The clinical association of programmed death-1/PD-L1 axis, myeloid derived suppressor cells subsets and regulatory T cells in peripheral blood of stable COPD patients.

Background: Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients. Methods: Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood. Results: Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs (p < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs (p < 0.01) was detected in COPD patients. The expression of PD-1 on CD4+ Tcells and Tregs, but not CD8+Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs (p < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, p < 0.0001) and CTLA-4 (r = 0.42, p = 0.0014) on Tregs in COPD. Conclusion: The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD.

The distribution of myeloid-derived suppressor cells subsets and up-regulation of programmed death-1/PD-L1 axis in peripheral blood of adult CAP patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP). METHODS: This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. RESULTS: Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. CONCLUSIONS: In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients.

Long-Term Efficacy and Safety of Recombinant Human Growth Hormone in Children Born Small for Gestational Age.

There is a lack of long-term data on the benefit of growth hormone (GH) treatment in Chinese children born small for gestational age (SGA). This study was conducted to assess the long-term efficacy and safety of GH treatment in children born SGA. One hundred and twenty prepubertal SGA children who did not achieve catch-up growth with height remained less than -2 standard deviations (SD) below gender-specific height were enrolled in this two-year, randomized, dose-comparative study followed by an extension study of up to 10 years. Daily subcutaneous injections of 0.23 mg/kg/week [low-dose (LD) group] or 0.46 mg/kg/week [high-dose (HD) group] somatropin were given for 104 weeks. Dosing in the extension study was≤0.46 mg/kg/week. The main outcome measures were change in height SD score (ΔHT-SDS), height velocity, insulin-like growth factor (IGF)-1, and IGF-1/IGF binding protein-3 (IGFBP-3) molar ratio. ΔHT-SDS at week 104 was 0.91±0.53 and 1.52±0.64 in the LD and HD groups (intergroup p<0.0001), respectively, and continued in an upward trend throughout the extension study, remaining above+2 for those who received treatment for a total of 7 years or more. At week 104, significant improvements were observed in height velocity, IGF-1 SDS, and IGF-1/IGFBP-3 molar ratio. Adult HT-SDS was -0.81±1.68 for boys and -0.82±1.05 for girls (p=0.9837). Glucose metabolism and thyroid function were within the normal reference range throughout treatment. Long-term recombinant human GH treatment was tolerable and effective at improving height in children born SGA.

Peripheral blood T-lymphocyte subsets are potential biomarkers of disease severity and clinical outcomes in patients with ulcerative colitis: a retrospective study.

BACKGROUND: Ulcerative colitis (UC) is considered an immune-mediated disease. The disorder of T-lymphocyte subsets plays an important role in the pathogenesis of UC. The aim of this study was to evaluate the significance of peripheral blood T-lymphocyte subsets in assessing disease severity and predicting clinical outcomes in UC patients. METHODS: The retrospective case-control study was performed in 116 UC patients with active disease and 90 healthy controls (HC). The UC patients included were followed up for 180 days. Analyses of t-test, Spearman's correlation coefficient, multivariable Cox regression analysis, receiver operating characteristic (ROC) curves and cumulative survival analysis were done. RESULTS: The UC patients had lower proportions of CD4+T cells (42.85%±9.77% vs 45.71%±7.94%, P=0.021) and higher proportion of CD8+T cells (27.88%±8.86% vs 25.00%±6.47%, P=0.008) than HC. The severely active UC patients had higher proportion of CD3+HLA-DR+ T cells (8.83%±6.55% vs 2.80%±1.55%, P<0.001; 8.83%±6.55% vs 4.06%±5.01%, P<0.001) and CD8+T cells (31.35%±8.49% vs 26.98%±7.98%, P=0.029; 31.35%±8.49% vs 25.46%±9.15%, P=0.003) than mild and moderate group, whereas lower proportion of CD4+CD25+T cells (2.86%±1.35% vs 3.46%±1.07%, P=0.034) than mild group and CD4+T cells (40.40%±9.36% vs 44.73%±10.39%, P=0.049) than moderate group. The area under the curve (AUC) of CD3+HLA-DR+ T cells for assessing severely active UC was 0.885, with the cut-off value of 5.33%. The sensitivity was 76.32% and specificity was 89.74%. The combination of CD3+HLA-DR+ T cells and CRP had stronger assessment value with AUC of 0.929. The AUC of CD8+T cells, CD4+/CD8+ ratio and CD4+CD25+T cells for assessing disease severity was 0.677, 0.669 and 0.631 respectively. Within the 180 days follow-up, 24 patients (20.69%) had UC-related readmission or surgery, with higher proportion of CD3+HLA-DR+ T cells (10.66%±9.52% vs 3.88%±2.56%, P=0.003) and CD8+T cells (31.19%±10.59% vs 27.01%±8.20%, P=0.039) than those without readmission and surgery. The proportion of CD3+HLA-DR+ T cells was the independent predictor of UC-related readmission or surgery (HR=1.109, P=0.002). The AUC of CD3+HLA-DR+ T cells for predicting readmission or surgery was 0.796 with the cut-off value of 5.38%. UC patients with CD3+HLA-DR+T cells proportion>5.38% had a shorter time to readmission or surgery (log-rank test, P<0.001). CONCLUSIONS: The combination of CD3+HLA-DR+T cells and CRP may be potential biomarker of disease severity in UC patients. The high proportion of CD3+HLA-DR+T cells may be associated with an increased risk of readmission or surgery in UC patients.

