Viral infections in the respiratory tract are common, and, in recent years, severe acute respiratory syndrome coronavirus 2 outbreaks have highlighted the effect of viral infections on antiviral innate immune and inflammatory reactions. Specific treatments for numerous viral respiratory infections have not yet been established and they are mainly treated symptomatically. Therefore, understanding the details of the innate immune system underlying the airway epithelium is crucial for the development of new therapies. The present study aimed to investigate the function and expression of interferon (IFN)‑stimulated gene (ISG)60 in non‑cancerous bronchial epithelial BEAS‑2B cells exposed to a Toll‑like receptor 3 agonist. BEAS‑2B cells were treated with a synthetic TLR3 ligand, polyinosinic‑polycytidylic acid (poly IC). The mRNA and protein expression levels of ISG60 were analyzed using reverse transcription‑quantitative PCR and western blotting, respectively. The levels of C‑X‑C motif chemokine ligand 10 (CXCL10) were examined using an enzyme‑linked immunosorbent assay, and the effects of knockdown of IFN‑β, ISG60 and ISG56 were examined using specific small interfering RNAs. Notably, ISG60 expression was increased in proportion to poly IC concentration, and recombinant human IFN‑β also induced ISG60 expression. By contrast, knockdown of IFN‑β and ISG56 decreased ISG60 expression, and ISG60 knockdown reduced CXCL10 and ISG56 expression. These findings suggested that ISG60 is partly implicated in CXCL10 expression and that ISG60 may serve a role in the innate immune response of bronchial epithelial cells. The present study highlights ISG60 as a potential target for new therapeutic strategies against viral infections in the airway.

BACKGROUND: Appropriate selection of double-lumen tube sizes for one-lung ventilation is crucial to prevent airway damage. Current selection methods rely on demographic factors or 2D radiography. Prediction of left bronchial diameter is indispensable for choosing the adequate tube size. This prospective observational study investigates if current selection methods sufficiently predict individuals\' left bronchial diameters for DLT selection compared to the 3D reconstruction.
METHODS: 100 patients necessitating thoracic surgery with one-lung ventilation and left-sided double-lumen tubes, ≥ 18 years of age, and a set of chest X-rays and 2D thorax CT scans for 3D reconstruction of the left main bronchus were included between 07/2021 and 06/2023. The cross-validated prediction error and the width of the 95%-prediction intervals of the 3D left main bronchial diameter utilizing linear prediction models were based on current selection methods.
RESULTS: The mean bronchial diameter in 3D reconstruction was 13.6 ± 2.1 mm. The ranges of the 95%-prediction intervals for the bronchial diameter were 6.4 mm for demographic variables, 8.3 mm for the tracheal diameter from the X-ray, and 5.9 mm for bronchial diameter from the 2D-CT scans. Current methods violated the suggested \'≥1 mm\' safety criterion in up to 7% (men) and 42% (women). Particularly, 2D radiography overestimated women\'s left bronchial diameter. Current methods even allowed the selection of double-lumen tubes with bronchial tube sections greater than the bronchial diameter in women.
CONCLUSIONS: Neither demographic nor 2D-radiographic methods sufficiently account for the variability of the bronchial diameter. Wide 95%-prediction intervals for the bronchial diameter hamper accurate individual double-lumen tube selection. This increases women\'s risk of bronchial damage, particularly if they have other predisposing factors. These patients may benefit from 3D reconstruction of the left main bronchus.
BACKGROUND: Not applicable.

The topology of the basement membrane (BM) affects cell physiology and pathology, and BM thickening is associated with various chronic lung diseases. In addition, the topology of commercially available poly (ethylene terephthalate) (PET) membranes, which are used in preclinical in vitro models, differs from that of the human BM, which has a fibrous and elastic structure. In this study, we verified the effect of BM thickness on the differentiation of normal human bronchial epithelial (NHBE) cells. To evaluate whether the thickness of poly-ε-carprolactone (PCL) mesh affects the differentiation of NHBE cells, cells were grown on thin- (6-layer) and thick-layer (80-layer) meshes consisting of electrospun PCL nanofibers using an air-liquid interface (ALI) cell culture system. It was found that the NHBE cells formed a normal pseudostratified epithelium composed of ciliated, goblet, and basal cells on the thin-layer PCL mesh; however, goblet cell hyperplasia was observed on the thick-layer PCL mesh. Differentiated NHBE cells cultured on the thick-layer PCL mesh also demonstrated increased epithelial-mesenchymal transition (EMT) compared to those cultured on the thin-layer PCL mesh. In addition, expression of Sox9, nuclear factor (NF)-κB, and oxidative stress-related markers, which are also associated with goblet cell hyperplasia, was increased in the differentiated NHBE cells cultured on the thick-layer PCL mesh. Thus, the use of thick electrospun PCL mesh led to NHBE cells differentiating into hyperplastic goblet cells via EMT and the oxidative stress-related signaling pathway. Therefore, the topology of the BM, for example, thickness, may affect the differentiation direction of human bronchial epithelial cells.

In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.
重度支气管肺发育不良（bronchopulmonary dysplasia, BPD）的患儿可合并严重肺叶气肿造成通气障碍，临床管理非常困难，少数患儿需要切除过度气肿的肺叶才能改善通气。但是这些患儿在术前很难评估肺叶切除后剩余的肺叶是否能够提供足够的通气，且术前准备及术中/术后管理也都具有很大的挑战性。该文报道1例重度BPD伴重度右上叶气肿的患儿通过多学科紧密协作，在纤维支气管镜引导下行支气管封堵试验，评估右上肺叶切除手术的安全性及有效性后，安全行右上肺叶切除术的治疗过程，以帮助同行了解支气管封堵术在重度BPD伴严重肺叶气肿患儿评估肺叶切除安全性及有效性中的应用。重度BPD患儿已经存在严重肺发育不良及肺损伤，肺叶切除应被视为非常规治疗手段，不应随意进行。支气管封堵试验对于重度BPD合并肺气肿患儿可以是术前评估肺叶切除风险和获益的有效手段，但技术难度大，需在经验丰富的多学科团队紧密协作下完成。.

BACKGROUND: Tracheobronchial injuries caused by blunt chest trauma are rare in children, and such injuries usually involve multiple organs. Most cases involve respiratory failure on the way to the hospital, and the mortality rate is high. Herein, we describe the case of a 5-year-old patient who fell from an electric vehicle, causing complete rupture of the bilateral main bronchus.
METHODS: We treated a 5-year-old patient with complete bilateral main bronchus rupture. Chest computed tomography (CT) failed to detect bronchial rupture. Continuous closed thoracic drainage resulted in a large amount of bubble overflow. Tracheal rupture was suspected. Fibreoptic bronchoscopy revealed complete rupture of the right main bronchus and rupture of the left main bronchus. Emergency tracheoplasty was performed under cardiopulmonary bypass (CPB). During the operation, we found that the bilateral main bronchi were completely ruptured. Postoperative recovery was smooth. The traditional surgical method for treating these injuries is lateral thoracotomy. However, a median sternotomy provides a better opportunity for selective repair. Extracorporeal circulation-assisted surgery is required for patients with unstable breathing.
CONCLUSIONS: Complete fractures of the bilateral main bronchi are rare. Bronchial rupture should be suspected in the presence of expansion defect-dropped lungs and massive air leakage despite tube thoracostomy in haemopneumothorax developing after thoracic trauma. Extracorporeal circulation-assisted tracheoplasty is a relatively safe option for children whose respiratory system is difficult to maintain, thus ensuring oxygenation ventilation and a clear surgical field.

OBJECTIVE: Symptomatic radiation pneumonitis (SRP) is a complication of thoracic stereotactic body radiotherapy (SBRT). As visual assessments pose limitations, artificial intelligence-based quantitative computed tomography image analysis software (AIQCT) may help predict SRP risk. We aimed to evaluate high-resolution computed tomography (HRCT) images with AIQCT to develop a predictive model for SRP.
METHODS: AIQCT automatically labelled HRCT images of patients treated with SBRT for stage I lung cancer according to lung parenchymal pattern. Quantitative data including the volume and mean dose (Dmean) were obtained for reticulation + honeycombing (Ret + HC), consolidation + ground-glass opacities, bronchi (Br), and normal lungs (NL). After associations between AIQCT\'s quantified metrics and SRP were investigated, we developed a predictive model using recursive partitioning analysis (RPA) for the training cohort and assessed its reproducibility with the testing cohort.
RESULTS: Overall, 26 of 207 patients developed SRP. There were significant between-group differences in the Ret + HC, Br-volume, and NL-Dmean in patients with and without SRP. RPA identified the following risk groups: NL-Dmean ≥ 6.6 Gy (high-risk, n = 8), NL-Dmean < 6.6 Gy and Br-volume ≥ 2.5 % (intermediate-risk, n = 13), and NL-Dmean < 6.6 Gy and Br-volume < 2.5 % (low-risk, n = 133). The incidences of SRP in these groups within the training cohort were 62.5, 38.4, and 7.5 %; and in the testing cohort 50.0, 27.3, and 5.0 %, respectively.
CONCLUSIONS: AIQCT identified CT features associated with SRP. A predictive model for SRP was proposed based on AI-detected Br-volume and the NL-Dmean.

暂无摘要。

Background CT-derived bronchial parameters have been linked to chronic obstructive pulmonary disease and asthma severity, but little is known about these parameters in healthy individuals. Purpose To investigate the distribution of bronchial parameters at low-dose CT in individuals with healthy lungs from a Dutch general population. Materials and Methods In this prospective study, low-dose chest CT performed between May 2017 and October 2022 were obtained from participants who had completed the second-round assessment of the prospective, longitudinal Imaging in Lifelines study. Participants were aged at least 45 years, and those with abnormal spirometry, self-reported respiratory disease, or signs of lung disease at CT were excluded. Airway lumens and walls were segmented automatically. The square root of the bronchial wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10), luminal area (LA), wall thickness (WT), and wall area percentage were calculated. Associations between sex, age, height, weight, smoking status, and bronchial parameters were assessed using univariable and multivariable analyses. Results The study sample was composed of 8869 participants with healthy lungs (mean age, 60.9 years ± 10.4 [SD]; 4841 [54.6%] female participants), including 3672 (41.4%) never-smokers and 1197 (13.5%) individuals who currently smoke. Bronchial parameters for male participants were higher than those for female participants (Pi10, slope [β] range = 3.49-3.66 mm; LA, β range = 25.40-29.76 mm2; WT, β range = 0.98-1.03 mm; all P < .001). Increasing age correlated with higher Pi10, LA, and WT (r2 range = 0.06-0.09, 0.02-0.01, and 0.02-0.07, respectively; all P < .001). Never-smoking individuals had the lowest Pi10 followed by formerly smoking and currently smoking individuals (3.62 mm ± 0.13, 3.68 mm ± 0.14, and 3.70 mm ± 0.14, respectively; all P < .001). In multivariable regression models, age, sex, height, weight, and smoking history explained up to 46% of the variation in bronchial parameters. Conclusion In healthy individuals, bronchial parameters differed by sex, height, weight, and smoking history; male sex and increasing age were associated with wider lumens and thicker walls. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Emrich and Varga-Szemes in this issue.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs.
METHODS: Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca2+/CaMKII signaling pathway and autophagy were evaluated. An autophagy inhibitor 3-MA was used to examine Wnt5a in the regulation of autophagy during EMT. Furthermore, we used a CaMKII inhibitor KN-93 to determine whether Wnt5a induced autophagy overactivation and EMT via the Ca2+/CaMKII signaling pathway.
RESULTS: Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy.
CONCLUSIONS: This study illustrates a new link in the Wnt5a-Ca2+/CaMKII-autophagy axis to triggering airway remodeling. Our findings may provide novel strategies for the treatment of EMT-related diseases.

SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients.