Search PubMed⌕ Search

Biomedical subjects

Barry Make

Publications and source records attributed to Barry Make.

13 recordsLinked to original sources
PubMed2026

Recommendations for return of secondary genomic findings in observational cohort studies.

The return of secondary genomic findings (ROSF) to participants in observational cohort studies has evolved from a topic of debate to an accepted standard. This Perspective synthesizes the proceedings of a 2024 National Heart, Lung and Blood Institute-sponsored workshop and the broader literature to provide updated guidance for ROSF. Building on the 2010 National Heart, Lung and Blood Institute Working Group recommendations and the 2014 Clinical Sequencing Exploratory Research/Electronic Medical Records and Genomics 'floor and ceiling' framework, we address four areas: an integrated ethical framework for observational cohort settings; the emerging challenge of returning novel result types beyond monogenic variants, including polygenic risk scores, somatic mosaicism and pharmacogenomic findings; health equity and community engagement as structural prerequisites for ethical ROSF; and scalability challenges, including technology-assisted disclosure. Drawing on implementation experience from large-scale sequencing programs, we offer recommendations that balance researcher obligations with participant autonomy and equitable access to the benefits of genomic research.

Journal Article↗
PubMed2006

Predictors of mortality in patients with emphysema and severe airflow obstruction.

PURPOSE: Limited data exist describing risk factors for mortality in patients having predominantly emphysema. SUBJECTS AND METHODS: A total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). RESULTS: Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p=0.001), oxygen utilization (p=0.04), lower total lung capacity % predicted (p=0.05), higher residual volume % predicted (p=0.04), lower maximal cardiopulmonary exercise testing workload (p=0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p=0.005), and lower upper-to-lower-lung perfusion ratio (p=0.007), and modified BODE (p=0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p=0.005), but not in multivariate analysis (p=0.21). CONCLUSION: Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.

Adult↗
PubMed2006

Genetic association analysis of functional impairment in chronic obstructive pulmonary disease.

RATIONALE: Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions. OBJECTIVES: To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms. METHODS: In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test-replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study. RESULTS: The test-replication approach identified four genes-microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-beta binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-beta1 (TGFB1)-that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p < or = 0.03) and in LTBP4 (p < or = 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (p < or = 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (p < or = 0.04). Three SNPs in TGFB1 were associated with dyspnea (p < or = 0.002), one of which replicated in the family study (p = 0.02). CONCLUSIONS: Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV(1). These associations may identify genes in pathways important for COPD pathogenesis.

Aged↗
PubMed2005

Treatments for COPD.

The multicomponent nature of chronic obstructive pulmonary disease (COPD) has provided a challenging environment in which to develop successful treatments. A combination of pharmacological and non-pharmacological approaches is used to combat this problem, and an overview of these approaches and their possible future direction is given. Bronchodilators are the mainstay of COPD treatment and can be combined with inhaled corticosteroids for greater efficacy and fewer side effects. A new generation of pharmacotherapeutic agents, most notably phosphodiesterase-4 inhibitors, which are already in the advanced stages of clinical development, and leukotriene B4 inhibitors (in early clinical development), may shape future treatment as further insight is gained into the pathological mechanisms underlying COPD. Non-pharmacologic treatments for COPD include long-term oxygen therapy (LTOT), nasal positive pressure ventilation (nPPV), pulmonary rehabilitation and lung-volume-reduction surgery (LVRS). Apart from smoking cessation, LTOT is the only treatment to date which has been shown to modify survival rates in severe cases; thus its role in COPD is well defined. The roles of nPPV and LVRS are less clear, though recent progress is reported here. In the future, it will be important to establish the precise value of the different treatments available for COPD--evaluating both clinical and physiological endpoints and using the data to more accurately define candidate patients accordingly. The challenge will be to develop this base of knowledge in order to shape future research and allow clinicians to deliver tailored COPD management programmes for the growing number of patients afflicted with this disease.

Bronchodilator Agents↗
PubMed2005

The efficacy and safety of inhaled fluticasone propionate/salmeterol and ipratropium/albuterol for the treatment of chronic obstructive pulmonary disease: an eight-week, multicenter, randomized, double-blind, double-dummy, parallel-group study.

BACKGROUND: The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components. OBJECTIVE: The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD. METHODS: We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure was morning preadministration forced expiratory volume in 1 second (FEV(1)). Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC, percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and overall daytime symptom score. Additional measures included sleep symptoms, supplemental albuterol use, and nighttime awakenings due to respiratory symptoms. Safety evaluations were based on clinical adverse events and COPD exacerbations. RESULTS: Baseline characteristics were similar between the FSC (n = 180) and IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively), mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91% white), and sex (64% and 62% male). FSC resulted in greater improvements in morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P < 0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024), percentage of symptom-free nights (P = 0.010), nighttime awakenings due to respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021 and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8 increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001 between groups). The type and incidence of adverse events were similar between the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%) subjects in the FSC and IB/ALB groups, respectively. CONCLUSION: In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.

Administration, Inhalation↗
PubMed2005

Winter air pollution and disease parameters in advanced chronic obstructive pulmonary disease panels residing in Denver, Colorado.

