Background: It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. Objective: The aim of this study is to identify prognostic determinants in these patients. Methods: The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. Results: Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). Conclusion: The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery.

IntroductionThis study was conducted in order to investigate the diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative computed tomography (CT) in patients with COPD.Patients and methodsMedical records of 174 stable COPD patients were retrospectively reviewed to obtain the patients’ clinical data, including the pulmonary function and imaging data. According to the software-based quantification of the degree of emphysema and airway wall thickness, the patients were classified into the “normal by CT” phenotype, the airway-dominant phenotype, the emphysema-dominant phenotype, and the mixed phenotype. The pulmonary function, including the respiratory impedance evaluated by using the forced oscillation technique (FOT) and the reversibility of airway obstruction in response to inhaled short-acting β2-agonists, was then compared among the four phenotypes.ResultsThe respiratory system resistance at 5 and 20 Hz (R5 and R20) was significantly higher, and the respiratory system reactance at 5 Hz (X5) was significantly more negative in the airway-dominant and mixed phenotypes than in the other phenotypes. The within-breath changes of X5 (ΔX5) were significantly greater in the mixed phenotype than in the “normal by CT” and emphysema-dominant phenotypes. The FOT parameters (R5, R20, and X5) were significantly correlated with indices of the degree of airway wall thickness and significantly but weakly correlated with the reversibility of airway obstruction. There was no significant correlation between the FOT parameters (R5, R20, and X5) and the degree of emphysema.ConclusionThere is a diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative CT in patients with COPD. The FOT measurements may reflect the degree of airway disease and aid in detecting airway remodeling in patients with COPD.

The dominant pathogenesis underlying the combined pulmonary fibrosis and emphysema (CPFE) remains unresolved. The receptor for advanced glycation end-products (RAGE) is highly expressed in lung tissues and interacts with distinct multiple ligands, implicating it in certain lung diseases. To elucidate the pathogenesis of CPFE, we genotyped three single nucleotide polymorphisms (SNPs: rs2070600, rs1800625, and rs2853807) of the gene encoding RAGE (AGER) in 111 CPFE patients and 337 chronic obstructive pulmonary disease (COPD) patients of Japanese by using StepOne Real-Time PCR System for SNP genotyping assay. Serum levels of soluble RAGE (sRAGE) were measured by ELISA. We found that the allele frequency of rs2070600 was significantly different between the two groups [corrected P (Pc) = 0.015]. In addition, the minor allele was associated with CPFE patients relative to COPD patients in a dominant effect model (Odds Ratio = 1.93; Pc = 0.018). Moreover, the serum sRAGE level was significantly lower in the CPFE group than the COPD group (P = 0.014). The rs2070600 minor allele was significantly associated with reduced sRAGE level in CPFE patients and independently affected sRAGE level reduction in this group (P = 0.020). We concluded that the AGER rs2070600 minor allele (Gly82Ser mutation) is associated with the pathogenesis of pulmonary fibrosis in CPFE in Japanese patients. Some patients with chronic obstructive pulmonary disease (COPD) have concomitant pulmonary fibrosis in addition to emphysema, which is known as combined pulmonary fibrosis and emphysema (CPFE) 1. CPFE is characterized by upper-lobe emphysema and lower-lobe fibrosis on high-resolution computed tomography (HRCT) of the chest and preserved lung volume with serious diminished gas exchange capacity in pulmonary function tests. Because of frequent complications with pulmonary hypertension, acute lung injury, and lung cancer, the prognosis of CPFE is significantly poor relative to that of patients with emphysema only 1,2. To date, the pathogenesis of CPFE remains to be elucidated in terms of how the two conditions co-occur when they are considered to have different physiological and radiological characteristics. Our previous study demonstrated that enrichment of gene expression in fibrotic tissue differs from that in emphysematous lesions in lung tissues from patients with CPFE 3. Genetic factors have been suggested to be involved in CPFE pathogenesis. The receptor for advanced glycation end-products (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface molecules 4. It interacts with distinct multiple ligands in ways that implicate it in homeostasis, development, inflammation, and certain lung diseases through modulation of multiple intracellular signaling pathways 4. RAGE is constitutively highly expressed in the lung 5 , where decreased expression is associated with pulmonary fibrosis 6 and lung cancer 7 and upregulated expression has been observed in COPD 8. The soluble form of RAGE (sRAGE) in the circulation is produced thro...

Background:The interstitial lung disease-gender-age-physiology (ILD-GAP) index and staging system have been reported as a clinical prognostic factor for ILD, including all ILD subtypes. Objectives:The purpose of this study was to clarify the association of various prognostic indices, including the ILD-GAP index, with the prognosis, the incidence of acute exacerbations of ILD (ILD-AE), and the use of long-term oxygen therapy (LTOT) after surgery in surgically resected patients with ILD and concomitant lung cancer, to provide additional information when considering whether it is safe to perform surgery. Methods: The medical records of patients with ILD and concomitant lung cancer who had undergone surgery at Shinshu University Hospital between August 2001 and September 2016 were retrospectively analyzed. Results: There were significant differences in survival between the ILD-GAP index: 0-1 and ≥4 groups (p = 0.0001) and between the ILD-GAP index: 2-3 and ≥4 groups (p = 0.0236). A higher ILD-GAP index was independently associated with the risk of death (hazard ratio [HR] 1.32030; p = 0.0059). A higher body mass index (BMI) and a higher serum C-reactive protein (CRP) level were independently associated with the incidence of ILD-AE (HR 1.28336; p = 0.0206 and HR 26.3943; p = 0.0165, respectively). A higher severity of ILD on chest high-resolution computed tomography (HRCT) was independently associated with the use of LTOT (HR 2.78670; p = 0.0313). Conclusions: The ILD-GAP index can predict the prognosis in surgically resected patients with ILD and concomitant lung cancer. The BMI and serum CRP levels were independent determinants that predicted the incidence of ILD-AE. The severity of ILD on chest HRCT was an independent determinant that predicted the use of LTOT.

Objective: Several software-based quantitative computed tomography (CT) analysis methods have been developed for assessing emphysema and interstitial lung disease. Although the texture classification method appeared to be more successful than the other methods, the software programs are not commercially available, to our knowledge. Therefore, this study aimed to investigate the usefulness of a commercially available software program for quantitative CT analyses.Methods: This prospective cohort study included 80 patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). Results:The percentage of low attenuation volume and high attenuation volume had high sensitivity and high specificity for detecting emphysema and pulmonary fibrosis, respectively. The percentage of diseased lung volume (DLV%) was significantly correlated with the lung diffusion capacity for carbon monoxide in all patients with COPD and IPF patients. Conclusions:The quantitative CT analysis may improve the precision of the assessment of DLV%, which itself could be a useful tool in predicting lung diffusion capacity in patients with the clinical diagnosis of COPD or IPF.