Assessing the Impact of Tiotropium on Lung Function and Physical Activity in GOLD Stage II COPD Patients who are Naïve to Maintenance Respiratory Therapy: A Study Protocol

Physical activity status is increasingly recognized as a reliable predictor of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). The reduction in physical activity occurs earlier in the clinical course of COPD than previously appreciated, possibly arising from breathlessness, reduced exercise tolerance, and adoption of a more sedentary lifestyle. To date, no clinical trial has evaluated the impact of pharmacotherapy on both lung function and physical activity. We recently designed a study that evaluates the impact of tiotropium (a once-daily inhaled anticholinergic) on lung function and physical activity in a maintenance/treatment-naïve Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II COPD cohort. Previous studies have demonstrated that tiotropium improves lung function and exercise tolerance; whether these benefits translate into improvements in physical activity is the focus of the current work. Here we describe the rationale and challenges in developing and implementing this study and review its unique features and novel design, including: utility of direct activity monitoring in multicenter clinical trials; importance of behavioral-modification techniques (including motivational interviewing to improve patient self-efficacy and adherence for a healthy, more active lifestyle); utility of individualized activity plans that provide an integrated approach with pharmacotherapy and behavioral modification to help patients achieve a more active lifestyle

A Pilot Study Of Group Mindfulness‐Based Cognitive Therapy (Mbct) For Combat Veterans With Posttraumatic Stress Disorder (Ptsd)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98769/1/da22104.pd

Taking Healthy Steps: rationale, design and baseline characteristics of a randomized trial of a pedometer-based internet-mediated walking program in veterans with chronic obstructive pulmonary disease

Abstract Background Low levels of physical activity are common in patients with chronic obstructive pulmonary disease (COPD), and a sedentary lifestyle is associated with poor outcomes including increased mortality, frequent hospitalizations, and poor health-related quality of life. Internet-mediated physical activity interventions may increase physical activity and improve health outcomes in persons with COPD. Methods/Design This manuscript describes the design and rationale of a randomized controlled trial that tests the effectiveness of Taking Healthy Steps, an Internet-mediated walking program for Veterans with COPD. Taking Healthy Steps includes an uploading pedometer, a website, and an online community. Eligible and consented patients wear a pedometer to obtain one week of baseline data and then are randomized on a 2:1 ratio to Taking Healthy Steps or to a wait list control. The intervention arm receives iterative step-count feedback; individualized step-count goals, motivational and informational messages, and access to an online community. Wait list controls are notified that they are enrolled, but that their intervention will start in one year; however, they keep the pedometer and have access to a static webpage. Discussion Participants include 239 Veterans (mean age 66.7 years, 93.7% male) with 155 randomized to Taking Healthy Steps and 84 to the wait list control arm; rural-living (45.2%); ever-smokers (93.3%); and current smokers (25.1%). Baseline mean St. George’s Respiratory Questionnaire Total Score was 46.0; 30.5% reported severe dyspnea; and the average number of comorbid conditions was 4.9. Mean baseline daily step counts was 3497 (+/- 2220). Veterans with COPD can be recruited to participate in an online walking program. We successfully recruited a cohort of older Veterans with a significant level of disability including Veterans who live in rural areas using a remote national recruitment strategy. Trial registration Clinical Trials.gov NCT01102777http://deepblue.lib.umich.edu/bitstream/2027.42/109506/1/12890_2014_Article_479.pd

Gender influences health-related Quality of Life in IPF

Disclosure statements Dr. Han has received research support from the NIH. Dr. Bartholmai has received research support from the NIH and GlaxoSmithKline. Dr. Murray has received research support from the NIH. Dr. Giardino has received research support from the VAHS. Dr. Flaherty has received research support from Intermune and the NIH, consulting honorarium from GlaxoSmithKline and is a member of advisory boards for Boehringer Ingelheim and Gilead. Dr. Thompson has received research support from the NIH. Dr. Frederick has received research support from the NIH. Ms. Li has received research support from the NIH. Dr. Schwarz has received research support from the NIH. Dr. Limper received consulting fees and a research grant from Novartis and has received research support from the NIH. Dr. Martinez is a member of a steering committee for Actelion, Gilead, Centocor, and Genzyme and has received research support from Actelion and the NIH.Background HRQL in IPF patients is impaired. Data from other respiratory diseases led us to hypothesize that significant gender differences in HRQL in IPF also exist. Methods Data were drawn from the NIH-sponsored Lung Tissue Research Consortium (LTRC). Demographic and pulmonary physiology data along with MMRC, SF-12, and SGRQ scores from women vs. men were compared with two-sample t-tests. Multivariate linear regression was used to examine the association between SF-12 component scores and gender while adjusting for other relevant variables. Results The study sample consisted of 147 men and 74 women. Among several baseline variables, only DLCO% predicted differed between women and men, (43.7 vs. 38.0, p = 0.03). In general, men exhibited lower (better) MMRC scores (1.7 vs. 2.4, p = 0.02), particularly those with milder disease as measured by DLCO% predicted. In an adjusted analysis, SF-12 PCS scores in men were lower (worse) than women (p = 0.01), an effect that was more pronounced in men with greater dyspnea scores. In a similar analysis, SF-12 MCS scores in women were lower than men (worse) (48.3 vs. 54.4, p = 0.0004), an effect that was more pronounced in women with greater dyspnea scores. Conclusions Significant gender differences in HRQL exist in IPF. As compared to women, men reported less severe dyspnea, had worse SF-12 PCS scores, but better SF-12 MCS scores. Dyspnea appears to have a greater impact on the physical HRQL of men and the emotional HRQL of women. An improved understanding of the mechanism behind these differences is needed to better target interventions.This work is supported by the Lung Tissue Research Consortium (N01 HR46158 (Bartholmai), N01 HR46160 (Schwarz), N01 HR46161 (Limper), N01 HR46162 (Han, Martinez), N01 HR46164 (Li, Frederick, Thompson), KL2 RR024987 (Han), K24 HL04212 (Martinez).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91956/1/2010 Respiratory Medicine - Gender Influences health-related Quality of Life in IPF.pd

