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Correlation of neutrophil percentage-to-albumin ratio with lung function in American adults: a population study

BMC Pulmonary Medicine volume 25, Article number: 86 (2025) Cite this article

Abstract

Background

Chronic respiratory diseases pose a significant threat to global health, underscoring the urgent need for effective preventative and therapeutic interventions. The neutrophil-to-albumin ratio (NPAR), an emerging biomarker for inflammation and nutritional status, has shown promising associations with respiratory health, necessitating an investigation into its potential for predicting lung function decline.

Objective

This study aimed to delineate the relationship between the NPAR and pulmonary function within a sample of the American adult population and assess the viability of the NPAR as a prognostic indicator for compromised lung function.

Methods

With data available from the National Health and Nutrition Examination Survey (NHANES) for the years 2007 to 2012, 10,055 American adults who met the exclusion criteria were included in the current study. Multivariate linear regression, smoothed curve fitting, and subgroup analyses were applied to evaluate the associations observed between the NPAR and lung function indicators.

Results

Even after accounting for all potential confounding factors, a significant inverse relationship persisted between the NPAR and key lung function indicators, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEF). This association remained robust even after potential confounding factors were considered. Subgroup analysis revealed that the negative correlation was more pronounced in certain demographic groups, such as young individuals, males, and current smokers. The study also revealed an “N-shaped” relationship between the NPAR and fractional exhaled nitric oxide (FENO), suggesting that the NPAR may play a role in promoting airway inflammation.

Conclusions

A significant correlation between the NPAR and the decline in lung function among American adults was revealed in this research, emphasizing the potential clinical relevance of the NPAR as a respiratory health biomarker, as well as the importance of considering systemic inflammation in the management and prevention of respiratory disorders.

Peer Review reports

Introduction

The capacity of the lungs to exchange gases is a fundamental physiological process [1]. Any factor that impairs pulmonary gas exchange can lead to severe health complications and a reduction in quality of life [2,3,4,5,6]. Assessing lung function through spirometry provides key measurements such as the FEV1 and FVC, which are crucial in diagnosing and monitoring respiratory diseases [7]. Respiratory diseases represent a global health issue, and their high incidence and mortality rates impose a significant economic burden on healthcare systems and society at large [8, 9]. Therefore, there is an urgent need for new biomarkers to enhance our understanding of this disease and provide insights into potential therapeutic targets.

Indicators of the inflammatory response, such as C-reactive protein, eosinophils and neutrophils, are known to be independent predictors of certain lung function parameters [10]. Neutrophils are considered major factors in lung function impairment [11]. Inflammatory biomarkers based on lymphocyte, neutrophil, monocyte, and platelet counts have been found to be positively correlated with the prevalence of chronic obstructive pulmonary disease (COPD) [12,13,14]. Recently, as a novel inflammatory marker, the NPAR has demonstrated better performance than other methods in the prediction of diseases involving acute kidney injury, stroke-associated pneumonia, and free wall rupture after acute myocardial infarction [15,16,17]. Moreover, the NPAR has also been proven to influence the clinical outcomes of various diseases, such as chronic heart failure, hip fracture in elderly individuals, sepsis, stroke and myocardial infarction [18,19,20,21,22,23,24]. For instance, A recent research has demonstrated that the NPAR is linked to all-cause mortality among critically ill patients suffering from acute myocardial infarction, underscoring its potential as a prognostic indicator in cardiovascular diseases [24]. Another study has shed light on the predictive value of NPAR in forecasting mortality rates among patients with COPD [25]. Additionally, an elevated NPAR has been correlated with increased all-cause mortality in individuals with severe sepsis or septic shock [21]. These insights, combined with the observation of low serum albumin levels in stable COPD patients, emphasize the multifaceted role of NPAR as a marker for both inflammation and nutritional status, which may significantly impact disease progression and the decline in lung function [26].

However, few studies have investigated the NPAR and respiratory diseases, and no population-based investigations have examined the connection between NPAR levels and lung function. Therefore, with the data available from the NHANES 2007–2012, the current research aims to investigate the potential correlation of the NPAR with lung function among American adults and to inform strategies for the prevention and treatment of chronic respiratory diseases.

Methods

Study design

Data from the NHANES conducted between 2007 and 2012 were used in the current study. The NHANES project generated nationally representative cross-sectional datasets with a stratified, multistage probabilistic sampling methodology. Approval for the research was obtained from the research Ethics Review Board (ERB) of the National Centre for Health Statistics (NCHS), and every participant signed the written informed consent [27]. Publicly available data were utilized for this study; therefore, no additional ethical review or informed consent was needed. After initial screening of 30,442 adults in the United States, our study ultimately included 10,055 participants on the basis of the exclusion criteria (Fig. 1).

Fig. 1
figure 1

Participant selection flowchart

Full size image

NPAR assessment

The NPAR is a novel blood inflammation index calculated as follows: (neutrophil percentage * 100/albumin [g/dL]) [25]. The neutrophil percentage, as well as the neutrophil count, monocyte count, lymphocyte count, and platelet count, were obtained with the complete blood count profile from the NHANES. The levels of albumin and high-density lipoprotein cholesterol were determined through standard biochemical profiles from the NHANES.

Lung function assessment

Spirometry, an objective and reproducible method, was employed to assess lung capacity and airflow dynamics, providing an accurate reflection of lung function. Lung function indicators include FEV1, FVC, FEV1/FVC%, PEF, forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and FENO [28]. Data for FENO were obtained from the average of two repeatable FENO measurements.

Covariates

In exploring the connection between the NPAR and lung function, several covariates that may influence this relationship were considered. Data on these covariates were derived from in-person interviews, medical examinations, and laboratory tests carried out within the NHANES period.

(1) Population characteristics, including age, sex, ethnicity/race, educational classification and marital status. In accordance with the standards of the World Health Organization, the body mass index (BMI) was categorized as low weight (below 18.5 kg/m²), regular weight (ranging from 18.5 to 24.9 kg/m²), overweight (ranging from 25 to 29.9 kg/m²), or obese (over or equal to 30 kg/m²) [29].

(2) Economic status: Economic status is mainly measured by the poverty income ratio (PIR), which is divided into three groups: poor (PIR less than or equal to 1.3), middle class (1.3 less than PIR less than or equal to 3.5), and affluent (PIR greater than 3.5) [30].

(3) Lifestyle factors: Tobacco and alcohol consumption behaviors, which refer mainly to people who smoked at least 100 cigarettes in life or consumed alcohol 12 times in the past year, were examined. “never smokers” as individuals who report having smoked fewer than 100 cigarettes in their entire lifetime, with their smoking status indicated as “NO”. Conversely, those who have smoked more than 100 cigarettes throughout their life are categorized as smokers, with their smoking status marked as “Yes”. The same goes for alcohol consumption.

(4) Medical history: the diagnosis of diabetes or hypertension was based on self-reported previous physician diagnoses.

Statistical analysis

Empower Stats (version 2.0) and R software (version 4.1.0) were used in this study to ensure rigorous methodology and precise data analysis. Data are presented as the means ± standard deviations for continuous variables as well as frequencies and percentages for categorical variables, weighted to reflect the wider American population. Stratified weighted multivariate linear regression was performed to evaluate the relationships of the NPAR with lung function, adjusted for demographic and clinical covariates. The models presented are listed below: unadjusted for Model 1; adapted for sex, age and ethnicity/race for Model 2; and adjusted for Model 3. Smoothed curve fitting was applied to explore potential nonlinear relationships, and subgroup analyses were performed to identify differences between various demographic and clinical subgroups. P value less than 0.05 was considered statistically significant.

Results

Baseline characteristics

A total of 10,055 individuals were initially identified as participants from the NHANES database (Table 1). These participants were stratified into different levels on the basis of the quartiles of the NPAR, and significant differences were observed across most demographic and clinical variables. Notably, as the quartiles of the NPAR increased, the levels of FENO increased progressively (P < 0.0001). Lung function parameters, including FEV1, FEF25%-75%, and FEV1/FVC%, tended to decrease (P < 0.0001). Within the NPAR quartiles, no significant differences were observed for variables such as race, alcohol intake, PIR, FVC, PEF, monocyte count, or platelet count (P > 0.05).

Table 1 Baseline characteristics of NHANES participants from 2007 to 2012 (n = 10,055)
Full size table

Correlations of the NPAR with lung function indicators

Correlations between the NPAR and various lung function indicators were assessed via weighted multivariate linear regression models (Table 2). An increase in FENO in the totally adjusted model (Model 3) was connected to a rising level of NPAR (β = 0.08, 95% CI: 0.07 to 0.08, P < 0.0001). In addition, with increasing NPAR by one unit, decreases in β = -0.52 (95% CI: -0.75 to -0.29, P < 0.0001), FVC (β = -0.37, 95% CI: -0.65 to -0.10, P = 0.0076), PEF (β = -1.28, 95% CI: -1.93 to -0.63, P = 0.0001), and FEF25%-75% (β = -0.99, 95% CI: -1.40 to -0.58, P < 0.0001) were observed.

Table 2 Association of NPAR with lung function parameters
Full size table

As a key indicator of lung function, the FEV1/FVC% was also significantly negatively related to the NPAR (β = -0.01, 95% CI: -0.01 to -0.00, P < 0.0001). These findings suggest that elevated NPAR values may indicate an intensified pulmonary inflammatory response, suggesting impaired lung function.

Nonlinear relationship between the NPAR and lung function

Visualization of the nonlinear link between the NPAR and lung function parameters was performed via smoothed curve fitting (Fig. 2). An “N-shaped” relationship exists between NPAR and FENO. The other curves demonstrated a clear negative trend, highlighting the increasingly detrimental effect of elevated NPAR levels on lung function.

Fig. 2
figure 2

Smooth curve fitting: nonlinear relationships between NPAR and pulmonary function indices. The solid red line represents the smooth curve fitting between variables. The blue bands indicate the 95% confidence interval of the fitting

Full size image

Subgroup analysis

Subgroup analyses were performed to explore the robust relationship of NPAR with lung function (Supplementary Fig. 1). The findings revealed that the adverse correlation of NPAR with lung function was markedly stronger among younger individuals, males, and smokers, pointing to a greater risk for these populations in terms of respiratory health when NPAR levels were elevated.

Discussions

This cross-sectional study explored the intricate relationships between the NPAR and lung function indicators among adults in the United States. To the best of our knowledge, no previous studies have evaluated the association between the NPAR as a new biomarker and indicators of lung function. Our study elucidated the correlation between the NPAR and several lung function indicators, including FEV1, FVC, PEF, and FEF25%-75%. From the 2007 to 2012 NHANES data, a significant negative correlation was observed between the NPAR and lung function indicators. The reliability and validity of our findings were significantly bolstered by the consistency of this association, which remains robust even after consideration of various confounding factors, including age, sex, ethnicity/race, smoking status, and comorbidities. Subgroup analysis of lung function parameters revealed subtle relationships. Studies have revealed that age is one of the main causes of lung function decline, especially in elderly individuals. However, this study revealed that the negative correlation of the NPAR with lung function was particularly pronounced in individuals younger than 60 years, male, divorced, with a smoking history, and without a history of alcohol consumption or diabetes (P < 0.0001). This specific cohort might be particularly vulnerable to consequences for lung function caused by systemic inflammation.

Despite the observed negative correlation between NPAR and FVC in most subgroups, an unexpected positive correlation emerged among individuals with diabetes, which differs from many other studies. Numerous studies suggest that diabetes can lead to a decline in lung function, potentially due to factors such as hyperglycemia, insulin resistance, chronic inflammation, and metabolic disorders causing microvascular changes in the lungs and a reduction in lung elasticity [31,32,33]. Future research should conduct a more in-depth subgroup analysis of diabetic patients, considering various types of diabetes (such as Type 1 and Type 2 diabetes), disease duration, treatment regimens, and other factors to explore their impact on the relationship between NPAR and lung function.

In our study, the observed correlation between the NPAR and the decline in lung function offers new perspectives for managing respiratory diseases such as asthma, COPD, and interstitial pneumonia (IP). Evidences have shown that an increase in the neutrophil count is associated with a decrease in lung function. For example, workers in smelting plants experienced a rapid decline in lung function, with significantly elevated blood and airway neutrophil levels [34]. Additionally, follow-up studies of COVID-19 survivors have revealed an association between elevated neutrophil levels during hospitalization and poorer lung function test results after discharge [35]. NPAR, as an accessible biomarker, may help identify individuals at risk of respiratory dysfunction, allowing for early intervention. Inflammation is widely considered the main driver of impaired lung function [36, 37]. Neutrophils, through the release of proteases and reactive oxygen species such as myeloperoxidase and neutrophil elastase, can destroy alveolar structure and exacerbate inflammation, leading to harmful cascade reactions [38, 39]. Albumin, known for its antioxidant properties, can neutralize free radicals, reduce oxidative damage, and regulate cell behavior and inflammatory responses through interactions with cell surface receptors, mitigating oxidative stress in the lungs and protecting alveolar epithelial cells from injury [40,41,42]. Hypoalbuminemia may disrupt the fluid balance in the lung interstitium, thereby impairing the gas exchange efficiency of the alveolar‒capillary membrane [40, 42, 43]. Particularly in COPD, neutrophils are significant effector cells mediating inflammation. In asthma, neutrophils may contribute to airway remodeling, a characteristic feature of chronic asthma, which includes cellular and extracellular matrix changes, epithelial cell apoptosis, smooth muscle cell proliferation, and fibroblast activation [44, 45]. Compared with the normal population, asthma patients have lower serum albumin levels, which indirectly supports our results in this study [46]. For IP, NPAR could serve as an emerging biomarker to assess inflammation and monitor disease progression, potentially aiding in slowing the decline in lung function and improving patient outcomes [47]. Elevated neutrophils can lead to higher progression of pulmonary fibrosis, while decreased serum albumin is associated with increased IP mortality [48, 49]. These findings emphasize the importance of considering systemic inflammation in the management and prevention of respiratory diseases and support the development of precision medicine approaches for personalized treatment strategies. The role of neutrophils in chronic inflammation is becoming increasingly recognized, and they are now seen as potential targets for therapy. This underscores the significance of NPAR as a biomarker in respiratory health, reflecting the complex interplay between inflammation, nutritional status, and lung function.

Prior studies have shown that a proinflammatory diet may contribute to an increased prevalence of early-stage COPD and a decline in lung function [50, 51]. In contrast, diets rich in antioxidants, omega-3 fatty acids, and dietary fiber have been shown to significantly modulate the levels of inflammatory markers, potentially exerting a substantial anti-inflammatory effect and reducing the risk of respiratory diseases associated with inflammation [52,53,54,55,56,57]. A prospective study in a Chinese population revealed a significant correlation between a higher intake of protein-rich diets (such as soy, meat, poultry, fish or seafood, eggs and dairy products) and a lower incidence of COPD [58]. Studies from the United States and South Korea have corroborated the association between a high-protein diet and improved lung function [59,60,61]. Adequate protein intake is instrumental in mitigating the loss of muscle mass and strength in respiratory muscles, thereby ameliorating respiratory muscle fatigue [58, 62, 63].

Our findings further support the complex associations between nutrition, inflammation, and respiratory health. NPAR, as an easily accessible and measurable biomarker, offers a promising approach for providing opportunities for the early recognition of individuals at risk of respiratory dysfunction. Clinical studies have confirmed the superior predictive power of the NPAR for assessing the risk of death in heart failure, acute kidney injury, and dialysis patients. An 8-year follow-up study demonstrated the advantage of the NPAR over other blood inflammatory biomarkers in the prediction of COPD mortality [25]. Our study fills a gap in the literature by examining a broader age range of adults and focusing on lung function parameters rather than individual disease states.

Incorporating the findings of our study with the broader context of respiratory diseases, we observe that the correlation between NPAR and lung function decline may extend to asthma and IP, in addition to COPD. In asthma, characterized by chronic airway inflammation, NPAR could serve as a systemic inflammation marker, reflecting disease severity and systemic impact. For IP, where lung tissue scarring and impaired gas exchange are prominent, NPAR might mirror the underlying inflammatory processes contributing to disease progression. Our study’s findings, which highlight NPAR’s predictive value in COPD mortality, align with these diseases’ pathophysiological traits and underscore the potential of NPAR as a biomarker in respiratory health. By integrating NPAR into clinical assessments, we can enhance personalized approaches to managing and preventing impaired respiratory function, benefiting both the general population and individuals with specific respiratory diseases. This aligns with the principles of precision medicine, aiming to improve patient care by aligning medical research with tailored therapies. Future research should focus on elucidating the mechanistic links between NPAR and respiratory diseases, validating its role as a prognostic and diagnostic tool, and ultimately, advancing precision medicine to provide personalized care to patients with respiratory diseases.

In our study, we have demonstrated a significant correlation between the NPAR and the decline in lung function among American adults. This finding not only underscores the potential clinical relevance of NPAR as a respiratory health biomarker but also prompts us to consider its broader implications in other disease contexts. Recent research has shed light on NPAR’s association with cardiovascular outcomes. Studies have shown that elevated NPAR levels are significantly linked to an increased risk of cardiovascular disease prevalence, cardiovascular disease-related death and all-cause mortality [64,65,66]. This association is particularly significant as it positions NPAR as a potential prognostic marker in cardiovascular health. Furthermore, NPAR has been identified as an independent predictor for long-term all-cause mortality in critically ill patients with acute myocardial infarction, reinforcing its clinical relevance in cardiovascular outcomes [24]. In the realm of metabolic diseases, elevated NPAR has been correlated with a higher risk of all-cause and cardiovascular mortality among individuals with diabetes [67]. Interestingly, NPAR has also been implicated in the prevalence of gallstones, suggesting its influence may extend to digestive system diseases [68]. These findings collectively suggest that NPAR is not only a significant marker in respiratory health but also has broader implications in a spectrum of other diseases. This underscores the need for further research into the mechanistic role of NPAR and its potential therapeutic applications across different medical specialties.

In addition, our findings revealed an “N-shaped” association between the NPAR and FENO. This connection may be attributed to the unique role of FENO in airway inflammation. Excessive production of reactive nitrogen species in the airways of COPD patients leads to tissue inflammation and damage [69]. As a biomarker of airway inflammation, FENO is positively correlated with the severity of airway inflammation, while NPAR may reflect the state of systemic inflammation to a greater extent [70]. Furthermore, the “N-shaped” relationship between FENO and NPAR could be influenced by various factors, including threshold effects, feedback mechanisms, and the distinct roles of eosinophils and neutrophils in airway diseases. Eosinophils are associated with allergic inflammation, whereas neutrophils are linked to acute inflammation and infection. FENO is closely related to eosinophil activity, while NPAR may more significantly reflect the activity and inflammatory state of neutrophils [71]. It is possible that before reaching a certain level of inflammation, eosinophils may not necessarily increase, leading to a less pronounced rise or even a decrease in FENO, but once this threshold is surpassed, FENO levels can rise sharply [72]. As FENO levels increase, they, in turn, exacerbate the inflammatory response. These factors collectively contribute to the unique dynamic relationship between NPAR and FENO, while relationships with other lung function variables may exhibit different patterns due to the absence of similar mechanisms.

