Tracheobronchial mucosal keratosis: A literature review of this rare disorder.

Background: Tracheobronchial mucosal keratosis (TBMK) is a rare airway disease that may cause refractory cough and airway stenosis. The characteristics of this disease remain unknown. In the present study, we describe this disorder based on a review of the current literature, emphasizing its diagnostic and therapeutic aspects. Methods: A comprehensive search of TBMK was performed in Medline, Google Scholar, Web of Science, Cochrane Library (UK), Embase, China National Knowledge Infrastructure (CNKI) (China), and Wan Fang Med Online (China). The following data were collected: patient characteristics, chest imaging findings, bronchoscopy, histopathologic findings, pathogen testing, treatment, and prognosis. Results: As of 2023, eighteen cases of TBMK have been reported. The main clinical manifestations were cough and expectoration. Chest imaging findings were non-specific. The main bronchoscopy findings were nodular protrusion of airway lumen and yellow-white purulent moss above the nodular lesion. The lesions were mainly located in the trachea and mainstem bronchus. The main pathological manifestations include keratinocytes or keratinocyte beads, squamous metaplasia, and mucosal inflammatory changes. The treatments that were administered include antibiotics, symptomatic treatment, and glucocorticoids. All methods were ineffective except for bronchoscopy-guided high-frequency electric knife and recombinant human epidermal growth factor treatment. Conclusions: TBMK is a rare respiratory disease with atypical clinical manifestations and chest computed tomography findings. Bronchoscopy revealed that nodular hyperplasia of the airway and purulent fur-covered lesions are typical manifestations. The final diagnosis needs to be confirmed by histopathological examination. There is a lack of effective treatment for this disease, and bronchoscopy-guided intervention therapy may be a candidate treatment.

Tiao-bu-fei-shen formula promotes downregulation of the caveolin 1-p38 mapk signaling pathway in COPD - Associated tracheobronchomalacia cell model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tiao-bu-fei-shen (TBFS) formula, extensively used in Traditional Chinese Medicine (TCM), can enhance therapeutic efficacy and reduce the frequency of acute exacerbations of lung-kidney Qi deficiency in patients with chronic obstructive pulmonary disease (COPD). According to both TCM theory and long-term observation of practice, TBFS has become an effective treatment for COPD-associated tracheobronchomalacia (TBM). AIM OF THE STUDY: To investigate the mechanism of the TBFS formula in treating COPD-associated TBM based on caveolin 1-p38 MAPK signaling and apoptosis. MATERIALS AND METHODS: A rat COPD model was prepared by exposure to smoking combined with tracheal lipopolysaccharide injection. The trachea or bronchus chondrocytes from COPD rats were isolated, cultured, and treated with 10 ng/mL IL-1ß for 24 h to develop a model of COPD-associated TBM. Normal rats were administered TBFS to prepare drug-containing serum, and CCK8 assays were used to screen the optimal drug-containing serum concentration and SB203580 dose. TBFS drug-containing serum and SB203580 were processed separately for the control, model, drug-containing serum, blocker, and drug-containing serum combined with blocker groups. Flow cytometry and CCK8 assays were used to detect apoptosis and proliferative activity. Toluidine blue staining and immunohistochemistry were used to analyze the chondrocyte proteoglycan and type II collagen content. Western blotting was used to detect the expression of caveolin 1, p-p38 MAPK, TNF-α, IL-1ß, MMP-13, Bax, and Bcl-2 proteins. Quantitative PCR was used to detect the expression of caveolin 1, p38 MAPK, IL-1ß, MMP-13, Bax, Bcl-2, and miR-140-5p. RESULTS: The isolation and identification of bronchial chondrocytes from COPD rats revealed that 10 ng/mL IL-1ß can produce a stable COPD-associated TBM model. Screened via the CCK8 method, fourth-generation bronchial chondrocytes were determined as the optimal cells, and 5 µM SB203580 and 5% low-dose drug-containing serum were the optimal intervention doses. The experimental chondrocytes of each group were treated separately for 48 h. Toluidine blue staining and immunohistochemical analysis revealed that TBFS drug-containing serum, SB203580, and TBFS drug-containing serum combined with SB203580 can effectively increase the proteoglycan and type II collagen content after chondrocyte degradation. Flow cytometry of cells treated with SB203580 and TBFS drug-containing serum combined with SB203580 revealed significantly reduced cell apoptosis and enhanced cell proliferation activity. Western blot and qPCR analyses revealed that the TBFS drug-containing serum, SB203580, and TBFS drug-containing serum combined with SB203580 effectively inhibit the expression of caveolin 1, p-p38 MAPK, MMP-13, IL-1ß, TNF-α, and Bax proteins while promoting Bcl -2 protein expression. Treatment with TBFS drug-containing serum and SB203580 effectively inhibited the expression of MMP-13, p38 MAPK, caveolin 1, and Bax genes, and promoted the expression of Bcl-2 and miR-140-5p genes. CONCLUSIONS: A concentration of 10 ng/mL of IL-1ß can generate a stable COPD-associated TBM cell model. TBFS can improve the proteoglycan and type II collagen content, increase cell activity, and reduce the amount of chondrocyte apoptosis. The role of TBFS may be related to mechanisms of inhibiting the expression of the key signaling molecules caveolin 1 and p-p38 MAPK in the caveolin 1-p38 MAPK signaling pathway, thereby reducing the expression of the downstream effector products MMP-13, IL-1ß, and TNF-α, while inhibiting the expression of the apoptotic gene Bax and improving the expression of Bcl-2 and miR-140-5p genes.

Bronchoscopy-Guided Intervention Therapy With Extracorporeal Membrane Oxygenation Support for Relapsing Polychondritis With Severe Tracheobronchomalacia: A Case Report and Literature Review.

Relapsing polychondritis is an immune disorder of unknown etiology involving multiple systems that is characterized by persistent inflammation and destruction of cartilage, including the ears, nose, costal, joint, and airways. Airway involvement caused by relapsing polychondritis is common, and tracheobronchomalacia is the most serious complication, which is life-threatening. Currently, the exact mechanism of relapsing polychondritis with tracheobronchomalacia is unknown. Although glucocorticoids and immunosuppressive agents are administered, failures often occur. Currently, bronchoscopy-guided intervention therapy used in tracheobronchomalacia caused by chronic obstructive pulmonary disease or other etiology has gradually increased, but bronchoscopy-guided intervention therapy with extracorporeal membrane oxygenation assist used in tracheobronchomalacia caused by relapsing polychondritis has not been reported. Here, we report a case of relapsing polychondritis with severe tracheobronchomalacia. Although drug therapy was provided and airway stent implantation was performed, the tracheal stenosis was further aggravated. Because conventional anesthesia and mechanical ventilation cannot meet the needs of bronchoscopy-guided intervention therapy or guarantee sufficient safety. The intervention treatment was performed with the support of extracorporeal membrane oxygenation, which was successfully completed without obvious complications. The symptoms were significantly improved, and the patient was discharged uneventfully.

Retrospective study of clinical and pathologic features of pulmonary papillary adenoma: A rare tumor and 15 cases report.

Pulmonary papillary adenoma is extremely rare. The limited number of published articles describing pulmonary papillary adenoma emphasize that it is always detected by physical examination, is difficult to diagnose, and has malignant potential. To further expand our understanding of this disease, we report on 15 cases of pulmonary papillary adenoma diagnosed from 2013 to 2019 in our hospital.The clinical and pathological data of 15 cases of pulmonary papillary adenoma were collected from the medical record system of our hospital. All the clinical data were checked by 2 independent researchers. All pathology outcomes were independently reassessed by 2 pathologists. A review of the relevant literature was performed.Of 15 patients identified, 6 were men and 9 were women, and the average age at disease onset was 61.3 years. Chest computed tomography (CT) indicated pneumonia, an isolated nodule, bronchiectasis, a mass, ground glass opacity, and local interstitial fibrosis under the pleura. Thirteen cases had benign histopathology upon microscopy and immunohistochemistry examination: a papillary morphology, grade 2 or 3 papillary branches, and a slender nipple axis composed of fibers and vessels. More than 80% of the papillary epithelial cells were columnar or cubic, and single-layered or pseudostratified, with a round nucleus at the bottom of the cell. The cytoplasm was rich in mucus and neutral mucopolysaccharides. Except the above-mentioned features, there was also local epithelial dysplasia, carcinogenesis, and interstitial infiltration in two cases. The 2 patients with a cancerous mass underwent surgical resection, whereas the other patients were kept under surveillance. While one patient with cancer is deceased, follow-up indicates that the remaining patients have experienced a good outcome.Pulmonary papillary adenoma is very rare in clinical practice, and its clinical manifestations and CT images are not specific. Some cases may be cancerous and surgical resection should be the preferred treatment.

