Project description:One measurement of hs-CRP (high-sensitivity C-reactive protein) is associated with increased risk of cardiovascular disease (CVD). The objective of this study was to characterize the association of cumulative exposure to increased hs-CRP with incident cardiovascular events. We included 53 065 participants with hs-CRP measured at 3 examinations in 2006, 2008, and 2010. Cumulative exposure to hs-CRP was calculated as the weighted sum of the average hs-CRP level for each time interval (level×time). Participants were classified into nonexposed group (hs-CRP<3.0 mg/L in all 3 examinations), 1-exposed group (hs-CRP≥3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs-CRP≥3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs-CRP with incident CVD. The study showed a dose-response pattern with risk of CVD and myocardial infarction as the number of years of exposure to hs-CRP increases. Participants in the 3-exposed group had significantly increased CVD risk with hazard ratio (95% confidence interval) of 1.38 (1.11-1.72), in comparison with 1.28 (1.07-1.52) for participants in the 2-exposed group and 1.13 (0.97-1.31) for those in the 1-exposed group (P<0.05); meanwhile, the similar and significant associations were also observed for myocardial infarction with respective hazard ratio (95% confidence interval) of 2.13 (1.42-3.18), 1.60 (1.12-2.27), and 1.57 (1.17-2.10). The associations between stroke and cumulative hs-CRP were not statistically significant (P=0.360). Cumulative exposure to hs-CRP was dose dependently associated with a subsequent increased risk of CVD and myocardial infarction. URL: https://www.clinicaltrials.gov/. Unique identifier: ChiCTR-TNC-11001489.
Project description:RationaleCharacterization of bacterial populations in infectious respiratory diseases will provide improved understanding of the relationship between the lung microbiota, disease pathogenesis, and treatment outcomes.ObjectivesTo comprehensively define lung microbiota composition during stable disease and exacerbation in patients with bronchiectasis.MethodsSputum was collected from patients when clinically stable and before and after completion of antibiotic treatment of exacerbations. Bacterial abundance and community composition were analyzed using anaerobic culture and 16S rDNA pyrosequencing.Measurements and main resultsIn clinically stable patients, aerobic and anaerobic bacteria were detected in 40 of 40 (100%) and 33 of 40 (83%) sputum samples, respectively. The dominant organisms cultured were Pseudomonas aeruginosa (n = 10 patients), Haemophilus influenzae (n = 12), Prevotella (n = 18), and Veillonella (n = 13). Pyrosequencing generated more than 150,000 sequences, representing 113 distinct microbial taxa; the majority of observed community richness resulted from taxa present in low abundance with similar patterns of phyla distribution in clinically stable patients and patients at the onset of exacerbation. After treatment of exacerbation, there was no change in total (P = 0.925), aerobic (P = 0.917), or anaerobic (P = 0.683) load and only a limited shift in community composition. Agreement for detection of bacteria by culture and pyrosequencing was good for aerobic bacteria such as P. aeruginosa (κ = 0.84) but poorer for other genera including anaerobes. Lack of agreement was largely due to bacteria being detected by pyrosequencing but not by culture.ConclusionsA complex microbiota is present in the lungs of patients with bronchiectasis and remains stable through treatment of exacerbations, suggesting that changes in microbiota composition do not account for exacerbations.
Project description:Bronchiectasis, which is characterized by irreversibly damaged and dilated bronchi, causes significant symptoms, poor quality of life, and increased economic burden and mortality rates. Despite its increasing prevalence and clinical significance, bronchiectasis was previously regarded as an orphan disease, and ideal treatment of this disease has been poorly understood. The European Respiratory Society and British Thoracic Society have recently published guidelines to assist physicians in the clinical field. Guidelines and reports suggest comprehensive management that includes both non-pharmacological and pharmacological treatment. Physiotherapy and pulmonary rehabilitation are two of the most important non-pharmacologic therapies in bronchiectasis patients; long-term inhaled antibiotics and macrolide therapy have gained significant evidence in reducing exacerbation risk in frequent exacerbators. In this review, we summarize recent updates on bronchiectasis treatment to prevent exacerbation and manage clinical deterioration.
Project description:Background and objectiveBronchiectasis exacerbations are significant events in the natural course of the disease and determine long-term clinical outcomes. This review aims to discuss the definition, causes, risk factors, management and prevention of bronchiectasis exacerbations.MethodsThe PubMed database was searched for relevant articles published in English between January 1990 and March 2022 using keywords "bronchiectasis" and "exacerbation".Key content and findingsCauses of bronchiectasis exacerbation are multifactorial; it can be associated with bacterial and viral pathogens, host inflammatory responses, and external environmental effects. In addition, recent advances in bronchiectasis research highlight the phenotype of patients who are more prone to exacerbations, including those with chronic Pseudomonas aeruginosa infection, worse symptoms, greater lung inflammation and comorbid airway diseases. Once bronchiectasis exacerbations occur, antibiotics are the mainstay treatment. Preventing exacerbations is of paramount importance because frequent exacerbations are linked to a detrimental disease course and higher mortality. To prevent frequent exacerbations, clinicians should attempt to understand the risk factors for exacerbation that are amenable to therapeutic intervention: so called "treatable traits". Treatments are personalised but include improving mucociliary clearance by physiotherapy and mucoactive therapy, reducing airway infection by inhaled antibiotics, and inflammation by long-term macrolide or in specific subpopulations, inhaled corticosteroids (ICS). Novel approaches to prevent exacerbations including direct anti-inflammatory therapies are in development for bronchiectasis.ConclusionsFuture research is needed to better manage and prevent exacerbations in patients with bronchiectasis, although recent studies have characterised frequent exacerbator phenotype and enhanced our understanding of various aspects of exacerbations.
Project description:BACKGROUND:A hospitalized-based cohort study suggested that elevated C-reactive protein (CRP) levels are associated with radiographic sacroiliitis progression in ankylosing spondylitis (AS) patients. However, data from community-based populations are limited. OBJECTIVE:We sought to determine the association between elevated CRP levels and AS diagnosis in a prospective community-based study of 129,681 Chinese adults over a follow-up period of 8 years. METHODS:We measured the plasma CRP concentration at baseline and every 2 years thereafter with the high-sensitivity (hs)-CRP test. Incident AS cases were confirmed on the basis of modified New York diagnostic criteria after review of medical records. We used Cox proportional-hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for AS on the basis of hs-CRP concentrations, adjusting for age, sex, education, income, cigarette smoking, alcohol intake, physical activity, body mass index, blood-pressure status, blood glucose status, total cholesterol, history of cardiovascular disease, and use of antihypertensives, lipid-lowering agents, and aspirin. RESULTS:During 1,033,609 person-years (average 7.97 ± 1.36 years per person) of follow-up, we identified 55 incident AS cases. Baseline hs-CRP was positively associated with the risk of future AS. Compared with hs-CRP <1 mg/L, the HR was 1.28 (95% CI 0.54-3.08) for hs-CRP of 1.00-2.99 mg/L, 4.71 (95% CI 2.26-9.81) for hs-CRP of 3.00-9.99 mg/L, and 19.8 (95% CI 9.6-40.9) for hs-CRP ?10.00 mg/L (P-trend <0.001) after adjustment for potential confounders. We found similar results after excluding AS cases that occurred in the first 2 years of follow-up, and using the cumulative average hs-CRP concentration as a predictor. CONCLUSION:This is the first study in a community-based cohort to demonstrate that CRP plasma concentrations predict the risk of future AS, thus providing a test that is easy to routinely perform in the clinic to assess for AS risk.
Project description:ObjectiveTo determine whether high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) predict stroke, vascular events, and mortality in a prospective cohort study.BackgroundMarkers of inflammation have been associated with risk of myocardial infarction (MI). Their association with stroke is controversial.MethodsThe Northern Manhattan Study includes a stroke-free community-based cohort study in participants aged > or =40 years (median follow-up 7.9 years). hsCRP and SAA were measured using nephelometry. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of markers with risk of ischemic stroke and other outcomes after adjusting for demographics and risk factors.ResultshsCRP measurements were available in 2,240 participants (mean age 68.9 +/- 10.1 years; 64.2% women; 18.8% white, 23.5% black, and 55.1% Hispanic). The median hsCRP was 2.5 mg/L. Compared with those with hsCRP <1 mg/L, those with hsCRP >3 mg/L were at increased risk of ischemic stroke in a model adjusted for demographics (HR = 1.60, 95% CI 1.06-2.41), but the effect was attenuated after adjusting for other risk factors (adjusted HR = 1.20, 95% CI 0.78-1.86). hsCRP >3 mg/L was associated with risk of MI (adjusted HR = 1.70, 95% CI 1.04-2.77) and death (adjusted HR = 1.55, 95% CI 1.23-1.96). SAA was not associated with stroke risk.ConclusionIn this multiethnic cohort, high-sensitivity C-reactive protein (hsCRP) was not associated with ischemic stroke, but was modestly associated with myocardial infarction and mortality. The value of hsCRP and serum amyloid A may depend on population characteristics such as age and other risk factors.
