Pain in Veterans with COPD: relationship with physical activity and exercise capacity.

BACKGROUND: Pain is a common but underappreciated symptom experienced by people with Chronic Obstructive Pulmonary Disease (COPD). The relationships between pain and physical activity (PA) and exercise capacity are poorly understood. METHODS: This retrospective secondary analysis includes three cohorts of Veterans with COPD who participated in longitudinal studies evaluating PA and exercise capacity with objective measures of daily step counts and 6-min walk test (6MWT) distance, respectively. Pain was assessed using the bodily pain domain of the Veterans RAND-36. In two cohorts, participants were randomly assigned to a web-based, pedometer-mediated PA intervention which has previously been demonstrated to improve PA. RESULTS: Three-hundred and seventy-three (373) unique study participants were included in this analysis. Eighty-three percent (n = 311) of the population reported at least mild pain and/or at least a little bit of interference due to pain at baseline. Cross-sectionally, greater bodily pain was associated with lower 6MWT distance (ß = 0.51; 95% CI 0.20, 0.82; p = 0.0013). Longitudinally, worsening bodily pain was associated with a decline in 6MWT distance (ß = 0.30; 95% CI 0.03, 0.58; p = 0.0312). There was no association between baseline bodily pain and baseline daily step counts, baseline bodily pain and change in PA, or change in bodily pain and change in PA. Compared to usual care, our PA intervention improved bodily pain scores (ß = 6.17; 95% CI 1.84, 10.45; p = 0.0054). Bodily pain scores did not affect the impact of the intervention on daily step counts. CONCLUSION: Pain is highly prevalent and significantly associated with lower exercise capacity among Veterans with COPD. Worsening pain co-occurred with decline in exercise capacity but not PA. Our intervention reduced pain, although pain did not affect the impact of the intervention on PA.

Correction: Plasma vitamin D, past chest illness, and risk of future chest illness in chronic spinal cord injury (SCI): a longitudinal observational study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: Clinical associations with telomere length in chronic spinal cord injury.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plasma vitamin D, past chest illness, and risk of future chest illness in chronic spinal cord injury (SCI): a longitudinal observational study.

STUDY DESIGN: Observational study. OBJECTIVE: Assess associations between vitamin D levels and other risk factors on future chest illness in a chronic spinal cord injury (SCI) cohort. SETTING: Veterans Affairs Boston and the Boston, MA community. METHODS: Between August 2009 and August 2017, 253 participants with chronic SCI were followed over a median of 3.2 years (up to 7.4 years) with two to four visits a median of 1.7 years apart. At each visit, plasma 25-hydroxyvitamin D level was obtained, spirometry performed, and a respiratory questionnaire assessing chest illnesses since last visit was completed. Repeated measures negative binomial regression was used to assess chest illness risk longitudinally. RESULTS: At entry, 25% had deficient vitamin D levels (<20 nanograms/milliliter (ng/ml)), 52% were insufficient (20 to <30 ng/ml), and 23% were sufficient (≥30 ng/ml). Over 545 study visits, chest illnesses (n = 106) were reported by 60 participants. In multivariable models (including previous chest illness history), deficient vitamin D levels (compared with those with sufficient levels) were associated with future chest illness though with wide confidence limits (relative risk (RR) = 1.36, 95% confidence intervals (CI) = 0.74, 2.47). The strongest association with chest illness during the follow-up period was in persons who reported pneumonia/bronchitis after injury and a chest illness in the three years before study entry (RR = 7.62; 95% CI = 3.70, 15.71). CONCLUSION: Assessed prospectively in chronic SCI, there was a suggestive association between deficient vitamin D levels and future chest illness. Past chest illness history was also strongly associated with future chest illness.

Clinical associations with telomere length in chronic spinal cord injury.

