objectives 
  1. Describe physical exam findings suggestive of severe ventilatory restriction warranting urgent therapy.
  2. Describe the goals of goals of initial patient evaluation and staging
    1. Delineation of the goals of care
    2. Estimation of patients overall functional status and surgical candidacy
    3. Delineation of Etiology of LTS
    4. Determination of affected airway subsite (glottis, subglottis or trachea)
    5. Differentiation of mucosal fibrosis from cartilaginous “framework” deficiency
References 
  1. Central airway obstruction. BMJ best practice. Accessed on May 15, 2018. 
  2. Gelbard A, Francis DO, Sandulache VC, Simmons JC, Donovan DT, Ongkasuwan J. Causes and consequences of adult laryngotracheal stenosis. Laryngoscope. 2015 May;125(5):1137-43.
  3. Koempel JA, Cotton RT. History of pediatric laryngotracheal reconstruction. Otolaryngologic clinics of North America. 2008;41:825-35, vii.

Measurement of Functional Status

Learning Objectives 
  1. Speech
  2. Swallowing
  3. Breathing
  4. Global quality of life
References 
  1. Smith ME, Roy N, Stoddard K, Barton M. How does cricotracheal resection affect the female voice? Ann Otol Rhinol Laryngol. 2008 Feb;117(2):85-9.
  2. Lennon CJ, Gelbard A, Bartow C, Garrett CG, Netterville JL, Wootten CT. Dysphagia Following Airway Reconstruction in Adults. JAMA Otolaryngol Head Neck Surg. 2016;142:20-4.
  3. Nouraei SA, Randhawa PS, Koury EF, et al. Validation of the Clinical COPD Questionnaire as a psychophysical outcome measure in adult laryngotracheal stenosis. Clin Otolaryngol. 2009 Aug;34(4):343-8. 
  4. Gilony D, Gilboa D, Blumstein T, et al. Effects of tracheostomy on well-being and body-image perceptions. Otolaryngol Head Neck Surg. 2005;133:366-71.

Imaging

Learning Objectives 
  1. Be familiar with utility of CT and MRI imaging modalities in the work-up of a patient with Glottic or Subglottic Stenosis.
    1. Be familiar with Dynamic CT protocols (inspiratory/expiratory)
    2. Be familiar with the correlation of CT findings to Operative Bronchoscopy findings
References 
  1. Kuo GP, Torok CM, Aygun N, Zinreich SJ. Diagnostic imaging of the upper airway. Proc Am Thorac Soc. 2011;8:40-5.
  2. Morshed K, Trojanowska A, Szymanski M, et al. Evaluation of tracheal stenosis: comparison between computed tomography virtual tracheobronchoscopy with multiplanar reformatting, flexible tracheofiberoscopy and intra-operative findings. Eur Arch Otorhinolaryngol. 2011 Apr;268(4):591-7. 
  3. Lee EY, Litmanovich D, Boiselle PM. Multidetector CT evaluation of tracheobronchomalacia. Radiol Clin North Am. 2009;47:261-9.

Pathology

Learning Objectives 

Recognize the histologic differences between iSGS and post-intubation LTS.

References 
  1. Mark EJ, Meng F, Kradin RL, Mathisen DJ, Matsubara O. Idiopathic tracheal stenosis: a clinicopathologic study of 63 cases and comparison of the pathology with chondromalacia. Am J Surg Pathol. 2008;32:1138-43.
  2. Welkoborsky HJ, Hinni ML, Moebius H, Bauer L, Ostertag H. Microscopic examination of iatrogenic subglottic tracheal stenosis: observations that may elucidate its histopathologic origin. Ann Otol Rhinol Laryngol. 2014;123:25-31.

Medical Therapies

Learning Objectives 
  1. Recognize the role for corticosteroids (including evidence to support inhalation, direct local transcutaneous injection, or oral systemic routes)
  2. Recognize the role for Antibiotics (Trimethoprim-sulfamethoxazole, Azithromycin)
References 
  1. Shabani S, Hoffman MR, Brand WT, Dailey SH. Endoscopic Management of Idiopathic Subglottic Stenosis. Ann Otol Rhinol Laryngol. 2017 Feb;126(2):96-102.
  2. Ghosh A, Philiponis G, Lee JY, et al. Pulse steroid therapy inhibits murine subglottic granulation. Otolaryngol Head Neck Surg. 2013;148:284-90.
  3. Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med. 1996;335:16-20.
  4. Vos R, Verleden SE, Ruttens D, et al. Azithromycin and the treatment of lymphocytic airway inflammation after lung transplantation. Am J Transplant. 2014;14:2736-48.

Pharmacology

Learning Objectives 

Discuss Role for treatment of Laryngophayrngeal or Gastroesophageal reflux disease in LTS.

References 
  1. Blumin JH, Johnston N. Evidence of extraesophageal reflux in idiopathic subglottic stenosis. Laryngoscope. 2011;121:1266-73.
  2. Gelbard A, Donovan DT, Ongkasuwan J, et al. Disease homogeneity and treatment heterogeneity in idiopathic subglottic stenosis. Laryngoscope. 2016;126:1390-6.

Surgical Therapies

Learning Objectives 
  1. Know the primary goals of treatment for Laryngotracheal Stenosis and understand the relationship of these goals to the choice of surgical approach:
    1. Re-establish adequate airway luminal diameter (posterior glottic, subglottic, or tracheal) to support physiologic demands, while minimizing the loss of phonatory and deglutitive function
  2. Understand the guiding principles of surgical therapy for glottic and subglottic stenosis.
    1. Replace pathologic mucosal fibrosis with healthy mucosa
    2. Replace deficient cartilaginous framework with healthy new structure
  3. Understand the differences between surgical approaches for glottic and subglottic stenosis.

Endoscopic management of glottic stenosis is primarily ablative, while open procedures are primarily augmentative

  1. Endoscopic Approaches for glottic stenosis
    1. Endoluminal stenting
    2. Cordotomy/Arytenoidectomy
    3. Endoscopic posterior cricoid split
  2. Open Approaches for glottic stenosis
    1. Tracheostomy
    2. Laryngotracheoplasty
    3. Extended Cricotracheal Resection

Endoscopic management of subglottic and tracheal stenosis is primarily dilational, while open procedures include augmentation, resection with re-anastomosis, or resection with slide tracheoplasty.

  1. Endoscopic Approaches for subglottic and tracheal stenosis
    1. Endoluminal stenting
    2. Endoscopic dilation
  2. Open Approaches for subglottic and tracheal stenosis
    1. Tracheostomy
    2. Laryngotracheoplasty
    3. Tracheal / Cricotracheal resection
    4. Slide Tracheoplasty
References 
  1. Yamamoto K, Kojima F, Tomiyama K, Nakamura T, Hayashino Y. Meta-analysis of therapeutic procedures for acquired subglottic stenosis in adults. Ann Thorac Surg. 2011;91:1747-53.
  2. Yawn RJ, Daniero JJ, Gelbard A, Wootten CT. Novel application of the Sonopet for endoscopic posterior split and cartilage graft laryngoplasty. Laryngoscope. 2016;126:941-4.
  3. Inglis AF, Jr., Perkins JA, Manning SC, Mouzakes J. Endoscopic posterior cricoid split and rib grafting in 10 children. Laryngoscope. 2003;113:2004-9.
  4. Terra RM, Minamoto H, Carneiro F, Pego-Fernandes PM, Jatene FB. Laryngeal split and rib cartilage interpositional grafting: treatment option for glottic/subglottic stenosis in adults. J Thorac Cardiovasc Surg.  2009;137:818-23.
  5. Dedo HH, Sooy CD. Endoscopic laser repair of posterior glottic, subglottic and tracheal stenosis by division or micro-trapdoor flap. Laryngoscope. 1984;94:445-50.
  6. Ossoff RH, Duncavage JA, Shapshay SM, Krespi YP, Sisson GA, Sr. Endoscopic laser arytenoidectomy revisited. Ann Otol Rhinol Laryngol. 1990;99:764-71.
  7. Milczuk H. Laryngotracheal Reconstruction for Subglottic and Proximal Tracheal Stenosis. In: Cohen J, Clayman, G., ed. Atlas of Head & Neck Surgery. Philadelphia, PA: Elsiever; 2011:58-76.
  8. Anderson P. Cricotracheal Resection for Subglottic Stenosis. In: Cohen J, Clayman, G., ed. Atlas of Head & Neck Surgery. Philadelphia, PA: Elsiever; 2011:77-90.
  9. Grillo HC. Laryngotracheal Reconstruction. Surgery of the trachea and bronchi. Hamilton, Ont. ; Lewiston, NY: BC Decker; 2004:549-68.
  10. de Alarcon A, Rutter MJ. Cervical slide tracheoplasty. Arch Otolaryngol Head Neck Surg. 2012;138:812-6.
  11. Wright CD, Grillo HC, Wain JC, et al. Anastomotic complications after tracheal resection: prognostic factors and management. J Thorac Cardiovasc Surg. 2004;128:731-9.

Rehabilitation

Learning Objectives 
  1. Dysphonia
    1. Voice restoration (injection medialization or Type I Laryngoplasty for UVFP)
    2. SLP for voice therapy (phonatory alterations in females after CTR)
  2. Dysphagia
    1. Relationship to acute surgical reconstruction
  3. Pain
    1. Donor site morbidity (costochondral grafts)
    2. Ambulation and postoperative pulmonary toilet
  4. Rehabilitative services
    1. Speech pathology/Swallow therapy
    2. Physical therapy
    3. Occupational therapy
References 
  1. Lennon CJ, Gelbard A, Bartow C, Garrett CG, Netterville JL, Wootten CT. Dysphagia Following Airway Reconstruction in Adults. JAMA Otolaryngol Head Neck Surg. 2016;142:20-4.

