• Investigating the Challenges o...

*Result*: Investigating the Challenges of Managing Coexisting Subglottic Stenosis and Bronchopulmonary Diseases Medically Using Computational Modeling.

Title:
Investigating the Challenges of Managing Coexisting Subglottic Stenosis and Bronchopulmonary Diseases Medically Using Computational Modeling.
Authors:
Gao K; Duke University School of Medicine, Durham, North Carolina, USA.; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, North Carolina, USA., Luzum NA; Duke University School of Medicine, Durham, North Carolina, USA.; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, North Carolina, USA., Cohen S; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, North Carolina, USA., Frank-Ito DO; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, North Carolina, USA.
Source:
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery [Otolaryngol Head Neck Surg] 2026 Feb; Vol. 174 (2), pp. 479-488. Date of Electronic Publication: 2025 Dec 31.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Wiley Country of Publication: England NLM ID: 8508176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6817 (Electronic) Linking ISSN: 01945998 NLM ISO Abbreviation: Otolaryngol Head Neck Surg Subsets: MEDLINE
Imprint Name(s):
Publication: 2023- : [Oxford] : Wiley
Original Publication: [Rochester, Minn.] : The Academy, [c1981-
MeSH Terms:
Laryngostenosis*/complications , Laryngostenosis*/drug therapy , Computer Simulation* , Fluticasone*/administration & dosage , Pregnenediones*/administration & dosage, Humans ; Administration, Inhalation ; Aerosols ; Drug Delivery Systems
References:
Mann DG, Kirchner JA. Bronchopulmonary dysplasia (or subglottic stenosis?). Laryngoscope. 1982;92(9):976‐979.
Whigham AS, Howell R, Choi S, Peña M, Zalzal G, Preciado D. Outcomes of balloon dilation in pediatric subglottic stenosis. Ann Otol Rhinol Laryngol. 2012;121(7):442‐448.
Hysinger EB. Central airway issues in bronchopulmonary dysplasia. Pediatr Pulmonol. 2021;56(11):3518‐3526.
Downing GJ, Kilbride HW. Evaluation of airway complications in high‐risk preterm infants: application of flexible fiberoptic airway endoscopy. Pediatrics. 1995;95(4):567‐572. doi:10.1542/peds.95.4.567.
Schweiger C, Marostica PJC, Smith MM, Manica D, Carvalho PRA, Kuhl G. Incidence of post‐intubation subglottic stenosis in children: prospective study. J Laryngol Otol. 2013;127(4):399‐403. doi:10.1017/s002221511300025x.
Manica D, Schweiger C, Maróstica PJC, Kuhl G, Carvalho PRA. Association between length of intubation and subglottic stenosis in children. Laryngoscope. 2013;123(4):1049‐1054. doi:10.1002/lary.23771.
Berges AJ, Lina IA, Chen L, Ospino R, Davis R, Hillel AT. Delayed diagnosis of idiopathic subglottic stenosis. Laryngoscope. 2022;132(2):413‐418. doi:10.1002/lary.29783.
Ntouniadakis E, Sundh J, Söderqvist J, von Beckerath M. How can we identify subglottic stenosis in patients with suspected obstructive disease. Eur Arch Otrhinolaryngol. 2023;280(11):4995‐5001. doi:10.1007/s00405-023-08141-3.
Aravena C, Almeida FA, Mukhopadhyay S, et al. Idiopathic subglottic stenosis: a review. J Thorac Dis. 2020;12(3):1100‐1111. doi:10.21037/jtd.2019.11.43.
Wang H, Wright CD, Wain JC, Ott HC, Mathisen DJ. Idiopathic subglottic stenosis: factors affecting outcome after single‐stage repair. Ann Thorac Surg. 2015;100(5):1804‐1811. doi:10.1016/j.athoracsur.2015.05.07.
Agrawal A, Baird BJ, Madariaga MLL, Blair EA, Murgu S. Multi‐disciplinary management of patients with benign airway strictures: a review. Respir Med. 2021;187:106582. doi:10.1016/j.rmed.2021.106582.
Gelbard A, Donovan DT, Ongkasuwan J, et al. Disease homogeneity and treatment heterogeneity in idiopathic subglottic stenosis. Laryngoscope. 2016;126(6):1390‐1396.
Maldonado F, Loiselle A, DePew ZS, et al. Idiopathic subglottic stenosis: an evolving therapeutic algorithm. Laryngoscope. 2014;124(2):498‐503.
Gelbard A, Katsantonis NG, Mizuta M, et al. Molecular analysis of idiopathic subglottic stenosis for Mycobacterium species. Laryngoscope. 2017;127(1):179‐185.
van de Loo M, Van Kaam A, Offringa M, Doyle LW, Cooper C, Onland W. Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews. Cochrane Database Syst Rev. 2024:4.
Janahi IA, Rehman A, Baloch NUA. Corticosteroids and their use in respiratory disorders. In: Corticosteroids. InTech Open;2018:47‐57.
Galletta F, Li Pomi A, Manti S, Gitto E. Inhaled and systemic steroids for bronchopulmonary dysplasia: targeting inflammation and oxidative stress. Antioxidants. 2025;14(7):869.
de Vries TW, Rottier BL, Gjaltema D, Hagedoorn P, Frijlink HW, de Boer AH. Comparative in vitro evaluation of four corticosteroid metered dose inhalers: consistency of delivered dose and particle size distribution. Respir Med. 2009;103(8):1167‐1173.
Tamura G. Comparison of the aerosol velocity of Respimat® soft mist inhaler and seven pressurized metered dose inhalers. Allergol Int. 2015;64(4):390‐392.
Gelbard A, Francis DO, Sandulache VC, Simmons JC, Donovan DT, Ongkasuwan J. Causes and consequences of adult laryngotracheal stenosis. Laryngoscope. 2015;125(5):1137‐1143.
Gelbard A, Shyr Y, Berry L, et al. Treatment options in idiopathic subglottic stenosis: protocol for a prospective international multicentre pragmatic trial. BMJ Open. 2018;8(4):e022243.
Longest PW, Holbrook LT. In silico models of aerosol delivery to the respiratory tract—development and applications. Adv Drug Deliv Rev. 2012;64(4):296‐311.
Gosman RE, Sicard RM, Cohen SM, Frank‐Ito DO. A computational analysis on the impact of multilevel laryngotracheal stenosis on airflow and drug particle dynamics in the upper airway. Exp Comput Multiphase Flow. 2023;5:235‐246.
Frank‐Ito DO, Cohen SM. Orally Inhaled Drug Particle Transport in Computerized Models of Laryngotracheal Stenosis. Otolaryngol Head Neck Surg. 2021;164(4):829‐840.
Gosman RE, Sicard RM, Cohen SM, Frank‐Ito DO. Comparison of inhaled drug delivery in patients with one‐and two‐level laryngotracheal stenosis. Laryngoscope. 2023;133(2):366‐374.
Allon R, Bhardwaj S, Sznitman J, et al. A novel trans‐tracheostomal retrograde inhalation technique increases subglottic drug deposition compared to traditional trans‐oral inhalation. Pharmaceutics. 2023;15(3):903. doi:10.3390/pharmaceutics15030903.
Contributed Indexing:
Keywords: bronchopulmonary; computational model; medication; orally inhaled; subglottic stenosis
Substance Nomenclature:
CUT2W21N7U (Fluticasone)
0 (Aerosols)
0 (Pregnenediones)
S59502J185 (ciclesonide)
Entry Date(s):
Date Created: 20251231 Date Completed: 20260131 Latest Revision: 20260131
Update Code:
20260131
DOI:
10.1002/ohn.70097
PMID:
41474177
Database:
MEDLINE

