Serum and Sputum Iron Trends Distinguigh Responders and Non-Responders to Treatment of Cystic Fibrosis Pulmonary Exacerbation

Abstract Background: The cystic fibrosis (CF) community seeks to explain the heterogeneity of pulmonary exacerbation (PEX) treatment outcomes. Studies suggest that certain substances in serum and sputum offer objective evidence of PEX onset in people with CF (PwCF) and identify those at risk for inadequate treatment responses. However, it is clinically impractical to measure most of these substances, and a lack of correlative clinical information limits their utility as drivers of medical decision-making. Here, we questioned whether routinely available indices of iron homeostasis and systemic inflammation could identify PwCF with and without sustained symptom and lung function responses to PEX treatment. Methods: We prospectively evaluated health-related quality-of-life (HRQoL) and lung function and measured biochemical indices associated with iron homeostasis in serum and sputum in twenty adults during a PEX cycle. 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 following initial improvement during PEX treatment. We used linear mixed models (LMMs) to explore whether treatment-related trends in lung function and hematologic and sputum parameters of interest differed between SRs and NSRs.Results: We identified ten SRs and ten NSRs. Subjects were adults with baseline lung function and symptom burden similar to other CF cohorts in the literature. SRs and NSRs were treated for similar durations. SRs had higher model-predicted trends in lung function than NSRs during treatment. Serum interleukin-6 (IL-6) and serum hepcidin-25 fell during treatment in SRs and NSRs. Trends in serum and sputum iron levels differed significantly between SRs and NSRs. Conclusions: In adults with CF treated for PEX, symptomatic non-response may be associated with lack of lung function improvement, initial increase but terminal decline in serum iron concentration, and initial decline but terminal increase in sputum iron concentration. Future work is needed to confirm the findings and understand possible mechanisms for these alterations in iron homeostasis during CF PEX.