Dataset Information

Urine and Plasma Markers of Platelet Activation and Respiratory Symptoms in COPD.

ABSTRACT:

Introduction

Antiplatelet therapy has been associated with fewer exacerbations and reduced respiratory symptoms in chronic obstructive pulmonary disease (COPD). Whether platelet activation is associated with respiratory symptoms in COPD is unknown.

Methods

Former smokers with spirometry-confirmed COPD had urine 11-dehydro-thromboxane B2 (11dTxB2), plasma soluble CD40L (sCD40L), and soluble P-selectin (sP-selectin) repeatedly measured during a 6- to 9-month study period. Multivariate mixed-effects models adjusted for demographics, clinical characteristics, and medication use evaluated the association of each biomarker with respiratory symptoms, health status, and quality of life.

Results

Among 169 participants (average age 66.5±8.2 years, 51.5% female, 47.5±31 pack years, forced expiratory volume in 1 second percent predicted 53.8±17.1), a 100% increase in 11dTxB2 was associated with worse respiratory symptoms reflected by higher scores on the COPD Assessment Test (β 0.77, 95% confidence interval [CI]: 0.11-1.4) and Ease of Cough and Sputum Clearance Questionnaire β 0.77, 95%CI: 0.38-1.2, worse health status (Clinical COPD Questionnaire β 0.13, 95%CI: 0.03-0.23) and worse quality of life (St George's Respiratory Questionnaire β 1.9, 95%CI: 0.39-3.4). No statistically significant associations were observed for sCD40L or sP-selectin. There was no consistent statistically significant effect modification of the relationship between urine 11dTxB2 and respiratory outcomes by history of cardiovascular disease, subclinical coronary artery disease, antiplatelet therapy, or COPD severity.

Conclusions

In stable moderate-severe COPD, elevated urinary11dTxB2, a metabolite of the platelet activation product thromboxane A2, was associated with worse respiratory symptoms, health status, and quality of life.

SUBMITTER: Fawzy A

PROVIDER: S-EPMC9995228 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Urine and Plasma Markers of Platelet Activation and Respiratory Symptoms in COPD.

Fawzy Ashraf A Putcha Nirupama N Raju Sarath S Woo Han H Lin Cheng Ting CT Brown Robert H RH Williams Marlene S MS Faraday Nauder N McCormack Meredith C MC Hansel Nadia N

Chronic obstructive pulmonary diseases (Miami, Fla.) 20230101 1

<h4>Introduction</h4>Antiplatelet therapy has been associated with fewer exacerbations and reduced respiratory symptoms in chronic obstructive pulmonary disease (COPD). Whether platelet activation is associated with respiratory symptoms in COPD is unknown.<h4>Methods</h4>Former smokers with spirometry-confirmed COPD had urine 11-dehydro-thromboxane B2 (11dTxB2), plasma soluble CD40L (sCD40L), and soluble P-selectin (sP-selectin) repeatedly measured during a 6- to 9-month study period. Multivaria ...[more]

PMID: 36367951

Similar Datasets

Project description:BackgroundSymptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.MethodsThis study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset.ResultsIn each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman's rho; p < 0.01, all comparisons listed here): FEV1% predicted (-0.19, -0.14, -0.15); St. George's Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (-0.30, -0.14) and incremental shuttle walk (ISWT) (-0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.ConclusionsResults suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.Trial registrationMPEX: NCT00739648 ; AZ1: NCT00949975 ; AZ 2: NCT01023516.

Project description:BackgroundReducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS(™): COPD) scale (formerly EXACT-RS).MethodsData were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.ResultsOf 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted. Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.ConclusionsAclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients' level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms.Trial registrationATTAIN (ClinicalTrials.gov identifier: NCT01001494 ) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397 ).

Project description:Phthalates are known endocrine disruptors and found in almost all people with several associated adverse health outcomes reported in humans and animal models. Limited data are available on the relationship between exposure to endocrine disrupting chemicals and the human metabolome. We examined the relationship of metabolomic profiles in plasma and urine of 115 pregnant women with eleven urine phthalate metabolites measured at 26 weeks of gestation to identify potential biomarkers and relevant pathways. Targeted metabolomics was performed by selected reaction monitoring liquid chromatography and triple quadrupole mass spectrometry to measure 415 metabolites in plasma and 151 metabolites in urine samples. We have chosen metabolites with the best defined peaks for more detailed analysis (138 in plasma and 40 in urine). Relationship between urine phthalate metabolites and concurrent metabolomic markers in plasma and urine suggested potential involvement of diverse pathways including lipid, steroid, and nucleic acid metabolism and enhanced inflammatory response. Most of the correlations were positive for both urine and plasma, and further confirmed by regression and PCA analysis. However, after the FDR adjustment for multiple comparisons, only 9 urine associations remained statistically significant (q-values 0.0001-0.0451), including Nicotinamide mononucleotide, Cysteine T2, Cystine, and L-Aspartic acid. Additionally, we found negative associations of maternal pre-pregnancy body mass index (BMI) with more than 20 metabolomic markers related to lipid and amino-acid metabolism and inflammation pathways in plasma (p = 0.01-0.0004), while Mevalonic acid was positively associated (p = 0.009). Nicotinic acid, the only significant metabolite in urine, had a positive association with maternal BMI (p = 0.002). In summary, when evaluated in the context of metabolic pathways, the findings suggest enhanced lipid biogenesis, inflammation and altered nucleic acid metabolism in association with higher phthalate levels. These results provide new insights into the relationship between phthalates, common in most human populations, and metabolomics, a novel approach to exposure and health biomonitoring.

Project description:BackgroundPatients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation. This study evaluated the association between St George's Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation.MethodsData from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort. Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups. We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group.ResultsOf the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation. Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score. The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients (r=-0.103, p=0.002) and weak in the severe-to-very severe COPD patients (r=-0.219, p<0.001). Multiple logistic regression analysis revealed that age, being an ex- or current smoker, lower level of education, cough, dyspnea, and number of comorbidities with congestive heart failure, hyperlipidemia, and depression were significantly associated with high SGRQ-C score in mild-to-moderate COPD patients. In comparison, being an ex-smoker and having respiratory symptoms including sputum and dyspnea were significant factors associated with high SGRQ-C score in severe-to-very severe COPD patients.ConclusionsIn addition to the respiratory symptoms of dyspnea and cough, high SGRQ-C score was associated with extra-pulmonary comorbidities in mild-to-moderate COPD patients. However, only respiratory symptoms such as sputum and dyspnea were significantly associated with high SGRQ-C score in severe-to-very severe COPD patients. This indicates the need for an improved management strategy for relieving respiratory symptoms in COPD patients with poor HRQoL. In addition, attention should be paid to extra-pulmonary comorbidities, especially in mild-to-moderate COPD patients with poor HRQoL.

Dataset Information

Urine and Plasma Markers of Platelet Activation and Respiratory Symptoms in COPD.

Introduction

Methods

Results

Conclusions

Publications

Urine and Plasma Markers of Platelet Activation and Respiratory Symptoms in COPD.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets