Dietary iron overload in southern African rural blacks

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum ferritin concentrations in black miners.

Serum ferritin concentrations were measured in 651 Black male miners who originated from rural areas throughout southern Africa and who were aged between 17 and 57 years. The mean serum ferritin concentration of 229 microgram/l was above the normal range reported for White subjects, and in 52,8% of the subjects the values were greater than 200 microgram/l. The serum ferritin concentration rose with age, as did the proportion of subjects in each age group who exhibited high values (more than 200 microgram/l). The lowest mean ferritin concentration (112 microgram/l) as well as the lowest proportion of high values (22,9%) were found in subjects from the most northerly area studied. Similarly, the highest mean proportion of high values (66,3%) was seen in the most southerly group studied. Calculations from the present data suggest that the degree of iron overload is currently greater in rural than in urban Black male subjects.     

Effect of body iron stores on serum aluminum level in hemodialysis patients.

To evaluate the influence of body iron stores on the serum aluminum (Al) level, we studied the correlation between iron status (the serum ferritin, serum iron and transferrin saturation) and serum Al levels in 68 severely anemic hemodialysis patients. Among them, 36 underwent the desferrioxamine (DFO) mobilization test. These 68 patients were divided into three groups according to their serum ferritin level. The basal Al level in the patient group was 41.4 +/- 37.4 micrograms/l (control, 4.1 +/- 2.4 micrograms/l). The serum Al level after DFO infusion of the patient group was 111.1 +/- 86.8 micrograms/l. A significantly higher basal Al and peak Al level after DFO infusion were found in group 1 patients (serum ferritin less than 300 micrograms/l) when compared to group 2 (serum ferritin 300-1,000 micrograms/l) and group 3 (serum ferritin greater than 1,000 micrograms/l) patients. A significant negative correlation between serum ferritin and basal serum Al (r = -0.544, p = 0.0001), as well as peak serum Al after DFO infusion (r = -0.556, p = 0.0001), was noted. Similarly, a negative relationship between serum Al (both basal and peak) and either serum iron or transferrin saturation was noted. However, there was no correlation between the serum Al level and the dosage of aluminum hydroxide. In conclusion, serum ferritin, serum iron and transferrin saturation were inversely correlated with serum Al in our hemodialysis patients. Iron deficiency may probably increase Al accumulation in these patients.     

An evaluation of the Ramco kit for serum ferritin assay

The determination of serum ferritin levels may be of diagnostic importance in medicine. To establish whether values obtained using a commercially available kit (Ramco) were adequate for this purpose, a comparison was undertaken using a two-site immunoradiometric assay that had been developed and standardized in our laboratories. Over the range 6 micrograms/l to greater than 2 000 micrograms/l there was a correlation coefficient between the two methods of 0,8284 (P less than 0.001). It is concluded that the Ramco kit is suitable for use in clinical practice.     

Serum beta-2-microglobulin in the differential diagnosis of monoclonal gammopathies

Serum beta-2-microglobulin (B2m) concentrations were determined in 43 southern African black patients with multiple myeloma (MM), in 130 black patients with monoclonal gammopathy of undetermined significance (MGUS) and in 70 control subjects. The results showed median values for serum B2m in patients with MM, MGUS and the control group to be 8.10 mg/l, 3.05 mg/l, and 2.35 mg/l, respectively; these values differed significantly from one another (P less than 0.01), even when patients with normal renal function (serum creatinine value less than 110 mumol/l) were considered separately. The median serum B2m concentration for IgG MM (22 cases) was 4.3 mg/l, for IgA MM (8 cases) 7.3 mg/l, and 24.2 mg/l for Bence Jones MM (12 cases). These differences were also significant (P = 0.001), but not in the restricted group of MM patients with normal renal function. In the 43 MM patients serum B2m concentrations had a significant positive correlation with serum creatinine (r = 0.706; P less than 0.005) and a significant negative correlation with haemoglobin values (r = -0.459; P = 0.006). In 28 MM patients with normal renal function, serum B2m values had a significant negative correlation with serum albumin (r = -0.602, P = 0.003). Sixty-five per cent of the 43 MM patients and 18.5% of the MGUS patients had raised serum B2m values (greater than 4.7 mg/l). An optimum cut-off value for serum B2m of 6.9 mg/l for differentiating MM from MGUS was determined using a classification rule. Despite lacking specificity, serum B2m measurement was useful in differentiating MM from MGUS, and was the best second choice variable in relation to serum albumin and haemoglobin in patients with normal renal function.     

