ABSTRACT
BACKGROUND: Monocytes play a crucial role in innate immune responses for host defense, however, their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lungs of COPD patients. METHODS: Using flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes isolated from the peripheral blood of patients with COPD was also examined. CD45+CD206-CD14+IL-6Rhi and CD45+CD206-CD14+IL-6R-/lo cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate the IL-6 responsiveness of IL-6R+ monocytes. RESULTS: The number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, whereas CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced changes in the expression of genes linked to chemotaxis and organism development. CONCLUSION: In patients with COPD, CD14+IL-6Rhi monocytes are increased in lung tissues compared to those in CNS. They exhibit a transcriptome profile different from that of CD14+IL-6R-/lo monocytes.
Subject(s)
Lung , Monocytes , Pulmonary Disease, Chronic Obstructive , Receptors, Interleukin-6 , Humans , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/genetics , Monocytes/metabolism , Monocytes/immunology , Receptors, Interleukin-6/genetics , Receptors, Interleukin-6/metabolism , Lung/metabolism , Male , Interleukin-6/metabolism , Interleukin-6/genetics , Lipopolysaccharide Receptors/metabolism , Aged , Female , Middle Aged , Gene Expression , Flow Cytometry , THP-1 CellsABSTRACT
Herein, we report a case of Hermansky-Pudlak syndrome (HPS) in which respiratory symptoms improved with pirfenidone treatment. A 43-year-old Japanese woman with oculocutaneous albinism presented with a cough and dyspnea. High-resolution computed tomography revealed areas of reticular and frosted lung opacities. The diagnosis of HPS was confirmed by a prolonged bleeding time and HPS1 gene mutation. Generally, there is no effective treatment for interstitial pneumonia associated with HPS except for lung transplantation. In the present case, the cough and dyspnea improved with pirfenidone administration. Therefore, clinicians should administer pirfenidone in challenging transplantation cases and during the waiting period for transplantation.
ABSTRACT
Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. However, subpopulations of AMs participating in chronic inflammation have been poorly characterized. We previously reported that Siglec-1 expression on AMs, which is important for bacteria engulfment, was decreased in COPD. Here, we show that Siglec-1-negative AMs isolated from COPD lung tissues exhibit a proinflammatory phenotype and are associated with poor clinical outcomes in patients with COPD. Using flow cytometry, we segregated three subsets of AMs based on the expression of Siglec-1 and their side scattergram (SSC) and forward scattergram (FSC) properties: Siglec-1+SSChiFSChi, Siglec-1-SSChiFSChi, and Siglec-1-SSCloFSClo subsets. The Siglec-1-SSCloFSClo subset number was increased in COPD. RNA sequencing revealed upregulation of multiple proinflammatory signaling pathways and emphysema-associated matrix metalloproteases in the Siglec-1-SSCloFSClo subset. Gene set enrichment analysis indicated that the Siglec-1-SSCloFSClo subset adopted intermediate phenotypes between monocytes and mature alveolar macrophages. Functionally, these cells produced TNF-α, IL-6, and IL-8 at baseline, and these cytokines were significantly increased in response to viral RNA. The increase in Siglec-1-negative AMs in induced sputum is associated with future exacerbation risk and lung function decline in patients with COPD. Collectively, the novel Siglec-1-SSCloFSClo subset of AMs displays proinflammatory properties, and their emergence in COPD airways may be associated with poor clinical outcomes.NEW & NOTEWORTHY Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. We find that Siglec-1-negative alveolar macrophages have a wide range of proinflammatory landscapes and a protease-expressing phenotype. Moreover, this subset is associated with the pathogenesis of COPD and responds to viral stimuli.
Subject(s)
Macrophages, Alveolar , Pulmonary Disease, Chronic Obstructive , Sialic Acid Binding Ig-like Lectin 1 , Aged , Female , Humans , Male , Middle Aged , Cytokines/metabolism , Inflammation/metabolism , Inflammation/pathology , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/pathology , Macrophages, Alveolar/immunology , Phenotype , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/immunology , Sialic Acid Binding Ig-like Lectin 1/metabolismABSTRACT
OBJECTIVES: Over half of Australia's disease burden is due to morbidity, predominantly chronic conditions. Health-related quality of life instruments provide measures of morbidity and health status across different dimensions with EQ-5D being one of the most widely used. This study reports EQ-5D-5L general population norms for Queensland, Australia using the recently published Australian value set. METHODS: Population survey results from cross-sectional computer-assisted telephone interviews for Queensland adults in 2022 and 2023 were analyzed. EQ-5D-5L, as well as modifiable risk factors and sociodemographic data were collected. Using the recently published final Australian EQ-5D-5L value set, mean utility scores were calculated for Queensland, as well as by sociodemographic characteristics, including remoteness and socioeconomic area-based measures, and modifiable risk factors, such as smoking and body mass index. Results were combined with life tables to estimate quality-adjusted life expectancy (QALE) for subgroups with different lifestyles. RESULTS: The EQ-5D utility score for the Queensland adult population was 0.916. Smoking daily, being obese or older in age, or living in the most disadvantaged socioeconomic area were associated with lower mean scores. QALE was 6.1 and 7.9 years shorter than the life expectancy for Queensland males and females, respectively, but generally, those who reported having healthier lifestyles had higher mean utility scores and thus longer QALE. CONCLUSIONS: In addition to reporting Queensland EQ-5D-5L general population norms, these results demonstrate potential QALE gains in people following healthier lifestyles. The results support investment in prevention and may motivate further studies in this important area.
Subject(s)
Quality of Life , Quality-Adjusted Life Years , Humans , Adult , Male , Queensland/epidemiology , Female , Middle Aged , Cross-Sectional Studies , Risk Factors , Aged , Young Adult , Sociodemographic Factors , Adolescent , Socioeconomic Factors , Health Status , Life ExpectancyABSTRACT
A 54-year-old woman presented with persistent productive cough, found to have an endobronchial tumor which obstructed the left upper lobe bronchus. Histopathological examination of a transbronchial biopsy of the endobronchial tumor suggested leiomyosarcoma. A positron emission tomography (PET)-CT revealed uterus tumor with moderate uptake of 18F-fluorodeoxyglucose, suggesting uterine malignancies. From the results of histological findings of the resected uterus and the biopsied bronchial specimen, she was diagnosed with uterine leiomyosarcoma and endobronchial metastasis. The systematic use of PET-CT could be useful for patients presenting with tumors that cause endobronchial metastasis of leiomyosarcomas.
ABSTRACT
Cryptosporidium spp. are enteric protozoan parasites that infect a wide range of hosts including humans, and domestic and wild animals. The aim of this study was to molecularly characterize the Cryptosporidium spp. found in calf faeces in Japan. A total of 80 pre-weaned beef and dairy calves' diarrhoeic faecal specimens were collected from nine different prefectures in Japan. A nested polymerase chain reaction targeting the small subunit 18S rRNA and GP60 genes were used to detect the Cryptosporidium genotypes and subtypes. 83.8% (67 out of 80) of the specimens were positive for Cryptosporidium spp.; Cryptosporidium was found in both beef and dairy calves. Cryptosporidium parvum was the predominant species, detected in 77.5% (31/40) of beef calves and 80% (32/40) of dairy calves. Cryptosporidium bovis was also detected, 5.0% (2/40) of dairy calves, and C. ryanae was also found 2.5% (1/40) of dairy calves. One mixed-species infection, 2.5% (1/40) was detected in a beef calf having C. parvum, and C. ryanae. We detected the most common subtype of C. parvum (i.e., IIaA15G2R1), as well as other subtypes (i.e., IIaA14G3R1, IIaA14G2R1, and IIaA13G1R1) that have not previously been detected in calves in Japan. Our results demonstrate the widespread diversity of Cryptosporidium infection in calves in Japan.
Subject(s)
Cattle Diseases/epidemiology , Cryptosporidiosis/epidemiology , Cryptosporidium/isolation & purification , Diarrhea/parasitology , Animals , Cattle , Cattle Diseases/parasitology , Cryptosporidiosis/complications , Cryptosporidiosis/parasitology , Cryptosporidium/classification , DNA, Protozoan/analysis , Female , Japan/epidemiology , Male , Prevalence , RNA, Ribosomal, 18S/analysisABSTRACT
This study aimed to evaluate the effects of live yeast (Saccharomyces cerevisiae) (LY) supplementation on serum oxidative stress biomarkers, antioxidant vitamin levels, and lactation performance in dairy cows during summer. A total of 16 lactating cows weighing 707.5 ± 13.1 kg (mean ± standard error) were enrolled and randomly assigned to either supplemented (n=8) or control group (n=8). In the supplemented group, the cows were administered with LY product at 10 g/day per cow from mid-July to mid-September for 8 weeks. The serum levels of derivatives of reactive oxygen metabolites in the supplemented group were lower (P<0.05) at week 6. The serum retinol and blood glucose concentrations in the supplemented group were higher (P<0.01) at week 8. LY supplementation did not affect physiological responses, such as rectal temperature, respiratory rate, protein and cholesterol metabolism, and lactation performance. During the study period, daily average milk yield decreased in both groups. The reduction rates of milk yield in the supplemented and control groups were 17.6 and 20.0%, respectively. These results suggest that LY supplementation may reduce oxidative stress and improve carbohydrate metabolism in lactating dairy cows during summer.