Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a complicated chronic inflammatory disease. It is important to investigate the characteristics of acute exacerbation of COPD to develop new therapeutic strategies. OBJECTIVE: This study aimed to determine the relationship between the human beta-defensin-2 (hBD-2) levels and aggravation of COPD. METHODS: We detected the sputum hBD-2 level of 254 patients from Guangzhou, China, for 2 years. The study participants were categorized into the COPD group (n = 203, GOLD 0-4) and the control group (n = 51, 40-79 years old). At baseline, 12th month, and 24th month, we detected the sputum hBD-2 level and levels of cytokines, such as CXCL10, CXCL11, and IFN. RESULTS: At baseline, there were no significant differences in the sputum and serum hBD-2 levels between the patients and the controls. However, the sputum hBD-2 levels of patients who had at least one symptom aggravation over the next 2 years were significantly lower than those of patients without any exacerbations (1130.9 ± 858.4 pg/mL vs. 2103.7 ± 1294.2 pg/mL, respectively; p = 0.001). Nevertheless, there were no statistically significant differences in the sputum hBD-2 levels between patients (no aggravation history) and controls (2084.9 ± 1317.6 pg/mL vs. 2152.5 ± 1251.6 pg/mL, respectively; p = 0.626). We used a logistic regression model to assess the relationship between aggravation and sputum hBD-2 levels. Interestingly, we found that low hBD-2 level (< 1000 pg/mL) was significantly associated with exacerbations. Specifically, patients with low hBD-2 levels were more likely to experience exacerbations in the next 12 months (0.333 vs. 0.117; p = 0.001). Moreover, we compared the hBD-2 levels between controls and patients with GOLD 3-4 and found that participants with bacteria (+) and/or viruses (+) had an association between hBD-2 level and disease severity (p = 0.02). CONCLUSION: Patients at risk of exacerbations are more likely to have lower sputum hBD-2 levels. These results have important implications for future therapies for COPD.

NCCT-CECT image synthesizers and their application to pulmonary vessel segmentation.

BACKGROUND AND OBJECTIVES: Non-contrast CT (NCCT) and contrast-enhanced CT (CECT) are important diagnostic tools with distinct features and applications for chest diseases. We developed two synthesizers for the mutual synthesis of NCCT and CECT and evaluated their applications. METHODS: Two synthesizers (S1 and S2) were proposed based on a generative adversarial network. S1 generated synthetic CECT (SynCECT) from NCCT and S2 generated synthetic NCCT (SynNCCT) from CECT. A new training procedure for synthesizers was proposed. Initially, the synthesizers were pretrained using self-supervised learning (SSL) and dual-energy CT (DECT) and then fine-tuned using the registered NCCT and CECT images. Pulmonary vessel segmentation from NCCT was used as an example to demonstrate the effectiveness of the synthesizers. Two strategies (ST1 and ST2) were proposed for pulmonary vessel segmentation. In ST1, CECT images were used to train a segmentation model (Model-CECT), NCCT images were converted to SynCECT through S1, and SynCECT was input to Model-CECT for testing. In ST2, CECT data were converted to SynNCCT through S2. SynNCCT and CECT-based annotations were used to train an additional model (Model-NCCT), and NCCT was input to Model-NCCT for testing. Three datasets, D1 (40 paired CTs), D2 (14 NCCTs and 14 CECTs), and D3 (49 paired DECTs), were used to evaluate the synthesizers and strategies. RESULTS: For S1, the mean absolute error (MAE), mean squared error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) were 14.60± 2.19, 1644± 890, 34.34± 1.91, and 0.94± 0.02, respectively. For S2, they were 12.52± 2.59, 1460± 922, 35.08± 2.35, and 0.95± 0.02, respectively. Our synthesizers outperformed the counterparts of CycleGAN, Pix2Pix, and Pix2PixHD. The results of ablation studies on SSL pretraining, DECT pretraining, and fine-tuning showed that performance worsened (for example, for S1, MAE increased to 16.53± 3.10, 17.98± 3.10, and 20.57± 3.75, respectively). Model-NCCT and Model-CECT achieved dice similarity coefficients (DSC) of 0.77 and 0.86 on D1 and 0.77 and 0.72 on D2, respectively. CONCLUSIONS: The proposed synthesizers realized mutual and high-quality synthesis between NCCT and CECT images; the training procedures, including SSL pretraining, DECT pretraining, and fine-tuning, were critical to their effectiveness. The results demonstrated the usefulness of synthesizers for pulmonary vessel segmentation from NCCT images.

Correlations of Computed Tomography Measurement of Distal Pulmonary Vascular Pruning with Airflow Limitation and Emphysema in COPD Patients.