STUDY DESIGN: Cross-sectional study OBJECTIVES: To determine clinical factors associated with telomere length in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center, Boston, MA. METHODS: Two hundred seventy-eight participants with chronic SCI provided blood samples for measurement of C-reactive protein (CRP), interleukin-6 (IL-6), and telomere length, completed respiratory health questionnaires, underwent dual X-ray absorptiometry (DXA) to assess body fat, and completed spirometry. High-throughput real-time PCR assays were used to assess telomere length in leukocyte genomic DNA. Linear regression models were used to assess cross-sectional associations with telomere length. RESULTS: Telomere length was inversely related to age (p < 0.0001). In age-adjusted models, gender, race, injury duration, %-total and %-trunk fat, body mass index (BMI), %-predicted forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), chronic cough or phlegm, CRP, IL-6, wheeze, smoking, diabetes, heart disease, chronic obstructive pulmonary disease (COPD), skin ulcer, urinary tract infection (UTI), or chest illness history were not significantly associated with telomere length. There was a suggestive age-adjusted association between persons with the most severe SCI (cervical motor complete and AIS C) and shorter telomere length (p = 0.055), an effect equivalent to ~8.4 years of premature aging. There were similar age-adjusted associations with telomere length between persons using a wheelchair (p = 0.059) and persons with chronic urinary catheter use (p = 0.082) compared to persons without these characteristics. CONCLUSIONS: Our results suggest that clinical characteristics such as decreased mobility and bladder dysfunction that are common in individuals with more severe SCI are associated with shorter telomere length.

Vitamin D, diet, and lifestyle in a chronic SCI population.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine dietary, lifestyle, and clinical factors associated with plasma 25-hydroxyvitamin D [25(OH)D] levels in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA. METHODS: 174 participants completed food frequency and health questionnaires, provided a blood sample, and underwent dual x-ray absorptiometry (DXA) to assess %total body fat. Linear regression models were used to assess cross-sectional associations of personal, lifestyle, and nutritional factors with plasma 25(OH)D. RESULTS: Independent factors positively associated with higher plasma 25(OH)D included vitamin D intake, age, hours of planned exercise, female sex, white race, wine consumption, and if a never or former smoker. The most important predictor of 25(OH)D was supplement intake. The majority of subjects (98.9% for vitamin D and 74.1% for calcium) did not meet the recommended daily allowance for adults from their diet alone. Level and completeness of SCI, injury duration, mobility, %total body fat, time outside, and comorbid diseases were not associated with plasma 25(OH)D. CONCLUSIONS: Plasma 25(OH)D level in chronic SCI is not associated with clinical factors specific to SCI such as injury level and completeness, injury duration, and mobility mode, but related to supplement intake and other lifestyle factors.

FEV1 and FVC and systemic inflammation in a spinal cord injury cohort.

BACKGROUND: Systemic inflammation has been associated with reduced pulmonary function in individuals with and without chronic medical conditions. Individuals with chronic spinal cord injury (SCI) have clinical characteristics that promote systemic inflammation and also have reduced pulmonary function. We sought to assess the associations between biomarkers of systemic inflammation with pulmonary function in a chronic SCI cohort, adjusting for other potential confounding factors. METHODS: Participants (n = 311) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma C-reactive protein (CRP) and interleukin-6 (IL-6) with forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: There were statistically significant inverse relationships between plasma CRP and IL-6 assessed in quartiles or continuously with FEV1 and FVC. In fully adjusted models, each interquartile range (5.91 mg/L) increase in CRP was associated with a significant decrease in FEV1 (-55.85 ml; 95% CI: -89.21, -22.49) and decrease in FVC (-65.50 ml; 95% CI: -106.61, -24.60). There were similar significant findings for IL-6. There were no statistically significant associations observed with FEV1/FVC. CONCLUSION: Plasma CRP and IL-6 in individuals with chronic SCI are inversely associated with FEV1 and FVC, independent of SCI level and severity of injury, BMI, and other covariates. This finding suggests that systemic inflammation associated with chronic SCI may contribute to reduced pulmonary function.