Critical role of iron overload in the increased susceptibility of haemodialysis patients to bacterial infections. Beneficial effects of desferrioxamine

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.     

Assessment of iron status by erythrocyte ferritin in uremic patients with or without recombinant human erythropoietin therapy.

Erythrocyte ferritin may be a better estimator of iron bioavailability than the conventional markers of iron stores (serum ferritin and transferrin saturation). To investigate the accuracy of these conventional markers in uremic patients compared with erythrocyte ferritin, we studied 29 chronic hemodialysis patients on erythropoietin (EPO) therapy, 18 without EPO therapy, and 22 healthy control subjects. Apart from the red blood cell indices, serum ferritin, transferrin saturation, and erythrocyte ferritin, the analytical study included red blood cell protoporphyrin and plasma aluminum levels. The control group showed erythrocyte ferritin concentrations between 8.3 and 12.5 attograms/cell (95% confidence interval). In the EPO group, red blood cell protoporphyrin correlated negatively with erythrocyte ferritin, but not with serum ferritin or transferrin saturation. In the non-EPO group, serum ferritin, erythrocyte ferritin, and transferrin saturation did not correlate with red blood cell protoporphyrin. Even though erythrocyte ferritin correlated well with serum ferritin in the EPO group (r = 0.61, P = 0.0003), the sensitivity of normal serum ferritin levels (30 to 300 ng/mL) to discard a low erythrocyte ferritin concentration (erythrocyte ferritin less than 7 ag/cell) was 0.53, while the sensitivity of serum ferritin at levels less than 30 ng/mL to indicate an absolute iron deficiency expressed as a low erythrocyte ferritin concentration was 0.28. Only values of serum ferritin and transferrin saturation greater than 300 ng/mL and 35%, respectively, could rule out a relative iron deficiency expressed as a low erythrocyte ferritin and high red blood cell protoporphyrin concentration. Plasma aluminum levels did not correlate with red blood cell protoporphyrin or erythrocyte ferritin levels in either uremic group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutritional anaemia in 11-year-old schoolchildren in the western Cape

A nutritional anaemia survey was carried out on 610 11-year-old coloured, black and white schoolchildren in urban and rural communities in the western Cape. The mean (+/- 1 SD) haemoglobin concentration was 13.0 +/- 1.2 g/dl. The coloured and black subgroups considered together had a significantly lower mean haemoglobin concentration than the white subgroup (12.8 +/- 1.2 g/dl v. 13.4 +/- 1.0 g/dl) (F = 37.47; P less than 0.0001). The urban population as a whole had a significantly lower geometric mean (1 SD range) serum ferritin concentration than the rural population (25.6 (13.5-48.6) micrograms/l v. 34.1 (21.3-54.6) micrograms/l) (F = 42.94; P less than 0.0001). The lowest geometric mean serum ferritin values were found in the urban coloured (23.1 (11.5-46.4) micrograms/l) and urban black schoolchildren (23.7 (13.2-42.6) micrograms/l), with figures of less than 12 micrograms/l in 11.7% and 12.5% respectively. Although 28% of the children had red cell folate values below the recommended lower limit of normal (175 ng/ml), probability plot analysis of the data suggested that folate deficiency was not a major problem in the study population. The calculated daily iron and folate intakes were below the age-related recommended dietary allowance (RDA) in all the subgroups, yet anaemia was relatively uncommon. These findings suggest that the RDA values are too high. Overall the prevalence of nutritional anaemia was low and only the urban coloured subgroup showed significant second populations with low haemoglobin and serum ferritin measurements.     

