Overstretching alveolar epithelial type II cells decreases surfactant secretion via actin polymerization and intracellular trafficking alteration.

Pulmonary surfactant is essential for maintaining proper lung function. Alveolar epithelial type II (AE2) cells secrete surfactants via lamellar bodies (LBs). In tidal loading during each breath, the physiological cyclic stretching of AE2 cells promotes surfactant secretion. Excessive stretching inhibits surfactant secretion, which is considered to contribute to the development of lung damage. However, its precise mechanism remains unknown. This study tested whether actin polymerization and intracellular transport are required for pulmonary surfactant secretion and the association of actin polymerization and transport in identical human AE2-derived A549 cells using live-cell imaging, not in the bulk cells population. We found that overstretching approximately doubled actin polymerization into filaments (F-actin) and suppressed LB secretion by half in the fluorescent area ratio, compared with physiological stretching (F-actin: 1.495 vs 0.643 (P < 0.01); LB: 0.739 vs 0.332 (P < 0.01)). An inhibitor of actin polymerization increased LB secretion. Intracellular tracking using fluorescent particles revealed that cyclic stretching shifted the particle motion perpendicularly to the direction of stretching according to the orientation of the F-actin (proportion of perpendicular axis motion prior particle: 0h 40.12 % vs 2h 63.13 % (P < 0.01)), and particle motion was restricted over time in the cells subjected to overstretching, indicating that overstretching regulates intracellular transport dynamics (proportion of stop motion particle: 0h 1.01 % vs 2h 11.04 % (P < 0.01)). These findings suggest that overstretching changes secretion through the cytoskeleton: overstretching AE2 cells inhibits pulmonary surfactant secretion, at least through accelerating actin polymerization and decreasing intracellular trafficking, and the change in actin orientation would modulate intracellular trafficking.

A case of allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia successfully treated with benralizumab.

We herein report a case of allergic bronchopulmonary aspergillosis (ABPA) with marked eosinophilia and high attenuation mucus (HAM) on chest computed tomography (CT), which demonstrated a rapid and remarkable improvement with benralizumab treatment. A 67-year-old Japanese woman, who was diagnosed with asthma at the age of 64 years, was admitted with dyspnea. Her blood test results showed marked eosinophilia (peripheral blood eosinophil count 24403/µL) and elevated serum IgE levels. Chest CT also revealed ground-glass opacity. Sputum cytology detected filamentous fungi, suggesting an infection with Aspergillus spp. Based on these findings, ABPA was diagnosed. Following systemic corticosteroid treatment, her respiratory symptoms and chest radiography findings showed improvements. However, with the gradual tapering and eventual discontinuance of the corticosteroid therapy, a concomitant increase in the peripheral blood eosinophils and a recurrence of the clinical symptoms, was observed. In addition, her pulmonary function decreased and chest CT revealed worsened bronchial mucus plugs. To control the asthma with ABPA exacerbation, benralizumab was administered. Following treatment with benralizumab, the patient's asthmatic symptoms improved, together with a decrease in her peripheral eosinophil count. Mucus plugs were no longer visible on chest CT. Pulmonary function test result also showed a remarkable improvement. There was no relapse of dyspnea and no reappearance of the mucus plugs. This case suggests that benralizumab may be a suitable treatment option for patients with ABPA with marked eosinophilia and HAM on chest CT.

Remarkable response to nivolumab in sarcomatoid malignant pleural mesothelioma with high PD-L1.

We report herein a case of sarcomatoid malignant pleural mesothelioma (MPM) with high PD-L1 expression who was refractory to standard chemotherapy but had a remarkable and sustained response to nivolumab. A 78-year-old man presented with right chest pain. Computed tomography (CT) showed a solid mass extending to the right pleura. Histopathological examination revealed the proliferation of spindle to pleomorphic ovoid shaped tumour cells, which are positive for calretinin and podoplanin. The patient was diagnosed with sarcomatoid MPM. Despite treatment with carboplatin and pemetrexed, the primary lesion rapidly progressed and new multiple pleural metastases were observed. Although his performance status decreased with advancing of symptoms and adverse events, nivolumab was administered. After the nivolumab treatment, CT showed a significant reduction in pleural tumours with a marked improvement in symptoms. In the primary specimens, TPS of PD-L1 was 80%. The patient has continued this treatment with sustained and remarkable effectiveness with good quality of life (QOL).

Acute limb ischemia of the lower extremity associated with left upper lobe surgery for primary lung cancer.

Thrombosis formation in the pulmonary vein stump after pulmonary lobectomy has recently been reported to be an extremely rare cause of arterial embolism. We herein report the first case series of acute limb ischemia encountered after video-assisted thoracoscopic left upper lobectomy or left upper division segmentectomy for primary lung cancer. The patients underwent embolectomy, and their perioperative courses were uneventful. It should be recognized that the pulmonary vein stump can cause acute limb ischemia after pulmonary lobectomy.