This research pioneers the investigation into how various measures of visceral adiposity and BMI correlate with PRISm, utilizing data from the NHANES. Our results show a direct relationship: higher levels of these metrics are associated with an elevated risk of PRISm. Furthermore, the nomogram developed using LASSO regression was found to be an effective diagnostic tool for PRISm.
The interest in PRISm has surged because of its widespread occurrence and its strong link to disease advancement [30]. It has been proposed as a clinical precursor to COPD abnormal spirometry measurement, replacing terms such as “unclassified and restrictive spirometry” as defined by the Global Initiative for Chronic Obstructive Lung Disease. In a representative sample of U.S. adults from 2007 to 2012, our research revealed a stable trend in PRISm, with a prevalence of 9.90%. A cross-sectional study involving current or former smokers aged 45 to 80 years [30] found that approximately 22.2%−35.8% of PRISm cases may advance to COPD within five years, underscoring its significance as a target for early intervention [31].
Prior epidemiological studies have shown that visceral lipid accumulation is linked to an increased risk of respiratory disorders [32]. The association between important indicators of obesity and lung function remains controversial. Despite obesity being associated with a decrease in FEV1/FVC and a reduction in total lung capacity (TLC), some obese individuals often maintain lung function values within the normal range [33]. Nirupama Putcha et al. found that compared to other BMI categories, overweight and obese participants had better baseline lung function [34], and overweight or obese patients have a lower mortality rate of COPD. This phenomenon commonly referred to as the “obesity paradox”. However, commonly used measures of obesity are only crude indicators of body composition and do not allow quantification of fat accumulation, and lack accuracy in explaining the heterogeneity of local fat deposits [35]. Previous studies have found that the prevalence of COPD is related to the increase of ectopic fat accumulation, but not to BMI [36]. Furthermore, findings from the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) study indicated a direct inverse relationship between WHtR and pulmonary function [15]. Our study indicated that the risk of PRISm rose in tandem with increases in both the visceral fat index and BMI. Visceral lipid accumulation, as an important indicator of fat accumulation, was more significantly associated with PRISm than BMI.
Further investigation is required to understand how increased visceral fat contributes to a higher risk of PRISm. Adipose tissue may cause lung function impairment through a triple pathway of inflammation, oxidative stress and metabolic disorders. Visceral fat accumulation can significantly increase the expression levels of inflammatory factors such as TNF-α, IL-1β, IL-6, and MCP-1 [37, 38]. Through the circulatory system, it activates lung epithelial cells and alveolar macrophages, recruits inflammatory cell populations [39], and eventually causes chronic inflammation of lung tissue. Meanwhile, this inflammatory process is accompanied by the generation of reactive oxygen species (ROS) and lipid peroxides [40], and further induces cytokine cascades to trigger pulmonary airway remodeling and fibrosis by activating signaling pathways such as IL-6/NF-κB and AP-1 [41, 42]. Hypertrophic adipocytes will show accelerated fatty acid turnover and local tissue hypoxia, triggering endoplasmic reticulum stress and activation of Toll-like receptor 4 (TLR4), promoting adipose tissue to enter a persistent low-grade inflammatory state. This state has been proven to be closely related to chronic inflammation of lung tissue [43, 44].
Excessive accumulation of visceral fat is closely related to metabolic disorders, such as insulin resistance, which can intensify inflammatory responses and affect the functions of pulmonary vascular endothelium and airway smooth muscle [45, 46], and is closely associated with respiratory diseases [47, 48]. Our findings suggest that the combination of visceral fat accumulation and metabolic abnormalities, referred to as METS-VF, has a better predictive effect for PRISm. This also explains that visceral fat accumulation and its potential metabolic abnormalities may cause lung endothelial cell damage and dysfunction through inflammation and oxidative stress, thereby affecting lung function.
The findings of this study have direct implications for patient care. By integrating visceral fat accumulation indicators such as VAI into clinical practice, healthcare providers can more accurately identify patients at high risk for PRISm. This targeted approach allows for earlier interventions, potentially improving patient outcomes by preventing the progression of respiratory impairments [49]. The model’s good discrimination ability, as evidenced by the nomogram, provides a practical tool for clinicians to assess individual risk and tailor treatment plans accordingly [50]. This could lead to more effective management of lung function and a reduction in the prevalence of PRISm-related complications.
The integration of these indicators into routine assessments can enhance the monitoring and follow-up of lung function, particularly for patients with comorbidities like diabetes, hypertension, and cardiovascular diseases [51]. By strengthening these aspects of care, the study’s findings can contribute to improved prognoses and a better quality of life for patients. The ability to screen for comorbidities using visceral fat indicators also offers a proactive strategy for managing metabolic health, potentially reducing the burden of disease on both patients and the healthcare system [52].Future research should focus on implementing these indicators in diverse clinical settings and populations, as well as exploring their utility in predicting response to interventions. Additionally, investigating the mechanisms linking visceral fat to PRISm could uncover new therapeutic targets.
Addressed
The study’s strengths lie in its comprehensive assessment model, developed through LASSO regression analysis, which considered multiple indicators such as BMI, LAP, VAI, METS-IR, METS-VF, and WHtR. This multi-faceted approach enhances the robustness of the findings. The model demonstrated good discrimination ability, crucial for accurately identifying individuals at risk of PRISm. The nomogram visually presented each variable’s contribution to the predicted outcome, aiding in identifying key risk factors and providing a basis for clinical intervention. The focus on visceral fat accumulation indicators, like VAI, offers a novel perspective for identifying high-risk patients for PRISm.
The study’s limitations include its cross-sectional design, which does not allow for the establishment of causality. Information bias or measurement errors could impact the precision of the findings, and there may be unaccounted confounders despite attempts to control for them. While our study adheres to previously established criteria for defining PRISm, we acknowledge the limitations associated with using a fixed FEV1/FVC ratio. The GLI-2012 guidelines suggest using LLN values, which could provide a more accurate assessment of airflow limitation. Future research should consider adopting this approach to refine the diagnosis of PRISm and improve the accuracy of associated risk assessments.
Our model provides a useful tool for assessing PRISm risk, there is room for further improvement to enhance its discriminative power. The translational potential of our model lies in its comprehensive assessment of multiple risk factors. However, the practical challenges include the time and resources needed to calculate the nomogram’s variables, as well as the need for healthcare professionals to be trained in its use. These factors may limit its immediate uptake in clinical settings.