Few randomised controlled trials (RCTs) of interventions for the treatment of adolescent obesity have taken place outside the western world. This RCT tested whether a simple ‘good practice’ intervention for the treatment of adolescent obesity would have a greater impact on weight status and other outcomes than a referral to primary care (control) in adolescents in Kuwait City.
We report on an assessor-blinded RCT of a treatment intervention in 82 obese 10- to 14-year-olds (mean age 12.4, SD 1.2 years), randomised to a good practice treatment or primary care control group over 6 months. The good practice intervention was intended as relatively low intensity (6 hours contact over 24 weeks, group-based), aiming to change sedentary behaviour, physical activity, and diet. The primary outcome was a change in body mass index (BMI) Z score; other outcomes were changes in waist circumference and blood pressure.
The retention of subjects to follow up was acceptable (n = 31 from the intervention group, and n = 32 from the control group), but engagement with both the intervention and control treatment was poor. Treatment had no significant effect on BMI Z score relative to control, and no other significant benefits to intervention were observed.
The trial was feasible, but highlights the need to engage obese adolescents and their families in the interventions being trialled. The trial should inform the development of future adolescent obesity treatment trials in the Gulf States with the incorporation of qualitative assessment in future intervention trials.
RCT Registered as National Adolescent Treatment Trial for Obesity in Kuwait (NATTO):
http://www.controlled-trials.com/ISRCTN37457227, 1 December 2009.
obesity; overweight; adolescents; treatment; BMI; randomised controlled trial
To assess relationships between current physical activity (PA), dietary intake and body mass index (BMI) in English children.
Design and setting
Longitudinal birth cohort study in northeast England, cross-sectional analysis.
425 children (41% of the original cohort) aged 6–8 years (49% boys).
Main outcome measures
PA over 7 days was measured objectively by an accelerometer; three categories of PA were created: ‘active’ ≥60 min/day moderate-to-vigorous-intensity PA (MVPA); ‘moderately active’ 30–59 min/day MVPA; ‘inactive’ <30 min/day MVPA. Dietary intake over 4 days was measured using a prospective dietary assessment tool which incorporated elements of the food diary and food frequency methods. Three diet categories were created: ‘healthy’, ‘unhealthy’ and ‘mixed’, according to the number of portions of different foods consumed. Adherence to the ‘5-a-day’ recommendations for portions of fruit and vegetables was also assessed. Children were classified as ‘healthy weight’ or ‘overweight or obese’ (OW/OB) according to International Obesity Taskforce cutpoints for BMI. Associations between weight status and PA/diet categories were analysed using logistic regression.
Few children met the UK-recommended guidelines for either MVPA or fruit and vegetable intake, with just 7% meeting the recommended amount of MVPA of 60 min/day, and 3% meeting the 5-a-day fruit and vegetable recommendation. Higher PA was associated with a lower OR for OW/OB in boys only (0.20, 95% CI 0.04 to 0.88). There was no association detected between dietary intake and OW/OB in either sex.
Increasing MVPA may help to reduce OW/OB in boys; however, more research is required to examine this relationship in girls. Children are not meeting the UK guidelines for diet and PA, and more needs to be done to improve this situation.
Public Health; Epidemiology
The quantity and quality of studies in child and adolescent physical activity and sedentary behaviour have rapidly increased, but research directions are often pursued in a reactive and uncoordinated manner.
To arrive at an international consensus on research priorities in the area of child and adolescent physical activity and sedentary behaviour.
Two independent panels, each consisting of 12 experts, undertook three rounds of a Delphi methodology. The Delphi methodology required experts to anonymously answer questions put forward by the researchers with feedback provided between each round.
The primary outcome of the study was a ranked set of 29 research priorities that aimed to be applicable for the next 10 years. The top three ranked priorities were: developing effective and sustainable interventions to increase children’s physical activity long-term; policy and/or environmental change and their influence on children’s physical activity and sedentary behaviour; and prospective, longitudinal studies of the independent effects of physical activity and sedentary behaviour on health.
These research priorities can help to guide decisions on future research directions.
Physical activity; Sedentary behaviour; Research priorities; Children; Adolescents
Evaluate the predictive validity of ActiGraph energy expenditure equations and the classification accuracy of physical activity intensity cut-points in preschoolers.
