The initial angle of the maximum expiratory flow-volume curve: a novel start-of-test criteria of spirometry in children.

The aim of the present study was to define an initial angle called ß and to assess its diagnostic value for identifying poor-quality maneuvers in spirometry testing in children. Furthermore, its predictive equation or normal value was explored. Children aged 4-14 years with respiratory symptoms who underwent spirometry were enrolled. Based on the efforts labeled during maneuvering and the quality control criteria of the guidelines, children were categorized into good-quality and poor-quality groups. According to ventilatory impairment, children in the good-quality group were divided into three subgroups: normal, restricted, and obstructed. Angle ß was the angle between the line from the expiratory apex to the origin of coordinates and the x-axis of the maximal expiratory flow-volume (MEFV) curve. Demographic characteristics, angle ß, and other spirometric parameters were compared among groups. The diagnostic values of angle ß, forced expiratory time (FET), and their combination were assessed using receiver operating characteristic curves. Data from 258 children in the good-quality group and 702 healthy children in our previous study were used to further explore the predictive equation or normal value of angle ß. The poor-quality group exhibited a significantly smaller angle ß (76.44° vs. 79.36°; P < 0.001), significantly lower peak expiratory flow (PEF), FET, and effective FET (ETe), and significantly higher expiratory volume at peak flow rate (FEV-PEF) and ratio of extrapolated volume and forced vital capacity (EV/FVC) than the good-quality group. There was no significant difference in angle ß among the normal, restricted, and obstructed groups. Logistic regression analysis revealed that smaller angle ß and FET values indicated poor-quality MEFV curves. The combination of angle ß < 74.58° and FET < 4.91 s had a significantly larger area under the curve than either one alone. The normal value of angle ß of children aged 4-14 years was 78.40 ± 0.12°.   Conclusions: Angle ß contributes to the quality control evaluation of spirometry in children. Both angle ß < 74.58° and FET < 4.91 s are predictors of poor-quality MEFV curves, while their combination offers the highest diagnostic value. What is Known: • A slow start is one of the leading causes of poor-quality maximal expiratory flow-volume (MEFV) curves, which is a particularly prominent issue among children due to limited cooperation, especially those younger than 6 years old. • It is relatively difficult to differentiate between ventilatory dysfunction and poor cooperation when a slow start occurs in children; therefore, there is an urgent need for an objective indicator that is unaffected by ventilatory impairment to evaluate quality control of spirometry. What is New: • The initial angle ß, which was introduced at the ascending limb of the MEFV curve in the present study, has a certain diagnostic value for poor-quality MEFV curves in children. • Angle ß < 74.58° is a predictor of poor-quality MEFV curves, and its combination with FET < 4.91 s offers a higher diagnostic value.

Histone acetylation regulates ORMDL3 expression-mediated NLRP3 inflammasome overexpression during RSV-allergic exacerbation mice.

Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1-like protein 3 (ORMDL3) and lead to NOD-like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV-induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV-bronchiolitis follow-up. In BEAS-2B, ORMDL3-induced NLRP3 inflammasome expression. BEAS-2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3-small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.

Multicenter analysis of epidemiological and clinical features of pediatric acute lower respiratory tract infections associated with common human coronaviruses in China, 2014-2019.

The common human coronaviruses (HCoVs) HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 which are members of the coronavirus family are long co-existed with humans and widely distributed globally. Common HCoVs usually cause mild, self-limited upper respiratory tract infections (URTI), and also associated with lower respiratory tract infections (LRTI), especially in children. However, there are little multicentre studies have been conducted in children of several different areas in China, and the epidemic potential of common HCoVs remains unclear. Understanding of the common HCoVs is valuable for clinical and public health. Herein, we retrospectively analysed the medical records of children with acute lower respiratory tract infection admitted to 9 hospitals from different regions in China from 2014 to 2019. Of the 124 patients who tested positive for coronaviruses, OC43 was the predominant type, accounting for 36.3% (45/124) of the detections. Children aged ≤ 6 months and 12-23 months had the highest detection rate of common HCoVs, and the detection rate gradually declined after 2 years old. These four HCoVs could be detected all year round. Among the areas of our study, the overall positive rate was higher in southern China, especially in Guangzhou (29/124, 23.4%). Moreover, common HCoV-positive patients were codetected with 9 other common respiratory pathogens. 229E (11/13, 84.6%) was the most frequently associated with codetection, with EV/RhV was the most frequently codetected virus. Cough (113/124, 91.1%) and fever (73/124, 58.9%) were the most common symptoms of common HCoVs infection.

