Expression of redox sensing factor Nrf2 in lung macrophages and type II pneumocytes as a prognostic factor in pneumothorax recurrence

Abstract

Background: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence. Methods: Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs.Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. Results: Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P<0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively). Conclusions: High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidenceof-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence.

Spatial Analysis of NQO1 in Non-Small Cell Lung Cancer Shows Its Expression Is Independent of NRF1 and NRF2 in the Tumor Microenvironment

“…NRF2 has previously been shown to regulate chronic lung inflammation through the maturation of dendritic cells and by producing proinflammatory cytokines for priming B cell response to non-typeable H. influenzae (NTHI)-induced airway inflammation in mice [ 40 ]. Furthermore, increased NRF2 expression in alveolar macrophages and type II pneumocytes has been correlated with better incidence-of-recurrence primary spontaneous pneumothorax [ 41 ]. These findings indicate that NRF2 may be exerting a protective effect in normal respiratory epithelium and lung cancer, particularly in this early-stage cohort.…”

Incidence and risk factors for recurrent primary spontaneous pneumothorax after video-assisted thoracoscopic surgery: a systematic review and meta-analysis

“…A total of five studies ( 27 , 30 , 33 - 35 ) examined the association between weight and recurrence, with two showing a significant association. All studies were comparable because they reported the same unit of weight; therefore, they were included in the meta-analysis.…”

Excessive aggregation of fine particles may play a crucial role in adolescent spontaneous pneumothorax pathogenesis

“…As the primary phagocyte, AMs play a vital role in the local immune defense by initiating the local inflammatory response. Thus, AMs can be used as an indicator to evaluate the pulmonary inflammatory response ( Chiu et al, 2017 ). Our observation reveals that the accumulation of a large number of AMs and inflammatory cell infiltration were clearly observed.…”