Forty children aged 4–6 years (5.3±1.0 years) completed a ∼150-min room calorimeter protocol involving age-appropriate sedentary, light and moderate-to vigorous-intensity physical activities. Children wore an ActiGraph GT3X on the right mid-axillary line of the hip. Energy expenditure measured by room calorimetry and physical activity intensity classified using direct observation were the criterion methods. Energy expenditure was predicted using Pate and Puyau equations. Physical activity intensity was classified using Evenson, Sirard, Van Cauwenberghe, Pate, Puyau, and Reilly, ActiGraph cut-points.
The Pate equation significantly overestimated VO2 during sedentary behaviors, light physical activities and total VO2 (P<0.001). No difference was found between measured and predicted VO2 during moderate-to vigorous-intensity physical activities (P = 0.072). The Puyau equation significantly underestimated activity energy expenditure during moderate-to vigorous-intensity physical activities, light-intensity physical activities and total activity energy expenditure (P<0.0125). However, no overestimation of activity energy expenditure during sedentary behavior was found. The Evenson cut-point demonstrated significantly higher accuracy for classifying sedentary behaviors and light-intensity physical activities than others. Classification accuracy for moderate-to vigorous-intensity physical activities was significantly higher for Pate than others.
Available ActiGraph equations do not provide accurate estimates of energy expenditure across physical activity intensities in preschoolers. Cut-points of ≤25counts⋅15 s−1 and ≥420 counts⋅15 s−1 for classifying sedentary behaviors and moderate-to vigorous-intensity physical activities, respectively, are recommended.
Obesity impairs health related quality of life (HRQL) in adolescents, but most evidence in this area has mostly come from western societies. We wanted to test the hypothesis that obesity impairs HRQL in Kuwaiti adolescents, and to test for differences in HRQL assessed by self-report and parent-proxy report.
In 500 Kuwaiti 10–14 year olds HRQL was assessed using the Peds QLTM with both adolescent self-reports (n = 500) and parent-proxy reports (n = 374).
Obesity was not significantly associated with HRQL in regression analysis. In a paired comparison of 98 pairs of obese adolescents vs. 98 healthy weight peers, impairment of HRQL reached significance only for physical score (95% CI = −1.5, -9.4), not for psychosocial score or total score. In a paired comparison of parent-proxy vs. self-reports for the obese adolescents, total score (95% CI = −4.9, -10.9), physical score (95% CI = −3.2, -11.0), and psychosocial score (95% CI = −4.2, -10.8) were all significantly lower in the parent reports.
Obesity is not associated with marked impairment of HRQL in adolescents in Kuwait, in contrast to studies in western societies. This may reflect cultural differences in attitudes towards obesity.
Obesity; Adolescent; Health-related quality of life
Rationale and Objectives
The airway tree is a primary conductive structure, and airways’ morphologic characteristics, or variations thereof, may have an impact on airflow, thereby affecting pulmonary function. The objective of this study was to investigate the correlation between airway tree architecture, as depicted on computed tomography, and pulmonary function.
Materials and Methods
A total of 548 chest computed tomographic examinations acquired on different patients at full inspiration were included in this study. The patients were enrolled in a study of chronic obstructive pulmonary disease (Specialized Center for Clinically Oriented Research) and underwent pulmonary function testing in addition to computed tomographic examinations. A fully automated airway tree segmentation algorithm was used to extract the three-dimensional airway tree from each examination. Using a skeletonization algorithm, airway tree volume–normalized architectural measures, including total airway length, branch count, and trachea length, were computed. Correlations between airway tree measurements with pulmonary function testing parameters and chronic obstructive pulmonary disease severity in terms of the Global Initiative for Obstructive Lung Disease classification were computed using Spearman’s rank correlations.
Non-normalized total airway volume and trachea length were associated (P < .01) with lung capacity measures (ie, functional residual capacity, total lung capacity, inspiratory capacity, vital capacity, residual volume, and forced expiratory vital capacity). Spearman’s correlation coefficients ranged from 0.27 to 0.55 (P < .01). With the exception of trachea length, all normalized architecture-based measures (ie, total airway volume, total airway length, and total branch count) had statistically significant associations with the lung function measures (forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced expiratory vital capacity), and adjusted volume was associated with all three respiratory impedance measures (lung reactance at 5 Hz, lung resistance at 5 Hz, and lung resistance at 20 Hz), and adjusted branch count was associated with all respiratory impedance measures but lung resistance at 20 Hz. When normalized for lung volume, all airway architectural measures were statistically significantly associated with chronic obstructive pulmonary disease severity, with Spearman’s correlation coefficients ranging from −0.338 to −0.546 (P < .01).
Despite the large variability in anatomic characteristics of the airway tree across subjects, architecture-based measures demonstrated statistically significant associations (P < .01) with nearly all pulmonary function testing measures, as well as with disease severity.
Airway tree architecture; chronic obstructive pulmonary disease; computed tomography; pulmonary function; lung diseases
Prevention of obesity in childhood and adolescence remains a worthwhile and realistic goal, but preventive efforts have been beset by a number of problems, which are the subject of this review. The review draws on recent systematic reviews and evidence appraisals and has a United Kingdom (UK) perspective because there is a rich evidence base in the United Kingdom that may be helpful to obesity prevention researchers elsewhere. Recent evidence of a leveling off in child and adolescent obesity prevalence in some Western nations should not encourage the belief that the obesity prevention problem has been solved, although a better understanding of recent secular trends might be helpful for prevention strategy in future. An adequate body of evidence provides behavioral targets of preventive interventions, and there are frameworks for prioritizing these targets logically and models for translating them into generalizable interventions with a wide reach (e.g., school-based prevention interventions such as Planet Health). An improved understanding of the “energy gap” that children and adolescents experience would be helpful to the design of preventive interventions and to their tailoring to particular groups. In the United Kingdom, some recent etiological evidence has been taken as indicative of the need for paradigm shifts in obesity prevention, but this evidence from single studies has not been replicated, and paradigm shifts probably occur only rarely. Ensuring that the evidence base on etiology and prevention influences policy effectively remains one of the greatest challenges for childhood obesity researchers.
Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.
We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.
Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production.
Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75±2.19 vs. 3.86±3.06 days for zileuton vs. placebo, p=0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p=0.63) despite a decline in urinary LTE4 levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine −1.38± 1.19 vs. 0.14±1.51, p<0.0001) and 72 hours (−1.32±2.08 vs. 0.26±1.93, p<0.006). Adverse events were similar in both groups.
While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE4 levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.
Chronic Obstructive Pulmonary Disease (COPD); Acute exacerbation of COPD (AECOPD); Leukotrienes; Zileuton; Clinical trial
Sitting time and breaks in sitting influence cardio-metabolic health. New monitors (e.g. activPAL™) may be more accurate for measurement of sitting time and breaks in sitting although how to optimize measurement accuracy is not yet clear. One important issue is the minimum sitting/upright period (MSUP) to define a new posture. Using the activPAL™, we investigated the effect of variations in MSUP on total sitting time and breaks in sitting, and also determined the criterion validity of different activPAL™ settings for both constructs.
We varied setting of MSUP in 23 children (mean (SD) age 4.5 y (0.7)) who wore activPAL™ (24 hr/d) for 5–7 d. We first studied activPAL™ using the default setting of 10 s MSUP and then reduced this to 5 s, 2 s and 1 s. In a second study, in a convenience sample of 30 pre-school children (mean age 4.1 y (SD 0.5)) we validated the activPAL™ measures of sitting time and breaks in sitting at different MSUP settings against direct observation.
Comparing settings of 10, 5, 2 and 1 s, there were no significant differences in sitting time (6.2 hr (1.0), 6.3 hr (1.0), 6.4 hr (1.0) and 6.3 hr (1.6), respectively) between settings but there were significant increases in the apparent number of breaks - (8(3), 14(2), 21(4) and 28 (6)/h) at 10, 5, 2 and 1 s settings, respectively. In comparison with direct observation, a 2 s setting had the smallest error relative to direct observation (95% limits of agreement: -14 to +17 sitting bouts/hr, mean difference 1.83, p = 0.2).
With activPAL™, breaks in sitting, but not total sitting time, are highly sensitive to the setting of MSUP, with 2 s optimal for young children. The MSUP to define a new posture will need to be empirically determined if accurate measurements of number of breaks in sitting are to be obtained.