A multicentre study on the incidence of respiratory viruses in children with community-acquired pneumonia requiring hospitalization in the setting of the zero-COVID policy in China.

BACKGROUND: Stringent nonpharmaceutical interventions (NPIs) have been implemented worldwide to combat the COVID-19 pandemic, and the circulation and seasonality of common respiratory viruses have subsequently changed. There have been few multicentre studies or comparisons of the prevalence of respiratory viruses accounting for community-acquired pneumonia (CAP) in hospitalized children between the pre-COVID period and the period after community and school reopening in the setting of the zero-COVID policy. METHODS: We included 1543 children with CAP who required hospitalization from November 1, 2020 to April 30, 2021 (period 1), and 629 children with the same conditions from November 1, 2018, to April 30, 2019 (period 2), in our study. All respiratory samples from these patients were screened for six respiratory viruses (respiratory syncytial virus [RSV], adenovirus [ADV], influenza A virus [Flu A], influenza B virus [Flu B], parainfluenza virus type 1 [PIV1], and parainfluenza virus type 3 [PIV3]) using a multiplex real-time PCR assay. RESULTS AND CONCLUSIONS: The median ages of the enrolled patients at the time of diagnosis were 1.5 years and 1.0 years for period 1 and period 2, respectively. In period 1, viral pathogens were detected in 50.3% (776/1543) of the enrolled patients. The most frequently identified viral pathogen was RSV (35.9%, 554/1543), followed by PIV3 (9.6%, 148/1543), PIV1 (3.6%, 56/1543), ADV (3.4%, 52/1543), Flu A (1.0%, 16/1543), and Flu B (0.8%, 13/1543). The total detection rates of these six viruses in the peak season of CAP were at the pre-COVID level. The prevalence of Flu A decreased dramatically, and circulation activity was low compared to pre-COVID levels, while the incidence of PIV3 increased significantly. There were no significant differences in the detection rates of RSV, ADV, Flu B, and PIV1 between the two periods. Our results showed that respiratory viruses accounted for CAP in hospitalized children at pre-COVID levels as communities and schools reopened within the zero-COVID policy, although the prevalence aetiology spectrum varied.

Clinical features and risk factors of plastic bronchitis caused by refractory Mycoplasma pneumoniae pneumonia in children: a practical nomogram prediction model.

Early assessment of refractory Mycoplasma pneumoniae pneumonia (RMPP) with plastic bronchitis (PB) allows timely removal of casts using fiberoptic bronchoscopic manipulation, which relieves airway obstruction and limit sequelae development. This study aimed to analyze clinical data for risk factors and develop a nomogram for early predictive evaluation of RMPP with PB. The clinical data of 1-14 year-old patients with RMPP were retrospectively analyzed. Patients were classified into a PB or non-PB group. The general characteristics, clinical symptoms, laboratory test results, imaging findings, and microscopic changes of the two groups were compared. A statistical analysis of the risk factors for developing PB was performed, and a nomogram model of risk factors was constructed. Of 120 patients with RMPP included, 68 and 52 were in the non-PB and PB groups, respectively. Using multivariate logistic regression analysis, fever before bronchoscopy, extrapulmonary complications, pleural effusion, cough duration, and lactate dehydrogenase (LDH) levels were identified as risk factors. A nomogram was constructed based on the results of the multivariate analysis. The area under the receiver operating characteristic curve value of the nomogram was 0.944 (95% confidence interval: 0.779-0.962). The Hosmer-Lemeshow test displayed good calibration of the nomogram (p = 0.376, R2 = 0.723). CONCLUSION: The nomogram model constructed in this study based on five risk factors (persistent fever before bronchoscopy, extrapulmonary complications, pleural effusion, cough duration, and LDH levels) prior to bronchoscopy can be used for the early identification of RMPP-induced PB. WHAT IS KNOWN: • Refractory Mycoplasma pneumoniae pneumonia (RMPP) in children has been increasingly reported and recognized, which often leads to serious complications. • Plastic bronchitis (PB) is considered to be one of the causes of RMPP, and bronchoscopic treatment should be improved as soon as possible to remove plastic sputum thrombus in bronchus. WHAT IS NEW: • This study determined the risk factors for RMPP-induced PB. • The nomogram model constructed in this study prior to bronchoscopy can be used for the early identification of RMPP-induced PB, which facilitate the early bronchoscopic removal of casts, thereby promoting recovery and reducing cases with poor RMPP prognosis.

