Methods of classifying pleural fluid are disclosed. The methods typically include determining the level of indicator nanoparticles, such as lipids, particularly large lipids, in the pleural fluid of a subject. The level of lipids can be determined by nuclear magnetic resonance (NMR), such as proton NMR (1H-NMR) by measuring the NMR signal corresponding to methyl protons, methylene protons, methene protons, or combinations thereof. The level of large lipids in pleural fluid can be carried out in vitro on a sample of pleural fluid obtained from the subject or in vivo using magnetic resonance spectroscopy (MRS). The pleural fluid can be classified as exudate or transudate with a sensitivity, selectivity, or combination thereof of 85%, 90%, 95%, 99%, or higher, a selectivity of 85%, 90%, 95%, 99%. The method can be coupled with diagnosing and/or treating the subject with a disease, disorder, or condition.