Physical Activity, Exercise Capacity, and Body Composition in U.S. Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Differences in body composition may contribute to variability in exercise capacity (EC) and physical activity (PA) in individuals with chronic obstructive pulmonary disease (COPD). Most studies have used bioimpedance-based surrogates of muscle (lean) mass; relatively few studies have included consideration of fat mass, and limited studies have been performed using dual X-ray absorptiometry (DXA) to assess body composition. Objectives: To determine whether DXA-assessed muscle (lean) and fat mass exhibit differential correlations with EC and PA in subjects with COPD. Methods: U.S. veterans with COPD (defined as forced expiratory volume in 1 second/forced vital capacity < 0.7 or emphysema on clinical chest computed tomography) had DXA-assessed body composition, EC (6-minute-walk distance), objective PA (average daily step counts), and self-reported PA measured at enrollment. Associations among EC, PA, and body composition were examined using Spearman correlations and multivariable models adjusted a priori for age, sex, race, and lung function. Results: Subjects (n = 98) were predominantly White (90%), obese (mean body mass index, 30.2 ± 6.2 kg/m2), and male (96%), with a mean age of 69.8 ± 7.9 years and moderate airflow obstruction (mean forced expiratory volume in 1 second percentage predicted, 68 ± 20%). Modest inverse correlations of EC and PA with fat mass were observed (Spearman's rho range, -0.20 to -0.34), whereas measures of muscle (lean) mass were not significantly associated with EC or PA. The ratio of appendicular skeletal muscle mass (ASM) to weight, which considers both muscle (lean) and fat mass, was consistently associated with EC (8.4 [95% confidence interval, 2.9-13.8] meter increase in 6-minute walk distance per 1% increase in ASM-to-weight ratio), objective PA (194.8 [95% confidence interval, 15.2-374.4] steps per day per 1% increase in ASM-to-weight ratio), and self-reported PA in multivariable-adjusted models. Conclusions: DXA-assessed body composition measures that include consideration of both lean and fat mass are associated with cross-sectional EC and PA in COPD populations. Clinical trial registered with www.clinicaltrials.gov (NCT02099799).

Performance of bioelectrical impedance analysis compared to dual X-ray absorptiometry (DXA) in Veterans with COPD.

We examined the performance of a commercially-available handheld bioimpedance (BIA) device relative to dual X-ray absorptiometry (DXA) to assess body composition differences among Veterans with chronic obstructive pulmonary disease (COPD). Body composition was measured using DXA and BIA (Omron HBF-306C) at a single time point. Correlations between BIA- and DXA-assessed percent fat, fat mass, and fat-free mass were analyzed using Spearman (ρ) and Lin Concordance Correlation Coefficients (ρc). Mean differences in fat mass were visualized using Bland-Altman plots. Subgroup analyses by obesity status (BMI < 30 versus ≥ 30) were performed. Among 50 participants (96% male; mean age: 69.5 ± 6.0 years), BIA-assessed fat mass was strongly correlated (ρ = 0.94) and demonstrate excellent concordance (ρc = 0.95, [95%CI: 0.93-0.98]) with DXA, with a mean difference of 2.7 ± 3.2 kg between BIA and DXA. Although Spearman correlations between BIA- and DXA-assessed percent fat and fat-free mass were strong (ρ = 0.8 and 0.91, respectively), concordance values were only moderate (ρc = 0.67 and 0.74, respectively). Significantly stronger correlations were observed for obese relative to non-obese subjects for total percent fat (ρobese = 0.85 versus ρnon-obese = 0.5) and fat mass (ρobese = 0.96 versus ρnon-obese = 0.84). A handheld BIA device demonstrated high concordance with DXA for fat mass and moderate concordance for total percent fat and fat-free mass.ClinicalTrials.gov: NCT02099799.

Tadalafil for veterans with chronic obstructive pulmonary disease-pulmonary hypertension: A multicenter, placebo-controlled randomized trial.

