Impact of self-reported Gastroesophageal reflux disease in subjects from COPDGene cohort

Abstract Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.http://deepblue.lib.umich.edu/bitstream/2027.42/134572/1/12931_2014_Article_1500.pd

Impact of self-reported Gastroesophageal reflux disease in subjects from COPDGene cohort

Abstract Background The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes. Methods Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score. Results GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association. Conclusions In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.http://deepblue.lib.umich.edu/bitstream/2027.42/109476/1/12931_2014_Article_1500.pd

Association Between Interstitial Lung Abnormalities and All-Cause Mortality.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.To investigate whether interstitial lung abnormalities are associated with increased mortality.Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).Interstitial lung abnormality status as determined by chest CT evaluation.All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.National Institutes of Health (NIH) T32 HL007633 Icelandic Research Fund 141513-051 Landspitali Scientific Fund A-2015-030 National Cancer Institute grant 1K23CA157631 NIH K08 HL097029 R01 HL113264 R21 HL119902 K25 HL104085 R01 HL116931 R01 HL116473 K01 HL118714 R01 HL089897 R01 HL089856 N01-AG-1-2100 HHSN27120120022C P01 HL105339 P01 HL114501 R01 HL107246 R01 HL122464 R01 HL111024 National Heart, Lung, and Blood Institute's Framingham Heart Study contract N01-HC-2519.5 GlaxoSmithKline NCT00292552 5C0104960 National Institute on Aging (NIA) grant 27120120022C NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) NIA 27120120022

Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism

Brown adipose tissue (BAT) is an attractive therapeutic target for treating obesity and metabolic diseases. Octacosanol is the main component of policosanol, a mixture of very long chain aliphatic alcohols obtained from plants. The current study aimed to investigate the effect of octacosanol and policosanol on high-fat diet (HFD)-induced obesity. Mice were fed on chow, or HFD, with or without octacosanol or policosanol treatment for four weeks. HFD-fed mice showed significantly higher body weight and body fat compared with chow-fed mice. However, mice fed on HFD treated with octacosanol or policosanol (HFDo/p) showed lower body weight gain, body fat gain, insulin resistance and hepatic lipid content. Lower body fat gain after octacosanol or policosanol was associated with increased BAT activity, reduced expression of genes involved in lipogenesis and cholesterol uptake in the liver, and amelioration of white adipose tissue (WAT) inflammation. Moreover, octacosanol and policosanol significantly increased the expression of Ffar4, a gene encoding polyunsaturated fatty acid receptor, which activates BAT thermogenesis. Together, these results suggest that octacosanol and policosanol ameliorate diet-induced obesity and metabolic disorders by increasing BAT activity and improving hepatic lipid metabolism. Thus, these lipids represent promising therapeutic targets for the prevention and treatment of obesity and obesity-related metabolic disorders

Investigation of bimodal characteristics of the droplet size distribution in condensation spray

Abstract To understand the generation process of airborne droplets during exhalation, this study investigates the mechanism of bimodal characteristics of the size distribution of droplets generated in a condensed spray flow. The phase change process in the condensed spray flow was estimated based on the droplet size distribution measured by a phase Doppler particle analyzer and the temperature distribution measured by a thermistor. On the central axis, the size distribution was unimodal in the spray interior. In contrast, bimodality of the size distribution at the outer edge of the spray flow was observed. At the edge of the spray flow, a large temperature gradient was formed. This indicates that condensation actively occurred at the outer edge. For the same reason as outlined above, condensation did not progress at the spray center because of the consumption of water vapor at the outer edge by the condensation, and the droplet diameter did not change significantly. Hence, owing to the difference in the local phase change process between the center and outer edge of the spray, large and small droplets can exist simultaneously in the middle region. As a result, the size distribution of the condensation spray is bimodal

Radiology of Fractures in Intoxicated Emergency Department Patients: Locations, Mechanisms, Presentation, and Initial Interpretation Accuracy.

The purpose of this study was to investigate the relationship of alcohol intoxication to time-to-presentation following injury, fracture type, mechanism of injury leading to fracture, and initial diagnostic radiology interpretation performance of emergency physicians versus diagnostic radiologists in patients who present to the emergency department (ED) and are subsequently diagnosed with fracture. Medical records of 1286 patients who presented to the ED and were diagnosed with fracture who also underwent plain film or computed tomography (CT) imaging were retrospectively reviewed. The subjects were divided into intoxicated and sober groups. Patient characteristics, injury-to-presentation time, fracture location, and discrepancies between initial clinical and radiological evaluations were compared. Of 1286 subjects, 181 patients were included in the intoxicated group. Only intoxicated patients presented with head/neck fractures more than 24 hours after injury. The intoxicated group showed a higher rate of head/neck fractures (skull 23.2% vs 5.8%, face and orbit 30.4% vs 9.5%; P &lt; 0.001) and a lower rate of extremity injuries. The rate of nondiagnosis of fractures by emergency physicians later identified by radiologists was the same in both groups (7.7% vs 7.7%, P = 0.984). While the same proportion of intoxicated patients presented more than 24 hours following injury, only intoxicated patients presented with craniofacial and cervical spinal fractures during this period. Alcohol-related injuries are more often associated with head/neck fractures but less extremity injuries. The rate of fractures missed by emergency physicians but later diagnosed by radiologists was the same in intoxicated and sober patients