Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of mortality globally, causing 3.23 million deaths in 2019 and imposing a substantial burden on healthcare systems (1). Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio ≥0.7 and FEV₁ <80% of the predicted value, with a global prevalence reported between 7.1% to 20.3% (2–4). Compared with normal spirometry, those with PRISm exhibit higher morbidity and poor health outcomes, including increased respiratory symptoms, decreased exercise tolerance, and higher rates of respiratory-related hospitalizations and fatalities (2, 5, 6). PRISm does not always normalize over time, and 20–30% of individuals progress to obstructive ventilation dysfunction (7). Research has indicated that the PRISm population is more likely to be clinically diagnosed with asthma and COPD (2). The 2024 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines noted that the PRISm population should be regarded as “patients” and receive care and treatment (7). PRISm may be a precursor of COPD in some individuals, and its reversibility is particularly important (6, 8). Despite the increasing attention that PRISm has received, the mechanisms of PRISm development, longitudinal trajectories, and therapeutic management have not been fully described. Given the substantial effects that COPD has on population health and economy, early identification of PRISm and suitable interventions are crucial for COPD prevention.

Obesity is a significant risk factor for chronic noncommunicable diseases worldwide and is closely related to increased disease incidence and mortality (9). Several studies have demonstrated a strong correlation between obesity and inflammatory respiratory conditions, such as COPD and asthma (10–12). Previous research has identified risk factors for PRISm, including advanced age, smoking, and an abnormal body mass index (BMI) (13). Notably, both low and high BMI were associated with an increased risk for PRISm (13). Recently, central obesity has been recognized as a more representative manifestation of obesity-related systemic inflammation and metabolic damage (14). Central obesity is more closely associated with changes in dynamic lung function parameters than BMI (15). The weight-adjusted waist index (WWI), proposed by Park et al. (16); is more accurately reflects central obesity by capturing adipose tissue distribution. WWI combines the advantages of waist circumference, overcomes the limitations of BMI, and provides a more robust assessment of fat and muscle mass (17). This characteristic makes WWI potentially more reliable and sensitive in assessing obesity-related health risks.

PRISm represents a distinct pulmonary function phenotype potentially indicative of early COPD. Despite central obesity’s established role in respiratory pathophysiology, no studies have yet explored the relationship between WWI and PRISm. This study investigates (1) the association between WWI and PRISm, and (2) WWI’s linkage to all-cause mortality in U.S. adults with and without PRISm.

Publicly accessible data were derived from the National Health and Nutrition Examination Survey (NHANES) (18), which started releasing public-use data in 1999 and continues to do so every 2 years. To create a representative and randomized sample of the noninstitutionalized civilian population in the U.S., the NHANES data collection is designed with stratified, multistage, and cluster sampling (18). The study protocol was approved by the U.S. National Center for Health Statistics Institutional Review Board (Protocol #2005-06, #2011-17), and all participants provided written informed consent.

This study revealed the associations between WWI and PRISm as well as all-cause mortality using data from NHANES 2007–2012. We found a nonlinear relationship between WWI and PRISm, with lower WWI values associated with increased PRISm risk. Notably, WWI exhibited a U-shaped association with all-cause mortality in the PRISm population but a linear positive relationship in non-PRISm individuals and the overall cohort. Maintaining WWI within an optimal range may reduce mortality risk in PRISm patients.

Obesity is well known to be associated with a variety of diseases and an increased risk for mortality (28). However, the “obesity paradox” in COPD suggests that obesity/overweight may improve survival in COPD patients (29–31). Slight obesity is also considered a protective factor for lung function in people at risk of COPD (32). PRISm is a prodromal symptom of COPD, 22.2% to 35.8% of PRISm cases progress to COPD within 5 years (2, 8, 33). Recently, central obesity has been shown to be a significant risk factor for impaired lung function (34, 35). Research has proposed that FEV₁ and FVC are better predicted by measurements of abdominal adiposity, such as waist circumference, than BMI (36, 37). In a 10-year cohort study, central obesity was found to be an independent risk predictor for COPD (38). In addition, another cohort study revealed that the visceral adiposity index (VAI) and lung function had a U-shaped association, with both excessively high and low VAI values being strongly linked to decreased lung function (39).

WWI is a novel obesity assessment index that plays a unique role in accurately reflecting central obesity (40, 41). Subsequent studies have also shown significant associations between WWI and visceral fat and muscle mass (42, 43). PRISm is a high-risk group of COPD patients, and there is still a lack of research on the management of PRISm. On the basis of previous studies related to obesity and COPD, we hypothesized that there might be some association between WWI and PRISm, and our study confirms this. The results revealed a nonlinear relationship between the WWI and PRISm, even after adjustment for confounders, including BMI. Fat distribution may be an important factor in the development of PRISm. Studies have shown that in the case of a high visceral fat load, the body may activate protective mechanisms or adjust metabolic pathways, such as antioxidant defense systems or anti-inflammatory molecules, to mitigate the effects of excessive fat accumulation in organs (44, 45). Some individuals with high WWI values may have greater subcutaneous fat storage capacity, which exerts a weaker effect on inflammation and metabolism than visceral fat and may even be protective (46, 47).

Given the older age, higher prevalence of obesity, and obesity-related comorbidities in PRISm (48), a higher all-cause mortality linked to PRISm than normal spirometry is not unexpected. Compared with normal spirometry, PRISm considerably increases the risks of respiratory disease, cardiovascular disease (CVD), and all-cause death (13, 49, 50). In real-world biomedical research, the effects of many research factors on outcome variables are not simple linear patterns but rather complex threshold effects. Specifically, these factors may have a positive or negative effect on the outcome variable within a certain range, but the direction of the effect changes once a certain cutoff point exceeds (51). For example, studies have reported a threshold effect between WWI and CVD risk (52). Another study revealed a nonlinear correlation between the WWI and all-cause mortality; only in the top quartile of WWI levels (≥11.2 cm/√kg) was the risk of mortality significantly increased (53). A similar phenomenon was found in our results. On one side, when WWI is greater than 10.8974, the effect of abdominal obesity on PRISm shifts from negative to positive. Apart from that, we found a U-shaped association between WWI and all-cause mortality in PRISm. Specifically, when the WWI was near the range of the second quartile, the risk of all-cause mortality was lowest in the PRISm population.

This phenomenon may be the result of a combination of various mechanisms. On the one hand, visceral fat is a metabolically active tissue that can release various proinflammatory cytokines, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) (54). Through systemic inflammatory responses, these proinflammatory substances impact lung tissue, resulting in oxidative stress and chronic inflammation (55). The infiltration of adipose tissue by activated macrophages and their interaction can also induce systemic inflammation, which may also contribute to pulmonary function impairment (56). In addition, fat deposition in the mediastinum and abdominal cavity alters breathing patterns and respiratory system compliance, which impair pulmonary function parameters through mechanical factors (57).

On the other hand, obesity may involve not only fat accumulation but also a decline in skeletal muscle mass. Research has demonstrated a correlation between sarcopenia and the severity of respiratory diseases (58). The WWI threshold effect may be linked to changes in muscle mass. Therefore, the impacts of muscle loss may offset the contribution of visceral fat to all-cause mortality in PRISm when the WWI surpasses a certain threshold. Second, obesity is a sign of lower cumulative tobacco exposure, and individuals who quit smoking gain more weight over time than do those who continue smoking (59). Among individuals with similar amounts of tobacco exposure, obesity might be protective against disease progression. The protective function of obesity in reducing mortality has been confirmed in COPD patients in another study, which revealed that a BMI greater than 30 kg/m² was associated with increased spirometry parameters (FEV₁ and FVC) (60). This dual effect of obesity and adipose tissue on the organism may account for the complex relationship between WWI and PRISm as well as all-cause mortality.

This is the first study to examine the association between central obesity and PRISm. We used an emerging obesity assessment metric, which offers new perspectives for future application of WWI in PRISm studies. However, several limitations of the study should be noted. First, the cross-sectional design of this study makes it impossible to determine a causal relationship between WWI and PRISm. Future prospective or longitudinal studies could be conducted to confirm causality, and Mendelian randomization could also be considered to strengthen causal inference. Second, because of the sample size limitations for postbronchodilator data, we used prebronchodilator spirometry values. Previous studies on PRISm utilizing NHANES data have been published with the same limitations (23, 61, 62). Future studies with larger sample sizes should use postbronchodilator data to more accurately assess the relationship between PRISm and WWI. Nevertheless, our findings still provide meaningful insights. Third, even though we adjusted for various potential confounders, such as demographic characteristics, lifestyle, and physical activity levels, we were unable to rule out all potential residual confounders, particularly unmeasured variables. Finally, because NHANES is limited to the U.S. adults, our results may lack representativeness for other countries and regions. Future studies should incorporate imaging data, inflammatory biomarkers (e.g., CRP, IL-6), or metabolic pathways (e.g., insulin resistance, oxidative stress) to investigate potential mechanisms through which WWI may influence PRISm. Clinical trials evaluating targeted interventions, such as central obesity control or weight management are warranted to assess their effects on PRISm progression and mortality.

The present study revealed that lower WWI value is associated with an increased risk of PRISm. We further identified a U-shaped association between WWI and all-cause mortality in the PRISm population, indicating both excessively low and high WWI levels elevate mortality risk. Central obesity likely mediates PRISm pathogenesis, and maintaining WWI within an optimal range may reduce mortality risk in individuals with PRISm. Integrating WWI assessment and targeted interventions into PRISm management protocols could mitigate disease progression and lower mortality rates.