ODAD1 variants resulting from splice-site mutations retain partial function and cause primary ciliary dyskinesia with outer dynein arm defects.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by defects in motile ciliary function and/or structure. Outer dynein arm docking complex subunit 1 (ODAD1) is an important component of the outer dynein arm docking complex (ODA-DC). To date, 13 likely pathogenic mutations of ODAD1 have been reported. However, the pathogenesis of ODAD1 mutations remains elusive. To investigate the pathogenesis of splice-site mutations in ODAD1 discovered in this study and those reported previously, molecular and functional analyses were performed. Whole-exome sequencing revealed a compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) in a patient with PCD, with c.598-2A>C being a novel mutation that resulted in two mutant transcripts. The compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) led to aberrant splicing that resulted in the absence of the wild-type ODAD1 and defects of the outer dynein arm in ciliary axonemes, causing a decrease in ciliary beat frequency. Furthermore, we demonstrated that the truncated proteins resulting from splice-site mutations in ODAD1 could retain partial function and inhibit the interaction between wild-type ODAD1 and ODAD3. The results of this study expand the mutational and clinical spectrum of PCD, provide more evidence for genetic counseling, and offer new insights into gene-based therapeutic strategies for PCD.

Associations between long-term blood pressure trajectory and all-cause and CVD mortality among old people in China.

Background: Optimal blood pressure (BP) management strategy among the elderly remains controversial, with insufficient consideration of long-term BP trajectory. This study aimed to identify BP trajectory patterns as well as terminal BP trajectory among the Chinese elderly and to explore the relationships between BP trajectories and all-cause mortality and cardiovascular disease (CVD) mortality. Methods: We included 11,181 participants older than 60 at baseline (mean age, 80.98 ± 10.71) with 42,871 routine BP measurements from the Chinese Longitudinal Healthy Longevity Survey. Latent class trajectory analysis and Cox proportional hazard model were conducted to identify trajectory patterns and their associations with mortality. Furthermore, we also applied mixed-effects model to identify terminal BP trajectories among the elderly. Results: Compared with stable at normal high level trajectory, excess systolic BP (SBP) trajectory with decreasing trend was associated with a 34% (HR = 1.34, 95% CI: 1.23-1.45) higher risk of all-cause mortality. Considering the competing risk of non-CVD death, excess BP trajectory with decreasing trend had a more pronounced effect on CVD mortality, in which HR (95% CI) was 1.67 (1.17, 2.37). Similar results were also found in diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) trajectories. We further conducted a mixed-effects model and observed that SBP and PP trajectories first increased and began to decline slightly six years before death. In contrast, DBP and MAP showed continuous decline 15 years before death. Conclusion: Long-term BP trajectory was associated with all-cause mortality, especially CVD mortality. Keeping a stable BP over time may be an important way for CVD prevention among the elderly.

Association of sleep behavior with depression: a cross-sectional study in northwestern China.

Background: This study aimed to examine the association between sleep duration, sleep problems, and depression in Northwest China. Method: Depression was diagnosed at the hospital and self-reported by the participants in the baseline survey. Sleep duration and problems, including difficulty initiating and maintaining sleep, early morning awakening, daytime dysfunction, use of sleeping pills or drugs, and any sleep problems, were obtained by a self-reported questionnaire. Logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CIs) for exploring the association between sleep duration, sleep problems, and depression, adjusting for demographic and socioeconomic characteristics and health behaviors. The association between depression and sleep duration was also evaluated continuously with restricted cubic spline curves based on logistic models. Results: 36,515 adults from Regional Ethnic Cohort Study in Northwest China were included. About 24.04% of participants reported short sleep duration (<7 h), and 15.64% reported long sleep duration (≥9 h). Compared with standard sleep duration (7-9 h), short sleep duration was associated with a higher risk of depression (OR: 1.69, 95%CI: 1.26-2.27, p = 0.001). Self-reported sleep problems were also related to four times depression risk increased (OR: 4.02, 95%CI: 3.03-5.35, p < 0.001) compared with no sleep problems. In addition, a nonlinear relationship was found between sleep duration and depression after adjusting covariates (p = 0.043). Conclusion: Sleep duration and sleep problems are associated with depression. Enough sleep time and healthy sleep habits in life course might be a practical health promotion approach to reduce depression risk in Northwest Chinese adults. A further study from cohort study is needed to verify the temporal association.

Mechanistic Regulation of Wnt Pathway-Related Progression of Chronic Obstructive Pulmonary Disease Airway Lesions.

