Comparison of Inhaled Drug Delivery in Patients With One‐ and Two‐level Laryngotracheal Stenosis

Gosman, Raluca; Sicard, Ryan M.; Frank‐Ito, Dennis O.

doi:10.1002/lary.30212

Cited by 6 publications

(5 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study showed an advantage of trans-tracheostomal inhalation over trans-oral inhalation in the amount of drug particles that deposit in the subglottis (total deposition fraction of 3.63% for trans-tracheostomal vs. 0.11% for trans-oral, ~30 times higher). The low deposition fraction of drug in the subglottis via trans-oral inhalation was also observed in recent studies by Frank-Ito et al, which showed drug depositions between 0.06% to 2.6% in models of subglottic and tracheal stenosis [ 19 , 32 ]. These low fractions emphasize the need to increase drug deposition in the stenotic areas.…”

Section: Discussionsupporting

confidence: 55%

“…In such a case, the patient may benefit from both trans-oral and trans-tracheostomal inhalations. This idea was supported by a simulation study of trans-oral inhalation in two multilevel stenosis subjects [ 32 ], with a superior deposition shown at the lower (tracheal) stenosis in both subjects. In addition to the lower deposition rate in the lungs, TRCI also demonstrated a lower deposition rate in the oral cavity and pharynx compared to the trans-oral technique (7.9% vs. 10.5%, respectively).…”

Section: Discussionmentioning

confidence: 92%

“…These low fractions emphasize the need to increase drug deposition in the stenotic areas. Suggested options in previous studies included the use of a spacer chamber and mild actuation of the inhaler, along with tidal volume modification that improved deposition [ 19 , 32 , 33 , 34 ]. We believe trans-oral inhalation is relatively ineffective in treating subglottic stenosis, especially in tracheotomized patients who breathe through a tracheostomy tube.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Trans-Tracheostomal Retrograde Inhalation Technique Increases Subglottic Drug Deposition Compared to Traditional Trans-Oral Inhalation

et al. 2023

View full text Add to dashboard Cite

Subglottic stenosis represents a challenging clinical condition in otolaryngology. Although patients often experience improvement following endoscopic surgery, recurrence rates remain high. Pursuing measures to maintain surgical results and prevent recurrence is thus necessary. Steroids therapy is considered effective in preventing restenosis. Currently, however, the ability of trans-oral steroid inhalation to reach and affect the stenotic subglottic area in a tracheotomized patient is largely negligible. In the present study, we describe a novel trans-tracheostomal retrograde inhalation technique to increase corticosteroid deposition in the subglottic area. We detail our preliminary clinical outcomes in four patients treated with trans-tracheostomal corticosteroid inhalation via a metered dose inhaler (MDI) following surgery. Concurrently, we leverage computational fluid-particle dynamics (CFPD) simulations in an extra-thoracic 3D airway model to gain insight on possible advantages of such a technique over traditional trans-oral inhalation in augmenting aerosol deposition in the stenotic subglottic region. Our numerical simulations show that for an arbitrary inhaled dose (aerosols spanning 1–12 µm), the deposition (mass) fraction in the subglottis is over 30 times higher in the retrograde trans-tracheostomal technique compared to the trans-oral inhalation technique (3.63% vs. 0.11%). Importantly, while a major portion of inhaled aerosols (66.43%) in the trans-oral inhalation maneuver are transported distally past the trachea, the vast majority of aerosols (85.10%) exit through the mouth during trans-tracheostomal inhalation, thereby avoiding undesired deposition in the broader lungs. Overall, the proposed trans-tracheostomal retrograde inhalation technique increases aerosol deposition rates in the subglottis with minor lower-airway deposition compared to the trans-oral inhalation technique. This novel technique could play an important role in preventing restenosis of the subglottis.