Treating Veterans with chronic obstructive pulmonary disease complicated by pulmonary hypertension (COPD-PH) using phosphodiesterase type-5 inhibitor pharmacotherapy is common, but efficacy data are lacking. To address this further, patients with COPD-PH from five Department of Veterans Affairs hospitals were randomized (1∶1) to receive placebo or oral tadalafil (40 mg/day) for 12 months. The primary endpoint was changed from baseline in 6-min walk distance at 12 months. Secondary endpoints included change from baseline in pulmonary vascular resistance, mean pulmonary artery pressure, and symptom burden by the University of California San Diego shortness of breath questionnaire scale at 6 months. A total of 42 subjects (all male; 68 ± 7.6 years old) were randomized to placebo (N = 14) or tadalafil (N = 28). The group imbalance was related to under-enrollment. Compared to placebo, no significant difference was observed in the tadalafil group for change from the primary endpoint or change in mean pulmonary artery pressure or pulmonary vascular resistance from baseline at 6 months. A clinically meaningful improvement was observed in the secondary endpoint of shortness of breath questionnaire score in the tadalafil versus placebo group at 6 months. There was no significant difference in major adverse events between treatment groups, and tadalafil was well tolerated overall. For Veterans with COPD-PH enrolled in this study, once-daily treatment with tadalafil did not improve 6-min walk distance or cardiopulmonary hemodynamics although a decrease in shortness of breath was observed. Under-enrollment and imbalanced randomization confound interpreting conclusions from this clinical trial and limit the generalization of our findings.

Molecular markers of aging, exercise capacity, & physical activity in COPD.

BACKGROUND: Exercise capacity (EC) and physical activity (PA) are independent, potentially modifiable predictors of clinical outcomes in COPD. Molecular measures of biological age may help characterize variability in EC and PA observed among COPD patients. METHODS: Veterans with COPD (FEV1/FVC<0.7 or emphysema on chest computed tomography) enrolled in 2 cohorts at VA Boston completed questionnaires, a 6-min walk distance (6MWD) for EC, and blood collection at enrollment. PA data (average daily step count) was collected using an HJ-720 ITC pedometer over ≥5 days. A subset of subjects returned for repeat assessment after 12 weeks. DNA methylation data was generated using the HumanMethylationEPIC platform; epigenetic estimates of biological age and age acceleration were generated using established algorithms. Multivariable models examined the associations between biological age, 6MWD, PA and future acute exacerbations (AEs), adjusting for chronological age, sex, race, smoking status, pack-years, body mass index, cohort, and estimated cell counts. RESULTS: Subjects (n = 269) were predominantly male (98.5%), white (92.9%), and elderly (70.6 ± 8.5 years) with average FEV1% of 57.7 ± 21.1, 6MWD of 374.3 ± 93.5 m, and daily steps of 3043.4 ± 2374 at baseline. In adjusted models, multiple measures of baseline epigenetic age and age acceleration were inversely associated with 6MWD; only GrimAge was inversely associated with PA. Longitudinal change in Hannum-Age was inversely associated with change in EC at 12 weeks (n = 94). No measures of biological age were significantly associated with prospective AEs over 1.3 ± 0.3 years. CONCLUSIONS: Epigenetic measures of biological age are independent predictors of EC and PA, but not AEs, among individuals with COPD.

The Effect of a web-based physical activity intervention on COPD knowledge: A secondary cohort study.

BACKGROUND: Novel strategies to complement current methods of education delivery by healthcare providers in clinic encounters or in pulmonary rehabilitation are needed to promote COPD self-management. METHODS: We developed a COPD web-based platform that delivers education as part of a physical activity intervention. We examined COPD knowledge in persons with COPD who used a web-mediated, pedometer-based physical activity intervention. Knowledge was assessed with the Bristol COPD Knowledge Questionnaire (BCKQ) at baseline, 3, 6, 9, and 12 months. Scores range from 0 to 100, with higher scores indicating greater knowledge. Repeated measures ANOVA (PROC MIXED, SAS 9.4) examined trends across the 12 months and identified changes from baseline at 3, 6, 9, and 12 months. RESULTS: We enrolled 72 participants with COPD, 93% males with mean ± sd age of 69 ± 7 years and FEV1% predicted of 60 ± 23%. There was a significant increase from baseline to 9 months (p = 0.012), although this increase did not persist at 12 months. Among the 13 topics, participants scored the highest at baseline on smoking knowledge (65.3 ± 17.4) and the lowest on inhaled steroids (9.7 ± 15.4). Across the 12 months, there were significant increases in knowledge about inhaled bronchodilators (p = 0.011) and inhaled steroids (p = 0.035). At 12 months, there were significant improvements in knowledge about exercise (p = 0.004), vaccination (p = 0.027), inhaled bronchodilators (p = 0.002), and inhaled steroids (p = 0.002). CONCLUSION: An internet-mediated intervention may provide another option for COPD education delivery and support for disease self-management.

