Abstract
Objectives
This study aimed to investigate whether inflammation affects the outcome of swallowing ability to improve treatment for sarcopenic dysphagia.
Design
A retrospective observational cohort study was performed using data from the Japanese sarcopenic dysphagia database.
Setting
The database was constructed using data from 19 hospitals and one home visiting rehabilitation team.
Participants
Patients with sarcopenic dysphagia with measurements of C-reactive protein (CRP) and serum albumin (Alb) were included.
Measurements
Patients were assigned to two groups using CRP, Alb, and the Japanese modified Glasgow Prognostic Score (mGPS). The Food Intake LEVEL Scale (FILS) was measured at the times of admission and follow-up (FILS follow-up) to assess swallowing function.
Results
A total of 197 patients were included. Mean or median values of each parameter were as follows: age: 83.8±8.7, Alb: 3.2 ± 0.6 g/dL, CRP: 8.0 [3.0, 29.0] mg/L, mGPS: 1 [1–2], FILS: 7 [6–8], FILS follow-up: 8 [7–8], and duration of follow-up: 57.0 [27.0, 85.0] days. The FILS score at follow-up was significantly lower in the high CRP group (≥ 5.0 mg/L) than in the low CRP group (< 5.0 mg/L) (p = 0.01). Further, the FILS score at follow-up was significantly lower in the high mGPS group (class; 2) than in the low mGPS group (class; 0 and 1) (p = 0.03). In the multiple linear regression analyses without FILS at baseline, CRP and mGPS were independent risk factors for FILS follow-up. When FILS at baseline was entered, CRP and mGPS were not an independent risk factors for FILS follow-up.
Conclusions
Inflammation could modify the outcome of the patients with sarcopenic dysphagia. Inflammation may be an important risk factor in evaluating patients with sarcopenic dysphagia.
Key words: Sarcopenic dysphagia, modified Glasgow Prognostic Score (mGPS), Food Intake LEVEL Scale (FILS), malnutrition
Background
Sarcopenic dysphagia is a swallowing dysfunction caused by sarcopenia of the whole-body skeletal muscles and swallowing-related muscles (1, 2). Sarcopenic dysphagia is associated with whole-body sarcopenia, activities of daily living (ADL), low tongue pressure, and malnutrition (3, 4, 5, 6, 7). Sarcopenia and dysphagia are common conditions in older people (1). Risk factors for systemic sarcopenia are aging, undernutrition, inactivity, and disease (8, 9). Inflammation itself is associated with a risk of skeletal muscle atrophy, and in inflammatory diseases, altered metabolism causes skeletal muscle atrophy (10, 11). A study of aspiration pneumonia in mice has pointed out that the tongue muscle, a swallowing-related muscle, was atrophied (12). Further investigation of the risk factors of sarcopenic dysphagia, including inflammation, is important because it could contribute to improved assessment methods and treatments for sarcopenic dysphagia.
High levels of inflammation were detected in patients with sarcopenic dysphagia. There are four reports of sarcopenic dysphagia that describe C-reactive protein (CRP) as an indicator of inflammation (13, 14, 15, 16). Wakabayashi et al. (16) found in a single-center study that patients with sarcopenic dysphagia had higher CRP than patients without sarcopenic dysphagia (n = 35, mean of CRP = 37 [9–62] mg/L), and reported there was a single correlation between Food Intake LEVEL Scale (FILS) (17) and CRP. In the case reports of Wakabayashi et al. (13) and Hashida et al. (14), CRP was 8.6 mg/L and 5.2 mg/L, which exceeded standard values. However, in Uno et al. (15), CRP was 2.2 mg/L, which was within the standard range. Komatsu et al. (12) reported a decrease in trunk skeletal muscle in patients with aspiration pneumonia; the average of CRP for eight patients was 160 ± 46 mg/L. The swallowing-related muscles of patients with sarcopenic dysphagia may be affected by inflammation, and if the risk of sarcopenic dysphagia can be inferred from the intensity of inflammation, its diagnosis and appropriate treatment should be made. However, there are no reports of multivariate analysis of the effects of inflammation on sarcopenic dysphagia using multicenter data.
Here, we used a multicenter database to analyze whether inflammation is associated with swallowing function in patients with sarcopenic dysphagia, using multiple factors.