The Use of Exercise Challenge Testing and Fractional Exhaled Nitric Oxide in Diagnosis of Chest Tightness Variant Asthma in Children.

BACKGROUND: Chest tightness variant asthma (CTVA) in children presents with chest tightness as the sole manifestation. Diagnostic tests are needed given the lack of typical asthma symptoms. The present study aimed to investigate the diagnostic value of exercise challenge testing (ECT) and fractional exhaled nitric oxide (FeNO) in pediatric CTVA. METHODS: We included 98 children aged 6-13 years with chest tightness as the sole symptom for >4 weeks. All subjects underwent FeNO measurement, spirometry and ECT, and received 4-week budesonide/formoterol treatment. According to treatment responses, children were categorized into CTVA (n = 12) and non-CTVA (n = 86) groups. Differences in clinical characteristics and FeNO, spirometry, and ECT results were compared between the two groups. The FeNO and ECT diagnostic performances were determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Children with CTVA exhibited significantly higher Mycoplasma pneumoniae IgG, total IgE, and FeNO values; greater post-ECT forced expiratory volume in 1 s (FEV1) fall; and more frequent sensitization to mites and pets than those without CTVA. Further logistic regression revealed that higher FEV1 fall (OR, 1.39; 95% CI: 1.11-1.74; p = 0.004) and higher FeNO values (OR, 1.04; 95% CI: 1.01-1.08; p = 0.014) were risk factors associated with CTVA. FEV1 fall and FeNO had similar areas under the ROC curve (AUCs) (0.79 vs. 0.78; p = 0.924), and their optimal CTVA-prediction cutoff values were 9.9% and 15.0 ppb, respectively. The AUC of FEV1 fall and FeNO combination was higher at 0.86 (95% CI: 0.78-0.93); however, no difference was observed using the single test (p > 0.05). Their combination exhibited a relatively higher sensitivity than that of FEV1 fall alone (0.75 vs. 0.67) and higher positive predictive value than that of FeNO alone (0.60 vs. 0.29). CONCLUSION: CTVA is a cause of unexplained recurrent chest tightness in children. FeNO ≥15.0 ppb and post-ECT FEV1 fall ≥9.9% are diagnostically valuable for CTVA in children, with their combination potentially contributing to greater diagnostic accuracy.

Carbenoxolone Ameliorates Allergic Airway Inflammation through NF-κB/NLRP3 Pathway in Mice.

Asthma is a respiratory disease characterized by heterogeneous chronic airway inflammation. Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome is involved in the development of many pulmonary inflammatory diseases. The role and regulatory mechanism of carbenoxolone (CBX) in ovalbumin (OVA)-induced asthma models are not fully clear. Therefore, the study investigated whether CBX ameliorates airway inflammation and remodeling, as well as its mechanism in OVA induced-inflammation in mice. Wright-Giemsa staining was used to count inflammatory cells in bronchoalveolar lavage fluid (BALF). The level of inflammatory cells infiltration, mucus cell proliferation, and collagen deposition in lung tissue were separately assessed by hematoxylin and eosin, periodic acid-Schiff, and Masson trichrome staining, respectively. Airway resistance (AR) was measured by non-invasive airway system. Immunohistochemical assay was used to observe NLRP3 expression area. The expression of nuclear factor-kappaB (NF-κB), p-NF-κB, inhibitor of kappaB (IκB)-α, p-IκB-α, NLRP3, pro-caspase-1, caspase-1, and interleukin (IL)-1ß in lung tissue were measured using quantitative real-time PCR or Western blotting. Our results showed that CBX can significantly attenuate the leukocyte count and the percentage of eosinophils and neutrophils in the BALF, peribronchial inflammation, airway mucus secretion, collagen deposition area, and AR in OVA-induced airway inflammation. In addition, the expression of p-NF-κB, p-IκB-α, NLRP3 and related factors were dramatically alleviated after CBX treatment. These data suggest that CBX has a significant protective effect on allergic airway inflammation by suppressing the activation of NLRP3 inflammasome through NF-κB pathway in asthmatic mice.

Fructose-1,6-bisphosphatase aggravates oxidative stress-induced apoptosis in asthma by suppressing the Nrf2 pathway.