Gender Differences in Symptoms and Care Delivery for Chronic Obstructive Pulmonary Disease

Abstract Background: Morbidity and mortality for women with chronic obstructive pulmonary disease (COPD) are increasing, and little is known about gender differences in perception of COPD care. Methods: Surveys were administered to a convenience sample of COPD patients to evaluate perceptions about symptoms, barriers to care, and sources of information about COPD. Results: Data on 295 female and 273 male participants were analyzed. With similar frequencies, women and men reported dyspnea and rated their health as poor/very poor. Although more women than men reported annual household income <$30,000, no significant gender differences in frequency of health insurance, physician visits, or ever having had spirometry were detected. In adjusted models (1) women were more likely to report COPD diagnostic delay (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.13-2.45, p=0.01), although anxiety (OR 1.83, 95% CI 1.10-3.06, p=0.02) and history of exacerbations (OR 1.60, 95% CI 1.08-2.37, p=0.01) were also significant predictors, (2) female gender was associated with difficulty reaching one's physician (OR 2.54, 95% CI 1.33-4.86, p=0.004), as was prior history of exacerbations (OR 2.25, 95% CI 1.21-4.20, p=0.01), and (3) female gender (OR 2.15, 95% CI 1.10-4.21, p=0.02) was the only significant predictor for finding time spent with their physician as insufficient. Conclusions: Significant gender-related differences in the perception of COPD healthcare delivery exist, revealing an opportunity to better understand what influences these attitudes and to improve care for both men and women.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98466/1/jwh%2E2012%2E3650.pd

Anxiety is associated with diminished exercise performance and quality of life in severe emphysema: a cross-sectional study

Background: Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with selfreported disability. The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea. Methods: Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St. Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI). Results: Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001). Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ. Conclusion: In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91944/1/2010 RR Anxiety is associated with diminished exercise performance and quality of life in severe emphysema.pd

Sex Differences in Severe Pulmonary Emphysema

Rationale: Limited data on sex differences in advanced COPD are available. Objectives: To compare male and female emphysema patients with severe disease. Methods: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower bodymass index (BMI), shorter smoking history, less severe airflow obstruction, lower DLCO and arterial PO2, higher arterial PCO2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of packyears, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.The National Emphysema Treatment Trial (NETT) was supported by contracts with the National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119); the Centers for Medicare and Medicaid Services (CMS; formerly the Health Care Financing Administration); and the Agency for Healthcare Research and Quality (AHRQ). J.L.C. is supported by funding from a Research Enhancement Award Program (REAP) from the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91968/1/2007 Martinez AJRCCM Sex Differences in Empy.pd

Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis

FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4+ but lower than normal CD8+ cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulated that these effects would be more prominent early in life. To test this hypothesis, we analyzed TEC subset frequency and phenotype, early thymic progenitor (ETP) cell count, and expression of FOXN1 target genes (Ccl25, Cxcl12, Dll4, Scf, Psmb11, Prss16, and Cd83) in Foxn1nu/+ (nu/+) mice and age-matched wild-type (+/+) littermate controls. Both the frequency and the absolute count of ETP were significantly reduced in nu/+ mice up to 3 weeks of age. Analysis of the TEC compartment showed reduced expression of FOXN1 target genes and delayed maturation of the medullary TEC compartment in nu/+ mice. These observations establish a FOXN1 gene dosage effect on thymic function and identify FOXN1 haploinsufficiency as an important genetic determinant of T cell lymphopenia at birth

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure