The objective of this study was to compare the diagnostic value of galactomannan (GM) detection in bronchoalveolar lavage fluid (BALF) and serum samples from nonneutropenic patients with invasive pulmonary aspergillosis (IPA) and determine the optimal BALF GM cutoff value for pulmonary aspergillosis. GM detection in BALF and serum samples was performed by enzyme-linked immunosorbent assay (ELISA) in 128 patients with clinically suspected nonneutropenic pulmonary aspergillosis between June 2014 and June 2016. On the basis of the clinical and pathological diagnoses, 8 patients were excluded because their diagnosis was uncertain. The remaining 120 patients were diagnosed with either IPA ( n = 37), community-acquired pneumonia (CAP; n = 59), noninfectious diseases ( n = 19), or tuberculosis ( n = 5). At a cutoff optical density index (ODI) value of ≥0.5, the sensitivity of BALF GM detection was much higher than that of serum GM detection (75.68% versus 37.84%; P = 0.001), but there was no significant difference between their specificities (80.72% versus 87.14%; P = 0.286). At a cutoff value of ≥1.0, the sensitivity of BALF GM detection was still much higher than that of serum GM detection (64.86% versus 24.32%; P < 0.001), and their specificities were similar (90.36% versus 95.71%; P = 0.202). Receiver operating characteristic (ROC) curve analysis showed that when the BALF GM detection cutoff value was 0.7, its diagnostic value for pulmonary aspergillosis was optimized, and the sensitivity and specificity reached 72.97% and 89.16%, respectively. BALF GM detection was valuable for the diagnosis of IPA in nonneutropenic patients, and its diagnostic value was superior to that of serum GM detection. The optimal BALF GM cutoff value was 0.7.

Pentraxin 3 (PTX3) plays an important role in resistance to Aspergillus infections. Previous studies have suggested that PTX3 polymorphisms influence the risk of invasive aspergillosis among transplantation recipients. This study investigated the association between PTX3 gene polymorphisms and pulmonary aspergillosis in a chronic obstructive pulmonary disease (COPD) population. We included 173 consecutive inpatients with COPD. Thirty-six case patients were finally diagnosed with pulmonary aspergillosis. Among these, 25 case patients had invasive pulmonary aspergillosis (IPA), and 11 case patients had chronic pulmonary aspergillosis (CPA). Three single nucleotide polymorphisms (SNPs; rs2305619, rs3816527, and rs1840680) in the PTX3 gene were detected by polymerase chain reaction direct sequencing, and their associations with aspergillosis were evaluated. Plasma PTX3 levels were measured by enzyme-linked immunosorbent assay. Three SNPs were consistent with Hardy-Weinberg equilibrium. The recessive model for SNP rs1840680 suggests that the AA homozygote is associated with a higher risk for pulmonary aspergillosis (both IPA and CPA) in COPD patients. However, for genotypic and allele frequencies of rs2305619 and rs3816527, no association was observed. The distribution of haplotypes (rs2305619 and rs3816527) also showed no significant differences. Plasma PTX3 levels significantly increased in IPA patients. In the IPA group, the rs1840680 AA genotype subjects showed lower plasma PTX3 levels than those harboring AG and GG genotypes. This study showed a significant association between PTX3 rs1840680 polymorphisms and the susceptibility of pulmonary aspergillosis in patients with COPD. Plasma PTX3 levels may be potentially used as indicators for the diagnosis of IPA in COPD patients.

