Hypoferremia is a marker of disease severity in cystic fibrosis (CF). The effect of systemic antibiotics on iron homeostasis during CF pulmonary exacerbation (CFPE) is unknown. Our central hypotheses were that, by the completion of treatment, serum iron would increase, serum concentrations of interleukin-6 (IL-6) and hepcidin-25, two mediators of hypoferremia, would decrease, and sputum iron would decrease. Methods: Blood and sputum samples were collected from 12 subjects with moderate-to-severe CF (median percent-predicted forced expiratory volume in one second (FEV1%) = 29%; median weight = 56 kg) within 24 hours of starting and completing a course of systemic antibiotics. Results: After treatment, subjects showed median FEV1% and body weight improvements of 4.5% and 2.0 kg, respectively (p <0.05). Median serum iron rose by 2.4 μmol/l (p <0.05), but 75% of patients remained hypoferremic. Median serum IL-6 and hepcidin-25 levels fell by 12.1 pg/ml and 37.5 ng/ml, respectively (p <0.05). Median serum erythropoietin (EPO) and hemoglobin levels were unaffected by treatment. We observed a trend toward lower sputum iron content after treatment. Conclusions: Hypoferremia is a salient characteristic of CFPE that improves with waning inflammation. Despite antibiotic treatment, many patients remain hypoferremic and anemic due to ineffective erythropoiesis.

Summary Introduction This cross-sectional study was conducted to assess the relationship between iron levels in the plasma and sputum of cystic fibrosis (CF) patients. Methods: Demographic, clinical, and iron-related laboratory data were prospectively obtained from 25 patients with stable clinical features and 14 patientswith worsened clinical features since their most recent evaluations. Results Compared to patients with stable clinical features, those who experienced clinical deterioration demonstrated significantly worse lung function and were more frequently malnourished and diabetic. Members of the latter group were also significantly more hypoferremic and had higher sputum iron content than patients with stable clinical features. No significant correlation was found between plasma and sputum iron levels when the groups were analyzed together and separately. Conclusions Sputum iron content does not correlate with iron-related hematologic tests. Hypoferremia is common in CF and correlates with poor lung function and overall health.

Background Iron supplementation for hypoferremic anemia could potentiate bacterial growth in the cystic fibrosis (CF) lung, but clinical trials testing this hypothesis are lacking. Methods Twenty-two adults with CF and hypoferremic anemia participated in a randomized, double-blind, placebo-controlled, crossover trial of ferrous sulfate 325mg daily for 6 weeks. Iron-related hematologic parameters, anthopometric data, sputum iron, Akron Pulmonary Exacerbation Score (PES), and the sputum microbiome were serially assessed. Fixed-effect models were used to describe how ferrous sulfate affected these variables. Results Ferrous sulfate increased serum iron by 22.3% and transferrin saturation (TSAT) by 26.8% from baseline (p <0.05) but did not affect hemoglobin, sputum iron, Akron PES, and the sputum microbiome. Conclusions Low-dose ferrous sulfate improved hypoferremia without correcting anemia after 6 weeks. We did not observe significant effects on sputum iron, Akron PES, and the sputum microbiome. Although we did not identify untoward health effects of iron supplementation, a larger blinded randomized controlled trial would be needed to fully demonstrate safety.

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