https://orcid.org/0000-0003-4155-4547
Figures
Abstract
Background
Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is associated with an increased risk of infection disease. Low muscle mass has been linked to higher levels of inflammatory markers and weakened immune response, which may impact the susceptibility to nasal MRSA colonization. The relationship between muscle function and immune response to pathogens may be bidirectional. This study investigates the association between muscle mass and nasal MRSA colonization in adults.
Methods
The present cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Appendicular skeletal muscle mass (ASM) adjusted by body mass index (BMI) (ASM/BMI) was used to evaluate muscle mass. Multivariate logistic regression, adjusted for demographic and infection factors, was used to analyze the association between muscle mass and nasal colonization by MRSA. A subgroup analysis based on age and gender was performed to assess the impact of muscle mass on nasal MRSA colonization.
Results
Nasal MRSA colonization was more prevalent in females, those with smaller household sizes, lower income, lower ASM/BMI, those who had stayed in healthcare facilities in the past 12 months, and individuals with diabetes and smoking habits. After adjusting for confounding factors, a dose-dependent association was found between decreasing quartiles of ASM/BMI and the risk of nasal MRSA colonization (p < 0.05). Additionally, per 1 unit increase in ASM/BMI was related to a 64% lower risk of nasal MRSA colonization.
Citation: Chen B, Li S, Lin S, Dong H (2024) Investigating the relationship between muscle mass and nasal Methicillin-Resistant Staphylococcus aureus (MRSA) colonization: Analysis of the National Health and Nutrition Examination Survey (NHANES). PLoS ONE 19(1): e0294400. https://doi.org/10.1371/journal.pone.0294400
Editor: Tze Shien Lo, University of North Dakota, UNITED STATES
Received: April 16, 2023; Accepted: November 1, 2023; Published: January 2, 2024
Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=2001-2004.
Funding: This work was funded by National Natural Science Foundation of China (82004390), National Studio Construction projects for the famous experts in Traditional Chinese Medicine (Huang Feng studio N75, 2022). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Sarcopenia is a well-known condition characterized by loss of muscle mass and function, which is commonly associated with aging [1]. It has been identified as a risk factor for several chronic diseases, including cardiovascular disease, diabetes, and cancer [2]. However, its potential effects on infection susceptibility have not been extensively studied [3, 4]. Skeletal muscle plays a critical role in maintaining homeostasis across organ systems, particularly in response to stress [5], and a reduction in muscle mass has been linked to an increased risk of infection, with Staphylococcus aureus being a common causative agent [6, 7].
S. aureus is a bacterium that can colonize different parts of the body, including the skin and nasal passages, which is estimated that 20–30% of healthy adults have persistent nasal colonization of S. aureus [8–11]. Persistent nasal colonization with S. aureus is a major risk factor for infections with this bacterium. Moreover, individuals colonized with Methicillin-resistant Staphylococcus aureus (MRSA), a type of S. aureus that is resistant to certain antibiotics, are at a higher risk of becoming infected with MRSA in the future [12, 13]. Therefore, identifying and understanding risk factors that predispose individuals to S. aureus colonization is essential for a comprehensive assessment of infection risk. While some risk factors may be challenging to modify, such as muscle mass in frail patients, this knowledge can still contribute to better-targeted infection prevention strategies.
Sarcopenia has been linked to a higher risk of infection after surgery [14], possibly due to the immune senescence, which play a role in mediating immune responses. Chronic inflammation, which is associated with loss of muscle strength [4, 15, 16], has also been linked to S. aureus colonization [17–19]. However, it is not clear whether sarcopenia is an independent risk factor for S. aureus colonization in the general population. As sarcopenia is associated with changes in body composition, even a small increase in the risk of S. aureus colonization may have significant implications for the overall burden of S. aureus disease [20, 21].
Thus, the primary objective of this study is to explore the possible links between muscle mass and the risk of nasal MRSA colonization among the US population. To accomplish this objective, we will analyze data from the National Health and Nutrition Examination Survey (NHANES) that was conducted between 2001 and 2004. The findings of this investigation may provide valuable insights into the connection between sarcopenia and nasal MRSA carriage.
