Asthma is a prevalent global chronic non-communicable disease marked by bronchospasm and airway inflammation, affecting approximately 334 million people worldwide (1). It accounts for 1.1% of global disability-adjusted life years (DALYs) (2). Common symptoms include dyspnea, chest tightness, and wheezing (2). Asthma also elevates the risk of cardiovascular disease and mortality, with its prevalence increasing after age 50, peaking at 6.8–12% (3–6). This trend suggests a growing socioeconomic and healthcare burden. Diabetes mellitus, characterized by elevated blood glucose levels, affected 451 million people globally in 2017, with projections estimating 693 million adults with diabetes by 2045 (7). People with diabetes are at higher risk for asthma and other chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and pneumonia, and this increased risk may be a result of decreased lung function in people with diabetes (8).

Oxidative stress is caused by an imbalance between the cell’s antioxidant scavenging system and the reactive oxygen species (ROS) production process (9). Immune cells involved in the inflammatory response in asthma, such as eosinophils and neutrophils, can produce excessive ROS, contributing to oxidative stress and exacerbating asthma symptoms (10). The oxidative balance score (OBS) is a measure that assesses an individual’s antioxidant status by objectively quantifying the antioxidant and pro-oxidant components of dietary and lifestyle factors (11, 12). Findings suggest a strong association between OBS and reduced all-cause mortality, CVD-related mortality, and cancer-related mortality in populations adhering to the Mediterranean diet (13). One study noted that a composite index (inflammatory burden index) combining multiple inflammatory markers such as C-reactive protein (CRP), neutrophil count and lymphocyte count was independently associated with an increased risk of all-cause as well as respiratory disease mortality in patients with asthma and COPD (14, 15). To improve disease management and health outcomes, it is crucial to understand the impact of OBS on mortality in older asthma patients with diabetes. Therefore, this study aimed to investigate the association between OBS and all-cause, CVD mortality and respiratory-related mortality in older asthma patients with diabetes.

The data for this investigation were sourced from the National Health and Nutrition Examination Survey (NHANES) public database, which is managed by the Centers for Disease Control and Prevention (CDC) in the USA. The NHANES database collects vital health statistics for the nation, utilizing a refined and intricate methodology to periodically select a representative sample of the U.S. population. Its primary objective is to assess the health and nutritional status of individuals in the United States. To ensure ethical compliance, the survey has received approval from The National Center for Health Statistics (NCHS) Research Ethics Review Board (ERB; Approval number: Protocol #98-12/Protocol #2005-06/Continuation of Protocol #2005-06/Protocol #2011-17/Continuation of Protocol #2011-17/Protocol #2018–01), and all participants provided written informed consent prior to their inclusion in the study. NHANES encompasses a comprehensive range of data, including demographics, dietary habits, medical examination results, laboratory findings, and questionnaire responses. The data are released in 2-year cycles. The datasets used in this study are publicly accessible on the CDC website.

In this study of 611 older asthma patients with diabetes, we identified a negative association between the OBS and all-cause and CVD mortality. However, we did not observe a significant association between OBS and respiratory-related mortality. RCS analysis demonstrated that this inverse relationship was linear. Subgroup analyses and interaction tests indicated the negative association between the OBS and CVD mortality was significantly influenced by alcohol consumption. While the subgroup analyses showed no significant interactions between the OBS and all-cause mortality among the stratification variables. In conclusion, our findings suggest that the OBS is a valuable marker for assessing all-cause and CVD mortality risk in older asthma patients with diabetes and may contribute to the development of effective death prevention strategies. In addition, we also analysed the relationship between lifestyle/dietary OBS and all-cause and CVD mortality. The results showed that lifestyle OBS was negatively associated with all-cause mortality, while dietary OBS was inversely associated with CVD mortality. Last but not least, we did not observe OBS could reduce respiratory-related mortality in older asthma patients with diabetes.

Previous studies have explored the relationship between OBS levels and both all-cause and CVD mortality. Findings from a nationally representative sample indicate that higher OBS may lower the risk of these outcomes, particularly in individuals aged 45 or younger, male, Non-Hispanic White, non-smokers, and those who exercise regularly (24). Another study linked higher OBS to a reduced risk of H. pylori infection, with dietary OBS correlating with lower all-cause mortality in H. pylori-positive individuals and lifestyle OBS associated with lower mortality in H. pylori-negative participants (23). Elevated OBS is also associated with a decreased risk and severity of metabolic syndrome, as well as reduced all-cause mortality in those with the condition (25). Additionally, a positive correlation exists between OBS and reduced prevalence of CVD and mortality in adults with nonalcoholic fatty liver disease (NAFLD), especially among younger and more educated individuals (26). A similar association with reduced all-cause mortality has been observed in older adults (16). In our present study, an independent association was observed between OBS and all-cause and CVD mortality in older asthma patients with diabetes, and RCS analysis revealed a linear negative association between OBS and mortality in older asthma patients with diabetes. Studies have also explored the relationship between OBS and chronic respiratory diseases and lung function. One study found that higher OBS was negatively associated with chronic bronchitis, wheezing, and restrictive spirometry patterns, but positively related to predicted values of FVC and FEV1 (18). Another study in Korean adults showed that OBS significantly improved exertional spirometry (11). However, findings on COPD were mixed; while an increase in OBS was generally linked to a lower prevalence of COPD, excessive OBS showed a non-significant decrease or even increased risk of COPD, indicating an L-shaped association (17).