Chronic obstructive pulmonary disease (COPD) is a chronic disease associated with inflammation and structural changes in the airways and lungs, resulting from a combination of genetic and environmental factors. This interaction highlights significant genes in early life, particularly those involved in lung development, such as the Wnt signaling pathway. The Wnt signaling pathway plays an important role in cell homeostasis, and its abnormal activation can lead to the occurrence of related diseases such as asthma, COPD, and lung cancer. Due to the fact that the Wnt pathway is mechanically sensitive, abnormal activation of the Wnt pathway by mechanical stress contributes to the progression of chronic diseases. But in the context of COPD, it has received little attention. In this review, we aim to summarize the important current evidence on mechanical stress through the Wnt pathway in airway inflammation and structural changes in COPD and to provide potential targets for COPD treatment strategies.

Maternal Dietary Inflammatory Potential and Offspring Birth Outcomes in a Chinese Population.

BACKGROUND: Chronic inflammation perturbations during pregnancy may impact fetal growth; however, research on the association between dietary inflammation and birth outcomes is limited and inconsistent. OBJECTIVES: This study seeks to assess whether the dietary inflammatory potential is related to birth outcomes among pregnant women in China. METHODS: A total of 7194 mothers aged 17-46 y and their infants in China were included in this cross-sectional study. Dietary intake was assessed by a FFQ, which yielded scores on the energy-adjusted dietary inflammatory index (E-DII). Birth outcomes included birth weight, gestational age, birth weight z score, low birth weight (LBW), macrosomia, preterm birth, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and birth defects. Generalized estimating equation and restricted cubic spline fit each outcome on continuous or quartiles of E-DII after adjusting for covariates. RESULTS: The maternal E-DII ranged from -5.35 to 6.77. Overall, birth weight and gestation age (mean ± SD) were 3267.9 ± 446.7 g and 39.6 ± 1.3 wk, respectively, and the birth weight z score was 0.02 ± 1.14. A total of 3.2% of infants were born with LBW, 6.1% with macrosomia, 3.0% were preterm birth, 10.7% were born SGA, 10.0% were born LGA, and 2.0% were born with birth defects. E-DII was associated with a 9.8 g decrease in birth weight (95% CI: -16.9, -2.6) and a 1.09-fold (95% CI: 1.01, 1.18), 1.11-fold (95% CI: 1.02, 1.21), and 1.12-fold (95% CI: 1.02, 1.24) greater risk of LBW, preterm birth, and birth defects, respectively. The maternal E-DII score was nonlinearly associated with gestational age (P for linearity = 0.009, P for curvature = 0.044). CONCLUSIONS: Among pregnant Chinese women, proinflammatory diets during pregnancy were related to reduced offspring birth weight and an increased risk of LBW, preterm birth, and birth defects. These findings might inform potential prevention strategies for pregnant women in China.

The Association between Plant-Based Diet Indices and Metabolic Syndrome in Chinese Adults: Longitudinal Analyses from the China Health and Nutrition Survey.

OBJECTIVES: To investigate the association between a plant-based diet and metabolic syndrome (MetS) among Chinese adults. METHODS: Based on the data from the 2004-2015 China Health and Nutrition Survey and the corresponding edition of China Food Composition, we calculated the healthy plant-based diet indices (hPDI) and unhealthy plant-based diet indices (uPDI). The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for MetS. Mediation analysis was further conducted to explore the mediator role of Body Mass Index (BMI) in the association between hPDI and MetS. RESULTS: We included 10,013 participants, and over a median follow-up of 5 years, 961 patients (9.60%) developed MetS. Compared to those in the lowest quintile of hPDI score, we found that those in the highest quintile of hPDI score had a 28% lower ([HR]: 0.72, 95% CI 0.56-0.93, Ptrend = 0.021) risk of developing MetS and had a 20% lower (hazard ratio [HR]: 0.80, 95% CI 0.70-0.92, Ptrend = 0.004) risk of developing abdominal obesity. No significant associations were observed between uPDI and the MetS, but those in the highest quintile of uPDI score had a 36% higher (hazard ratio [HR]: 1.36, 95% CI 1.20-1.64, Ptrend < 0.001) risk of developing abdominal obesity, compared to those in the lowest quintile of uPDI score. In exploratory analysis, we observed that BMI at baseline mediated 27.8% of the association between hPDI and incident MetS, and BMI at baseline mediated 29.7% of the association between hPDI and abdominal obesity. CONCLUSION: The current findings reveal a possible causal relationship between a healthy plant-based diet and a reduced risk of MetS, especially abdominal obesity. It is observed that BMI may mediate the relationship between hPDI score and MetS. Controlling early dietary patterns and BMI may help reduce the risk of MetS.

Association between physical activity and major adverse cardiovascular events in northwest China: A cross-sectional analysis from the Regional Ethnic Cohort Study.

Background: To examine the association between daily physical activity (PA) and major adverse cardiovascular events (MACEs) in northwest China. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. This study used standardized self-reported total physical activity (continuous and categorical variables) and self-reported outcomes of MACEs. All analyses were conducted using the logistic regression model and stratified by age, sex, body mass index (BMI), and region. The dose-response relationships were assessed with a restricted cubic spline. Results: The average level of total PA was 17.60 MET hours per day (MET-h/d). Every increase of four MET-h/d of total PA was associated with a lower risk of MACEs [adjusted OR = 0.95 (95% CI, 0.93~0.98)]. Compared with participants in the bottom quartile of total PA, a lower risk of MACEs was observed in the top quartile group [≥23.3 MET-h/d, 0.68 (0.55~0.83)]. Stratified analyses showed similar results in males, females, participants over 45 years old, participants in the rural region, and normal weight range participants (BMI < 24 kg/m2). Total participants also observed a dose-response relationship after adjusting for socioeconomic and lifestyle factors. Conclusions: A higher level of PA was associated with a lower MACE risk. Future research should examine the longitudinal association of prospectively measured PA and the risk of MACEs.

Preference for Stronger Taste Associated with a Higher Risk of Hypertension: Evidence from a Cross-Sectional Study in Northwest China.

Background: Dietary modulation is a primary lifestyle approach for reducing the risk of hypertension. However, evidence of the potential role that a dietary taste preference plays in the risk of hypertension remains limited. Methods: A cross-sectional analysis was conducted based on the Shaanxi baseline survey of the Regional Ethnic Cohort Study. We used self-reported salt consumption and intensity preferences for sourness and spiciness to calculate the taste preference score, which was categorized into bland, moderate, and strong. A generalized linear mixed model and quantile regression were performed to estimate associations between taste preferences and hypertension/blood pressure. Results: Among 27,233 adults, 72.2% preferred a moderate taste and 21.4% preferred a strong taste. Compared with a bland taste, a stronger taste preference might be associated with a higher risk of hypertension (adjusted OR for a moderate taste = 1.25, 95% CI: 1.06, 1.49; adjusted OR for a strong taste = 1.41, 95% CI: 1.15, 1.71; P trend = 0.002), especially in females (adjusted OR for a moderate taste = 1.43, 95% CI: 1.24, 1.66; adjusted OR for a strong taste = 1.55, 95% CI: 1.32, 1.83; P trend < 0.001). Quantile regression showed that the taste preference was positively associated with diastolic blood pressure (DBP) (P 5-P 80) in females, with an average increase of 3.31 mmHg for a strong taste (ß = 3.31, P < 0.001) and 1.77 mmHg for a moderate taste (ß = 1.77, P = 0.008). Conclusions: A preference for stronger multitastes of salty, sour, and spicy might be associated with a higher risk of hypertension, especially in females. This relationship possibly occurs through increasing DBP. Dietary modulation with the promotion of a bland taste is encouraged.

Dabigatran ameliorates airway smooth muscle remodeling in asthma by modulating Yes-associated protein.

Accumulating evidence indicates that thrombin, the major effector of the coagulation cascade, plays an important role in the pathogenesis of asthma. Interestingly, dabigatran, a drug used in clinical anticoagulation, directly inhibits thrombin activity. The aim of this study was to investigate the effects and mechanisms of dabigatran on airway smooth muscle remodeling in vivo and in vitro. Here, we found that dabigatran attenuated inflammatory pathology, mucus production, and collagen deposition in the lungs of asthmatic mice. Additionally, dabigatran suppressed Yes-associated protein (YAP) activation in airway smooth muscle of asthmatic mice. In human airway smooth muscle cells (HASMCs), dabigatran not only alleviated thrombin-induced proliferation, migration and up-regulation of collagen I, α-SMA, CTGF and cyclin D1, but also inhibited thrombin-induced YAP activation, while YAP activation mediated thrombin-induced HASMCs remodeling. Mechanistically, thrombin promoted actin stress fibre polymerization through the PAR1/RhoA/ROCK/MLC2 axis to activate YAP and then interacted with SMAD2 in the nucleus to induce downstream target genes, ultimately aggravating HASMCs remodeling. Our study provides experimental evidence that dabigatran ameliorates airway smooth muscle remodeling in asthma by inhibiting YAP signalling, and dabigatran may have therapeutic potential for the treatment of asthma.

Emerging roles of YAP/TAZ in lung physiology and diseases.

The YAP and TAZ, as the downstream effectors of Hippo pathway, have emerged as important translational co-activators of a wide variety of biological processes. YAP/TAZ plays a crucial role in the lung development and physiology. Dysregulation of YAP/TAZ signaling pathway contributes to the development and progression of chronic lung diseases, including lung cancer, pulmonary fibrosis, pulmonary hypertension, COPD, asthma, and lung infection. Therefore, owing to its critical functions, delineation of the signaling mechanisms of YAP/TAZ in pathological conditions will shed light on developing strategies for its therapeutic targeting. Currently, the complex regulation of this pathway is under extensive investigation. In this review, we summarize and present recent findings of molecular mechanisms of YAP/TAZ in the lung physiological and pathological conditions, as well as the implications of YAP/TAZ for lung diseases treatment and regeneration.

Efficacy of bilevel positive airway pressure and continuous positive airway pressure therapy in patients with obesity hypoventilation syndrome: protocol for systematic review and meta-analysis.

INTRODUCTION: Obesity hypoventilation syndrome (OHS) is a major respiratory complication caused by severe obesity, being associated with significant morbidity, negative impacts on quality of life and reduced survival if not treated appropriately. Positive airway pressure therapy is the first-line treatment for OHS although the optimal modality remains unclear. The goal of this study is to identify the efficacy of home bilevel positive airway pressure therapy by comparison to continuous positive airway pressure therapy and determine the best strategy for patients with OHS. METHODS AND ANALYSIS: This study will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. We will search the following databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Ongoing studies will be identified through the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform Search Portal. Grey literature will be recognised through Google Scholar and other search engines. Only randomised controlled trials meeting the eligibility criteria will be included. The risk of bias of the included studies will be evaluated through the Cochrane Collaboration's tool. RevMan V.5.3.5 software will be used for data analysis. The Q statistic and I2 index will be used for investigating heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required because this study contains no primary data collected from humans. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42017078369.

Tiotropium inhibits methacholine-induced extracellular matrix production via ß-catenin signaling in human airway smooth muscle cells.

Background: Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear. Purpose: In this study, we attempted to investigate the influence of tiotropium on ECM production by ASMCs and the underlying mechanism. Methods: Tiotropium was added 30 minutes before the addition of methacholine to primary cultured human ASMCs. Protein expression was analylized by Western Blot and mRNA abundance was determined by real-time PCR. Results: We found that tiotropium reduced collagen I protein expression, and the mRNA abundance of collagen I, fibronectin, and versican. ß-catenin signaling was inactivated by inhibiting glycogen synthase kinase 3ß (GSK3ß) phosphorylation in this process. Tiotropum inhibited the amount of active ß-catenin and its transcription activity. Furthermore, overexpression of active ß-catenin by adenoviruses carrying the S33Y mutant resisted the suppressive effect of tiotropium on collagen I protein expression. However, silencing ß-catenin by specific small interfering RNA enhanced the negative effect of tiotropium. Conclusion: These findings suggest that relaxation of ASMCs by tiotropium can prevent ECM production through ß-catenin signaling.

Chinese version of the severe respiratory insufficiency questionnaire for patients with COPD receiving long-term oxygen therapy.

Purpose: Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients' symptoms and increase survival. As COPD is incurable, improving patients' health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods: We analyzed reliability using Cronbach's α coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results: In total, 161 patients participated in this study. The Cronbach's α coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion: The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China.

Methacholine induces extracellular matrix production by human airway smooth muscle cells through ß-catenin signaling.

Altered extracellular matrix (ECM) production by airway smooth muscle cells (ASMCs) is an important feature of airway remodeling. Muscarinic receptor agonists contribute to ECM production in vivo, but the mechanisms involved remain unclear. This study attempted to investigate the role of methacholine in promoting ECM production by human ASMCs (HASMCs) and the underlying mechanism. We found that methacholine induced the expression of collagen I protein and multiple ECM genes. ß-catenin signaling was activated in this process upon GSK3ß phosphorylation, leading to upregulation of total and active ß-catenin. Silencing ß-catenin by specific small interfering RNA (siRNA) or with the ß-catenin inhibitor, PKF115-584, decreased collagen I expression. Conversely, overexpression of active ß-catenin by adenoviruses carrying the S33Y-ß-catenin mutant increased the methacholine-induced collagen I expression. Furthermore, methacholine induced TGF-ß expression in HASMCs, while pan-TGF-ß-neutralizing antibody only partially decreased collagen I expression. These findings suggest that methacholine induced ECM production through ß-catenin signaling and partially through TGF-ß.

Author Correction: High-pressure versus low-pressure home non-invasive positive pressure ventilation with built-in software in patients with stable hypercapnic COPD: a pilot study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Contraction-dependent TGF-ß1 activation is required for thrombin-induced remodeling in human airway smooth muscle cells.

AIMS: Thrombin is a serine proteinase that is not only involved in coagulation cascade, but also mediates a number of biological responses relevant to tissues repair, and induces bronchoconstriction. TGF-ß plays a pivotal role in airway remodeling due to its effects on airway smooth muscle proliferation and extracellular matrix (ECM) deposition. Recently, bronchoconstriction itself is found to constitute a form of strain and is highly relevant to asthmatic airway remodeling. However, the underlying mechanisms remain unknown. Here, we investigated the role of contraction- dependent TGF-ß activation in thrombin-induced remodeling in human airway smooth muscle (HASM) cells. MATERIALS AND METHODS: Primary HASM cells were treated with or without thrombin in the absence or presence of anti-TGF-ß antibody, cytochalasin D and formoterol. CFSE labeling index or CCK-8 assay were performed to test cell proliferation. RT-PCR and Western blotting were used to examined ECM mRNA level and collagen Iα1, α-actin protein expression, respectively. Immunofluorescence was also used to confirm contraction induced by thrombin in HASM cells. KEY FINDING: Thrombin stimulation enhanced HASM cells proliferation and activated TGF-ß signaling. Thrombin induced ECM mRNA and collagen Iα1 protein expression, and these effects are mediated by TGF-ß. Abrogation of TGF-ß activation by contraction inhibitors cytochalasin D and formoterol prevents the thrombin-induced effects. SIGNIFICANCE: These findings suggest that contraction-dependent TGF-ß activation could be a mechanism by which thrombin leads to the development of asthmatic airway remodeling. Blocking physical forces with bronchodilator would be an intriguing way in reducing airway remodeling in asthma.

High-pressure versus low-pressure home non-invasive positive pressure ventilation with built-in software in patients with stable hypercapnic COPD: a pilot study.

High-pressure non-invasive positive pressure ventilation (NPPV) is a new strategy targeted at maximally reducing arterial carbon dioxide. However, high inspiratory positive airway pressure (IPAP) might cause respiratory adverse events likely to diminish the benefit of NPPV. In the setting of ventilatory support, monitoring NPPV efficacy and resolving problems promptly are critical. This study assessed the treatment effect of high and low-pressure NPPV in chronic hypercapnic COPD using home ventilator with built-in software. In this pilot study, we investigated 34 patients using NPPV for 3 months. 13 patients used high-pressure ventilation and 21 patients used low-pressure ventilation. The primary outcome was daytime partial pressure of arterial blood carbon dioxide (PaCO2). There were no between-group differences in daytime PaCO2 and FEV1, but a trend favouring high-pressure NPPV was observed. Significant between-group differences were found in the transition dyspnoea index (TDI) (high-pressure, 1.69 ± 1.75, versus low-pressure, -0.04 ± 2.71, p = 0.044). No differences were found in usage time, leakage, health-related quality of life, spirometry, or 6-minute walk test. High-pressure NPPV with built-in software monitoring in patients with chronic hypercapnic COPD is associated with improvement in TDI scores and a positive trend in favour of high-pressure NPPV for improving PaCO2 is observed.

The Chinese version of the Severe Respiratory Insufficiency questionnaire for patients with chronic hypercapnic chronic obstructive pulmonary disease receiving non-invasive positive pressure ventilation.

OBJECTIVES: The Severe Respiratory Insufficiency (SRI) questionnaire is the best assessment tool for health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) receiving non-invasive positive pressure ventilation (NIPPV). This study aimed to translate the SRI Questionnaire into Chinese and to validate it. DESIGN: Prospective validation study. SETTING AND PARTICIPANTS: A total of 149 participants with chronic hypercapnic COPD receiving NIPPV completed the study. METHODS: The SRI questionnaire was translated into Chinese using translation and back-translation. Reliability was gauged using Cronbach's α coefficient. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess construct validity. Content validity was confirmed by evaluating the relationship between the score of each item and the total score of the relevant subscale. RESULTS: Cronbach's α coefficients for each subscale and summary scale were above 0.7. Using EFA, one factor was extracted from the anxiety and summary scales and two factors were extracted from the remaining six subscales. Based on the EFA results, subsequent CFA revealed a good model fit for each subscale, but the extracted factors of each subscale were correlated. Content validity was confirmed by the good relationship between the score of each item and the total score of the relevant subscale. CONCLUSION: The Chinese version of the SRI questionnaire is valid and reliable for patients with chronic hypercapnic COPD receiving NIPPV in China. TRIAL REGISTRATION NUMBER: NCT02499718.

Home noninvasive positive pressure ventilation with built-in software in stable hypercapnic COPD: a short-term prospective, multicenter, randomized, controlled trial.

BACKGROUND: The benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial. It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes. With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use. This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring. METHODS: The current multicenter prospective, randomized, controlled trial enrolled patients with stable GOLD stages III and IV hypercapnic COPD. Patients were randomly assigned via a computer-generated randomization sequence, with a block size of four patients, to continue optimized treatment (control group) or to receive additional NPPV (intervention group) for 3 months. The primary outcome was arterial carbon dioxide pressure (PaCO2). Data were derived from built-in software and analyzed every 4 weeks. Analysis was carried out with the intention to treat. This study is registered with ClinicalTrials.gov, number NCT02499718. RESULTS: Patients were recruited from 20 respiratory units in China from October 1, 2015, and recruitment was terminated with a record of the vital statistics on May 31, 2016. A total of 115 patients were randomly assigned to the NPPV group (n=57) or the control group (n=58). Patients complied well with NPPV therapy (mean [± standard deviation] day use 5.6±1.4 h). The mean estimation of leaks was 37.99±13.71 L/min. The changes in PaCO2 (-10.41±0.97 vs -4.32±0.68 mmHg, P=0.03) and 6-min walk distance (6MWD) (38.2% vs 18.2%, P=0.02) were statistically significant in the NPPV group versus the control group. COPD assessment test (CAT) showed a positive trend (P=0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not different between groups. CONCLUSION: Ventilators equipped with built-in software provided methodology for monitoring NIV use at home, which could facilitate the improvement of compliance and quality control of NIV use. It was shown that three months use of NIV at home could reduce the PaCO2 and improve exercise tolerance (6MWD) in chronic hypercapnic COPD patients.

Evaluation of carbon dioxide rebreathing during exercise assisted by noninvasive ventilation with plateau exhalation valve.

Noninvasive ventilation with a plateau exhalation valve (PEV) is often used as an adjunct to exercise to achieve a physiologic training effect in severe chronic obstructive pulmonary disease (COPD) patients. However, during exercise, with the increase of exhalation flow and respiratory rate and limited capability of PEV to exhale gases out of the circuit, it is still unknown whether CO2 rebreathing occurs in COPD patients ventilated during exercise assisted by single-limb circuit with a PEV. A maximal symptom-limited cycle exercise test was performed while ventilated on pressure support (inspiratory:expiratory pressure 14:4 cmH2O) in 18 male patients with stable severe COPD (mean ± standard deviation, forced expiratory volume in 1 s: 29.5%±6.9% predicted). At rest and during exercise, breathing pattern, mean expiratory flow, mean expiratory flow of PEV, and the mean inspiratory fraction of CO2 (tidal fractional concentration of inspired CO2 [FiCO2]) reinsufflated from the circuit was measured for each breath. In comparison with rest, with the significant increase of mean expiratory flow (0.39±0.15 vs 0.82±0.27 L/s), fractional concentration of end-tidal CO2 (2.6%±0.7% vs 5.5%±0.6%), and the significant decrease of mean expiratory flow of PEV (0.41±0.02 vs 0.39±0.03 L/s), tidal FiCO2 significantly increased at peak exercise (0.48%±0.19% vs 1.8%±0.6%) in patients with stable severe COPD. The inflection point of obvious CO2 rebreathing was 0.67±0.09 L/s (95% confidence interval 0.60-0.73 L/s). Ventilated by a single-limb tubing with PEV caused CO2 rebreathing to COPD patients during exercise. Patients with mean expiratory flow >0.60-0.73 L/s may be predisposed to a higher risk of CO2 rebreathing.