MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.

Tissue fibrosis remains unamenable to meaningful therapeutic interventions and is the primary cause of chronic graft failure after organ transplantation. Eukaryotic translation initiation factor (eIF4E), a key translational regulator, serves as convergent target of multiple upstream profibrotic signaling pathways that contribute to mesenchymal cell (MC) activation. Here, we investigate the role of MAP kinase-interacting serine/threonine kinase-induced (MNK-induced) direct phosphorylation of eIF4E at serine 209 (Ser209) in maintaining fibrotic transformation of MCs and determine the contribution of the MNK/eIF4E pathway to the pathogenesis of chronic lung allograft dysfunction (CLAD). MCs from patients with CLAD demonstrated constitutively higher eIF4E phosphorylation at Ser209, and eIF4E phospho-Ser209 was found to be critical in regulating key fibrogenic protein autotaxin, leading to sustained ß-catenin activation and profibrotic functions of CLAD MCs. MNK1 signaling was upregulated in CLAD MCs, and genetic or pharmacologic targeting of MNK1 activity inhibited eIF4E phospho-Ser209 and profibrotic functions of CLAD MCs in vitro. Treatment with an MNK1/2 inhibitor (eFT-508) abrogated allograft fibrosis in an orthotopic murine lung-transplant model. Together these studies identify what we believe is a previously unrecognized MNK/eIF4E/ATX/ß-catenin signaling pathway of fibrotic transformation of MCs and present the first evidence, to our knowledge, for the utility of MNK inhibitors in fibrosis.

Advancements in Interventional Pulmonology: Harnessing Ultrasound Techniques for Precision Diagnosis and Treatment.

Medical ultrasound has emerged as an indispensable tool within interventional pulmonology, revolutionizing diagnostic and procedural practices through its non-invasive nature and real-time visualization capabilities. By harnessing the principles of sound waves and employing a variety of transducer types, ultrasound facilitates enhanced accuracy and safety in procedures such as transthoracic needle aspiration and pleural effusion drainage, consequently leading to improved patient outcomes. Understanding the fundamentals of ultrasound physics is paramount for clinicians, as it forms the basis for interpreting imaging results and optimizing interventions. Thoracic ultrasound plays a pivotal role in diagnosing conditions like pleural effusions and pneumothorax, while also optimizing procedures such as thoracentesis and biopsy by providing precise guidance. Advanced ultrasound techniques, including endobronchial ultrasound, has transformed the evaluation and biopsy of lymph nodes, bolstered by innovative features like elastography, which contribute to increased procedural efficacy and patient safety. Peripheral ultrasound techniques, notably radial endobronchial ultrasound (rEBUS), have become essential for assessing pulmonary nodules and evaluating airway structures, offering clinicians valuable insights into disease localization and severity. Neck ultrasound serves as a crucial tool in guiding supraclavicular lymph node biopsy and percutaneous dilatational tracheostomy procedures, ensuring safe placement and minimizing associated complications. Ultrasound technology is suited for further advancement through the integration of artificial intelligence, miniaturization, and the development of portable devices. These advancements hold the promise of not only improving diagnostic accuracy but also enhancing the accessibility of ultrasound imaging in diverse healthcare settings, ultimately expanding its utility and impact on patient care. Additionally, the integration of enhanced techniques such as contrast-enhanced ultrasound and 3D imaging is anticipated to revolutionize personalized medicine by providing clinicians with a more comprehensive understanding of anatomical structures and pathological processes. The transformative potential of medical ultrasound in interventional pulmonology extends beyond mere technological advancements; it represents a paradigm shift in healthcare delivery, empowering clinicians with unprecedented capabilities to diagnose and treat pulmonary conditions with precision and efficacy. By leveraging the latest innovations in ultrasound technology, clinicians can navigate complex anatomical structures with confidence, leading to more informed decision-making and ultimately improving patient outcomes. Moreover, the portability and versatility of modern ultrasound devices enable their deployment in various clinical settings, from traditional hospital environments to remote or resource-limited areas, thereby bridging gaps in healthcare access and equity.

Acute exacerbation of interstitial lung diseases and mortality post-cryobiopsy: a multicenter cohort study.

Background: Interstitial lung diseases (ILDs) are a group of pulmonary disorders affecting the lung's structure. Acute exacerbation of ILD (AE-ILD) following medical procedures is a significant clinical concern. Lung cryoprobe transbronchial biopsy (cryobiopsy) is a relatively new diagnostic technique for ILD, but data on AE-ILD post-cryobiopsy is limited. This study aims to fill this gap by examining the prevalence, risk factors, and outcomes of AE-ILD following cryobiopsy. Methods: This multicenter retrospective study analyzed data from patients who underwent cryobiopsy for ILD diagnosis at three U.S. institutions between January 2014 and August 2022. The study included patients over 18 years with confirmed or suspected ILD, categorized into those who experienced AE-ILD post-cryobiopsy and those who did not. Results: Out of 111 patients, 3.6% experienced AE-ILD, with a 50% mortality rate in these cases. The study cohort was predominantly white, with a median age of 69.0 years. Common comorbidities included tobacco use and hypertension. Patients who developed AE-ILD had an increased median number of biopsies. The overall 30-day mortality was 1.8%. Overall complication rate was 32%, including pneumonia, pneumothorax, AE-ILD, and bleeding requiring intervention. The study findings suggest that bronchoscopic cryobiopsy may be associated with lower overall mortality, particularly in patients with compromised lung function. Conclusions: This study provides significant insights into AE-ILD following cryobiopsy, underscoring the need for careful patient selection and procedural assessment. While cryobiopsy may offer a safer alternative to surgical lung biopsy in specific patient cohorts, the elevated risk of AE-ILD necessitates further research to optimize patient outcomes and procedural safety.

The adherence to asthma medication for hospitalized children with asthma: A cross-sectional study in a tertiary hospital in Riyadh, Saudi Arabia.

AIM: The aim of the study was to assess adherence to asthma controller therapy and factors that influence asthma control and to determine the association between asthma knowledge of the caregiver and asthma control among admitted children with asthma. SETTINGS AND DESIGN: A cross-sectional study was conducted between November 2022 and May 2023 in a tertiary care hospital. Children with a diagnosis of asthma aged 2-14 years, who were admitted to the hospital with an exacerbation of asthma were identified. METHODS: Caregivers of the admitted children were interviewed using the Asthma Knowledge Questionnaire and Pediatric Inhaler Adherence Questionnaire. STATISTICAL ANALYSIS USED: Demographic and clinical data were described using descriptive analyses, where mean and standard deviation were used for normally distributed continuous variables, median and interquartile range (IQR), if otherwise. A P < 0.05 was set as a cutoff for statistical significance. RESULTS: A total of 144 caregivers completed the survey. Median score for parents' knowledge of asthma was 64%, with an IQR of 59-67. Both mother's and father's educational levels were associated with a good level of knowledge: odds ratio (OR) = 2.48, 95% confidence interval (CI) = 1.1-5.6, and OR = 5.33, 95% CI = 2.23-12.7, respectively. Median adherence to metered dose inhaler (MDI) was 4 (IQR = 2-6). Children who had been admitted to the general ward in the last 6 months were three times more likely to be nonadherent to MDI (OR = 3.03, 95% CI = 1.18-7.82). Forty-three percent of children who were nonadherent to MDI were less likely to have their asthma controlled (OR = 0.43, 95% CI = 0.17-1.06). CONCLUSION: This study revealed that a low level of knowledge among caregivers of asthma patients is linked to inadequate adherence to asthma controller therapy. As medication adherence is crucial for achieving desirable asthma control and improving the quality of life for this population, efforts need to be made to enhance the knowledge level of parents of children with asthma.

An alternative bronchoscopic transparenchymal nodule access by "invisible tunnel" technique under electromagnetic navigation without the transbronchial access tool.

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) is still challenging. We describe a novel method for sampling PPL without bronchial signs by creating invisible tunnel under electromagnetic navigation without the transbronchial access tool (TABT). METHODS: During electromagnetic navigation, we adjust the angle of the edge extended working channel catheter based on the real-time position of the lesion in relation to the locating guide rather than preset route. A biopsy brush or biopsy forceps is used to punch a hole in the bronchial wall. A locating guide is then re-inserted to real-time navigate through the lung parenchyma to the lesion. Safety and feasibility of this method was analyzed. RESULTS: A total of 32 patients who underwent electromagnetic navigation bronchoscopy were retrieved. The mean size of the lesion is 23.1 mm. The mean operative time of all patients was 12.4 min. Ten of the patients did not have a direct airway to the lesion, thus creating an invisible tunnel. For them, the length of the tunnel from the bronchial wall POE to the lesion was 11-30 mm, with a mean length of 16.9 mm and a mean operation time of 14.1 min. Adequate samples were obtained from 32 patients (100%), and the diagnostic yield was 87.5% (28/32). Diagnostic yield of with create the invisible tunnel TBAT was 90% (9/10), and one patient undergone pneumothorax after operation. CONCLUSIONS: This method is feasible and safe as a novel approach sampling pulmonary lesions without bronchial signs, and it further improves current tunnel technique.

Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs.

Gas flow is fundamental for driving tidal ventilation and thus the speed of lung motion, but current bias flow settings to support the preterm lung after birth are without an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not impact lung mechanics, mechanical power or gas exchange compared to those currently used in clinical practice (8-10 L/min). Speed of pressure and volume change during inflation were faster with higher flow rates. Lower flow rates resulted in less bronchoalveolar fluid protein, better lung morphology and fewer detached epithelial cells. Overall, relative to unventilated fetal controls, there was greater protein change using 8-10 L/min, which was associated with enrichment of acute inflammatory and innate responses. Slowing the speed of lung motion by supporting the preterm lung from birth with lower flow rates than currently used clinically resulted in less lung injury without compromising tidal ventilation or gas exchange.

Pediatric chest radiograph interpretation in a real-life setting.

Chest radiography is a frequently used imaging modality in children. However, only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. Most studies were not performed in real-world clinical settings. Our aims were to examine the agreement between emergency department pediatricians and board-certified radiologists in a pediatric real-life setting and to identify clinical risk factors for the discrepancies. Included were children aged 3 months to 18 years who underwent chest radiography in the emergency department not during the regular hours of radiologist interpretation. Every case was reviewed by an expert panel. Inter-observer agreement between emergency department pediatricians and board-certified radiologists was assessed by Cohen's kappa; risk factors for disagreement were analyzed. Among 1373 cases, the level of agreement between emergency department pediatricians and board-certified radiologists was "moderate" (k = 0.505). For radiographs performed after midnight, agreement was only "fair" (k = 0.391). The expert panel identified clinically relevant disagreements in 260 (18.9%) of the radiographs. Over-treatment of antibiotics was identified in 121 (8.9%) of the cases and under-treatment in 79 (5.8%). In a multivariable logistic regression, the following parameters were found to be significantly associated with disagreements: neurological background (p = 0.046), fever (p = 0.001), dyspnea (p = 0.014), and radiographs performed after midnight (p = 0.007). CONCLUSIONS: Moderate agreement was found between emergency department pediatricians and board-certified radiologists in interpreting chest radiographs. Neurological background, fever, dyspnea, and radiographs performed after midnight were identified as risk factors for disagreement. Implementing these findings could facilitate the use of radiologist expertise, save time and resources, and potentially improve patient care. WHAT IS KNOWN: • Only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. • Most studies were not performed in real-world clinical settings. Clinical risk factors for disagreements have not been reported. WHAT IS NEW: • In this study, which included 1373 cases at the emergency department, the level of agreement between interpreters was only "moderate." • The major clinical parameters associated with interpretation discrepancies were neurological background, fever, dyspnea, and interpretations conducted during the night shift.