Diabetes is a significant factor associated with an increased risk of developing asthma. Research indicates that the incidence of asthma is nearly twice as high in individuals with diabetes compared to those without diabetes (27). A large study of Danish twins also found that the risk of asthma was nearly double in patients with Type 2 Diabetes Mellitus (T2DM) compared to non-T2DM patients (28). Additionally, a study of veterans revealed that approximately 5% of diabetics had asthma, compared to 2.9% of healthy controls, regardless of other comorbid conditions (29). Findings from a Taiwanese study similarly showed that individuals with T2D had a 30% higher risk of developing asthma (30). Children with asthma have been found to have higher HbA1c levels compared to healthy controls (31). Asthma can act synergistically with obesity and insulin resistance to increase circulating levels of inflammatory cytokines, which can lead to an increased risk in people with type 2 diabetes (32). In turn, high levels of glucose and insulin in the lungs and low-grade inflammation throughout the body further contribute to collagen deposition and airway remodeling, which leads to decreased lung function in diabetic patients (33–36). Furthermore, asthma management often involves high doses of inhaled or oral glucocorticoids, which can elevate blood glucose levels and potentially accelerate diabetes progression (37). Consequently, asthma is often poorly controlled in diabetic patients, leading to a higher likelihood of disease progression, complications, and hospitalization (38, 39). This chronic systemic inflammation induces a pro-oxidant state, causing an imbalance between pro-oxidant and antioxidant factors, and resulting in excessive production of reactive oxygen species (ROS). OBS, as an indicator of the overall antioxidant/oxidant balance, reflects more comprehensively the overall oxidative stress state of the body, and by evaluating the impact of OBS on all-cause and CVD mortality in older asthmatic patients with comorbid diabetes mellitus, it is possible to make further targeted recommendations for the management of these patients. It is important to note that due to the design of the NHANES study, there is some uncertainty regarding the medications taken by the patients, and therefore more detailed follow-up prospective studies are needed.

In our study, we also observed that compared to never-smokers, current and former smokers benefited more from OBS in reducing CVD mortality. This could be because oxidative stress is a key feature of the pathophysiology of asthma, and components in cigarette smoke, such as nicotine and free radicals, can directly induce the production of ROS in the body (10, 40–43). The accumulation of ROS further exacerbates oxidative stress, leading to cellular and tissue damage, inducing airway hyperreactivity and airway remodeling, which aggravates asthma. Furthermore, in smokers, prolonged elevation of serum CRP and interleukin-6 (IL-6) concentrations is closely associated with reduced lung function (44). Increased oxidative stress due to smoking can also lead to tissue damage through lipid peroxidation (45). Some studies have found that treatments aimed at reducing pro-inflammatory factors and increasing anti-inflammatory factors can reduce the risk of chronic airway inflammation in current and former smokers. However, these treatments did not show a statistically significant protective effect for never-smokers against the risk of chronic airway inflammation (46–48). The OBS includes both oxidative stress and antioxidant defenses. For smokers, interventions that improve antioxidant status (through diet, supplementation, or lifestyle changes) can be more effective at reducing oxidative damage and its negative health consequences. Former smokers still carry a higher oxidative burden than never smokers, as the effects of smoking linger in the body even after quitting. However, over time, former smokers often experience improvements in oxidative balance due to the reduction in exposure to tobacco smoke. Current smokers have the highest levels of oxidative stress, as they are continuously exposed to the harmful substances in tobacco smoke (40, 49). The OBS can be an effective measure for identifying individuals at high risk and motivating interventions that help balance oxidative stress and antioxidant levels. Never smokers generally have a lower baseline level of oxidative stress compared to smokers, so the potential for improvement in oxidative balance is less pronounced. This is why the OBS is less effective in reducing mortality rates in never smokers; they already start from a more balanced oxidative state. In summary, the oxidative balance score is particularly effective in reducing all-cause and CVD mortality among current and former smokers because these individuals experience higher levels of oxidative stress due to smoking. Addressing oxidative imbalance through lifestyle changes and antioxidant support can significantly lower their risk of developing chronic diseases and improve long-term health outcomes. Never smokers, on the other hand, generally start with a more balanced oxidative state, making the OBS less impactful in their case.

This study has several notable strengths. Firstly, we utilized nationally representative data from the NHANES database, which is derived from a national population sample and collected using standardized protocols and stratified, multistage sampling methods, ensuring a representative non-institutional population. Secondly, we took measures to minimize potential biases. Thirdly, our research contributes significantly by examining the association between OBS and all-cause as well as cardiovascular mortality among older U.S. asthmatics with comorbid diabetes. Finally, we conducted various sensitivity and subgroup analyses to further enhance the robustness of our findings.

This study has several limitations. First, many variables in the NHANES were self-reported, which may undermine the credibility of our findings due to the potential inaccuracy of these reports compared to objective records. Second, our analysis is based on observational data, which does not directly address the mechanisms by which the OBS affects mortality in older asthmatics with comorbid diabetes. Further research is needed to explore the biological link between the OBS and mortality to identify potential therapeutic targets. Additionally, using a single 24-h dietary recall to assess pro-oxidants and antioxidants may not fully capture day-to-day dietary variations, though this method helps reduce recall bias. The presence of unquantified variables in our analysis does not exclude the possibility of unrecognized confounding effects. Finally, causal relationships between variables might be weakened, so our findings should be interpreted with caution. Future prospective cohort studies are needed to confirm these results.

The investigation proved a linear and inverse relationship between the OBS and all-cause and CVD mortality in older asthma patients with diabetes. In summary, our findings suggest that OBS could be a useful predictor of all-cause and CVD mortality risk in older asthma patients with diabetes. Future studies with larger sample sizes are necessary to further validate the regulation mechanisms of OBS in older asthma patients with diabetes.