Table 1.

Biomarkers in context

Sample	Measures	Context	Problems	Benefit
Plasma/serum	Cytokines/peptides/products Acute phase proteins Cell activation markers and secreted/shed products Tissue damage products Lung leakage	Systemic inflammation Systemic response Inflammatory cells Tissue damage Lung inflammation	Coagulation may activate cells/proteins/peptides Distant from the lung May not be lung specific Clearance of cytokines by receptor binding	Easy to obtain Repeated sampling acceptable No dilutional problems
Exhaled breath condensate	Cytokines Markers of oxidant stress pH as a marker of inflammation	Airways/oropharyngeal inflammation	Many measures are below the lower limit of quantification/detection Site not localized Variable dilution by condensate	Repeated sampling
Lung lavage	Cytokines/peptides Markers of oxidant stress Cells number and function Protein leakage from plasma Damage markers	More localized to the lung	Lavage of many regions Bronchial contamination Variable dilution by instillate Not readily repeatable Proinflammatory	More direct lung sampling Can be regionally targeted
Sputum/induced sputum	Cytokines/peptides/proteins Markers of oxidant stress Cell number and function Damage markers	More localized to the lung	Samples bronchial secretions Oropharyngeal contamination Variable dilution Induced is proinflammatory	Spontaneous sputum is readily repeatable Variability can be reduced by sequential sampling
DNA	Variation in genetic sequence	Underlying susceptibility and pathophysiology	Often nonfunctional May be indirect, reflecting nearby genetic abnormalities	Not subject to collection or disease state influences
Physiology	End-organ damage	Assesses the change in lung function as a result of damage	Does not determine the degree, site, or pathological damage with precision	Reasonably well understood Correlates with health status, activity, and mortality
CT scan	Lung density Changes in architecture	Localizes abnormalities that influence clinical outcome	Radiation exposure Repeat measures limited	Identifies pathology Predicts mortality Sensitive to emphysema progression
Biopsy	Cells Architecture Cytokines Damage products	Lung tissue	Variability between samples Not easy to repeat Only samples a small portion of the lung	It is the most direct way of studying the process in situ

Abbreviations: CT, computed tomography; DNA, deoxyribonucleic acid.