Integrating multi-level interactive network and in vivo/vitro studies to explore the protective mechanism of Ampelopsis grossedentata in hyperuricemia.

The strategies or drugs for preventing and treating Hyperuricemia (HUA) are still lacking. As a traditional Chinese medicine (TCM) with a profound history, Ampelopsis grossedentata has been shown to play diverse biological roles. The purpose of the present study was to evaluate hypouricemic effect of A. grossedentata, and investigate its involved material basis and mechanism. A HUA mice model was established to evaluate the therapeutic effects of A. grossedentata. And then some extracts from A. grossedentata were prepared, isolated and analyzed. Furthermore, network pharmacology, based on the above results, was used to discover potential active ingredients and therapeutic targets, and they were further verified and explored by molecular docking and in vitro experiments. In vivo experiments showed that A. grossedentata exerted hypouricemic effect on mice of HUA. The core active ingredients (quercetin, myricetin and dihydromyricetin etc.) and core targets (PTGS2, XOD and ABCG2 etc.) for A. grossedentata to treat HUA were predicted by network pharmacology. And molecular docking showed that the spontaneous binding activities of above components and targets were marvelous. In vitro experiments further demonstrated that A. grossedentata exerted hypouricemic effect by decreasing the levels of UA, XOD, antioxidant factors, inflammatory factors, GLUT9 and URAT1 in HK-2 cells of HUA. Taken together, this study integrates multi-level interaction network with in vivo/vitro experiments to systematically reveal the material basis and mechanism of A. grossedentata in treating HUA, which provides a scientific basis for further study of A. grossedentata and HUA.

Anti-inflammatory and analgesic effects of Streblus indicus.

The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1ß, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.

(±)-Gentiovarisin A and gentiovarisin B, unusual secoiridoid dimer skeletons from gentiopicroside.

Gentiana scabra, a famous traditional Chinese medicine (TCM), has been documented in Chinese Pharmacopoeia for the treatment of hepatitis. Its index component gentiopicroside could not be detected in the decoction, which suggested that the quality control of the TCM with this ingredient needs attention. The transformed products were obtained from gentiopicroside, mimicking the traditional process of G. scabra. Further investigation of the heat-transformed products yielded two secoiridoid dimers, gentiovarisin A (1) and B (2), with an unprecedented 6/6/6/6/6-fused pentacyclic skeletons. Their structures were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction analysis, and the absolute configurations of 1 were confirmed as (+)-1 and (-)-1 by ECD method. Plausible transformation pathways of the isolates were also proposed. Compounds 1 and 2 exhibited in vitro hepatoprotective activity similar to gentiopicroside, while (+)-1 displayed a more potent hepatoprotective activity than N-Acetyl-L-cysteine.

(±)-Zanthonitidumines A and B: Two new benzophenanthridine alkaloids enantiomers from Zanthoxylum nitidum and their anti-inflammatory activity.

Two new benzophenanthridine alkaloids enantiomers (±)-zanthonitidumines A (1) and B (2), along with seven known analogues (3-9), were isolated from Zanthoxylum nitidium. Their structures were elucidated on the basis of extensive spectroscopic techniques and ECD data. Compound 2 exhibited the most significant inhibition of IL-6 generation as well as TNF-α release which suggest that it may be a potential anti-inflammatory agent.

Serum Leukocyte Cell-Derived Chemotaxin 2 (LECT2) Level Is Associated with Osteoporosis.

