Evaluation of a novel saliva-based epidermal growth factor receptor mutation detection for lung cancer: A pilot study.

BackgroundThis article describes a pilot study evaluating a novel liquid biopsy system for non-small cell lung cancer (NSCLC) patients. The electric field-induced release and measurement (EFIRM) method utilizes an electrochemical biosensor for detecting oncogenic mutations in biofluids.MethodsSaliva and plasma of 17 patients were collected from three cancer centers prior to and after surgical resection. The EFIRM method was then applied to the collected samples to assay for exon 19 deletion and p.L858 mutations. EFIRM results were compared with cobas results of exon 19 deletion and p.L858 mutation detection in cancer tissues.ResultsThe EFIRM method was found to detect exon 19 deletion with an area under the curve (AUC) of 1.0 in both saliva and plasma samples in lung cancer patients. For L858R mutation detection, the AUC of saliva was 1.0, while the AUC of plasma was 0.98. Strong correlations were also found between presurgery and post-surgery samples for both saliva (0.86 for exon 19 and 0.98 for L858R) and plasma (0.73 for exon 19 and 0.94 for L858R).ConclusionOur study demonstrates the feasibility of utilizing EFIRM to rapidly, non-invasively, and conveniently detect epidermal growth factor receptor mutations in the saliva of patients with NSCLC, with results corresponding perfectly with the results of cobas tissue genotyping

Reticulation is a Risk Factor of Progressive Subpleural non-Fibrotic Interstitial Lung Abnormalities

Rationale: Interstitial lung abnormalities (ILAs) are being increasingly identified in clinical practice. In particular for subpleural non-fibrotic ILAs, the risk of progression over time and the risk factors for progressive behavior are still largely unknown. Objectives: To determine the age band prevalence of ILAs and the risk of radiological progression of subpleural non-fibrotic ILAs over time in a large health check-up population, and to identify how reticulation contributes to the risk of radiological progression. Methods: Based on ILAs definition by the Fleischner Society, low-dose chest CT images from community-dwelling population undergone health check-up were evaluated for ILAs. Multivariable logistic regression was used to assess the risk of radiological progression. Measurements and Main Results: Among 155,539 individuals, 3,300 (2.1%) were confirmed to have ILAs: the vast majority (81.7%) were defined as subpleural non-fibrotic ILAs. The prevalence of ILAs increased linearly with age (P for trend<0.0001). Of 454 individuals with subpleural non-fibrotic ILAs, 198 (43.6%) had radiological progression over 4 years. The presence of reticulation on initial imaging was an independent predictor of radiological progression (OR 1.9; 95%CI 1.2-3.0, P=0.0040). No difference in radiological progression was identified between subpleural non-fibrotic ILAs with extensive reticulation and subpleural fibrotic ILAs (73.0% vs. 68.8%, P=0.7626). Conclusions: The prevalence of ILAs increases linearly with age. Nearly half of subpleural non-fibrotic ILAs progress radiologically over 4 years. The presence of reticulation is a risk factor for radiological progression. Subpleural non-fibrotic ILAs with extensive reticulation are likely to be a feature of subpleural fibrotic ILAs

Clinical characteristics and predictors of pulmonary hypertension in chronic obstructive pulmonary disease at different altitudes

Abstract Background Pulmonary hypertension (PH) is a common complication in patients with chronic obstructive pulmonary disease (COPD) and is closely associated with poor prognosis. However, studies on the predictors of PH in COPD patients are limited, especially in populations living at high altitude (HA). Objectives To investigate the differences in the clinical characteristics and predictors of patients with COPD/COPD and PH (COPD-PH) from low altitude (LA, 600 m) and HA (2200 m). Methods We performed a cross-sectional survey of 228 COPD patients of Han nationality admitted to the respiratory department of Qinghai People’s Hospital (N = 113) and West China Hospital of Sichuan University (N = 115) between March 2019 and June 2021. PH was defined as a pulmonary arterial systolic pressure (PASP) > 36 mmHg measured using transthoracic echocardiography (TTE). Results The proportion of PH in COPD patients living at HA was higher than that in patients living at LA (60.2% vs. 31.3%). COPD-PH patients from HA showed significantly different in baseline characteristics, laboratory tests and pulmonary function test. Multivariate logistic regression analysis indicated that the predictors of PH in COPD patients were different between the HA and LA groups. Conclusions The COPD patients living at HA had a higher proportion of PH than those living at LA. At LA, increased B-type natriuretic peptide (BNP) and direct bilirubin (DB) were predictors for PH in COPD patients. However, at HA, increased DB was a predictor of PH in COPD patients

Association between Dietary Anthocyanidins and Risk of Lung Cancer

Background: Anthocyanidins are a kind of water-soluble flavonoids widely found in flowers and fruits of many plants. Although the beneficial effect of anthocyanidins in cancer prevention has been discussed, the value of anthocyanidins in lung cancer prevention requires further investigation. In this study, we aimed to explore the role of dietary anthocyanidins in the prevention of lung cancer in population-based prospective studies. Methods: Data of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in Cox proportional hazards regression for the association of dietary anthocyanidins and lung cancer risk. The dose-response relationship was explored between total anthocyanidins and the incidence of lung cancer. Results: A total of 97,993 participants were included in this study. The calculated HRs showed a trend that a higher quartile of total anthocyanidins indicated lower risk of lung cancer after adjusting for covariates (HRQ4vsQ1: 0.63; 95% CI: 0.55,0.73; p for trend < 0.001). A non-linear association between total anthocyanidins and lung cancer risk was found in the restricted cubic spline model. Conclusion: A protective association between dietary anthocyanidins and risk of lung cancer in Americans was investigated

Efficacy and Safety of JAK Inhibitors for Rheumatoid Arthritis: A Meta-Analysis

Background: More and more trials have been conducted. We aimed to assess the efficacy and safety of different JAKinibs in RA. Methods: A systematic search of randomized controlled trials (RCTs) with JAKinib treatment in RA published in the Medline, Embase, and Cochrane databases up to May 2021 was performed. Results: 37 trials involving 15,174 patients were identified. Pooled analysis revealed that JAKinibs were associated with significant therapeutic improvement in RA patients as determined by ACR20 (RR = 2.03, 95% CI: 1.85 to 2.28) and HAQ-DI (MD = &minus;0.31, 95% CI: &minus;0.33 to &minus;0.28) over placebo. Compared to placebo, JAKinib treatment was also associated with more adverse events (RR = 1.10, p &lt; 0.001; RR = 1.29, p &lt; 0.001; RR = 1.59, p = 0.02). Baricitinib and upadacitinib were related to more frequent adverse events (RR = 1.10; 95% CI: 1.01, 1.21; RR = 1.19; 95% CI: 1.11, 1.28) and infection (RR = 1.22; 95% CI: 1.09, 1.37; RR = 1.38; 95% CI: 1.22, 1.56), whereas only baricitinib was associated with more herpes zoster (RR = 3.15; 95% CI: 1.19, 8.33). Conclusions: JAKinibs were superior to placebo for improving signs, symptoms, and health-related quality of life in RA patients at short term, whereas the overall risk of adverse events and infections were greater with baricitinib and upadacitinib, and a higher risk of herpes zoster was only associated with baricitinib. More trials are needed to investigate the long-term safety

Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation

Background: Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored. Objective: To study the association between SMM and clinical features of asthma, including asthma control and exacerbation, and to construct a model based on SMM to predict the risk of asthma exacerbation (AEx). Methods: In this prospective cohort study, we consecutively recruited patients with asthma (n = 334), classified as the SMM Normal group (n = 223), SMM Low group (n = 88), and SMM High group (n = 23). We investigated the association between SMM and clinical asthma characteristics and explored the association between SMM and asthma control and AEx within a 12-month follow-up period. Based on SMM, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort (n = 157). Results: Compared with the SMM Normal group, SMM Low group exhibited more airway obstruction and worse asthma control, while SMM High group had a reduced eosinophil percentage in induced sputum. Furthermore, SMM Low group was at a significantly increased risk of moderate-to-severe exacerbation compared with the SMM Normal group (relative risk adjusted 2.02 [95% confidence interval (CI), 1.35–2.68]; p = 0.002). In addition, a model involving SMM was developed which predicted AEx (area under the curve: 0.750, 95% CI: 0.691–0.810). Conclusions: Low SMM was an independent risk factor for future AEx. Furthermore, a model involving SMM for predicting the risk of AEx in patients with asthma indicated that assessment of SMM has potential clinical implications for asthma management

SPDEF regulates goblet cell hyperplasia in the airway epithelium

Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo

Evaluation of a novel saliva-based epidermal growth factor receptor mutation detection for lung cancer: A pilot study.

BackgroundThis article describes a pilot study evaluating a novel liquid biopsy system for non-small cell lung cancer (NSCLC) patients. The electric field-induced release and measurement (EFIRM) method utilizes an electrochemical biosensor for detecting oncogenic mutations in biofluids.MethodsSaliva and plasma of 17 patients were collected from three cancer centers prior to and after surgical resection. The EFIRM method was then applied to the collected samples to assay for exon 19 deletion and p.L858 mutations. EFIRM results were compared with cobas results of exon 19 deletion and p.L858 mutation detection in cancer tissues.ResultsThe EFIRM method was found to detect exon 19 deletion with an area under the curve (AUC) of 1.0 in both saliva and plasma samples in lung cancer patients. For L858R mutation detection, the AUC of saliva was 1.0, while the AUC of plasma was 0.98. Strong correlations were also found between presurgery and post-surgery samples for both saliva (0.86 for exon 19 and 0.98 for L858R) and plasma (0.73 for exon 19 and 0.94 for L858R).ConclusionOur study demonstrates the feasibility of utilizing EFIRM to rapidly, non-invasively, and conveniently detect epidermal growth factor receptor mutations in the saliva of patients with NSCLC, with results corresponding perfectly with the results of cobas tissue genotyping