The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity () was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The of the male and female adolescents were 73.9±5.7 ml. kg−1. min−1 and 61.5±6.3 ml. kg−1. min−1, respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8–13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ. day−1, 5.4±3.0 MJ. day−1 and 2.2±0.6. 70.6% of the variation in was explained by sex (partial R2 = 54.7%) and body mass index (partial R2 = 15.9%). Energy expenditure and physical activity variables did not predict variation in once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success.
Background and Aims
Timing of obesity development during childhood and adolescence is unclear, hindering preventive strategies. The primary aim of the present study was to quantify the incidence of overweight and obesity throughout childhood and adolescence in a large contemporary cohort of English children (the Avon Longitudinal Study of Parents and Children, ALSPAC; children born 1991–1992). A secondary aim was to examine the persistence of overweight and obesity.
Longitudinal data on weight and height were collected annually from age 7–15 years in the entire ALSPAC cohort (n = 4283), and from 3 to 15 years in a randomly selected subsample of the cohort (n = 549; ‘Children in Focus’ CiF). Incidence of overweight and obesity (BMI (Body mass index) at or above the 85th and 95th centiles relative to UK reference data) was calculated. Risk ratios (RR) for overweight and obesity at 15 years based on weight status at 3, 7, and 11 years were also calculated.
In the entire cohort, four-year incidence of obesity was higher between ages 7 and 11 years than between 11 and 15 years (5.0% vs 1.4% respectively). In the CiF sub-sample, four-year incidence of obesity was also highest during mid-childhood (age 7–11 years, 6.7%), slightly lower during early childhood (3–7 years, 5.1%) and lowest during adolescence (11–15 years 1.6%). Overweight and obesity at all ages had a strong tendency to persist to age 15 years as indicated by risk ratios (95% CI (Confidence interval)) for overweight and obesity at 15 years from overweight and obesity (relative to healthy weight status) at 3 years (2.4, 1.8–3.1), 7 years (4.6, 3.6–5.8), and 11 years (9.3, 6.5–13.2).
Mid–late childhood (around age 7–11 years) may merit greater attention in future obesity prevention interventions.
ALSPAC; Obesity; Aetiology; Prevention; Overweight; Children; Adolescents
Objectively measured physical activity is low in British children, and declines as childhood progresses. Observational studies suggest that dog-walking might be a useful approach to physical activity promotion in children and adults, but there are no published public health interventions based on dog-walking with children. The Children, Parents, and Pets Exercising Together Study aims to develop and evaluate a theory driven, generalisable, family-based, dog walking intervention for 9-11 year olds.
The Children, Parents, and Pets Exercising Together Study is an exploratory, assessor-blinded, randomised controlled trial as defined in the UK MRC Framework on the development and evaluation of complex interventions in public health. The trial will follow CONSORT guidance. Approximately 40 dog-owning families will be allocated randomly in a ratio of 1.5:1 to receive a simple behavioural intervention lasting for 10 weeks or to a 'waiting list' control group. The primary outcome is change in objectively measured child physical activity using Actigraph accelerometry. Secondary outcomes in the child, included in part to shape a future more definitive randomised controlled trial, are: total time spent sedentary and patterning of sedentary behaviour (Actigraph accelerometry); body composition and bone health from dual energy x-ray absorptiometry; body weight, height and BMI; and finally, health-related quality of life using the PedsQL. Secondary outcomes in parents and dogs are: changes in body weight; changes in Actigraph accelerometry measured physical activity and sedentary behaviour. Process evaluation will consist of assessment of simultaneous child, parent, and dog accelerometry data and brief interviews with participating families.
The Children, Parents, and Pets Exercising Together trial should be the first randomised controlled study to establish and evaluate an intervention aimed at dog-based physical activity promotion in families. It should advance our understanding of whether and how to use pet dogs to promote physical activity and/or to reduce sedentary behaviour in children and adults. The trial is intended to lead to a subsequent more definitive randomised controlled trial, and the work should inform future dog-based public health interventions such as secondary prevention interventions in children or adults.
Trial registration number
Obesity; children; dogs; accelerometry; exercise; CPET
In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume.