The research of Tuna Huichun Gong on pulmonary function, exercise tolerance, and quality of life in patients with chronic obstructive pulmonary disease based on the concept of early pulmonary rehabilitation.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common high-burden and highly disabling lung disease. The quality of life and exercise endurance of patients with COPD is often low because of atrophy of the respiratory and skeletal muscles. Although recommended by the global initiative for chronic obstructive lung disease guidelines, pulmonary rehabilitation (PR) has not been used widely because of its inherent limitations. Tuna-Hui-Chun-Gong (TNHCG) is a popular traditional exercise used to treat COPD in China. We aim to evaluate the safety and efficacy of TNHCG for PR of COPD. METHODS: The provided protocol is for a single-blind randomized controlled trial in which 120 COPD patients will be randomly and equally divided into the experimental or control group. The control group will be treated with standard COPD drugs while the experimental group will perform TNHCG exercises apart from standard drug treatment. The duration of treatment will be 24 weeks and a follow-up for 48 weeks. The primary outcome will be the 6-Minute Walk Test. The secondary outcomes will include the pulmonary function test, St George's respiratory questionnaire, COPD assessment test, modified medical research council dyspnea scale, Hospital Anxiety and Depression Scale, and exacerbation frequency. A safety assessment will also be performed during the trial. DISCUSSION: Our study will provide evidence to support TNHCG exercise as an additional measure for PR of COPD. TRIAL REGISTRATION: ChiCTR1900028332, Registered December 29, 2019. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Sichuan Traditional Chinese Medicine Regional Ethics Review Committee (No. 2019KL-050).

Bronchoscopy-guided intervention therapy with extracorporeal membrane oxygenation support for advanced cancer metastasis to the central airway: A case report.

INTRODUCTION: Dyspnea due to tracheal invasion by malignant tumors is a common oncological emergency that is difficult to manage, and a common cause of death among patients with advanced cancer. Bronchoscopy-guided intervention therapy under conventional ventilation is very risky for patients with severe central airway stenosis. Extracorporeal membrane oxygenation (ECMO) provides strong cardiopulmonary support, but is rarely used in bronchoscopy-guided interventional therapy. PATIENT CONCERNS: The patient had advanced esophageal cancer with metastases to the trachea and left and right main bronchi. Despite several sessions of radiotherapy, chemotherapy, and bronchoscopy-guided intervention therapy, the tumor in the airway became enlarged, the lumen was severely narrow, and the patient experienced respiratory distress. DIAGNOSIS: A thoracic computed tomography scan performed at our hospital revealed invasion of the trachea and opening of the left and right main bronchi by the esophageal cancer, blockage of the stent by the tumor, and severe luminal narrowing. An emergency bronchoscopy showed slit-like stenosis of the middle and lower part of the trachea and the left and right main bronchi, and the tumor was highly vascular. INTERVENTIONS: To reduce the risk of major airway bleeding and asphyxia during bronchoscopy under conventional ventilation, we finally performed argon plasma coagulation with a high frequency electric knife and cryotherapy with ECMO support. OUTCOMES: We successfully cleared the tumor tissue in the airway under ECMO support. The trachea and left and right main bronchi recovered smoothly, and the patient was soon discharged. CONCLUSION: ECMO can meet the oxygenation needs during bronchoscopy-guided intervention therapy. For patients with severe central airway obstruction due to malignant tumors, ECMO should be considered if conventional respiratory support cannot guarantee the safety of surgery.

A case report and review of literature of Dieulafoy's disease of bronchus: A rare life-threatening pathologic vascular condition.

RATIONALE: Dieulafoy's lesions are characterized by the presence of a dysplastic artery in the submucosa, most frequently associated with gastrointestinal hemorrhage. They are rarely identified in the bronchial submucosa and can cause massive or fatal hemoptysis PATIENT CONCERNS:: The patient was a 62-year-old male farmer with intermittent hemoptysis of approximately 2 years duration and a definite diagnosis could not be established. DIAGNOSIS: A thorax-computed tomography at our hospital revealed that the bronchus of left lower lobe was narrowed with associated local atelectasis, and lung cancer was suspected. A bronchoscopy showed a slit-like stenosis of the left lower lobe, swollen and smooth mucosa, and a significantly wider subsection carina. INTERVENTIONS: A fatal hemorrhage occurred during biopsy and, rescue and resuscitation measures were immediately taken. A double-lumen endotracheal intubation was implanted and single-lung ventilation was started to maintain oxygenation. Hemoptysis completely stopped after bronchial artery embolization. OUTCOMES: The patient eventually died of disseminative intravascular coagulation and multiple organ failure. Bronchial arteriography and subsequent autopsy confirmed Dieulafoy's disease of the bronchus. LESSONS: In cases with recurrent unexplained hemoptysis, where CT chest or thoracic radiography show no abnormalities, pulmonologist should suspect a bronchial Dieulafoy's disease and avoid blindly performing bronchoscopy guided biopsy, which may result in fatal hemoptysis.