*Further Information*

*Objective: Subglottic stenosis (SGS) coexists with bronchopulmonary disease, complicating topical therapy given the distinct anatomical targets. Optimizing inhaled medication delivery to both regions remain a therapeutic challenge. This study evaluates the ability of orally inhaled aerosol particles to achieve dual‑site deposition in SGS and bronchopulmonary regions.
Study Design: Computational modeling of orally inhaled drug particle delivery.
Setting: Academic Medical Center.
Methods: Digitally modified airways simulating 8 SGS variants, combining McCaffrey Stage I (5 mm) and II (15 mm) subglottic lengths with Cotton‑Myer Grade I (10%, 30%), Grade II (60%), and Grade III (90%) luminal constrictions. Oral inhalation at 15 L/min and particle transport were simulated for fluticasone propionate (FP; mean aerosol velocity 9.19 m/s, particle size range 1-8 μm) and ciclesonide (CIC; mean aerosol velocity 4.26 m/s, particle size range 1-4 μm) inhaler characteristics, and 6 particle‑size distributions M <subscript>1</subscript> (1-5 μm), M <subscript>2</subscript> (6-10 μm), M <subscript>3</subscript> (1-10 μm) while maintaining the respective parent (CIC and FP) mean aerosol velocity.
Results: In the normal airway, CIC and FP inhalers achieved >80% bronchial deposition but ≤0.02% subglottic delivery. Among modified devices, M <subscript>2</subscript> CIC optimized dual targeting, providing the highest subglottic deposition (0.09%) with preserved bronchial efficiency (69.46%). In SGS models, M <subscript>2</subscript> CIC and M <subscript>2</subscript> FP consistently achieved the most balanced delivery, with maximum deposition of M <subscript>2</subscript> CIC = 8.4% and M <subscript>2</subscript> FP = 7.86% at subglottic region, and M <subscript>2</subscript> CIC = 69.89% and M <subscript>2</subscript> FP = 61.02% at bronchial site. M <subscript>3</subscript> variants offered intermediate dual deposition at advanced and Grade III stenosis stages.
Conclusion: M <subscript>2</subscript> CIC and M <subscript>2</subscript> FP inhaler modifications optimized dual-site supporting tailored device strategies for SGS with coexisting bronchopulmonary disease.
(© 2025 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)*