Early-onset meningitis associated with atezolizumab treatment for non-small cell lung cancer: case report and literature review.

Immune checkpoint inhibitors (ICIs) have improved the overall survival of many patients with advanced cancers. However, unlike cytotoxic and targeted drugs, ICIs may cause various immune-related adverse events (irAEs). Among these irAEs, autoimmune meningitis is very rare. Here, we report a case of early-onset, atezolizumab-induced meningitis after administration of one dose of atezolizumab. A 56-year-old man with lung adenocarcinoma had received seventh-line treatment with atezolizumab when he experienced dysarthria. Blood examinations, including the measurement of electrolytes, glucose, and organ functions, were unremarkable, but enhanced head magnetic resonance imaging T1-weighted images showed meningeal enhancement. Although cerebral spinal fluid (CSF) examinations revealed elevated lymphocyte and protein levels, no cancer cells were detected in the CSF. CSF cultures and serological tests, including polymerase chain reaction for herpes simplex virus, were negative. The patient was therefore diagnosed with atezolizumab-triggered autoimmune meningitis. With steroid treatment, the patient's clinical and neurological state improved immediately and he recovered to baseline conditions. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of autoimmune meningitis.

Evaluation of the severity of small airways obstruction and alveolar destruction in chronic obstructive pulmonary disease.

BACKGROUND: Airflow limitation in COPD is caused by a mixture of small airways obstruction and alveolar destruction. OBJECTIVE: To evaluate the contributions of these factors to airflow limitation through measurement of two biomarkers, pentosidine and vascular endothelial growth factor (VEGF), which reflect pathology or function of the lower respiratory tract of COPD. METHODS: We measured pentosidine and VEGF levels in induced sputum from 23 non-smokers, 26 smokers without COPD, and 43 smokers with COPD. We evaluated the correlations of two biomarkers levels with the grade of low attenuation area (LAA) in high-resolution computed tomographic scans and the Δ N2 from the nitrogen washout curve. RESULTS: Pentosidine levels were significantly higher in smokers with COPD than in non-smokers and smokers without COPD. In contrast, VEGF levels were significantly lower in smokers without COPD than in non-smokers, and further decreased in smokers with COPD. In the four-stage classification of LAA grading, pentosidine levels steeply increased from grade I to Ⅳ, while VEGF levels decreased with increasing severity of LAA grade. Pentosidine levels were positively correlated with Δ N2 in COPD patients with mild emphysema. In contrast, VEGF levels were inversely correlated with Δ N2 in COPD patients with severe emphysema. CONCLUSION: Pentosidine level is responsible for the severity of small airways obstruction, while VEGF level reflects the magnitude of alveolar destruction. Thus, simultaneous measurement of pentosidine and VEGF levels may be a promising approach to discriminate the severity of small airways obstruction and alveolar destruction in the lower respiratory tract of COPD.