Long-acting PEGylated growth hormone in children with idiopathic short stature.

Objective: To evaluate the safety and efficacy of weekly PEGylated-recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS) in China. Design and methods: This was a multicenter, phase II study in which all subjects were randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (low-dose (LD) group) or 0.2 mg/kg/week (high-dose (HD) group) or control for 52 weeks. The primary end point was change (Δ) in height s.d. score (HT-SDS) from baseline to week 52. Secondary end points were height velocity (HV), bone maturity, insulin-like growth factor-1 (IGF-1) SDS, and IGF-1/insulin-like growth factor-binding protein-3 (IGFBP-3) molar ratio. Results: A total of 360 children with ISS were recruited in the study (n = 120 in each group). At week 52, ΔHT-SDS was 0.56 ± 0.26, 0.98 ± 0.35, and 0.20 ± 0.26 in the LD, HD, and control groups, respectively (within-group P < 0.0001; intergroup P < 0.0001). Statistically significant values of ΔHV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs. Conclusion: Fifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.

The pharmacokinetic and pharmacodynamic properties and short-term outcome of a novel once-weekly PEGylated recombinant human growth hormone for children with growth hormone deficiency.

Objectives: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD). Methods: A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 µg/kg/week of YPEG-rhGH groups and daily rhGH 35 µg/kg/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12. Results: A dose-dependent response of maximum plasma concentration (Cmax) and area under the concentration-time curves from 0 to 168 hours (AUC0-168h) were observed for YPEG-rhGH. The ratio of Cmax and the ratio of AUC0-168h from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm/year, and 11.58 cm/year for YPEG-rhGH 100, 120, and 140 µg/kg/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported. Conclusion: The PK/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 µg/kg/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 µg/kg/day in children with GHD. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04513171].

Risk Factors for Short Stature in Children Born Small for Gestational Age at Full-Term.

Objective: This study aims to identify the risk factors associated with short stature in children born small for gestational age (SGA) at full-term. Methods: This was a retrospective study. The subjects were full-term SGA infants who were followed up until the age of 2 years. The risk factors for short stature were identified with univariate and multivariate analyses. Results: Of 456 full-term SGA children enrolled in this study, 28 cases had short stature at 2 years of age. A significant decrease in placental perfusion was found in the short children group with intravoxel incoherent motion (IVIM) technology, which was an advanced bi-exponential diffusion-weighted imaging (DWI) model of magnetic resonance imaging (MRI) (p = 0.012). Compared to non-short children born SGA at full-term, the short children group underwent an incomplete catch-up growth. Mothers who suffered from systemic lupus erythematosus were more likely to have a short child born SGA (p = 0.023). The morbidity of giant placental chorioangioma was higher in the short children group. The pulsatility index (PI), resistivity index (RI), and systolic-diastolic (S/D) ratio of umbilical artery were higher in the short children group than in the non-short control group (p = 0.042, 0.041, and 0.043). Multivariate analysis demonstrated that decrease of perfusion fraction (f p) in IVIM of placental MRI, chromosomal abnormalities, short parental height, and absence of catch-up growth were associated with a higher risk of short stature in children born SGA at full-term. Conclusion: Risk factors for short stature in full-term SGA children at 2 years of age included a decrease of perfusion fraction f p in IVIM of placental MRI, chromosomal abnormalities, and short parental height.

A Randomized Controlled Phase 3 Study on the Efficacy and Safety of Recombinant Human Growth Hormone in Children With Idiopathic Short Stature.

