Cystic Fibrosis Sputum Rheology Correlates With Both Acute and Longitudinal Changes in Lung Function

Abstract

Cystic fibrosis (CF) airway secretions are abnormal, contributing to decreased clearance and a cycle of infection and inflammation. CF sputum properties may predict disease progression. We hypothesized that sputum viscoelasticity and clearance abnormalities would inversely correlate with pulmonary function during exacerbation and that sputum properties would return to baseline after therapy. We collected sputa longitudinally from 13 subjects with CF with moderate to severe lung disease during both clinical stability and exacerbation. Dynamic rheology was analyzed, using a cone-and-plate rheometer. Mucociliary clearability was measured on mucus-depleted frog palate, cough clearability in a simulated cough machine, and sputum hydration as percent solids was measured following lyophilization. Elastic modulus G' and viscous modulus G'' increased during exacerbation and returned to baseline levels with recovery (P< .05 for both). Solid content did not change. Sputum mucociliary clearability decreased during exacerbations (P< .01) but not cough clearance. FEV1 %predicted was inversely correlated with G' and G'' (P< .01 for both). The regression slope of the natural log-transformed G' and G'' vsFEV1 %predicted was statistically homogeneous among subjects (estimated common slope m= -3.84, P< .001 and m= -8.53, P< .0001, respectively). Among these subjects with CF, there is a striking identity of the slope defining the relationship between ln G' or ln G'' and FEV1. There are dramatic increases in dynamic viscosity and elasticity during a pulmonary exacerbation with return to baseline at recovery. This suggests that sputum viscoelastic properties are tightly associated with lung function and disease status.