Co-occurrence of pain and dyspnea in Veterans with COPD: Relationship to functional status and a pilot study of neural correlates using structural and functional magnetic resonance imaging.

Persons with COPD experience co-occurring dyspnea and pain. Little is known about the relationship between symptom co-occurrence with physical activity (PA) and exercise. Novel diagnostic tools are needed for accurate symptom discrimination. In this secondary analysis, we examined relationships between baseline assessments of pain, dyspnea, objectively measured PA, and exercise capacity in persons with COPD who previously enrolled in three PA studies. Pain was assessed with the bodily pain domain of the Veterans RAND-36 (VR-36), and dyspnea with the modified Medical Research Council (mMRC) scale. Average daily step count was assessed with the Omron HJ-720ITC or FitBit Zip pedometer, and exercise capacity with 6-minute walk test (6MWT). We also conducted a pilot neuroimaging study. Neuroimaging data were acquired on a Siemens 3-Tesla Magnetom Prismafit whole-body scanner. Analysis of variance assessed trends in daily step count and 6MWT distance across categories of co-occurring pain and dyspnea. General linear models examined relationships between cortical thickness and resting state functional connectivity (fc) with symptoms and functional status. In 373 Veterans, 98% were male with mean age 70.5± 8.3 years and FEV1% predicted 59 ± 21%. Compared to those with no co-occurrence of pain and dyspnea, those with co-occurrence walked 1,291-1,444 fewer steps per day and had an 80-85 m lower 6MWT distance. Ten males participated in the pilot neuroimaging study. Predominant findings were that lower cortical thickness and greater fc were associated with higher pain and dyspnea, p<0.05. Greater cortical thickness and lower fc were associated with higher daily step count and 6MWT distance, p<0.05. Regional patterns of associations differed for pain and dyspnea, suggesting that cortical thickness and fc may discriminate symptoms. Co-occurring dyspnea and pain in COPD are associated with significant reductions in PA and exercise capacity. It may be feasible for neuroimaging markers to discriminate between pain and dyspnea.

A randomised trial of a web-based physical activity self-management intervention in COPD.

Improving exercise capacity is a primary objective in COPD. Declines in exercise capacity result in reduced physical activity and health-related quality of life (HRQoL). Self-management interventions can teach patients skills and behaviours to manage their disease. Technology-mediated interventions have the potential to provide easily accessible support for disease self-management. We evaluated the effectiveness of a web-based self-management intervention, focused on physical activity promotion, on exercise capacity in COPD. This 6-month randomised controlled trial (NCT02099799) enrolled 153 persons with COPD at two US sites (VABoston, n=108; VABirmingham, n=45). Participants were allocated (1:1) to the web-based self-management intervention (physical activity promotion through personalised, progressive step-count goals, feedback, online COPD-related education and social support via an online community) or usual care. The primary outcome was exercise capacity (6-min walk distance (6 MWD)). Secondary outcomes included physical activity (daily steps per day), HRQoL (St. George's Respiratory Questionnaire Total Score), dyspnoea, COPD-related knowledge and social support. Change in step-count goals reflected intervention engagement. Participants' mean age was 69 (sd=7), and mean forced expiratory volume in 1 s % predicted was 61% (sd=21%). Change in 6MWD did not differ between groups. Intervention participants improved their mean daily step counts by 1312 more than those in the usual care group (p<0.001). Groups did not differ on other secondary outcomes. VABirmingham participants were significantly more engaged with the intervention, although site did not modify the effect of the intervention on 6MWD or secondary outcomes. The intervention did not improve exercise capacity but improved physical activity at 6 months. Additional intervention modifications are needed to optimise its COPD self-management capabilities.

