The present study investigated a potential association between lung function and blood markers of nutritional status in male current or former smokers. This study was unique in that non-COPD subjects were categorized into three groups based on FEV1
/FVC tertiles. In contrast, most previous studies in this field simply compared the COPD group with the non-COPD group without further dividing the subjects with non-COPD into groups. COPD is now defined as a preventable disease;3
therefore, from the perspective of prevention, it is important to focus on those with risk factors such as smoking history and advanced age but who do not fulfil the COPD diagnostic criteria, especially men with an FEV1
/FVC close to 70%.
Our main results were as follows: (1) lower FEV1/FVC was linearly associated with lower RBCc, Hb, hematocrit, TP, and LDL-c after adjustments for all potential confounders; (2) FEV1/FVC was not associated with intake of total energy, protein, fat, carbohydrate, or cholesterol. Together, these results support our hypothesis that reduced lung function is associated with reduced nutritional status in non-COPD aging men with smoking history. This suggests that in those men, trends toward reduced nutritional status and anemia may emerge independently as changes in blood test results, along with decreased lung function, even before the onset of COPD.
TP and albumin are markers of nutritional status.15
In the present study, FEV1
/FVC was linearly associated with TP in all adjusted models, and the decrease in adjusted TP between the non-T3 and non-T1 groups was larger than that between the non-T1 and COPD groups. Nevertheless, FEV1
/FVC was not associated with adjusted intake of total energy and nutrients, except iron. To the best of our knowledge, this is the first study to report that decreasing degree of TP in non-COPD aging men with smoking history could be comparable to or greater than that in COPD patients. In contrast to TP, the association between albumin and FEV1
/FVC was slight. One possible explanation for this is that albumin is pooled in the extravascular space and is then mobilized to the intravascular space as needed with its degradation rate decreasing, which allows a relatively constant blood level to be maintained.16
COPD has been reported to be associated with anemia,19
which is causally related to dyspnoea, reduced exercise capacity,21
and health-related QOL.22
The mechanism of COPD is believed to be similar to that of other chronic diseases. In patients with chronic diseases, elevated levels of inflammatory cytokines could shorten RBC survival, impair mobilization or utilization of iron, and impair the marrow erythropoietic response.19
In the present study, lower FEV1
/FVC was linearly associated with lower RBCc, Hb, and hematocrit after adjustments for all potential confounders. In contrast, FEV1
/FVC was inversely associated with adjusted iron intake; subjects with a lower FEV1
/FVC had a greater iron intake. These findings suggest that RBC dysregulation, in which impaired utilization of iron is implicated, could occur in male current or former smokers as FEV1
/FVC decreases even before the onset of COPD. It has been shown that cigarette smoking alters iron homeostasis, greatly increases lung iron concentration, and generates oxidative stress and inflammation,24
which may increase the iron requirement. A meta-analysis by Gan et al indicated that WBCc may be a useful marker of systemic inflammation in COPD patients.25
Van Hoydonck et al reported that male current smokers and female current or former smokers had greater iron intake than male former smokers and female never smokers, respectively.26
In the present study, WBCc and iron intake in the non-T1 and COPD groups were greater than those in the non-T3 and non-T2 groups, implying that there is an association between inflammation and iron requirement in male current or former smokers, even before the onset of COPD. In the present study, the levels of anemia markers in each subject group were all within the normal range, which can be explained as follows: first, the prevalence of anemia is actually not very high, even in COPD patients. In a cross-sectional study by John et al,20
the prevalence of anemia in COPD patients was 13%, and that in a retrospective study by Cote et al21
was 17%. Second, three-fourths of the subjects in the present study were in the non-COPD group. Further studies focusing on associations between FEV1
/FVC and serum iron, transferrin, ferritin, transferrin receptor, and inflammatory cytokines in male current or former smokers with non-COPD are needed.
Although several previous studies have reported an association between lung function and diabetes,27
most used FEV1
or FVC, not FEV1
/FVC, as markers of lung function, which seems to be insufficient to evaluate whether chronic airflow obstruction is related to glucose metabolism. In the present study, FEV1
/FVC was not associated with glucose or HbA1c, suggesting that chronic airflow obstruction is not independently associated with glucose control. The present result was consistent with that of a large prospective study by Ford et al,28
in which FEV1
, FVC, and FEV1
% pred were significantly negatively associated with the incidence of diabetes, whereas FEV1
/FVC was not. In the present study, subjects who took drugs for hyperglycemia or diabetes were excluded so that medication use did not mask impaired glucose control, which may also result in the disassociation of FEV1
/FVC with glucose and HbA1c.
The present study had several limitations. First, we cannot completely rule out the possibility of chance due to relatively small sample size. In spite of the relatively small sample size, however, it was noted that lower FEV1
/FVC was significantly associated with lower TP and Hb, and future studies are warranted to confirm these results in larger samples. Second, while it is essential to consider physical activity for nutritional assessment, the data on physical activity was not available in the present study; this may somewhat confound associations between FEV1
/FVC and nutritional markers. Although it has been reported that men with COPD have elevated resting energy expenditure29
or daily activity energy expenditure,31
most subjects had relatively high FEV1
/FVC, and it is less likely that the present findings are fully explained by the residual confounding. Although it remains unknown whether energy expenditure tended to be elevated among men whose FEV1
/FVC fell close to 70%, future studies should aim to reduce the confounding due to physical activity by measuring resting energy expenditure and daily activity energy expenditure.
In summary, the present study shows that lower FEV1/FVC is independently linearly associated with lower blood markers of nutritional status and anemia. The present results suggest that, in non-COPD aging men with smoking history, slight but significant trends toward reduced nutritional status and anemia may emerge along with decreased lung function even before the onset of COPD. Further studies are needed to examine the mechanism by which disease progression occurs in current or former smokers with non-COPD.