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Trans-Tracheostomal Retrograde Inhalation Technique Increases Subglottic Drug Deposition Compared to Traditional Trans-Oral Inhalation

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Clinical usage of inhaled corticosteroids is typically limited to systemic delivery. However, inhalation‐based delivery systems have been investigated and could offer more localized delivery of drug‐loaded microparticles 29 . Our approach extends this concept with the addition of a stent, which helps to ensure the drug‐eluting particles remain at the injury site, limiting chances of off‐target effects from the drug.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone eluting polydopaminated polycaprolactone‐poly (lactic‐co‐glycolic) acid for treatment of tracheal stenosis

Morand,

McClellan,

Isali

et al. 2024

J Biomedical Materials Res

View full text Add to dashboard Cite

Tracheal stenosis is commonly caused by injury, resulting in inflammation and fibrosis. Inhibiting inflammation and promoting epithelization can reduce recurrence after initial successful treatment of tracheal stenosis. Steroids play an important role in tracheal stenosis management. This study in vitro evaluated effectiveness of a polydopaminated polycaprolactone stent coated with dexamethasone‐eluting poly(lactic‐co‐glycolic) acid microparticles (μPLGA) for tracheal stenosis management. Polydopamination was characterized by Raman spectroscopy and promoted epithelialization while dexamethasone delivery reduced macrophage activity, assessed by individual cell area measurements and immunofluorescent staining for inducible nitric oxide synthase (iNOS). Dexamethasone release was quantified by high‐performance liquid chromatography over 30 days. Activation‐related increase in cell area and iNOS production by RAW 264.7 were both reduced significantly (p < .05) through dexamethasone release. Epithelial cell spreading was higher on polydopaminated polycaprolactone (PCL) than PCL‐alone (p < .05). Force required for stent migration was measured by pullout tests of PCL‐μPLGA stents from cadaveric rabbit and porcine tracheas (0.425 ± 0.068 N and 1.082 ± 0.064 N, respectively) were above forces estimated to occur during forced respiration. Biomechanical support provided by stents to prevent airway collapse was assessed by comparing compressive circumferential stiffness, and stiffness of the stent was about 1/10th of the rabbit trachea (0.156 ± 0.023 N/mm vs. 1.420 ± 0.194 N/mm, respectively). A dexamethasone‐loaded PCL‐μPLGA stent platform can deliver dexamethasone and exhibits sufficient mechanical properties to anchor within the trachea and polydopamination of PCL is conducive to epithelial layer formation. Therefore, a polydopaminated PCL‐μPLGA stent is a promising candidate for in vivo evaluation for treatment of tracheal restenosis.

show abstract

“…To ensure numerically accurate flow simulation results, the Shear-Stress Transport k -ω turbulent model (SST k -ω) was employed to simulate the inspiratory and expiratory airflow for fast-breathing conditions (45 L/min) [ 27 ]. The turbulence length scale was considered 0.001 m, and turbulent intensity was assumed to be 5% at the inlet and outlet [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway

Borojeni

Asgharian

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

The extrathoracic oral airway is not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1–30 µm particles was predicted in 11 CT-based models of the oral airways of adults. Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/nebulizer use (18 L/min) and of dry powder inhaler (DPI) use (45 L/min). Consistent with previous in vitro studies, there was a large intersubject variability in oral deposition. For an optimal size distribution of 1–5 µm for pharmaceutical aerosols, our data suggest that >75% of the inhaled aerosol is delivered to the intrathoracic lungs in most subjects when using a nebulizer but only in about half the subjects when using a DPI. There was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition, which shows significantly different patterns between the two breathing phases. These results highlight the need for incorporating a morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

show abstract

Comparison of Inhaled Drug Delivery in Patients With One‐ and Two‐level Laryngotracheal Stenosis

Cited by 6 publications

References 70 publications

A Novel Trans-Tracheostomal Retrograde Inhalation Technique Increases Subglottic Drug Deposition Compared to Traditional Trans-Oral Inhalation

A Novel Trans-Tracheostomal Retrograde Inhalation Technique Increases Subglottic Drug Deposition Compared to Traditional Trans-Oral Inhalation

Dexamethasone eluting polydopaminated polycaprolactone‐poly (lactic‐co‐glycolic) acid for treatment of tracheal stenosis

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway

Contact Info

Product

Resources

About