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Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Introduction Cigarette and tobacco use is a leading cause of chronic obstructive pulmonary disease, lung cancer, and other malignant tumors. In China, people prefer to engage in mental activities (gambling, overtime work, playing video games, or other mental activities) on the weekends or during spare time, especially in the evening before they prepare for bed. In China, smokers frequently consume tea while smoking. The relationship between smokers who consume tea, engage in mental activities after dinner, or both (drinking tea and engaging in cognitive activities after dinner together), and daily cigarette smoking or nicotine addiction must be clarified. Methods A total of 438 smokers were included in the study. Age, gender, body mass index (BMI), smoking habits, Fagerström test for nicotine dependence scores, and behaviors, were recorded. The study excluded smokers with a Fagerström score

ABSTRACT Objective: Transbronchial lung cryobiopsy (TBCB) has developed rapidly and has become one of the research hotspots of lung biopsy technology. The present study sought to evaluate the efficacy of TBCB guided by radial-probe EBUS (RP-EBUS) and a guide sheath (GS) without fluoroscopy for peripheral pulmonary lesions. Methods: In this retrospective study, McNemar’s test was used in order to compare TBCB and transbronchial forceps biopsy (TBFB) in terms of diagnostic performance. A multivariate logistic regression model was designed to explore the association between predictive variables and the diagnostic yield of TBCB. Results: A total of 168 patients underwent GS-guided RP-EBUS. Of those, 157 had lesions that were visible and 11 had lesions that were not. Of those 157 patients, 24 were excluded because of missing data or an unclear final diagnosis. Therefore, 133 patients underwent RP-EBUS-GS-guided TBFB and TBCB. The pooled diagnostic yield of RP-EBUS-GS-guided TBCB without fluoroscopy was 71.5% (103/144). In 133 patients, the diagnostic yield of TBCB was significantly higher than that of TBFB (77.4% vs. 59.4%; p < 0.05). Multivariate analysis indicated that lesion size and site were independently associated with the diagnostic yield of TBCB (OR = 2.8, p = 0.03 and OR = 4.1, p = 0.01, respectively), although cryoprobe size was not. There was no significant difference between the 1.1-mm cryoprobe and the 1.9-mm cryoprobe in terms of diagnostic performance (78.4% vs. 76.8%; p > 0.05). Conclusions: GS-guided RP-EBUS is regarded as a practical option for guiding cryobiopsy, although it may not be able to replace fluoroscopy. Peripheral pulmonary lesions not located in the upper lobes or larger than 30 mm are significantly associated with a higher diagnostic yield of cryobiopsy.

Background: The diagnosis of peripheral pulmonary nodules (PPNs) still is the key and difficult point. Previous studies have demonstrated that the diagnostic yield of radial endobronchial ultrasound (rEBUS) visible nodules is significantly higher than that of invisible nodules. The traditional method of predicting the rEBUS-visibility of nodules is based on the CT-bronchus signs, but its effectiveness may be unsatisfactory. Objective: We innovate a valuable predictive model based on virtual bronchoscopic navigation to identify beforehand which PPNs are likely to be successfully visualized by rEBUS. The innovative predictor is the ratio of the size of lesions (S) to the shortest straight-line distance (D) from the terminal point of the virtual navigation path to the localization point of the nodule. Methods: This is a retrospective study. On the training dataset of 214 patients, a receiver operating characteristic curve was drawn to understand the utility of the predictive model and get the optimal cut-off points. Ninety-two cases were enrolled in the validation dataset to validate the external predictive accuracy of the predictor. Results: The optimal cut-off point of the curve was 1.84 with the Youden index of 0.65, at which point the area under the curve was 0.85 (95% CI: 0.76-0.95). The predictor has a good performance in the validation dataset with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 81%, 100%, 100%, 71%, and 87%, respectively. Conclusion: The S/D ratio is a valuable and innovative method to identify beforehand which PPNs are likely to be successfully visualized by rEBUS. If the S/D ratio of the nodule is greater than 1.84, it will be visualized by rEBUS.