Background: Pulmonary vascular alteration is an important feature of chronic obstructive pulmonary disease (COPD), which is characterized by distal pulmonary vascular pruning in angiography. We aimed to further investigate the clinical relevance of pulmonary vasculature in COPD patients using non-contrast computed tomography (CT). Methods: Seventy-one control subjects and 216 COPD patients completed the questionnaires, spirometry, and computed tomography (CT) scans within 1 month and were included in the study. Small pulmonary vessels represented by percentage of cross-sectional area of pulmonary vessels smaller than 5 mm2 or 5-10 mm2 to the total lung fields (%CSA<5 or %CSA5-10, respectively) were measured using ImageJ software. Spearman correlation was used to investigate the relationship between %CSA<5 and airflow limitation. A receiver operating characteristic (ROC) curve was built to evaluate the value of %CSA<5 in discriminating COPD patients from healthy control subjects. Segmented regression was used to analyze the relationship between %CSA<5 and %LAA-950 (percentage of low-attenuation areas less than -950 HU). Results: We found a significant correlation between %CSA<5 and forced expiratory volume in one second (FEV1) percentage of predicted value (%pred) (r = 0.564, P < 0.001). The area under the ROC curve for the value of %CSA<5 in distinguishing COPD was 0.816, with a cut-off value of 0.537 (Youden index J, 0.501; sensitivity, 78.24%; specificity, 71.83%). Since the relationship between %CSA<5 and %LAA-950 was not constant, performance of segmented regression was better than ordinary linear regression (adjusted R2, 0.474 vs 0.332, P < 0.001 and P < 0.001, respectively). As %CSA<5 decreased, %LAA-950 slightly increased until an inflection point (%CSA<5 = 0.524) was reached, after which the %LAA-950 increased apparently with a decrease in %CSA<5. Conclusion: %CSA<5 was significantly correlated with both airflow limitation and emphysema, and we identified an inflection point for the relationship between %CSA<5 and %LAA-950.

Changes of quantitative CT-based airway wall dimensions in patients with COVID-19 during early recovery.

BACKGROUND: As the coronavirus disease 19 (COVID-19) pandemic evolves, the need for recognizing the structural pulmonary changes of the disease during early convalescence has emerged. Most studies focus on parenchymal destruction of the disease; but little is known about whether the disease affects the airway. This study was conducted to investigate the changes in airway dimensions and explore the associated factors during early convalescence in patients with COVID-19. METHODS: We retrospectively analyzed quantitative computed tomography (CT)-based airway measures of 69 patients with COVID-19 from 5 February to 17 March 2020, and 32 non-COVID-19 participants from 1 January 2018 to 31 December 2019 from Guangzhou, China. The well-established measures of wall area fraction and the square root of the wall area of a hypothetical bronchus with an inner perimeter of 10 mm, were used to describe airway wall dimensions. We described the characteristics of the dimensions and inner area of airways in 66 patients with COVID-19 at the initial and convalescent stages of the disease, and compared them with the non-COVID-19 group. Linear regression models were constructed to investigate the association of airway dimensions with duration of hospitalization or disease severity after recovery. Partial correlation coefficients were calculated to investigate whether inflammatory markers were related to airway dimensions. RESULTS: Among 66 patients with COVID-19, airway dimensions were greater during disease initiation than early convalescence, which was significantly greater than in non-COVID-19 participants. No significant difference was found between the patients with COVID-19 at the initial stage and the non-COVID-19 controls regarding the first to eighth generations of the inner area. In adjusted regression models, duration of hospitalization was negatively associated with wall area fraction of the first to the sixth generation of airways. No significant associations exist between airway dimensions and disease severity, or airway dimensions with inflammatory markers. CONCLUSIONS: Airway dimensions in patients with COVID-19 during disease initiation are greater than those in non-COVID-19 participants. Such structural airway changes continue to remain significantly greater during early convalescence. No evidence shows that disease severity or inflammatory markers are associated with airway dimensions, implying that the primary lesion attacked by COVID-19 might not be the airways.

Expression level of NUAK1 in human nasopharyngeal carcinoma and its prognostic significance.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is notable for its high incidence rates in select geographic and ethnic populations, especially among Chinese and Malay populations in Southeastern Asia. However, relevant biomarkers for the development and prognosis of NPC are not yet clear; therefore, discovering novel biomarkers will facilitate prediction of prognosis and development of targeted therapeutic tactics. This study aims to quest the potential prognostic value of NUAK1 (a downstream member of Akt) in NPC. METHODS: Immunohistochemistry was performed to measure the expression of NUAK1 in paraffin-embedded NPC samples. Statistical analysis, encompassing chi-square tests and Student's t test, was also employed to evaluate the association between the expression of NUAK1 and clinicopathologic features. In addition, the survival analysis was used to detect the prognostic significance of NUAK1 in NPC. RESULTS: Excessive expression of NUAK1 was found in NPC tissues at mRNA levels. Statistical analysis revealed a correlation of NUAK1 expression with maximum neck lymph node diameter (p = 0.025) and WHO histological type (p = 0.021). Furthermore, according to survival analysis, there was clinical relevance between the upregulation of NUAK1 in NPC and DFS. Subgroup analysis indicated that the expression of NUAK1 was strongly associated with DFS (p = 0.027) and OS (p = 0.026) duration in the patients of N1-3 tumors, but not in patients with N0 tumors. The expression of NUAK1 was also strongly associated with OS (p = 0.044) and DFS (p = 0.007) in patients of late stage tumour (UICC3-5), but not in patients of early stage tumour (UICC1-2). In addition, COX regression illustrated that N classification and NUAK1 expression were independent prognostic factors for disease-free survival. CONCLUSION: Our study postulated that NUAK1 is excessively expressed in NPC and may serve as a potential predictor of prognosis for NPC.