Introduction This study aimed to evaluate the utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus-infected patients. Methods We conducted a retrospective study. A total of 60 non-human immunodeficiency virus-infected PJP patients and 134 patients diagnosed with non-PJP pneumonia were included. P. jirovecii and other co-pathogens identified by mNGS in bronchoalveolar lavage fluid and/or blood samples were analyzed. Using clinical composite diagnosis as the reference standard, we compared the diagnostic performance of mNGS in PJP with conventional methods, including Gomori methenamine silver staining and serum (1,3)-β-d-glucan. Modifications of antimicrobial treatment for PJP patients after the report of mNGS results were also reviewed. Results mNGS reached a sensitivity of 100% in diagnosing PJP, which was remarkably higher than Gomori methenamine silver staining (25.0%) and serum (1,3)-β-d-glucan (67.4%). The specificity of mNGS (96.3%) significantly surpassed serum (1,3)-β-d-glucan (81.4%). Simultaneous mNGS of bronchoalveolar lavage fluid and blood samples was performed in 21 out of 60 PJP patients, and it showed a concordance rate of 100% in detecting P. jirovecii. Besides, mNGS showed good performance in identifying co-pathogens of PJP patients, among which cytomegalovirus and Epstein-Barr virus were most commonly seen. Initial antimicrobial treatment was modified in 71.7% of PJP patients after the report of mNGS results. Conclusion mNGS is a useful diagnostic tool with good performance for the diagnosis of PJP and the detection of co-pathogens. mNGS of bronchoalveolar lavage fluid and/or blood samples is suggested in patients with presumptive diagnosis of PJP. Blood samples may be a good alternative to bronchoalveolar lavage fluid for mNGS when bronchoscopic examination is not feasible.

Neutrophilic asthma (NA) is a distinct airway inflammation disease with prominent neutrophil infiltration. The role played by neutrophil extracellular traps (NETs) in NA, however, is quite unclear. This study was based on the hypothesis that NETs are responsible for the second neutrophil wave and therefore contribute significantly to inflammation. The proinflammatory effects of NETs were evaluated in vitro and in vivo. Formation of NETs and neutrophil swarming was seen in a mouse model of NA. Additionally, NETs were found to stimulate airway cells to express CXCL1, CXCL2, and CXCL8 via the TLR4/NF-κB pathway, which recruits neutrophils to the inflammation site. Furthermore, prevention of NET formation decreased the recruitment of lung neutrophils and hence reduce neutrophilic inflammation. Additionally, the structural integrity of NETs had no effect on the recruitment of lung neutrophils and neutrophilic inflammation. In NA mice, NETs could trigger airway and alveolar epithelial cells to express chemokines which recruit more neutrophils via activation of the TLR4/NF-κB pathway.

Legionella pneumonia is a relatively rare but extremely progressive pulmonary infection with high mortality. Traditional cultural isolation remains the gold standard for the diagnosis of Legionella pneumonia. However, its harsh culture conditions, long turnaround time, and suboptimal sensitivity do not meet the clinical need for rapid and accurate diagnosis, especially for critically ill patients. So far, pathogenic detection techniques including serological assays, urinary antigen tests, and mass spectrometry, as well as nucleic acid amplification technique, have been developed, and each has its own advantages and limitations. This review summarizes the clinical characteristics and imaging findings of Legionella pneumonia, then discusses the advances, advantages, and limitations of the various pathogenetic detection techniques used for Legionella pneumonia diagnosis. The aim is to provide rapid and accurate guiding options for early identification and diagnosis of Legionella pneumonia in clinical practice, further easing healthcare burden.

Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.

Adults with chronic diseases often experience a decline in their quality of life along with frequent exacerbations. These diseases can cause anxiety and impose a significant economic burden. Self-management is a crucial aspect of treatment outside of the hospital and can improve quality of life and reduce the financial burden resulting from unexpected hospitalizations. With the COVID-19 pandemic, telehealth has become a vital tool for both medical professionals and patients; many in-person appointments have been canceled due to the pandemic, leading to increased reliance on online resources. This article aimed to discuss various methods of chronic disease management, both traditional self-management and modern telehealth strategies, comparing before and after the COVID-19 outbreak and highlighting challenges that have emerged.

Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. Methods: Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. Results: The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. Conclusion: The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ.