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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.