Radiomics approach for survival prediction in chronic obstructive pulmonary disease.

OBJECTIVES: To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS). METHODS: This study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. RESULTS: The five features remaining after the LASSO analysis were %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm. The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio [HR], 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index. CONCLUSIONS: A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality. KEY POINTS: • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm were selected to generate a radiomics model. • A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group. • Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups.

Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathymodulation of brain-derived neurotrophic factor expression.

OBJECTIVE: Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice. METHODS: To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF). RESULTS: Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area. CONCLUSIONS: LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.

Fibrinogen as a potential biomarker for clinical phenotype in patients with chronic obstructive pulmonary disease.

BACKGROUND: Under the Food and Drug Administration's drug development tool qualification program, fibrinogen is the first biomarker drug development tool used in chronic obstructive pulmonary disease (COPD). However, the correlation between fibrinogen and exacerbations among Korean patients with COPD remains unclear. METHODS: In this retrospective cross-sectional study, we included patients with COPD for whom plasma fibrinogen assessment results, without exacerbation, were available. Then, we compared subgroups according to fibrinogen level (threshold: 350 mg/dL). We used multivariate linear regression analysis to investigate the clinical phenotype of COPD with high fibrinogen level, analyzed the correlation between the COPD severity indexes and fibrinogen level. RESULTS: Of 140 patients, we confirmed 48 (34.3%) patients in the high-level fibrinogen group. The high-level group demonstrated a medical history of more exacerbations than the low-level group. Lung functions [forced expiratory volume in 1 s (FEV1), forced vital capacity, and 6-minute walk distance] were more deteriorated in the high-level group. Multivariate regression analysis revealed that fibrinogen level was associated with high COPD assessment test score, and experience of exacerbation. Fibrinogen level exhibited a statistically significant positive correlation with COPD severity indexes. CONCLUSIONS: High fibrinogen level seems to reflect frequent exacerbation and severe symptomatic phenotypes in Korean patients with COPD.

Quantitative assessment of pulmonary vascular alterations in chronic obstructive lung disease: Associations with pulmonary function test and survival in the KOLD cohort.

PURPOSE: Despite the high prevalence of pulmonary vascular alterations and their substantial impact on chronic obstructive pulmonary disease (COPD), tools for the direct in vivo assessment of pulmonary vascular alterations remain limited. Thus, the purpose of this study was to automatically extract pulmonary vessels from volumetric chest CT and evaluate the associations between the derived quantitative pulmonary vessel features and clinical parameters, including survival, in COPD patients. METHODS: This study included 344 adult COPD patients. Pulmonary vessels were automatically extracted from volumetric chest CT data. Quantitative pulmonary vessel features were obtained from various lung surface areas (LSAs), which are theoretical surface areas drawn at different depths from the pleural borders. The total number of vessels (Ntotal) and number of vessels with vessel area (VA) less than 5 mm2 (N<5mm) were counted as both robust values and as values per 10 cm2 of LSA (Ntotal/LSA; N<5mm/LSA). The average VA (VAmean) and percentage of measured VA in the corresponding LSA (%VA) were measured. Associations between quantitative pulmonary vessel features and clinical parameters, including survival and the pulmonary function test (PFT), were evaluated. RESULTS: The pulmonary vessels were automatically extracted with 100% technical success. Cox regression analysis showed Ntotal/LSA, N<5mm/LSA, VAmean, and %VA to be significant predictors of survival (hazard ratio (HR), 0.80, 0.75, 0.70, 0.49, respectively). Patients classified into high-risk groups by %VA18mm (cut-off = 3.258), chosen because it demonstrated the strongest statistical influence on survival in a univariate Cox analysis, were associated with worse overall survival before (HR, 4.83; p < 0.001) and after adjustment for patient age and BMI (HR, 2.18; p = 0.014). Of the quantitative pulmonary vessel features, Ntotal/LSA, N<5mm/LSA, and %VA were correlated with FEV1, FEV1/FVC, and DLCO in all LSAs. The strongest correlation with PFTs was noted at LSA9mm for both Ntotal (FEV1, r = 0.33; FEV1/FVC, r = 0.51) and N<5mm (FEV1, r = 0.35; FEV1/FVC, r = 0.52). For %VA, the association was most evident at LSA18mm (FEV1, r = 0.27; FEV1/FVC, r = 0.47). Significant moderate to strong correlations were consistently observed between the extent of emphysema and quantitative pulmonary vessel features (r = 0.44-0.66; all p < 0.001). CONCLUSIONS: The automated extraction of pulmonary vessels and their quantitative assessment are technically feasible. Various quantitative pulmonary vessel features demonstrated significant relationships with survival and PFT in COPD patients. Of the various quantitative features, the percentage of total VA measured at 18 mm depth from the pleural surface (%VA18mm) and the number of small vessels counted per 10 cm2 of LSA at 9 mm depth from the pleural surface (N<5mm/LSA9mm) had the strongest predictability for the clinical parameters.

