Sputum Analysis Could Be an Alternative Source of Biomarkers for IPF

Measuring disease-associated factors in sputum may be a less invasive way of tracking molecular changes in idiopathic pulmonary fibrosis (IPF) than bronchoalveolar washing, which involves sucking material from the lungs with a syringe, according to a study.

Researchers found several factors in IPF patients at higher levels than in healthy people and patients with chronic obstructive pulmonary disease (COPD). Some of the factors might be used as biomarkers of disease severity, they said.

The study, “Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7,” was published in the journal PLOS ONE.

Researchers at University Hospital Center Liège and the University of Liège in Belgium compared 15 patients with IPF to 30 healthy volunteers and 32 patients with COPD. The COPD patients were included since the condition also involves fibrotic processes, but in the airway wall rather than the lungs.

All participants inhaled salbutamol and saline to trigger coughing, allowing researchers to collect sputum. Salbutamol is an aerosol that opens up the airways.

When analyzing liquid collected during bronchoalveolar washing, researchers usually check cells. The research team wondered if the same could be done with sputum.

They found that IPF patients had higher numbers of several types of immune cells and epithelial cells — which line the lungs’ walls — in their sputum than controls. The cell count did not differ between IPF and COPD patients.

Next, the team analyzed the presence of factors the lungs secrete. Multiple factors were at higher levels in IPF patients than controls, and one called MMP-7 was also higher in IPF than COPD patients. Gene expression analyses confirmed that the genes that trigger most of these factors were more active than normal.

Several of the factors, including TGF- beta, IL-8, KL-6 and MMP-7, were examined in fibrotic processes in earlier studies. IPF patients had higher levels of them in both serum samples and bronchoalveolar washing fluid. This suggests that sputum analysis may also be a way to examine lung fibrosis patients.

Although cell analysis confirmed that inflammatory processes were very active, the proportions of inflammatory cells differed from those usually seen in bronchoalveolar washing fluid.

Importantly, the levels of two of the factors, KL-6 and MMP-7, correlated with total lung volume of IPF patients, but not controls. Since the study compared the groups at only one time point, researchers underscored that patients need to be followed over time to confirm that the factors are true predictors of lung volume, and thus disease severity.