Impact of dynapenia, presarcopenia and sarcopenia in chronic obstructive pulmonary disease: a prospective cohort study

Abstract

Background

Reduced muscle strength and decreased muscle mass (sarcopenia) are known predictors of poor prognosis in chronic obstructive pulmonary disease (COPD). Isolated muscle weakness (dynapenia) or low muscle mass alone (presarcopenia) may also negatively impact outcomes. This study aims to compare the prognostic significance of dynapenia, presarcopenia and sarcopenia.

Methods

This prospective study enrolled patients with spirometry-confirmed COPD at a tertiary medical centre. Participants were categorised into dynapenia, presarcopenia and sarcopenia based on the presence of reduced handgrip strength (<28 kg for men, <18 kg for women) and/or decreased muscle mass (<7.0 kg/m² for men, <5.7 kg/m² for women). Physical performance was assessed using a 6 min walk test and Short Physical Performance Battery (SPPB).

Results

A total of 494 patients were enrolled, comprising 211, 59, 111 and 113 patients in the control, presarcopenia, dynapenia and sarcopenia groups, respectively. Both dynapenia and sarcopenia groups had shorter 6 min walk distances and more SPPB score ≤9 than the control group (348.7 m and 304.4 m vs 420 m, p<0.001; 30% and 44% vs 11%, p=0.036). Patients with presarcopenia and sarcopenia were prone to severe exercise-induced desaturation than the dynapenia and control group (26% and 30% vs 9% and 18%, p=0.001). The 2-year mortality was similar in the control, presarcopenia and dynapenia groups but considerably less than that in the sarcopenia group (6.2% vs 10.2% vs. 9.0% vs. 25.7%, p<0.05). Univariate and multivariate analysis showed that only sarcopenia was associated with an increased risk of mortality (HR: 4.93, 95% CI 2.56 to 9.50, p<0.001; HR: 2.07, 95% CI 1.02 to 4.21, p<0.05).

Conclusions

Aside from sarcopenia, both presarcopenia and dynapenia are not associated with an increased risk of mortality in COPD. However, patients with dynapenia experience significant functional deterioration, while those with presarcopenia present with more severe exercise-induced desaturation. Identifying each phenotype is crucial for the holistic management of COPD.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Patients with chronic obstructive pulmonary disease (COPD) and sarcopenia had worse clinical outcomes. The clinical impacts of presarcopenia (low muscle mass but preserved strength) and dynapenia (reduced strength but preserved muscle mass) are uncertain.

WHAT THIS STUDY ADDS

• Despite similar lung function, symptom and mortality risk to the control group, patients with presarcopenia are prone to severe exercise-induced desaturation, while those with dynapenia have severe functional deterioration.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Identifying each phenotype ensures early detection and enables timely intervention in the holistic care of COPD.

Introduction

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive and mostly irreversible inflammatory disease.^{1 2} The hallmark of this illness is airflow obstruction caused by airway or alveolar destruction.^{3 4} Despite major advances in pharmacotherapy, COPD remains the third leading cause of death worldwide.^{2 4 5} High mortality is partly explained by the presence of multiple comorbidities.^{3 6 7} Nutritional status is an important extrapulmonary factor that strongly influences prognosis.⁸ Low body mass index (BMI) has been identified as a prognostic marker closely linked to mortality in patients with COPD.⁹ Recent studies have shown that longitudinal loss of fat-free mass is common among older adults with COPD and is associated with higher all-cause mortality.^{10 11} Consequently, COPD is now considered a risk factor and incorporated into routine evaluations for sarcopenia.12,14 However, low muscle mass alone does not necessarily indicate reduced physical function or adverse outcomes.^{15 16} In a study of 765 community-dwelling older adults, those with isolated low muscle mass had a risk of falls similar to participants with normal muscle strength and mass, and they demonstrated a lower risk of metabolic syndrome, suggesting better overall health.¹⁵ However, this may not apply to patients with COPD, as lower fat-free mass has been reported in those with severe airway obstruction and is associated with higher mortality.¹⁷ Therefore, this study investigated the impact of presarcopenia, defined as low muscle mass with preserved handgrip strength, on symptoms, functional capacity and clinical outcomes in patients with COPD.

