Indices of iron homeostasis correlate with airway obstruction in an NHANES III cohort

Figures & data

Table 1 Characterization of the study population

Group	N	Percentage
Total	7,251	100
Smoking status
Non-smoker	4,702	64.9
Smoker	2,549	35.2
Race
White	4,972	68.5
Black	1,999	27.6
Other	280	3.9
Gender
Male	3,016	41.6
Female	4,235	58.4
Age
20–29 years	1,855	25.6
30–39 years	1,696	23.4
40–49 years	1,166	16.1
50–59 years	732	10.1
60–69 years	829	11.4
70–79 years	553	7.6
80–89 years	380	5.2
90 years and older	40	0.6
FEV1/FVC
>75%	5,519	76.1
60%–<75%	1,505	20.8
<60%	227	3.1

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced volume capacity.

Figure 1 Changes in serum ferritin, iron, and transferrin saturation for smokers and non-smokers with age. Serum ferritin increased with age (A), whereas both serum iron (B) and transferrin saturation (C) decreased with age. Serum ferritin was elevated in smokers until 70 years of age, whereas serum iron and serum transferrin were elevated in smokers until 50 and 60 years of age, respectively.

Table 2 Correlations between age, indices of iron homeostasis, and pulmonary function endpoints (n=7,251). Pearson product-moment correlation coefficients and P-values are provided

	Age (years)	Serum ferritin (ng/mL)	ln (serum ferritin)	Serum iron (µg/dL)	ln (serum iron)	Serum transferrin saturation (%)	ln (serum transferrin saturation)	Serum C-reactive protein (mg/dL)	ln (C-reactive protein)	FVC, largest value (mL)	FEV1 at 1 s, largest value (mL)	FEV1/FVC
Age (years)	1	0.182	0.224	−0.132	−0.102	−0.059	−0.030	0.100	0.128	−0.502	−0.621	−0.459
		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.01	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Serum ferritin (ng/mL)	0.182	1	0.768	0.161	0.167	0.248	0.248	0.064	0.060	0.094	0.048	−0.114
	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
ln (serum ferritin)	0.224	0.768	1	0.242	0.308	0.349	0.429	0.057	0.045	0.162	0.101	−0.157
	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.0001	<0.0001	<0.0001	<0.0001
Serum iron (µg/dL)	−0.132	0.161	0.242	1	0.939	0.926	0.872	−0.207	−0.241	0.245	0.233	0.002
	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.87
ln (serum iron)	−0.102	0.167	0.308	0.939	1	0.878	0.945	−0.267	−0.272	0.245	0.228	−0.011
	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.34
Serum transferrin saturation (%)	−0.059	0.248	0.349	0.926	0.878	1	0.926	−0.194	−0.233	0.233	0.210	−0.034
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.004
ln (serum transferrin saturation)	−0.030	0.248	0.429	0.872	0.945	0.926	1	−0.237	−0.256	0.229	0.203	−0.045
	0.01	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	0.0001
Serum C-reactive protein (mg/dL)	0.100	0.064	0.057	−0.207	−0.267	−0.194	−0.237	1	0.801	−0.165	−0.162	−0.016
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	0.17
ln (C-reactive protein)	0.128	0.060	0.045	−0.241	−0.272	−0.233	−0.256	0.801	1	−0.240	−0.239	−0.034
	<0.0001	<0.0001	0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	0.004
FVC, largest value (mL)	−0.502	0.094	0.162	0.245	0.245	0.233	0.229	−0.165	−0.240	1	0.943	0.035
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	0.003
FEV1 at 1 s, largest value (mL)	−0.621	0.048	0.101	0.233	0.228	0.210	0.203	−0.162	−0.239	0.943	1	0.346
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001
FEV1/FVC	−0.459	−0.114	−0.157	0.002	−0.011	−0.034	−0.045	−0.016	−0.034	0.035	0.346	1
	<0.0001	<0.0001	<0.0001	0.87	0.34	0.004	0.0001	0.17	0.004	0.003	<0.0001

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced volume capacity.

Table 3 Correlations between age, indices of iron homeostasis, and pulmonary function endpoints for smokers (n=2,549). Pearson product-moment correlation coefficients and P-values are provided

