Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering.

Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2 g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin glycation and (iii) reactive carbonyl species sequestering in twelve (M/F=10/2) sedentary, overweight-to-obese (BMI: 30.0+/-2.7 kg/m2) adults (40.1+/-6.2 years). Muscle carnosine concentration (Proton Magnetic Resonance Spectroscopy; 1H-MRS), dynamics of muscle energy metabolism (Phosphorus Magnetic Resonance Spectroscopy; 31P-MRS), body composition (Magnetic Resonance Imaging; MRI), resting energy expenditure (indirect calorimetry), glucose tolerance (oGTT), habitual physical activity (accelerometers), serum carnosine and carnosinase-1 content/activity (ELISA), albumin glycation, urinary carnosine and carnosine-propanal concentration (mass spectrometry) were measured. Supplementation-induced increase in muscle carnosine was paralleled by improved dynamics of muscle post-exercise phosphocreatine recovery, decreased serum albumin glycation and enhanced urinary carnosine-propanal excretion (all p<0.05). Magnitude of supplementation-induced muscle carnosine accumulation was higher in individuals with lower baseline muscle carnosine, who had lower BMI, higher physical activity level, lower resting intramuscular pH, but similar muscle mass and dietary protein preference. Level of supplementation-induced increase in muscle carnosine correlated with reduction of protein glycation, increase in reactive carbonyl species sequestering, and acceleration of muscle post-exercise phosphocreatine recovery.

The association between septicemia and the risk of multiple sclerosis: a nationwide register-based retrospective cohort study in Taiwan.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Few studies focused on the relationship between septicemia and MS. AIM: To evaluate the potential impact of septicemia on risk for MS. DESIGN: Two cohorts of patients with septicemia and without septicemia were followed up for the occurrence of MS. METHODS: Patients of 482 790 with septicemia was enrolled from the National Health Insurance Research Database between 2001 and 2011 as the study group to match the 1 892 820 individuals, as the control group, by age and gender. Incidence of MS in both groups was calculated. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR) for MS between groups. RESULTS: Septicemia patients had a 3.06-fold (95% CI: 2.16-4.32, P < 0.001) greater risk of developing MS than the matched group. In addition, higher severity of septicemia was associated with higher risk of developing MS (moderate: HR = 4.03, 95% CI: 2.53-6.45, P < 0.001; severe: HR = 11.1, 95% CI: 7.01-17.7, P < 0.001). Similar results also occurred in both male and female patients with septicemia (male: HR = 4.06, 95% CI: 2.17-7.58, P < 0.001; female: HR = 2.72, 95% CI: 1.79-4.11, P < 0.001). Patients without counterpart comorbidities had a significantly higher risk of MS than the controlled group (HR = 3.02, 95% CI: 2.10-4.35, P < 0.001). CONCLUSION: The results indicated septicemia is linked to an increased risk for MS. Aggressively preventing and treating septicemia may be warranted for one of precautionary strategies of MS.

Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis.

OBJECTIVES: To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)-BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays-on the detection of viral respiratory infections. METHODS: A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay. RESULTS: Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848-0.949), 0.949 (95% confidence interval, 0.882-0.979) and 0.954 (95% confidence interval, 0.871-0.985), respectively. The three mPCRs were comparable in terms of detection of FluA. CONCLUSIONS: Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.

The potential impact of sleep-related movement disorders on stroke risk: a population-based longitudinal study.

BACKGROUND: Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. AIM: To explore the relationship between SRMD and stroke in the general population. DESIGN: Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. METHODS: The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. RESULTS: Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42-3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11-5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12-3.44) and 45-64 years (HR = 1.07, 95% CI = 1.02-1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74-4.50) than that of females (HR = 1.94, 95% CI = 1.01-3.77). CONCLUSIONS: Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