Despite antifungal treatment, chronic pulmonary aspergillosis (CPA) is associated with substantial morbidity and mortality. We conducted a systematic review and meta-analysis to evaluate rates of mortality and its predictors in CPA. A systematic literature search was conducted across MEDLINE (PubMed), Scopus, Embase, and Web of Science to identify studies in English, reporting mortality in CPA, from database inception to Aug 15, 2023. We included clinical studies, observational studies, controlled trials, and abstracts. Case reports, animal studies, letters, news, and literature reviews were excluded. Authors of studies published since 2016 were also contacted to obtain anonymised individual patient data (IPD); for other studies, summary estimates were extracted. Subgroup analysis was done for differences in overall 1-year and 5-year mortality, data source, study design, risk of bias, country, Human Development Index, age groups, and the underlying lung disease. We used random-effects meta-analyses to estimate pooled mortality rates. Subgroup analyses and meta-regression were done to explore sources of heterogeneity. One-stage meta-analysis with a stratified Cox proportional hazards model was used to estimate the univariable and hazards for mortality, adjusting for age, sex, type of CPA, treatment, and underlying pulmonary comorbidities. This study was registered with PROSPERO (CRD42023453447). We included 79 studies involving 8778 patients in the overall pooled analysis and 15 studies involving 1859 patients in the IPD meta-analysis. Pooled mortality (from 70 studies) was estimated at 27% overall (95% CI 22-32; I² =95·4%), 15% at 1 year (11-19; I² =91·6%), and 32% at 5 years (25-39; I² =94·3%). Overall mortality in patients with CPA with pulmonary tuberculosis as the predominant predisposing condition was 25% (16-35; I² =87·5%; 20 studies) and with chronic obstructive pulmonary disease was 35% (22-49; I² =89·7%; 14 studies). Mortality in cohorts of patients who underwent surgical resection was low at 3% (2-4). In the multivariable analysis, among predisposing respiratory conditions, pulmonary tuberculosis history had the lowest mortality hazard (relative to an absence of the disease at baseline), whereas worse outcomes were seen with underlying malignancy; subacute invasive pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis subtypes of CPA were also significantly associated with increased mortality relative to simple aspergilloma on multivariable analysis. Mortality hazard increased by 25% with each decade of age (adjusted hazard ratio 1·25 [95% CI 1·14-1·36], p<0·0001). CPA is associated with substantial mortality. Advancing age, CPA subtype, and underlying comorbidities are important predictors of mortality. Future studies should focus on identifying appropriate treatment strategies tailored to different risk groups. None.

Disordered tumor cell metabolism is involved in the process of tumorigenesis. Proline metabolism is of critical importance for tumor cells, and pyrroline‑5‑carboxylate reductase 1 (PYCR1), a key proline biosynthesis enzyme, has been reported to be overexpressed in prostate cancer and to promote tumor cell growth in breast cancer. The present study investigated the relationship between PYCR1 and non‑small cell lung cancer (NSCLC). The results revealed that PYCR1 was overexpressed in NSCLC tumor tissues compared with adjacent normal tissues. High PYCR1 expression was associated with poor prognosis in patients with NSCLC. Following knockdown of PYCR1 by small interfering RNA, cell proliferation was revealed to be significantly inhibited and the cell cycle was arrested, while apoptosis was increased in SPC‑A1 and H1703 NSCLC cells. Furthermore, the silencing of PYCR1 resulted in the downregulation of expression of the cell cycle regulator cyclin D1, the regulator of the mitochondrial apoptotic pathway B‑cell lymphoma‑2, and B‑cell lymphoma‑extra large. The results of the present study indicated the involvement of PYCR1 in the proliferation and apoptosis of NSCLC. Therefore, PYCR1 may be a novel therapeutic target for inhibiting cell proliferation in lung cancer.

Background: Differentiating Pneumocystis jirovecii infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage fluid (BAL) metagenomic next-generation sequencing (mNGS) and serum 1,3-β-D-glucan (BDG) tests in differentiating colonisation and infection with P. jirovecii.Methods: From January 2018 to March 2021, 47 patients were enrolled in this study at the Hunan Provincial People’s Hospital. The final diagnosis was used as a reference, and cases were classified into the P. jirovecii pneumonia (PJP) group or the P. jirovecii colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.Result: The fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 vs. 5.61 ± 0.88 in the PJP and PJC groups, respectively (P < 0.0001). BDG also significantly differed between the two groups, with a median titre of 233.60 ± 39.65 pg/ml in the PJP group and 68.48 ± 19.21 pg/ml in the PJC group (P = 0.0006). The area under the curve was 0.973 (95%CI: 0.868–1.007) for mNGS of the BAL and 0.879 (95%CI: 0.769–0.989) for the serum BDG. The optimal threshold value for discriminating P. jirovecii infection from colonisation appeared to be 14 reads (sensitivity, 83.3%; specificity, 95.7%; positive likelihood ratio, 19.2) and BDG = 88.6 pg/ml (sensitivity, 79.2%; specificity, 92.9%; positive likelihood ratio, 18.2). No correlation between mNGS reads and the BDG titre was found in mNGS-positive patients (r² = 0.0076, P = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.Conclusion: BAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of P. jirovecii.