Effect of tiotropium on neural respiratory drive during exercise in severe COPD.

BACKGROUND: Studies have shown that tiotropium once daily reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. Mechanisms underlying the effects of the muscarinic receptor antagonist tiotropium on COPD have not been fully understood. OBJECTIVE: In this study, we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD. METHODS: Twenty subjects with severe COPD were randomized into two groups: no treatment (Control, n = 10, 63.6 ± 4.6 years, FEV1 29.6 ± 13.3%pred) or inhaled tiotropium 18 µg once daily for 1 month (n = 10, 66.5 ± 5.4 years, FEV1 33.0 ± 11.1%pred). All subjects were allowed to continue their daily medications other than anti-cholinergics during the study. Constant cycle exercise with 75% of maximal workload and spirometry were performed before and 1 month after treatment. Diaphragmatic EMG (EMGdi) and respiratory pressures were recorded with multifunctional esophageal catheter. Efficiency of neural respiratory drive, defined as the ratio of minute ventilation (VE) and diaphragmatic EMG (VE/EMGdi%max), was calculated. Modified British Medical Research Council Dyspnea Scale (mMRC) was used for the evaluation of dyspnea before and after treatment. RESULTS: There was no significant difference in spirometry before and after treatment in both groups. Diaphragmatic EMG decreased significantly at rest (28.1 ± 10.9% vs. 22.6 ± 10.7%, P < 0.05) and mean efficiency of neural respiratory drive at the later stage of exercise increased (39.8 ± 2.9 vs. 45.2 ± 3.9, P < 0.01) after 1-month treatment with tiotropium. There were no remarkable changes in resting EMGdi and mean efficiency of neural respiratory drive post-treatment in control group. The score of mMRC decreased significantly (2.5 ± 0.5 vs. 1.9 ± 0.7, P < 0.05) after 1-month treatment with tiotropium, but without significantly difference in control group. CONCLUSION: Tiotropium significantly reduces neural respiratory drive at rest and improves the efficiency of neural respiratory drive during exercise, which might account for the improvement in exercise tolerance in COPD.

Network pharmacology to explore the mechanism of traditional Chinese medicine in the treatment of ground glass nodules.

Background: Ground glass nodules (GGNs) in the lung are considered to be a high-risk factor of lung adenocarcinoma. Immediate surgery is not recommended for GGNs patients, and low-dose computed tomography (CT) is often used for observation and follow-up, which brings high psychological and economic burden to the patient. Methods: Three traditional Chinese medicine (TCM) prescriptions for the treatment of GGNs were found through database including PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI), Scopus and so on. The possible targets of the active ingredients of the TCM preparations and the gene targets of GGNs were screened out from Traditional Chinese Medicine Systems Pharmacology (TCMSP), UniProt and GeneCards. Network visualization was realized via STRING, Cytoscape 3.7.2, Evenn, DAVID and Hiplot. Finally, molecular docking Vina and PyMOL software were performed to further explore the possibility of drug-target interactions using PubChem compounds, protein data bank (PDB) database, Autodocktools and Autodock. Results: Three TCM preparations could target the same 13 potential therapeutic targets in GGNs. From network pharmacology, 14 signaling pathways, the functions of the significant targets, an effective ingredient in TCM prescriptions and its functions were obtained. Conclusions: Chinese herbal formulas containing quercetin could be a potential treatment for GGNs, targeting C-reactive protein (CRP), tumor necrosis factor (TNF), interferon gamma (IFN-γ), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor A (VEGFA) through the hypoxia-inducible factor 1 (HIF-1) pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and leukocyte transendothelial migration.

[Prevalence of central sleep apnea in different age groups of children with sleep apnea-hypopnea].

OBJECTIVE: To explore the prevalence of central sleep apnea in different age groups of children with sleep apnea-hypopnea (SAH). METHODS: A total of 431 children with SAH diagnosed by overnight polysomnography at our Sleep Center were retrospectively studied. They were divided into 3 groups based on their ages: toddler group (1 - < 3 years old), preschool group (3 - < 6 years old) and school group (6 - < 13 years old). The relationship between age and different types of apnea-hyponea index (AHI) was analyzed. And the prevalence of central sleep apnea and sleep structure were compared between the groups. RESULTS: A negative correlation existed between age and central sleep apnea index (r = -0.322, P < 0.01). However, there was no correlation between age and obstructive apnea index (P > 0.05). AHI was similar in different age groups, but the medians of central sleep apnea index for toddler, preschool and school groups were 2.35, 1.50 and 0.90 events/h respectively (all P < 0.01). Sleep structure was similar between the groups (P > 0.05). CONCLUSIONS: Central sleep apnea is common in children with sleep disordered breathing. The younger their ages, a higher prevalence of central sleep apnea.

[Comparison of manual versus automatic titration in pressure determination for long-term therapy of continuous positive airway pressure in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To compare the continuous positive airway pressure (CPAP) of automatic titration with that of manual titration. METHODS: A total of 58 patients with obstructive sleep apnea and hypopnea syndrome (OSAHS) diagnosed by overnight polysomnography at sleep center of First Affiliated Hospital, Guangzhou Medical University were studied between December 2010 and December 2012. Manual titration was performed under full polysmnography and auto-titration at home for 3-7 nights. RESULTS: There were 52 males and 6 females with an age range of (48 ± 11) years. CPAP pressure titrated by automatic device (10.0 ± 2.2) cm H2O (1 cm H2O = 0.098 kPa) was significantly higher than that titrated manually (7.5 ± 1.5) cm H2O (P = 0.000). Apnea-hyponea index decreased significantly from (54.0 ± 21.0) events/h pre-treatment to (3.8 ± 2.5) events/h post-treatment under manual titration (P < 0.01). CONCLUSIONS: CPAP pressure titrated by automatic device is usually higher than that titrated manually. Manual titration should be performed if a patient can not tolerate the CPAP pressure titrated by an automatic device.

Blood Eosinophil Endotypes across Asthma and Chronic Obstructive Pulmonary Disease (COPD).

Background: Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods: Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results: We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p < 0.001; COPD: P = 0.001); in asthma and COPD, the number of eosinophils in males was more significant than that in females (asthma: p < 0.001; COPD: p = 0.012). Second, asthma patients had higher blood eosinophil counts than those with COPD and ACO (p < 0.001). Moreover, we found out that eosinophil levels were highly expressed in the stable group of all three diseases. Finally, we found that most cytokines in ACO patients showed a downward trend when the level of eosinophils was low, whereas the results were reversed in asthma patients; 7 cytokines had similar trends in COPD and ACO patients. Conclusions: In conclusion, eosinophils have their own unique endotypes in asthma, COPD, and ACO patients, which were reflected in the fluctuation of their levels and changes in cytokine secretion.

Clinical application of fractional exhaled nitric oxide and nasal nitric oxide levels for the assess eosinophilic inflammation of allergic rhinitis among children.

BACKGROUND: Allergic rhinitis is one of the most common nasal inflammatory diseases among children. Assessment of clinical symptoms, skin prick test and serum immunoglobulin E (IgE) are common methods used to diagnose allergic rhinitis and assess inflammation degree in clinical settings. However, via blood tests assess eosinophils inflammation is invasive, and may cause fear in children. It makes have burden of the diagnosis of allergic rhinitis. Nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) are noninvasive, inexpensive, and can provide immediate results. These methods may therefore be preferable to assess the inflammation of allergic rhinitis. METHODS: This study was a retrospective analysis. We recruited 61 children with allergic rhinitis from November 2019 to March 2020. The participants were assessed using the FeNO and nNO tests. We also administered questionnaires and carried out traditional allergen and blood tests. We analyzed the relationship between diagnosis results and FeNO and nNO levels before and after the treatment of allergic rhinitis, to investigate the clinical application of FeNO and nNO levels for assess eosinophilic inflammation of allergic rhinitis in children. RESULTS: We observed a significant association both FeNO, nNO level with eosinophils, total IgE. In different levels of eosinophils (EOS), the correlation of detection parameters had obvious change. FeNO and nNO levels were obvious higher compared to pre-treatment. CONCLUSIONS: Using NO concentration can indicates the extent of allergic inflammation and can measure allergy treatment effects combine other influence indexes. The combined use of FeNO and nNO levels may be a useful method for assess the degree of eosinophilic inflammation of allergic rhinitis in children.

Short­term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats.

Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86 ± 9.73, vs. 45.60 ± 5.51%; P=0.025) and left ventricular fractional shortening (25.31 ± 6.30, vs. 15.42 ± 8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07 ± 2.63, vs. 19.95 ± 5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11 ± 0.50, vs. 1.54 ± 0.57 cm(3); P=0.032) and left ventricular end systolic volume (0.50 ± 0.28, vs. 0.87 ± 0.36 cm(3); P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP.

Food allergy and related risk factors in 2540 preschool children: an epidemiological survey in Guangdong Province, southern China.

BACKGROUND: Although the number of studies on allergic diseases in the general population of southern China is increasing, only a few have addressed food allergy (FA) in children in this region. The present study aimed to investigate the prevalence, clinical manifestations, spectrum of allergens, and related risk factors of FA in preschool children in Guangdong Province, southern China. METHODS: A random cluster-sampling method was used to select 24 kindergartens from 12 cities in Guangdong Province. The parents or guardians of the children were requested to complete a questionnaire on general information and data regarding FA diagnosis and symptoms in the children and their first-degree relatives. Thereafter, the Chi-square test, multivariate regression analysis, and Spearman's rank-order correlation coefficient analysis were performed to identify statistically significant differences. RESULTS: Analysis of 2540 valid questionnaires revealed an FA prevalence rate of 4%. Adverse food reactions were due to the consumption of shrimp (4.4%), crab (3.2%), mango (2.3%), cow's milk and dairy products (1.9%), and eggs (1.4%). Logistic regression analysis indicated that a history of FA and a history of allergic rhinitis in the first-degree relatives were the major factors leading to FA in children. CONCLUSIONS: The incidence of FA in children in Guangdong Province is higher than that commonly believed. An individual's genetic background is an important risk factor for FA. Hence, mitigation of the impact of lifestyle and environmental factors should be carefully considered to reduce the incidence of childhood FA.