Modern auscultation, using digital stethoscopes, provides a better solution than conventional methods in sound recording and visualization. However, current digital stethoscopes are too bulky and nonconformal to the skin for continuous auscultation. Moreover, motion artifacts from the rigidity cause friction noise, leading to inaccurate diagnoses. Here, we report a class of technologies that offers real-time, wireless, continuous auscultation using a soft wearable system as a quantitative disease diagnosis tool for various diseases. The soft device can detect continuous cardiopulmonary sounds with minimal noise and classify real-time signal abnormalities. A clinical study with multiple patients and control subjects captures the unique advantage of the wearable auscultation method with embedded machine learning for automated diagnoses of four types of lung diseases: crackle, wheeze, stridor, and rhonchi, with a 95% accuracy. The soft system also demonstrates the potential for a sleep study by detecting disordered breathing for home sleep and apnea detection.

Auscultation with stethoscope has been an essential tool for diagnosing the patients with respiratory disease. Although auscultation is non-invasive, rapid, and inexpensive, it has intrinsic limitations such as inter-listener variability and subjectivity, and the examination must be performed face-to-face. Conventional stethoscope could not record the respiratory sounds, so it was impossible to share the sounds. Recent innovative digital stethoscopes have overcome the limitations and enabled clinicians to store and share the sounds for education and discussion. In particular, the recordable stethoscope made it possible to analyze breathing sounds using artificial intelligence, especially based on neural network. Deep learning-based analysis with an automatic feature extractor and convoluted neural network classifier has been applied for the accurate analysis of respiratory sounds. In addition, the current advances in battery technology, embedded processors with low power consumption, and integrated sensors make possible the development of wearable and wireless stethoscopes, which can help to examine patients living in areas of a shortage of doctors or those who need isolation. There are still challenges to overcome, such as the analysis of complex and mixed respiratory sounds and noise filtering, but continuous research and technological development will facilitate the transition to a new era of a wearable and smart stethoscope.

Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. Methods: This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. Results: The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4⁺CD25⁺CD127^loFoxP3⁺ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4⁺CD25⁺CD127^loFoxP3⁺ Treg cells and PD-1⁺CD4⁺CD25⁺CD127^loFoxP3⁺ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). Conclusion: Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

Recent advancements in spatial transcriptomics (ST) have revolutionized our understanding of the lung’s cellular organization and pathological alterations. By preserving the spatial distribution of gene expression, ST reveals localized immune niches, stromal–epithelial interactions, and disease-associated transcriptional “hotspots” that cannot be captured by conventional sequencing methods alone. In lung cancer, ST-based investigations have delineated distinct tumor microenvironments between tumor cores and invasive fronts, revealing prognostically significant gene signatures and identifying subpopulations with differential responses to immunotherapy and chemotherapy. Similarly, in chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis, ST has mapped the ecosystem, including immune cells, inflammatory mediators, and fibroblast subtypes, of discrete regions within diseased lung tissue, offering mechanistic insights into disease progression and tissue remodeling. In addition, a more recent ST study provides spatial information for where drugs act within tissues. This review highlights the emerging role of spatial transcriptomics in respiratory research, demonstrating its potential to refine disease classification, elucidate mechanisms of therapeutic resistance, and inform spatially guided personalized interventions in respiratory diseases.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

Background: The addition of cryobiopsy to conventional biopsy methods improves the diagnostic yield of peripheral pulmonary lesions. Moreover, cryobiopsy with a guide sheath (GS) provides additional diagnostic benefits. Semi-real-time biopsy can be repeatedly performed using conventional biopsy devices and a GS, and subsequent cryobiopsy can be easily performed at the same location. Recently, a disposable 1.1 mm-diameter ultrathin cryoprobe has been developed and can be used with a 1.95 mm GS in a 2.0 mm working channel. In this study, we evaluated the diagnostic performance of transbronchial lung cryobiopsy (TBLC) with the 1.1 mm cryoprobe and a GS in patients with peripheral pulmonary lesions. Methods: We retrospectively reviewed the medical records of patients who underwent endobronchial ultrasound transbronchial lung biopsy with a guide sheath and TBLC from July 23, 2021 to April 30, 2022 at Chungnam National University Hospital. Results: Of a consecutive series of 229 patients, 199 were included. The diagnostic yields of forceps biopsy and cryobiopsy were 65.3% (130/199) and 84.4% (168/199), respectively, and the total diagnostic yield was 91.5% (182/199) (P20 mm (P=0.026; adjusted OR 3.816) and ‘within’ orientation (P=0.004; adjusted OR 6.174) were associated with a significantly greater overall diagnostic yield. Conclusion: TBLC using an ultrathin cryoprobe and GS markedly improves the diagnostic yield.