Predictors of postoperative acute exacerbation of interstitial lung disease: a case-control study.

INTRODUCTION: Patients with interstitial lung disease (ILD) are known to develop an acute exacerbation (AE) after surgery. Previous studies have evaluated the predictors of postoperative AE. However, it remains unclear whether the results of those studies can be generalised to patients with different types of ILD and/or extrapolated to those who undergo non-pulmonary surgery. This study aimed to elucidate the predictors of the development of AE after surgery with general anaesthesia in patients with ILD. METHODS: We conducted a nested matched case-control study of 700 patients from an initial cohort of 50 840 patients. We excluded those who underwent solid organ or bone marrow transplantation. The cases were patients with ILD who developed AE within 30 days postoperatively, whereas the controls did not develop AE. Each case (n=28) was matched with four controls (n=112) for sex, year of surgery and multiple operations within 30 days. Furthermore, a multivariable conditional logistic regression analysis was used to identify significant predictors, as indicated by a p value of <0.05. RESULTS: After adjusting for potential confounders, the multivariable conditional logistic regression analysis identified honeycombing on CT (OR 3.09; 95% CI 1.07 to 8.92), a per cent predicted FVC <80% (OR 4.21; 95% CI 1.46 to 12.2) and an ARISCAT score ≥45 (OR 6.14; 95% CI 2.10 to 18.0) significantly associated with the development of postoperative AE. CONCLUSIONS: We found that the three factors were independent predictors for the development of postoperative AE in patients with ILD. These predictors are advantageous because they can be readily evaluated before surgery by surgeons and anaesthesiologists even without consulting experienced pulmonologists.

Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.

Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.

Lung fibroblasts express a miR-19a-19b-20a sub-cluster to suppress TGF-ß-associated fibroblast activation in murine pulmonary fibrosis.

Lung fibroblasts play a pivotal role in pulmonary fibrosis, a devastating lung disease, by producing extracellular matrix. MicroRNAs (miRNAs) suppress numerous genes post-transcriptionally; however, the roles of miRNAs in activated fibroblasts in fibrotic lungs remain poorly understood. To elucidate these roles, we performed global miRNA-expression profiling of fibroblasts from bleomycin- and silica-induced fibrotic lungs and investigated the functions of miRNAs in activated lung fibroblasts. Clustering analysis of global miRNA-expression data identified miRNA signatures exhibiting increased expression during fibrosis progression. Among these signatures, we found that a miR-19a-19b-20a sub-cluster suppressed TGF-ß-induced activation of fibroblasts in vitro. Moreover, to elucidate whether fibroblast-specific intervention against the sub-cluster modulates pathogenic activation of fibroblasts in fibrotic lungs, we intratracheally transferred the sub-cluster-overexpressing fibroblasts into bleomycin-treated lungs. Global transcriptome analysis of the intratracheally transferred fibroblasts revealed that the sub-cluster not only downregulated expression of TGF-ß-associated pro-fibrotic genes, including Acta2, Col1a1, Ctgf, and Serpine1, but also upregulated expression of the anti-fibrotic genes Dcn, Igfbp5, and Mmp3 in activated lung fibroblasts. Collectively, these findings indicated that upregulation of the miR-19a-19b-20a sub-cluster expression in lung fibroblasts counteracted TGF-ß-associated pathogenic activation of fibroblasts in murine pulmonary fibrosis.