Methods
Study design
This was a retrospective observational cohort study using data from the Japanese sarcopenic dysphagia database (JSDD) (18). The JSDD consists of data from 19 hospitals, including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation team. The database includes 467 dysphagic patients, aged 20 years and older. Target patients had sarcopenic dysphagia with high inflammation at the time of initial evaluation. The comparison group included patients with sarcopenic dysphagia with low inflammation. The primary outcome was the FILS score at the follow-up point.
Participants
Patients with sarcopenic dysphagia registered in the JSDD were included. Patients without CRP and serum albumin (Alb) data were excluded because we used the Japanese modified Glasgow Prognostic Score (mGPS), which includes CRP and Alb levels, as an indicator of inflammation (19, 20). This is because mGPS is associated with recovery of physical function, and the higher the class, the higher the CRP (21 – 24). Systemic inflammation is closely associated with sarcopenia and poor functional outcomes in the recovery stage of stroke (21), and mGPS classes are strongly associated with inflammation. Stefan et al. (23) reported the median of the CRP as: mGPSO, 3.0; mGPSl, 24.0; mGPS2, 46.0 (p <0.001, n = 547). Patients without these parameters were excluded from this analysis. Patients with extremely high CRP (>150 mg/L) were excluded because the FILS score and swallowing function could be affected by severe disease, regardless of inflammation. Autoimmune diseases such as connective tissue diseases and inflammatory bowel diseases were not included. There were no patients whose FILS was affected for reasons other than dysphagia, such as ileus or inflammatory bowel disease, because patients with FILS 8 or lower for reasons other than dysphagia were not included in the database study (JSDD).
Outcome measures
FILS was recorded as a measure of swallowing function. FILS levels 1, 2 and 3 indicated severe dysphagia, in which the patient cannot feed by mouth. FILS levels 4, 5 and 6 were defined as moderate dysphagia, in which the patient can partially feed by mouth. FILS levels 7, 8 and 9 were defined as mild dysphagia, in which the patient can feed well by mouth. FILS level 10 is defined as no dysphagia. The FILS score at the time of admission and after three months or at the time of discharge (FILS follow-up) was evaluated. The difference of FILS levels between admission and FILS follow-up was calculated.
Parameters
The diagnoses that led to hospitalization were investigated. Age, sex, classification of facilities (acute, rehabilitation, recuperation), presence of polypharmacy, category of sarcopenic dysphagia (possible, probable) were recorded as basic information. Polypharmacy was defined as taking six or more drugs. Sarcopenic dysphagia was diagnosed using a validated, reliable diagnostic algorithm for sarcopenic dysphagia (25, 26). In the database study (18), the presence of a neurological disease, such as cerebrovascular disease, was acceptable if the diagnosis on admission was clearly not the cause of the dysphagia (27, 28). Calf circumferences, height, weight, body mass index (BMI) and hand grip strength were recorded as anthropometric measurements. CRP, Alb and mGPS were measured as inflammation-related indicators. First, the patients were divided into two groups based on CRP: those with low inflammation (CRP < 5.0 mg/L) and those with high inflammation (CRP ≥ 5.0 mg/L). The cut off value was defined as 5.0 mg/L according to mGPS standards. Next, patients were divided into three groups using the CRP value according to commonly used standards (normal: < 3.0 mg/L, mild: 3.0 mg/L ≤ CRP < 10.0 mg/L, high: ≥ 10.0 mg/L) (29). Then, Alb was used as a criterion to separate patients using a cut off value of 3.5 mg/dL. The mGPS includes the CRP and Alb values, and patients then were categorized into three classes as “0” (CRP ≤ 5.0 mg/L and Alb ≥3.5g/dL), “1” (CRP > 5.0 mg/L or Alb <3.5g/dL) or “2” (CRP > 5.0 mg/L and Alb <3.5/dL) (19, 20). The mGPS was treated as an inflammation indicator in this study because the score is associated with ADL, swallowing function, and sarcopenia (21, 28, 30). Patients with class 0 and 1 were assigned to the low mGPS group, and patients with class 2 were assigned to the high mGPS group. Class “2” indicates that both biomarkers, “high CRP” and “low Alb”, are abnormal. We considered class 2 status to reflect a greater effect on physical function than the other two classes.