Background: To evaluate the safety and efficacy of daily somatropin (Jintropin®), a recombinant human growth hormone, in prepubertal children with ISS in China. Methods: This study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (△) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included △height from baseline; △bone age (BA)/CA; △height velocity (HV) and △insulin-like growth factor 1 (IGF-1 SDS). Results: △HT-SDS at week 52 was 1.04 ± 0.31 in the treatment group and 0.20 ± 0.33 in the control group (P < 0.001). At week 52, statistical significance was observed in the treatment group compared with control for △height (10.19 ± 1.47 cm vs. 5.85 ± 1.80 cm; P < 0.001), △BA/CA (0.04 ± 0.09 vs. 0.004 ± 0.01; P < 0.001), △HV (5.17 ± 3.70 cm/year vs. 0.75 ± 4.34 cm/year; P < 0.001), and △IGF-1 SDS (2.31 ± 1.20 vs. 0.22 ± 0.98; P < 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related. Conclusions: Daily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile. Trial Registration: ClinicalTrials.gov (identifier: NCT03635580). URL: https://clinicaltrials.gov/ct2/show/NCT03635580.

An open label, multicenter clinical trial that investigated the efficacy and safety of leuprorelin treatment of central precocious puberty in Chinese children.

BACKGROUND: Leuprorelin is an analog of gonadotropin-releasing hormone that is used for the therapy of central precocious puberty (CPP). The aims of this prospective, open label, multicenter clinical trial were to establish its efficacy and safety during long-term use. METHODS: Patients, who were all children, were treated with 1.88 to 3.75 mg leuprorelin subcutaneously once every 4 weeks for a total of 96 weeks between 2015 and 2018. The primary endpoint was the rate of occurrence of adverse events (AEs) and the secondary endpoint was no progression in the Tanner stage or regression by week 96 compared to baseline. RESULTS: A total of 307 CPP patients, 305 (99.3%) females and 2 males (0.7%), completed the 96-weeks of treatment. Due to limited data for male patients, they are not discussed in the efficacy results. Treatment-emergent AEs (TEAEs) were reported for 252 (82.1%) patients, mostly (79.5%) being mild or moderate and only 33 (10.7%) of patients experienced TEAEs related to leuprorelin therapy. The most frequent (>2%) drug-related TEAEs were injection site induration (4.6%, 14/307) and vaginal bleeding (2.3%, 7/305). After treatment, 83.5% of patients had regression or no progression in the Tanner stage (95% confidence interval: 78.68%, 87.62%) and the majority had decreased gonadotropin-releasing hormone-stimulated peak luteinizing hormone and follicle-stimulating hormone concentrations, as well as reduced sex hormone concentrations and a reduction in the bone age/chronological age ratio compared to baseline. CONCLUSIONS: The trial revealed that CPP was effectively treated in most patients who received leuprorelin for nearly 2 years. Any drug-related AEs were reported with low incidence (<5%) and were consistent with the known safety profile of leuprorelin. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (registration number: NCT02427958).

Deregulated microRNA-22-3p in patients with sepsis-induced acute kidney injury serves as a new biomarker to predict disease occurrence and 28-day survival outcomes.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of sepsis. MicroRNA-22-3p (miR-22-3p) has been found to be involved in septic AKI progression. The purpose of this study was to analyze both the serum and urinary expression of miR-22-3p in septic AKI patients, and evaluated the clinical value of miR-22-3p in the diagnosis and prognosis of sepsis-induced AKI. METHODS: Serum and urinary expression of miR-22-3p was examined using qRT-PCR. The risk factors related with septic AKI onset were assessed using logistic analysis. A receiver-operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of miR-22-3p, and the Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the predictive value of miR-22-3p for the 28-day survival of septic AKI patients. RESULTS: Both serum and urinary miR-22-3p expression was decreased and negatively correlated with kidney injury biomarkers in septic AKI patients. MiR-22-3p expression was a risk factor for AKI onset and had diagnostic accuracy in septic AKI patients. The expression of both serum and urinary miR-22-3p was lower in patients who died, and served as a prognostic biomarker to predict 28-day survival in septic AKI patients. CONCLUSION: Serum and urinary miR-22-3p was reduced in sepsis-induced AKI patients, and served as a biomarker to predict AKI occurrence and 28-day survival in sepsis patients.

Diffuse pulmonary lymphangiomatosis: A rare case report in an adult.

RATIONALE: Diffuse pulmonary lymphangiomatos (DPL) is a rare aggressive lymphatic disorder characterized by proliferation of anastomozing lymphatic vessels and extremely rare in adult patients. PATIENT CONCERNS: We report a case of diffuse pulmonary lymphangiomatosis in 59-year-old man presented with cough and sputum for 2 months. DIAGNOSES: Combining clinical manifestations with results of radiological, bronchoscopy, and surgical lung biopsy, it was consistent with the diagnosis of DPL. INTERVENTIONS: After bronchoalveolar lavage and biopsy, symptom of cough got worse suddenly accompanied by excessive chyloptysis. The patient received an emergency surgical intervention and low fat medium chain fat treatment. OUTCOMES: The patient was discharged with a much better health condition. LESSONS: This case report is the oldest patient reported in the English literature, to the best of our knowledge. Serious complications of bronchoscopy should be considered, especially in DPL patients with severely enlarged mediastinum or with thin-walled translucent vesicles under endoscopy.

Neuromuscular electrical stimulation improves exercise capacity in adult patients with chronic lung disease: a meta-analysis of English studies.

BACKGROUND: Neuromuscular electrical stimulation (NMES) has been suggested as an alternative rehabilitative therapy to enhance exercise performance and skeletal muscle function in adult patients with chronic lung disease. However, the results of individual studies have been inconsistent. We performed a meta-analysis to evaluate the effectiveness of NMES with regard to increasing exercise capacity, quadriceps strength, muscle mass, cross-sectional area, and quality of life and decreasing dyspnea in adult patients with chronic lung disease. METHODS: A systematic search was conducted of the PubMed, Cochrane Library and EMBASE databases for randomized controlled trials (RCTs) published in English-language journals before January 2018. Data were extracted using standardized forms, and the weighted mean difference (WMD) or standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated. RESULTS: Eleven RCTs involving 368 patients were included in this meta-analysis. The pooled results showed that NMES significantly improved the 6-min walk distance (WMD: 37.93 m, 95% CI: 19.53-56.33 m; P<0.0001; P for heterogeneity =0.11; I2=47%) but not the incremental shuttle walk test (WMD: 18.18 m, 95% CI: -79.41 to 115.77 m, P=0.72; P for heterogeneity <0.0001, I2=94%) or endurance shuttle walk test (ESWT) (WMD: 96.73 m, 95% CI: -45.58 to 239.03 m, P=0.18; P heterogeneity =0.22, I2=34%). Moreover, NMES was associated with a significant improvement in quadriceps strength (SMD: 1.14, 95% CI: 0.86-1.43, P<0.00001; P heterogeneity =0.02, I2=58%). CONCLUSIONS: This systemic review and meta-analysis provided evidence supporting the beneficial role of NMES in improving exercise capacity in patients with chronic respiratory disease.

Effect of IRAK-M on Airway Inflammation Induced by Cigarette Smoking.

BACKGROUND: IRAK-M, negatively regulating Toll-like receptor, is shown the dual properties in the varied disease contexts. We studied the effect of IRAK-M deficiency on cigarette smoking- (CS-) induced airway inflammation under acute or subacute conditions in a mouse model. METHODS: A number of cellular and molecular techniques were used to detect the differences between IRAK-M knockout (KO) and wild type (WT) mice exposed to 3-day or 7-week CS. RESULTS: Airway inflammation was comparable between IRAK-M KO and WT mice under 3-day CS exposure. Upon short-term CS exposure and lipopolysaccharide (LPS) inhalation, IRAK-M KO mice demonstrated worse airway inflammation, significantly higher percentage of Th17 cells and concentrations of proinflammatory cytokines in the lungs, and significantly elevated expression of costimulatory molecules CD40 and CD86 by lung dendritic cells (DCs) or macrophages. Conversely, 7-week CS exposed IRAK-M KO mice demonstrated significantly attenuated airway inflammation, significantly lower concentrations of proinflammatory cytokines in the lungs, significantly increased percentage of Tregs, and lower expression of CD11b and CD86 by lung DCs or macrophages. CONCLUSIONS: IRAK-M plays distinctive effect on CS-induced airway inflammation, and influences Treg/Th17 balance and expression of costimulatory molecules by DCs and macrophages, depending on duration and intensity of stimulus.