Ascorbic acid does not augment the restoration effect of iron treatment for empty iron stores in patients after gastrointestinal surgery

The effect of a 6-week combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) on the empty iron stores in 20 patients after gastrointestinal surgery was examined from changes of serum ferritin. One group of 20 patients with similar clinical characteristics served as controls. The treatment replaced the empty iron stores. Since mean serum ferritin concentrations increased from 9 +/- 8 to 29 +/- 11 micrograms/l (P less than 0.001) in males and from 8 +/- 8 to 26 +/- 10 micrograms/l (P less than 0.001) in the females. Also blood hemoglobin and serum iron concentrations increased significantly (P less than 0.01). Among the controls there were no marked changes in serum ferritin, blood hemoglobin or serum iron concentrations. However, the increase of serum ferritin caused by this combined treatment was similar with that caused previously by pure ferrous sulfate treatment. Thus, it is considered that the combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) restores the empty iron stores in patients after gastrointestinal surgery, but that the increase is not augmented by the ascorbic acid. Thus, a pure iron therapy is recommended to fill up the empty iron stores in these patients.     

Alcohol consumption among South African blacks and its relationship to iron overload

The drinking habits of 123 black men (28 from Cape Town and 95 from Pietermaritzburg) were recorded, and their weekly alcoholic iron intakes calculated. Serum ferritin levels and liver function were measured in 57 subjects (Cape Town 12, Pietermaritzburg 45). Sorghum beer, with its high iron content, was considerably more popular in Pietermaritzburg than Cape Town, and the weekly iron consumption in Pietermaritzburg was significantly higher (P less than 0.05) than in Cape Town. The serum ferritin level was significantly higher in Cape Town than in Pietermaritzburg (P less than 0.05), no significant correlation being found between iron intake and serum ferritin. Age was positively correlated with serum ferritin (P less than 0.01). Of the subjects studied, 74% had abnormal lactate dehydrogenase levels. These results are considered in the light of the numerous problems associated with this type of project. The need for prospective studies in order to demonstrate a causal relationship between alcoholic iron intake and iron overload is emphasized.     

Relationship between serum nickel concentrations and anaemia in chronic haemodialysis patients

Thirty chronic haemodialysis patients were examined with respect to the relationship between renal anaemia and serum nickel concentrations. Red blood cell counts, haemoglobin values, haematocrit values, serum iron values, serum ferritin levels and serum nickel concentrations were measured. No significant relationships were found between serum nickel levels and serum iron values or serum ferritin levels. Dialysis anaemia was found to have a significant correlation with serum nickel concentrations in chronic haemodialysis patients.     

Phenotypic expression of the HLA-linked iron-loading gene in the Afrikaner population of the western Cape

A previous study conducted on a group of Afrikaans-speaking subjects in the south-western Cape indicated a high frequency (0.115) of the HLA-linked iron-loading gene which causes idiopathic haemochromatosis. The results of phenotypic and genotypic studies on the first degree relatives of identified homozygotes and heterozygotes are now reported. There was considerable heterogeneity of phenotypic expression in the group of heterozygotes, with overlap between the homozygous and heterozygous subjects. The heterozygous relatives of heterozygous index cases, who had been identified on the basis of a serum ferritin concentration greater than 400 micrograms/l, appeared to have more frequent and more marked abnormalities of iron measurements than the heterozygote relatives of homozygous index cases (serum ferritin value greater than 400 micrograms/l, percentage transferrin saturation greater than 60). This suggests that the screening test was identifying a group of more significantly affected heterozygotes, with biochemical abnormalities that overlapped with the identified homozygotes. The index cases were followed up over a period of 5 years and during this time the 7 subjects diagnosed as heterozygotes showed a progressive increase in serum ferritin concentrations, which suggests some iron accumulation. Individual pedigrees included instances of gene recombination within the major histocompatibility complex, and of probable false-positive genotype assignment. The overall results confirm a high frequency of the gene in this particular community.     

