| Type of sample | Advantages | Disadvantages |
| Bronchoalveolar lavage fluid | Collected from specific area of the lung Collected under clinical and reproducible conditions Pre-existing proof of principle in this sample type Reasonably complex analytical matrix | High salt content Dilute analytes; often requires concentration before analysis, leading to variability Difficult to normalise for sample dilution Possible bias towards leakage of tissue or inflammatory cell components in diseased patients Collection procedure may cause tissue damage Not well tolerated as a procedure, particularly in diseased patients Cannot perform longitudinal sampling |
| Induced sputum | “Natural” biofluid Internationally recognised SOP for collection Choice of sample type (i.e. with/without mucolytic agent) Reasonably complex analytical matrix | High salt content Difficult to normalise for sample dilution (amylase sometimes used) Source in the lungs poorly defined Use of reducing agents can affect analyte characteristics Presence of cellular and/or bacterial debris Potential high content of plasma infiltration components, especially in asthma Salivary contamination during collection High quantities of mucins affect proteomics readouts |
| Blood (serum or plasma) | Minimally invasive Easy to collect with standardised protocols Widely used in proteomics and lipidomics studies, composition relatively well documented Relatively consistent and easy to define protocol in multicentre studies Contains a large number of potential targets | Large dynamic range of protein content (∼10 orders of magnitude) Lipid composition dominated by lipoproteins, possibly masking minor components Distant from the tissue of interest, so potential bias towards systemic changes in disease |
| Exhaled breath condensate | Noninvasive Suitable for analysis of non-volatile components Suitable for longitudinal study Safe Feasible in children Metabolomic analysis by NMR spectroscopy validated | Very dilute, often requires concentration steps leading to variability Potential variability due to differences in droplet dilution Samples whole airway, difficult to localise changes Difficult to normalise protein/chemical composition for total content High variability in sample quality Relatively few proteins present |
| Exhaled air volatiles | Noninvasive (Pseudo) real-time Inexpensive and portable equipment available Diagnostic accuracies confirmed between independent centres | Data not exchangeable between devices Samples airways, lungs and systemic volatiles (not specific) Requires standardisation of sampling and analysis |
| Urine | Noninvasive Easy to collect with standardised protocols Conducive to longitudinal sampling regimens Ideal for eicosanoids | Distant from the tissue of interest, so biases towards systemic changes in disease Excretion of metabolites may be changed by kidney or liver diseases |
| Lung tissues | Collected from specific area of lung Reflects local changes Essential for transcriptomics analysis Can be combined with immunohistochemistry Results can be compared to genomic and cytology data Complex proteome | Difficult to obtain, either post mortem or using bronchoscopy Contains multiple cellular types, difficult to identify origin of biomarkers Homogenisation of tissue can be difficult Limited quantity of tissue |
SOP: standard operating procedure; NMR: nuclear magnetic resonance.