Efficacy and Safety of Tiotropium in the Treatment of Severe Persistent Asthma:Meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma. METHODS: Reports of randomized controlled trials (RCTs) describing tiotropium for treatment of severe persistent asthma published from January 1946 to February 2015 were searched in Cochrane Library, ClinicalTrials.gov, PubMed, Ovid Medline, CNKI, and CSJD. The data of the included RCTs were extracted and the data quality was evaluated. Meta-analyses were performed with Revman 5.3 software. RESULTS: Five RCTs including 1433 patients were analyzed. Meta-analysis of the data showed that compared with the placebo group, tiotropium treatment significantly improved the patients' peak forced expiratory volume in one second (FEV1) [weighted mean difference (WMD): 0.13 L, 95% confidence interval (CI): 0.10-0.16 L, P<0.00001], trough FEV1 (WMD: 0.09 L, 95%CI: 0.06-0.12 L, P<0.00001), peak forced vital capacity (FVC) (WMD: 0.10 L, 95%CI: 0.06-0.14 L, P<0.00001), trough FVC (WMD: 0.12 L, 95%CI: 0.08-0.17 L, P<0.00001), morning peak expiratory flow (PEF) (WMD: 9.21 L/min, 95%CI: 4.2-14.23 L/min, P=0.0003), evening PEF (WMD: 22.06 L/min, 95%CI 13.05-31.08 L/min, P<0.00001). The scores of asthma control questionnaire (ACQ) (WMD: 0.01, 95% CI: -0.07-0.09, P=0.86) or asthma quality of life questionnaire (AQLQ)(WMD: 0.06, 95% CI:-0.18-0.06, P=0.33) were not affected by tiotropium. No significant difference with adverse events between tiotropium group and placebo group were reported in these included studies (P>0.05). CONCLUSIONS: Tiotropium for severe persistent asthma treatment can improve FEV1, FVC, and PEF but may not improve the quality of life of the patients. Tiotropium is well tolerated and can be an add-on therapy for severe persistent asthma.

[Clinical Analysis of 35 Inpatients with Diffuse Panbronchiolitis in Peking Union Medical College Hospital].

OBJECTIVE: To summarize the clinical features of diffuse panbronchiolitis (DPB). METHOD: We retrospectively analyzed the clinical data of 35 patients who had been admitted to Peking Union Medical College Hospital from December 1996 to July 2014 due to DPB,which was confirmed basing on the diagnostic criteria proposed in 1998 by a working group of the Ministry of Health and Welfare of Japan or histopathological examination. RESULTS: The average age of these 35 patients (20 men and 15 women,with a sex ratio of 1.33 to 1) was (42.2<15.6) years,mainly distributed in the 40-49 age group. The average clinical history was (8.4<8.5) years. The main symptoms and signs of DPB included chronic cough (n=35,100%),copious purulent sputum production (n=31,88.6%),exertional dyspnoea (n=24,68.6%),end-inspiratory crackles (n=28,80.0%). Also,26 patients (74.3%) had a history of sinusitis. Cold agglutination test in 15 out of 15 patients were negative. Pseudomonas aeruginosa and Haemophilus influenza were isolated from 22 patients (73.3%,22/30),and 26 patients (83.9%,26/31) had hypoxemia. The mean values of forced expiratory volume in the first second/forced vital capacity,residua volume/total lung volume,maximum forced expiratory volume of 50% lung volume,and maximum forced expiratory volume of 25% lung volume were 60.5%,53.8%,25.9%,and 31.2%,respectively. The most common CT findings from this cohort of patients were bronchiectasis and bronchiolitis,with nodular shadows distributed in a centrilobular pattern. Finally,29 patients were misdiagnosed as other conditions such as pulmonary infection and bronchiectasis. CONCLUSIONS: DPB in Chinese populations have different presentations compared to that Japanese populations:for instance,the serum cold agglutination test always shows negative results,which is often inconsistent with the pathogens in sputum. DPB usually is misdiagnosed. Clinicians should take DPB into consideration when patients had pulmonary infection and sinusitis.

Respiratory motor output during an inspiratory capacity maneuver is preserved despite submaximal exercise.

It is unknown whether respiratory motor output is constrained during exhaustive exercise in healthy adults. We hypothesised that neural inhibition did occur; to test this hypothesis we measured diaphragm EMG from a maximal inspiratory capacity maneuver (EMG(di)-IC) at rest and during exercise. EMG(di)-IC was measured before and after the amplitude of the diaphragm EMG entered a plateau phase in eleven healthy adults undertaking exercise at 60% and 80% of maximal workload achieved from incremental exercise. The mean EMG(di)-IC at rest was 65 ± 16% of the maximum that could be obtained from a battery of inspiratory tasks. Before and after the plateau phase of diaphragm EMG, EMG(di)-IC was 68 ± 13% and 72 ± 12% (p > 0.05) during 60% of the maximum workload, and was 70 ± 13% and 78 ± 13% (p > 0.05) during 80% of the maximum workload achieved on an incremental test. A further sub-study in which 5 participants exercised at 90% of the maximum workload also showed that EMG(di)-IC was not diminished during exercise. Our data show that exercise condition does not reduce the magnitude of EMG(di)-IC. This argues against neural inhibition as feature of submaximal exercise in healthy adults.