	Age (years)	Serum ferritin (ng/mL)	ln (serum ferritin)	Serum iron (µg/dL)	ln (serum iron)	Serum transferrin saturation (%)	ln (serum transferrin saturation)	Serum C-reactive protein (mg/dL)	ln (C-reactive protein)	FVC, largest value (mL)	FEV1 at 1 s, largest value (mL)	FEV1/FVC
Age (years)	1	0.152	0.172	−0.138	−0.138	−0.078	−0.084	0.160	0.224	−0.441	−0.605	−0.557
		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Serum ferritin (ng/mL)	0.152	1	0.786	0.200	0.196	0.254	0.250	0.064	0.076	0.117	0.071	−0.085
	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.001	0.0001	<0.0001	0.0003	<0.0001
ln (serum ferritin)	0.172	0.786	1	0.240	0.297	0.317	0.388	0.066	0.068	0.209	0.145	−0.114
	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	0.0009	0.0006	<0.0001	<0.0001	<0.0001
Serum iron (µg/dL)	−0.138	0.200	0.240	1	0.944	0.933	0.884	−0.213	−0.249	0.214	0.211	0.045
	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.02
ln (serum iron)	−0.138	0.196	0.297	0.944	1	0.886	0.951	−0.267	−0.284	0.232	0.228	0.046
	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.02
Serum transferrin saturation (%)	−0.078	0.254	0.317	0.933	0.886	1	0.930	−0.191	−0.224	0.210	0.193	0.007
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.73
ln (serum transferrin saturation)	−0.084	0.250	0.388	0.884	0.951	0.930	1	−0.240	−0.258	0.230	0.213	0.012
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	0.53
Serum C-reactive protein (mg/dL)	0.160	0.064	0.066	−0.213	−0.267	−0.191	−0.240	1	0.825	−0.174	−0.175	−0.053
	<0.0001	0.001	0.0009	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	0.01
ln (C-reactive protein)	0.224	0.076	0.068	−0.249	−0.284	−0.224	−0.258	0.825	1	−0.256	−0.262	−0.087
	<0.0001	0.0001	0.0006	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001
FVC, largest value (mL)	−0.441	0.117	0.209	0.214	0.232	0.210	0.230	−0.174	−0.256	1	0.920	0.101
	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001
FEV1 at 1 s, largest value (mL)	−0.605	0.071	0.145	0.211	0.228	0.193	0.213	−0.175	−0.262	0.920	1	0.466
	<0.0001	0.0003	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001
FEV1/FVC	−0.557	−0.085	−0.114	0.045	0.046	0.007	0.012	−0.053	−0.087	0.101	0.466	1
	<0.0001	<0.0001	<0.0001	0.02	0.02	0.73	0.53	0.01	<0.0001	<0.0001	<0.0001

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced volume capacity.

Table 4 Correlations between age, indices of iron homeostasis, and pulmonary function endpoints for non-smokers (n=4,702). Pearson product-moment correlation coefficients and P-values are provided

	Age (years)	Serum ferritin (ng/mL)	ln (serum ferritin)	Serum iron (µg/dL)	ln (serum iron)	Serum transferrin saturation (%)	ln (serum transferrin saturation)	Serum C-reactive protein (mg/dL)	ln (C-reactive protein)	FVC, largest value (mL)	FEV1 at 1 s, largest value (mL)	FEV1/FVC
Age (years)	1	0.223	0.274	−0.115	−0.075	−0.032	0.009	0.078	0.091	−0.517	−0.626	−0.463
		<0.0001	<0.0001	<0.0001	<0.0001	0.0303	0.53	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Serum ferritin (ng/mL)	0.223	1	0.759	0.117	0.136	0.228	0.234	0.065	0.048	0.054	0.016	−0.110
	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.0009	0.0002	0.2825	<0.0001
ln (serum ferritin)	0.274	0.759	1	0.228	0.302	0.354	0.439	0.053	0.031	0.109	0.058	−0.155
	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	0.0003	0.0348	<0.0001	<0.0001	<0.0001
Serum iron (µg/dL)	−0.115	0.117	0.228	1	0.938	0.920	0.866	−0.209	−0.242	0.243	0.232	−0.001
	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.94
ln (serum iron)	−0.075	0.136	0.302	0.938	1	0.874	0.942	−0.269	−0.269	0.234	0.217	−0.026
	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.07
Serum transferrin saturation (%)	−0.032	0.228	0.354	0.920	0.874	1	0.926	−0.200	−0.244	0.225	0.205	−0.034
	0.0303	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.019
ln (serum transferrin saturation)	0.009	0.234	0.439	0.866	0.942	0.926	1	−0.238	−0.259	0.210	0.185	−0.059
	0.53	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
Serum C-reactive protein (mg/dL)	0.078	0.065	0.053	−0.209	−0.269	−0.200	−0.238	1	0.791	−0.165	−0.158	0.005
	<0.0001	<0.0001	0.0003	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	<0.0001	0.74
ln (C-reactive protein)	0.091	0.048	0.031	−0.242	−0.269	−0.244	−0.259	0.791	1	−0.241	−0.231	0.002
	<0.0001	0.0009	0.0348	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	<0.0001	0.865
FVC, largest value (mL)	−0.517	0.054	0.109	0.243	0.234	0.225	0.210	−0.165	−0.241	1	0.956	0.039
	<0.0001	0.0002	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001	0.008
FEV1 at 1 s, largest value (mL)	−0.626	0.016	0.058	0.232	0.217	0.205	0.185	−0.158	−0.231	0.956	1	0.310
	<0.0001	0.2825	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001		<0.0001
FEV1/FVC	−0.463	−0.110	−0.155	−0.001	−0.026	−0.034	−0.059	0.005	0.002	0.039	0.310	1
	<0.0001	<0.0001	<0.0001	0.94	0.07	0.019	<0.0001	0.74	0.865	0.008	<0.0001

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced volume capacity.

Figure 2 Indices of iron homeostasis change with FEV₁/FVC. Serum ferritin (A) significantly increased in both smokers and non-smokers with FEV₁/FVC values ranging from 60% to 74% and less than 60%, respectively. However, comparable elevation in serum iron (B) and transferrin saturation (C) among those with FEV₁/FVC values from 60% to 74% and less than 60%, respectively, were observed to be significant only in non-smokers. *Significant difference relative to that group (smokers and non-smokers) with FEV₁/FVC ≥75%.

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced volume capacity.

Figure 3 C-reactive protein among smokers and non-smokers with varying FEV₁/FVC. C-reactive protein was increased in smokers with the lowest values of FEV₁/FVC, but there were no differences among non-smokers with and without obstruction. *Significant difference relative to smokers with FEV₁/FVC ≥75%.

Abbreviations: FEV₁, forced expiratory volume in 1 s; FVC, forced volume capacity.