Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).
There are differences in serum biomarker levels between women and ...men with COPD.
Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.
We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD.
The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes.
In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic obstructive pulmonary disease (COPD) clinical trials evaluating hard endpoints (mortality, hospitalized exacerbations) require a large number of subjects and prolonged observational periods. ...We hypothesized that a composite endpoint of respiratory outcomes (CERO) can help evaluate safety and benefit in COPD trials.
Retrospective analysis of 5992 patients enrolled in the 4-year UPLIFT® trial, a randomized trial of tiotropium versus placebo in patients with moderate-to-severe COPD. Patients were permitted to continue using their usual COPD medications except for other anticholinergics. The CERO included deaths, respiratory failure, hospitalized exacerbations, and trial dropout due to COPD worsening. The incidence rates (IRs) per 100 patient-years and risk ratios (RRs and 95 % CI) were determined at years 1 to 4. The effect of treatments on CERO was similarly assessed. A power analysis helped calculate the sample size needed to achieve outcome differences between treatments.
The CERO IRs at years 1 to 4 for tiotropium versus placebo were 16, 13, 11, and 11, and 21, 16, 14, and 13, respectively. The RRs of CERO between tiotropium and placebo at the same time points were: RR-year 0.76 (0.67, 0.86), 0.80 (0.72, 0.88), 0.81 (0.74, 0.89), and 0.84 (0.77, 0.92). Using the IRs and RRs, the sample size (alpha = 0.05 two-sided, 90 % power) for studies of 1, 2, 3, and 4 years would be 1546, 1392, 1216, and 1504 per treatment group, respectively, with 575, 810, 930, 1383 required events, respectively, for hypothetical, event-driven studies.
A composite endpoint incorporating relatively infrequent serious or significant COPD-related safety outcomes could be useful in clinical trials. In UPLIFT®, CERO events were significantly reduced in patients receiving tiotropium compared with placebo.
NCT00144339 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bronchodilator Reversibility in COPD Hanania, Nicola A., MD, FCCP; Celli, Bartolome R., MD, FCCP; Donohue, James F., MD, FCCP ...
Chest,
10/2011, Letnik:
140, Številka:
4
Journal Article
Recenzirano
COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The diagnosis of COPD is based on spirometric evidence of airways obstruction following ...bronchodilator administration. Although it used to be commonly believed that patients with COPD have largely irreversible airflow obstruction, evidence now suggests that a considerable proportion of patients exhibit clinically significant bronchodilator reversibility. The complexity and inherent variability of a patient's acute response to a bronchodilator and the lack of a standardized procedure for assessing bronchodilator reversibility have led to significant confusion surrounding this concept. Although bronchodilator reversibility commonly is defined based on thresholds for improvement in FEV1 , lung volume-based measures of pulmonary function may be of particular importance in patients with severe COPD. The usefulness of acute reversibility to short-acting bronchodilators in predicting a patient's long-term response to bronchodilator maintenance therapy is also unclear, although most studies suggest that a lack of acute response to short-acting bronchodilators does not preclude a beneficial long-term response to maintenance bronchodilator treatment. This review outlines recent findings about the prevalence and usefulness of bronchodilator reversibility in patients with COPD based on the available literature and proposes areas of future research.
The epilepsies are common neurologic disorders characterized by spontaneous recurrent seizures. Boys, girls, men, and women of all ages are affected by epilepsy and, in many cases, by associated ...comorbidities as well. The primary courses of treatment are pharmacological, dietary, and/or surgical, depending on several factors, including the areas of the brain affected and the severity of the epilepsy. There is a growing appreciation that sex differences in underlying brain function and in the neurobiology of epilepsy are important factors that should be accounted for in the design and development of new therapies. In this review, we discuss the current knowledge on sex differences in epilepsy and associated comorbidities, with emphasis on those aspects most informative for the development of new pharmacotherapies. Particular focus is placed on sex differences in the prevalence and presentation of various focal and generalized epilepsies; psychiatric, cognitive, and physiologic comorbidities; catamenial epilepsy in women; sex differences in brain development; the neural actions of sex and stress hormones and their metabolites; and cellular mechanisms, including brain-derived neurotrophic factor signaling and neuronal-glial interactions. Further attention placed on potential sex differences in epilepsies, comorbidities, and drug effects will enhance therapeutic options and efficacy for all patients with epilepsy. SIGNIFICANCE STATEMENT: Epilepsy is a common neurological disorder that often presents together with various comorbidities. The features of epilepsy and seizure activity as well as comorbid afflictions can vary between men and women. In this review, we discuss sex differences in types of epilepsies, associated comorbidities, pathophysiological mechanisms, and antiepileptic drug efficacy in both clinical patient populations and preclinical animal models.