A major advantage derived from our study was the use of a large sample from the NHANES database, which enhanced the generalizability of our results. The comprehensive application of multivariate regression models and smooth curve fitting allowed for a thorough examination of the relationships that exist within the context of the NPAR and lung function. However, like any observational study, we cannot establish causality and must consider potential residual confounding factors. The limitations inherent in the cross-sectional approach of the study prevent the determination of the temporal sequence of the associations that were noted. Consequently, we cannot ascertain whether these associations were present at the moment observed in the study or whether they developed over time.

Future research should explore the biological mechanisms linking the NPAR with lung function, particularly the interaction between neutrophil-mediated inflammation and lung tissue homeostasis. Future efforts will include joint analysis of data from multiple large databases and synchronous validation using Chinese data to expand the applicability of our conclusions. Moreover, exploring the interaction between the NPAR and genetic, environmental, and behavioral factors may provide personalized risk assessment and intervention strategies. Additionally, considering the potential of both anti-inflammatory diets and high-protein diets to increase lung function and reduce the inflammatory response, the inclusion of these two diets may generate new insights into the relationship between the NPAR and lung function.

Conclusions

A significant correlation between the NPAR and the decline in lung function among American adults was revealed in this research, emphasizing the potential clinical relevance of the NPAR as a respiratory health biomarker, as well as the importance of considering systemic inflammation in the management and prevention of respiratory disorders. Future research should explore the biological mechanisms linking the NPAR with lung function and investigate personalized risk assessment and intervention strategies.

Data availability

The survey information can be publicly accessed online for use by researchers and data professionals worldwide. For more information, please refer to the website: https://www.cdc.gov/nchs/nhanes. The data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

ERB:

Ethics Review Board

IP:

Interstitial pneumonia

NCHS:

National Centre for Health Statistics

NPAR:

Neutrophil percentage-to-albumin ratio

NHANES:

National Health and Nutrition Examination Survey

FEV1:

Forced expiratory volume in first second

FVC:

Forced vital capacity

PEF:

Peak expiratory flow rate

FENO:

Fractional exhaled nitric oxide

COPD:

Chronic obstructive pulmonary disease

FEF25%-75%:

Forced expiratory flow between 25% and 75% of FVC

BMI:

Body mass index

PIR:

Poverty income ratio

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Acknowledgements

Appreciation for the significant contribution of the NHANES participants to this research is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Geriatrics, Beilun District People’s Hospital, Beilun Branch of the First Affiliated Hospital, School of Medicine, Zhejiang University, Ningbo, Zhejiang, 315800, China

    Xiaolin Zhang, Fan Bai, Haibin Ni, Shiyuan Chen, Dan Fu, Haiyan Ren & Bin Hu

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  1. Xiaolin Zhang
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  2. Fan Bai
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Contributions

X.Z.: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft. F.B.: Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft. H.N.: Data curation, Investigation, Methodology, Supervision, Writing – review and editing. S.C.: Data curation, Investigation, Methodology, Supervision, Writing – review and editing. D.F.: Data curation, Investigation, Methodology, Writing – original draft. H.R.: Data curation, Investigation, Methodology, Validation, Writing – original draft. B.H.: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review and editing.

Corresponding author

Correspondence to Bin Hu.

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Ethics approval and consent to participate

The protocol numbers for approval by the NCHS ERB are #2005-06 and #2011-17. All participants had signed the written informed consent. For further information, please refer to the website: https://www.cdc.gov/nchs/nhanes/irba98.htm.

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Supplementary Material 1

: Supplementary Fig. 1. Subgroup analyses between NPAR and lung function in NHANES participants between 2007 and 2012.

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Zhang, X., Bai, F., Ni, H. et al. Correlation of neutrophil percentage-to-albumin ratio with lung function in American adults: a population study. BMC Pulm Med 25, 86 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03537-9

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Keywords

BMC Pulmonary Medicine

ISSN: 1471-2466

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