Increase of body iron stores estimated by the increase of serum ferritin concentration during a treatment of 200 mg Fe++ daily after gastrointestinal surgery

A 6-week iron therapy of 200 mg Fe++ daily was given to 13 men and 12 women who had previously undergone various kinds of common gastrointestinal surgery and who had empty iron stores estimated from low serum ferritin concentration. The results were compared with those of a control group corresponding to the study group in respect of sex, number of patients, primary disease, previous operation, empty iron stores (serum ferritin), blood hemoglobin, serum iron, sedimentation rate, blood leukocytes, serum transferrin, folate and vitamin B12. The iron therapy restored the lack of body iron, for the serum ferritin concentrations increased from 12 +/- 7 to 30 +/- 11 micrograms/l (p less than 0.001) in the men and from 10 +/- 6 to 30 +/- 12 micrograms/l (p less than 0.001) in the women, whereas the corresponding changes in the control group were from 10 +/- 9 to 11 +/- 8 micrograms/l and from 11 +/- 8 to 13 +/- 11 micrograms/l in the men and women, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum ferritin levels after renal transplantation: a prospective study

A prospective study was made of the evolution of serum ferritin levels in 112 renal transplant recipients with good graft function. The rise in hemoglobin value is accompanied by a decrease in basal serum ferritin levels which are lowest at the sixth month: 54.9 (2-1,516) vs. 109.6 (21-4,420) micrograms/l, p less than 0.001 (Xg and range). After this time, ferritin values increase, although they do not reach basal levels. Evolution after transplantation is mainly determined by the previous state of iron stores at the time of transplantation. While in the patients with high basal serum ferritin values these gradually decreased during the follow-up period, patients with low basal serum ferritin levels tend to replenish their iron stores after renal transplantation. These differences disappear at the third year when serum ferritin values are similar in all groups. An association between persistence of posttransplant anemia and low serum ferritin levels is observed. This event is not clinically relevant as anemia disappears in almost all cases and dietary iron is enough to normalize serum ferritin levels.     

Clinical significance of serum and urinary neopterins in patients with chronic renal disease

To determine the clinical significance of serum and urinary neopterins in patients with chronic renal disease, we measured these values using IMMUtest Neopterin RIA kits. Serum neopterin levels in patients with chronic glomerulonephritis (CGN) (10.2 +/- 8.1 nmol/l) and in those with chronic renal failure (CRF) (109 +/- 90) were significantly increased compared with the control subjects (C) (4.2 +/- 2.4) (p less than 0.001). The levels of serum neopterins in patients on chronic hemodialysis (HD) (212 +/- 106) were increased almost twofold compared with CRF (p less than 0.001). In CGN and CRF, a strong positive correlation was demonstrated between serum neopterin levels and serum creatinine concentrations (r = 0.95, p less than 0.001). In HD patients, neopterin levels and serum were not correlated with the length of time on dialysis. The urinary neopterin excretion ratios (urinary neopterin/urinary creatinine level) in CRF (227 +/- 114 mumols/molCr) were significantly increased compared with C (116 +/- 43) (p less than 0.01). A significantly negative correlation was observed between the urinary neopterin levels and the creatinine clearance in CGN and CRF (p less than 0.01). These data suggest that, in patients with chronic renal disease, the neopterin levels in serum are closely linked with glomerular filtration rate and yet the urinary neopterin/creatinine ratios may reflect the predominance of increased tubular secretion of neopterin over the renal injury per se.     