Variations in cognitive demand affect heart rate in typically developing children and children at risk for developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD) is a diagnosis for children who present with movement difficulties, but are of normal intelligence without neurological deficits. Previous studies have demonstrated that children with DCD exhibit perceptual deficits and lower cognition performance. To date, their autonomic nervous system (ANS) responses during tasks requiring cognitive and perceptual effort have not been compared to typically developing children (TDC). OBJECTIVE: The present study investigated heart rate variability (HRV) as a marker for ANS response differences between DCD and TDC, and the impact of different levels of task difficulty. METHODS: Participants were 60 individuals (9-10 years); 30 children at risk for DCD, and 30 TDC. Each participant performed two tasks each of which demanded enhanced cognitive effort: a visual signal detection task and a digit memory task-each task had two levels of difficulty, low (LD) and high (HD). Heart rate responses were continuously recorded during performance of each task. Frequency domain analysis and heart rate sample entropy (SampEn) were computed to determine ANS responses in each of the tasks. RESULTS: HRV differences were detected between the two levels of task difficulty, LD and HD, for the visual signal detection task, but not for the digit memory task. HRV differences between LD and HD conditions were greater for TDC children than DCD when engaged in visual signal detection task, compare to the memory task. INTERPRETATION: The results suggest that children at risk for DCD may show decreased HRV as a marker for altered ANS responses and potential deficits in the linkage between their perceptions and actions.

Newly diagnosed gastroesophageal reflux disease increased the risk of acute exacerbation of chronic obstructive pulmonary disease during the first year following diagnosis--a nationwide population-based cohort study.

BACKGROUND: While prior studies have demonstrated that chronic obstructive pulmonary disease (COPD) is associated with gastroesophageal reflux disease (GERD), and that GERD is associated with acute exacerbations of COPD (AECOPD), no study to date has been able to establish temporality in this relationship. The purpose of this cohort study was to explore the impact of a new diagnosis of GERD on the risk of subsequent AECOPD. METHODS: We used a retrospective population-based cohort design to analyse the data of 1976 COPD subjects with GERD as an exposure cohort and 3936 COPD subjects without GERD as a comparison group. We individually tracked each subject in this study for 12 months and identified those subjects who experienced an episode of AECOPD. Hazard ratios (HR) were calculated using Cox proportional hazards regression analysis. RESULTS: The incidence of AECOPD was 4.08 and 2.79 per 100 person-year in individuals with and without GERD, respectively (p = 0.012). Following adjustment for sex, age, ischaemic heart disease, heart failure, atrial fibrillation, hypertension, osteoporosis, anxiety, diabetes mellitus, angina, stroke, anaemia, dementia, occupational category, monthly insurance premium, number of OPD visits and COPD severity. The stepwise Cox regression analysis revealed that GERD was independently associated with an increased risk of AECOPD (HR = 1.48, 95% CI = 1.10-1.99). CONCLUSION: This study demonstrated that GERD is an independent risk factor for AECOPD. Caution should be exercised when assessing GERD symptoms in patients with COPD.

Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation.

The antitumor activity of an inhibitor of 26S proteasome bortezomib (Velcade) has been observed in various malignancies, including colon cancer, prostate cancer, breast cancer, and ovarian cancer. Bortezomib has been proposed to stimulate autophagy, but scientific observations did not always support this. Interactions between ERK activity and autophagy are complex and not completely clear. Autophagy proteins have recently been shown to regulate the functions of ERK, and ERK activation has been found to induce autophagy. On the other hand, sustained activation of ERK has also been shown to inhibit the maturation step of the autophagy process. In this study, we sought to identify the mechanism of autophagy regulation in cancer cells treated with bortezomib. Our results indicate that bortezomib blocked the autophagic flux without inhibiting the fusion of the autophagosome and lysosome. In ovarian cancer, as well as endometrial cancer and hepatocellular carcinoma cells, bortezomib inhibited protein degradation in lysosomes by suppressing cathepsins, which requires the participation of ERK phosphorylation, but not JNK or p38. Our findings that ERK phosphorylation reduced cathepsins further explain how ERK phosphorylation inhibits the autophagic flux. In conclusion, bortezomib may induce ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors. The inhibition of cisplatin-induced autophagy by bortezomib can enhance chemotherapy efficacy in ovarian cancer. As we also found that bortezomib blocks the autophagic flux in other cancers, the synergistic cytotoxic effect of bortezomib by abolishing chemotherapy-related autophagy may help us develop strategies of combination therapies for multiple cancers.

Postural sway and perception of affordances in children at risk for developmental coordination disorder.

Gibson (The ecological approach to visual perception, Houghton Mifflin, Boston, 1979/1986) defined affordances as opportunities for motor behaviors, and highly emphasized the interaction between perception and action. Research on children with developmental coordination disorder commonly reports difficulties in judgments of affordances (perception) and in postural control (action). However, how perception and action are coupled has not been studied yet. The present study sought to evaluate the relationship between control of postural sway and perception of affordances in children at risk for developmental coordination disorder (RDCD) and typically developing children (TDC). We hypothesized that the relationship between perception and action would differ between groups. Participants made a series of judgments about their maximum sitting height (SHmax) while standing with and without wearing 10 cm blocks on feet. Postural sway and the judgment accuracy were recorded. Our findings showed that RDCD swayed more during judgment sessions and made less accurate judgments compared to TDC. In addition, TDC reduced postural sway from inter-judgment to judgment sessions, whereas the postural sway of RDCD remained identical between sessions. Last, while TDC reduced postural sway across judgment trials and revealed a learning effect of the judgments about SHmax in the block condition, RDCD never modulated postural sway and did not learn their SHmax in both non-block and block conditions. Overall, modulation of postural sway differed between groups during judgment sessions and between inter-judgment and judgment sessions, whereby their perceptual judgments about SHmax were differentially influenced. To summarize, this study demonstrated a difference in perception and action coupling between RDCD and TDC.

Kefir improves fatty liver syndrome by inhibiting the lipogenesis pathway in leptin-deficient ob/ob knockout mice.

OBJECTIVE: Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. RESULTS: In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator-activated receptor α (PPARα) or hepatic carnitine palmitoyltransferase-1α (CPT1α) in the livers of ob/ob mice. CONCLUSION: On the basis of these results, we conclude that kefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.

Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional recurrence.

PURPOSE: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97% of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. RESULTS: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1%, respectively. A total of 27 patients had locoregional recurrence: 85.2% in-field failures, 11.1% marginal failures, and 3.7% out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9%) compared to those receiving conservative treatment (32.0%, p=0.051). In patients treated with 1 course of radiotherapy, grade ≥3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6% of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. CONCLUSION: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome.

Phosphorylation of signal transducer and activator of transcription 1 reduces bortezomib-mediated apoptosis in cancer cells.

The potent and selective proteasome inhibitor bortezomib has shown remarkable antitumor activity and is now entering clinical trials for several cancers. However, the molecular mechanisms by which bortezomib induces cytotoxicity in ovarian cancer cells still remain unclear. In this study, we show that bortezomib induced apoptosis, which was demonstrated by the downregulation of antiapoptotic molecules (Bcl-2, Bcl-XL, p-Bad, and p-AKT) and the upregulation of proapoptotic proteins (p21, p27, and cleaved-Bid) in ovarian cancer cell lines. Moreover, bortezomib stimulates Janus kinase (JAK) phosphorylation and activates heat-shock transcription factor-1 (HSF-1) and heat-shock protein 70 (HSP70), ultimately leading to signal transducer and activator of transcription 1 (STAT1) phosphorylation. Phosphorylated STAT1 partially counteracted apoptosis induced by bortezomib in cancer cells. These findings suggest that the antitumor activity of bortezomib in ovarian cancer can be improved by inhibiting bortezomib-induced STAT1 phosphorylation. This effect can be achieved by STAT1 knockdown, HSP70 knockdown, JAK inhibition, or the addition of cisplatin, one of the most commonly used anticancer drugs. These results provide the first evidence that STAT1 phosphorylation can play a role in bortezomib resistance by exerting antiapoptotic effects. They also suggest the possibility to abolish or reduce bortezomib chemoresistance in ovarian cancer by the addition of cisplatin or JAK inhibitors.

Reversal of ophthalmic artery flow as a predictor of intracranial hemodynamic compromise: implication for prognosis of severe carotid stenosis.

BACKGROUND AND PURPOSE: High-grade cervical carotid stenosis (70-99%) or occlusion often accompanies reversed ophthalmic artery flow (ROAF), but its potential clinical significances remain poor understood. This study assessed ROAF and the related variables caused by carotid hemodynamic compromise in patients with unilateral severe cervical carotid stenosis. METHODS: The study consisted of 200 patients diagnosed as unilateral high-grade cervical carotid stenosis/occlusion using ultrasonography. The hemodynamic parameters of 152 patients, excluding 48 with cervical carotid occlusion, were compared based on the presence of ROAF. Out of 200 patients, 159 underwent brain magnetic resonance imaging and were analysed for risk factors impacting functional outcomes including ROAF. RESULTS: The patients (n = 48) with internal carotid artery occlusion had significantly higher incidence (62.5%) of ROAF compared with that of 25.0% in those patients (n = 152) with unilateral high-grade carotid stenosis (P < 0.001). In ROAF patients (n = 38) with the unilateral high-grade stenosis, a significant retrobulbar arteries hemodynamic difference was observed between the stenotic and non-stenotic vessels. The patients (n = 159) with history of stroke (P = 0.035), ROAF (P = 0.023) and intracranial stenosis (P < 0.001) exhibited significantly higher incidence of poor functional outcome compared with the corresponding control groups. In the same patients (n = 159), those with both cervical and intracranial stenosis showed sevenfold higher risk (OR, 7.60; 95% CI, 3.44-16.81) for ROAF than those with only cervical stenosis. CONCLUSIONS: ROAF may result from intracranial hemodynamic compromise. Patients with unilateral high-grade cervical carotid stenosis/occlusion in combination with intracranial stenosis appear to be a significant risk factor for poor functional outcome and increased incidence of ROAF.

Regulation of ovarian cancer progression by microRNA-187 through targeting Disabled homolog-2.

MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be expressed at higher levels in ovarian cancers than in benign tumors. In patients with ovarian cancer, however, higher levels of miR-187 and miR-200a expression were paradoxically associated with better OS and recurrence-free survival. Further, multivariate analysis showed that miR-187 served as an independent prognostic factor for patients with ovarian cancer (n=176). Computational prediction and microarray results indicated that miR-187 directly targeted Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the target site of miR-187 was located at the 3'-UTR of the Dab2 gene. Generally considered as a tumor-suppressor gene, Dab2 may actually promote tumor progression in advanced cancers through epithelial-to-mesenchymal transition (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation, but continued overexpression of miR-187 suppressed Dab2 and inhibited migration. Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes of patients. Collectively, these results demonstrate distinct dual roles of Dab2 in cell proliferation and tumor progression. In the initial steps of tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation. During the later stages, however, continued increased levels of miR-187 inhibits the Dab2-dependent EMT that is associated with tumor invasiveness, which is presumed to be the reason why cancers with high miR-187 levels were associated with better survivals.

Postural responses to a suprapostural visual task among children with and without developmental coordination disorder.

We sought to determine the effects of varying the perceptual demands of a suprapostural visual task on the postural activity of children with developmental coordination disorder (DCD), and typically developing children (TDC). Sixty-four (32 per group) children aged between 9 and 10 years participated. In a within-participants design, each child performed a signal detection task at two levels of difficulty, low (LD) and high difficulty (HD). During performance of the signal detection tasks we recorded positional variability of the head and torso using a magnetic tracking system. We found that task difficulty had a greater effect on task performance among the TDC group than among children with DCD. Overall positional variability was greater the DCD group than in the TDC group. In the TDC group, positional variability was reduced during performance of the HD task, relative to sway during performance of the LD task. In the DCD group, positional variability was greater during performance of the HD task than during performance of the LD task. In children, DCD may reduce the strength of functional integration of postural activity with the demands of suprapostural visual tasks.