Exacerbation frequency and course of COPD Halpin, David M G; Decramer, Marc; Celli, Bartolome ...
International journal of chronic obstructive pulmonary disease,
01/2012, Letnik:
7, Številka:
default
Journal Article
Recenzirano
Odprti dostop
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over ...time using data from a large, long-term trial.
This retrospective analysis of data from the 4-year UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo. Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2). Spirometry and the St George's Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).
In total, 5992 patients (mean age 65 years, 75% male) were randomized. Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV(1)) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units). Corresponding rates of decline in postbronchodilator FEV(1) (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium). Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium). The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium). The proportion of patients who died (intention-to-treat analysis until four years 1440 days) for the entire cohort increased with increasing frequency of hospitalized exacerbations.
Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD. Increasing rates of hospitalized exacerbations are associated with increasing risk of death.
Haskap berries commonly refer to fruits of Lonicera caerulea L., recognized by the Japanese aborigines as the “elixir of life.” Due to their recent arrival on the North American market, haskap ...berries have not yet been positioned among other berries and compared in terms of their phytochemical content. Haskap berries have higher ascorbic acid and anthocyanin content than other berries known for their health-promoting benefits, such as blueberries. In this article, we give a brief description of the phytochemical content and limitations of current methods used for their quantification, as well as a critical review of the techniques available to assess the antioxidant capacity of haskap extract in comparison to other berries. We then present results from recent studies with haskap extracts used in in vitro (bacterial and human cell cultures), preclinical trials (in animal models), and a first-in-human study to assess the implications for human health. Finally, we discuss current commercial products and the potential of encapsulation technology to preserve the bioactivity and increase stability of the extracts, thus creating a new range of value-added haskap products.
Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased ...risk of cardiovascular disease, however nothing is known about the EAT volume in this population.
To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.
We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.
COPD patients had a higher EAT volume 143.7 (P25-75, 108.3-196.6) vs 129.1 (P25-75, 91.3-170.8) cm(3), p = 0.02) and the EAT volume was significantly associated with CAC (r = 0.38, p<0.001) and CRP (r = 0.32, p<0.001) but not with microalbuminuria (r = 0.12, p = 0.13). In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV1%, 6 MWD, MMRC and HTN. Multivariate analysis showed that only pack-years (B = 0.6, 95% CI: 0.5-1.3), BMI (B = 7.8, 95% CI: 5.7-9.9) and 6 MWD (B = -0.2, 95% CI: -0.3--0.1), predicted EAT volume.
EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Global evidence-based treatment strategies for chronic obstructive pulmonary disease (COPD) recommend using long-acting bronchodilators (LABDs) as maintenance therapy. However, COPD patients are ...often undertreated. We examined COPD treatment patterns among Medicare beneficiaries who initiated arformoterol tartrate, a nebulized long-acting beta
agonist (LABA), and identified the predictors of initiation.
Using a 100% sample of Medicare administrative data, we identified beneficiaries with a COPD diagnosis (ICD-9 490-492.xx, 494.xx, 496.xx) between 2010 and 2014 who had ≥1 year of continuous enrollment in Parts A, B, and D, and ≥2 COPD-related outpatient visits within 30 days or ≥1 hospitalization(s). After applying inclusion/exclusion criteria, three cohorts were identified: (1) study group beneficiaries who received nebulized arformoterol (n=11,886), (2) a subset of the study group with no LABD use 90 days prior to initiating arformoterol (n=5,542), and (3) control group beneficiaries with no nebulized LABA use (n=220,429). Logistic regression was used to evaluate predictors of arformoterol initiation. Odds ratios (ORs), 95% confidence intervals (CIs), and
values were computed.
Among arformoterol users, 47% (n=5,542) had received no LABDs 90 days prior to initiating arformoterol. These beneficiaries were being treated with a nebulized (50%) or inhaled (37%) short-acting bronchodilator or a systemic corticosteroid (46%), and many received antibiotics (37%). Compared to controls, beneficiaries who initiated arformoterol were significantly more likely to have had an exacerbation, a COPD-related hospitalization, and a pulmonologist or respiratory therapist visit prior to initiation (all
<0.05). Beneficiaries with moderate/severe psychiatric comorbidity or dual-eligible status were significantly less likely to initiate arformoterol, as compared to controls (all
<0.05).
Medicare beneficiaries who initiated nebulized arformoterol therapy had more exacerbations and hospitalizations than controls 90 days prior to initiation. Findings revealed inadequate use of maintenance medications, suggesting a lack of compliance with evidence-based treatment guidelines.
There is a differential response to eosinophilic modulation between patients with asthma and those with chronic obstructive pulmonary disease (COPD). There is also evidence of different subtypes of ...eosinophils in murine models. However, no study has compared eosinophil subtypes in individuals with COPD and in those with asthma.
Study the differences in eosinophils subtypes based in the surface protein expression in COPD patients and asthmatic patients.
We studied 10 stable subjects in each of four groups: subjects with COPD, subjects with asthma, smokers without COPD, and healthy volunteers. Subjects with COPD and those with asthma were matched by age, sex, and FEV
% predicted. The following variables were determined: anthropometrics, smoking, exacerbation history, medication use, lung function, and comorbidities. Using flow cytometry and confocal microscopy from blood samples, we determined differences in eosinophil surface proteins and classified them as
) resident eosinophils (Siglec-8
CD62L
IL-3R
) or
) inflammatory eosinophils (iEos; Siglec-8
CD62L
IL-3R
). IL-5 receptor was also determined. Findings were validated in 59 patients with COPD and in 17 patients with asthma.
Patients with asthma had a higher proportion of iEos (25 ± 15%) compared with those with COPD (0.5 ± 1%), smokers without COPD (0.14 ± 0.24%), and healthy volunteers (0.67 ± 1.72%). In patients with asthma, the proportion of iEos was independent of total eosinophil number. iEos had more IL-5 receptors than resident eosinophils (777.02 ± 124.55 vs. 598.35 ± 318.69;
< 0.01). In patients with COPD, there was no relation between iEos number and inhaled corticosteroid use, disease severity, or exacerbations rate. The findings in patients with COPD and those with asthma were confirmed in validation cohorts.
There are differences in the subtypes of circulating eosinophils between patients with asthma and those with COPD. This could have clinical implications in the interpretation of eosinophil significance and the approach to therapy in these patients.
In Bayesian persuasion, an informed sender has to design a signaling scheme that discloses the right amount of information so as to influence the behavior of a self-interested receiver. This kind of ...strategic interaction is ubiquitous in real-world economic scenarios. However, the seminal model by Kamenica and Gentzkow makes some stringent assumptions that limit its applicability in practice. One of the most limiting assumptions is, arguably, that the sender is required to know the receiver's utility function to compute an optimal signaling scheme. We relax this assumption through an online learning framework in which the sender repeatedly faces a receiver whose type is unknown and chosen adversarially at each round from a finite set of possible types. We are interested in no-regret algorithms prescribing a signaling scheme at each round of the repeated interaction with performances close to that of a best-in-hindsight signaling scheme. First, we prove a hardness result on the per-round running time required to achieve no-α-regret for any α<1. Then, we provide algorithms for the full and partial feedback models with regret bounds sublinear in the number of rounds and polynomial in the size of the instance. Finally, we show that, by relaxing the persuasiveness constraints on signaling schemes, it is possible to design an algorithm with a better running time and small regret.
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