OBJECTIVE: The aim of this study was to examine serum leukocyte cell-derived chemotaxin 2 (LECT2) levels in osteoporosis subjects to confirm its association with osteoporosis. METHODS: A total of 204 adult subjects were recruited. Bone mineral densities (BMD) were assessed and blood samples were collected for measurements of biomedical parameters and the bone turnover markers. Serum LECT2 levels were measured by enzyme-linked immunosorbent assay. The relationships between serum LECT2 levels and other parameters were analyzed using the Spearman correlation coefficient. RESULTS: Serum LECT2 levels were significantly increased in osteoporosis subjects over controls. We found a significantly negative correlation of serum LECT2 with BMD, 25-hydroxy-vitamin D, and creatinine and a significantly positive correlation with C-terminal telopeptide of type 1 collagen and total cholesterol. CONCLUSION: Serum LECT2 levels were significantly upregulated in osteoporosis subjects and correlated with the severity of bone loss. Serum LECT2 could be a potential biomarker to assess the risk of bone loss.

Hepatoprotective Polysaccharides from Geranium wilfordii: Purification, Structural Characterization, and Their Mechanism.

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1ß, TNF-α, and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF-α, involved in the STAT1/T-bet signaling pathway.

[Results and analysis of pulmonary function examination in 76 698 cases of physical examination crowd in Henain Province].

Objective: Pulmonary function testing (PFT) and electrocardiograph (ECG) are the vital components of the cardiopulmonary exercise test (CPET). This study is to investigate clinical characteristics of abnormal PFT as pulmonary ventilation dysfunction, small airway dysfunction and gas exchange (diffusion) dysfunction. Methods: Across-sectional study was conducted The 76 698 outpatient subjects who received health examination from December 2016 to February 2019 in Henan Provincial People's Hospital were recruited. The results of the ECG, PFT were compared among different sex and age sub-groups. Then the severity of their impaired PFT were analyzed. Results: Among 76 698 subjects, 39 237 subjects were male and 37 461 subjects were female. There were total 71.04% patients with abnormal ECG. There were total 28 273 (36.86%) patients with abnormal pulmonary ventilation function. The 17 570 patients (44.78%) (17 570/39 237) were male, 10 703 patients (28.57%) (10 703/37 461) were female, both the number and percentage of abnormal pulmonary ventilation function in male was significantly more than these in female (P<0.01). The percentage detectable rates of male were significant higher than that of female in all the different age sub-groups: 20~29, 30~39, 40~49, 50~59, 60~69 and ≥70 year (P<0.01). The total detectable abnormal rate of small airway dysfunction were 43 160 and 56.26% (43 160/76 698). The 57.73% (22 661/39 237) in male was significantly higher than 54.72% (20 499/37 461) in female (x2=74.87, P<0.01). The detectable abnormal rate of small airway dysfunction in male were lower than female in 30~39 year and 40~49year sub-groups (P<0.05), but were significantly higher in 20~29, 50~59, 60~69, and ≥70 yr sub-groups (P<0.05). Abnormal gas exchange (diffusion) dysfunction were detected in 28.54% (12 940/45 107) subjects. They were 7 433 (30.55%) in male,and 5 507 (26.50%)in female with significant gender difference (P<0.05). The abnormal diffusion detectable rate in 30~39 year sub-group was significant higher in female than in male (P<0.05), and were slightly higher without significant difference in 20~29 and 40~49 year sub-groups (P>0.05), but were significant lower in female than male in 50~59, 60~69 and ≥70 year sub-groups (P<0.05). Conclusion: The abnormal detectable rates in ECG, pulmonary ventilation dysfunction, gas exchange dysfunction and small airway dysfunction were higher in male than female, and higher in elder ≥70 year subgroup than all other younger age subgroups.

Unusual matrine-adenine hybrids isolated from Sophora davidii and their inhibitory effects on human cytomegalovirus.

A phytochemical investigation on the flowers of Sophora davidii resulted in the isolation of three unusual matrine-adenine hybrids, sophovicines A-C, together with biogenetically related analogue sophocarpine. Their structures and absolute configurations were determined by NMR analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data. Since sophovicines represent the first example of matrine-adenine hybrids, a putative biosynthetic pathway toward sophovicines A-C was proposed. In addition, computational molecular modeling suggested that compounds sophovicines B and C may have potent activities against human cytomegalovirus (HCMV). So, the inhibit effects of isolates on HCMV were evaluated. The results show that sophovicines B and C can inhibit HCMV replication effectively with IC50 values of 7.12 and 7.32 µM, respectively.

Correlation between upper and lower airway inflammations in patients with combined allergic rhinitis and asthma syndrome: A comparison of patients initially presenting with allergic rhinitis and those initially presenting with asthma.

Allergic rhinitis (AR) and asthma often coexist. The terminology combined allergic rhinitis and asthma syndrome (CARAS) was introduced to describe patients with combined AR and asthma. The aim of the present study was to evaluate the correlation between eosinophilic inflammation in the upper and lower airways of patients with CARAS. Stable patients with CARAS initially presenting with AR or asthma were recruited. Healthy subjects and patients with AR alone were recruited as controls. Clinical characteristics, including disease history, lung function, nasal airway inspiratory resistance and upper and lower airway eosinophilic inflammation were evaluated and compared. A total of 73 subjects (22 patients with CARAS initially presenting with AR, 15 patients with CARAS initially presenting with asthma, 25 patients with AR alone and 11 healthy subjects) were studied. The nasal symptoms visual analogue scale scores at the week prior to enrollment and nasal airway inspiratory resistances were comparable among the groups. The percentage of predicted forced expiratory volume in 1 sec and percentage of predicted maximal middle expiratory flow in patients with CARAS initially presenting with asthma were significantly lower compared with the other three groups (P<0.05). No significant different in the percentage of eosinophils in the nasal lavage was observed between patients with CARAS and those with AR only; however, it was significantly increased compared with healthy subjects (P<0.05). The fractional concentration of exhaled nitric oxide and percentage of eosinophils in the sputum were significantly increased in patients with CARAS compared with those in the AR only and healthy subject groups (P<0.05). The difference in the percentage of eosinophils in the nasal lavage and sputum between patients with CARAS initially presenting with AR and initially presenting with asthma was not significant; however, a positive correlation between the percentage of eosinophils in the upper and lower airways was present in patients with CARAS initially presenting with AR only (r=0.526, P=0.030).

Adenosine monophosphate is not superior to histamine for bronchial provocation test for assessment of asthma control and symptoms.

BACKGROUND: Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation test (BPT) in asthma is not fully elucidated. OBJECTIVES: To compare both BPTs and determine their utility in reflecting changes of asthmatic symptoms. METHODS: BPTs were performed in a cross-over fashion, at 2-4 day intervals. Cumulative doses eliciting 20% FEV1 fall (PD20 FEV1 ), diagnostic performance and adverse events (AEs) were compared. Patients with PD20 FEV1 lower than geometric mean were defined as responders, otherwise poor responders. Patients with uncontrolled and partly controlled asthma, who maintained their original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and asthmatic symptoms 3 and 6 months after. RESULTS: Nineteen uncontrolled, 22 partly controlled and 19 controlled asthmatic patients and 24 healthy subjects were recruited. Lower PD20 FEV1 geometric means were associated with poorer asthma control in His-BPT (0.424 µmol vs 1.684 µmol vs 3.757 µmol), but not AMP-BPT (11.810 µmol vs 7.781 µmol vs 10.220 µmol). Both BPTs yielded similar overall diagnostic performance in asthma (area under curve: 0.842 in AMP-BPT vs 0.850 in His-BPT). AEs, including wheezing and tachypnea, were similar and mild. Ten patients with uncontrolled and 10 partly controlled asthma were followed-up. At months 3 and 6, we documented an increase in PD20 FEV1 -AMP and PD20 FEV1 -His, which did not correlate with reduction asthmatic symptom scores. This overall applied in responders and poor responders of AMP-BPT and His-BPT. CONCLUSION: Despite higher screening capacity of well-controlled asthma, AMP-BPT confers similar diagnostic performance and safety with His-BPT. AMP-BPT might not preferentially reflect changes asthmatic symptoms.