The Global Leadership Initiative on Malnutrition (GLIM) criteria (31) were collected as a measure of nutritional status (no problem, moderate, severe). A two-step model for risk screening and diagnosis assessment is included in the GLIM. In the first step, a validated screening tool is used. In the second step, weight loss, BMI, and reduced muscle mass are examined. If there is one or more relevant item, it is considered to meet the phenotype criteria. Reduced food intake or assimilation, and disease burden/inflammation are examined. If there is one or more relevant item, it is considered to meet the etiologic criteria. If the patients met the phenotype criteria and etiologic criteria, the patient was diagnosed with malnutrition. The nutrition route was grouped as “Yes” or “No”. Patients with a feeding tube were assigned to the “Yes” group, and patients without a feeding tube were assigned to the “No” group. The Barthel Index (BI) score, a measure of abilities of daily living, was collected to measure patients' independence in daily activities. BI was recorded at two points, namely the primary evaluation and follow-up evaluation. FILS was recorded as a measure of swallowing function. FILS levels 1, 2 and 3 indicated severe dysphagia, in which the patient cannot feed by mouth. FILS levels 4, 5 and 6 were defined as moderate dysphagia, in which the patient can partially feed by mouth. FILS levels 7, 8 and 9 were defined as mild dysphagia, in which the patient can feed well by mouth. FILS level 10 is defined as no dysphagia. The FILS score at the time of admission and after three months or at the time of discharge (FILS follow-up) was evaluated. The difference of FILS levels between admission and FILS follow-up was calculated. The duration of follow-up with the FILS was examined.
Statistical analyses
Means were calculated for age, hand grip strength, calf circumference, height, weight, BMI, and Alb. Medians were calculated for CRP, BI, BI follow-up, mGPS, FILS, FILS follow up, and duration of follow-up with the FILS. Proportions were calculated for the categories of medical facilities, sarcopenic dysphagia, nutritional status, nutrition route, polypharmacy, and mGPS.
The t-test, Mann-Whitney U test, and Chi-squared test were performed to compare high and low inflammation groups. Multiple linear regression analysis was performed to evaluate swallowing function based on the FILS follow-up score using CRP groups, Alb groups and mGPS groups. In the analysis, in addition to these inflammation-related groups, age, sex, BMI, and duration of follow-up with the FILS were used as independent variables as they were considered to be risk factors for swallowing disorders and sarcopenic dysphagia (21, 25, 32, 33). We speculated the duration of the follow-up period could be related to the recovery of physical function. Additionally, we conducted an analysis of patients in rehabilitation hospitals only. We performed multiple linear regression analyses including CRP and mGPS groups as well as the overall analyses for all patients. A p-value < 0.05 was considered statistically significant. In the analyses, two types of models were created to investigate risk factors for FILS follow-up. Because we considered both «FILS change during the period» and «FILS at discharge, not FILS change» to be important, we created and compared models that excluded the initial state from the variables, and other models that included the initial state. In model 1, the dependent variable was FILS follow-up. The explanatory variables always included age, gender, BMI, and duration of the observation period, as well as one other group, either the CRP group, the Alb group, or the mGPS group. In model 2, the dependent valuable was FILS follow-up. The explanatory variables always include age, gender, BMI, FILS (at baseline) and duration (observation period), as well as one other group, either the CRP group, the Alb group, or the mGPS group. The difference between Model 1 and Model 2 is whether or not FILS at baseline is included as an explanatory factor. The effect of factors on FILS at follow-up time were compared using the results of multiple linear regression analyses.
The statistical software EZR (34) was used for the calculations and analyses. EZR is a modified version of R Commander (35).
Ethical information
The ethics committee of the Yokohama City University Medical Center approved the study (Approval ID: B190700074). All participants provided informed consent prior to enrollment or were given the right to refuse participation in the study (opt out).
Results
A total of 197 patients were analyzed in this study (Figure 1). There were 287 patients with sarcopenic dysphagia registered in the JSDD. Of these, CRP and Alb were available in 208 patients. Eleven patients with very high CRP (≥ 150 mg/L) were excluded. Two data items for handgrip strength and one item for calf circumference were unavailable in 197 patients. No patients had autoimmune conditions. The diagnoses that led to hospitalization were hip fracture (n = 57), cerebrovascular disease (n = 34), pneumonia (n = 26), heart failure (n = 19), spinal fracture (n = 18), disuse syndrome (n = 10), urinary tract infection (n = 4), pelvic fracture (n = 4), and other diagnoses in 25 patients. Table 1 shows demographic data for all patients and for each CRP group. The number of males was 71, and females was 126. Seventy patients were in acute hospitals, 114 in rehabilitation hospitals, and 13 in recuperation facilities. Mean and median values for each parameter were age: 83.8 ± 8.7, Alb: 3.2 ± 0.6 g/dL, CRP: 8.0 [3.0, 29.0] mg/L, and mGPS: 1 [1–2]. The median FILS score at baseline was 7 [6–8] and at 57.0 [27.0, 85.0] days was 8 [7–8]. The difference between FILS scores was 0 [0–1]. The low inflammation group (CRP < 5.0 mg/L) and high inflammation group (CRP ≥ 5.0 mg/L) included 67 and 130 patients, respectively. There was no significant difference in age (p = 0.171) or BMI (p = 0.622) between the low and high inflammation groups. However, there were significant differences in the BI score (p = 0.008) and BI follow-up score (p < 0.001). Although there was no significant difference in the FILS score (p = 0.089) or the duration of follow-up with FILS (p = 0.326), the FILS follow-up significantly lower in the high inflammation group compared to the low inflammation group (p = 0.013).
Figure 1.
Flowchart of patient selection
The JSDD include 467 patients. There were 287 patients with sarcopenic dysphagia in the JSDD. Of these, 79 patients were excluded because CRP or Alb were unavailable. Eleven patients with very high CRP (≥ 15.0 mg/L) were excluded. Finally, 197 patients were included.
Table 1.
Patients' characteristics
| Overall | Low inflammation group CRP < 5.0 | High inflammation group CRP ≥ 5.0 | p | |
|---|---|---|---|---|
| Number | 197 | 67 | 130 | |
| Age (years) | 83.8 ± 8.7 | 82.8 (9.6) | 84.6 (8.2) | 0.171 |
| Gender | 0.876 | |||
| male | 71 (36.0) | 25 (37.3) | 46 (35.4) | |
| female | 126 (64.0) | 42 (62.7) | 84 (64.6) | |
| Medical facilities | 0.002* | |||
| Acute (%) | 70 (35.5) | 14 (20.9) | 56 (43.1) | |
| Rehabilitation (%) | 114 (57.9) | 50 (74.6) | 64 (49.2) | |
| Recuperation (%) | 13 (6.6) | 3 (4.5) | 10 (7.7) | |
| Height (cm) | 151.6 ± 10.2 | 151.7 (11.1) | 151.6 (9.7) | 0.930 |
| Weight (kg) | 44.7 ± 9.7 | 45.2 (10.4) | 44.4 (9.3) | 0.562 |
| BMI (kg/m2) | 19.4 ± 3.3 | 19.5 (3.8) | 19.3 (3.4) | 0.622 |
| Calf circumference (cm) | 27.1 ± 3.4 | 28.1 (3.4) | 26.5 (3.3) | 0.001* |
| Hand grip (kg) | 10.9 ± 7.5 | 12.9 (7.8) | 9.9 (7.1) | 0.008* |
| Alb (g/dL) | 3.2 ± 0.6 | 3.5 (0.5) | 3.1 (0.6) | <0.001* |
| CRP (mg/L) | 8.0 [3.0, 29.0] | 2.0 [1.0, 3.0] | 21.0 [8.0, 52.0] | <0.001* |
| Sarcopenic dysphagia | 0.274 | |||
| Possible (%) | 128 (65.0) | 40 (59.7) | 88 (67.7) | |
| Probable (%) | 69 (35.0) | 27(40.3) | 42 (32.3) | |
| Nutrition route | 0.168 | |||
| Yes (%) | 162 (82.2) | 59 (88.1) | 103 (79.2) | |
| Polypharmacy | 0.019 | |||
| Yes (%) | 36 (17.8) | 18 (26.9) | 17 (13.1) | |
| Nutritional status (GLIM) | 0.001* | |||
| No problem (%) | 4 (2.0) | 3 (4.5) | 1 (0.8) | |
| Moderate (%) | 46 (23.4) | 26 (38.8) | 20 (15.4) | |
| Severe (%) | 147 (74.6) | 38 (56.7) | 109 (83.8) | |
| Barthel Index (points) | 25 [5,50] | 40 [20, 50] | 20 [1.3, 48.8] | 0.008* |
| Barthel Index follow up (points) | 55 [15,8] | 70 [40, 80] | 45 [10, 70.0] | <0.001* |
| FILS (points) | 7 [6, 8] | 7 [6, 8] | 7 [5, 8] | 0.089 |
| FILS follow-up (points) | 8 [7, 8] | 8 [7, 8] | 7 [7, 8] | 0.013* |
| FILS difference (points) | 0 [0, 1] | 0 [0, 2] | 0.0 [0, 1] | 0.276 |
| Duration of follow-up with FILS (days) | 57.0 [27.0, 85.0] | 61.0 [41.5, 84.5] | 54.0 [21.0, 85.5] | 0.326 |
| mGPS | ||||
| Level 0 (%) | 42 (21.3) | 36 (53.7) | 64 (6) | <0.001* |
| Level 1 (%) | 69 (35.0) | 31 (46.3) | 38 (29.2) | |
| Level 2 (%) | 86 (43.7) | 0 (0.0) | 86 (66.2) | |
| mGPS (points) | 1 [1.00, 2.00] | 0.0 [0.0, 1.0] | 2.0 [1.0, 2.0] | <0.001* |
BMI, Body Mass Index; mGPS, Japanese modified Glasgow Prognostic Scale (0, 1, 2, 0 = low, 2 = high; mGPS is an indicator of inflammation and nutrition based on CRP and serum albumin); GLIM, The Global Leadership Initiative on Malnutrition; CRP, C-Reactive Protein; FILS, Food Intake LEVEL Scale at baseline (1, 2, 3, 4, 5, 6, 7, 8, 9, 10; “1” = severe, “10” = normal, FILS is a ranking scale of swallowing function); FILS follow-up, FILS at follow-up time; FILS difference, difference of FILS at follow-up time; p, p value of t-test or Mann-Whitney U test or Chi-squared test; * = p <0.05
There were 114 patients in rehabilitation hospitals, 50 of whom were included in the low inflammation group (CRP < 5.0 mg/L) and 64 in the high inflammation group (CRP ≥ 5.0 mg/L). The median FILS scores at baseline (low inflammation group / high inflammation group) were 8 [7, 8] / 7 [6.8, 8]. The median FILS follow-up scores also were 8 [7, 9]/7 [7, 8], with a difference between baseline and follow-up of 0 [0, 1.8]/0 [0, 1] (p = 0.017). Seventy-four patients in rehabilitation hospitals were included in the low mGPS group and 40 in the high mGPS group. The median FILS scores (low mGPS/high mGPS) were 7 [7, 8]/7 [5.3, 8.0]. The FILS follow-up scores were 8 [7, 9]/7 [7, 8], with a difference between baseline and follow-up of 0 [0, 1.8]/0 [0, 1]. The FILS score at baseline was not significantly different between the two groups (p = 0.096). However, the FILS follow-up score was significantly lower in the high inflammation group than in the low inflammation group (p = 0.046).
Table 2 shows the comparison of swallowing function among the three CRP groups. There was a significant difference in the FILS score at baseline (p = 0.003). There was no significant difference in age, the FILS follow-up score, difference in the FILS score, or duration of follow-up with the FILS. Table 3 shows the comparison of swallowing function among mGPS group and Alb groups. Although there was no significant difference in the FILS score at baseline or the duration of follow-up, the FILS follow-up score was significantly different in the two groups (p = 0.026). In the comparison of Alb group, there was no significant difference between groups except for age.
Table 2.
Comparison of swallowing function among three CRP groups
| CRP < 3.0 | 3.0 ≤ CRP < 10.0 | CRP ≥ 10.0 | p | |
|---|---|---|---|---|
| Number (male) | 43 (15) | 65 (22) | 89 (34) | |
| FILS | 7 [6, 8] | 8 [7, 8] | 7 [3, 7] | 0.003* |
| FILS follow-up | 8 [7, 8] | 8 [7, 8] | 7 [7, 8] | 0.111 |
| FILS difference | 1.0 [0, 2] | 0.0 [0, 1] | 0.0 [0, 1] | 0.123 |
| Duration (days) | 59.5 [23.8, 84.0] | 61.0 [38.0, 81.0] | 52.0 [19.0 89.0] | 0.511 |
CRP groups was consisted with three groups as patient with “CRP < 3.0”, “3.0 ≤ CRP < 10.0” and “CRP ≥ 10.0”. FILS, Food Intake LEVEL Scale; Duration, duration of follow-up with FILS; p, p value of t-test or Mann-Whitney U test; * = p <0.05
Table 3.
Comparison of swallowing function among mGPS groups and Alb groups
| mGPS 0 and 1 | mGPS 2 | p | Alb < 3.5 | Alb ≥ 3.5 | p | |
|---|---|---|---|---|---|---|
| Number (male) | 111 (39) | 86 (32) | 124 (43) | 73 (28) | ||
| FILS | 7 [6, 8] | 7 [5, 8] | 0.211 | 7 [6, 8] | 7 [6, 8] | 0.420 |
| FILS follow-up | 8 [7, 8] | 7 [7, 8] | 0.026* | 7 [7, 8] | 8 [7, 8] | 0.072 |
| FILS difference | 0.0 [0, 2] | 0.0 [0, 1] | 0.052 | 0.0 [0, 1] | 0.0 [0, 2] | 0.133 |
| Duration (days) | 60.0 [37.5, 84.5] | 52.0 [20.0, 85.5] | 0.283 | 59.5 [23.8, 84.0] | 56.0 [30.0, 86.0] | 0.654 |
mGPS group was consisted with two groups as patient with mGPS class “0 and 1” and class “2”; Alb group was consisted with two groups as patient with “Alb < 3.5” and “Alb ≥ 3.5”; FILS, Food Intake LEVEL Scale; Duration, duration of follow-up with FILS; p, p value of t-test or Mann-Whitney U test; * = p <0.05
Table 4 shows the results of multiple linear regression analysis for the FILS follow-up including the CRP groups, Alb groups, and mGPS groups. In Model 1, CRP was an independent risk factor for swallowing based on the FILS follow-up score (p = 0.035). There was a trend in the Alb group as a predictor of swallowing function (p = 0.054). The mGPS was an independent risk factor for swallowing based on the FILS follow-up score (p = 0.015). In the analyses for the patients in rehabilitation hospitals, CRP, age, and mGPS were independent risk factors for swallowing based on the FILS follow-up score (CRP group: p = 0.042, age: p = 0.035/Table 9; age = 0.030, mGPS group: p = 0.041). In Model 2, the CRP group, the Alb group, and mGPS group were not independent risk factors. Only FILS (at baseline) was an independent risk factor in all analyses (all p < 0.001) (for detailed results, see supplementary tables).
Table 4.
Multiple linear regression analysis for FILS follow-up including CRP group or Alb group or mGPS group
| Overall (n = 197) | Rehabilitation only (n = 114) | |||||||
|---|---|---|---|---|---|---|---|---|
| Model 1 | Model 2 | Model 1 | Model 2 | |||||
| ß | p | ß | p | ß | p | ß | p | |
| CRP Group | −0.151 | 0.035* | −0.057 | 0.300 | −0.191 | 0.042* | −0.020 | 0.764 |
| Alb Group | 0.144 | 0.054 | 0.068 | 0.236 | 0.1.84 | 0.065 | −0.006 | 0.936 |
| mGPS Group | −0.177 | 0.015* | −0.102 | 0.064 | −0.194 | 0.041* | −0.008 | 0.904 |
Model 1; Multiple linear regression analysis model No.1. The dependent valuable is FILS follow-up. The explanatory variables always include age, gender, BMI, and duration (observation period), and one other group, either the CRP group, the Alb group, or the mGPS group. Model 2; Multiple linear regression analysis model No.2. The dependent valuable is FILS follow-up. The explanatory variables always include age, gender, BMI, FILS (at baseline) and duration (observation period), and one other group, either the CRP group, the Alb group, or the mGPS group. The CRP group, Alb group, and mGPS group means factors that were added in addition to the essential explanatory factors for each model. ß, estimated standardized partial regression coefficient; p, p — value of multiple linear regression analysis
Discussion
We draw two major conclusions from this study. First, when patients with sarcopenic dysphagia are grouped by CRP using 5.0 mg/L as a cut off, high inflammation affects the prognosis of swallowing in addition to the initial state of the swallowing function. Second, the mGPS, a prognostic tool that includes an inflammatory index in addition to baseline swallowing function, could be an indicator predicting the prognosis of sarcopenic dysphagia.
Functional prognosis of sarcopenic dysphagia is associated with inflammation based on CRP. We detected 66% of the patients with a CRP of 5.0 mg/L or higher. Although there was no significant difference in swallowing function at baseline or at follow-up within each group, the swallowing function at the time of follow-up was significantly lower in the high inflammation group compared to the low inflammation group. CRP was an independent risk factor even after adjusting for age, gender, BMI and follow-up period. On the other hand, in the model 2, a multivariate linear regression analysis with baseline FILS as an explanatory factor, the only independent risk factor was baseline FILS itself. The prognosis of swallowing function is strongly influenced by its initial state. However, in model 1, which excluded baseline FILS influence, CRP was found to be an independent risk factor. Thus, the functional prognosis of patients with sarcopenic dysphagia is influenced by baseline FILS and CRP could be one of the predictors of the functional outcome.
The mGPS may be predictive of sarcopenic dysphagia. CRP was related to the swallowing function at follow-up and there was a trend for Alb to predict swallowing function on its own. Furthermore, a high mGPS (class; 2) was associated with swallowing function at the follow-up. In the model 1, which excluded baseline FILS influence, mGPS was found to be an independent risk factor as well as CRP. In the model 2, only baseline FILS was an independent risk factor. Thus, the mGPS (class; 2) could be a predictor for functional prognosis of patients with sarcopenic dysphagia as well as CRP.
There is possibility that inflammation is associated with weakness of swallowing muscles. When the inflammatory reaction increases, protein catabolism increases in skeletal muscle, releasing amino acids (10, 11). Komatsu et al. (12) revealed the association between aspiration pneumonia and the degeneration of swallowing muscles in mice. It is possible that there could be an association between inflammation and weakness of the swallowing muscles in humans. We speculate that a lower degree of recovery of swallowing function was observed in the patients in our study because of the presence of inflammation, which promotes muscle weakness. Yoshimura et al. (21) reported that systemic inflammation was closely associated with sarcopenia and poor functional outcomes measured by the FIM-motor subscale in the recovery stage of stroke. It is possible that the recovery of swallowing function could be affected by inflammation in the same way as the recovery of whole-body motor function. The results of this study showing the association of inflammation and recovery of the swallowing function may be useful for predicting the prognosis of patients with sarcopenic dysphagia.
There are some limitations in this study. First, ideally, we should divide patients into three groups based on inflammation, namely mGPS classes of 0, 1, and 2. However, because of the small sample size, we used two groups in this study. Second, the type of inflammation could not be determined. Weak chronic inflammation could be a cause of sarcopenia (10, 11) and should be considered separately from acute inflammation. The present data did not allow us to determine whether the patients had a history of minor chronic inflammation.
Conclusion
Inflammation could modify the outcome of the swallowing function of the patients with sarcopenic dysphagia in addition to the initial sate of the swallowing function. There is possibility that high inflammation leads to poor recovery of swallowing function in patients with sarcopenic dysphagia. The level of inflammation may be an important factor in evaluating patients with sarcopenic dysphagia.
Acknowledgment
We thank the members of the Japanese Working Group on Sarcopenic Dysphagia for helpful discussions.
Disclosure statement
Hidetaka Wakabayashi reports grants from JSPS KAKENHI, Grant Number 19H03979. Takashi Mori, Masako Kishima, Masataka Itoda, Ichiro Fujishima, Kenjiro Kunieda, Tomohisa Ohno, Takashi Shigematsu, Fumiko Oshima, Nami Ogawa, Shinta Nishioka, Ryo Momosaki, Akio Shimizu, Yuto Saito, Minoru Yamada, and Sumito Ogawa have nothing to disclose.
Electronic Supplementary Material
Supplementary material is available for this article at https://doi.org/10.1007/s12603-022-1769-9 and is accessible for authorized users.
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