Characteristics of studies included in the meta-analysis of association between baseline C-reactive protein (CRP) level and mortality in chronic obstructive pulmonary disease (COPD) patients

First author [ref.]YearStudy design; recruitment period; locationPatients nType of patients#Main aimOutcomeCRPPrognostic value+Cut-off mg·L−1
Kuller [35]1996Retrospective, multicentric; 1973–1976; UK/USA737Smokers; stableTo investigate the relationship between CRP, α1-acid glycoprotein and albumin and subsequent risk of myocardial infarction and coronary heart disease death in a nested case–control study among the Multiple Risk Factor Intervention Trial participantsLate mortalityAloneMultivariate; 2.8 (1.4–5.4); age, tobacco dose, blood pressure, triglycerides, cholesterol levelsNot reported (fourth quartile)
Man [36]2006Prospective, multicentric; 5 years; USA/Canada4803COPD; stableTo determine whether serum CRP is associated with increased risk of all-cause and disease-specific causes of mortality, increased risk of fatal and nonfatal cardiovascular events, and an accelerated decline in lung function in COPD patientsLate mortalityAloneMultivariate; 1.79 (1.25–2.56); age, sex, race, smoking status, pack-years, BMI, FEV17.06
Dahl [37]2007Prospective, multicentric (epidemiological study); 1991–1994; Denmark1302COPD; stableTo determine whether increased serum CRP in individuals with airway obstruction predicts future hospitalisation and death from COPDLate mortalityAloneMultivariate; 1.4 (1.1–1.8); age, sex, tobacco consumption, FEV1, cardiovascular disease3
de Torres [38]2008Prospective, multicentric; 2000–2004; Spain/USA218COPD; stableTo determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parametersLate mortalityAloneMultivariate; 1.00 (0.82–1.22); age, sex, pack-years, cardiovascular disease, corticosteroidsNot reported
Mehrotra [39]2010Prospective, community-based observational cohort (Pittsburgh, PA and Memphis, TN); 1997–1998; USA268COPD; stableTo identify significant covariates in addition to spirometry that predict mortality in elderly subjects with obstructive airway diseaseLate mortalityAloneMultivariate; 1.12 (0.90–1.30); age, sex, race, smoking status, cardiovascular diseaseNot reported
Liu [40]2011Prospective, single-institution; 2005–2006; China114COPD; stableTo investigate the predictive value of combined serum CRP and BODE index score for mortality in COPD patientsLate mortalityAloneMultivariate; 5.15 (1.65–16.60); BODE index3
Zhang [41]2011Prospective, single-institution; 2001–2003; the Netherlands405COPD; stableTo quantify the effect of cardiovascular determinants on mortality in patients with a diagnosis of COPDLate mortalityAloneMultivariate; 1.78 (1.15–2.82); age, FEV1, angina pectoris3
Høiseth [42]2012Prospective, single-institution; 2005–2006; Norway99COPD; acuteTo test the hypothesis that N-terminal pro-brain natriuretic peptide independently predicts long-term mortality following acute exacerbations of COPDLate mortalityAloneMultivariate; 2.4 (1.7–3.2); age, sex, comorbidity, BMI, SaO2, troponin level50
Deng [43]2014Prospective, single-institution; 2009–2012; China116COPD; stableTo evaluate whether circulating CRP levels are a biomarker of systemic inflammation and a significant predictor of future COPD outcomeLate mortalityAloneUnivariate; 2.71 (1.05–6.99)3
Moberg [44]2014Prospective, single-institution; 2005–2011; Denmark423COPD; stableTo investigate if leukocytes, CRP and vitamin D are independent predictors of mortality and hospitalisation after adjusting for disease severity with an integrative index (i-BODE index)Late mortalityAloneMultivariate; 1.50 (1.07–2.10); age, sex, i-BODE index10
Cano [45]2014Prospective, multicentric; recruitment period 1 year; France637COPD; stableTo investigate predictors of long-term survival, including respiratory, nutritional and inflammatory dimensions, in a prospective cohort of home-treated patients with chronic respiratory failureLate mortalityAloneMultivariate; 1.51 (1.13–2.02); age, PaO2, PaCO2, BMI, FEV1/FVC, 6MWT distance, transthyretin5 
Ford [46]2015Prospective, multicentric; 1988–1994; USA1144COPD; stableTo examine the association between elevated inflammatory marker count (white blood cell count, CRP and fibrinogen) on all-cause mortality in a national sample of US adults with obstructive lung functionLate mortalityAlone/combined (white blood cell count, fibrinogen)Univariate for CRP alone; 1.26 (0.95–1.66)/multivariate for CRP combined; 2.08 (1.29–3.37); age, sex, race, education, smoking status, comorbidity, physical activity, alcohol use, BMI, FEV1/FVC, blood pressure, cholesterol level, urinary albumin/creatinine ratio, cancer history3
Kleber [47]2015Prospective, single-institution; 1997–2001; Germany777Smokers; stableTo characterise the diagnostic value of two independent risk factors for cardiovascular events (high-sensitivity CRP and lipoprotein-associated phospholipase A2), which provide information on inflammation and plaque stability in active smokers and never-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) studyLate mortalityCombined (lipoprotein-associated phospholipase A2)Multivariate; 1.94 (1.10–3.45); age, sex, comorbidity BMI, cholesterol level, triglycerides3.6
Blumenthal [48]2015Prospective (randomised controlled trial), multicentric; 2009–2014; USA326COPD; stableTo examine the prognostic value of select biobehavioural factors in patients with COPD in a secondary analysis of participants from the INSPIRE-II trialLate mortalityAloneMultivariate; 2.25 (1.02–4.96); age, Charlson score, COPD duration, GOLD, corticosteroids, coping skills trainingNot reported
Loprinzi [49]2016Retrospective, single-institution; 2003–2006; USA385COPD; stableTo examine the association between objectively measured physical activity and all-cause mortality among a national sample of COPD patients, with stratification by inflammatory statusLate mortalityAloneMultivariate; 1.33 (1.02–1.72); age, sex, comorbidity, race, BMI, physical activity, poverty/income ratio, cotinineNot reported
Saltürk [50]2015Retrospective, single-institution; 2013–2014; Turkey647COPD; acuteTo assess whether eosinophilic COPD exacerbations have better outcomes than noneosinophilic COPD exacerbations in the intensive care unitEarly mortalityAloneMultivariate; 1.78 (1.01–3.14); age, sex, BMI, NLR, eosinophilia, invasive mechanical ventilation, noninvasive mechanical ventilation, APACHE II score, septic shock, resistant pathogen500
Murphy [51]2010Retrospective, single-institution; 2004–2007; UK60COPD; acuteTo determine if routine clinical assessment could reliably predict in-hospital death in patients admitted with acute exacerbation of COPDEarly mortalityAloneMultivariate; 1.22 (0.95–1.14); Charlson score, pH, ureaNot reported
Zhao [52]2014Prospective, single-institution; 2010–2011; China159COPD; acuteTo investigate the COPD assessment test, serum copeptin, procalcitonin and CRP levels as potential predictive factors for recurrence of acute exacerbation and all-cause mortality in 6 months in COPD inpatientsEarly mortalityAloneUnivariate; 0.90 (0.82–1.01)Not reported
Stolz [53]2008Prospective, single-institution; 2003–2005; Germany167COPD; acuteTo investigate whether plasma pro-endothelin-1 and/or pro-adrenomedullin on admission to the hospital for acute exacerbation predict survival in patients with COPDEarly SurvivalAloneMultivariate; 1.02 (0.92–1.13); age, Charlson score, PaO2, PaCO2, pro-adrenomedullin, endothelin-1, BMI, FEV1, leukocyte counts, procalcitonin, pulmonary arterial hypertensionNot reported
Duman [54]2015Retrospective, single-Institution; 2014 (1 year); Turkey1704COPD; acuteTo evaluate mortality and outcomes of eosinophilic and noneosinophilic COPD exacerbations, and identify new biomarkers that predict survivalEarly mortalityAloneMultivariate; 1.32 (1.01–1.71); cardiovascular disease, corticosteroids, length of stay, readmission, NLR19
Tofan [55]2012Prospective, single-institution; 1999–2010; Iran60COPD; acuteTo assess the clinical utility of serum high-sensitivity CRP at admission in predicting outcome in hospitalised patients with acute exacerbation COPDEarly mortalityAloneUnivariate; 4.04 (1.32–12.33)100
Zhang [56]2014Prospective, single-institution; 2007–2012; China378COPD; acuteTo assess the association of high-sensitivity CRP with in-hospital outcomes in patients with COPD undergoing percutaneous coronary interventionEarly mortalityAloneMultivariate; 1.78 (1.15–2.82); FEV1, left ventricular ejection fraction, three-vessel disease, β-blocker use3
Andreassen [57]2014Retrospective, multicentric; 2005; Norway/Sweden731COPD; acuteTo find the proportion of patients with pneumonia among admissions due to acute exacerbations COPD and whether pneumonia has an impact on the length of stay, usage of noninvasive ventilation or in-hospital mortalityEarly mortalityAloneMultivariate; 0.71 (0.28–1.82); age, sex, GOLD40
Guertler [58]2011Prospective, multicentric; 2006–2008; Switzerland877COPD; acuteTo investigate the long-term prognostic performance of the Pneumonia Severity Index score and the association of clinical parameters and different blood biomarkers with long-term mortality rate in a large cohort of patients with community-acquired pneumoniaEarly mortalityAloneMultivariate; 0.3 (0.2–0.5); age, sex, comorbidity, temperature, chills, pro-adrenomedullinNot reported (fourth quartile)
Moghbeli [59]2005Prospective, multicentric; 1997–1999; USA1862Smokers; acuteTo investigate the role of inflammation, as measured by high-sensitivity CRP levels, in cardiovascular risk in smokers who have acute coronary syndromeEarly mortalityAloneMultivariate; 2.60 (1.42–4.79); age, comorbidity, previous treatment, troponin level15
Haja Mydin [60]2013Prospective, single-institution; 2009–2010; 23 months; UK65COPD; acuteTo identify factors associated with inpatient mortality from hypercapnic respiratory failure with respiratory acidosis due to COPDEarly mortalityAloneUnivariate; 3.43 (0.38–30.55)3

HR: hazard ratio; BMI: body mass index; FEV1: forced expiratory volume in 1 s; BODE: BMI, airflow obstruction, dyspnoea and exercise capacity; SaO2: arterial oxygen saturation; PaO2: arterial oxygen tension; PaCO2: arterial carbon dioxide tension; FVC: forced vital capacity; 6MWT: 6-min walk test; GOLD: Global Initiative for Chronic Obstructive Lung Disease; NLR: neutrophil/lymphocyte ratio. #: COPD or smokers; stable or acute; : alone or combined; +: univariate or multivariate; HR (95% CI); adjusted covariables.