BAS patients in the Second Affiliated Hospital of Guangxi Medical University in Guangxi, China were retrospectively analyzed from January 2017 to December 2022. Data concerning etiology, stenosis site, symptoms and treatments were collected. Selection criteria were as follows: patients who were aged over 14 and confirmed by bronchoscopy, chest computed tomography (CT) or pathology owing to various factors, such as endometrial tuberculosis, endotracheal intubation, tracheotomy, pulmonary surgery, external compression and airway foreign body (FB). Exclusion criteria were as follows: patients who were aged under 14, with unknown etiology unknown and insufficient data.

BAS granulations were obtained with bronchoscopy, and normal tissues were obtained from the surgical lobectomy of lung cancer. The specimens were fixed in a 4% paraformaldehyde solution for 48 h, then embedded and sliced for subsequent detection. Adjacent slices received H&E and Masson’s staining, and slides were scanned with an inverted microscope (Olympus, Japan). The primary antibodies for IHC, transforming growth factor-β1 (TGF-β1), E-cadherin, α-smooth muscle actin (α-SMA), collagen type I protein (COL-I) and vimentin for IHC were purchased from Servicebio, China. Slices for IHC were stained with TGF-β1, E-cadherin, α-SMA, COL-I and vimentin, then scanned with 3DHistech Digital Pathology System (Bio-One, China). Representative slice areas were shown in screenshots. Subsequently, Image J was used to read and analyze the positivity intensity of the measured areas.

The study was approved by the Ethics Committee of the Second Affiliated Hospital of Guangxi Medical University, Nanning, China. Approval number [No. 2021-KY(0172)] and was conducted according to the principles outlined in the Declaration of Helsinki. Informed consent was obtained from all the subjects.

Statistical Package for the Social Sciences (SPSS) statistics software (version 26) was utilized to conduct all statistical analyses. GraphPad Prism 8 software was used for plotting. Qualitative variables were expressed as percent distributions in each category, and quantitative ones were expressed as means ± standard deviations and medians (ranges) for normally and non-normally distributed variables, respectively. The statistical test was an unpaired t-test, and a p < 0.05 was considered to show statistical significance.

Among 881 airway stenosis cases included, 46 had unknown etiology, and 218 were diagnosed as malignant airway stenosis. As a result, 617 BAS patients were recruited. Of 218 malignant airway stenosis cases, most (n = 191, 87.61%) were attributed to lung cancer, while others were caused by lymphoma, esophageal cancer, mediastinal tumors, lung metastases, etc. Most of the 46 patients with unknown etiology (n = 41, 89.13%) refused pathological biopsy and diagnosis, and five patients remained unclearly diagnosed after pathological biopsy and diagnosis. As shown in Table 1, 617 BAS patients were finally enrolled and consisted of 333 (53.97%) females and 284 (46.03%) males, with an average age of 48.93 ± 18.30 (ranging from 14 to 87 years). In addition, 218 patients (35.33%) were younger than 40, 181 (29.34%) ranged from 40 to 59 years old, and 218 (35.33%) were over 60 years old. Tuberculosis (n = 306, 49.59%) and trauma (n = 179, 29.02%) were the two leading etiologies of BAS, while the other etiologies contained airway FB (n = 74, 11.99%), external compression (n = 25, 4.05%) and other etiologies (n = 33, 5.35%). The other etiologies covered seven cases caused by non-specific bacterial infections, five esophagotracheal fistula, three tracheobronchopathia osteochondroplastica, tracheobronchial amyloidosis and nontuberculous mycobacteriosis. They also included two bronchial calculus and bronchial hamartoma, as well as one rheumatoid arthritis with lung disease, Sjogren’s syndrome with lung disease, Rosai–Dorfman disease, tracheosquamous epithelial papilloma, trachea schwannoma, recurrent polychondritis, radiotherapy and chlorine gas (Table 2).

The most common stenosis site was the trachea (n = 222, 35.98%), while the other stenosis sites were left (n = 153, 24.80%) and right bronchi (n = 203, 32.90%), as well as multiple sites (n = 39, 6.32%). In total, 512 patients (82.98%) received comprehensive interventional therapy, including balloon dilatation, high-frequency electric, laser and argon plasma thermal ablation, snare resection, etc. Furthermore, 72, 28, and 70 patients (11.67, 4.54, and 11.35%) received stent implantation, surgery and other conservative treatments, respectively.

Follow-ups were conducted on 535 of these patients by telephone, WeChat or on the site, with a period of 6 months to 5 years, while the other 82 patients dropped out. It was found that most of them (n = 328, 61.31%) had a partial recovery, 27.85% (n = 149) had a complete recovery, and 10.84% (n = 58) had died. Of the 58 deaths, 38 died of respiratory failure or lung infection, while the remaining 20 died of other underlying diseases (Table 3).

The data of 306 tuberculous tracheobronchial stenosis (TBTS) patients are summarized in Table 1. A majority of patients were females (n = 215, 70.26%), with a mean age of 44.57 ± 18.64 (range, 14–88), including 147 (48.04%) under 40, 72 (23.53%) from 40 to 59, and 87 (28.43%) over 60. All patients developed symptoms, including cough (n = 281, 91.83%), dyspnea (n = 165, 53.92%), fever (n = 36, 11.76%), chest pain (n = 29, 9.48%), loss of weight (n = 14, 4.58%), bloody sputum (n = 12, 3.92%) and hemoptysis (n = 11, 3.59%). Comorbidities of TBTS in this study encompassed hypertension (n = 40, 13.07%), diabetes (n = 18, 5.88%), coronary heart disease (n = 16, 5.23%), cerebrovascular disease (n = 5, 1.63%) and respiratory failure (n = 4, 1.31%). TBTS primarily occurred in right bronchi (n = 147, 48.04%), including 70 cases in the right middle bronchus, 46 in the right main bronchi, and 31 in the right branch, followed by left bronchi (n = 119, 38.89%) which included 97 cases in left main bronchus and 22 in the left branch. Multiple sites (n = 33, 10.78%) and trachea (n = 7, 2.29%) were the other stenosis sites. Most TBTS patients (n = 259, 84.64%) were treated by interventional therapy, while 15, two and 47 received stent implantation (4.90%), surgery (0.65%), and conservative treatments (15.36%), respectively. Of the 15 patients implanted with airway stents, 10 had V-shaped silicone stents implanted, and three were implanted with Y-shaped silicone stents and two metal stents.

As depicted in the report of representative cases (Figure 1A), a 39-year-old female patient was diagnosed with active TBTS, whose most notable symptoms were cough and dyspnea. A computed tomography (CT) scan revealed stenosis in right main and right upper bronchi, and a big tuberculous cavity was found in the right upper lobe. Mucosal swelling, granulation hyperplasia, lumen deformation and stenosis were observed with a bronchoscopy. Pathology showed that extensive granulation tissue hyperplasia, and acid-fast bacilli and staining were positive, with the aggregation of inflammatory cells.

Another representative case report is presented in Figure 1B. In the report, a 23-year-old female patient was also diagnosed with active TBTS, whose main symptoms were cough and dyspnea. Here, the CT scan showed stenosis in the left main bronchus and the enlargement of mediastinal lymph nodes. A bronchoscopy demonstrated the obvious stenosis of the left main bronchus, a large amount of gray and white cheesy necrosis and visible bronchial lymph node fistula. H&E staining revealed cheesy necrosis and inflammatory cell aggregation. Masson staining showed fibrosis in the granulation tissues of TBTS compared with the normal control group (Figure 2).

Here, different treatments are shown in Figure 3. A was a patient treated by interventional therapy, while B, C and D were implanted with V-shape silicone, Y-shape and metallic stents, respectively. Airway stenosis was relieved after interventional therapy or stent plantation. Of 262 TBTS patients followed up, 42 (16.03%) had a complete recovery after treatment, 204 (77.86%) had an incomplete recovery, and 16 (6.11%) died of respiratory failure or lung infection (Table 3).

A total of 179 traumatic airway stenosis (TAS) patients were enrolled in this study (Table 1). Their etiologies included tracheal intubation (n = 92), tracheotomy (n = 69), injury (n = 15), and surgery (n = 3), which mainly occurred in the trachea (n = 173, 96.65%). Four cases (2.23%) were located in right bronchi, one (0.56%) in left bronchi, and one in multiple sites. Most of the TAS patients were males (n = 111, 62.01%), with a mean age of 49.75 ± 16.93 (range 14–82). A total of 51 patients (28.49%) were younger than 40, 68 (37.99%) were aged between 40 and 59, and 60 (33.52%) were at the age of over 60. Their main symptoms were dyspnea (n = 154, 86.03%) and cough (n = 100, 55.87%). Nearly half of them were complicated with cerebrovascular disease (n = 86, 48.04%), hypertension (n = 76, 42.46%) and diabetes (n = 37, 20.67%).

As depicted in the report of representative cases (Figure 4), a 51-year-old man was diagnosed with post-tracheotomy stenosis and a 27-year-old man with post-intubation stenosis. Their most notable symptoms were dyspnea. CT and bronchoscopy showed severe tracheal stenosis, which resulted from massive granulation tissue hyperplasia. Pathology showed extensive granulation tissue hyperplasia. The staining results revealed the presence of squamous epithelial hyperplasia, the severe thickening of mucosa, hyperplasia, the repair of scar tissues in lamina propria and submucosa, the staggered formation of numerous mature and coarse collagen fibers, the appearance of countless capillaries, frequent vascular dilatation, mild inflammatory reaction, and the infiltration of a few lymphocytes. Masson’s staining indicated the proliferation of plentiful blue collagen fibers (Figure 2). All of them received interventional therapy, and stenosis was relieved.

