The purpose of this study was to evaluate whether obstructive sleep apnea (OSA)-related chronic intermittent hypoxia (CIH) influences lung cancer progression and to elucidate the associated mechanisms in a mouse model of lung cancer. C57/BL6 mice in a CIH group were exposed to intermittent hypoxia for two weeks after tumor induction and compared with control mice (room air). Hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis-related matrix metalloproteinases (MMP) were measured. The expression levels of several hypoxia-related pathway proteins including HIF-1α, Wnt/ß-catenin, the nuclear factor erythroid 2-related factor 2 (Nrf2) and mammalian target of rapamycin-ERK were measured by western blot. The number (P < 0.01) and volume (P < 0.05) of tumors were increased in the CIH group. The activity of MMP-2 was enhanced after CIH treatment. The level of VEGF was increased significantly in the CIH group (p < 0.05). ß-catenin and Nrf2 were translocated to the nucleus and the levels of downstream effectors of Wnt/ß-catenin signaling increased after IH exposure. CIH enhanced proliferative and migratory properties of tumors in a mouse model of lung cancer. ß-catenin and Nrf2 appeared to be crucial mediators of tumor growth.

Patients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF). ILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study. Out of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002–1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955–0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366–3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192–0.984 (IPAF vs IPF), respectively) showed significant association. Compared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.

Objectives: A significant proportion of non-small cell lung cancer (NSCLC) patients are never-smokers. However, the clinical impact of spirometrically diagnosed chronic obstructive pulmonary disease (COPD) on the prognosis of never-smoking NSCLC has not been evaluated in the context of treatment modalities and other cancer-related factors. In the present study, we evaluated the clinical impact of COPD in non-smoking NSCLC patients, and correlations between COPD and other previously unevaluated clinical variables. Materials and methods: Lung cancer patients (stages I to IV) diagnosed with NSCLC between January 2008 and December 2015 at six university hospitals were enrolled in the study cohort and retrospectively evaluated. Clinical parameters were compared between spirometrically diagnosed COPD and non-COPD groups. Correlations between COPD status and other variables were evaluated. In order to reduce the effect of potential confounders and selection bias, we performed adjustment for differences in baseline parameters by using propensity score matching (PSM). After PSM, clinical variables were evaluated for their effects on overall survival (OS). Results: Of the 345 patients enrolled in the study, 277 were categorized as non-COPD and 68 as COPD. Old age, male gender, and wild-type EGFR were significantly correlated with COPD. By univariate analysis of 218 patients in a propensity score matched cohort, not receiving active anticancer treatment, advanced stage, and COPD were significantly associated with shorter OS. Multivariate analysis showed that not receiving active anticancer treatment, advanced cancer stage, and COPD (P=0.044, HR: 1.526, 95% CI: 1.012–2.300) were significant predictors of shorter OS. Conclusion: In the present study, never-smoker NSCLC patients with COPD had shorter OS times, compared to non-COPD never-smoker NSCLC patients.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. Methods: This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. Results: Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48–0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37–0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. Conclusions: Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.