In this longitudinal study, spirometric values were measured twice in male smokers, who participated in an annual health check. At visit 2, AC was evaluated in these subjects, and a significant correlation between rate of decline in FEV1 and AC was retrospectively demonstrated. Furthermore, multivariate logistic regression analysis revealed that a decline in FEV1 was associated with AC, independently of age, cigarette consumption (Brinkman index) and ΔBMI. In addition, a decline in FEV1 was more prevalent among subjects with Mets, and the rate of decline in FEV1 in these subjects was significantly greater than that in subjects without Mets.
Mets is a common disease that is characterized by abdominal obesity, high blood pressure, hypertriglyceridemia, low HDL-c levels, and high fasting glucose levels 24
. Data from the Third National Health and Nutrition Examination Survey indicates that this syndrome is present in almost a quarter of US residents aged 20 years or older 25
. Although Mets is less prevalent in Asian compared with Western populations, a survey of the incidence of acute myocardial infarction suggested that the prevalence of Mets is also increasing in Japan, resulting in an increased incidence of myocardial infarction among men 26
. Mets is associated with an increased risk of diabetes mellitus and cardiovascular disease, leading to increased cardiovascular and all-cause mortality 14
. Recent studies have demonstrated that systemic inflammation, derived from visceral fat, is an important mechanism in the pathogenesis of Mets 13
. Because both Mets and COPD are associated with the same comorbidities, including atherosclerosis and diabetes, and involve a state of chronic systemic inflammation, the pathogenesis of the two diseases is thought to share a common inflammatory pathway. A recent study showed that the prevalence of Mets is greater in subjects with COPD compared to those without COPD 11,27
The mechanism underlying the rapid decline in pulmonary function in male smokers with a high AC has not been fully elucidated. One possible mechanism that might explain this phenomenon is endothelial dysfunction in subjects with Mets 28
. Accumulating evidence suggests that endothelial dysfunction is one of the important features in the development of COPD 29
. In particular, pulmonary endothelial cell apoptosis is thought to play an important role in the loss of pulmonary vasculature 30,31
. Systemic inflammation may play a significant role in endothelial dysfunction in COPD patients 32
. Mets is characterized by systemic low-grade inflammation, and endothelial dysfunction resulting from this systemic inflammation leads to functional impairment of organ systems 33,34
. In addition, long term exposure to cigarette smoke induces systemic inflammation 35
. Therefore, in active smokers with Mets, systemic inflammation may be enhanced because it is derived from two sources, namely visceral fat and exposure of the lungs to cigarette smoke. This may result in enhanced endothelial dysfunction and a rapid decline in pulmonary function.
Abdominal obesity may change the compliance of the diaphragm and chest wall. Chen and colleagues reported that a 1-cm increase in AC was associated with a 13-mL reduction in FVC and a 11-mL reduction in FEV1
. In the present study, there was no difference in mean BMI between visit 1 and visit 2, although AC was not measured at visit 1. In addition, multivariate logistic regression analysis demonstrated that AC was a significant factor for discrimination of decline in FEV1
, independently of ΔBMI (Table ). It is unlikely that the decline in FEV1
observed in the present study is explained by weight gain during follow-up.
In the present study, the longitudinal decrease in FEV1
was significantly greater in subjects with Mets, and the prevalence of a decline in FEV1
was significantly greater in subjects with Mets than in those without Mets. However, FEV1
/FVC did not differ significantly between subjects with or without Mets. Even after adjustment of FEV1
/FVC for age, there was no difference in FEV1
/FVC between the two groups. This finding was in keeping with those from previous studies, which demonstrated that FEV1
/FVC was not reduced in subjects with Mets compared to those without Mets 36,37
This study had several limitations. First, there may have been sampling bias. Takahata town has a resident population of 15,222 adults aged 40 years or older. For visit 1, data for a total of 3,257 enrolled subjects was entered into the final statistical analysis. Among the 1,502 male subjects, there were 523 active smokers. However, follow-up spirometry in 2009 was only performed for 147 subjects who had continued to smoke; the remaining subjects were lost to follow-up or quit smoking before visit 2. The number of subjects who were followed-up was not large, but the only significant difference between participants and non-participants in 2009 was age (see Method section). Thus, we thought the participants in 2009 were not largely different from non-participants. Differences between participants and non-participants in type of employment, socio-economic status or life style may have influenced the results. However, this information was not available in the present study. Second, pulmonary function testing at visit 2 in 2009 was only performed for male current smokers, not for male non-smokers, ex-smokers or females. This was only because we could not find a sufficient number of testers in 2009. Therefore we needed to focus on the data for the subjects who were assessed in the present study. Because of this limitation, the results from the present study may not be applicable to females or ex-smokers. Third, AC measurements were performed at visit 2, not visit 1. Therefore, the association between decline in FEV1 and AC was retrospectively demonstrated in this study. It should be noted that it could not be concluded that AC is predictive for decline in FEV1 among male smokers. However, despite these limitations we think this study is clinically significant as an initial investigation, and future prospective studies have the potential to confirm AC as a new and simple biomarker for discriminating subjects with a decline in FEV1 among active smokers.
In conclusion, AC was significantly associated with the rate of decline in FEV1 among male smokers in this study population. A decline in FEV1 was more prevalent among subjects with Mets, and the rate of decline in FEV1 was significantly greater in subjects with Mets compared to those without Mets. This retrospective analysis suggested that measurement of AC may be a simple and useful method of discriminating subjects with a decline in FEV1 among male smokers.