This study’s results support the hypothesis tested – increasing high fructose corn syrup sweetened soft drink consumption is significantly correlated with adult chronic bronchitis. Adults consuming non-diet soft drinks ≥ 5 times a week were nearly twice as likely to have chronic bronchitis as non/ low non-diet soft drink consumers, independent of all covariates, including smoking and history of smoking, P = 0.047. To our knowledge, this is the first US study to assess an association between soft drinks and chronic bronchitis. The results are consistent with another study, which showed an association between excess free fructose beverages consumption and pediatric asthma - a chronic childhood lung disease that significantly increases the risk of developing chronic bronchitis in adulthood [5]. Specifically, high consumption of excess free fructose beverages, including apple juice, fruit drinks and non-diet soda, was significantly correlated with asthma in children ages 2–9 y [10].

Results are similarly consistent with another recent study of mothers and their children. Children whose mothers drank high fructose corn syrup sweetened soft drinks during their first and second trimesters were 22 % more likely to have asthma as children whose mothers who did not drink non-diet soft drinks. Analyses with their children at ages 7–8 years showed that children, who drank juice other than orange juice, were 34 % more likely to have asthma than children who didn’t drink juice. It was suggested that early life exposure to fructose may influence asthma development in children [42].

However, their findings are more consistent with the conclusion that it is the excess free fructose that is associated with childhood asthma, because the association with asthma included consumption of high fructose corn syrup sweetened soft drinks by mothers during pregnancy, and included consumption of 100 % juice by their children, exclusive of orange juice. The conclusion that the asthma association is with fructose is less clear, because although the total fructose amounts in apple juice and orange juice are comparable, their excess free fructose contents are significantly different; per 100 g, apple juice contains 6.4 g and orange juice contains 4.5 g of fructose. [23]. In contrast, the excess free fructose content in an 8 oz cup of apple juice is 9.3 g (NDB No. 09400) and in orange juice it is 0.4 g (NDB No. 09207) [23].

Similarly, high fructose corn syrup sweetened soft drinks, as apple juice, contain significantly more excess free fructose than orange juice [16, 23, 43]. Average US per capita consumption of HFCS has been estimated to be just under 0.5 kg (1 lb.) per week, or approximately 65 g per day [44]. In HFCS that is made of 60 % fructose and 40 % glucose monomers [16], 65 g contains 13 g of excess free fructose. As one 20 oz bottle of cola contains 65 g of HFCS [45], a person who drinks 20 oz of cola sweetened with the 60/40 variant of HFCS, consumes 13 g of EFF in a single beverage serving. Notably, in fructose malabsorption research, 10 % of healthy adults challenged with 12 g of excess free fructose tested positive for fructose malabsorption [19–21].

In another recent cross-sectional asthma study, researchers identified a statistically significant association between increased non-diet soft drink consumption and asthma among high-schoolers [9]. It was suggested that preservatives might explain the correlation. However, given the results of existing epidemiology, their findings are more consistent with the possibility that the association with asthma is more likely to be attributed to the effects of excess free fructose.

The repeatability of EFF’s association with lung pathophysiology across age groups provides support for the hypothesis that increased excess free fructose consumption is associated with lung disease. In existing fructose malabsorption research, excess free fructose or just fructose is associated with fructose malabsorption, but not sucrose or equal amounts of fructose and glucose monomers [17–22]. This observation is consistent with the possibility that fructose malabsorption may underlie the association between excess free fructose consumption and lung disease.

Notably, the correlation between excess free fructose and chronic bronchitis was independent of co-morbidity factors often associated with COPD, including obesity, smoking, exposure to in-home smoking, pre-diabetes and diabetes. Existing research has provided evidence of elevated levels of AGEs/RAGE in COPD patients who underwent lobectomy [15]. Researchers suggested that the nexus between COPD and diabetes may be due to the elevated concentrations of AGEs/RAGE associated with diabetic hyperglycemia [15].

However, results of this study showed that the association between increased excess free fructose intake and chronic bronchitis was independent of pre-diabetes and diabetes, suggesting that the link between increased excess free fructose consumption and chronic bronchitis is independent of the glycemic load thought to contribute to AGEs formation in the systemic circulation of individuals with diabetes. Our results support the possibility that the in situ formation of enFruAGEs, resulting from the interaction between unabsorbed excess free fructose and dietary proteins, may be a source of elevated levels of advanced glycation end-products in COPD patients, independent of diabetes.

Equally noteworthy is that the association between increased excess free fructose consumption and higher odds of chronic bronchitis was independent of smoking. This suggests that high excess free fructose consumption may, in part, explain the idiopathic prevalence of chronic bronchitis among non-smokers. Results are consistent with and provide support for recent research that suggests that smoking associated emphysema and non-smoking associated chronic bronchitis - entities that are traditionally considered to be overlapping within COPD - may in fact be distinct disorders [7].

It is interesting that a 2008 population-based study found that COPD patients were more likely to have symptoms of inflammatory bowel disease than history of smoking [26]. The recent evidence that intestinal distress is increased in COPD patients [24–26] is consistent with, and provides further support for, the “intestinal enFruAGEs fructositis” hypothesis. Research indicating that AGEs are elevated in lung tissues of COPD patients [14] and that overexpression of RAGE and AGEs was observed in bronchiolar epithelia, type II alveolar pneumocytes, alveolar macrophages and endothelia in pathological conditions associated with inflammation and lung damage [11] should be considered in the context of evidence that intestinal compromise is a newly identified component of COPD [27]. The suggestion that COPD is a multisystem disorder that involves aberrant intestinal symptomology [27] is consistent with this study’s results.

Reports by the American Lung Association indicate that children who suffered from severe, persistent asthma are nearly 32 times more likely to develop COPD in adulthood [6]. The statistically significant correlations between increased excess free fructose consumption and prevalent adult chronic bronchitis - and increased excess free fructose consumption and prevalent pediatric asthma [10] - support the possibility that excess free fructose and enFruAGE are risk factors in lung disease across age groups.

This study is subject to limitations. First, the associations are cross-sectional; therefore, the exposures and outcome are simultaneously assessed. For this reason, cross-sectional studies do not provide evidence of a temporal relationship between exposures and outcome. Follow-up longitudinal studies are needed. Second, chronic bronchitis status in NHANES is based on self-report, so there is potential for reporting bias. Third, other possible confounders for COPD and chronic bronchitis, including environmental factors, such as outdoor air quality, could not be accounted for because these data were not available. Fourth, high excess free fructose beverages are only one food category that could contribute to daily excess free fructose load. Numerous other food categories contain HFCS as an added sweetener, and therefore, also contribute to daily excess free fructose load. However, among US adults, soft drinks are the most significant source of high fructose corn syrup in the American diet [46].