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Cyclooxygenase-2 inhibition for the prevention of subglottic stenosis.

ABSTRACT: To evaluate the role of targeted cyclooxygenase-2 inhibition in reducing scarring associated with a subglottic airway mucosal injury.Thirty-four New Zealand white rabbits underwent anterior cricothyroidotomy. Subglottic stenosis (SGS) was created by carbon dioxide laser injury.Treatment consisted of intraperitoneal injection of celecoxib or vehicle for 4 days. Endoscopies were performed to assess injury and healing. Subglottic mucosal secretions were collected with Gelfoam swabs (Pfizer Inc) before and after injury and at subsequent time points. Animals were humanely killed at 3 or 8 weeks after injury and airways were excised, followed by gross examination and histologic analysis to assess the severity of SGS. Secretions were analyzed for interleukin-1?, prostaglandin E2 (PGE2), and matrix metalloproteinase-8 by enzyme-linked immunosorbent assays.Endoscopy showed mild to moderate stenosis in the celecoxib group, but mild to severe stenosis in the vehicle group. Histologic assessment confirmed and quantified reduction in stenosis and scarring as well as advanced reepithelialization. In the healing tissue, mucosal thickening (stenosis) was reduced significantly (P = .02) in celecoxib-treated animals compared with those treated with vehicle, at 3 and 8 weeks (decrease in thickness by 32% and 49%, respectively). Collagen density (fibrosis) was also reduced 25% at both 3 and 8 weeks but the difference was not statistically significant (P = .20). Reduced level of PGE2 in the subglottic mucosal secretions was correlated with mucosal thickness at 8 weeks (P = .02).Short-duration, anti-inflammatory therapy resulted in reduced stenosis and fibrosis with correlation of PGE2 levels in subglottic mucosal secretions.

SUBMITTER: Cetin S

PROVIDER: S-EPMC4126655 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Cyclooxygenase-2 inhibition for the prevention of subglottic stenosis.

Cetin Selma S Tobey Allison B AB Sandulache Vlad C VC Yang Tianbing T Barsic Mark M Lin Yan Y Dohar Joseph E JE Hebda Patricia A PA

Archives of otolaryngology--head & neck surgery 20121001 10

<h4>Objective</h4>To evaluate the role of targeted cyclooxygenase-2 inhibition in reducing scarring associated with a subglottic airway mucosal injury.<h4>Design</h4>Thirty-four New Zealand white rabbits underwent anterior cricothyroidotomy. Subglottic stenosis (SGS) was created by carbon dioxide laser injury.<h4>Intervention</h4>Treatment consisted of intraperitoneal injection of celecoxib or vehicle for 4 days. Endoscopies were performed to assess injury and healing. Subglottic mucosal secreti ...[more]

PMID: 23069827

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Project description:ImportanceSurgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research.ObjectiveTo prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease.Design, setting, and participantsIn this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook.Main outcomes and measuresThe primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications.ResultsOf 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n?=?603; 74.4%), ERMT (n?=?121; 14.9%), and CTR (n?=?86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk.Conclusions and relevanceIn this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

Project description:ObjectiveIdiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle-aged women of White race and non-Latino or Hispanic ethnicity. To better characterize its phenotype and pathogenesis, we assessed the proteomic and genomic methylation signatures of subglottic tissue collected from iSGS patients compared to controls.Study designMolecular analysis of clinical biospecimens.MethodsWe collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age-, sex-, and race/ethnicity-matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label-free quantitative mass spectrometry techniques, and acquired genome-wide methylation data using bisulfite conversion and a microarray platform. We compared molecular profiles across the iSGS and control groups, and with respect to clinical course in the iSGS group. Eight of the 12 iSGS patients underwent subsequent blood collection and plasma isolation for further assessment.ResultsProteomic analysis revealed 42 differentially abundant proteins in the iSGS biopsies compared to controls, inferring enrichment of biological pathways associated with early wound healing, innate immunity, matrix remodeling, and metabolism. Proteome-based hierarchical clustering organized patients into two iSGS and one control subgroups. Methylation analysis revealed five hypermethylated genes in the iSGS biopsies compared to controls, including the biotin recycling enzyme biotinidase (BTD). Follow-up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data.ConclusioniSGS exhibits distinct proteomic and genomic methylation signatures. These signatures expand current understanding of the iSGS phenotype, support the possibility of disease subgroups, and should inform the direction of future experimental studies.Level of evidenceNot applicable Laryngoscope, 131:E540-E546, 2021.

Project description:OBJECTIVES:Subglottic stenosis (SGS) is one of the most common airway disorders in pediatric patients. Currently, treatment decisions rely primarily on the Cotton-Myer scale, which classifies SGS severity based on percentage reduction in airspace cross-sectional area (CSA). However, the precise relationship between upper airway resistance and subglottic CSA is unknown. We hypothesize that airway resistance can be described by the Bernoulli Obstruction Theory, which predicts that airway resistance is inversely proportional to airspace CSA ( R?A-1) in cases of severe constriction. METHODS:Computed tomography (CT) scans of six healthy subjects and five SGS patients were used to create three-dimensional models of the respiratory tract from nostrils to carina. Cylindrical segments of varying lengths and varying diameters were digitally inserted in the subglottis of the healthy subjects to create simulated SGS models. Computational fluid dynamics simulations were run, and airway resistance was computed in the simulated SGS models and actual SGS models. RESULTS:Constriction diameter had a greater impact in airway resistance than constriction length. In agreement with the Bernoulli Obstruction Theory, airway resistance in the simulated SGS models was well represented by the power law R=aAb, where a is a constant and the exponent b ranged from -0.85 to -1.07. The percentage reduction in airflow (QOBSTRUCTIONQHEALTHY) at a constant pressure drop was found to be directly proportional to the percentage reduction in CSA (AOBSTRUCTIONAHEALTHY) in the limit of severe constrictions, namely QOBSTRUCTIONQHEALTHY=kAOBSTRUCTIONAHEALTHY, where k=2.25 ± 0.15. Airway resistances in the simulated SGS models were similar to resistances in models based on CT scans of actual SGS patients, suggesting that our simulated SGS models were representative of airway resistance in actual SGS patients. CONCLUSION:Our computer simulations suggest that the degree of airflow limitation in SGS patients may be estimated based on anatomic measurements alone. Future studies are recommended to test these predictions in larger cohorts. LEVEL OF EVIDENCE:4. Laryngoscope, 128:1551-1557, 2018.

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Cyclooxygenase-2 inhibition for the prevention of subglottic stenosis.

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Cyclooxygenase-2 inhibition for the prevention of subglottic stenosis.

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