Modified two-scope technique for transbronchial lung cryobiopsy of peripheral pulmonary lesions.

Bleeding mitigation is an important part of any transbronchial lung cryobiopsy (TBLC) procedure, either for interstitial lung disease (ILD) or peripheral pulmonary lesions (PPL). The two-scope technique has been previously described for ILD and PPL-TBLC, but it has its own limitations and technical and logistical complexities. In this case series, we describe a modified two-scope technique that enhances the conventional two-scope technique by maintaining a small equipment footprint and longer bronchoscopic vision without the need for intra-procedure switching of bronchoscopes. Three cases of PPLs were navigated by standard radial endobronchial ultrasound and biopsied with the 1.1 mm flexible ultrathin cryoprobe. All cases achieved a conclusive diagnosis with adequate specimens for immunohistochemical staining and molecular analysis; only Grade 1 bleeding reported in two cases. The challenges and limitations of this modified two-scope technique were also explored in this series.

Pediatric asthma knowledge: Insights from a Portuguese central hospital study.

BACKGROUND: Asthma is a common chronic condition in children, with parental and child health literacy affecting health outcomes and asthma control. This study examined pediatric asthma knowledge at a Portuguese central hospital and its determinants. METHODS: We conducted a comparative cross-sectional study, applying the Asthma Knowledge Questionnaire (QCSA), answered by adolescents and/or caregivers. The sample was categorized into two groups based on the presence or absence of respiratory conditions, such as asthma or recurrent wheezing, in children. Those with such conditions (Group A) were further divided into two subgroups: those receiving general pediatric care (Group A2) and those receiving specialized care, followed in pulmonology or allergology consultations (Group A1). RESULTS: The study involved 154 participants, predominantly female (74%) with an average age of 31.2 years ( ± 13.4). The average QCSA score was 14.8 ( ± 3.2), and Group A exhibited a statistically higher score, 15.5 points ±3.2 versus Group B, 14.2 points ± 3.2, p = .034. Group A1 achieved significantly better scores (16 points: range 4-21) than Group A2 (14 points: range 9-21) (p = .029). Scores were correlated positively with the duration of specialized follow-up (ρ = .326; p = .027). Asthma knowledge was correlated with the level of education (r = .468; p < .001). The number of wheezing episodes (r = -.466; p < .001) within the past year were associated to QCSA scores. CONCLUSION: In summary, the presence of respiratory condition, the follow-up in specialized appointments and higher levels of education were associated with greater asthma knowledge.

xTrends in racial and ethnic disparities in pediatric lung transplantation in the United States.

BACKGROUND: Racial and ethnic disparities in pediatric lung transplantation (LTx) related to the shifting cystic fibrosis (CF) population receiving highly effective modulator therapy (HEMT) has not been well investigated. METHODS: The UNOS Registry was queried for patients age 1-25 years undergoing bilateral LTx between 1 January 2012 and 31 December 2021. Race and ethnicity were classified as non-Hispanic White, non-Hispanic Black, Hispanic, or none of the above. The primary outcome was posttransplant mortality. Trends in the association between race/ethnicity and mortality were examined using transplant year as a continuous variable and stratifying year based on introduction of HEMT (triple combination therapy) in November 2019. RESULTS: In the study sample (N = 941), 7% of patients were non-Hispanic Black, 15% were Hispanic, and 2% were some other racial or ethnic group. One hundred (11%) received LTx after approval of triple combination therapy, and 407 (43%) died during follow-up. We identified a statistically significant disparity in mortality hazard (hazard ratio: 1.91; 95% confidence interval: 1.31, 2.80) in non-Hispanic Black compared to non-Hispanic White patients in the pre-triple combination therapy era. CONCLUSIONS: We found higher mortality hazard among non-Hispanic Black compared to non-Hispanic White children undergoing LTx in the United States. Further monitoring of LTx outcomes to identify and address disparities is needed in the current era of triple combination therapy for CF.

Transcriptional analysis of primary ciliary dyskinesia airway cells reveals a dedicated cilia glutathione pathway.

Primary ciliary dyskinesia (PCD) is a genetic condition that results in dysmotile cilia. The repercussions of cilia dysmotility and gene variants on the multiciliated cell remain poorly understood. We used single-cell RNA sequencing, proteomics, and advanced microscopy to compare primary culture epithelial cells from patients with PCD, their heterozygous mothers, healthy individuals, and induced pluripotent stem (iPS) cells generated from a PCD patient. Transcriptomic analysis revealed unique signatures in PCD airway cells compared to their mothers and healthy individuals. Gene expression in heterozygous mothers' cells diverged from both control and PCD cells, marked by increased inflammatory and cellular stress signatures. Primary and iPS-derived PCD multiciliated cells had increased expression of glutathione-S-transferases, GSTA2 and GSTA1, as well as NRF2 target genes, accompanied by elevated levels of reactive oxygen species (ROS). Immunogold labeling in human cilia and proteomic analysis of the ciliated organism, Chlamydomonas reinhardtii, demonstrated that GSTA2 localizes to motile cilia. Loss of human GSTA2 and C. reinhardtii GSTA resulted in slowed cilia motility pointing to local cilia regulatory roles. Our findings identify cellular responses unique to PCD variants and independent of environmental stress and uncover a dedicated ciliary GSTA2 pathway essential for normal motility that may be a therapeutic target.

Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis.

Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed 2 distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug-related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing patients with ILD, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a noninvasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.

Innovations in Childhood Interstitial and Diffuse Lung Disease.

Children's interstitial and diffuse lung diseases (chILDs) are a heterogenous and diverse group of lung disorders presenting during childhood. Infants and children with chILD disorders present with respiratory signs and symptoms as well as diffuse lung imaging abnormalities. ChILD disorders are associated with significant health care resource utilization and high morbidity and mortality. The care of patients with chILD has been improved through multidisciplinary care, multicenter collaboration, and the establishment of patient research networks in the United Stated and abroad. This review details past and current innovations in the diagnosis and clinical care of children with chILD.

Clinical Outcomes Following SARS-CoV-2 Infection in Pediatric Cystic Fibrosis Patients.

Background Cystic fibrosis (CF) is a genetic disorder of the cystic fibrosis transmembrane conductance regulator chloride channel that leads to impaired mucus clearance in the airways, which leads to deteriorations in lung function and chronic respiratory infection. These effects of CF contribute to the hypothesis that patients with CF may be at increased risk of complications when they catch coronavirus disease 2019 (COVID-19), which swept the world in a global pandemic starting in 2019. Overall, however, the role of CF in COVID-19 has not been well studied, particularly in pediatric patients. Methods In this retrospective review, pediatric patients with CF who contracted COVID-19 (3/1/2020-3/1/2023) (N=69) were compared to two equally sized control cohorts of patients with only CF or COVID-19 matched based on demographics and clinical baselines. Occurrences of adverse outcomes (emergency room visits, hospitalizations, CF pulmonary exacerbations, etc.) were assessed for each subject. The mean percentage of predicted forced expiratory volume in 1 second (FEV1%pred) was also assessed for CF patients. Fisher's exact test assessed differences between the proportions of subjects who experienced each outcome. Independent two-variable t-testing assessed mean FEV1%pred differences. Analysis was conducted using IBM SPSS Statistics for Windows, Version 29 (Released 2023; IBM Corp., Armonk, New York, United States) with a significance α=0.05. Ad hoc power analysis was conducted using G*Power v3.1. Results Overall, CF/COVID subjects fared similarly to control groups without either CF or COVID-19 history, including among subgroups stratified based on baseline respiratory function, P. aeruginosa colonization status, and COVID-19 vaccination status. One notable finding was that CF/COVID subjects experienced significantly fewer pulmonary exacerbations compared to CF-only subjects (p=0.004).  Conclusion In conclusion, pediatric CF patients performed similarly to their peers without CF with regard to COVID-19 and generally did not demonstrate significant deteriorations in pulmonary function following infection. Lower incidence of pulmonary exacerbations in CF/COVID subjects could be explained by stringent monitoring by parents, quarantine, or close pulmonology follow-up. These findings will provide guidance on management and care for pediatric CF patients with COVID-19.

Transbronchial lung cryobiopsy under real-time radial EBUS: First report on a novel twist of the classical technique.

Transbronchial lung cryobiopsy (TBLC) is a relatively new technique for obtaining lung biopsies, known for being the least invasive method while offering a high diagnostic yield, a favourable safety profile, and a significant reduction in morbidity, mortality, and hospital stay length compared to surgical lung biopsy. Radial-EBUS (r-EBUS) represent a cornerstone modality for accessing 'invisible' peripheral pulmonary lesions. However, a major drawback of these techniques is the lack of 'real-time' visualization of the biopsy being obtained. In this case report, we present a young woman who was referred to us with a cough, haemoptysis, and a non-resolving lung consolidation. She underwent TBLC under real-time rEBUS guidance. This clinical case demonstrates that, in specific clinical scenarios, TBLC with real-time rEBUS is an excellent diagnostic tool.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Targeting CEBPA to restore cellular identity and tissue homeostasis in pulmonary fibrosis.

Fibrosis in the lung is thought to be driven by epithelial cell dysfunction and aberrant cell-cell interactions. Unveiling the molecular mechanisms of cellular plasticity and cell-cell interactions is imperative to elucidate lung regenerative capacity and aberrant repair in pulmonary fibrosis. By mining publicly available RNA-seq datasets, we identified loss of CCAAT enhancer-binding protein alpha (CEBPA) as a candidate contributor to idiopathic pulmonary fibrosis (IPF). We used conditional knockout mice, scRNA-seq, lung organoids, small-molecule inhibition and novel gene manipulation methods to investigate the role of CEBPA in lung fibrosis and repair. Long term (6 month+) of Cebpa loss in AT2 cells caused spontaneous fibrosis and increased susceptibility to bleomycin-induced fibrosis. Cebpa knockout in these mice significantly decreased AT2 cell numbers in the lung and reduced expression of surfactant homeostasis genes, while increasing inflammatory cell recruitment as well as upregulating S100a8/a9 in AT2 cells. In vivo treatment with an S100A8/A9 inhibitor alleviated experimental lung fibrosis. Restoring CEBPA expression in lung organoids ex vivo and during experimental lung fibrosis in vivo rescued CEBPA deficiency-mediated phenotypes. Our study establishes a direct mechanistic link between CEBPA repression, impaired AT2 cell identity, disrupted tissue homeostasis, and lung fibrosis.

Exploring explainable AI features in the vocal biomarkers of lung disease.

This review delves into the burgeoning field of explainable artificial intelligence (XAI) in the detection and analysis of lung diseases through vocal biomarkers. Lung diseases, often elusive in their early stages, pose a significant public health challenge. Recent advancements in AI have ushered in innovative methods for early detection, yet the black-box nature of many AI models limits their clinical applicability. XAI emerges as a pivotal tool, enhancing transparency and interpretability in AI-driven diagnostics. This review synthesizes current research on the application of XAI in analyzing vocal biomarkers for lung diseases, highlighting how these techniques elucidate the connections between specific vocal features and lung pathology. We critically examine the methodologies employed, the types of lung diseases studied, and the performance of various XAI models. The potential for XAI to aid in early detection, monitor disease progression, and personalize treatment strategies in pulmonary medicine is emphasized. Furthermore, this review identifies current challenges, including data heterogeneity and model generalizability, and proposes future directions for research. By offering a comprehensive analysis of explainable AI features in the context of lung disease detection, this review aims to bridge the gap between advanced computational approaches and clinical practice, paving the way for more transparent, reliable, and effective diagnostic tools.