BACKGROUND: Ambient pollution might worsen chronic obstructive pulmonary disease (COPD). OBJECTIVE: We explored the associations of pollution to pulmonary function, rescue medication, and symptoms over 2 winters in 2 panels of subjects with advanced COPD in Denver, Colorado. METHODS: Subjects measured lung function and recorded symptoms and rescue medications. Daily ambient pollution concentrations for particulate matter (PM(10) and PM(2.5)), carbon monoxide (CO), and nitrogen dioxide (NO(2)) were obtained for Denver. Estimated effects of pollution on outcomes were derived for the same day and 1 and 2 days after pollution measurements (lags 0, 1, and 2, respectively). RESULTS: Sixteen (mean age, 65.8 years; mean FEV 1 , 42.3% of predicted value) and 18 (mean age, 67.4 years; mean FEV 1 , 39.4% of predicted value) subjects participated in the first and second winters, respectively. There were no differences in demographic or disease characteristics between the 2 panels. In the first winter no detrimental associations were found. In the second winter, however, there were significant detrimental associations of CO in the morning and PM(10), CO, and NO(2) in the evening, increasing medication use at lag 0. Total symptom score increased at lag 0 with NO(2). The concentrations of particulates were increased in the second winter compared with in the first winter, and this winter was colder and more humid. CONCLUSIONS: In the second winter, subjects with severe COPD had worse lung function at lags 0 and 1 and increased rescue medication at lag 0 with increases in ambient air pollution. The effects of pollution varied between the 2 winters, perhaps related to levels of pollution and weather patterns. Significant effects were seen despite ambient pollution levels that conformed to US Environmental Protection Agency standards.

Aged↗
PubMed2005

Improved neurobehavioral functioning in emphysema patients following lung volume reduction surgery compared with medical therapy.

STUDY OBJECTIVES: The goal of this study was to evaluate the neuropsychological and psychological functioning of emphysema patients following lung volume reduction surgery (LVRS) compared with patients receiving only medical therapy (MT). DESIGN: Patients with moderate-to-severe emphysema who were enrolled in the National Emphysema Treatment Trial at two sites (National Jewish Medical and Research Center and Ohio State University) were given a neuropsychological battery at baseline, 6 to 10 weeks later (following participation in pulmonary rehabilitation), and at 6 months following randomization to either LVRS or MT treatment. SUBJECTS AND MEASUREMENTS: Twenty patients randomized to MT, 19 patients randomized to LVRS, and 39 matched, healthy control subjects completed a battery of tests that measured cognitive functioning, depression, anxiety, and quality of life (QoL). RESULTS: Controlling for practice, patients in the LVRS treatment arm at the 6-month follow-up demonstrated significant improvement compared with MT patients in cognitive tasks involving sequential skills and verbal memory. The LVRS patients also showed significant reductions in depression compared with the MT patients, as well as improved physical and psychosocial QoL. Correlational analysis indicated that improved immediate verbal memory in the LVRS group was related to improved QoL. No associations were found between changes in cognitive function and changes in depression, exercise performance, or pulmonary functioning. CONCLUSION: Patients who received LVRS demonstrated improvement in specific neuropsychological functions, depression, anxiety, and QoL scores compared with patients with continued MT treatment 6 months following randomization. However, mechanisms for these neurobehavioral changes are unclear. Improved verbal memory and sequential skills following LVRS were not directly associated with depression or exercise capacity. Nonetheless, LVRS led to a strong and likely clinically significant improvement in neuropsychological functioning over and above that explained by practice effects or MT. This finding adds to the growing list of clinical benefits of LVRS over MT, and supports additional research into the underlying mechanisms of this therapeutic effect.

Colorado↗
PubMed2003

Complement activation in a model of chronic fatigue syndrome.

BACKGROUND: A need exists to identify biological markers in chronic fatigue syndrome (CFS). OBJECTIVE: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms. METHODS: Patients with CFS (n = 32) and age-matched, normal control patients (n = 29) exercised for 20 minutes on a stationary bike at 70% of their predicted max work load (Watts). Patients from each group with positive skin test results were also challenged with intranasally administered relevant allergens. Symptoms were recorded for 2 weeks before and 1 week after each challenge, using 3 different instruments. Blood samples were taken before, and 0, 1, 6, and 24 hours after challenges. Levels of complement split products, cell-associated cytokines, and eosinophilic cationic protein were measured. Mean preexercise and postexercise symptom scores were evaluated for each group. RESULTS: Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P <.01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P <.03) and a weekly diary (P <.01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories "reduced activity" and "mental fatigue" were significantly increased in the CFS group only (P <.04 and P <.02, respectively). CONCLUSIONS: Exercise challenge may be a valuable tool in the development of diagnostic criteria and tests for CFS. Establishment of a role for complement activation products as markers or participants in production of illness require further study.

Adult↗
PubMedDate not supplied

Neurobehavioral improvement after brief rehabilitation in patients with chronic obstructive pulmonary disease.

PURPOSE: Depressive symptoms, physiologic function, and cognition were examined in patients with chronic obstructive pulmonary disease (COPD) after 3 weeks of rehabilitation. METHODS: Patients with COPD completed measures of depression, neuropsychological function, exercise, and spirometry before and after a 3-week rehabilitation program. The 30 rehabilitation patients with COPD were compared with 29 untreated patients with COPD and 21 healthy controls similar in age, education, and gender. RESULTS: A significant group by time interaction effect was found on the Beck Depression Inventory (BDI). A significant interaction effect was also found on the 6-minute walk. Patients in the COPD rehabilitation program had decreased depressive symptoms and increased 6-minute walk distance compared with the untreated groups. Across the 3 groups, no significant interaction effects were found on neuropsychological tests. However, clinically significant improvement in sustained visual attention, verbal retention, and visuospatial ability were reported in the most impaired patients with COPD in the rehabilitation group. CONCLUSION: Compared with control groups, decline in depressive symptoms and increased exercise capacity occurred in patients with COPD after brief rehabilitation. Clinical improvement in visual attention, verbal memory, and visuospatial functions occurred in the impaired patients with COPD participating in treatment. Neurobehavioral improvements after such a brief rehabilitation intervention are relevant for clinical care and warrant continued investigation in well-designed clinical trials.

Aged↗