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Table 3 Lung biomarkers measured during clinically stability (baseline) as predictors of ECOPD frequency

From: Pulmonary biomarkers in COPD exacerbations: a systematic review

Sample Biomarker Ref. Comment
Exhaled air FeNO [81] ↔: frequent (≥3/year), infrequent (≤2/year) ECOPD
  [75] Intra-individual FeNO variability is positively associated with the ECOPD frequency
eNOCoV ≥ 40%: twofold increase in ECOPD rate as compared to COPD with eNOCoV <40%*
  VOCs [76] Several compounds were associate with the number of ECOPD in the previous year
EBC pH [82] No significant correlation with ECOPD frequency over the following 6M
Spontaneous sputum Elastase [83] ↔: frequent (≥3/year), infrequent (≤2/year) ECOPD
IL-8 [83] ↔: frequent (≥3/year), infrequent (≤2/year) ECOPD
LTB4 [83] ↔: frequent (≥3/year), infrequent (≤2/year) ECOPD
MPO [83] ↔: frequent (≥3/year), infrequent (≤2/year) ECOPD
Protein leakage [83] ↔: frequent (≥3/year), infrequent (≤2/year) ECOPD
Induced sputum ECP [77] Not statistically significant hazard for ECOPD after cessation of ICS
IL-6 [53] Correlated with the frequency of ECOPD
IL-8 [84] Correlated with the total bacterial count. Bacterial colonization at baseline was associated with ECOPD frequency
[53] Correlated with the frequency of ECOPD
LTB4 [77] Not statistically significant hazard for ECOPD after cessation of ICS
MPO [77] In the monovariate analysis (but not in the multivariate analysis) sputum MPO per neutrophil was a significant hazard for ECOPD after cessation of ICS. MPO level per se were not a significant hazard.
SLPI [83] Negative correlation with ECOPD frequency over the preceding year
[84] Lower levels in samples colonized with a possible pathogen. Bacterial colonization in the stable state was associated with increased frequency of ECOPD.
Induced and spontaneous sputum ET-1 [85] ET-1 at stability and the rise of ET-1 during ECOPD did not correlate with the frequency of ECOPD
IL-6 [86] Patients with frequent ECOPD (≥2.52/y) had a faster rise over time in sputum IL6
IL-8 [86] No significant relation to exacerbation frequency
Small volume lavage of the large airways Albumin [87] ↔: patients with ≥3 antibiotic treated ECOPD during the past 2 years, patients without recurrent ECOPD
ECP [87] ↔: patients with ≥3 antibiotic treated ECOPD during the past 2 years, patients without recurrent ECOPD
Hyaluronan [87] Not statistically significant difference in regard to recurrent ECOPD
IL-6 [87] ↔: patients with ≥3 antibiotic treated ECOPD during the past 2 years, patients without recurrent ECOPD
IL-8 [87] ↔: patients with ≥3 antibiotic treated ECOPD during the past 2 years, patients without recurrent ECOPD
MPO [87] ↔: patients with ≥3 antibiotic treated ECOPD during the past 2 years, patients without recurrent ECOPD
Tryptase [87] ↔: patients with ≥3 antibiotic treated ECOPD during the past 2 years, patients without recurrent ECOPD
BAL MPO [78] ↔: frequent (≥3/year), infrequent (<3/year) ECOPD
IL-8 [78] Higher levels in patients with frequent ECOPD, 1 pg/ml increase in IL-8 was associated with 1fold increase in the risk of frequent ECOPD
NE [78] ↔: frequent (≥3/year), infrequent (<3/year) ECOPD
TNF-α [78] ↔: frequent (≥3/year), infrequent (<3/year) ECOPD
  1. Data concerning mRNA expression of biomarkers were not included in this table.
  2. Abbreviations: eNOCoV intra-individual FeNO coefficient of variation, ECP eosinophil cationic protein, ET-1 endothelin 1, FeNO exhaled nitric oxide, ICS inhaled corticosteroids, IL interleukin, LTB4 leukotriene B4, MPO myeloperoxidase, NE neutrophil elastase, SLPI secretory leukoprotease inhibitor, TNFα tumor necrosis factor alpha, VOCs: volatile organic compounds.
  3. Symbols: ↔: no difference.
  4. *The FeNO monthly intra-subject variability was retrospectively assessed by calculating the CoV (mean/SD)x100.
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