Daily Respiratory Research Analysis

BACKGROUND: The clinical value of shotgun metagenomic next-generation sequencing (mNGS) in improving the detection rates of respiratory pathogens is well-established. However, mNGS is complex and expensive. This study designed and evaluated the performance of targeted NGS (tNGS) in diagnosing respiratory infections. METHODS: We retrospectively included samples from 281 patients with lower respiratory tract infections to establish thresholds of pathogens. Subsequently, target pathogens were selected and a probe hybridization system was established. The performance and clinical manifestations of tNGS for 306 pathogens were evaluated using clinical and simulated samples. RESULTS: The tNGS method took 16 h with sequencing data sizes of 5 M reads. The limit-of-detection of tNGS was 100-200 CFU/mL, respectively. Bioinformatics simulation confirmed the method's high specificity and robustness. In 281 patients of clinical validation cohort, tNGS exhibited a sensitivity of 97.73% and specificity of 75.41% compared to the composite reference standard, which notably surpasses those of culture-based and conventional microbiological methods (CMT). In detecting bacterial and viral infection, tNGS demonstrated superior sensitivity relative to CMT. Notably, 61.40% of target viruses were subtype-resolved with the initial establishment of reliable typing cutoffs, with the subtyping results being completely consistent with the PCR results. tNGS allowed for concurrent identification of antimicrobial resistance (AMR) markers and viral subtyping. 80.56% of AMR markers identified by tNGS were consistent with antimicrobial susceptibility testing. CONCLUSION: This research established the robust performance of our tailored tNGS assay in the simultaneous detection of DNA and RNA pathogens, underscoring its prospective suitability for widespread use in clinical diagnostics.

INTRODUCTION: Although several potential respiratory and cardiovascular health effects of e-cigarettes have been reported, their association with incident cardiometabolic conditions remains unclear. AIMS AND METHODS: We used longitudinal data from the All of Us research program to investigate the association between current exclusive e-cigarette use (EE), exclusive combustible cigarette use (ECC), and dual use (DU) with incident cardiometabolic conditions, including hypertension, type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD), using Cox regression analyses adjusted for age, sex, race and ethnicity, and body mass index. ECC use was used as a positive control to validate our methodology and findings. RESULTS: Among 249 190 individuals (67.2% female, 52.0% non-Hispanic White, 21.5% non-Hispanic Black) followed for 3.7-3.9 years, EE, compared with nonuse, was not significantly associated with hypertension (1.01 [95% CI 0.83 to 1.23]), T2DM (0.88 [0.66-1.16]), ASCVD (1.05 [0.59-1.86]), or HF (0.82 [0.47-1.41]), but was significantly associated with COPD (2.29 [1.42-3.71]). Among individuals aged 30-70 years, EE was significantly associated with hypertension (1.39 [1.09-1.77]). ECC and DU were strongly associated with all outcomes, with DU having higher point estimates but overlapping confidence intervals compared to ECC for all outcomes except ASCVD (2.18 [1.82 to 2.62]) where risk with DU appeared higher. CONCLUSION: We demonstrated a significant longitudinal association between exclusive e-cigarette use and COPD, and hypertension only among individuals aged 30-70 years. ECC and DU were strongly associated with all conditions, with DU potentially associated with higher ASCVD risk. These findings highlight some potential risks of e-cigarette use and provide context to inform advisories and regulatory policies on novel products on their health risks. IMPLICATIONS: These findings help to clarify the potential risks associated with e-cigarette use. Understanding these risks can aid the Food and Drug Administration in developing regulatory frameworks for tobacco products.

OBJECTIVES: Transbronchial lung cryobiopsy (TBLC) has been identified to be a new technique to diagnosis interstitial lung disease (ILD). The study was conducted to investigate the safety and the diagnostic accuracy of TBLC contrast with transbronchial lung biosy (TBLB) in patients with ILD. METHODS: In a cross-sectional and comparative study, patients with suspected ILD who underwent TBLC or TBLB were evaluated from June 2018 to September 2022 in Nanjing drum tower hospital. TBLC and TBLB procedure details and clinical multidisciplinary discussion (MDD) diagnosis based on clinical, radiological, and histopathological information were retrospectively analyzed. Diagnostic yield and complications of TBLC and TBLB were evaluated. RESULTS: 187 patients who underwent TBLC and 176 patients who underwent TBLB following a standardized protocol were enrolled. The diagnostic yield of TBLC and TBLB in patients with ILD were 85.0% and 63.1%, respectively. In TBLC, 162 patients (86.6%) had no or mild bleeding and 25 patients (13.4%) had moderate bleeding. None of the patients had severe bleeding and the rate of pneumothorax was 14.4%. Comparatively, pooled incidences of complications were 91.5% for no or mild bleeding, 8.5% for moderate bleeding and 5.1% for pneumothorax after TBLB. There was no difference in the occurrence of bleeding among TBLC group and TBLB group. CONCLUSIONS: This study indicated that the clinical applicability of TBLC in ILD diagnostic algorithms, with a diagnostic yield of 85.0% and an acceptable safety profile.