In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O2 pulse=VO2/HR) at baseline and 6 months. Medical and surgical patients were divided into “deflators” and “non-deflators” based on change in RV/TLC from baseline (ΔRV/TLC). We defined deflation as the ΔRV/TLC experienced by 75% of surgical patients. We examined changes in O2 pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs.
In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O2 pulse (median ΔRV/TLC −18.0% vs. −9.3%, p=0.0003; median ΔO2 pulse 13.6% vs. 1.8%, p=0.12). Surgical deflators also improved iso-work O2 pulse (0.53 mL/beat, p=0.04 at 20 watts). In the validation cohort, surgical deflators experienced a greater improvement in peak O2 pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical deflators improvements in O2 pulse at rest and during unloaded pedaling (0.32 mL/beat, p<0.0001 and 0.47 mL/beat, p<0.0001, respectively) corresponded with significant reductions in HR and improvements in VO2. On multivariate analysis, deflators were 88% more likely than non-deflators to have an improvement in O2 pulse (OR 1.88, 95% CI 1.30–2.72, p=0.0008).
In COPD, decreased hyperinflation through lung volume reduction is associated with improved O2 pulse.
cardiac function; hyperinflation; lung volume reduction surgery; oxygen pulse
Background and objective
The increasing prevalence of childhood obesity has led to interest in its prevention, particularly through school-based and family-based interventions in the early years. Most evidence reviews, to date, have focused on individual behaviour change rather than the ‘obesogenic environment’.
This paper reviews the evidence on the influence of the food environment on overweight and obesity in children up to 8 years.
Electronic databases (including MEDLINE, EMBASE, Cochrane Controlled Trials Register (CCTR), DARE, CINAHL and Psycho-Info) and reference lists of original studies and reviews were searched for all papers published up to 31 August 2011.
Study designs included were either population-based intervention studies or a longitudinal study. Studies were included if the majority of the children studied were under 9 years, if they related to diet and if they focused on prevention rather than treatment in clinical settings.
Data included in the tables were characteristics of participants, aim, and key outcome results. Quality assessment of the selected studies was carried out to identify potential bias and an evidence ranking exercise carried out to prioritise areas for future public health interventions.
Thirty-five studies (twenty-five intervention studies and ten longitudinal studies) were selected for the review. There was moderately strong evidence to support interventions on food promotion, large portion sizes and sugar-sweetened soft drinks.
Reducing food promotion to young children, increasing the availability of smaller portions and providing alternatives to sugar-sweetened soft drinks should be considered in obesity prevention programmes aimed at younger children. These environment-level interventions would support individual and family-level behaviour change.
Preventive Medicine; Public Health
To study the relationship between emphysema, airflow obstruction and lung cancer in a high risk population we performed quantitative analysis of screening computed tomography (CT) scans.
Subjects completed questionnaires, spirometry and low-dose helical chest CT. Analyses compared cases and controls according to automated quantitative analysis of lung parenchyma and airways measures.
Our case-control study of 117 matched pairs of lung cancer cases and controls did not reveal any airway or lung parenchymal findings on quantitative analysis of screening CT scans that were associated with increased lung cancer risk. Airway measures including wall area %, lumen perimeter, lumen area and average wall HU, and parenchymal measures including lung fraction < −910 Hounsfield Units (HU), were not statistically different between cases and controls.
The relationship between visual assessment of emphysema and increased lung cancer risk could not be verified by quantitative analysis of low-dose screening CT scans in a high risk tobacco exposed population.
Rationale: Chromosome 12p has been linked to chronic obstructive pulmonary disease (COPD) in the Boston Early-Onset COPD Study (BEOCOPD), but a susceptibility gene in that region has not been identified.
Objectives: We used high-density single-nucleotide polymorphism (SNP) mapping to implicate a COPD susceptibility gene and an animal model to determine the potential role of SOX5 in lung development and COPD.
Methods: On chromosome 12p, we genotyped 1,387 SNPs in 386 COPD cases from the National Emphysema Treatment Trial and 424 control smokers from the Normative Aging Study. SNPs with significant associations were then tested in the BEOCOPD study and the International COPD Genetics Network. Based on the human results, we assessed histology and gene expression in the lungs of Sox5−/− mice.
