Qin et al. BMC Endocrine Disorders (2017) 17:18 DOI 10.1186/s12902-017-0168-4 RESEARCHARTICLE Open Access Impaired lung function is associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in middle-aged and elderly Chinese Li Qin1,2†, Weiwei Zhang1,2†, Zhen Yang1,2*, Yixin Niu1,2, Xiaoyong Li1,2, Shuai Lu1, Yin Xing1, Ning Lin1,2, Hongmei Zhang1,2, Guang Ning3, Jiangao Fan4 and Qing Su1,2* Abstract Background: Associations between lung function and non-alcoholic fatty liver disease (NAFLD) have been reported. However, evidence from large-scale populations about the relationship is scarce. The objective of the study was to evaluate the relationship between lung function and NAFLD in middle-aged and elderly Chinese. Methods: A total of 1842 participants aged 40 years or older were recruited from Chongming District, Shanghai, China. Lung function, evaluated by forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) was measured with standard spirometry. The NAFLD was evaluated by ultrasonography. Results: The subjects with NAFLD had lower FVC (% predicted) (0.85 ± 0.26 vs. 0.90 ± 0.28, p <0.001)andFEV1 (% predicted) (0.93 ± 0.29 vs. 0.98 ± 0.34, p < 0.001) than non-NAFLD. After adjusting for potential risk factors, the lowest quartile of FVC (% predicted) and FEV1 (% predicted) was associated with increased prevalence of NAFLD, with the fully adjusted odds ratio of 1.37 and 1.24 (95% confidence interval [CI] 1.18–1.97, p < 0.001, 95% CI 1.11–1.87, p = 0.009), respectively. Conclusions: Impaired lung function is associated with non-alcoholic fatty liver disease, independent of conventional metabolic risk factors. Keywords: Lung function, Non-alcoholic fatty liver disease, Chinese, Metabolic risk factors Background risk factors of NAFLD, such as central obesity, insulin Nonalcoholic fatty liver disease (NAFLD) is character- resistance, systemic inflammation, current smoking, dia- ized by excessive hepatic fat accumulation of patients betes, and oxidative stress, contribute to, but cannot who have no history of alcohol abuse [1]. Recently, the fully explain the increased risk of NAFLD in the general combination of overnutrition condition and less physical population [3–5]. activity have made NAFLD become the most common Recently, lung function parameters, estimated by disease of chronic liver damage, with increased preva- forced vital capacity (FVC) and forced expiratory volume lence of obesity, diabetes, and metabolic syndrome in in one second (FEV1) were proved to be well associated developed and developing counties [2]. The traditional with the development of diabetes, cardiovascular disease, inflammation process and metabolic syndrome [6–25]. * Correspondence: [email protected]; [email protected] NAFLD has been considered as a hepatic manifestation †Equal contributors of the metabolic syndrome and is associated with various 1Department of Endocrinology, Xinhua Hospital Chongming Branch, metabolic abnormalities, including hyperlipidemia, cen- Shanghai Jiao Tong University School of Medicine, Shanghai, China Full list of author information is available at the end of the article tral obesity, and type 2 diabetes [1, 26, 27]. So, reduced © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Qin et al. BMC Endocrine Disorders (2017) 17:18 Page 2 of 7 lung function may link to an increased risk of NAFLD. Japan) three times consecutively with 1 min intervals In a previous study, association of reduced lung function after at least 5 min rest in the seated position; the three with NAFLD was detected among men in a health readings were averaged for analysis. Body mass index examination program [28]. However, evidence from (BMI) was calculated as weight in kilograms divided by large-scale populations about the relationship between the square of height in meters. reduced lung function and NAFLD is scarce. In addition, All subjects were assessed after overnight fasting for at it is unclear whether the association can be observed in least 10 h, Overnight fasting and 2 h OGTT (Oral Chinese population. Glucose Tolerance Test) 75 g glucose blood samples For this purpose, the aims of this study were to test the were collected in tubes containing EDTA and were cen- hypotheses that reduced lung function is independently trifuged at 4 °C and stored at−80 °C until analysis. The associated with NAFLD in a cross-sectional population fasting glucose, glucose 2 h after oral glucose tolerance study of 1,842 middle-aged and older Chinese subjects. test, total cholesterol (TC), triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipopro- Methods tein (HDL) cholesterol were measured on an automatic Study population analyzer (Hitachi 7080; Tokyo, Japan). Fasting insulin In 2011, China launched a national survey of Risk was determined by RIA (Linco Research, St. Charles, Evaluation of cAncers in Chinese diabeTic Individuals: a MO). The homeostasis model assessment of insulin re- lONgitudinal (REACTION) study, which was conducted sistance (HOMA-IR) was calculated according to the among 259,657 adults, aged 40 years and older in 25 equation described by Matthews et al. [32]. communities across mainland China, from 2011 to 2012 [29]. The data presented in this article are based on the Definition of NAFLD baseline survey of subsamples from Shanghai in eastern Hepatic ultrasonic examination was performed on all China [30, 31]. All studied individuals came from the participants by two trained ultrasonographists who were Chongming District in Shanghai, China. There were blinded to the clinical and laboratory data, using a high- 9930 participants who had complete information about resolution B-mode tomographic ultrasound system age; sex; smoking and alcohol consumption habits; and a (Esaote Biomedica SpA, Italy) with a 3.5-MHz probe. medical history including the use of medications, BMI, Diagnosis of fatty liver by ultrasonography was defined and a hepatic ultrasonic examination. Participants meet- by the presence of at least two of three abnormal ing the following criteria were excluded: 1) those with a history of known liver diseases such as hepatitis, cirrho- sis, or malignancy; 2) those with alcohol consumption greater than 140 g/wk for men and 70 g/wk for women. Thus, a total of 8850 participants were eventually in- cluded in this analysis. Of these, two communities par- ticipants received lung function test. 1,842 participants were eventually included in the analysis. The protocol was approved by the Institutional Review Board of Xinhua Hospital affiliated with Shanghai Jiao-Tong University School of Medicine. Data collection A standardized questionnaire was used by trained physi- cians to collect information such as age; sex; current smok- ing (yes/no); current drinker (yes/no). Physical activity level was classified as low, moderate, or high according to the International Physical Activity Questionnaire scoring protocol. According to participants’ responses to the corre- sponding questions, family history of diabetes was classi- fied as yes or no. The details of anthropometric measurements including height, weight, waist circumference, hip circumference were carried by trained physicians. Blood pressure was Fig. 1 The levels of FVC (% pred) and FEV1 (% pred) in subjects with measured at the right arm with an automated electronic NAFLD and without NAFLD. Data are shown as means ± SE after adjustment for age and sex. (A for FVC and B for FEV1) device (OMRON Model1 Plus; Omron Company, Kyoto, Qin et al. BMC Endocrine Disorders (2017) 17:18 Page 3 of 7 findings: diffusely increased echogenicity of the liver (0.85 ± 0.26 vs. 0.90 ± 0.28, 0.93 ± 0.29 vs. 0.98 ± 0.34; both relative to the kidney, ultrasound beam attenuation, and p < 0.001) (Fig. 1). Individuals with NAFLD were elder, poor visualization of intrahepatic structures. NAFLD more likely to be metabolic syndrome, current drinker, and was diagnosed by hepatic ultrasound after the exclusion heavy smoking, and had higher levels of BMI, SBP, DBP, of alcohol abuse and other liver diseases. waist circumference, hip circumference, waist-hip ratio, fasting plasma glucose FPG, postprandial 2-h plasma glu- Lung function measurements cose,A1C,HOMA-IR,TG,TC,LDL-c,AST,ALTand Lung function tests including FVC and FEV1 were GGT (all p values < 0.001), and had lower levels of conducted by a trained physician using Electronic HDL-c (p < 0.001) (Table 1). Spirometer (Model BF-II, Jintan, China). Each par- When analyzed by quartiles of FVC (% pred) or FEV1 ticipant received at least two tests (with acceptable (% pred) levels, as summarized in Tables 2 and 3, the sub- maneuvers) at a seated position and with nose clips in jects with lower FVC (% pred) or FEV1 (% pred) were place. The predicted values for FVC and FEV1 were more likely to be more metabolic syndrome (p <0.001), calculated from the following equations obtained in a more smoker (p < 0.001), more drinker (p <0.001),more representative sample of Chinese population [25]. aged (p < 0.001), With respect to metabolic parameters, Predicted FVC of man = −4.33058–(0.01326× age the subjects in the higher FVC (% pred) or FEV1 (% pred) [years]) + (0.04669× height [cm]) + (0.01664× weight [kg]). quartiles exhibited low er levels of LDL cholesterol Predicted FVC of woman = −4.79287– (0.01326× age [years]) + (0.04669× height [cm]) + (0.01664× weight [kg]). Predicted FEV1 of man = −3.65523– (0.01850× age Table 1 Baseline characteristics of the study participants, [years]) + (0.04283× height [cm]) + (0.009228832× weight grouped according to NAFLD status [kg]).