Biomarkers in chronic obstructive pulmonary disease may be useful in aiding diagnosis, defining specific phenotypes of disease, monitoring exacerbations and evaluating the effects of drugs. Exhaled breath condensate is a noninvasive means of sampling the airways, allowing biomarkers of airway inflammation and oxidative stress to be measured. In the present review, the use of exhaled breath condensate biomarkers in chronic obstructive pulmonary disease is explored and potential applications in diagnosis, disease phenotyping, exacerbation monitoring and clinical trials are considered. Exhaled breath condensate biomarkers are comprehensively reviewed in terms of method validation, reproducibility, disease specificity and sensitivity to detect changes in airway inflammation.The commonly used exhaled breath condensate methodologies in chronic obstructive pulmonary disease patients are shown to have considerable variability, due to technical issues concerning both sample collection and analysis. Despite these issues, there is still data to support the use of exhaled breath condensate biomarkers for monitoring chronic obstructive pulmonary disease exacerbations and the response to pharmacological intervention. Further improvements to sample collection and analysis methods will improve the sensitivity of these biomarkers. The use of cytokine arrays, mass spectrometry and nuclear magnetic resonance profiling of exhaled breath condensate has opened a new avenue for analysis, as hypothesis generation from such profiling may lead to further selection of biomarkers for specific analysis.

IOS reactance measurements are more closely related than resistance measurements to other pulmonary function measurements in COPD patients. The IOS reactance measurements appear to be indicative of changes in pulmonary compliance caused by airflow obstruction.

Multiple flow rates of exhaled nitric oxide (eNO) fraction (Fe,NO) data can be modelled to estimate airway wall concentration of nitric oxide (Caw,NO), diffusing capacity of nitric oxide (Daw,NO), alveolar nitric oxide concentration (Calv,NO) and total maximal flux of nitric oxide in the airway compartment (J9aw,NO).Fe,NO at 10, 30, 50, 100 and 200 mL?s -1 from 50 chronic obstructive pulmonary disease (COPD) patients and 35 healthy controls (smokers and nonsmokers) modelled using five different methods was compared and the effect of the number of flow rates was investigated.All methods showed that current smoking reduced Caw,NO in COPD patients, with some methods showing that smoking reduced J9aw,NO. Smoking did not affect Calv,NO or Daw,NO. The methods gave similar results for Caw,NO but there was variability between methods for J9aw,NO, Calv,NO and Daw,NO. The median error by least squares fitting between modelled and actual data was significantly lower for the nonlinear method (1.96) compared with the mixed methods (3.31 and 3.62). Parameters calculated using the nonlinear method using five and four flow rates were significantly different. The ratio (95% confidence interval) of Caw,NO was 2.02 (1.45-2.83).Nitric oxide models give different results, although airway conductance of nitric oxide is relatively model independent. Nonlinear modelling has the least error, suggesting it is the best method. The number of flow rates should be standardised.

BackgroundMany of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) over one year and examined the relationships between these systemic markers in COPD.MethodsFifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-α were measured. Repeatability was expressed by intraclass correlation coefficient (Ri) and the Bland–Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits.ResultsThere was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001) between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α). CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively). There were no other significant associations between the systemic markers at either of the visits.ConclusionsSystemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.