Measurements and Main Results: In the case-control analysis, 27 SNPs were significant at P ≤ 0.01. The most significant SNP in the BEOCOPD replication was rs11046966 (National Emphysema Treatment Trial–Normative Aging Study P = 6.0 × 10−4, BEOCOPD P = 1.5 × 10−5, combined P = 1.7 × 10−7), located 3′ to the gene SOX5. Association with rs11046966 was not replicated in the International COPD Genetics Network. Sox5−/− mice showed abnormal lung development, with a delay in maturation before the saccular stage, as early as E16.5. Lung pathology in Sox5−/− lungs was associated with a decrease in fibronectin expression, an extracellular matrix component critical for branching morphogenesis.
Conclusions: Genetic variation in the transcription factor SOX5 is associated with COPD susceptibility. A mouse model suggests that the effect may be due, in part, to its effects on lung development and/or repair processes.
chronic obstructive pulmonary disease; emphysema; knockout mice; lung development; single nucleotide polymorphism
Allograft rejection remains a major limitation to successful solid organ transplantation. Here, we investigated the biosynthesis and bioactions of the pro-resolving mediators lipoxin A4 and resolvin E1 in host responses to organ transplantation. In samples obtained during screening bronchoscopy after human lung transplantation, bronchoalveolar lavage fluid levels of lipoxin A4 were increased in association with the severity of allograft rejection that was graded independently by clinical pathology. Lipoxin A4 significantly inhibited calcineurin activation in human neutrophils, and lipoxin A4 stable analogs prevented acute rejection of vascularized cardiac and renal allografts. Transgenic animals expressing human lipoxin A4 receptors revealed important sites of action in host tissues for lipoxin A4’s protective effects. Resolvin E1 displays counter-regulatory actions for leukocytes, in part, via increased lipoxin A4 biosynthesis, yet RvE1 administered (1 µg, iv) to donor (days −1 and 0) and recipient mice (day −1, 0 and +4) was even more potent than a lipoxin stable analog (1 µg, iv) in prolonging renal allograft survival (median survival time = 74.0 days with RvE1 and 37.5 days with a LXA4 analog). Together, these results highlight the potential for pro-resolving mediators in prolonging survival of solid organ transplants.
Randomized controlled trials (RCT) are required to test relationships between physical activity and cognition in children, but these must be informed by exploratory studies. This study aimed to inform future RCT by: conducting practical utility and reliability studies to identify appropriate cognitive outcome measures; piloting an RCT of a 10 week physical education (PE) intervention which involved 2 hours per week of aerobically intense PE compared to 2 hours of standard PE (control).
64 healthy children (mean age 6.2 yrs SD 0.3; 33 boys) recruited from 6 primary schools. Outcome measures were the Cambridge Neuropsychological Test Battery (CANTAB), the Attention Network Test (ANT), the Cognitive Assessment System (CAS) and the short form of the Connor's Parent Rating Scale (CPRS:S). Physical activity was measured habitually and during PE sessions using the Actigraph accelerometer.
Test- retest intraclass correlations from CANTAB Spatial Span (r 0.51) and Spatial Working Memory Errors (0.59) and ANT Reaction Time (0.37) and ANT Accuracy (0.60) were significant, but low. Physical activity was significantly higher during intervention vs. control PE sessions (p < 0.0001). There were no significant differences between intervention and control group changes in CAS scores. Differences between intervention and control groups favoring the intervention were observed for CANTAB Spatial Span, CANTAB Spatial Working Memory Errors, and ANT Accuracy.
The present study has identified practical and age-appropriate cognitive and behavioral outcome measures for future RCT, and identified that schools are willing to increase PE time.
Trial registration number
COGNITION; EXECUTIVE FUNCTION; CHILDREN; PHYSICAL ACTIVITY; EXERCISE
Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS).
Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS.
Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy.
Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information.
Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung.
perfusion; computed tomography; emphysema; mortality; lung volume reduction surgery
Rationale: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q.
Objectives: We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q.
Methods: Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families in the Boston Early-Onset COPD Study.
Measurements and Main Results: Merging the results of the two case-control analyses, 14 of the 790 overlapping SNPs had a combined P < 0.01. Two of these 14 SNPs were consistently associated with COPD in the ICGN families. The association with one SNP, located in the gene XRCC5, was replicated in the Boston Early-Onset COPD Study, with a combined P = 2.51 × 10−5 across the four studies, which remains significant when adjusted for multiple testing (P = 0.02). Genotype imputation confirmed the association with SNPs in XRCC5.
Conclusions: By combining data from COPD genetic association studies conducted in four independent patient samples, we have identified XRCC5, an ATP-dependent DNA helicase, as a potential COPD susceptibility gene.
emphysema; genetic linkage; metaanalysis; single nucleotide polymorphism
Delineating the extent and distribution of emphysema is an essential component of the evaluation of candidates for lung volume reduction surgery (LVRS). Imaging also may identify contraindications to LVRS, including bronchiectasis and pleural scarring. The chest X-ray is of limited utility in LVRS evaluation. Chest computed tomography (CT) scanning is an essential component of the evaluation, demonstrating the presence of emphysema and its amount and distribution. Clinical experience has shown that a substantial minority of chest CT scans will also demonstrate pulmonary nodules, some of which represent lung cancers. Published series, including the National Emphysema Treatment Trial, consistently demonstrate that patients with upper lobe predominant or heterogeneous emphysema are most likely to benefit from LVRS. Heterogeneity and distribution can also be assessed by radionuclide ventilation perfusion scanning, but this modality adds little additional information to CT scanning.
emphysema; lung volume reduction surgery; CT scanning; pulmonary nodule; preoperative evaluation
To assess the association of emphysema and airway disease assessed by volumetric computed tomography (CT) with exercise capacity in subjects with chronic obstructive pulmonary disease (COPD).
We studied 93 subjects with COPD (Forced Expiratory Volume in 1 s [FEV1] %predicted mean ± SD 57.1 ± 24.3%, female gender = 40) enrolled in the Lung Tissue Research Consortium. Emphysema was defined as percentage of low attenuation areas less than a threshold of −950 Hounsfield units (%LAA-950) on CT scan. The wall area percentage (WA%) of the 3rd to 6th generations of the apical bronchus of right upper lobe (RB1) were analyzed. The six-minute walk distance (6MWD) test was used as a measure of exercise capacity.
The 6MWD was inversely associated with %LAA-950 (r = −0.53, p<0.0001) and with the WA% of 6th generation of RB1 only (r = −0.28, p = 0.009). In a multivariate regression model including CT indices of emphysema and airway disease that were adjusted for demographic and physiologic variables as well as brand of CT scanner, only the %LAA-950 remained significantly associated with exercise performance. Holding other covariates fixed, this model showed that a 10% increase of CT emphysema reduced the distance walked in six minutes 28.6 meters (95% Confidence Interval = −51.2, −6.0, p = 0.01).
These results suggest that the extent of emphysema but not airway disease measured by volumetric CT contributes independently to exercise limitation in subjects with COPD.
COPD; CT; emphysema; airways; 6-minute walk test
To identify non-invasive gene expression markers for chronic obstructive pulmonary disease (COPD), we performed genome-wide expression profiling of peripheral blood samples from 12 subjects with significant airflow obstruction and an equal number of non-obstructed controls. RNA was isolated from Peripheral Blood Mononuclear Cells (PBMCs) and gene expression was assessed using Affymetrix U133 Plus 2.0 arrays.
Tests for gene expression changes that discriminate between COPD cases (FEV1< 70% predicted, FEV1/FVC < 0.7) and controls (FEV1> 80% predicted, FEV1/FVC > 0.7) were performed using Significance Analysis of Microarrays (SAM) and Bayesian Analysis of Differential Gene Expression (BADGE). Using either test at high stringency (SAM median FDR = 0 or BADGE p < 0.01) we identified differential expression for 45 known genes. Correlation of gene expression with lung function measurements (FEV1 & FEV1/FVC), using both Pearson and Spearman correlation coefficients (p < 0.05), identified a set of 86 genes. A total of 16 markers showed evidence of significant correlation (p < 0.05) with quantitative traits and differential expression between cases and controls. We further compared our peripheral gene expression markers with those we previously identified from lung tissue of the same cohort. Two genes, RP9and NAPE-PLD, were identified as decreased in COPD cases compared to controls in both lung tissue and blood. These results contribute to our understanding of gene expression changes in the peripheral blood of patients with COPD and may provide insight into potential mechanisms involved in the disease.
Microarray; Biomarkers; PBMC