Introduction Nicotine dependence (ND) is a maladaptive pattern of tobacco smoking with withdrawal symptoms similar to other drug addictive disorders. It is very common in clinical practice that smokers always have different degrees of nicotine dependence with the same amount of tobacco consumption. Behaviors may influence daily cigarette consumption or smoking status. Hence it is critical to ascertain the association between concurrent behaviors and high nicotine dependence among smokers. Methods A total of 343 patients who attended a clinic for smoking cessation were recruited, and the information on concurrent behaviors were recorded. Factors associated and not associated with nicotine dependence were recorded. Nicotine dependence was determined by Fagerström test for nicotine dependence (FTND). Results High ND patients (FTND >5) showed significant behaviors distribution compared with mild and moderate ND patients (FTND ≤5). There is no single behavior that was significantly different between high ND and mild and moderate ND smokers. However, the combined effects of nicotine dependence influencing behaviors of caffeine drinking and mental activities after dinner have an association with high ND (OR=1.939; 95% CI: 1.154–3.258, p=0.012). In addition, the combined effects of inadequate sleep time (

Abstract Tobacco smoking is the main risk factor for many diseases such as chronic obstructive pulmonary disease as well as lung cancer and cigarettes. Smokers usually keep continuing to smoke during their mental activities in the evening between dinner and sleep time on work days. So it is critical to elucidate the relationship between cigarettes daily consumption and mental activities after dinner. A survey designed by ourselves was finished among 369 patients who came to our clinic for smoking cessation. Age, gender, BMI, cigarettes consumption were recorded and analyzed. Statistically, Pearson correlation test and general linear model test were used. Compared to ≤ 40 years’ group, patients with mental activities after dinner consumed more cigarettes than those without mental activities (22.80 ± 10.86 vs. 30.88 ± 18.69, P value

In recent years, various biomarkers have been gradually applied on bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis (IPA). The objective of this study is to assess the value of the liquid-based cytopathology test (LCT) for improving the identification of IPA in BAL fluid from possible IPA patients, following special staining with periodic acid-Schiff staining (PAS) or Grocott’s methenamine silver (GMS). A total of 47 consecutive possible IPA patients who underwent bronchoscopy with BAL fluid from January 2017 to December 2018 were included. 45 people had a pair of BAL fluid specimens and 2 patients had two BAL fluid specimens. The 49 pairs of BAL fluid specimens were processed for culture, tuberculosis acid fast staining smear, direct microbial smear, and LCT with special staining (PAS and GMS), respectively. Then, we compared the sensitivity and specificity of PAS and GMS in BAL fluid in high-risk patients. Among 47 possible IPA patients, 25 patients had proven/probable IPA, and 11 patients had other invasive fungal diseases. The sensitivity of GMS was higher than that of PAS (92.11% versus 81.58%; P=0.175). The specificity of GMS was 81.82%, which was higher than that of PAS (81.82% versus 72.73%; P=0.611). The negative predictive value (NPV) for PAS and GMS were 53.33% and 75.00%, respectively. The positive predictive value (PPV) for PAS and GMS were 91.18% and 94.59%, respectively. This study showed that special staining of LCT in BAL fluid may be a novel method for the diagnosis of IPA, and the GMS of LCT had higher sensitivity and specificity, which was superior to PAS.

Objective. This epidemiological investigation aimed at determining the current situation regarding the diagnosis and treatment of chronic obstructive pulmonary disease (COPD), especially missed diagnosis and missed treatment, in a group of individuals residing in an island area of Ningbo. Methods. Adults ≥60 years of age were selected from an island area of Ningbo. All participants completed a COPD-Screening Questionnaire and underwent a post-bronchodilator pulmonary function test. COPD-positive individuals then completed a questionnaire surveying the status of diagnosis and treatment of COPD and the reasons for missed diagnosis and treatment. The data were collated and analyzed using SPSS version 22.0 (IBM Corporation, Armonk, NY, USA). Findings. (1) A total of 1526 individuals were screened, of whom 1371 (89.8%) were eventually included in data analysis. From these, 254 were diagnosed with spirometry-defined COPD, corresponding to an overall prevalence of 18.5%. Prevalence was higher in men (28.9%) than in women (8.3%) among the sample. (2) According to chi-squared test results, risk factors for COPD included sex, age, smoking history (pack-years), cough, and dyspnea. Body mass index, family history of respiratory diseases, and exposure to biomass smoke from cooking were not risk factors for COPD. (3) Multivariate logistic regression analysis revealed that age and smoking were independent risk factors for COPD. (4) Receiver operating curve analysis revealed that, at a cutoff of 19.5, the highest sum of sensitivity and specificity was 69.7% and 75.5%, respectively. The COPD-Screening Questionnaire could be used as a preselection method to screen for COPD in primary care settings. (5) Of 254 individuals diagnosed with COPD, only 10 had a history of COPD and only 35 had a previous diagnosis of pneumonia or bronchitis. These data revealed that the rate of missed diagnosis of COPD in the Ningbo island area was 96.1%. Conclusion. The prevalence of COPD among elderly individuals in the Ningbo island area was significantly higher than in other parts of China. Moreover, the rate of missed diagnosis of COPD in the Ningbo island area was extremely high. Smoking and age were independent factors for the occurrence of COPD.

Background. We evaluated the utility of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods. A total of 183 patients were included in the final analysis. Bronchoscopies and the detection of GM in BALF were all performed on them. Results. Ten cases of IPA were diagnosed. ROC data demonstrated that, for diagnosing IPA, an optimal cutoff value for GM in BALF of 0.76 yielded a sensitivity of 100.0% and a specificity of 76.2%. Symptoms and radiological findings had no significant difference between proven or probable IPA group and non-IPA group. In our case-control analysis, although nine patients with false-positive results received treatment with Piperacillin/tazobactam, there was no significant difference between case and control group. Conclusions. BALF GM detection is a valuable adjunctive diagnostic tool. Our retrospective study suggests that the optimal value of GM detection in BALF is 0.76 in nonneutropenic patients.

BACKGROUND: To investigate whether VEGF polymorphisms (-460 T/C, +405 G/C, and +936 C/T)/haplotypes influence the susceptibility of obstructive sleep apnea (OSA). METHOD: A prospective case-control study was conducted to evaluate the genetic effects of VEGF polymorphisms on the development of OSA. 150 patients and 225 healthy controls were recruited for this study and their genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression analysis. RESULT: Our study showed that the -460 C allele (C vs. T: OR = 1.95, 95% CI = 1.38-2.76) and +936 T allele (T vs. C: OR = 1.48, 95% CI = 1.02-2.15) were associated with an increased OSA risk, whereas +405 C allele was associated with a decreased susceptibility to OSA (C vs. G: OR = 0.61, 95% CI = 0.45-0.83). Compared with the most common haplotype CCT, CGC (OR = 2.22, 95% CI = 1.19-4.13) and TGC (OR = 3.83, 95% CI = 1.56-9.40) were associated with a significantly increased risk of OSA. CONCLUSION: These observations implied that VEGF gene polymorphisms might be associated with the susceptibility to OSA. These results need to be validated by other independent studies, especially in diverse ethnic populations.

Background: Previous studies have found that vascular endothelial growth factor (VEGF) is associated with lung cancer, yet little is known about vascular endothelial growth factor-D (VEGF-D) in bronchoalveolar lavage fluid (BALF) of lung cancer patients. In this study, we aim to investigate the expression and evaluation of VEGF-D in BALF for lung cancer diagnosis. Methods: BALF samples were acquired from 81 patients: 40 with benign diseases and 41 with lung cancer. The expression of VEGF-D in BALF was measured using sandwich enzyme-linked immune sorbent assays (ELISA), and the evaluation of VEGF-D in BALF for lung cancer diagnosis was also investigated. Results: In the BALF samples, the levels of VEGF-D in the lung cancer group were higher than in the benign disease group; however, there was no statistical significance between the two groups (p > 0.05). In the pathological classification of lung cancer, the levels of VEGF-D in the BALF differed significantly between the lung squamous carcinoma group and the benign disease group (p < 0.05). The diagnostic accuracies of VEGF-D in BALF for discrimination between patients with squamous cell carcinoma and benign disease were reasonable based on receiver operating characteristic (ROC curve) analysis, with a corresponding sensitivity of 64.7% and specificity of 60%, respectively. Conclusions: This study demonstrated that the detection of VEGF-D levels in BALF is a valuable diagnostic tool for lung squamous carcinoma. [ABSTRACT FROM AUTHOR]

Background: YKL-40 is also called chitinase-3-like-1 (CHI3L1) protein and may be a marker for asthma. The aims of the present study were to investigate whether serum YKL-40 levels are stable or decreased in patients with asthma after appropriate treatment and to evaluate the correlation of YKL-40 levels with lung function and asthma control test (ACT) results. Methods: A total of 103 asthmatic patients (mean age 33.1 ± 0.9 years) with diagnosed asthma were enrolled in our study. All patients underwent a detailed clinical examination and completed the ACT questionnaire, serum YKL-40 measurement, and spirometry before (visit 1) and 8 weeks after initiation of treatment (visit 2). Results: At the follow-up, the median serum YKL-40 level was significantly decreased compared to the levels at visit 1 (75.2 [55.8-86.8] ng/ml versus 54.5 [46.4-58.4] ng/ml, p < 0.001). The serum YKL-40 level was negatively correlated with %FEV1 (r = -0.37, p < 0.001) and ACT score (r = -0.26, p = 0.007) at visit 1. The change in serum YKL-40 levels between the visits was significantly correlated with changes in FEV1 (r = -0.28, p = 0.006) and ACT score (r = -0.22, p = 0.037). Patients with elevated YKL-40 levels had significantly greater corticosteroid use than patients with lower levels. Conclusions: YKL-40 was reduced in the serum of asthmatic patients after appropriate treatment, and the levels correlated with improvements in %FEV1 and ACT. High levels of serum YKL-40 may be refractory to current asthma treatments. [ABSTRACT FROM AUTHOR]

Background YKL-40 is also called chitinase-3-like-1 (CHI3L1) protein and may be a marker for asthma. The aims of the present study were to investigate whether serum YKL-40 levels are stable or decreased in patients with asthma after appropriate treatment and to evaluate the correlation of YKL-40 levels with lung function and asthma control test (ACT) results. Methods A total of 103 asthmatic patients (mean age 33.1 ± 0.9 years) with diagnosed asthma were enrolled in our study. All patients underwent a detailed clinical examination and completed the ACT questionnaire, serum YKL-40 measurement, and spirometry before (visit 1) and 8 weeks after initiation of treatment (visit 2). Results At the follow-up, the median serum YKL-40 level was significantly decreased compared to the levels at visit 1 (75.2 [55.8-86.8] ng/ml versus 54.5 [46.4-58.4] ng/ml, p < 0.001). The serum YKL-40 level was negatively correlated with %FEV1 (r = -0.37, p < 0.001) and ACT score (r = -0.26, p = 0.007) at visit 1. The change in serum YKL-40 levels between the visits was significantly correlated with changes in FEV1 (r = -0.28, p = 0.006) and ACT score (r = - 0.22, p = 0.037). Patients with elevated YKL-40 levels had significantly greater corticosteroid use than patients with lower levels. Conclusions YKL-40 was reduced in the serum of asthmatic patients after appropriate treatment, and the levels correlated with improvements in %FEV1 and ACT. High levels of serum YKL-40 may be refractory to current asthma treatments. Trial registration ChiCTR-OCC-13003316 [ABSTRACT FROM AUTHOR]

Changes of cytokines in bronchoalveolar lavage fluid (BALF) reflect immunologic reactions of the lung in pulmonary malignancies. Detection of biomarkers in BALF might serve as an important method for differential diagnosis of lung cancer. A total of 78 patients admitted into hospital with suspected lung cancer were included in our study. BALF samples were obtained from all patients, and were analyzed for TGF-β1, IL-6, and TNF-α using commercially available sandwich ELISA kits. The levels of TGF-β1 in BALF were significantly higher in patients with lung cancer compared with patients with benign diseases (P = 0.003). However, no significant difference of IL-6 (P = 0.61) or TNF-α (P = 0.72) in BALF was observed between malignant and nonmalignant groups. With a cut-off value of 10.85 pg/ml, TGF-β1 showed a sensitivity of 62.2%, and a specificity of 60.6%, in predicting the malignant nature of pulmonary disease. Our data suggest that TGF-β1 in BALF might be a valuable biomarker for lung cancer. However, measurement of IL-6 or TNF-α in BALF has poor diagnostic value in lung cancer. [ABSTRACT FROM AUTHOR]

The article describes the case of a 46-year-old woman who presented with a dry cough of six month's duration and was considered to be having an unusual case of pulmonary tuberculosis presenting as extensive consolidation of the right hilar region which was initially diagnosed as squamous cell carcinoma of the lung.

The article discusses the diagnosis of the rare congenital anomaly Mounier-Kuhn syndrome marked by trachea and main bronchi dilation due to fiber atrophy in a previously healthy 54-year-old woman who complained of a productive cough.