Iron and CF-related anemia: expanding clinical and biochemical relationships

Abstract

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 patients with 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.

Fig. 1

Hierarchical cluster analysis of patient data. Shown is a heatmap of hematological measures, clinical data, and sputum iron levels for all patients in the study. Parameters are listed at the bottom of the panel. On the right side, patient status is listed (clinical stability: STABLE, clinical deterioration: WORSE). The data presented were transformed logarithmically from the raw data and ranked. Clustering was performed using complete clustering and Pearson correlation coefficients as the distance measure, which permitted grouping of data based on their similarity between adjacent columns or rows. The color key (top left) shows the color scale: red indicates relatively low values and yellow and white relatively high values (i.e., relative to the mean data). The histogram in the legend shows the number of cells achieving a particular rank. The black boxes labeled 1–6 are discussed in the text and highlight clustered sets of data.

Fig. 2

Patients with clinical deterioration display a characteristic profile of iron homeostasis and lung function. Patients were again divided into those with stable signs and symptoms (STABLE) and those with interval clinical worsening (WORSE) and analyzed for plasma iron (A), %FEV1 (B), plasma erythropoietin (C), and sputum iron (D). Patients with worsening clinical status displayed statistically significantly differences in all of these metrics. *P<0.05 for the comparison. In each figure the black horizontal line in the box is the median. The area inside the box shows the 25th–75th percentiles, and the vertical lines represent the minimum and maximum values.

Fig. 3

Relationship of plasma iron to sputum iron and %FEV1. A: Log-transformed plasma iron values are plotted versus log-transformed sputum iron values. R² was calculated as 0.03 (P=0.3), and thus did not indicate any significant correlation between blood and sputum iron levels on a patient-by-patient basis. B: Log-transformed plasma iron values are plotted versus log-transformed %FEV1 values. The relationship between these two parameters is significant (R²=0.48, P=1.0×10⁻⁶). For both plots, patients with worsened clinical features are shown in red and stable patients in green.