Abstract Background Transferrin saturation is widely considered the preferred screening test for hemochromatosis. Unsaturated iron-binding capacity has similar performance at lower cost. However, the ...within-person biological variability of both these tests may limit their ability at commonly used cut points to detect HFE C282Y homozygous patients. Methods The Hemochromatosis and Iron Overload Screening Study screened 101,168 primary care participants for iron overload using transferrin saturation, unsaturated iron-binding capacity, ferritin, and HFE C282Y and H63D genotyping. Transferrin saturation and unsaturated iron-binding capacity were performed at initial screening and again when selected participants and controls returned for a clinical examination several months later. A missed case was defined as a C282Y homozygote who had transferrin saturation below the cut point (45% for women, 50% for men) or unsaturated iron-binding capacity above the cut point (150 μmol/L for women, 125 μmol/L for men) at the initial screening or the clinical examination, or both, regardless of serum ferritin. Results There were 209 C282Y previously undiagnosed homozygotes with transferrin saturation and unsaturated iron-binding capacity testing performed at the initial screening and clinical examination. Sixty-eight C282Y homozygotes (33%) would have been missed at these transferrin saturation cut points (19 men, 49 women; median serum ferritin level of 170 μg/L; first and third quartiles, 50 and 474 μg/L), and 58 homozygotes (28%) would have been missed at the unsaturated iron-binding capacity cut points (20 men, 38 women; median serum ferritin level of 168 μg/L; first and third quartiles, 38 and 454 μg/L). There was no advantage to using fasting samples. Conclusions The within-person biological variability of transferrin saturation and unsaturated iron-binding capacity limits their usefulness as an initial screening test for expressing C282Y homozygotes.
Abstract Purpose We sought to determine the prevalence of elevated measures of iron status in African Americans and whether the combination of serum ferritin concentration >200 μg/L for women or >300 ...μg/L for men and transferrin saturation in the highest quartile represents increased likelihood of mutation of HFE , self-reported iron overload or self-reported liver disease. Subjects and Methods A cross-sectional observational study of 27,224 African Americans ≥25 years of age recruited in a primary care setting was conducted as part of the multi-center, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study. Measurements included serum ferritin concentration, transferrin saturation, testing for HFE C282Y and H63D, and self-reported iron overload and liver disease. Results Serum ferritin concentration >200 μg/L for women or >300 μg/L for men occurred in 5263 (19.3%) of African Americans, while serum ferritin concentration in this range with highest-quartile transferrin saturation (>29% women; >35% men) occurred in 1837 (6.7%). Adjusted odds of HFE mutation (1.76 women, 1.67 men), self-reported iron overload (1.97 women, 2.88 men), or self-reported liver disease (5.18 women, 3.73 men) were greater with elevated serum ferritin concentration and highest-quartile transferrin saturation than with nonelevated serum ferritin concentration (each P <.05). Conclusions Serum ferritin concentration >200 μg/L for women or >300 μg/L for men in combination with transferrin saturation >29% for women or >35% for men occurs in approximately 7% of adult African American primary care patients. Patients with this combination of iron test results should be evaluated for increased body iron stores or liver disease.
Background The diagnostic gold standard for neuroendocrine cell hyperplasia of infancy (NEHI) is demonstration of increased numbers of neuroendocrine cells (NECs) amid otherwise near-normal lung ...histology. Typical clinical and radiographic features often are present. However, NECs are also increased after lung injury and in other disorders, which can complicate biopsy specimen interpretation and diagnosis of suspected NEHI. Our objective was to determine whether NEC prominence is specific for the diagnosis of NEHI. Methods Bombesin immunoreactivity was quantified in lung biopsy specimens from 13 children with characteristic clinical presentation and imaging appearance of NEHI. The primary comparison group was 13 age-matched patients selected from children with lung disorders that are known to be associated with NEC prominence. Results Bombesin-immunopositive epithelial area was significantly increased in NEHI compared with other diseases. Patchy bronchiolar inflammation or fibrosis was frequently observed in NEHI, with no direct association between airway histopathology and bombesin-immunopositive area. NEC prominence correlated with severity of small airway obstruction demonstrated on infant pulmonary function testing. Immunohistochemical colocalization of bombesin with Ki67 did not reveal active NEC proliferation. There was wide intra- and intersubject variability in NEC number, which did not relate to radiographic appearance of the region biopsied. Conclusions Our findings demonstrate that NEC prominence is a distinguishing feature of NEHI independent of airway injury. The extent of intrasubject variability and potential for overlap with control subjects suggest that clinical-radiologic-pathologic correlation is required for diagnosis and that the abundance of NECs may not fully explain the disease pathogenesis.
Objective To assess the effects of Pseudomonas aeruginosa and Staphylococcus aureus infection on lower airway inflammation and clinical status in young children with cystic fibrosis (CF). Study ...design We studied 111 children age < 6 years who had 2 P aeruginosa –positive oropharyngeal cultures within 12 months. We examined bronchoalveolar lavage fluid (BALF) inflammatory markers (ie, cell count, differential, interleukin IL-8, IL-6, neutrophil elastase), CF-related bacterial pathogens, exotoxin A serology, and clinical indicators of disease severity. Results Young children with CF with both upper and lower airway P aeruginosa infection had higher neutrophil counts, higher IL-8 and free neutrophil elastase levels, increased likelihood of positive exotoxin A titers, and lower Shwachman scores compared with those with positive upper airway cultures only. S aureus was associated with increased lower airway inflammation, and the presence of both P aeruginosa and S aureus had an additive effect on concentrations of lower airway inflammatory markers. BALF markers of inflammation were increased with the number of different bacterial pathogens detected. Conclusions Young children with CF who have upper and lower airway P aeruginosa infection have increased endobronchial inflammation and poorer clinical status compared with those with only upper airway P aeruginosa infection. The independent and additive effects of S aureus on inflammation support the significance of polymicrobial infection in early CF lung disease.
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