Staging

Learning Objectives 

Compare the utility of the Cotton-Myer, and McCafrey staging systems in Adult patients.

References 
  1. Gelbard A, Francis DO, Sandulache VC, Simmons JC, Donovan DT, Ongkasuwan J. Causes and consequences of adult laryngotracheal stenosis. Laryngoscope. 2015 May;125(5):1137-43.

Case Studies

Bilateral TVF mobile, subglottic cicatrix evident on fiberoptic endoscopy.

On exam patient shows increased WOB, mild tachypnea at rest, audible insp. stridor. Not speaking in complete sentences. Appears uncomfortable. O2 saturations of 99% on room air.

Long soft palate with redundant lateral pharyngeal walls and symmetricly large tongue base on fiberoptic endoscopy. Examination of larynx shows Bilateral TVF immobile, with scar evident in the posterior commissure. 3-5 mm glottic airway.

  • Case 1. 56 y/o previously healthy Caucasian female with 18 months of progressive dyspnea. No history of dermatologic, renal, cardiac, or joint disease. Negative family rheumatologic history. Now can’t walk to mailbox without prolonged recovery. Denies significant voice changes, but does report frequent cough and thick mucus. No increased WOB or tachypnea at rest, but audible insp. stridor. Speaking in complete sentences.
    1. Diagnostic Work-up:
      1. Physical Examination
        1. Labs cANCA, others
        2. Imaging Studies
          1. PA & Lateral soft tissue radiograph
          2. CT (noncontrasted dynamic inspir/expriratory protocol)
          3. MRI
          4. U/S
        3. Operative Bronchcoscopy
      2. Physiologic testing:
        1. PFTs
        2. pH probe/impedance
    2. Treatment:
      1. Indications for procedure
        1. Patient symptoms
        2. Objective measures
      2. Discussion of therapeutic options:
        1. Endoscopic approaches
        2. Adjuvant Medical Therapies
        3. Open resection
  • Case 2. 66 year old African American male with history CAD and type II diabetes mellitus with recent intubation following non-ST segment elevation MI 8 weeks ago. Intubated for 10 days. No history of tracheostomy (and currently without a trach). Extubated as an inpatient without issues. After extubation, patient and family noticed prolonged rough dysphonia, and mild dysphagia to thin liquids. No initial issues with breathing at discharge, but over the last 4 weeks has noticed progressive difficulty walking up the 4 porch stairs to his front door. Cannot walk more than 10 feet without feeling winded. Trouble holding long conversations due to “running out of air”.
    1. Diagnostic Work-up: Recognize the physical exam findings mandating inpatient admission and urgent intervention.
    2. Acute Treatment:
      1. Timing of therapy (Urgent or Emergent?)
      2. Discussion of therapeutic options:
        1. Tracheostomy
        2. Endoscopic approaches
        3. Adjuvant Medical Therapies
    3. Chronic Treatment:
      1. Indication for procedure
        1. Patient symptoms
        2. Objective measures
      2. Discussion of therapeutic options:
        1. Endoscopic approaches
        2. Adjuvant Medical Therapies
        3. Open Laryngotracheoplasty

Complications

Learning Objectives 

Know the surgical complications associated with open airway reconstruction

  1. Airway obstruction
  2. Anastomotic dehiscence
  3. Graft extrusion
  4. Recurrent endoluminal fibrosis
  5. Arytenoid prolapse
  6. Pneumothorax
  7. Esophageal perforation
  8. Dysphagia
  9. Unilateral Vocal Fold Paralysis
  10. Bilateral Vocal Fold Paralysis
  11. Infection
References 
  1. Wright CD, Grillo HC, Wain JC, et al. Anastomotic complications after tracheal resection: prognostic factors and management. The Journal of thoracic and cardiovascular surgery. 2004;128:731-9.
  2. Bernal-Sprekelsen M. Complications in otolaryngology: head and neck surgery. Stuttgart ; New York: Thieme; 2013:xviii, 334.
  3. Rutter MJ, Link DT, Hartley BE, Cotton RT. Arytenoid prolapse as a consequence of cricotracheal resection in children. Ann Otol Rhinol Laryngol.  2001;110:210-4.

Review

Review Questions 
  1. What patient demographic is primarily affected in idiopathic subglottic stenosis (iSGS)?
  2. What patient-specific factors and intubation-specific factors have been shown to contribute to the pathogenesis of post-intubation glottic, subglottic and tracheal stenosis?
  3. What are the primary goals of initial diagnostic staging in Laryngotracheal stenosis?
  4. What are the possible endoscopic surgical treatments for Laryngotracheal stenosis?
  5. What are the possible open surgical treatments for Laryngotracheal stenosis?
Resources 

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