Physiology is a stronger predictor of survival than pathology in fibrotic interstitial pneumonia.

The histopathologic pattern provides the most important prognostic marker for idiopathic interstitial pneumonia; however, studies have suggested that short-term changes in lung function may be more important. We investigated the prognostic factors for fibrotic interstitial pneumonia. The clinical features and follow-up course of 179 patients (131 with idiopathic pulmonary fibrosis and 48 with nonspecific interstitial pneumonia; 41 fibrotic types and 7 cellular) were analyzed retrospectively. The lung function indices improved or stabilized in most patients with fibrotic nonspecific interstitial pneumonia in contrast to the deterioration or stable condition of most patients with idiopathic pulmonary fibrosis. The 5-year survival of patients with fibrotic nonspecific interstitial pneumonia (76.2%) was better than for those with idiopathic pulmonary fibrosis (43.8%) (p = 0.007). Multivariate analysis at the time of presentation revealed that pathologic pattern, age, and diffusion capacity had important prognostic implications. However, after 6 months of follow-up, changes in FVC, initial diffusion capacity, and sex were the only independent prognostic factors, with no additional prognostic information conferred by the histologic diagnosis. Our data confirmed the importance of physiological parameters including short-term change in FVC. However, at the time of diagnosis, histopathology was important for the prediction of prognosis and future change in lung function.

Morphometric effects of the recruitment maneuver on saline-lavaged canine lungs. A computed tomographic analysis.

BACKGROUND: In the face of widespread use of lung-protective, low-volume ventilation in patients with acute lung injury, interest in the recruitment maneuver (RM) is growing. Little is known about lung-morphometric effects of the RM as compared with positive end-expiratory pressure (PEEP) titration (PT) without the RM. METHODS: RM was defined as a stepwise change in PEEP from baseline to 10, 20, 30, and 20 cm H(2)O every 30 s, after which PEEP was reset at the lower inflection point + 2 cm H(2)O. For PT, PEEP was simply increased from baseline to the lower inflection point + 2 cm H(2)O. Both maneuvers were performed in 10 lung-lavaged dogs. Computed tomography of the lung was performed before and 30 s and 30 min after the maneuver. RESULTS: Thirty seconds after the maneuver, the decrease in the amount of nonaerated plus poorly aerated lung was greater and decreases in Hounsfield units in the caudal and dorsal lung regions were greater with the RM than with the PT. The hyper-aerated lung volume after the RM tended to be greater than that after the PT. At 30 s and 30 min after the maneuver, gas plus tissue volume, gas-only volume, and gas-tissue ratio of the lung were greater with the RM than with the PT. At both time points after the maneuver, the coefficient of variation of regional Hounsfield units, an index of regional heterogeneity of aeration, was lower with the RM than with the PT. CONCLUSIONS: Compared with PT, the RM resulted in a greater lung volume, better aeration of the most dependent lung, and less regional heterogeneity of aeration. However, the RM tended to induce a greater increase in hyperaerated lung volume than did the PT.