Asthma is a chronic airway disease that causes excessive inflammation, oxidative stress, mucus production and bronchial epithelial cell apoptosis. Fructose-1,6-bisphosphatase (Fbp1) is one of the rate-limiting enzymes in gluconeogenesis and plays a critical role in several cancers. However, its role in inflammatory diseases, such as asthma, is unclear. Here, we examined the expression, function and mechanism of action of Fbp1 in asthma. Gene Expression Omnibus (GEO) data sets revealed that Fbp1 was overexpressed in a murine model of asthma and in interleukin (IL)-4- or IL-13-stimulated bronchial epithelial cells. We confirmed the findings in an animal model as well as Beas-2B and 16HBE cells. In vitro investigations revealed that silencing of Fbp1 reduced apoptosis and the proportion of cells in the G2/M phase, whereas overexpression led to increases. Fbp1 knock-down inhibited oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, whereas Fbp1 overexpression aggravated oxidative stress by suppressingthe Nrf2 pathway. Moreover, the Nrf2 pathway inhibitor ML385 reversed the changes caused by Fbp1 inhibition in Beas-2B and 16HBE cells. Collectively, our data indicate that Fbp1 aggravates oxidative stress-induced apoptosis by suppressing Nrf2 signalling, substantiating its potential as a novel therapeutic target in asthma.

Clinical features and risk factors analysis of bronchitis obliterans due to refractory Mycoplasma pneumoniae pneumonia in children: a nomogram prediction model.

BACKGROUND: Early prediction of bronchitis obliterans (BO) is of great significance to the improvement of the long-term prognosis of children caused by refractory Mycoplasma pneumoniae pneumonia (RMPP). This study aimed to establish a nomogram model to predict the risk of BO in children due to RMPP. METHODS: A retrospective observation was conducted to study the clinical data of children with RMPP (1-14 years old) during acute infection. According to whether there is BO observed in the bronchoscope, children were divided into BO and the non-BO groups. The multivariate logistic regression model was used to construct the nomogram model. RESULTS: One hundred and forty-one children with RMPP were finally included, of which 65 (46.0%) children with RMPP were complicated by BO. According to the multivariate logistic regression analysis, WBC count, ALB level, consolidation range exceeding 2/3 of lung lobes, timing of macrolides, glucocorticoids or fiber bronchoscopy and plastic bronchitis were independent influencing factors for the occurrence of BO and were incorporated into the nomogram. The area under the receiver operating characteristic curve (AUC-ROC) value of nomogram was 0.899 (95% confidence interval [CI] 0.848-0.950). The Hosmer-Lemeshow test showed good calibration of the nomogram (p = 0.692). CONCLUSION: A nomogram model found by seven risk factor was successfully constructed and can use to early prediction of children with BO due to RMPP.

WITHDRAWN: M2 macrophage-derived exosomes carry microRNA-370 to alleviate asthma progression through inhibiting the FGF1/MAPK/STAT1 axis.

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[Role of peak expiratory flow in the assessment and management of asthma in children].

Peak expiratory flow (PEF) is a portable, reliable, and inexpensive method for lung function assessment. PEF can reflect expiratory airflow limitation and its variability can document reversibility, which provides an objective basis for the diagnosis of asthma in children. Short-term PEF monitoring can be an important aid in the management of acute asthma exacerbations, identification of possible triggers, and assessment of response to treatment. Long-term PEF monitoring can assist in the assessment of asthma control and warning of acute exacerbations, and this is useful for children with severe asthma. This article reviews the measurements, influencing factors, interpretation, and application of PEF, and its role in the diagnosis and management of asthma in children, to provide references for the clinical application of PEF in children.

[Correlation between bronchial dilation test and asthma control level in children with asthma].

OBJECTIVE: To study the correlation between the bronchial dilation test (BDT) and asthma control level in children with asthma. METHODS: A total of 153 children with asthma, aged 5-14 years, who attended the outpatient service from March 2016 to March 2018 were enrolled. According to the presence or absence of atopic constitution, they were divided into an allergic group with 79 children and a non-allergic group with 74 children. The correlation between BDT and Childhood Asthma Control Test (C-ACT) scores was analyzed for both groups. RESULTS: All basic pulmonary function parameters were positively correlated with C-ACT scores in the non-allergic group (P < 0.05). Except the forced vital capacity, peak expiratory flow and maximal expiratory flow at 25% vital capacity in percent predicted values, the other pulmonary function parameters were positively correlated with C-ACT scores in the allergic group (P < 0.05). The improvement rates of all BDT parameters (except maximal expiratory flow at 25% vital capacity in the allergic group and maximal expiratory flow at 50% vital capacity in the non-allergic group) were negatively correlated with C-ACT scores in the two groups (P < 0.05). CONCLUSIONS: The improvement rate of BDT is well correlated with C-ACT scores in children with asthma, suggesting that BDT can be used as an index for predicting asthma control level.

Establishment of a predictive equation for pulmonary ventilation function in school-aged children in northeast China: a prospective study. / ä¸œåŒ—åœ°åŒºå­¦é¾„æœŸå„¿ç«¥è‚ºé€šæ°”åŠŸèƒ½é¢„è®¡æ–¹ç¨‹å¼å»ºç«‹çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To establish a predictive equation for commonly used pulmonary ventilation function parameters in children aged 6-<16 years in northeast China. METHODS: A total of 504 healthy children from Liaoning, Jilin, and Heilongjiang provinces of China were selected for the prospective study, among whom there were 242 boys and 262 girls. The JAEGER MasterScreen Pneumo spirometer was used to measure pulmonary ventilation function. With the measured values of 10 parameters, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and back-extrapolated volume (BEV), as dependent variables and age, body height, and body weight as independent variables, the stepwise multivariate regression method was used to establish the regression equation for children of different sexes. The mean of relative prediction error was used to evaluate the applicability of the predictive equation. RESULTS: The boys aged 9-<10 years and 15-<16 years had significantly higher body height, FVC, and FEV1 than the girls of the same age (P<0.05), and the boys aged 9-<10, 10-<11, 11-<12, and 13-<14 years had a significantly lower FEV1/FVC ratio than the girls of the same age (P<0.05). The correlation analysis showed that all parameters, except FEV1/FVC ratio and BEV/FVC ratio, were significantly positively correlated with age, body height, and body weight (P<0.001). Further regression analysis showed that age and body height were the influencing factors for most parameters, while body weight was less frequently included in the regression equation. Compared with the predictive equations from previous studies, the regression equation established in this study had relatively good applicability in the study population. CONCLUSIONS: A new predictive equation for the main pulmonary ventilation function parameters has been established in this study for children aged 6-<16 years in northeast China, which provides a basis for accurate judgment of pulmonary function abnormalities in clinical practice.

Vasoactive intestinal peptide inhibits airway smooth muscle cell proliferation in a mouse model of asthma via the ERK1/2 signaling pathway.

Asthma is a heterogeneous clinical syndrome characterized by airway inflammation, hyper-responsiveness and remodeling. Airway remodeling is irreversible by current antiasthmatic drugs, and it is the main cause of severe asthma. Airway smooth muscle cells (ASMCs) act as the main effector cells for airway remodeling; the proliferation and hypertrophy of which are involved in airway remodeling. Caveolin (Cav)- 1 is present on the surface of ASMCs, which is involved in cell cycle and signal transduction regulation, allowing ASMCs to change from proliferation to apoptosis. The extracellular signal-regulated kinase (ERK)1/2 signaling pathway is a common pathway regulated by various proliferative factors, which demonstrates a regulatory role in airway remodeling of asthma. There have been many studies on the correlation between vasoactive intestinal peptide (VIP) and airway reactivity and inflammation in asthma, but the functions and related mechanisms of ASMCs remain unclear. In this study, we established an airway remodeling model in asthmatic mice, and concluded that VIP inhibits airway remodeling in vivo. The in vitro effect of VIP on interleukin-13-induced proliferation of ASMCs was studied by examining the effects of VIP on expression of ERK1/2, phospho-ERK1/2 and Cav-1 in ASMCs, as well as changes in cell cycle distribution. VIP inhibited phosphorylation of the ERK1/2 signaling pathway and expression of Cav-1 on ASMCs and decreased the proportion of S phase cells in the cell cycle, thus inhibiting the proliferation of ASMCs. This study provides a novel therapeutic mechanism for the treatment of asthma.

Chinese guidelines for childhood asthma 2016: Major updates, recommendations and key regional data.

OBJECTIVE: With increased industrialization and urbanization in China, pediatric asthma is becoming more prevalent. Despite a growing body of evidence, there remains a significant unmet need for adequate management of childhood asthma. The Subspecialty Group of Respiratory Diseases of the Society of Pediatrics, the Chinese Medical Association, and the editorial board of the Chinese Journal of Pediatrics have recently updated the "Guidelines for diagnosis and optimal management of asthma in children," first published in 2008. METHODS: This article reviews the major updates to the guidelines and covers the main recommendations for diagnosis, assessment, and treatment of pediatric asthma in China. Key regional data on epidemiology, clinical features, disease burden, knowledge among children and parents, and risk factors including pollution are provided to contextualize the recommendations. RESULTS: The major updates to the guidelines include: (1) A more practical definition of asthma; (2) assessment of asthma control that takes into account both current symptom control and future risk; (3) classification based on disease severity that corresponds with treatment step; (4) differentiation between difficult-to-treat and poorly controlled asthma; (5) an open-ended approach to pharmacological management; and (6) allergen immunotherapy (AIT) in mild- to moderate-persistent asthma. CONCLUSIONS: The updated "Guidelines for the diagnosis and optimal management of asthma in children (2016)" combine the latest national and international clinical evidence and experience to provide practical and reliable recommendations to Chinese clinicians.

Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor-E2-related factor 2/haem oxygenase (HO)-1 signalling pathway.

Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor-E2-related factor 2 (Nrf2)/haem oxygenase (HO)-1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent assay. Histological analyses were evaluated with haematoxylin-eosin and periodic acid-Schiff staining. Airway hyperresponsiveness was examined by whole-body plethysmography. Nuclear factor-E2-related factor 2, HO-1, nuclear factor-κB and inhibitory κB/p-inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor-α, interleukin (IL)-1ß, and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor-κB and p-inhibitory κB levels were elevated in the lung tissue of ovalbumin-challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase-1 and nuclear Nrf2 levels were enhanced in dose- and time-dependent manners in curcumin-treated RAW264.7 cells. Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-α, IL-1ß, and IL-6. After the cells were transfected with HO-1 or Nrf2 small interfering RNA, lipopolysaccharide-induced pro-inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway, potentially making it an effective drug in asthma treatment.

[Diagnostic values of fractional exhaled nitric oxide for typical bronchial asthma and cough variant asthma in children].

OBJECTIVE: To study the diagnostic values of fractional exhaled nitric oxide (FeNO) for typical bronchial asthma and cough variant asthma in children, and to explore whether FeNO can be applied to differentiate typical bronchial asthma from cough variant asthma in children. METHODS: A total of 150 children who were newly diagnosed with typical bronchial asthma between June 2012 and June 2014, as well as 120 children who were newly diagnosed with cough variant asthma during the same period, were selected as subjects. FeNO measurement, spirometry, and methacholine provocation test were performed for both groups. Meanwhile, 150 healthy children were selected as the control group, and their FeNO was measured. The diagnostic values of FeNO for typical bronchial asthma and cough variant asthma were analyzed using the receiver operating characteristic curve. RESULTS: The FeNO values in the typical bronchial asthma and cough variant asthma groups were significantly higher than in the control group (P<0.01), and the FeNO value in the typical bronchial asthma group was significantly higher than in the cough variant asthma group (P<0.01). FEV1/FVC%, FEV1%pred, and PD20 were significantly lower in the typical bronchial asthma group than in the cough variant asthma group (P<0.01). The optimal cut-off value of FeNO was 19.5 ppb for the diagnosis of typical bronchial asthma, with a sensitivity of 83.3% and a specificity of 86.7%; the optimal cut-off value of FeNO was 15.5 ppb for the diagnosis of cough variant asthma, with a sensitivity of 67.5% and a specificity of 78.0%; the optimal cut-off value of FeNO was 28.5 ppb for the differentiation between typical bronchial asthma and cough variant asthma, with a sensitivity of 60.7% and a specificity of 82.5%. CONCLUSIONS: Measurenment of FeNO may be useful in the diagnosis and differential diagnosis of typical bronchial asthma and cough variant asthma.

[Expression of leptin and its receptor in lungs of asthmatic BALB/c mice and effect of budesonide on their expression].

OBJECTIVE: To determine the changes in the expression of leptin and its receptor in the lungs of mice with varying degrees of asthma before and after budesonide treatment. METHODS: Forty Balb/c mice were randomly assigned into 4 groups with 10 animals in each. One group received no treatment (control group) and the other groups were challenged with either nebulized ovalbumin (OVA) for three days (3-day group) or seven days (7-day group), or with nebulized ovalbumin followed by budesonide administration (treatment group). Changes in airway inflammation were observed using hematoxylin-eosin staining. The protein and mRNA levels of leptin and its receptor in lung tissues were determined using immunohistochemistry/Western blot and real-time PCR, respectively. RESULTS: The two asthmatic groups showed more significant pathological changes in the airway than the control and the treatment groups. Mice that were challenged by OVA for seven days showed more marked pathological changes in the airway compared with mice challenged by OVA for three days. The protein and mRNA levels of leptin in the lung tissues of the 3-day group were significantly higher than those of the control group (P<0.01), but significantly lower than those of the 7-day group (P<0.01). The protein levels of leptin receptor in the lung tissues of the 3-day group were significantly lower than those of the control group (P<0.01). The treatment group showed increased protein levels of leptin receptor compared with the 7-day group (P<0.01). No significant difference was noted between the four groups with respect to the mRNA levels of leptin receptor in the lung tissues. CONCLUSIONS: Leptin is highly expressed whereas its receptor is lowly expressed in the lung tissues of asthmatic mice. Budesonide can increase the expression of leptin receptor, but has no significant impact on the expression of leptin.

[Effects of NK-1R inhibitor WIN62577 on the migration of airway smooth muscle cells in asthmatic rats with airway remodeling].

OBJECTIVE: To study the changes in the migration of airway smooth muscle cells (ASMC) in asthmatic rats with airway remodeling and the effect of NK-1R inhibitor WIN62577 on the migration of ASMC. METHODS: Sprague-Dawley rats were randomly assigned into two groups: airway remodeling induced by asthma and normal control. ASMC from rats with asthma and airway remodeling induced by ovalbumin (OVA) inhalation for 8 weeks were primary cultured and purified. Immunofluorescence and real-time PCR were used to measure the expression of NK-1R. With NK-1R inhibitor WIN62577 treatment, the changes in the migration of ASMC were measured by transwell chambers. RESULTS: NK-1R in ASMC was expressed mainly in the cytoplasm and cell membrane in the airway remodeling group, and the mRNA expression of NK-1R was higher than the normal control group (P<0.01). The number of the migrated ASMC in the airway remodeling group was significantly higher than that in the normal control group (P<0.01). Various concentrations (10-11 mol/L, 10-10 mol/L, 10-9 mol/L and 10-8 mol/L) of WIN62577 treatment decreased the number of the migrated ASMC (P<0.05). CONCLUSIONS: NK-1R may affect airway remodeling possibly through promoting the migration ability of ASMC in rats with asthma.

[Effect of dexamethasone on osteopontin expression in the lung tissue of asthmatic mice].

OBJECTIVE: To study the correlation between airway inflammation and osteopontin (OPN) level in the lung tissue, and to study the effect of dexamethasone (DXM) on OPN expression. METHODS: Fifty mice were randomly divided into 5 groups: normal control, ovalbumin (OVA)-challenged asthma groups (OVA inhalation for 1 week or 2 weeks) and DXM-treated asthma groups (DXM treatment for 1 week or 2 weeks). The mice were sensitized and challenged with OVA to prepare mouse model of acute asthma. Alterations of airway inflammation were observed by haematoxylin-eosin staining. Serum level of OVA-sIgE was evaluated using ELISA. OPN expression in the lung tissue was located and measured by immunohistochemistry and Western blot respectively. OPN mRNA level in the lung tissue was detected by real-time PCR. RESULTS: The asthma groups showed more pathological changes in the airway than the normal control and the DXM-treated groups. Compared with the OVA-challenged 1 week group, the pathological alterations increased in the OVA-challenged 2 weeks group. The level of OVA-sIgE in serum increased in the asthma groups compared with the control and the DXM groups (P<0.01). Serum OVA-sIgE sevel increased more significantly in the OVA-challenged 2 weeks group compared with the OVA-challenged 1 week group (P<0.01). OPN protein and mRNA levels were significantly raised in the asthma groups compared with the normal control and the DXM groups (P<0.01), and both levels increased more significantly in the OVA-challenged 2 weeks group compared with the OVA-challenged 1 week group (P<0.01). CONCLUSIONS: The increased OPN expression in the lung tissue is associated with more severe airway inflammation in asthmatic mice, suggesting that OPN may play an important role in the pathogenesis of asthma. DXM can alleviate airway inflammation possibly by inhibiting OPN production.