Tuberculosis and Respiratory Diseases最新文献

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomes but remains a major medical challenge due to variability in clinical presentation and the shortcomings of existing diagnostic tests. Medical history collection is the first and most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarette smoking. Systemic assessment for connective tissue disease is essential in the initial evaluation of patients with suspected IPF to identify potential causes of interstitial lung disease (ILD). Radiologic examination using high-resolution computed tomography plays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computed tomography images can be considered. If additional tests such as surgical lung biopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsy should be considered as an alternative to surgical lung biopsy in medical centers with experience performing this procedure. Diagnosis through multidisciplinary discussion (MDD) is strongly recommended as MDD has become the cornerstone for diagnosis of IPF, and the scope of MDD has expanded to monitoring of disease progression and suggestion of appropriate treatment options.

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.

Background: The human lung serves as a niche for a unique and dynamic bacterial community related to the development and aggravation of multiple respiratory diseases. Therefore, identifying the microbiome status is crucial to maintaining the microecological balance and maximizing the therapeutic effect on lung diseases. Therefore, we investigated the histological type-based differences in the lung microbiomes of patients with lung cancer.

Methods: We performed 16S rRNA sequencing to evaluate the respiratory tract microbiome present in bronchoalveolar lavage fluid. Patients with non-small cell lung cancer were stratified based on two main subtypes of lung cancer: adenocarcinoma and squamous cell carcinoma (SqCC).

Results: Among the 84 patients analyzed, 64 (76.2%) had adenocarcinoma, and 20 (23.8%) had SqCC. The α- and β-diversities showed significant differences between the two groups (p=0.004 for Chao1, p=0.001 for Simpson index, and p=0.011 for PERMANOVA). Actinomyces graevenitzii was dominant in the SqCC group (linear discriminant analysis [LDA] score, 2.46); the populations of Haemophilus parainfluenza (LDA score, 4.08), Neisseria subflava (LDA score, 4.07), Porphyromonas endodontalis (LDA score, 3.88), and Fusobacterium nucleatum (LDA score, 3.72) were significantly higher in the adenocarcinoma group.

Conclusion: Microbiome diversity is crucial for maintaining homeostasis in the lung environment, and dysbiosis may be related to the development and prognosis of lung cancer. The mortality rate was high, and the microbiome was not diverse in SqCC. Further large-scale studies are required to investigate the role of the microbiome in the development of different lung cancer types.

The stethoscope has long been used for the examination of patients, but the importance of auscultation has declined due to its several limitations and the development of other diagnostic tools. However, auscultation is still recognized as a primary diagnostic device because it is non-invasive and provides valuable information in real-time. To supplement the limitations of existing stethoscopes, digital stethoscopes with machine learning (ML) algorithms have been developed. Thus, now we can record and share respiratory sounds and artificial intelligence (AI)-assisted auscultation using ML algorithms distinguishes the type of sounds. Recently, the demands for remote care and non-face-to-face treatment diseases requiring isolation such as coronavirus disease 2019 (COVID-19) infection increased. To address these problems, wireless and wearable stethoscopes are being developed with the advances in battery technology and integrated sensors. This review provides the history of the stethoscope and classification of respiratory sounds, describes ML algorithms, and introduces new auscultation methods based on AI-assisted analysis and wireless or wearable stethoscopes.

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC).

Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase- 2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion.

Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs.

Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.

Chronic cough is a common problem that can be refractory to medical treatment. Nonpharmaceutical management of chronic cough has an important role in well selected patients. This review article outlines the history of chronic cough management, current approaches to speech pathology management of the condition and new modalities of nonpharmaceutical treatment. There is a need for further research into nonpharmaceutical options with well described randomised control trials.

Background: In patients with chronic obstructive pulmonary disease (COPD), decreased muscle mass is a frequently encountered comorbidity in clinical practice. However, the evaluation of muscle mass in patients with COPD in real-world practice is rare.

Methods: We retrospectively reviewed the electronic medical records of all patients with COPD who underwent bioelectrical impedance analysis at least once between January 2011 and December 2021 in three hospitals. Then, we analyzed the performance rate of muscle mass measurement in the patients and the correlation between muscle mass, clinical parameters, and COPD prognosis.

Results: Among the 24,502 patients with COPD, only 270 (1.1%) underwent muscle mass measurements. The total skeletal muscle mass index was significantly correlated with albumin, alanine transaminase, and creatinine to cystatin C ratio in patients with COPD (r=0.1614, p=0.011; r=0.2112, p=0.001; and r=0.3671, p=0.001, respectively). Acute exacerbation of COPD (AE COPD) was significantly correlated with muscle mass, especially the truncal skeletal muscle mass index (TSMI) in males (r=-0.196, p=0.007). In the multivariate analysis, TSMI and cystatin C were significant risk factors for AE COPD (hazard ratio, 0.200 [95% confidence interval, CI, 0.048 to 0.838] and 4.990 [95% CI, 1.070 to 23.278], respectively).

Conclusion: Low muscle mass negatively affects the clinical outcomes in patients with COPD. Despite its clinical significance, muscle mass measurement is performed in a small proportion of patients with COPD. Therefore, protocols and guidelines for the screening of sarcopenia in patients with COPD should be established.

The healing process of tracheobronchial tuberculosis (TB) results in tracheobronchial fibrosis causing airway stenosis in 11% to 42% of patients. In Korea, where pulmonary TB is still prevalent, post-TB tracheobronchial stenosis (PTTS) is one of the main causes of benign airway stenosis causing progressive dyspnea, hypoxemia, and often life-threatening respiratory insufficiency. The development of rigid bronchoscopy replaced surgical management 30 years ago, and nowadays PTTS is mainly managed by bronchoscopic intervention in Korea. Similar to pulmonary TB, tracheobronchial TB is treated with combination of anti-TB medications. The indication of rigid bronchoscopy is more than American Thoracic Society (ATS) grade 3 dyspnea in PTTS patients. First, the narrowed airway is dilated by multiple techniques including ballooning, laser resection, and bougienation under general anesthesia. Then, most of the patients need silicone stenting to maintain the patency of dilated airway; 1.5 to 2 years after indwelling, the stent could be removed, this has shown a 70% success rate. Acute complications without mortality develop in less than 10% of patients. Subgroup analysis showed successful removal of the stent was significantly associated with male sex, young age, good baseline lung function and absence of complete one lobe collapse. In conclusion, rigid bronchoscopy could be applied to PTTS patients with acceptable efficacy and tolerable safety.