Intragastric fructose administration interacts with emotional state in homeostatic and hedonic brain regions.

Background: Interoceptive properties of food may influence emotional state and its neural basis, as shown for fatty acids but remains unstudied for carbohydrates.Objectives: To study the effects of fructose and its interaction with sad emotion on brain activity in homeostatic and hedonic regions and investigate whether gut hormone responses can explain effects.Design: In 15 healthy subjects, brain activity for 40min after intragastric infusion of fructose (25g) or water was recorded using a cross-over pharmacological magnetic resonance imaging (phMRI) paradigm. Sad or neutral emotional states were induced by classical music and emotional facial expressions. Emotional state was assessed using the Self-Assessment Manikin. Blood samples were taken to assess gut hormone levels. Brain responses to fructose versus placebo, sad versus neutral emotion, and their interaction were analyzed over time in a single mask of a priori defined regions of interest at a voxel-level threshold of pFWEcorrected <0.05. Effects on emotion and hormones were tested using linear mixed models.Results: No main effects of fructose, emotion, or fructose-by-emotion interaction on emotional ratings were observed. Main effects of fructose, emotion and aninteraction effect were found on brain activity (medulla, midbrain, hypothalamus, basal ganglia, anterior insula, orbitofrontal cortex, anterior cingulate cortex and amygdala). An increase in circulating GLP-1 after fructose in neutral emotion was abolished during sad emotion (fructose-by-emotion-by-time, p=0.041). Ghrelin levels were higher in sad emotion (time-by-emotion, p=0.037).Conclusions: Emotional state interacts with brain and endocrine responses to intragastric infusion of 25 g of fructose, however such an effect was not found at behavioral level.Trial registration: ClinicalTrials.gov identifier: NCT02946983.

A Complex-Valued Self-Supervised Learning-Based Method for Specific Emitter Identification.

Specific emitter identification (SEI) refers to distinguishing emitters using individual features extracted from wireless signals. The current SEI methods have proven to be accurate in tackling large labeled data sets at a high signal-to-noise ratio (SNR). However, their performance declines dramatically in the presence of small samples and a significant noise environment. To address this issue, we propose a complex self-supervised learning scheme to fully exploit the unlabeled samples, comprised of a pretext task adopting the contrastive learning concept and a downstream task. In the former task, we design an optimized data augmentation method based on communication signals to serve the contrastive conception. Then, we embed a complex-valued network in the learning to improve the robustness to noise. The proposed scheme demonstrates the generality of handling the small and sufficient samples cases across a wide range from 10 to 400 being labeled in each group. The experiment also shows a promising accuracy and robustness where the recognition results increase at 10-16% from 10-15 SNR.

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms.

Objectives: Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects.Methods: Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women. Appetite-related sensations, plasma levels of gastrointestinal hormones and hedonic food intake (ad libitum drink test) were assessed.Results: Lower octanoylated ghrelin (P<0.04), total ghrelin (P<0.01), and motilin (P<0.01) plasma levels were found after QHCl administration, along with lower prospective food consumption ratings (P<0.02) and hedonic food intake (P<0.05). QHCl increased neural activity in the hypothalamus and hedonic (anterior insula, putamen, caudate, pallidum, amygdala, anterior cingulate cortex, orbitofrontal cortex, midbrain) regions, but decreased activity in the homeostatic medulla (all pFWE-corrected<0.05). Differential brain responses to QHCl versus placebo covaried with subjective and hormonal responses and predicted differences in hedonic food intake.Discussion: Intragastric QHCl decreases prospective and actual food intake in healthy women by interfering with homeostatic and hedonic brain circuits in a ghrelin- and motilin-mediated fashion. These findings suggest a potential of bitter tastants to reduce appetite and food intake, through the gut-brain axis.

Small airway disease: A different phenotype of early stage COPD associated with biomass smoke exposure.

BACKGROUND AND OBJECTIVE: Chronic exposure to biomass smoke (BS) can significantly compromise pulmonary function and lead to chronic obstructive pulmonary disease (COPD). To determine whether BS exposure induces a unique phenotype of COPD from an early stage, with different physiopathological features compared with COPD associated with smoking (cigarette-smoke (CS) COPD), we assessed the physiopathology of early COPD associated with BS exposure (BS COPD) by incorporating spirometry, high-resolution computed tomography (HRCT) imaging, bronchoscopy and pathological examinations. METHODS: In this cross-sectional study, we recruited 29 patients with BS COPD, 31 patients with CS COPD and 22 healthy controls, including 12 BS-exposed subjects who did not smoke and 10 healthy smokers without BS exposure. Spirometry, HRCT scans, bronchoscopy and bronchial mucosa biopsies were performed to assess lung function, emphysema and air trapping, as well as the pathological characteristics and levels of inflammatory cells in bronchoalveolar lavage fluid (BALF). RESULTS: Among COPD patients with mild-to-moderate airflow limitation, BS exposure caused greater small airway dysfunction in BS COPD patients, although these patients had less emphysema and air trapping, as detected by HRCT (P < 0.05). We also observed significantly thicker basement membranes and greater endobronchial pigmentation in BS COPD than in CS COPD (P < 0.05). Moreover, patients with BS COPD exhibited greater macrophage and lymphocyte infiltration but reduced neutrophil infiltration in their BALF (P < 0.05). CONCLUSION: We used both radiology and pathology to document a distinct COPD phenotype associated with BS exposure. This is characterized by small airway disease.

Association between exposure to ambient particulate matter and chronic obstructive pulmonary disease: results from a cross-sectional study in China.

OBJECTIVE: The association between exposure to ambient particles with a median aerodynamic diameter less than 10/2.5 µm (particulate matter, PM10/2.5) and COPD remains unclear. Our study objective was to examine the association between ambient PM10/2.5 concentrations and lung functions in adults. METHODS: A cross-sectional study was conducted in southern China. Seven clusters were randomly selected from four cities across Guangdong province. Residents aged ≥20 years in the participating clusters were randomly recruited; all eligible participants were examined with a standardised questionnaire and spirometry. COPD was defined as a post-bronchodilator FEV1/FVC less than 70%. Atmosphere PM sampling was conducted across the clusters along with our survey. RESULTS: Of the subjects initially recruited, 84.4% (n=5993) were included for analysis. COPD prevalence and atmosphere PM concentration varied significantly among the seven clusters. COPD prevalence was significantly associated with elevated PM concentration levels: adjusted OR 2.416 (95% CI 1.417 to 4.118) for >35 and ≤75 µg/m3 and 2.530 (1.280 to 5.001) for >75 µg/m3 compared with the level of ≤35 µg/m3 for PM2.5; adjusted OR 2.442 (95% CI 1.449 to 4.117) for >50 and ≤150 µg/m3 compared with the level of ≤50 µg/m3 for PM1. A 10 µg/m3 increase in PM2.5 concentrations was associated with a 26 mL (95% CI -43 to -9) decrease in FEV1, a 28 mL (-49 to -8) decrease in FVC and a 0.09% decrease (-0.170 to -0.010) in FEV1/FVC ratio. The associations of COPD with PM10 were consistent with PM2.5 but slightly weaker. CONCLUSIONS: Exposure to higher PM concentrations was strongly associated with increased COPD prevalence and declined respiratory function. TRIAL REGISTRATION NUMBER: ChiCTR-OO-14004264; Post-results.

Evanescent-Vacuum-Enhanced Photon-Exciton Coupling and Fluorescence Collection.

An evanescent optical mode existing in various nanophotonic structures always acts as a cavity mode rather than an electromagnetic vacuum in the study of cavity quantum electrodynamics (CQED). Here we show that taking the evanescent mode as an electromagnetic vacuum in which the nanocavity is located is possible through the optical mode design. The proposed evanescent vacuum enables us to enhance both the reversible photon-exciton interaction and fluorescence collection. By embedding the custom-designed plasmon nanocavity into the evanescent vacuum provided by a metallic or dielectric nanowire, the photon-exciton coupling coefficient can achieve 4.2 times that in vacuum due to the exponential decay of the evanescent wave, and spontaneously emitted photons with Rabi splitting can be guided by an evanescent wave with a collection efficiency of 47% at most. Electromagnetic vacuum engineering at subwavelength scale holds promise for controlling the light-matter interaction in quantum optics, CQED, and on-chip quantum information.

Plasmon-enhanced Kerr nonlinearity via subwavelength-confined anisotropic Purcell factors.

