Asthma, which manifests as a clinical syndrome of inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction, is a prevalent chronic airway disease (1). The prevalence of asthma has witnessed a significant rise in several nations over the last few decades. At present, the prevalence estimates for asthma among children and adults in the United States stand at 10.9% and 18.5%, respectively (2). Asthma was responsible for around 1.6 million visits to emergency departments and 183,000 hospitalizations in the United States in 2017, according to the survey (3). This caused a significant economic burden and a considerable number of missed school days.

Airway eosinophilia is a frequent clinical manifestation of asthma, a chronic inflammatory disease of the airways (4). Eosinophils play a role in multiple pathological processes, including airflow obstruction in asthma and chronic airway remodeling (5, 6). These processes include smooth muscle hypertrophy, neural plasticity, epithelial injury, and impaired tissue repair. The blood eosinophil count is a widely recognized and readily available biomarker that is of paramount importance in the management of asthma (7, 8). The correlation between elevated blood eosinophil levels and compromised disease control, as well as an increased susceptibility to severe asthma exacerbations, has been established by a multitude of studies (9–13). Additionally, blood eosinophils can be utilized to predict the response of asthma therapy and guide treatment decisions (14–17). In conclusion, blood eosinophils are an essential biomarker for asthma management and play a critical role in the onset, progression, and treatment of asthma.

Albumin is the predominant protein found in serum, making up over 60% of all blood proteins (18). It is solely produced in the liver and then released into the bloodstream. Serum albumin, with a half-life of 19 days, is crucial for regulating several physiological processes. Keeping the acid-base balance, transporting important molecules (like long-chain fatty acids, hormones, bilirubin, metal ions, etc.) through the bloodstream and to organs, stopping platelet function, Keeping the acid-base balance, transporting important molecules (like long-chain fatty acids, hormones, bilirubin, metal ions, etc.) through the bloodstream and to organs, stopping platelet function, keeping vascular permeability, and managing colloid osmotic pressure are some of these jobs (19). Furthermore, it demonstrates antioxidant properties and the ability to trap free radicals (20). Furthermore, serum albumin serves as an established clinical indicator for malnutrition (21). Asthmatic persons frequently experience malnutrition, which adversely affects their quality of life, exacerbation risk, duration of hospitalization, and overall healthcare costs (22, 23).

Recent research has shown that there is a correlation between low levels of albumin in the blood (hypoalbuminemia) and an extended duration of hospitalization in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) (24, 25). In individuals suffering from acute pulmonary embolism, low levels of serum albumin continue to serve as indicators of long-term mortality (20). However, there have been few investigations conducted to explore the connection between protein status and asthma thus far. Consequently, we utilized data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 cycles to examine the connection between protein intake, serum albumin and BEOC in patients with asthma.

The investigation is the first and most extensive cross-sectional investigation to quantify the connection between protein intake, serum albumin, and BEOC in asthma patients, to the best of our knowledge. In our study, we found a positive correlation of protein intake with BEOC, but only in the univariable regression model. However, in univariate and multivariate regression models, there was a negative correlation of serum albumin with BEOC in asthma people. In addition, we utilized the GAM and threshold effect model to verify the link between serum albumin and BEOC, which exhibited an inverted U-shaped correlation. The maximal BEOC occurred at a serum albumin concentration of 36 g/L. The XGBoost model proved that urine albumin, protein consumption, BMI, serum creatinine, PIR, ALT, AST, age, serum globulin, and serum albumin are the top 10 influential factors affecting BEOC. Our investigation gave unique insights into the connection of serum albumin with BEOC in patients with asthma.

Serum albumin is the most abundant plasma protein in the body, managing the distribution of vascular fluid and maintaining plasma colloid osmotic pressure. And serum albumin also possesses powerful anti-inflammatory and antioxidant properties due to its multiple binding sites, which provide an ideal substrate for free radical removal (26). In addition, it can still bind diverse inflammatory mediators and regulate the immune response during systemic inflammation (27). It has been postulated that serum albumin is responsible for over 70 percent of the total free radical–trapping activity, making it the predominant antioxidant in the circulatory system. Besides, albumin also has various biologic functions, such as the binding and transport of endogenous and exogenous molecules, endothelial stabilization, anti-thrombotic effects, and so on (26). Consequently, serum albumin is also a valuable biomarker for a variety of illnesses, which include obesity, diabetes, rheumatoid arthritis, and carcinoma, while it can be employed to treat various diseases, such as shock, trauma, hemorrhage, acute respiratory distress syndrome, hemodialysis, acute liver failure, chronic liver disease, hypoalbuminemia, and so on (28).

Additionally, serum albumin is also a valuable biomarker for a variety of respiratory disorders, including lung cancer, chronic obstructive pulmonary disease, acute pulmonary embolism, and bronchiectasis (20, 29–31). Meanwhile, some studies have reported the role of albumin in asthma, too. A case-control study in Nigeria involving 37 asthma cases and 30 controls has discovered that children with asthma have significantly lower serum albumin concentrations in comparison to controls and that there is a negative association between serum IgE and serum albumin, but that there is no significant association between serum albumin and blood eosinophil counts or eosinophil percentage (32). According to a Turkish case-control study involving 40 asthma cases and 40 healthy subjects, there is a significant decrease in serum albumin concentration among bronchial asthma patients compared to controls (33). Likewise, a Japanese investigation has observed that the serum albumin levels of asthmatic children are substantially lower than those of children without asthma, whereas the levels of children with wheezing symptoms or a history of allergic diseases are not significantly different (34). And another cross-sectional study in Australia has found that serum albumin is lower in people with more severe asthma and is positively related to lung function (35). Similarly, Khatri SB et al. have discovered that plasma albumin levels are substantially lower in asthmatics compared to nonasthmatics and are positively correlated with lung function (% forced expiratory volume in 1 second) in asthmatics (36). And a prospective, multicenter study in Spain has demonstrated that the onset of asthma exacerbations is negatively correlated with serum albumin levels (37). However, AbdulWahab et al. have reported that there is no significant difference in serum albumin levels between asthmatic children and control groups (38). In the same way, another study in Turkey found that serum albumin levels are not significantly different between asthmatic children and control groups (39). As well, a few investigations have looked into the connection between protein consumption and asthma. Huang SL et al. reported that protein-rich and fat-rich foods of animal origin were associated with a higher prevalence of asthma in teenagers (40). However, Schwartz J. et al. found no connection between dietary protein consumption and wheezing or asthma in children in the USA (41). Another South Korean study proved that protein consumption was shown to be slightly but significantly connected with allergic rhinitis but not with asthma (42). And Han YY et al. reported no significant connection between protein food consumption and the prevalence of asthma in Puerto Rican kids (43). Due to the inclusion of various confounders in previous studies, inconsistent conclusions have been drawn. Our investigation found no independent connection between asthmatics’ protein consumption and BEOC. But serum albumin and BEOC had an inverted U-shaped association.

In contrast to prior research, ours has some advantages. First, our inquiry provides a relatively large, nationally representative sample of adult asthmatics. Secondly, because confounders may influence the results, we use stratified analysis to determine the relationship of serum albumin with BEOC in various populations. Then, we employ the XGBoost model to determine the relative significance of selected indicators on BEOC. Lastly, the inflection point in the nonlinear relationship of serum albumin with BEOC is determined by using GAM and a two-piecewise linear regression model. But we have to acknowledge the inquiry’s shortcomings. Cross-sectional studies cannot prove a causal link between serum albumin and BEOC. Additionally, there are certain potential confounding factors that we may disregard. The medications that influenced blood eosinophils in our investigation were predominantly cortisol medications and other anti-allergy medications, excluding biologics. Asthma diagnosis is dependent on questionnaires. Future research endeavors should explore the potential influence of serum albumin in regulating and managing asthma while also elucidating potential mechanisms of action.

Our investigation discovered there was no independent link between asthmatics’ protein intake and BEOC. However, we observed an inverted U-shaped relationship of serum albumin with BEOC, suggesting a possible correlation between the overall nutritional status of asthmatics and immune system changes. Our findings provide new directions for future research in the field of asthma management and therapy.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The official website of NHANES provides access to all available data (http://www.cdc.gov/nchs/nhanes/index.htm).

The studies involving humans were approved by National Center for Health Statistics’ Research Ethics Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.

JW: Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft. JX: Data curation, Formal analysis, Writing – original draft. QH: Data curation, Formal analysis, Writing – review & editing. MG: Data curation, Formal analysis, Writing – review & editing. SG: Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review & editing.