Introduction. The diagnosis of pulmonary infection and the identification of pathogens are still clinical challenges in immunocompromised patients. Metagenomic next-generation sequencing (mNGS) has emerged as a promising infection diagnostic technique. However, its diagnostic value in immunocompromised patients needs further exploration. Purposes. This study was to evaluate the diagnostic value of mNGS compared with comprehensive conventional pathogen tests (CTs) in the etiology of pneumonia in immunocompromised patients and immunocompetent patients. Methods. We retrospectively reviewed 53 patients who were diagnosed with pneumonia from May 2019 to June 2021. There were 32 immunocompromised patients and 21 immunocompetent patients with pneumonia who received both mNGS and CTs. The diagnostic performance was compared between mNGS and CTs in immunocompromised patients, using the composite diagnosis as the reference standard. And, the diagnostic value of mNGS for mixed infections was further analyzed. Results. Compared to immunocompetent patients, the most commonly pathogens, followed by Cytomegalovirus, Pneumocystis jirovecii and Klebsiella pneumoniae in immunocompromised patients. Furthermore, more mixed infections were diagnosed, and bacterial-fungal-virus coinfection was the most frequent combination (43.8%). mNGS can detect more types of pathogenic microorganisms than CTs in both groups (78.1% vs. 62.5%, and 57.1% vs. 42.9%, ). The overall diagnostic positive rate of mNGS for pathogens was higher in immunocompromised patients ( ). In immunocompromised patients, a comparable diagnostic accuracy of mNGS and CTs was found for bacterial, fungal, and viral infections and coinfection. mNGS had a much higher sensitivity for bacterial infections (92.9% vs. 50%, ) and coinfections (68.8% vs. 48.3%, ), and it had no significant advantage in the detection of fungal infections, mainly due to the high sensitivity for Pneumocystis jirovecii in both groups. Conclusion. mNGS is more valuable in immunocompromised patients and exhibits apparent advantages in detecting bacterial and mixed infections. It may be an alternative or complementary diagnostic method for the diagnosis of complicated infections in immunocompromised patients.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria–fungi–virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Background: Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients. Methods: Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood. Results: Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs (p < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs (p < 0.01) was detected in COPD patients. The expression of PD-1 on CD4⁺ Tcells and Tregs, but not CD8⁺Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs (p < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, p < 0.0001) and CTLA-4 (r = 0.42, p = 0.0014) on Tregs in COPD. Conclusion: The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD.

Background: The programmed cell death protein 1 (PD‐1) inhibitor, as one of the immune checkpoint inhibitors (ICIs), is the standard treatment for advanced lung cancer. However, immune‐related adverse events (irAEs) remain poorly understood toxicities. It is unclear whether frailty plays a role in the occurrence of irAEs. Thus, we assess whether irAEs occur more often in frail patients than in non‐frail patients according to the Frailty Index (FI).Methods: A retrospective study was conducted. Medical records from lung cancer patients treated with PD‐1 inhibitors (Sintilimab, Camrelizumab, Tislelizumab, and Pembrolizumab) at Peking University First Hospital (May 2018–June 2022). Patients were categorized into non‐frail and frail groups according to a cut‐point of 0.25 by FI. The FI calculation included 28 baseline variables, all of which were health deficits measured by questionnaires and body measurements.Results: The statistical analysis included 114 advanced lung cancer patients. The median age was 66 years, and the male/female ratio was 4.7:1 (94/20). Approximately 39 (34%) were classified as frail. PD‐1 inhibitor‐related adverse events occurred in 17.5% of patients, and 6.1% experienced irAEs of grade ≥3. There was no significant difference in the occurrence of irAEs (14.7% vs. 23.1%, p = 0.26), grade ≥ 3 irAEs (5.3% vs. 7.7%, p = 0.93), and treatment discontinuation due to irAEs (12.0% vs. 17.9%, p = 0.39) between non‐frail and frail patients. However, frail patients are more likely to have more than one type of irAEs and are more possibly to have checkpoint inhibitor pneumonitis (CIP) than non‐frail patients when they use PD‐1 inhibitors (p < 0.05). Frail patients had a longer hospital stay (6 vs. 3 days, p = 0.01).Conclusions: Frailty is not associated with severe irAEs, but is related to CIP. Meanwhile, it predicts more than one type of irAEs and a longer hospital stay. Frailty screening has added value to the decision‐making process for frail patients eligible for PD‐1 inhibitors.

Background: Nontuberculous mycobacteria pulmonary disease (NTM-PD) frequently coexists with bronchiectasis. This study aimed to compare clinical profiles and identify risk factors between NTM-PD patients with/without bronchiectasis and explore differences between rapid- vs slow-growing non-tuberculous mycobacteria (NTM) species. Methods: A retrospective analysis was conducted on patients diagnosed with NTM-PD and admitted to Beijing Tsinghua Changgung Hospital between April 2021 and April 2025. Among 496 inpatients with pulmonary diseases who underwent metagenomic next-generation sequencing (mNGS) analysis of bronchoalveolar lavage fluid, NTM were identified in 57 patients. Ultimately, 43 of these cases were confirmed and diagnosed as having NTM-PD. Relevant clinical data were collected, and the association between each variable and adverse outcomes was assessed using univariate and multivariate logistic regression analyses. Results: Among the 43 confirmed NTM-PD patients, 24 had concurrent bronchiectasis (NTM-PD with bronchiectasis group) and 19 did not (NTM-PD group). In terms of baseline characteristics, the NTM-PD with bronchiectasis had a significantly higher proportion of females (79.17% vs 31.57%, P=0.002) and lower BMI (19.46 vs 22.46, P=0.023). Slow-growing NTM (SGM, mainly Mycobacterium avium complex [MAC]) was more common in the NTM-PD with bronchiectasis group (70.83% vs 31.58%, P=0.010); rapid-growing NTM (RGM, mainly M. abscessus) was more prevalent in the NTM-PD group (57.89% vs 20.83%, P=0.013). The positive rate of T-SPOT.TB in the NTM-PD group was higher than that in the NTM-PD with bronchiectasis group (47.37% vs 8.33%, P=0.010). Multivariate logistic regression identified female sex as an independent risk factor for NTM-PD complicated with bronchiectasis (OR=17.784, 95% CI: 1.103– 286.857, P=0.042), while T-SPOT.TB was not (OR=0.047, 95% CI: 0.002– 1.341, P=0.074). Conclusion: Female sex is an independent risk factor for NTM-PD complicated with bronchiectasis. NTM-PD patients with bronchiectasis are more likely to be infected with SGM (especially MAC), while those without bronchiectasis tend to have RGM (especially M. abscessus) infection.