We theoretically investigate the enhancement of Kerr nonlinearity through anisotropic Purcell factors provided by plasmon nanostructures. In a three-level atomic system with crossing damping, larger anisotropism of Purcell factors leads to more enhanced Kerr nonlinearity in electromagnetically induced transparency windows. While for fixed anisotropic Purcell factors, Kerr nonlinearity with orthogonal dipole moments increases with the decrease of its crossing damping, and Kerr nonlinearity with nonorthogonal dipole moments is very sensitive to both the value of crossing damping and the orientation of the dipole moments. We design the non-resonant gold nanorods array, which only provides subwavelength-confined anisotropic Purcell factors, and demonstrate that the Kerr nonlinearity of cesium atoms close to the nanorods array can be modulated at the nanoscale. These findings should have potential application in ultracompact quantum logic devices.

An efficient method to genotype the polymorphisms of cholinergic nicotinic receptor subunit genes and their associations with COPD onset risk.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the cholinergic nicotinic receptor subunit genes on chromosome 15q25.1, including CHRNA3, CHRNB4 and CHRNA5, are well-established biomarkers of chronic obstructive pulmonary disease (COPD) and lung cancer. Thus, there is great demand for a rapid, easy and inexpensive method to detect these variations for purpose of risk prediction in large populations. AIM OF THE STUDY: The aim of this study was to establish an accurate and efficient method for genotyping CHRN SNPs and testing their association with age at onset of COPD in Chinese population as well as the clinical stage in COPD patients. MATERIALS AND METHODS: We designed a method to specifically genotype 5 SNPs of CHRN genes based on a modified high-resolution melt (HRM) method and then validated the genotyping results by direct sequencing of 120 samples. We further used the HRM method to genotype these 5 SNPs in 1,013 COPD patients. RESULTS: Requiring little time, few material costs and only a simplified protocol, the modified HRM method could accurately distinguish the genotypes of CHRN SNPs, demonstrating kappa coefficients >0.96 based on the results from direct sequencing. Furthermore, the data showed that the GG genotype of SNP rs56218866 was associated with a significantly earlier age of COPD onset than A (AA+AG) genotypes (61.0 ± 8.93 vs. 67.8 ± 9.88; P = 0.031), which was not found for the other SNPs. No significant association was observed between the COPD stages and any of the above SNPs. CONCLUSION: A simple, rapid and efficient HRM method was introduced for CHRN SNP genotyping and a suggestion that the SNP rs56218866A>G is associated with early-onset COPD in a Chinese population was found.

The Association of High Arousal Threshold with Hypertension and Diabetes in Obstructive Sleep Apnea.

Objective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea-hypopnea index (AHI). Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR). Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07-1.62, P < 0.01) and 1.45 (95% CI = 1.01-2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02-3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes. Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.

Application Value of Cardiometabolic Index for the Screening of Obstructive Sleep Apnea with or Without Metabolic Syndrome.

Background: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP). Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points. Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively. Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.

Analysis of Airway Thickening and Serum Cytokines in COPD Patients with Frequent Exacerbations: A Heart of the Matter.

Background: Differences in lung function for Chronic Obstructive Pulmonary Disease (COPD) cause bias in the findings when identifying frequent exacerbator phenotype-related causes. The aim of this study was to determine whether computed tomographic (CT) biomarkers and circulating inflammatory biomarkers were associated with the COPD frequent exacerbator phenotype after eliminating the differences in lung function between a frequent exacerbator (FE) group and a non-frequent exacerbator (NFE) group. Methods: A total of 212 patients with stable COPD were divided into a FE group (n=106) and a NFE group (n=106) according to their exacerbation history. These patients were assessed by spirometry, quantitative CT measurements and blood sample measurements during their stable phase. Univariate and multivariate logistic regression were used to assess the association between airway thickening or serum cytokines and the COPD frequent exacerbator phenotype. Receiver operating characteristic (ROC) curves were calculated for Pi10, WA%, IL-1ß and IL-4 to identify frequent exacerbators. Results: Compared with NFE group, FE group had a greater inner perimeter wall thickness of a 10 mm diameter bronchiole (Pi10), a greater airway wall area percentage (WA%) and higher concentrations of IL-1ß and IL-4 (p<0.001). After adjusting for sex, age, BMI, FEV1%pred and smoking pack-years, Pi10, WA%, IL-ß and IL-4 were independently associated with a frequent exacerbator phenotype (p<0.001). Additionally, there was an increase in the odds ratio of the frequent exacerbator phenotype with increasing Pi10, WA%, IL-4, and IL-1ß (p for trend <0.001). The ROC curve demonstrated that IL-1ß had a significantly larger calculated area under the curve (p < 0.05) than Pi10, WA% and IL-4. Conclusion: Pi10, WA%, IL-4, and IL-1ß were independently associated with the frequent exacerbator phenotype among patients with stable COPD, suggesting that chronic airway and systemic inflammation contribute to the frequent exacerbator phenotype. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (https://www.chictr.org.cn). Its registration number is ChiCTR2000038700, and date of registration is September 29, 2020.

Establishment and Application Evaluation of an Improved Obstructive Sleep Apnea Screening Questionnaire for Chinese Community: The CNCQ-OSA.

Objective: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease. We aimed to establish an improved screening questionnaire without physical examinations for OSA named the CNCQ-OSA (Chinese community questionnaire for OSA). Methods: A total of 2585 participants who visited sleep medicine center and underwent overnight polysomnography were grouped into two independent cohorts: derivation (n = 2180) and validation (n = 405). The CNCQ-OSA was designed according to the baseline of patients in derivation cohort. We comprehensively analyzed the data to evaluate the predictive value of the CNCQ-OSA, compared to the GOAL questionnaire, STOP-Bang questionnaire (SBQ) and NoSAS questionnaire. Results: The CNCQ-OSA included seven variables: loud snoring, BMI ≥ 25 kg/m2, male gender, apnea, sleepiness, hypertension and age ≥30, with a total score ranging from 7 to 16.7 points (≥13.5 points indicating high risk of OSA, ≥14.5 points indicating extremely high risk). In the derivation and validation cohorts, the areas under the curve of the CNCQ-OSA were 0.761 and 0.767, respectively. In the validation cohort, the sensitivity and specificity of a CNCQ-OSA score ≥13.5 points for the apnea-hypopnea index (AHI) ≥5/h were 0.821 and 0.559, respectively (Youden index, 0.380), and the score ≥14.5 points were 0.494 and 0.887, respectively (Youden index, 0.375). The CNCQ-OSA had a better predictive value for AHI ≥ 5/h, AHI > 15/h and AHI > 30/h, with the highest Youden index, compared to the other questionnaires. Conclusion: The CNCQ-OSA can effectively identify the risk of OSA, which is appropriate for self-screening at home without physical examinations.

The relationship between obstructive sleep apnea and asthma severity and vice versa: a systematic review and meta-analysis.

BACKGROUND: There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa. METHODS: We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger's test for bias analysis. RESULTS: 34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA (OR = 0.87, 95%CI 0.763-0.998). Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients (WMD = 0.60, 95%CI 0.16-1.04). More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49-7.64). CONCLUSION: OSA was associated with more severe or difficult-to-control asthma with decreased %FEV1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment.

Application value of joint NoSAS score and Epworth Sleepiness Scale for assessment of obstructive sleep apnea hypopnea syndrome.

OBJECTIVE: By comparing the predictive value of the NoSAS (Neck circumference, Obesity, Snoring, Age and Sex) score combined with the Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire (STOP-Bang), STOP Questionnaire (STOP) and Berlin Questionnaire (Berlin), the application value of the NoSAS score combined with ESS in screening Obstructive sleep apnea hypopnea syndrome (OSAHS) in the population is evaluated. METHOD: 2560 suspected OSAHS patients visited the Sleep Medical Center of the First Hospital of Guangzhou Medical University between September 1, 2016 and October 31, 2020, and were monitored with a polysomnogram (PSG) after completing the NoSAS score, ESS, STOP-Bang, STOP and Berlin. The sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic (ROC) curve of each scale were calculated, and the accuracy in predicting OSAHS of the NoSAS score combined with ESS and each scale was analyzed. RESULTS: The areas under the ROC curve scored by Berlin were higher than those of the other four questionnaires with Apnea Hypopnea Index (AHI) cutoffs of ≥5 and ≥ 10 events/h, while the area under the ROC curve scored by the NoSAS score was the highest with AHI cutoffs of ≥15, ≥20, ≥25 and ≥ 30 events/h. Among the five scales, the diagnostic odds ratio (DOR) of the NoSAS score was the highest. When a NoSAS score of ≥7 was used as the cutoff point for diagnostic NoSAS, it had higher sensitivity and specificity with a NoSAS score of ≥8 as the cutoff point for diagnostic NoSAS. A NoSAS score of ≥7 combined with ESS significantly improved its specificity for predicted OSAHS patients. CONCLUSION: The NoSAS score is a simple and effective new tool for screening patients for OSAHS, while a NoSAS score of ≥7 combined with ESS can further improve its specificity. Thus, we suggest further screening with ESS after a NoSAS score of ≥7 in suspected populations.

Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial.

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD. Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment. Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group. Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.