Methods
Data source and study population
To assess the relationship between muscle mass and risk of nasal MRSA colonization, we conducted a cross-sectional analysis using data from the NHANES which was a population-based survey that collects data on various health-related factors. The survey randomly selected 5,000 American citizens each year who were permanent residents in the United States.
For our study, we used data from NHANES 2001–2004, during which S. aureus nasal swab cultures were measured and recorded. To be included in the analysis, participants had to meet the following criteria: 1) be over the age of 18, 2) have undergone dual-energy X-ray absorptiometry (DXA) scans, and 3) have undergone an S. aureus screen test. We excluded participants with missing data, resulting in a final sample of 6,575 subjects with measurements of muscle mass and results of the S. aureus test. Please refer to Fig 1 for a participant flow chart.
Ethics statement
The NHANES study was approved by the Research Ethics Review Board of the National Center for Health Statistics, and all participants provided informed consent. After anonymization, NHANES data was publicly accessible, allowing researchers to convert it into a study-ready format. We have committed to complying with the study’s data usage guidelines, ensuring that all data were used only for statistical analysis and that all experiments adhered to relevant laws and standards. Our research methods were conducted in accordance with the Declaration of Helsinki.
Body mass index and body composition
Weight and height data were obtained from NHANES and measured with light clothing and no shoes. The body mass index (BMI) was calculated by dividing weight (kg) by the square of height (m2). Lean body mass of the arms and legs was measured using a Hologic QDR-4500A fan-beam densitometer (Hologic, Inc., Bedford, Massachusetts). Since lean body mass and skeletal muscle mass were equivalent [22], we calculated the appendicular skeletal muscle mass (ASM) by summing the lean body mass of all four limbs [23]. To account for individual differences in body size, the measured skeletal muscle mass was corrected using ASM/BMI, as this method was considered more effective in detecting muscle mass in individuals with varying body sizes [24]. We thus used ASM/BMI for all subsequent analyses.
Assessment of S. aureus nasal colonization
The NHANES survey conducted between 2001–2004 included only eligible respondents, and their nasal swabs were tested using standard culture-based methods to detect S. aureus colonization. Further details about the nasal MRSA screening test can be found on the NHANES website, which describes the laboratory methodology in more detail [25, 26]. Briefly, disk diffusion was used to identify the susceptibility of isolated strains to methicillin. Swabs that tested negative were used as controls. Samples with positive results and resistance to methicillin were classified as MRSA, while those with positive results but not resistant to methicillin were classified as Methicillin-Sensitive Staphylococcus aureus (MSSA).
Other covariates
We collected demographic data including gender, age, race, family income, and the total number of individuals in the household as covariates for the multivariate analysis. We categorized the race and ethnicity (self-reported) as follows: non-Hispanic white, non-Hispanic black, Mexican American, other Hispanic, and other race. Income was dichotomized as earning less than or equal to $45,000 per year. The total number of individuals in the household was included as a continuous variable. Additionally, we gathered several S. aureus related indicators, such as diabetes, use of antibiotics, whether the respondent stayed in long-term care facilities in the previous 12 months, smoking status, and alcohol consumption. Time spent in long-term care facilities in the previous 12 months was determined by asking the respondents if they were a patient at a long-term care or rehabilitation facility during the past 12 months. Alcohol consumption was assessed by asking the respondents if they had at least 12 alcohol drinks in the past year and was dichotomized. Smoking status was assessed by asking the respondents if they had smoked at least 100 cigarettes in their entire life.
Survey weights
To ensure that our analysis accounts for the complex survey design of NHANES and produces unbiased national estimates, we followed the guidelines suggested by the National Center for Health Statistics (NCHS) and used the R survey package. The survey package allows for proper adjustment of the intricate, multistage sampling design of NHANES. Specifically, we used the sample weight, WTMEC2YR, which represented the full sample 2-year MEC exam weight, to weight our analysis. Additionally, we included cluster and strata variables from demographic datasets in our weighted analyses to adjust for survey design. This approach allowed us to accurately estimate population parameters and make inferences about the general population based on our sample data.