High serum osteoprotegerin levels in patients with hyperthyroidism: effect of medical treatment

This study was aimed at evaluating serum osteoprotegerin (OPG) concentrations in a cohort of patients with hyperthyroidism before and after methimazole (MMI) treatment. One hundred fourteen hyperthyroid patients [93 with Graves disease (GD) and 21 with toxic nodular goitre (TNG)] and 68 matched for sex and age healthy subjects were evaluated for serum free-thyroxine (FT4), free-triiodiothyronine (FT3), thyrotropin (TSH), TSH receptor antibodies (TRAb), bone alkaline phosphatase (BALP), C-telopeptides of type-1 collagen (CrossLaps), OPG levels, and bone mineral density (BMD). In hyperthyroid patients, the biochemical evaluations were performed before and after 6 and 12 months of MMI treatment, whereas BMD was measured at baseline and after 12 months of treatment. Hyperthyroidism was more severe in GD than TNG patients. Serum OPG levels were found to be significantly higher in hyperthyroid patients than in the healthy subjects (4.3 pmol/l, range: 1.6-12.0, vs. 2.2 pmol/l, range: 1.4-6.0; P < 0.001), the values being higher in GD patients than TNG. A significant correlation between serum OPG levels and age was found in the healthy subjects (r: 0.48; P < 0.001) but not in hyperthyroid patients (r: -0.03; P = 0.8). In the healthy subjects, serum OPG levels were also positively correlated with both serum FT4 (r: 0.23; P = 0.03) and FT3 (r: 0.24; P = 0.04) levels. In hyperthyroid patients, however, serum OPG was still correlated with FT3 levels (r: 0.38; P < 0.001), whereas the correlation with serum FT4 was lost (r: 0.19; P = 0.06). In hyperthyroid patients, but not in the healthy subjects, serum OPG levels were correlated positively with CrossLaps (r: 0.20; P = 0.03) and negatively with BALP (r: -0.24; P = 0.01) and BMD (r: -0.33; P = 0.01). After 6 months of MMI treatment, serum OPG concentrations decreased significantly in TNG patients (from 3.5 pmol/l, range: 1.6-8.0, to 2.3 pmol/l, range: 1.0-4.3; P < 0.001), whereas a not significant change in OPG levels occurred in GD patients (from 4.8 pmol/l, range: 1.8-12.0, to 4.2 pmol/l, range: 1.0-14.0; P = 0.7). At Month 12 of treatment, serum OPG concentrations were significantly lower than those measured at baseline in both TNG (2.5 pmol/l, range: 1.0-3.1, vs. 3.5 pmol/l, range: 1.6-8.0; P < 0.001) and GD (2.1 pmol/l, range: 1.0-8.6, vs. 4.8 pmol/l, range: 1.8-12.0; P < 0.001). At this time, no significant differences in serum OPG, CrossLaps, and BALP values were found between patients and control subjects. At the end of follow-up, BMD was higher than those measured at baseline but still significantly lower than those measured in the control subjects. This study shows that hyperthyroid patients have serum OPG concentrations significantly higher in comparison with euthyroid subjects, in relation to thyroid hormone excess and high bone turnover. Medical treatment of hyperthyroidism normalizes serum OPG levels in temporal relationship with the normalization of bone metabolism markers, even in presence of persistent abnormal bone structure as determined by ultrasonography.     

Nutritional anaemia in pregnant coloured women in Johannesburg

A nutritional anaemia survey was carried out in 224 pregnant coloured first-time attenders at Coronation Hospital antenatal clinic in Johannesburg during the second quarter of 1986. None had received any form of nutritional supplementation during pregnancy. Haemoglobin concentrations less than 11 g/dl were present in 18.9% of women in the third trimester of pregnancy, while 64% had a saturation of transferrin value of less than 16% and 68% a serum ferritin level less than 12 micrograms/l. Calculations suggested that mean iron stores in the first trimester were 228 mg, with 37.5% of women having absent stores. Comparable figures in the second and third trimesters were 74 mg and -92 mg respectively. The fact that many were iron deficient in the first trimester indicates a high frequency of iron deficiency in non-pregnant women in this population group. Although 20.8% of the women had red cell folate values below the normal range for non-pregnant subjects, folate deficiency did not appear to be a significant problem. Vitamin B12 deficiency was very uncommon.     

Endogenous erythropoietin levels and anemia in long-term renal transplant recipients

BACKGROUND/AIM: Although anemia is a common complication after renal transplantation (RT), data concerning endogenous erythropoietin (EPO) levels in long-term RT recipients are rare. The goal of this study was to evaluate the prevalence of anemia within 6 months to 5 years after RT and to assess the relationship between the serum concentrations of endogenous EPO, graft function and grade of improvement of anemia. METHODS: 140 patients who had undergone RT were included in the group: 89 males (63.6%) and 51 females (36.4%), with an average age 46.8 +/- 12.8 years. The serum concentrations of EPO and creatinine (Cr) were tested in all the individuals and the values of the red blood component of blood count, serum ferritin (SF), plasma iron concentration, plasma total iron-binding capacity (TIBC), transferrin saturation (TS), folic acid and vitamin B(12) levels in the serum were determined. A statistical analysis of the results was performed using the correlation analysis, Mann-Whitney U test and Duncan's multiple range test. RESULTS: Normal blood count values were found in 91 patients (65%), and a mild grade of anemia with a mean hemoglobin (Hb) 114.4 +/- 11.9 g/l was observed in 45 patients (32.1%), and 4 patients (2.9%) fulfilled the diagnostic criteria for post-transplantation erythrocytosis. Individuals with normal Hb values had a mean EPO serum concentration of 39.3 +/- 12.3 mU/ml (median 37.2) and the mean Cr was 133.8 +/- 36.9 micromol/l (median 122). Patients with anemia (Hb <120 g/l in females, Hb <130 g/l in males) had a mean EPO value of 47.0 +/- 26.6 mU/ml (median 36.0) and a mean Cr of 203.8 +/- 108.9 micromol/l (median 181). The difference in the Cr values was statistically significant (p < 0.0001), while the difference between the EPO concentrations was not significant. No relation of EPO serum concentration with regard to graft function was found in the analysis. A lack of storage iron (SF <10 microg/l in females, SF <22 microg/l in males) was found in 16 patients (11.4%), and a lack of functional iron (TS <20%) was found in 27 patients (19.3%). CONCLUSIONS: Theprevalence of anemia in patients after transplantation was 32.1%. The most common cause of anemia is insufficient graft function development. The achieved values of the red component of blood count have no relation to the endogenous EPO serum concentrations.     

Hyaluronan and type III procollagen peptide concentrations in bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis.

The connective tissue components hyaluronan (hyaluronic acid) and type III procollagen peptide were measured in bronchoalveolar lavage fluid in 22 patients with idiopathic pulmonary fibrosis and 21 healthy control subjects. The patients with idiopathic pulmonary fibrosis had higher concentrations of hyaluronan (median 46 micrograms/l) and type III procollagen peptide (median 0.45 micrograms/l) than the healthy controls (9 and less than 0.02 micrograms/l; p less than 0.001). The patients had normal serum concentrations of hyaluronan and of the procollagen peptide, and albumin concentrations in lavage fluid similar to those of the control subjects. Neutrophil and lymphocyte counts in lavage fluid were increased on average 10 and two fold respectively in the patients with idiopathic pulmonary fibrosis and both correlated with the amount of hyaluronan recovered (p less than 0.05). An inverse correlation was seen between the transfer factor for carbon monoxide and hyaluronan concentrations in lavage fluid in the patients (p less than 0.05). Deterioration in lung function and radiographic progression were seen over six months in 12 of the patients. These patients had higher lavage fluid concentrations of hyaluronan and type III procollagen peptide than the patients whose disease was stable (p less than 0.01). Increased synthesis of hyaluronan and type III procollagen peptide in lung parenchyma may reflect activation or proliferation (or both) of pulmonary fibroblasts in idiopathic pulmonary fibrosis and seems to be linked to the severity and activity of the lung disease.