Physical Activity in Overlap Syndrome of COPD and Obstructive Sleep Apnea: Relationship With Markers of Systemic Inflammation.

STUDY OBJECTIVES: Low physical activity (PA) is associated with poor health outcomes in chronic obstructive pulmonary disease (COPD). Overlap syndrome (OVS), the co-occurrence of COPD and obstructive sleep apnea (OSA), is highly prevalent. Little is known about PA in OVS, and its relationship with markers of systemic inflammation. METHODS: We studied 256 persons with stable COPD, 61 (24%) of whom had OVS, who were well characterized in two previous PA studies. PA was directly assessed with the Omron HJ-720ITC pedometer. C-reactive protein (CRP) and interleukin-6 (IL-6) were assayed from peripheral blood. Linear regression models, adjusting for age and forced expiratory volume in 1 second (FEV1) % predicted, assessed daily step counts and CRP and IL-6 levels in OVS, compared to COPD alone. Linear regression models, adjusting for age, FEV1 % predicted, and coronary artery disease, assessed the relationships between PA and CRP and IL-6 in those with OVS versus those with COPD alone. RESULTS: Compared to COPD alone, persons with OVS walked 672 fewer steps per day (95% CI -1,317 to -28, P = .041). Those with OVS had significantly higher levels of CRP and IL-6 compared to COPD alone. In OVS, each 1,000 fewer steps walked was associated with a 0.875 ng/mL (95% CI 0.767 to 0.997) increase in IL-6, independent of lung function. CONCLUSIONS: Persons with OVS have significantly lower levels of PA and higher levels of inflammatory biomarkers, compared to COPD alone. Lower PA is significantly associated with higher IL-6 levels in OVS.

Associations between vitamin D and pulmonary function in chronic spinal cord injury.

CONTEXT/OBJECTIVE: Individuals with chronic spinal cord injury (SCI) have an increased risk of morbidity and mortality attributable to respiratory diseases. Previous studies in non-SCI populations suggest that vitamin D may be a determinant of respiratory health. Therefore, we sought to assess if lower vitamin D levels were associated with decreased pulmonary function in persons with chronic SCI. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: 312 participants (260 men and 52 women) with chronic SCI recruited from VA Boston and the community participating in an epidemiologic study to assess factors influencing respiratory health. METHODS: Participants provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma 25-hydroxyviatmin D and spirometric measures of pulmonary function. OUTCOME MEASURES: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: Adjusted and unadjusted for a number of confounders, there was no significant association between plasma vitamin D levels and FEV1, FVC, or FEV1/FVC. For example, in fully adjusted models, each 10 ng/ml increase in vitamin D was associated with a 4.4 ml (95%CI -64.4, 73.2, P = 0.90) ml change in FEV1. Conclusion: There was no significant cross-sectional association between plasma vitamin D and FEV1, FVC, or FEV1/FVC in this cohort of individuals with chronic SCI.

Telomere length in COPD: Relationships with physical activity, exercise capacity, and acute exacerbations.

RATIONALE: Shorter leukocyte telomere length (LTL) is associated with reduced health-related quality of life and increased risk for acute exacerbations (AEs) and mortality in chronic obstructive pulmonary disease (COPD). Increased physical activity and exercise capacity are associated with reduced risk for AEs and death. However, the relationships between LTL and physical activity, exercise capacity, and AEs in COPD are unknown. METHODS: Data from 3 COPD cohorts were examined: Cohort 1 (n = 112, physical activity intervention trial), Cohorts 2 and 3 (n = 182 and 294, respectively, separate observational studies). Subjects completed a 6-minute walk test (6MWT) and provided blood for LTL assessment using real-time PCR. Physical activity was measured as average daily step count using an accelerometer or pedometer. Number of self-reported AEs was available for 1) the year prior to enrollment (Cohorts 1 and 3) and 2) prospectively after enrollment (all cohorts). Multivariate models examined associations between LTL and average daily step count, 6MWT distance, and AEs. RESULTS: A significant association between longer LTL and increased 6MWT distance was observed in the three combined cohorts (ß = 3x10-5, p = 0.045). No association between LTL and average daily step count was observed. Shorter LTL was associated with an increased number of AEs in the year prior to enrollment (Cohorts 1 and 3 combined, ß = -1.93, p = 0.04) and with prospective AEs (Cohort 3, ß = -1.3388, p = 0.0003). CONCLUSIONS: Among COPD patients, increased LTL is associated with higher exercise capacity, but not physical activity. Shorter LTL was associated with AEs in a subgroup of cohorts.

Plasma Leptin and Reduced FEV1 and FVC in Chronic Spinal Cord Injury.

BACKGROUND: Adipose tissue produces leptin, which is pro-inflammatory, and adiponectin, which has anti-inflammatory properties. Participants with chronic spinal cord injury (SCI) have increased body fat and are at increased risk for respiratory illness. OBJECTIVE: To assess the associations between leptin and adiponectin with pulmonary function in a chronic SCI cohort. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: A total of 285 participants (237 men and 48 women) with chronic SCI with mean (standard deviation) injury duration 17.8 (13.2) years from the VA Boston and the community participating in an epidemiologic study assessing factors associated with respiratory health. METHODS: Participants (24.6% cervical American Spinal Injury Association Impairment Scale (AIS) level A, B, and C; 33.6% other AIS A, B, and C; 41.8% AIS D) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma leptin and adiponectin with spirometric measures of pulmonary function adjusted for age, race, gender, and height. Level and severity of SCI, mobility mode, body mass index, smoking, chronic obstructive pulmonary disease, asthma, chest injury history, laboratory batch, and other potential confounders were also considered. MAIN OUTCOME MEASUREMENTS: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: There was a statistically significant inverse relationship between plasma leptin assessed in quartiles or as a continuous covariate with FEV1 and FVC. In fully adjusted models, each interquartile range (16,214 pg/mL) increase in leptin was associated with a significant decrease in FEV1 (-93.1 mL; 95% confidence interval = -166.2, -20.0) and decrease in FVC (-130.7 mL; 95% confidence interval = -219.4, -42.0). There were no significant associations between leptin and FEV1/FVC or between plasma adiponectin with FEV1, FVC, or FEV1/FVC. CONCLUSION: Plasma leptin in individuals with chronic SCI is inversely associated with FEV1 and FVC, independently of SCI level and severity and other covariates. This finding suggests that plasma leptin may contribute to reduced pulmonary function in chronic SCI. LEVEL OF EVIDENCE: II.

Associations between vitamin D, adiposity, and respiratory symptoms in chronic spinal cord injury.

Context/Objective Persons with chronic spinal cord injury (SCI) have an increased risk of respiratory-related morbidity and mortality and chronic respiratory symptoms are clinical markers of future respiratory disease. Therefore, we sought to assess potentially modifiable factors associated with respiratory symptoms, with a focus on circulating vitamin D and measures of body fat. Design Cross-sectional study. Setting Veterans Affairs Medical Center. Participants Three hundred forty-three participants (282 men and 61 women) with chronic SCI participating in an epidemiologic study to assess factors influencing respiratory health recruited from VA Boston and the community. Methods Participants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess % body fat. Logistic regression was used to assess cross-sectional associations between respiratory symptoms and plasma vitamin D and measures of body fat with adjustment for a number of potential confounders. Outcome Measures Chronic cough, chronic phlegm, any wheeze, persistent wheeze. Results After adjustment for a number of confounders (including smoking), participants with greater %-android, gynoid, trunk, or total body fat had increased odds ratios for any wheeze and suggestive associations with persistent wheeze, but not with chronic cough or phlegm. Vitamin D levels were not associated with any of the respiratory symptoms. Conclusion Increased body fat, but not vitamin D, was associated with wheeze in chronic SCI independent of a number of covariates.