Statistical analysis
Categorical variables were expressed as proportions and continuous variables were reported as mean (standard deviation [SD]). The t-test, Mann-Whitney U test, and chi-square test were used to analyze normally distributed, non-normally distributed, and categorical variables, respectively. To assess the relationship between ASM/BMI and nasal MRSA colonization, multivariate logistic regression was used. Three logistic regression models were developed, including unadjusted model; Model 2, which was adjusted for gender, age, race, total number of individuals in the household, and family income; and Model 3, which was adjusted for variables in Model 2 as well as use of antibiotics, stayed at healthcare facilities, diabetes, smoking status, and alcohol consumption. The association between increasing ASM/BMI quartiles and nasal MRSA colonization was assessed using a multivariate logistic regression model. Additionally, subgroup analyses were conducted based on age and gender to evaluate the impact of ASM/BMI on nasal MRSA colonization. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for all variables. Statistical significance was determined using a two-sided p < 0.05. To account for the complex sampling design of NHANES, the survey package and logistic regression models were used for all analyses [27, 28]. The entire analysis was conducted using R version 4.1.1.
Results
Descriptive analysis
A total of 6,575 participants aged 18 years or older were included in this study, as illustrated in Fig 1. The characteristics of the participants were summarized in Table 1. Individuals with nasal MRSA tended to be older, women, with smaller family sizes, lower income, lower ASM/BMI levels, stayed at healthcare facilities, with diabetes, and smoking, compared to the controls (p <0.05). The characteristics of the subjects across ASM/BMI quartiles were shown in Table 2. ASM/BMI quartiles were significantly associated with nasal MRSA colonization, age, gender, race, family size, income, diabetes, alcohol consumption, and smoking.
Analyzes of quantile logistic regression for risk of nasal MRSA colonization and ASM/BMI
We used logistic regression analysis to examine the association between ASM/BMI and nasal MRSA colonization, adjusting for various covariates (Table 3). In all models, a negative association was observed between ASM/BMI quartiles and the risk of nasal MRSA colonization.
In the unadjusted model, individuals in the first quartile of ASM/BMI had a significantly higher risk of nasal MRSA carriage, which decreased as ASM/BMI quartile increased (p for trend = 0.002). After adjusting for age, gender, race, family size, and income (Model 2), ASM/BMI remained an independent factor for nasal MRSA colonization (p for trend = 0.010). In Model 3, which contained additional covariates, including antibiotic use, stayed at healthcare facilities, diabetes, alcohol consumption, and smoking, higher ASM/BMI levels were still associated with a significantly lower risk of nasal MRSA colonization (p for trend = 0.019).
The risk of nasal MRSA colonization decreased by 82% and 78% in the fourth quartile of ASM/BMI compared to the first quartile in Models 2 and 3, respectively. Moreover, there was a significant negative association between per 1 unit increase in ASM/BMI levels and the risk of nasal MRSA colonization in the multivariate logistic regression analysis (p < 0.05).
Subgroup analysis of the association between ASM/BMI and nasal MRSA colonization for gender and age
We conducted subgroup analyses to investigate whether the association between ASM/BMI levels and nasal MRSA colonization differed by gender and age. The results, as presented in Table 4, showed a significant negative association between ASM/BMI levels and nasal MRSA colonization in females (p for trend = 0.024). In males, the negative association was only significant between the highest and lowest ASM/BMI quartiles.
In the age subgroup analysis, we found that the OR value for the risk of nasal MRSA colonization was significantly decreased with increasing ASM/BMI quartiles in the 18–50 age group (OR value between ASM/BMI quartiles 2, 3, and 4 compared with quartile 1 were 0.33, 0.23, and 0.12, and a significant decreasing trend was observed (p for trend = 0.016). For those aged 51–65, although the OR values for ASM/BMI quartiles 2, 3, and 4 were significantly decreased compared with quartile 1, the descending trend was not significant (p for trend > 0.05). There was no significant association between ASM/BMI levels and nasal MRSA colonization among those aged > 65 after multivariate adjustment. Taken together, the results suggest that higher ASM/BMI levels are associated with a reduced risk of nasal MRSA colonization in females and individuals aged 18–50.
Discussion
Our study aimed to investigate the association between ASM/BMI, a measure of muscle mass, and nasal MRSA colonization in adult individuals, which has not been studied before. We found a correlation between ASM/BMI and nasal MRSA colonization, which remained significant even after adjusting for various variables. Our results showed a consistent trend, with the risk of nasal MRSA colonization decreasing gradually with an increasing quartile of ASM/BMI across all models (p for trend < 0.05), and a significant negative linear association between ASM/BMI levels and the risk of nasal MRSA colonization.
These findings have important implications for further research. ASM/BMI, a relatively simple and objective measure of muscle mass, may serve as a valuable tool in identifying individuals at elevated risk of nasal MRSA colonization. The clinical utility of this association is underscored by the fact that MRSA colonization can precede and contribute to MRSA infections, which can pose significant challenges in healthcare settings. However, it is essential to recognize that our study, while demonstrating a robust association, does not establish causality. Future prospective investigations are needed to explore the causal relationship between ASM/BMI and MRSA colonization. Furthermore, our study focused on nasal colonization, and additional research can explore MRSA colonization at other body sites to provide a more comprehensive understanding of ASM/BMI’s relationship with MRSA.
An interesting finding of this study was that the relationship between muscle mass and nasal MRSA colonization varies by gender and age. Specifically, we found that females exhibit a stronger association between muscle mass and nasal MRSA colonization compared to males, even though females generally have less muscle mass than males. Despite having 40% less upper body and 30% less lower body muscle mass compared to men [29], women experience a smaller decrease in both absolute and relative muscle mass over time [30, 31]. Therefore, differences in basal muscle mass alone cannot account for the gender-specific risk of nasal MRSA colonization, and the relationship between colonization and muscle mass likely involves various factors such as sex hormone levels, nutrition, and exercise, which warrant further research [32]. Moreover, we observed a stronger association between nasal MRSA colonization and lower muscle mass in the aged 18 to 50. It is well-documented that muscle mass gradually decreases by 3–8% per decade after the age of 30, and the rate of decline is even higher after the age of 60 [33, 34]. This may be explained by the age-related decline in muscle mass and immune function [35, 36], which can weaken the host’s immune response and increase susceptibility to colonization and infection. In contrast, for those aged 50 and above, we found that the trend across increasing quartile ASM/BMI was not significant. However, these sub-groups had relatively small sample sizes due to the low prevalence of MRSA colonization within specific demographic and age categories. These small sub-group sizes may affect the precision of our estimates and the statistical power to detect associations. The reliability and generalizability of these findings may be enhanced in future research with larger sample sizes or through meta-analyses that combine data from multiple studies.
The definition of muscle mass has been a topic of debate among researchers, with different opinions on which method is most appropriate. The DXA-derived ASM/height2 method was the first to evaluate muscle mass and was found to be applicable to a large proportion of the population. [37]. However, Newman et al. argued that the ASM/height2 index cannot identify sarcopenia in individuals who are obese or overweight and suggested that fat mass should also be taken into account [38]. To address this issue, the ASM/weight index was introduced, but it has the drawback of not considering individuals’ body size and lacking clinical implications of sarcopenia. Therefore, the BMI-adjusted ASM, which combines weight and height, is considered a better index for assessing muscle mass. In our study, we used ASM/BMI to define muscle mass and found an inverse dose-response association between the risk of nasal MRSA and the increasing quartile of ASM/BMI.
This study has several limitations, including its cross-sectional design, which precludes any causal inference. The association between muscle mass and nasal MRSA colonization may be bidirectional, and the causality of this association remains unclear. Although our findings are suggestive, they do not establish causality. Further longitudinal studies are needed to assess the impact of muscle mass on the risk of nasal MRSA colonization. Additionally, it is important to note that in the human population, approximately 20% are persistently colonized while the remaining 80% are intermittently colonized [39]. Given the cross-sectional nature of our data, it is not possible to determine whether changes in ASM/BMI are related to persistent nasal MRSA colonization.
Conclusion
In this cross-sectional study, a significant association between ASM/BMI and nasal MRSA colonization was observed, with low ASM/BMI being an independently higher risk factor for nasal MRSA colonization. However, due to the nature of this study design, causal inference cannot be made, and further prospective studies are required to validate these findings and investigate the causal link between muscle mass and nasal MRSA colonization.
Supporting information
S1 Checklist. STROBE statement—Checklist of items that should be included in reports of cross-sectional studies.
https://doi.org/10.1371/journal.pone.0294400.s001
(DOCX)
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