Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) syndrome are highly prevalent respiratory conditions. Their coexistence is referred to as the overlap syndrome. They are both related to pulmonary hypertension (PH) development. This study investigated the effects of OSA on PH in patients with COPD and the associated factors. Methods: Consecutive patients with stable COPD were recruited for an observational cross-sectional study from September 2016 to May 2018 at Peking University Third Hospital. In total, 106 patients with COPD were enrolled and performed home portable monitoring and echocardiography. OSA was defined by an apnea hypopnea index (AHI) ≥10 events/h. Based on OSA absence or presence, patients were divided into the COPD with OSA and COPD without OSA groups. Factors affecting pulmonary artery pressure (PAP) and PH were identified using univariate analysis and logistic regression models. Results: In the 106 patients with COPD, the mean age was 69.52 years, 91.5% were men, and the mean forced expiratory volume in 1 s (FEV 1 ) percentage of predicted was 56.15%. Fifty-six (52.8%) patients with COPD were diagnosed with OSA, and 24 (22.6%) patients with COPD were diagnosed as PH. Compared with COPD without OSA group, the median PAP in COPD with severe OSA group increased by 5 mmHg (36.00 [26.00–50.00] mmHg vs. 31.00 [24.00–34.00] mmHg, P = 0.036). COPD with percent of night-time spent with oxygen saturation below 90% (T90) > 10% group had higher PAP than COPD with T90 ≤ 1% group (36.00 [29.00–50.00)] mmHg vs. 29.00 [25.50–34.00] mmHg, F = 7.889, P = 0.007). Univariate analysis revealed age, FEV 1 % predicted, T90, and Charlson index had statistically significant effects on PH. Multiple regression analysis showed a significant and independent effect of both FEV 1 % predicted (odds ratio [OR] = 3.46; 95% confidence interval [CI]: 1.15–10.46; P = 0.028) and AHI (OR = 3.20; 95% CI: 1.09–19.35; P = 0.034) on PH. Conclusions: Patients with COPD with OSA are more susceptible to PH, which is associated with declining lung function and increased severity of OSA. Thus, nocturnal hypoxemia and OSA in elderly patients with COPD should be identified and treated.

Purpose: To investigate whether hydrogen sulfide provide protective effects on atmosphere particulate matter (PM)-induced emphysema and airway inflammation and its mechanism.Methods: Wild type C57BL/6 and Nrf2 knockout mice were exposed to PM (200 µg per mouse). Hydrogen sulfide or propargylglycine were administered by intraperitoneal injection respectively 30 min before PM exposure, mice were anesthetized 29th day after administration. Mice emphysema, airway inflammation, and oxidative stress were evaluated, the expression of NLRP3, active caspase-1, and active caspase-3 were detected. Alveolar epithelial A549 cells line were transfected with control small interfering RNA (siRNA) or Nrf2 siRNA and then incubated with or without hydrogen sulfide for 30 min before exposed to fine particulate matter for 24 h, cell viability, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) assay, the secretion of interleukin (IL)-1b, ASC speck formation, the expression level of NLRP3, active caspase-1, and active caspase-3 were measured. Results: PM significantly increased mice emphysema and airway inflammation measured by mean linear intercept, alveolar destroy index and total cell, neutrophil counts, cytokines IL-6, tumor necrosis factor (TNF)-a, CXCL1, IL-1b in bronchoalveolar lavage fluid. PMinduced mice emphysema and airway inflammation was greatly attenuated by hydrogen sulfide, while propargylglycine aggravated that. PM-induced oxidative stress was reduced by hydrogen sulfide as evaluated by 8-OHdG concentrations in lung tissues. The expression of NLRP3, active caspase-1, and active caspase-3 enhanced by PM were also downregulated by hydrogen sulfide in mice lung. The protective effect of hydrogen sulfide on emphysema, airway inflammation, inhibiting oxidative stress, NLRP3 inflammasome formation, and anti-apoptosis was inhibited by Nrf2 knockout in mice. Similarly, hydrogen Frontiers in Pharmacology | www.frontiersin.org

PurposeTo investigate the gender difference in knowledge, attitude, and practice of COPD diagnosis and treatment in China.Patients and methodsA nationwide, multicenter, cross-sectional questionnaire study was carried out to investigate patients’ understanding and experience of COPD between September 2007 and December 2008.ResultsTwo thousand and seventy-two patients were recruited from eleven centers. The final effective questionnaires were those of 1,698 cases, of which 32% were female. Women were younger, had higher body mass index, were more never smokers, and had lesser pack-years (all P<0.01). More women had under elementary education level and monthly income <1,000 RMB (about 160 USD) (all P<0.01). Women had higher ratio of FEV1/FVC (54.1±10.9 vs 50.2±11.5), FEV1% (50.0±19.1 vs 45.4±29.0), and lower short form-36 mental component summary (57.5±26.8 vs 61.3±25.0) (all P<0.01). Fewer women reported severe exacerbation (defined as an acute worsening of respiratory symptoms that results in patient’s hospitalization) in the previous year (44.5% vs 51.6%, P<0.05). More women reported that they never heard of COPD before (67.0% vs 59.0%, P<0.01). Less women reported that physician had to tell them they had emphysema (50.5% vs 60.4%) or COPD (31.9% vs 37.9%). Less women had pulmonary function test (PFT) done before (65.2% vs 70.4%, P<0.05). More women reported that they would not repeat PFT annually (91.7% vs 87.6%, P<0.05) and did not know the PFT results (78.6% vs 73.1%, P<0.05). More women reported not having had pulmonary rehabilitation before (87.8% vs 83.6%, P<0.05). Fewer women reported knowing that COPD should be given combined therapy (38.3% vs 44.5%) and long-term treatment (46.1% vs 51.9%) (all P<0.05).ConclusionMale and female patients had different experiences on COPD diagnosis and treatment. Physicians should pay more attention to patients’ education on COPD, especially of women.

Retinoic acid-related orphan receptor alpha (RORA) suppression is associated with autism spectrum disorder (ASD) development, although the mechanism remains unclear. In this study, we aim to investigate the potential effect and mechanisms of RORA suppression on autism-like behavior (ALB) through maternal diabetes-mediated mouse model. Our in vitro study in human neural progenitor cells shows that transient hyperglycemia induces persistent RORA suppression through oxidative stress-mediated epigenetic modifications and subsequent dissociation of octamer-binding transcription factor 3/4 from the RORA promoter, subsequently suppressing the expression of aromatase and superoxide dismutase 2. The in vivo mouse study shows that prenatal RORA deficiency in neuron-specific RORA null mice mimics maternal diabetes-mediated ALB; postnatal RORA expression in the amygdala ameliorates, while postnatal RORA knockdown mimics, maternal diabetes-mediated ALB in offspring. In addition, RORA mRNA levels in peripheral blood mononuclear cells decrease to 34.2% in ASD patients (n = 121) compared to the typically developing group (n = 118), and the related Receiver Operating Characteristic curve shows good sensitivity and specificity with a calculated 84.1% of Area Under the Curve for ASD diagnosis. We conclude that maternal diabetes contributes to ALB in offspring through suppression of RORA and aromatase, RORA expression in PBMC could be a potential marker for ASD screening.

This study aims to investigate the characteristics of the phenotype and management of chronic obstructive pulmonary disease (COPD) patients in the general population in China. We analyzed spirometry-confirmed COPD patients who were identified from a population-based, nationally representative sample in China. All participants were measured with airflow limitation severity based on post-bronchodilator FEV1 percent predicted, bronchodilator responsiveness, exacerbation history, and respiratory symptoms. Among a total of 9134 COPD patients, 90.3% were non-exacerbators, 2.9% were frequent exacerbators without chronic bronchitis, 2.0% were frequent exacerbators with chronic bronchitis, and 4.8% were asthma-COPD overlap. Less than 5% of non-exacerbators ever had pulmonary function testing performed. The utilization rate of inhaled medication in non-exacerbators, exacerbators without chronic bronchitis, exacerbators with chronic bronchitis, and asthma-COPD overlap was 1.4, 23.5, 29.5, and 19.4%, respectively. A comprehensive strategy for the management of COPD patients based on phenotype in primary care is urgently needed.