Robust, globally consistent and fully automatic multi-image registration and montage synthesis for 3-D multi-channel images.

The need to map regions of brain tissue that are much wider than the field of view of the microscope arises frequently. One common approach is to collect a series of overlapping partial views, and align them to synthesize a montage covering the entire region of interest. We present a method that advances this approach in multiple ways. Our method (1) produces a globally consistent joint registration of an unorganized collection of three-dimensional (3-D) multi-channel images with or without stage micrometer data; (2) produces accurate registrations withstanding changes in scale, rotation, translation and shear by using a 3-D affine transformation model; (3) achieves complete automation, and does not require any parameter settings; (4) handles low and variable overlaps (5-15%) between adjacent images, minimizing the number of images required to cover a tissue region; (5) has the self-diagnostic ability to recognize registration failures instead of delivering incorrect results; (6) can handle a broad range of biological images by exploiting generic alignment cues from multiple fluorescence channels without requiring segmentation and (7) is computationally efficient enough to run on desktop computers regardless of the number of images. The algorithm was tested with several tissue samples of at least 50 image tiles, involving over 5000 image pairs. It correctly registered all image pairs with an overlap greater than 7%, correctly recognized all failures, and successfully joint-registered all images for all tissue samples studied. This algorithm is disseminated freely to the community as included with the Fluorescence Association Rules for Multi-Dimensional Insight toolkit for microscopy (http://www.farsight-toolkit.org).

Effects of topical corticosteroids on the sciatic nerve: an experimental study to adduce the safety in treating carpal tunnel syndrome.

Despite known detrimental effects on the blood flow and histology of nerves after intraneural corticosteroid injection, the neurotoxic effect of corticosteroids remains unclear. We investigated the effect of topical dexamethasone on nerve function. Two sponge strips soaked with dexamethasone at doses of 0.8, 1.6, and 3.2 mg were placed under and over the left sciatic nerve of adult Wistar rats for 30 minutes. Mixed-nerve-elicited somatosensory evoked potentials and dermatomal somatosensory evoked potentials were evaluated immediately and repeated together with functional tests and histology 2 weeks later. Evoked potential amplitude was dose-dependently lower and latency was prolonged in dexamethasone-treated sciatic nerves compared to controls. The suppression persisted with incomplete recovery for at least 4 hours, but differences between treated and control nerves were not significant after 2 weeks. Topical dexamethasone adversely affected neural conduction in a dose-dependent manner. Our results suggest that caution is required when using large doses of corticosteroid for injection of the carpal tunnel.

The role of body mass index in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Low body mass index (BMI) is a strong prognostic marker in stable chronic obstructive pulmonary disease (COPD); however, little is known about its role in acute exacerbations of COPD. OBJECTIVES: To determine the prevalence and determinants of low BMI in emergency department (ED) patients with acute exacerbations of COPD, and to examine whether low BMI was associated with more severe acute exacerbations, more intensive ED treatments and worse post-ED outcomes. METHODS: A secondary analysis was performed using data from a prospective multicentre cohort study involving 29 ED in the USA and Canada. Using a standard protocol, ED patients with acute exacerbations of COPD were interviewed and their charts reviewed. BMI was calculated using self-reported weight and height. Main outcome measures included hospital admission, post-ED relapse and ongoing exacerbation. RESULTS: 395 patients were enrolled. Their median age was 69 years (interquartile range 62-76); 52% were women. Thirteen per cent (95% CI 10% to 16%) were underweight, 37% normal weight, 27% overweight and 23% were obese. Current smoking was independently associated with underweight (OR 5.4, 95% CI 1.1 to 25.2). In the propensity-matched cohort, there were no significant differences in severity of exacerbation, treatments received in the ED, or short-term clinical outcomes, according to BMI. CONCLUSIONS: Low BMI is not uncommon in patients with acute exacerbations of COPD, and current smoking is associated with low BMI in these patients. Unlike its role in stable COPD, BMI appears to have little impact on exacerbation severity, treatments received in the ED, and short-term clinical outcomes in acute exacerbations of COPD.