Among 179 patients, 168 (93.85%) received comprehensive interventional therapy, including 47 (26.26%) cases who received stent implantation (36, eight, two and one cases of straight silicone stent, Montgomery T-tube implantation, metal stent and Y-shaped silicone stent, respectively), and seven (3.91%) who received surgical treatment. Finally, 11 cases (6.15%) received conservative medical treatment. Of 155 TAS patients followed up, 22 (14.19%) had a complete recovery after treatment, 97 (62.58%) had an incomplete recovery, and 16 and 20 (10.32 and 12.91%) died of respiratory failure or lung infection and other underlying diseases, respectively (Table 3).

A total of 74 cases of airway stenosis caused by airway FB were reported, including 59 males (79.73%) and 15 females (20.27%), with an average age of 58.22 ± 16.54 (range 14–87). Thirty-nine cases (52.70%) were aged over 60, and 15 (20.27%) were younger than 40. Most of the patients appeared to have a cough (n = 67, 90.54%), while some seemed to experience chest pain (n = 9, 12.16%), fever (n = 5, 6.76%), hemoptysis (n = 4, 5.41%), dyspnea (n = 2, 2.70%) and hemoptysis (n = 2, 2.70%). A history of definite choking was present in 52 (70.27%) patients. The longest case was a 28-year-old man who inhaled a whistle 18 years ago. Twenty-three cases (31.08%) were combined with hypertension, and 11 (14.86%) with cerebrovascular disease. Most airway FBs (n = 46, 62.16%) were in the right bronchus, while 26 (35.14%) were in the left bronchus, and two were in the trachea (Table 1).

The most common airway FBs included bones (n = 42, 56.76%), followed by nuts (n = 6), false teeth (n = 3), capsule drug (n = 1), and metallic (n = 5, caused by dental operation), plastic (n = 3), and unknown FBs (n = 14), as mentioned in Table 4. Among them, 59 cases (79.73%) had surrounding granulation tissue formation that led to airway stenosis, and 15 (20.27%) had no granulation tissue formation. Most of them (n = 72, 97.30%) received interventional comprehensive treatment, while only one received surgical treatment because of hemoptysis caused by FB. Different types of airway FBs are presented in Figure 5. Of the 65 patients we followed, none died, most patient was complete recovery, and only one case was not completely removed the FB.

A total of 25 BAS cases were attributable to the external compression of surrounding airway tissues (Table 1), including eight males (32.00%) and 17 females (68.00%), with an average age of 62.88 ± 14.04 (range 31–83). Dyspnea was observed to be the main symptom (n = 22, 88.00%), and cough was found in eight cases (32.00%). All 25 cases of stenosis were located in the main trachea, of which 22 (88.00%) were caused by thyroid goiter compression and the other three by mediastinal cyst, bronchial cyst and cervical hematoma compression, respectively. Seven patients received metal stent plantation. Two, 15 and eight patients received interventional therapy, surgical treatment and conservative treatment, respectively. The tracheal mucosa was intact, and the tracheal segment was compressed and deformed under bronchoscopy. Tracheal stenosis can be relieved after surgical treatment in 15 patients. Of the 24 patients we followed, only one died of heart disease.

As depicted in the report of representative cases (Figure 6), a 58-year-old woman was admitted to hospital due to “cervical mass found for more than one decade and shortness of breath for 2 days.” CT showed huge cervical goiter, and the upper tracheal segment was compressed. Bronchoscopy showed severe external compression stenosis in the trachea, and the tracheal mucous was normal. The tracheal stenosis was improved significantly after the implantation of a metal-coated stent.

Another representative case showed a 64-year-old woman admitted to hospital due to “shortness of breath for more than 1 month” and confirmed to have external compression tracheal stenosis by CT and bronchoscopy. The tracheal stenosis was also improved significantly after the implantation of a metal-coated stent (Figure 6).

IHC detection was performed on BAS granulation and normal tissues. Normal tissues were collected from a 57-year-old female patient and a 49-year-old male patient who accepted pulmonary lobectomy on account of lung adenocarcinoma and were diagnosed with lung cancer. BAS granulation tissues were gathered from a 57-year-old male patient diagnosed with TBTS and a 27-year-old male patient diagnosed with TAS. As evidenced in Figure 7, the expression of E-cadherin in BAS granulation tissues was down-regulated compared with normal control, while those of vimentin, α-SMA, COL-I, and TGF-β1 were up-regulated, with statistical significance (p < 0.001). These results suggested that EMT, fibrosis and the increased expression of TGF-β1 existed in BAS granulation tissues.