Pulmonary biomarkers in COPD exacerbations: a systematic review

Abstract

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required.

Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro

“…IL-8, myeloperoxidase, elastase) 4 were based on analysis of sputum or serum. Thus, our results represent the first biomarker that has been identified in vitro and, to our knowledge, M-CSF is the first to offer the possibility of discriminating between viral and bacterial causes of COPD exacerbations.…”

“…While hospitalization and mortality due to these diseases are often the consequences of exacerbations triggered by pathogens 2, 3 , there is currently no way to study these processes in human lung outside of the clinical setting. Animal models of asthma and COPD exist; however, their clinical relevance is questionable because the anatomy, immune system and inflammatory responses exhibited by animal lungs differ greatly from those in humans [4][5][6] . For example, mucin-producing cells, which are central to the development of asthma, are less frequent in the respiratory tree of mice and rats compared with humans 6 .…”

Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

“…Numerous studies have shown that fibrinogen levels are elevated in stable COPD (even outside exacerbations) in relation to the increasing decline of FEV1 along with other biomarkers (CRP, white blood cells, TNF-α, IL-6, IL-8). 6,[10][11][12]24 Increased fibrinogen certifies systemic inflammation in stable COPD and may partially explain some systemic side effects such as muscle wasting, osteoporosis and cardiovascular effects. 5,6,30 The ECLIPSE study has demonstrated that an elevated fibrinogen in COPD is a predictive marker of an increased risk for exacerbations, hospitalization and mortality.…”

“…6 The risk of having frequent exacerbations is clearly demonstrated by recognized studies in patients with specific criteria: previous exacerbation in the last year, decrease in FEV1s, increase in the score of St. George Questionnaire (life quality diminution), high levels of some inflammatory biomar-kers -neutrophils, C-reactive protein (CRP), fibrinogen, pro-calcitonin, eosinophils, IL-6, IL-8, chemokine ligand 18 (CCL-18/PARC), surfactant protein D (SP-D). [9][10][11] Simultaneously, elevated levels of CRP, fibrinogen and leukocyte count in COPD patients were associated with increased risk of having exacerbations. [12][13][14] In the same time, elevated levels of the three biomarkers are associated with an increased risk of major comorbidities in COPD.…”

Vasoactive intestinal peptide for diagnosing exacerbation in chronic obstructive pulmonary disease

“…Thus, practically, exacerbations are difficult to diagnose and therefore it is a worthwhile task to explore potential biomarkers that can be appointed for clinical use [12] . Although some proteins have been suggested as potential markers of COPD exacerbation, up to now there is no single factor that can decisively identify it [13,14] .…”