Proteomics of severity of lung damage in CF

Maher RE, Barrett E, Beynon RJ, Harman VM, Jones AM, McNamara
PS, Smith JA, Lord RW. (2022) The relationship between lung disease severity and the sputum proteome in cystic fibrosis. Respir Med. 2022 Nov-Dec;204:107002. doi: 10.1016/j.rmed.2022.107002.

BACKGROUND: Proteomics can reveal molecular pathways of disease and provide
translational perspectives to inform clinical decision making. Although several
studies have previously reported the cystic fibrosis airway proteome, the
relationship with severity of lung disease has not been characterised. The
objectives of this observational study were to investigate differences in the CF
sputum proteome associated with disease severity and identify potential markers
of disease with translational potential.
METHODS: Sputum samples from healthy volunteers and cystic fibrosis subjects
(some prescribed modulator therapies) were analysed using liquid-chromatography
tandem mass spectrometry. Severity of lung disease was based on baseline
spirometry (percentage predicted forced expiratory volume in 1 s, FEV1%).
RESULTS: Multiple sputum proteins (108 increased; 202 decreased) were
differentially expressed in CF (n = 38) and healthy volunteers (n = 32). Using
principal component analysis and hierarchical clustering, differences in sputum
proteome were observed associated with progressive lung function impairment. In
CF subjects, baseline FEV1% correlated with 87 proteins (positive correlation
n = 20, negative n = 67); most were either neutrophil derived, or opposed
neutrophil-driven oxidant and protease activity.
CONCLUSION: Predictable and quantifiable changes in the CF sputum proteome
occurred associated with progressive lung function impairment, some of which
might have value as markers of disease severity in CF sputum. Further work
validating these markers in other patient cohorts and exploring their clinical
utility is needed.