Project description:BackgroundAlthough blood eosinophil count (BEC) has been extensively studied as a biomarker in chronic obstructive pulmonary disease (COPD), there remain challenges and controversy in using a single reading. It has not been determined whether the difference in BEC between baseline and that during an acute exacerbation of COPD (AECOPD) has any role in predicting subsequent AECOPD.MethodsA prospective study was conducted to investigate the possible role of differences in BEC from baseline to that during AECOPD to predict future AECOPD risk. The BEC difference was expressed as absolute eosinophil difference: BEC at index moderate-to-severe exacerbation (Ei) - baseline BEC (E0).ResultsAmong 348 Chinese patients with COPD, 158 who experienced an index moderate-to-severe AECOPD were analyzed. Using the cut-off of 105 cells/µL for absolute eosinophil difference as determined by receiver operating characteristic (ROC) analysis, patients with absolute eosinophil difference ≥ 105 cells/µL had a shorter time to subsequent AECOPD with adjusted hazard ratio (aHR) of 1.68 (95% CI = 1.02-2.74; p = 0.040). They also had a higher annual number of subsequent AECOPD (2.49 ± 2.84/year vs 1.58 ± 2.44/year, p = 0.023). Similar findings were shown in the subgroup with stable-state baseline BEC < 300 cells/µL.ConclusionGreater difference in BEC between baseline and upon moderate-to-severe AECOPD might be associated with shorter time to next AECOPD, as well as more episodes of subsequent AECOPD.
Project description:Inflammation is associated with a number of chronic conditions, such as cancer and cardiovascular disease. Reducing inflammation may help prevent or treat these conditions. Diet has consistently been shown to modulate inflammation. To facilitate research into the inflammatory effect of diet on health in humans, we sought to develop and validate an Inflammatory Index designed to assess the inflammatory potential of individuals' diets. An Inflammatory Index was developed based on the results of an extensive literature search. Using data from a longitudinal observational study that carefully measured diet and the inflammatory marker, serum high-sensitivity (hs) C-reactive protein (CRP), in approximately 600 adults for 1 y, we conducted analyses to test the effect of Inflammatory Index score on hs-CRP as a continuous and dichotomous (<or=3 mg/L, >3 mg/L) indicator of inflammatory response, while controlling for important potential confounders. Results based on continuous measures of hs-CRP suggested that an increasing Inflammatory Index score (representing movement toward an antiinflammatory diet) was associated with a decrease in hs-CRP. Analyses using hs-CRP as a dichotomous variable showed that an antiinflammatory diet was associated with a decrease in the odds of an elevated hs-CRP (P = 0.049). The results are consistent with the ability of the Inflammatory Index to predict hs-CRP and provide additional evidence that diet plays a role in the regulation of inflammation, even after careful control of a wide variety of potential confounders.
Project description:A reliable, widely available method to detect osteoporosis prior to fracture is needed. Serum levels of C-reactive protein may independently predict low bone mineral density (BMD) and high fracture risk. Existing empirical data focus on sexually and/or racially homogenous populations. This study tests the hypotheses that: C-reactive protein (1) negatively correlates with BMD and (2) fracture history, and (3) independently predicts BMD and fracture history in a diverse population. NHANES 2017-2020 pre-pandemic cycle data were analyzed in R studio. Strength and direction of relationships (-1 to +1) between variables were determined using Kendall's rank correlation coefficient (τ). Linear models were optimized to predict femoral neck or lumbar spine BMD. C-reactive protein positively correlated with femoral (τ = 0.09, p<0.0001) and spine BMD (τ = 0.10, p<0.0001). Individuals identifying as female demonstrated more robust, but still weak, correlations between C-reactive protein and femoral neck (τ = 0.15, p<0.0001; male, τ = 0.06, p = 0.051) and spine BMD (τ = 0.16, p<0.0001; male, τ = 0.06, p = 0.04). C-reactive protein positively correlated with fracture history (τ = 0.083, p = 0.0009). C-reactive protein significantly predicted femoral neck (R2 = 0.022, p = 0.0001) and spine BMD (R2 = 0.028, p<0.0001) and fracture history (R2 = 0.015, p<0.0001). Exploratory analyses identified weight was the single best predictor for femoral neck (R2 = 0.24, p<0.0001) and spine BMD (R2 = 0.21, p<0.0001). In sum, C-reactive protein statistically correlates with and predicts femoral neck and spine BMD, but the magnitude is too low to be biologically meaningful. While weight is a more robust predictor, individuals who are overweight or obese account for nearly half of all osteoporotic fractures, limiting the predictive power of this variable at identifying individuals at risk for osteoporosis. Identification of a robust predictor of fracture risk in a diverse population and across of range of body weights and compositions is needed.