Proteomics can give translational views to guide therapeutic decision-making and disclose molecular disease pathways. Although the cystic fibrosis airway proteome has been described in a number of publications in the past, the association with the severity of lung disease has not been defined. For a study, researchers sought to determine the abnormalities in the CF sputum proteome linked to disease severity and find prospective disease markers with potential for translation.

Using liquid-chromatography tandem mass spectrometry, sputum samples from healthy volunteers and cystic fibrosis patients (some receiving modulator treatments) were analyzed. Baseline spirometry (percentage predicted forced expiratory volume in 1 s, FEV1%) was used to determine the severity of lung disease.

In CF patients (n = 38) and healthy volunteers (n = 32), there were differences in the expression of specific sputum proteins (108 increased; 202 reduced). Differences in sputum proteome were shown to be related to increasing lung function decline using principal component analysis and hierarchical clustering. Baseline FEV1% was linked with 87 proteins in CF patients (positive correlation n = 20, negative correlation n = 67); the majority were either produced from neutrophils or resisted neutrophil-driven oxidant and protease activities.

Progressive lung function degradation caused predictable and quantitative alterations in the CF sputum proteome, some of which may be useful as indicators of disease severity in CF sputum. It was necessary to research these indicators’ clinical value and validate them in other patient cohorts.