A pilot study of cystic fibrosis exacerbation response phenotypes reveals contrasting serum and sputum iron trends

Abstract

The cystic fibrosis (CF) community seeks to explain heterogeneous outcomes of pulmonary exacerbation (PEX) treatment. Serum and sputum inflammatory mediators may identify people with CF (PwCF) at risk for suboptimal responses. However, lack of an established association between response phenotypes and these mediators limits clinical application. In this pilot study, we prospectively characterized treatment response phenotypes by assessing health-related quality-of-life (HRQoL) during PEX. We also measured lung function and iron-related biochemical parameters in serum and sputum. We classified subjects as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) based on the absence or presence, respectively, of worsened symptom scores after initial improvement. We used linear mixed models (LMMs) to determine whether trends in lung function, hematologic, serum, and sputum indices of inflammation differed between response cohorts. In 20 PwCF, we identified 10 SRs and 10 NSRs with no significant differences in lung function at PEX onset and treatment durations. SRs had better model-predicted trends in lung function than NSRs during PEX. Non-linear trends in serum and sputum iron levels significantly differed between SRs and NSRs. In adults with cystic fibrosis, PEX treatment response phenotypes may be correlated with distinctive trends in serum and sputum iron concentrations.

Iron bioavailability regulates Pseudomonas aeruginosa interspecies interactions through type VI secretion expression

“… 24 As predicted, we observed that TseT had no impact on competition in an iron-deficient host environment. However, with the addition of iron at a concentration comparable with what is observed during viral co-infection and pulmonary exacerbations in CF, 17 , 32 , 33 competition with E. coli was significantly increased ( Figure 4A ). This increase in competition was due to the expression of TseT, as strains unable to secrete TseT performed significantly worse in competition in the host environment ( Figure 4A ).…”

“…Iron is a particularly important signal in the CF respiratory tract, as iron concentrations in the airway are increased not only during viral infection but also during pulmonary exacerbations. 32 , 33 As such, P. aeruginosa likely senses changes in iron bioavailability in the airway and responds to these signals by increasing the expression of the TseT effector.…”

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

“…Classification of CF patients in two groups as sustained symptom-responders (SRs) or non-sustained symptom-responders (NSRs) to treatment for a PEX allowed for the study of serum and sputum iron as a biomarker for this response difference [280]. SRs and NSRs had no significant differences in lung function at pulmonary exacerbation onset and treatment durations.…”