[Efficacy and Safety of Tiotropium Bromide in the Treatment of Chronic Obstructive Pulmonary Disease--a Multi-center Randomized Clinical Trial].

OBJECTIVE: To investigate the efficacy and safety of domestic tiotropium inhalation capsule in patients with chronic obstructive pulmonary disease (COPD) with multi-center randomized clinical trial. METHODS: Patients with stable slight to moderate COPD were randomized into trial group (n=109) with tiotropium 18 pg Qd or control group (n =111) with ipratropium 40 µg Qid for a treatment of four weeks. The spirometry and scoring questionaire were recorded at different visits during the treatment. Rescue medication consumption and adverse events were recorded. Results Forced expiratory volume in 1 s (FEV1) of both groups increased obviously 30 min and 3 h after first dosing. After four weeks treatments, FEV, and forced vital capacity (FVC) in both groups were improved obviously, and the improvement in tiotropium group was significantly higher than that ipratropium group. COPD symptom scores were significantly reduced in both groups, and the improvement in tiotropium group was significantly better than that in ipratropium group. There was no significant difference in rescue medication consumption between the two groups. The ratios of adverse events were 22. 02% and 15. 32% in tiotropium and ipratropium group, respectively (P=0. 23). CONCLUSION: Domestic tiotropium inhalation capsule is efficient and safe in the treatment of COPD.

Population pharmacokinetics of oral levofloxacin 500 mg once-daily dosage in community-acquired lower respiratory tract infections: results of a prospective multicenter study in China.

This study aimed to explore the pharmacokinetic features of levofloxacin (LVFX) in Chinese patients with infections and to confirm oral LVFX 500 mg once daily as an optimal treatment regimen based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. A total of 1052 plasma samples from 164 Chinese adult patients with community acquired lower respiratory tract infections (CALRTIs) and 18 healthy volunteers were used for population PK analysis. LVFX 500-mg tablets were given once daily. A nonlinear mixed effects model (NONMEM) program was used for population PK model-building and a two-compartment model with first-order absorption process was established. Creatinine clearance (CL(cr)) and body weight were identified as intrinsic factors which significantly affected oral clearance (CL(t)/F) and the apparent volume of distribution of the central compartment (V1/F), respectively. The final model is described as follows: CL(t)/F (l/h) = (8.97 + 0.917 x (CL(cr) (ml/min)-100.92) x 60/1000) x exp (eta(CLt/F)). V1/F (l) = (85.3 + 1.22 x (weight (kg)-60.75)) x exp (eta(V1/F)). Q/F (l/h) = 0.351. V2/F (l) = 6.81. k(a) (h(-1)) = 1.44 x exp(eta(ka)). Based on the population PK model, mean C(max) and AUC(0-24h) in CALRTI patients were estimated as 5.13 microg/ml and 58.98 microg.h/ml, respectively. A subgroup analysis showed that patients with mild renal dysfunction (50 ml/min < or = CL(cr) < 80 ml/min) had 34% higher AUC(0-24h) values compared to patients with normal renal function (CL(cr) > or = 80 ml/min). Postmodeling simulation using final population PK estimates also showed that C(max) and AUC(0-24h) increased markedly in patients with severe renal dysfunction. The results indicate that LVFX dosage adjustment should be individualized on the basis of the CL(cr), especially in those with CL(cr) less than 50 ml/min. None of the PK parameters had any correlation with the occurrence of adverse events. PK-PD analysis indicated that, in patients treated with LVFX 500 mg once daily, the AUC(0-24h)/MIC ratio exceeded the target for those major CALRTI pathogens isolated. In addition, the C(max)/MIC ratio reached 5 for Streptococcus pneumoniae, indicating that the emergence of LVFX-resistant S. pneumoniae could be prevented during the therapy with this dosage regimen. These results demonstrate that oral LVFX 500 mg once daily has favorable PK parameters and PK-PD features in patients with CALRTIs, and the results strongly support this dosage regimen for the treatment of CALRTI.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.