Anemia in Cystic Fibrosis (CF): Prevalence, Mechanisms and Correlation with Pulmonary Function.

CF is a chronic disease associated with inflammation and an unknown prevalence of anemia. In other settings anemia is associated with increased morbidity and mortality, and recognition and correction of anemia in CF patients might lead to better outcomes. We hypothesized that chronic inflammation (ACI), iron deficiency (IDA) and malabsorption may be important mechanisms contributing to the anemia in CF patients.

METHODS: Clinical charts and portCF.org visit logs of 218 patients of all ages (1 m to 61 yrs) with CF were reviewed for as many years as charts permitted (range 1–7 yrs). The following data were extracted: CBC, iron studies, pulmonary function tests (PFTs), vitamins A, D, and E levels, creatinine, pertinent medical history, and current medications. Anemia was defined by age- and gender-specific WHO criteria. Patients were considered anemic if low Hb was present on two separate occasions at least two months apart, or average annual Hb met WHO criteria. PFTs in 176 patients (all >6 yrs) included forced expiratory volume (FEV1) and forced vital capacity (FVC) as percent predicted of normal and were considered a reflection of patient performance. The most representative annual PFT from at least 4 annual tests was chosen for analysis since acute infection adversely influences daily performance. Semiannual vitamin levels of 47 adults were correlated with corresponding Hb values.

RESULTS: 61 of 218 patients, ages 1 m to 61 yrs, were anemic (prevalence 28%). The percent of anemia in different age groups varied. Children <11yrs had a prevalence of anemia of 18.5% while adolescents had a prevalence of only 4%. Of 111 adults >18 yrs, 48 were anemic (43%) with a progressive age-related increase in the prevalence of anemia reaching 58% in patients >40 yrs. Complete iron studies were available in 16/48 patients. 7 were identified as IDA, 4 as ACI, and 3 as combined; 2 others had renal failure. In 32 patients, iron studies were incomplete, but renal failure, hemoptysis, hematochezia and solid organ transplants were contributing factors in half. PFTs obtained in 176 patients >7 yrs were compared in anemic and non-anemic patients. Mean FEV1 and FVC at all ages were statistically significantly poorer in the anemic patients (p <0.005). There was no correlation between vitamin levels and Hb. Complete iron studies were also available in 9 non-anemic patients with impaired lung function. 8/9 patients had ferritins <35 ng/ml. Transferrin saturation was <18% in 7 and 21% and 23% in the remaining 2, suggesting relative iron deficiency.

CONCLUSIONS: The prevalence of anemia in CF patients is high and increases with age. In patients for whom iron studies were available, IDA was the prominent underlying mechanism, followed by ACI or a combination of both. There was no correlation between fat soluble vitamin levels and Hb, indicating malabsorption is not a major contributor to the anemia. There was a strikingly significant association between anemia and poor pulmonary function in all age groups. In addition, a group of non-anemic patients with poor lung function had relative iron deficiency. Our results indicate that iron deficiency in anemic CF patients, as well as relative iron deficiency in non-anemic CF patients might be underrecognized and undertreated. Since anemia is associated with poor pulmonary function, correction of anemia should be attempted. Identification of relative iron-deficient states in non- or borderline anemic CF patients with poor lung function could be important since iron supplementation might allow Hb levels to increase as an appropriate response to hypoxia.