Penicillium marneffei disseminates hematogenously and can infect most organs, though infection leading to osteolysis is extremely rare. We describe the clinical and laboratory features, management, and outcomes of patients with penicilliosis marneffei (PSM) with osteolytic lesions. This retrospective study was conducted between January 1, 2003 and May 1, 2014 at the First Affiliated Hospital of Guangxi Medical University. Patients who presented with culture and/or histopathologic proof of disseminated PSM within osteolytic lesions were included. P. marneffei infection was diagnosed in 100 patients (65 HIV-infected and 35 HIV-negative). Fourteen patients, all HIV-negative, (14/35, 40%) had osteolytic lesions. The most common comorbidity was diabetes mellitus, though previous glucocorticoid therapy, β-thalassemia, breast cancer, and Langerhans cell histiocytosis also occurred. Five patients had no comorbidity. Fever, malaise, ostealgia, weight loss, and anemia were the most common symptoms, followed by cutaneous lesions, lymphadenopathy, hepatosplenomegaly, cough, sputum, and stethalgia. Ostealgia, joint pain, and joint disorders were also recorded. White blood cell and neutrophil counts were increased (mean 22.3 ± 7.4 × 109 cells/L; mean 18.84 ± 4.5 × 109 cells/L, respectively). The most common sites were the vertebrae, skull and femur, ribs and ilium, though the clavicle, scapula, humerus, and tibia were also involved. Radiography and computed tomography (CT) showed multiple radiolucencies with moth-eaten bone destruction, periosteal proliferation, bone fracture, and surrounding soft-tissue swelling. Emission CT showed significantly increased uptake in many skeletal regions. Positron emission tomography/CT showed generalized lymphadenopathy, bone metabolic activity, and bone destruction. The 18 F-FDG standard uptake value was increased in the entire skeleton (mean 6.16). Twelve patients received antifungal therapy, four of whom died during treatment, and eight recovered, though four of these eight relapsed within 3–24 months. Two patients discontinued treatment because of severe multiple organ failure and died. Osteolysis is often overlooked in HIV-negative individuals with disseminated P. marneffei infection. However, P. marneffei involving the bone and leading to osteolysis may indicate severe systemic disturbance, and is characterized by a poor prognosis, high recurrence rate, and the need for prolonged antifungal treatment.

Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40⁺ and CD86⁺ mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.

Background and Purpose: Chronic obstructive pulmonary disease (COPD) is proposed to hasten lung aging. Erythromycin protects against oxidative stress and inflammatory responses. However, the potential anti-senescence effect of erythromycin remains disclosed. In the present study, we investigated whether erythromycin influenced oxidative stress-induced cellular senescence and investigated its related mechanisms.Methods: A cigarrete smoke (CS) -induced emphysema mouse model and a H₂O₂-induced premature senescence model in human bronchial epithelial cell line (BEAS-2B) were established. Senescence-related markers (P53, P21 and SA-β-Gal activity), and levels of oxidative stress biomarkers (MDA, SOD and ROS) were measured. Additionally, cells were pretreated with rapamycin (mTOR inhibitor) or erythromycin, and the expression levels of components of the PI3K-mTOR signaling pathway were measured in BEAS-2B cells.Results: Exposed to H₂O₂, increased SA-β-gal activity was observed in BEAS-2B cells suggesting premature senescence. Erythromycin inhibited the expression of P53 and P21 in the CS-induced emphysema mouse model. MDA levels significantly increased and SOD levels decreased in the CS-exposed mice and H₂O₂-induced BEAS-2B cells. Rapamycin and erythromycin significantly suppressed the expression of P53 and P21. Additionally, rapamycin and erythromycin inhibited the PI3K-mTOR signaling pathway.Conclusion: Our findings suggest that erythromycin ameliorates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway. Hence, we establish a theoretical foundation for the clinical application of erythromycin for COPD prevention and treatment.