NT-proBNP in stable COPD and future exacerbation risk: Analysis of the SPIROMICS cohort.
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ABSTRACT:
SUBMITTER: Labaki WW
PROVIDER: S-EPMC6084793 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
NT-proBNP in stable COPD and future exacerbation risk: Analysis of the SPIROMICS cohort.
Labaki Wassim W WW Xia Meng M Murray Susan S Curtis Jeffrey L JL Barr R Graham RG Bhatt Surya P SP Bleecker Eugene R ER Hansel Nadia N NN Cooper Christopher B CB Dransfield Mark T MT Wells J Michael JM Hoffman Eric A EA Kanner Richard E RE Paine Robert R Ortega Victor E VE Peters Stephen P SP Krishnan Jerry A JA Bowler Russell P RP Couper David J DJ Woodruff Prescott G PG Martinez Fernando J FJ Martinez Carlos H CH Han MeiLan K MK
Respiratory medicine 20180605
<h4>Background</h4>High N-terminal pro-brain natriuretic peptide (NT-proBNP) during COPD exacerbations is associated with worse clinical outcomes. The prognostic value of NT-proBNP measured during clinical stability has not been well characterized.<h4>Methods</h4>We studied SPIROMICS participants 40-80 years of age with COPD GOLD spirometric stages 1-4. The association between baseline NT-proBNP and incident COPD exacerbations within one year of follow-up was tested using zero-inflated Poisson r ...[more]
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Project description:BackgroundCardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD). NT-proBNP is an established risk factor in patients with heart failure. NT-proBNP may also be released from the right ventricle. Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD). The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied. Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD.MethodsA prospective cohort study of 99 patients with 217 admissions with AECOPD. Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables.ResultsMedian follow-up time was 1.9 years, and 57 patients died during follow-up. NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p<0.0001). After adjustment for age, gender, peripheral edema, cephalization and cTnT in a multivariable survival model, the corresponding hazard ratios for dying were 2.4 (0.95-6.0) and 3.2 (1.3-8.1) (with 95% confidence intervals in parentheses, p-value for trend 0.013).ConclusionsNT-proBNP is a strong and independent determinant of mortality after AECOPD.
| S-EPMC3495751 | biostudies-literature
Project description:Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls. Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown. We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195). BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV1 % predicted and exacerbation frequency. Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates. BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers. BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively. Similar associations were not observed with plasma ferritin. Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals.
| S-EPMC7324559 | biostudies-literature
Project description:Background: Decreased but measurable serum IgA levels (?70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD.Methods: Data were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed.Results: Mean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ?70 mg/dL. Participants with IgA ?70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ?70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01-2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30-6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (? 0.24, 95% CI 0.017-0.46, p = 0.035).Conclusions: Subnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction.
| S-EPMC5896903 | biostudies-literature
Project description:RATIONALE:Rural residence is associated with poor outcomes in several chronic diseases. The association between rural residence and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. OBJECTIVE:To determine the independent association between rural residence and COPD-related outcomes including COPD exacerbations, airflow obstruction and symptom burden. METHODS:A total of 1684 Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) participants with FEV1/FVC<0.70 had geocoding-defined rural-urban residence status determined (N=204 rural and N=1480 urban). Univariate and multivariate logistic and negative binomial regressions were performed to assess the independent association between rurality and COPD outcomes including exacerbations, lung function, and symptom burden. The primary exposure of interest was rural residence, determined by geocoding of home address to the block level at time of study enrollment. Additional covariates of interest included demographic and clinical characteristics, occupation, and occupational exposures.The primary outcome measures were exacerbations determined over the one-year course after enrollment by quarterly telephone calls and at an annual research clinic visit. Odds ratio and incidence rate of exacerbations that required treatment with medications including steroids or antibiotics (total exacerbations), and exacerbations leading to hospitalization (severe exacerbations) were determined after adjusting for relevant covariates. RESULTS:Rural residence was independently associated with 70% increase in odds of total exacerbations [OR 1.70 (95% CI 1.13-2.56); p=0.012] and 46% higher incidence rate of total exacerbations [IRR 1.46 (95% CI 1.02-2.10); p=0.039]. There was no association between rural residence and severe exacerbations. Agricultural occupation was independently associated with increased odds and incidence of total and severe exacerbations. Inclusion of agricultural occupation to analysis attenuated the association between rural residence and odds and incidence rate of total exacerbations [OR 1.52 (95% CI 1.00-2.32; p=0.05) and IRR 1.39 (95% CI 0.97 - 1.99); p=0.07]. There was no difference in symptoms or airflow obstruction between rural and urban participants. CONCLUSIONS:Rural residence is independently associated with increased odds and incidence of total, but not severe COPD exacerbations. These associations are not fully explained by agriculture-related exposures, highlighting the need for future research into potential mechanisms of increased risk of COPD exacerbations in the rural population.
| S-EPMC6207115 | biostudies-other
Project description:BackgroundThe relationship between 25-hydroxyvitamin D (25-OH-vitamin D) and COPD outcomes remains unclear. Using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), we determined associations among baseline 25-OH-vitamin D and cross-sectional and longitudinal lung function and COPD exacerbations.MethodsSerum 25-OH-vitamin D level was measured in stored samples from 1,609 SPIROMICS participants with COPD. 25-OH-vitamin D levels were modeled continuously and dichotomized as deficient (< 20 ng/mL) vs not deficient (≥ 20 ng/mL). Outcomes of interest included % predicted FEV1 (current and 1-year longitudinal decline) and COPD exacerbations (separately any and severe, occurring in prior year and first year of follow-up).ResultsVitamin D deficiency was present in 21% of the cohort and was more prevalent in the younger, active smokers, and blacks. Vitamin D deficiency was independently associated with lower % predicted FEV1 (by 4.11%) at enrollment (95% CI, -6.90% to -1.34% predicted FEV1; P = .004), 1.27% predicted greater rate of FEV1 decline after 1 year (95% CI, -2.32% to -0.22% predicted/y; P = .02), and higher odds of any COPD exacerbation in the prior year (OR, 1.32; 95% CI, 1.00-1.74; P = .049). Each 10-ng/mL decrease in 25-OH-vitamin D was associated with lower baseline lung function (-1.04% predicted; 95% CI, -1.96% to -0.12% predicted; P = .03) and increased odds of any exacerbation in the year before enrollment (OR, 1.11; 95% CI, 1.01-1.22; P = .04).ConclusionsVitamin D deficiency is associated with worse cross-sectional and longitudinal lung function and increased odds of prior COPD exacerbations. These findings identify 25-OH-vitamin D levels as a potentially useful marker of adverse COPD-related outcomes.
| S-EPMC7118244 | biostudies-literature
Project description:Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset of individuals with COPD with an inflammatory phenotype who are at increased risk for acute exacerbation (AECOPD). We analyzed Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene) cohorts for which baseline and prospective data were available. Elevated MMP-9 was defined based on >95th percentile plasma values from control (non-COPD) sample in SPIROMICS. COPD subjects were classified as having elevated or nonelevated MMP-9. Logistic, Poisson, and Kaplan-Meier analyses were used to identify associations with prospective AECOPD in both cohorts. Elevated MMP-9 was present in 95/1,053 (9%) of SPIROMICS and 41/140 (29%) of COPDGene participants with COPD. COPD subjects with elevated MMP-9 had a 13%-16% increased absolute risk for AECOPD and a higher median (interquartile range; IQR) annual AECOPD rate (0.33 [0-0.74] versus 0 [0-0.80] events/year and 0.9 [0.5-2] versus 0.5 [0-1.4] events/year for SPIROMICS and COPDGene, respectively). In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95%CI, 1.00-2.90; and OR, 3.03; 95%CI, 1.02-9.01), frequency (incidence rate ratio [IRR], 1.45; 95%CI, 1.23-1.7; and IRR, 1.24; 95%CI, 1.03-1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively. Elevated MMP-9 was independently associated with AECOPD risk in 2 well-characterized COPD cohorts. These findings provide evidence for MMP-9 as a prognostic biomarker and potential therapeutic target in COPD. ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). This work was funded by K08 HL123940 to JMW; R01HL124233 to PJC; Merit Review I01 CX000911 to JLC; R01 (R01HL102371, R01HL126596) and VA Merit (I01BX001756) to AG. SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) is funded by contracts from the NHLBI (HHSN268200900013C, HHSN268200900014C,HHSN268200900015C HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, and HHSN268200900020C) and a grant from the NIH/NHLBI (U01 HL137880), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals Inc.; Chiesi Farmaceutici; Forest Research Institute Inc.; GlaxoSmithKline; Grifols Therapeutics Inc.; Ikaria Inc.; Novartis Pharmaceuticals Corporation; Nycomed GmbH; ProterixBio; Regeneron Pharmaceuticals Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan. COPDGene is funded by the NHLBI (R01 HL089897 and R01 HL089856) and by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
| S-EPMC6302944 | biostudies-literature
Project description:BackgroundDemographic differences in expected NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration are not well established. We aimed to establish reference ranges for NT-proBNP and explore the determinants of moderately elevated NT-proBNP under the universal definition of heart failure criteria.MethodsThis is a cross-sectional study. NT-proBNP was measured in serum from 18 356 individuals without previous cardiovascular disease in the Generation Scotland Scottish Family Health Study. Age- and sex-stratified medians and 97.5th centiles were generated. Sex stratified risk factors for moderately elevated NT-proBNP (≥125 pg/mL) were investigated.ResultsIn males, median (97.5th centile) NT-proBNP concentration at age <30 years was 21 (104) pg/mL, rising to 38 (195) pg/ml at 50 to 59 years, and 281 (6792) pg/mL at ≥80 years. In females, median NT-proBNP at age <30 years was 51 (196) pg/mL, 66 (299) pg/mL at 50 to 59 years, and 240 (2704) pg/mL at ≥80 years. At age <30 years, 9.8% of females and 1.4% of males had elevated NT-proBNP, rising to 76.5% and 81.0%, respectively, at age ≥80 years. After adjusting for risk factors, an NT-proBNP ≥125 pg/mL was more common in females than males (OR, 9.48 [95% CI, 5.60-16.1]). Older age and smoking were more strongly associated with elevated NT-proBNP in males than in females (Psex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (Psex interaction=0.007).ConclusionsAn NT-proBNP ≥125 pg/mL is common in females without classical cardiovascular risk factors as well as older people. If NT-proBNP becomes widely used for screening in the general population, interpretation of NT-proBNP levels will require that age and sex-specific thresholds are used to identify patients with potential pathophysiology.
| S-EPMC9561238 | biostudies-literature
Project description: Not available
| S-EPMC10126609 | biostudies-literature
Project description:AimsExtensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis.Methods and resultsConsecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit).ConclusionNT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.
| S-EPMC8013330 | biostudies-literature
Project description:While acute kidney injury (AKI) alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics) in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107) and identified confounding factors.The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03) increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome.
| S-EPMC4592049 | biostudies-other