The Clinical Analysis And Establishment Of Animal Model Of Benign Tracheal Stenosis

Background and objective:Tracheal stenosis and/or rupture are potential complications of endotrachealintubation and mechanical ventilation in critically ill patients. Postintubation trachealstenosis remains the leading cause of tracheal obstruction, which may be life-threateningand often misdiagnosed. Although the endotracheal tube with high-volume low-pressurecuff has been shown to reduce the incidence of airway injury,19%of critical patients stilloccur tracheal stenosis after intubation. Cuff stenosis refers to stenosis at the site of thecuff of an endotracheal tube. The mechanism of cuff stenosis involves mucosal ischemiaand necrosis caused by excessive cuff pressure or over-sized tube, resulting in excessivegranulation developing and cicatricial healing of an area of transmural injury to theairway, which narrows the tracheal lumen. Moreover, pericondrium damaged, whichindicates adverse prognosis, was the key of tracheal stenosis, while cartilage degeneratedand collagen lost corresponding to area of the cuff were observed in the specimen of thehuman trachea excised for repair of tracheal stenosis because of intubation injury.Nevertheless, no further studies are reported by researchers above and thepathophysiological procedure of postintubation stenosis is not yet clear.A variety of interventional bronchoscopic techniques have recently been developed,balloon dilation, cauterization, cryotherapy and stent placement are less invasivecompared to surgical methods, but intractable complications sometimes occur, thuscausing poor clinical outcomes. Cicatricial stenotic lesions of the subglottis and tracheahave been challenging to study in human due to the high rate of restenosis. To investigatethe pathogenesis of postintubation tracheal stenosis and develop effective techniques, it isnecessary to establish an experimental animal model in which the pathologic changes oftracheal stenosis are similar to those seen in clinic cases.The present study aims to analysis the causes, clinical features and efficacy ofinterventional treatment of benign tracheal stenosis. In addition, We hypothesized that endotracheal intubation with excessive cuff pressure might lead to airway injury andtracheal stenosis. The purpose of this study is therefore to establish a simple and reliableanimal model of tracheal stenosis with use of endotracheal intubation.Part Ⅰ The clinical analysis and efficacy of benign trachealstenosisObjective:To analysis the causes and clinical features of benign tracheal stenosis and evaluatethe curative effect of intraluminal bronchoscopic treatment.Methods:158patients with benign tracheal stenosis in our hospital from September2005toSeptember2012were collected to retrospectively analysis the causes and clinic featuresof tracheal stenosis. Interventional treatments through bronchoscopy were used to treatthe benign tracheal stenosis and the curative effects were evaluated.Results:1.158cases of benign tracheal stenosis in our hospital were recruited to our study,69.6%of them were young and middle-aged. The main causes of benign tracheal stenosiswere as follows: secondary to postintubation in32.9%(52/158) and tracheotomy in28.5%(45/158), tuberculosis in16%(26/158), benign tumor in5.1%(8/158) and other27cases.94.3%patients improved in symptoms with alleviation immediately afterbronchoscopic treatment, the average tracheal diameter increased form (4.22±2.06) mmto (10.16±2.99) mm (t=21.48，P<0.01), dyspnea index decreased from2.29±0.75to0.63±0.67(t=19.85，P<0.01). The recurrence rate in1and3month after interventionaltreatment were38.3%and26.8%, respectively.2.52cases of postintubation tracheal stenosis patients in our hospital received theendoscopic treatments from September2005to September2012, accounting for32.9%of158patients with benign tracheal airway stenosis. There were29males and23females,with a median age of41years old (range from1to83years old). The mean endotracheal intubation period of52patients was14.3±12.1days (range from1to52days), while themean time between extubation and experience symptoms was51.4±70.4days (rangefrom7to180days).69.2%patients were developed2nd~3rd grade tracheal stenosis afterextubation and86.5%lesions were1~3cm in length. After interventional treatmentsthrough flexible bronchoscopy, the symptom such as cough and dyspnea improvementwas observed in92.3%patients, but because of tracheal stenosis recurrence afterinterventional treatments, only69.2%patients kept long-term efficacy.Conclusion:The cases of benign tracheal stenosis were increasing year by year. Postintubationwas the most common cause of benign tracheal stenosis. Interventional treatment throughbronchoscopy is effective in treating benign tracheal stenosis, but repeated interventionalprocedures may be required to maintain the favorable long-term effects. Part Ⅱ The establishment of a novel animal model ofbenign tracheal stenosisSection-1Beagle model of tracheal stenosis induced byendotracheal intubation with cuff overinflationObjectives:To establish a novel animal model of tracheal stenosis in beagle dogs byendotracheal intubation.Methods:10beagle dogs were included in the study. Induction of tracheal stenosis wasperformed by endotracheal intubation with cuff pressure up to200mmHg and causingtracheal mucosa and cartilage subjected to ischemic injury. The animals were observedafter extubation, the evaluation of stenosis progression was performed by endoscope and histological examinations.Results:All dogs revived after extuabtion without any complications related to endotrachealintubation. Tracheal stenosis developed in8of the10dogs by14th-day post extubation.At the end of the study, gross and endoscopic examination showed that stenosis had beeninduced, ranging from80%to92%in diameter.Section-2Comparation on the pathological changes ofpostintubation tracheal stenosis in animal model and clinicalpatientObjective:To compare the pathological changes of postintubation tracheal stenosis in animalmodel and clinical patient.Methods:Archival, paraffin-embedded tissue blocks were obtained from the PathologyDepartment of the first affiliated hospital of Guangzhou Medical University. Specimensconsisted of segments of the human trachea excised for repair of tracheal stenosis becauseof endotracheal intubation injury. Compared to clinical patients, pathological examinationwas performed to analysis the histological changes of tracheal segments excised from theanimal model of pointubation tracheal stenosis.Results:Histological examination of tracheal stenosis induced by endotracheal intubation,which stemmed from animal models and clinical patients, showed mucosal ulceration,submucosal thickening with formation of granulation tissues and collagen fibers, andcollapse of destroyed cartilage.Conclusions:The novel animal model of tracheal stenosis induced by endotracheal intubation with cuff overinflation (pressure at200mmHg for24hours) is technically simple, reliable andreproducible. The histological changes in animal model were similar to that of patientswith postintubation tracheal stenosis. This model may be useful for the further studies toexplore the pathogenesis of postintubation stenosis and develop new methods oftreatment for benign tracheal stenosis.