miR-146a regulates emphysema formation and abnormal inflammation in the lungs of two mouse models.

miR-146a, a microRNA (miRNA) that regulates inflammatory responses, plays an important role in many inflammatory diseases. Although an in vitro study had suggested that miR-146a is involved in abnormal inflammatory response, being a critical factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), in vivo evidence of its pathogenic role in COPD remains limited. Eight-week-old male B6(FVB)-Mir146tm1.1Bal/J [miR-146a knockout (KO)] and C57BL/6J mice were intratracheally administered elastase and evaluated after 28 days or exposed to cigarette smoke (CS) and evaluated after 5 mo. miR-146a expression was significantly increased in C57BL/6J mouse lungs due to elastase administration (P = 0.027) or CS exposure (P = 0.019) compared with that in the control group. Compared with C57BL/6J mice, elastase-administered miR-146a-KO mice had lower average computed tomography (CT) values (P = 0.017) and increased lung volume-to-weight ratio (P = 0.016), mean linear intercept (P < 0.001), and destructive index (P < 0.001). Moreover, total cell (P = 0.006), macrophage (P = 0.001), neutrophil (P = 0.026), chemokine (C-X-C motif) ligand 2/macrophage inflammatory protein-2 [P = 0.045; in bronchoalveolar lavage fluid (BALF)], cyclooxygenase-2, and matrix metalloproteinase-2 levels were all increased (in the lungs). Following long-term CS exposure, miR-146a-KO mice showed a greater degree of emphysema formation in their lungs and inflammatory response in the BALF and lungs than C57BL/6J mice. Collectively, miR-146a protected against emphysema formation and the associated abnormal inflammatory response in two murine models.NEW & NOTEWORTHY This study demonstrates that miR-146a expression is upregulated in mouse lungs because of elastase- and CS-induced emphysema and that the inflammatory response by elastase or CS is enhanced in the lungs of miR-146a-KO mice than in those of control mice, resulting in the promotion of emphysema. This is the first study to evaluate the protective role of miR-146a in emphysema formation and the associated abnormal inflammatory response in different in vivo models.

Blood Eosinophil Count as a Predictive Biomarker of Chronic Obstructive Pulmonary Disease Exacerbation in a Real-World Setting.

Introduction: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death, and COPD exacerbation worsens the prognosis. Eosinophilic airway inflammation is a COPD phenotype that causes COPD exacerbation and is correlated with peripheral blood eosinophil count. We analyzed real-world data of COPD patients to assess the risk factors of COPD exacerbation focusing on blood eosinophils. Materials and Methods: Patients with COPD who visited our hospital between January 1, 2018, and December 31, 2018, were recruited, and their background information, spirometry data, laboratory test results, and moderate-to-severe exacerbation events during the one-year follow-up period were collected from the electronic medical records and analyzed. The COPD exacerbation risk factors were assessed using univariate and multivariate logistic regression analyses. Results: Twenty-two of 271 (8.1%) patients experienced moderate-to-severe exacerbation. Patients with exacerbation showed worse pulmonary function, and we found that a high blood eosinophil count (≥350 cells/µL; p=0.014), low % FEV1 (<50%; p=0.002), increase in white blood cell (≥9000 cells/µL; p=0.039), and use of home oxygen therapy (p=0.005) were risk factors for future exacerbations. We also found a strong correlation between eosinophil count cut-offs and exacerbation risk (r = 0.89, p < 0.001). On the other hand, there was no relation between exacerbation risk and inhalation therapy for COPD. Conclusion: In a real-world setting, peripheral blood eosinophil count could be a predictor of future COPD exacerbation.