A Critical Review of the Quality of Cough Clinical Practice Guidelines.

BACKGROUND: Clinical practice guidelines (CPGs) have been developed to provide health-care practitioners with the best possible evidence, but the quality of these CPGs varies greatly. OBJECTIVE: The goal of this study was to systematically evaluate the quality of cough CPGs and identify gaps limiting evidence-based practice. METHODS: Systematic searches were conducted to identify cough CPGs in guideline databases, developers' Websites, and Medline. Four reviewers independently evaluated eligible guidelines by using the Appraisal of Guidelines for Research and Evaluation II assessment tool. Agreement among reviewers was measured by using the intraclass correlation coefficient. The number of recommendations, strength of recommendation, and levels of evidence were determined. RESULTS: Fifteen cough CPGs were identified. An overall high degree of agreement among reviewers was observed (intraclass correlation coefficient, 0.82 [95% CI, 0.79-0.85]). The quality ranged from good to acceptable in the scope and purpose (mean, 72%; range, 54%-93%) and clarity and presentation (mean, 68%; range, 50%-90%) domains but not in stakeholder involvement (mean, 36%; range, 18%-90%), rigor of development (mean, 36%; range, 9%-93%), applicability (mean, 23%; range, 9%-83%), and editorial independence domains (mean, 24%; range, 0-96%). Seven guidelines (46.7%) were considered "strongly recommended" or "recommended with modifications" for clinical practice. More than 70% of recommendations were based on nonrandomized studies (Level C, 30.4%) and expert opinion (Level D, 41.3%). CONCLUSIONS: The quality of cough CPGs is variable, and recommendations are largely based on low-quality evidence. There is significant room for improvement to develop high-quality guidelines, which urgently warrants first-class research to minimize the vital gaps in the evidence for formulation of cough CPGs.

Carbocisteine attenuates TNF-α-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-κB and ERK1/2 MAPK signaling pathways.

AIM: We previously proven that carbocisteine, a conventional mucolytic drug, remarkably reduced the rate of acute exacerbations and improved the quality of life in the patients with chronic obstructive pulmonary disease. In this study we investigated the mechanisms underlying the anti-inflammatory effects of carbocisteine in human alveolar epithelial cells in vitro. METHODS: Human lung adenocarcinoma cell line A549 was treated with TNF-α (10 ng/mL). Carbocisteine was administered either 24 h prior to or after TNF-α exposure. The cytokine release and expression were measured using ELISA and qRT-PCR. Activation of NF-κB was analyzed with Western blotting, immunofluorescence assay and luciferase reporter gene assay. The expression of ERK1/2 MAPK signaling proteins was assessed with Western blotting. RESULTS: Carbocisteine (10, 100, 1000 µmol/L), administered either before or after TNF-α exposure, dose-dependently suppressed TNF-α-induced inflammation in A549 cells, as evidenced by diminished release of IL-6 and IL-8, and diminished mRNA expression of IL-6, IL-8, TNF-α, MCP-1 and MIP-1ß. Furthermore, pretreatment with carbocisteine significantly decreased TNF-α-induced phosphorylation of NF-κB p65 and ERK1/2 MAPK, and inhibited the nuclear translocation of p65 subunit in A549 cells. In an NF-κB luciferase reporter system, pretreatment with carbocisteine dose-dependently inhibited TNF-α-induced transcriptional activity of NF-κB. CONCLUSION: Carbocisteine effectively suppresses TNF-α-induced inflammation in A549 cells via suppressing NF-κB and ERK1/2 MAPK signaling pathways.

Responsiveness to methacholine, but not leukotriene D4, correlates with fractional exhaled nitric oxide in asthma.

BACKGROUND AND AIMS: Correlation between fractional exhaled nitric oxide (FeNO) and responsiveness to inhaled leukotriene D4 (LTD4 ) and methacholine (MCh) might be different. This study aims to determine the correlation between FeNO and airway responsiveness to LTD4 and MCh, and to compare the airway responsiveness to inhaled LTD4 and MCh and FeNO in non-smokers, patients without rhinitis and non-smokers without rhinitis. METHODS: In this cross-over study, asthmatic patients and healthy subjects underwent LTD4 and MCh inhalation challenge at a 2- to 14-day interval. The FeNO was measured by using NIOX MINO, a portable instrument, at the initial visit, before spirometry and inhalation challenge tests. Subgroup analyses were performed in asthmatic patients based on the categorisation of never-smoker group, non-rhinitis group and never-smoker without rhinitis group. RESULTS: Of 62 asthmatic patients enrolled, 43 did not have self-reported rhinitis (asthmatic patients without rhinitis), 56 were never-smokers (asthmatic non-smokers), giving rise to 37 non-smokers who did not have rhinitis (asthmatic non-smokers without rhinitis). Twenty-one healthy subjects were enrolled. Overall, Log10 FeNO correlated with Log10 PD20 FEV1 -MCh but not Log10 PD20 FEV1 -LTD4 or Log10 (LTD4 /MCh potency ratio). Reduced FeNO was associated with significantly higher Log10 PD20 FEV1 -MCh but not Log10 PD20 FEV1 -LTD4 , except for non-smokers. Compared with all asthmatic patients, asthmatic non-smokers without rhinitis were characterised by markedly reduced levels of Log10 PD20 FEV1 -MCh but not Log10 PD20 FEV1 -LTD4 . The difference in all parameters did not reach statistical significance among asthmatic patients without rhinitis, asthmatic non-smokers and asthmatic non-smokers without rhinitis. CONCLUSION: FeNO correlates with airway responsiveness to inhaled MCh but not LTD4 , in asthmatic patients, particularly in asthmatic non-smokers without rhinitis.

Leukotriene D4 inhalation challenge for predicting short-term efficacy of montelukast: a pilot study.

INTRODUCTION: The convenient measure to predict efficacy of leukotriene receptor antagonist is lacking. OBJECTIVES: To determine if leukotriene D4 inhalation challenge predicts short-term efficacy of montelukast in asthma. METHODS: In this open-labelled 28-day trial, 45 patients with asthma were allocated to leukotriene-sensitive and leukotriene-insensitive group to receive montelukast monotherapy (10 mg, once daily) based on the positive threshold of leukotriene D4 inhalation challenge test (4.800 nmol). Miscellaneous measurements comprised fractional exhaled nitric oxide, methacholine inhalation challenge, Asthma Control Test and Asthma Quality of Life Questionnaire. Peak expiratory flow was self-monitored throughout the treatment. End point assessments were performed 3 to 5 days after montelukast withdrawal. RESULTS: Twenty-three patients in leukotriene-sensitive group and 10 leukotriene-insensitive group completed the study. Both groups differed neither in 28-day peak expiratory flow rate nor in maximal weekly peak expiratory flow (both P > 0.05). However, minimal weekly peak expiratory flow was significantly higher in leukotriene-insensitive group throughout the treatment course (all P < 0.05) except for week 1 (P > 0.05). Both groups did not differ statistically in the post-treatment improvement in forced expiratory volume in 1 s (FEV1 ) predicted% prior to inhalation challenge, fractional exhaled nitric oxide or the airway responsiveness to leukotriene D4 or methacholine (all P > 0.05). There was a marked increase in Asthma Control Test score and the symptom score of Asthma Quality of Life Questionnaire in both groups (both P < 0.05). The overall significance of Logistic regression model was unremarkable (P = 0.467). CONCLUSION: Responsiveness to inhaled leukotriene D4 alone might not be sufficient to predict the short-term efficacy of montelukast monotherapy in patients with asthma.

Classification of non-allergic rhinitis based on inflammatory characteristics.

The study aims to investigate nasal and lower airway inflammation in patients with non-allergic rhinitis (NAR), and to discuss a method of NAR classification based on inflammatory characteristics and its clinical significance. A total of 117 NAR patients admitted to our hospital from June 2010 to June 2011 were enrolled in this study, 162 healthy participants were employed as healthy controls. Nasal and lower airway inflammation were evaluated using the skin prick test, nasal and pulmonary visual analogue scale scoring, cell blood count, nasal douche, induced sputum assay, nasal provocation test, and bronchial provocation test. Compared to the healthy controls, NAR patients have significant higher levels of nasal douche eosinophils, more induced sputum eosinophils as well as blood eosinophils, and higher rates of nasal and bronchial provocation. Patient with high level of eosinophil in nasal douch tended to be with higher concentrations of eosinophils in induced sputum. Scores on the nasal and bronchial provocation tests are also correlated to each other. Among all NAR patients, 28 cases (23.9%) were with no abnormality detectable by eosinophil measurement or a provocation test, 39 cases (33.3%) were with elevated levels of eosinophils, and 50 cases (42.7%) exhibited a nasal provocation response. Based on this, all studied NAR cases were classified into 3 groups: non-specific type (group A, 28/117), increased eosinophil type (group B, 39/117), and hyper-reactive type (group C, 50/117). Some NAR cases may be considered as systemic inflammatory disease characterized by increased nasal eosinophil and nasal hyperreactivity.

Response--dose ratio is a surrogate of cumulative provocative dosage for bronchial provocation tests in asthma.

BACKGROUND: Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. OBJECTIVES: To compare the diagnostic value of RDR and PD, by conducting leukotriene D4 (LTD4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. METHODS: Healthy subjects and asthmatic patients underwent LTD4-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20% fall in forced expiratory volume in one second (PD20FEV1) and the RDR, defined as FEV1 fall (%) at the final step divided by the corresponding provocative dosage. RESULTS: Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log10RDR was positively correlated with log10PD20FEV1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD20FEV1 and higher RDR (both P < 0.05). The differences in PD20FEV1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log10PD20FEV1, the log10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤ 25th percentile) was associated with higher baseline FEV1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD20FEV1 led to an increased diagnostic value compared with either parameter alone. CONCLUSIONS: RDR is a surrogate of PD20FEV1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants.

Vibration response imaging in idiopathic pulmonary fibrosis: a pilot study.

BACKGROUND: Vibration response imaging (VRI) is a novel imaging technique and little is known about its characteristics and diagnostic value in idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the features of VRI in subjects with IPF. METHODS: We enrolled 23 subjects with IPF (42-74 y old) and 28 healthy subjects (42-72 y old). Subjects with IPF were diagnosed by lung biopsy and underwent VRI, spirometry, lung diffusion testing, and chest x-ray or computed tomography, which entailed assessment of the value of VRI indices. RESULTS: The total VRI score correlated statistically with single-breath carbon monoxide diffusing capacity percent predicted (r = -0.30, P = .04), but not with FVC percent predicted, FEV1 percent predicted, and FEV1/FVC (r = -0.27, -0.22, and 0.19; all P > .05). Compared with healthy subjects (17.9%), 20 subjects with IPF (86.96%, P < .01) presented with significantly increased crackles. The difference in quality lung data in all lung regions was unremarkable (all P > .05), except for the upper right and lower left lobes (P < .05). Overall, VRI parameters yielded acceptable assay sensitivity and specificity. Maximum energy frame was characterized by the highest diagnostic value (sensitivity, 1.00; specificity, 0.82), followed by presence of abundant crackles (sensitivity, 0.70; specificity, 0.96). Total VRI score was not a sensitive indicator of IPF, owing to low assay sensitivity (0.70) and specificity (0.64). CONCLUSIONS: VRI may be helpful to discriminate between IPF subjects and healthy individuals. Maximum energy frame and abundant crackles might serve as a diagnostic tool for IPF.

[Single-breath and rebreathing methods for measurement of pulmonary diffusing function: a comparative study].

OBJECTIVE: To compare the difference of pulmonary diffusing capacity measured by single-breath (SB) and re-breathing (RB) in normal subjects, patients with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). METHODS: We enrolled a cohort of subjects from the Guangzhou Institute of Respiratory Disease between September 2011 and February 2012: control group 29 (male 9, female 20, 42-74 y), ILD group 32 (male 15, female 17, 41-72 y), COPD group 32 (male 28, female 4, 40-75 y). All subjects underwent pulmonary diffusing capacity test using SB or RB method according to random figures order list. Diffusing capacity of carbon monoxide per predicted measured by SB method (SB-DLCO%pred) of the normal group was used as the standard to adjust the diffusing capacity of carbon monoxide per predicted measured by RB method (RB-DLCO%pred) and diffusing capacity of carbon monoxide per liter of VA per predicted measured by RB (RB-DLCO/VA%pred) in the 3 groups, respectively. Comparisons between 2 groups were performed by using the independent-sample t test, among more than 2 groups by using the One-Way ANOVA test, while the ROC curve was used to calculate the area under curve (AUC) and its 95%CI. RESULTS: In the control group, 15 subjects' RB-DLCO%pred was lower than 80%, and the mean value (78.8 ± 2.1)% was also lower than 80%. Using SB-DLCO%pred of the normal group as a standard to adjust the RB-DLCO%pred, the corrected value was 1.097, and then this value was used to adjust RB-DLCO/VA%pred in the 3 groups, respectively. Before correction DLCO%pred [the control group: (91.2 ± 1.9)% vs (78.8 ± 2.1)%; the ILD group: (45.8 ± 2.6)% vs (60.0 ± 1.9)%;the COPD group: (66.3 ± 2.9)% vs (56.6 ± 1.6)%]and DLCO/VA%pred [the control group: (99.8 ± 2.3)% vs (84.6 ± 4.5)%; the ILD group: (75.9 ± 3.0)% vs (88.5 ± 5.4)%; the COPD group: (80.2 ± 3.7)% vs (50.6 ± 2.5)% ] between the SB and RB were statistically different among the 3 groups. After correction, only the DLCO%pred [(45.8 ± 2.6)% vs (65.8 ± 2.1)%], DLCO/VA%pred [ (75.9 ± 3.0)% vs (102.2 ± 6.2)%] of the ILD group and the DLCO/VA%pred [(80.2 ± 3.7) vs (58.3 ± 2.8)%] of the COPD group had significant difference between the 2 methods (t = -6.00-4.68, all P < 0.01) . The test time of re-breathing in the COPD group (106 ± 5) s was significant longer than that of the ILD group (73 ± 4) s and the control group (79 ± 5) s (F = 11.99, P < 0.01), and the correlation between DLCO/VA%pred and the test time(r = -0.661, P < 0.01) was higher than the relationship between DLCO%pred and the test time (r = -0.391, P < 0.01). Furthermore, in the ILD group, the area of RB-DLCO%pred under ROC was 0.893, 95%CI being 0.817-0.970. In the COPD group, the area of RB-DLCO/VA%pred under ROC was 0.895, 95%CI being 0.811-0.979. CONCLUSIONS: There were differences between re-breathing and single-breath in measuring diffusing capacity. The present predicted value of the re-breathing method needed further study to confirm its applicability. Re-breathing method was more consistent with the respiratory physiology, and might be a better method to detect diseased states.

Responsiveness to leukotriene D4 and methacholine for predicting efficacy of montelukast in asthma.

A lower responsiveness to leukotriene D4 (LTD4) or higher LTD4/[methacholine (MCh)] potency ratio might suggest preferable outcomes of short-term montelukast monotherapy in terms of airway inflammation and lung function in asthmatic patients.