Dynapenia, defined as decreased physical strength with preserved muscle mass, has also gained increasing attention.18,20 Although loss of muscle mass and strength often appears to occur in parallel, their dissociation has long been recognised.^{18 20 21} Dynapenia has been linked to frailty, higher risk of cardiovascular events and increased all-cause mortality in adults with cardiovascular disease.²² However, it has rarely been examined in the context of COPD.23,25 We hypothesised that dynapenia may adversely affect clinical outcomes in patients with COPD.^{15 18}

Overall, this study aimed to test the hypothesis that, similar to sarcopenia, both presarcopenia and dynapenia negatively affect prognosis in patients with COPD. Using participants with preserved handgrip strength and muscle mass as the reference group, we first compared cross-sectional differences in lung function, symptom severity and physical performance. We then evaluated the associations of each phenotype with clinical outcomes over a 2-year follow-up period.

Material and methods

Study design

This prospective cohort study was conducted at the National Taiwan University Hospital, a university-affiliated medical centre in northern Taiwan. Participants were recruited between 1 October 2021 and 23 March 2023. The inclusion criteria were age over 20 years, a diagnosis of COPD confirmed by spirometry and no acute exacerbation (AE) within 3 months before enrolment. The exclusion criteria included pregnancy, history of lung surgery, end-stage renal disease requiring regular dialysis, pacemaker implantation or severe neuromuscular deficits limiting the ability to follow simple commands or participate in pulmonary rehabilitation programme. All patients were enrolled in a nationwide COPD pay-for-performance programme and received comprehensive pharmacological and non-pharmacological treatments according to the COPD guidelines of Taiwan.²⁶ Participants had follow-up visits every 3 months, during which clinical presentation, treatments and composite outcomes were systematically assessed and recorded. They were followed for 2 years or until death, whichever occurred first. The study protocol is summarised in online supplemental Figure S1.

Methods of measurement

Spirometry-confirmed COPD was defined as a postbronchodilator forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio of less than 70%, in accordance with the Global Initiative for Chronic Obstructive Lung Disease Report.⁴

Symptom severity was assessed using the modified Medical Research Council Dyspnoea Scale (mMRC) and the COPD Assessment Test.⁴

Body composition was measured using a direct segmental multifrequency bioelectrical impedance method with a body composition analyser (InBody S10, InBody, Seoul, Korea). Patients were instructed to sit with arms abducted 15° from the midline of the trunk and legs shoulder-width apart. After electrode placement, patients were required to remain still for 5 min until the completion of the examination.

A 6 min walk test was conducted following the guidelines of the American Thoracic Society Committee.²⁷ Exercise-induced desaturation during the test was classified into three grades based on the lowest peripheral oxygen saturation measured by pulse oximetry (online supplemental Table S1).28,30

The Short Physical Performance Battery (SPPB) consists of three components: a balance test (feet together, semi-tandem and tandem positions), gait speed (time to walk four metres at usual pace) and five chair stands (time to rise from a seated position five times). Each task was scored from 1 to 4, with 0 indicating inability to perform, based on previous reports.^{31 32} Scores from the three tasks were summed to yield a total of 0–12, with 12 representing the best performance. Criteria for impaired SPPB and its subdomains followed the Asian Working Group for Sarcopenia Consensus.¹⁴

Handgrip strength was measured in kilograms using a digital hydraulic handheld dynamometer (Jamar Plus Digital, Fabrication Enterprises, New York, USA). Patients were seated with the shoulder adducted and the elbow extended downward. Two trials of maximal isometric contraction were performed with the dominant hand, and the best result was recorded.^{14 33}

Definitions

According to the Asian Working Group for Sarcopenia Consensus, sarcopenia is defined as the coexistence of low muscle strength (handgrip strength <28 kg for men and <18 kg for women) and reduced height-adjusted muscle mass by bioimpedance (<7.0 kg/m² in men and <5.7 kg/m² in women) and/or low physical performance (gait speed <1.0 m/s or five chair-stand tests≥12 s or SPPB ≤9).¹⁴ Participants with low muscle strength (handgrip strength <28 kg for men and <18 kg for women) but preserved height-adjusted muscle mass (≥7.0 kg/m² in men and ≥5.7 kg/m² in women) were classified as dynapenia.^{15 18 34} Presarcopenia was defined as low height-adjusted muscle mass (<7.0 kg/m² in men and <5.7 kg/m² in women) with preserved muscle strength (handgrip strength ≥28 kg for men and ≥18 kg for women).^{15 34} Participants with normal height-adjusted muscle mass and normal strength were classified as the control group.

AE of COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease report.⁴ An event was characterised by worsening dyspnoea, with or without cough or sputum, within 2 weeks. Severe AE was defined as an event requiring hospitalisation or an emergency department visit.

Obesity was defined by the WHO classification for the Asia-Pacific region as a BMI >24.9 kg/m², whereas central obesity was defined as a waist circumference ≥90 cm in men and ≥80 cm in women.³⁵

Data collection and follow-up

Baseline characteristics, spirometry results, symptom severity, AE history and comorbidities were recorded. The 6 min walk test was performed annually per the pay-for-performance programme. The three components of the SPPB and the total score were documented at enrolment. Muscle strength and body composition parameters, including fat mass, fat-free mass and appendicular skeletal muscle index (ASMI), were also collected at enrolment. Severe AEs were prospectively recorded every 3 months with dates and event details. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology statement as a reporting guideline.³⁶

Pulmonary rehabilitation programme

All participants underwent at least one pulmonary rehabilitation evaluation. The arrangement of the pulmonary rehabilitation programme was determined based on the evaluation. The programme included introduction of self-management in response to AE, breathing technique education, endurance training, upper and lower limb resistance training, and inspiratory muscle training, with content tailored to individual needs. Patients could receive up to eight sessions, delivered by two experienced respiratory therapists. Programme completion was determined based on the evaluation and clinical judgement of the respiratory therapist.^{37 38}

Statistical analysis

Categorical variables were compared using the χ² test or Fisher’s exact test, as appropriate. Continuous variables were analysed using one-way analysis of variance with Bonferroni correction for post hoc comparison. Data were presented as numbers (percentages), medians (ranges) or means±SD, as appropriate. Missing data were minimal and excluded from the relevant analyses. Statistical significance was set at p<0.05 for general comparisons and p<0.0083 for post hoc tests. Kaplan-Meier curves were used to visualise the probability of severe AE or mortality, with significance analysed with log-rank test. Cox proportional hazards models were employed to analyse associations between covariates and clinical outcomes, with results expressed as HRs in univariate analysis. Covariates were selected based on clinical relevance and prior literature, and all were included in multivariate analysis.39,41 Because the ASMI and handgrip strength are components of the phenotypic classification criteria, these variables were evaluated only in univariate analysis to assess prognostic effects and excluded from multivariate models to avoid collinearity. Loss to follow-up was treated as censored at the date of last contact. Baseline and 1 year values of the 6 min walk test were compared using a paired t-test to determine mean differences. All analyses were performed with STATA V.14 (StataCorp), and graphics were generated using GraphPad Prism V.10.1.2 (GraphPad Software, Boston, USA).

Patient and public involvement

Before initiating the study, informal consultations were held with patients with COPD and their next of kin receiving care at our institution. Muscle health was identified as an important concern, and their feedback helped shape the research questions. However, patients and the public were not directly involved in the study design. Patients participated in recruitment, and their anthropometric measurements were shared with them immediately following assessment. Study results were planned for dissemination to the healthcare community through academic publication.

Results

Baseline demographics

A total of 500 patients with spirometry-diagnosed COPD were screened, and 494 met the inclusion criteria and completed all required measurements. Patients were categorised into control, presarcopenia, dynapenia and sarcopenia groups (figure 1), with 211 (42.7%), 59 (11.9%), 111 (22.5%) and 113 (22.9%) patients in each group, respectively. The mean follow-up time was 730±186 days.

Figure 1. Enrolment algorithm.

Baseline characteristics are summarised in table 1. Patients with dynapenia and sarcopenia were older than those in the control group (76.7 years and 78.8 years vs 69.2 years, p<0.001). Except for the dynapenia group (25.4 kg/m²), both the presarcopenia and sarcopenia groups had lower BMI compared with controls (21.4 kg/m² and 21.8 kg/m² vs 24.8 kg/m², p<0.001). A decline in FEV1 was observed in the presarcopenia and dynapenia groups and was significantly worse in the sarcopenia group compared with controls (1.54 L, 1.55 L and 1.28 L vs 1.71 L, p<0.001). Moreover, a significantly higher proportion of patients in the sarcopenia group had severe dyspnoea (mMRC≥2) compared with controls (75% vs 48%, p<0.001), whereas no significant differences were noted in the pre-sarcopenia (56%) or dynapenia (55%) groups.

Table 1. Baseline characteristics of the participants across the four groups.

	Control (n=211)	Presarcopenia (n=59)	Dynapenia (n=111)	Sarcopenia (n=113)	P value
Age (years)*†‡§	69.2 (9.51)	71.8 (8.31)	76.7 (8.62)	78.8 (8.25)	<0.001
Man (n, %)	183 (86.7)	50 (84.8)	101 (90.9)	98 (86.7)	0.591
Height (cm)†¶	165.8 (6.60)	163.2 (7.66)	163.9 (7.21)	160.1 (7.22)	<0.001
Weight (kg)†‡¶**	68.4 (9.76)	56.3 (7.78)	67.6 (9.57)	54.6 (7.98)	<0.001
BMI (kg/m2)†‡¶**	24.8 (3.08)	21.4 (3.16)	25.4 (3.21)	21.8 (2.86)	<0.001
FEV1(L)†§¶	1.71 (0.56)	1.54 (0.63)	1.55 (0.51)	1.28 (0.48)	<0.001
FVC (L)*†§	3.03 (0.79)	2.89 (0.89)	2.68 (0.75)	2.48 (0.71)	<0.001
mMRC≥2 (n, %)†§¶	102 (48.3)	33 (55.9)	61 (55)	85 (75)	<0.001
CAT≥10 (n, %)	51 (24.2)	17 (28.8)	29 (26.1)	39 (34.5)	0.259
Underlying disease
CHF (n, %)	7 (3.32)	2 (3.39)	2 (1.80)	1 (0.88)	0.517
CVA/TIA (n, %)	3 (1.42)	1 (1.69)	7 (6.31)	6 (5.31)	0.062
DM (n, %)	35 (16.6)	12 (20.3)	28 (25.2)	16 (14.2)	0.150
Charlson Comorbidity Index≥5 *†§	65 (30.8)	23 (39)	59 (53.2)	68 (60.2)	<0.001
≥1moderate-to-severe AE in previous 1 year (n, %)	30 (14.2)	10 (17.0)	13 (11.7)	23 (20.4)	0.308

Data were presented as n (%) or mean (SD).

^*Significant difference between control and dynapenia.

^†Significant difference between control and sarcopenia.

^‡Significant difference between presarcopenia and dynapenia.

^§Significant difference between presarcopenia and sarcopenia.

^¶Significant difference between dynapenia and sarcopenia.

^**Significant difference between control and presarcopenia.

AE, acute exacerbation; BMI, body mass index; CAT, COPD assessment test; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; DM, diabetes mellitus; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; mMRC, modified British Medical Research Council dyspnoea scale; TIA, transient ischaemic attack.

Comparison of body composition

As shown in online supplemental Table S2, male participants in the presarcopenia and sarcopenia groups, unlike those in the dynapenia group had smaller waist circumferences and lower absolute fat mass than controls (85.8 cm and 86.2 cm vs 93.0 cm, p<0.001; 14.1 kg and 15.4kg vs 17.5kg, p<0.001). Handgrip strength was lower in the dynapenia and sarcopenia groups compared with controls (women: 14.4 kg and 15.1 kg vs 22.2 kg, p<0.001; men: 22.5 kg and 21.2 kg vs 35.3 kg, p<0.001). Fat-free mass, ASMI and fat mass were reduced in the presarcopenia and sarcopenia groups, but not in the dynapenia group. A significantly higher proportion of participants in the dynapenia group were classified as obese and centrally obese compared with those in the presarcopenia and sarcopenia groups (obesity: 53.2% vs 13.6% and 12.4%, p<0.001; central obesity: 68.5% vs 28.8% and 35.4%, p<0.001).

Comparison of functional capacity

Table 2 compares functional capacity across the four groups. Patients in the control group had the longest 6 min walking distance, followed by the presarcopenia, dynapenia and sarcopenia groups (420 m vs 381.1 m vs 348.7 m vs 304.4, p<0.001). Percentages of predicted 6 min walk distance were lower in the presarcopenia and dynapenia groups, with the sarcopenia group showing the lowest value compared with controls (79.6% vs 79.8% vs. 71.6% vs 85.8%, p<0.001). Moreover, severe exercise-induced desaturation was more frequent in the presarcopenia and sarcopenia groups than in the control group (26.4% and 30.4% vs 18.1%, p<0.05). In the sarcopenia group, 6 min walk distance significantly declined after 1 year compared with baseline (figure 2A,B).

Table 2. Comparison of functional capacity across four groups.

	Control (n=211)	Presarcopenia (n=59)	Dynapenia (n=111)	Sarcopenia (n=113)	P value
6MWT (m)*†‡§	420 (100.04)	381.1 (89.16)	348.7 (113.97)	304.4 (110.42)	<0.001
6MWT (%)†	85.8 (19.06)	79.6 (18.28)	79.8 (24.06)	71.6 (24.71)	<0.001
Resting SpO2	97.5 (1.72)	98.1 (1.53)	97.1 (3.21)	97.8 (2.03)	0.050
Exercise-induced desaturation (EID)
Any degree of EID (n, %)§	149 (77.2)	42 (79.3)	68 (66.7)	87 (85.3)	0.017
Severe EID (n, %)§¶	35 (18.1)	14 (26.4)	9 (8.8)	31 (30.4)	0.001
Short Physical Performance Battery (SPPB)
Gait speed <1.0 m/s (n, %)*†‡	22 (12)	11 (21.2)	36 (37.9)	54 (53.5)	<0.001
Five chair stands test ≥12 s (n, %)*†‡	52 (28)	16 (30.8)	44 (45.8)	56 (55.5)	<0.001
SPPB score ≤9 (n, %)*†‡¶	20 (10.8)	6 (11.5)	29 (30.2)	44 (43.6)	<0.001

Data were presented as n (%) or mean (SD).

^*Significant difference between control and dynapenia.

^†Significant difference between control and sarcopenia.

^‡Significant difference between presarcopenia and sarcopenia.

^§Significant difference between dynapenia and sarcopenia.

^¶Significant difference between presarcopenia and dynapenia.

6MWT, 6 min walk test; 6MWT(%), 6MWT per cent of the predicted value; SpO2, oxygen saturation.

Figure 2. Comparison of the clinical outcomes among four groups. Nested scatter plot depicting the 6 min walk distance (A), percent of predicted value (B) and the changes over 1-year period across four groups; Kaplan-Meier curve illustrating the time to first severe AE (C) and the probability (D) of survival across four groups. *p<0.05; **p<0.01. AE, acute exacerbation.

Poor performance on SPPB was more common in the dynapenia and sarcopenia groups than in controls (30% and 44% vs 11%, p<0.001; table 2). Similarly, poor performance was more frequent in these groups on the 4 m gait speed test (38% and 54% vs 12%, p<0.001) and five chair stands test (46% and 56% vs 28%, p<0.001).

Comparison of the implementation rate of pulmonary rehabilitation

Online supplemental Table S3 compares pulmonary rehabilitation programme completion across the four groups. Completion rates were similar: 91.0% in the control group, 89.8% in the presarcopenia group, 85.6% in the dynapenia group, and 85.8% in the sarcopenia group (p=0.361).

Comparison of prognosis

Before comparing outcomes across the four groups, the prognostic impact of the classification variables, namely ASMI and handgrip strength, was evaluated. Higher ASMI was associated with a reduced risk of severe AE (HR: 0.71, 95% CI 0.570 to 0.881), but showed no significant association with mortality (HR: 1.02, 95% CI 0.976 to 1.068). In contrast, greater handgrip strength was not associated with severe AE (HR: 0.97, 95% CI 0.947 to 1.004) but was significantly associated with lower mortality (HR: 0.92, 95% CI: 0.886 to 0.963).

During the 2-year follow-up, only patients in the sarcopenia group had a significantly higher risk of severe AE compared with controls (log-rank p<0.05; figure 2C). After adjustment using the Cox proportional hazards model, neither presarcopenia nor dynapenia was an independent risk factor for severe AE (presarcopenia: HR: 0.94, 95% CI 0.48 to 1.86, p=0.862; dynapenia: HR: 1.24, 95% CI 0.72 to 2.12, p=0.439; table 3).

Table 3. Univariate and multivariate analysis of predictive factors for severe acute exacerbation and 2-year mortality based on Cox proportional hazard model.

Severe acute exacerbation
	Univariate analysis	P value	Multivariate analysis	P value
Presarcopenia vs control	1.14 (0.58 to 2.25)	0.701	0.94 (0.48 to 1.86)	0.862
Dynapenia vs control	1.45 (0.87 to 2.43)	0.155	1.24 (0.72 to 2.12)	0.439
Sarcopenia vs control	1.97 (1.23 to 3.18)	0.005	1.45 (0.85 to 2.47)	0.173
Age	1.01 (0.99 to 1.04)	0.161	0.98 (0.95 to 1.01)	0.188
FEV1	0.38 (0.26 to 0.57)	<0.001	0.39 (0.25 to 0.60)	<0.001
Charlson Comorbidity Index	1.19 (1.02 to 1.38)	0.027	1.28 (1.02 to 1.61)	0.035
Pulmonary rehabilitation completion vs incompletion	1.04 (0.57 to 1.89)	0.903	1.23 (0.67 to 2.26)	0.501

Mortality
Presarcopenia vs control	1.68 (0.64 to 4.43)	0.291	1.34 (0.51 to 3.56)	0.550
Dynapenia vs control	1.54 (0.67 to 3.52)	0.305	0.78 (0.33 to 1.83)	0.564
Sarcopenia vs control	4.93 (2.56 to 9.50)	<0.001	2.07 (1.02 to 4.21)	0.044
Age	1.07 (1.04 to 1.10)	<0.001	1.00 (0.96 to 1.05)	0.902
FEV1	0.20 (0.11 to 0.38)	<0.001	0.27 (0.14 to 0.53)	<0.001
Charlson Comorbidity Index	1.86 (1.50 to 2.30)	<0.001	1.87 (1.40 to 2.51)	<0.001
Pulmonary rehabilitation completion vs incompletion	0.58 (0.30 to 1.11)	0.100	0.57 (0.29 to 1.12)	0.103

FEV1, forced expiratory volume in 1 s.

Mortality rates were 6.2%, 10.2%, 9.0% and 25.7% in the control, presarcopenia, dynapenia and sarcopenia groups, respectively (p<0.05). Accordingly, only the sarcopenia group showed a significantly higher 2-year mortality risk than the control group (log-rank p<0.05; figure 2D). After adjusting for age, FEV1, Charlson comorbidity index and pulmonary rehabilitation completion, sarcopenia remained an independent risk factor for mortality (HR: 2.07, 95% CI 1.02 to 4.21, p=0.044; table 3).

Discussion

Among patients with COPD, the pre-sarcopenia and dynapenia groups exhibited comparable prognostic outcomes with the control group. However, dynapenia was associated with greater functional decline, whereas presarcopenia was linked to more severe exercise-induced desaturation. This study is the first to comprehensively evaluate the distinct impacts of dynapenia and presarcopenia on clinical and prognostic outcomes in COPD, highlighting that both may represent separate clinical phenotypes. Beyond reinforcing the importance of assessing both handgrip strength and muscle mass in routine care, these findings emphasise the potential value of early identification of these intermediate phenotypes. Such insights offer potential implications for novel phenotype-specific management targeting the muscular dimension of extrapulmonary trait in COPD.

Age-adjusted and sex-adjusted associations of handgrip strength and fat-free muscle mass index with severe AE and mortality have been reported in several previous studies but with variable results.1742,44 In this study, we also observed differing prognostic effects of ASMI and handgrip strength. Because ASMI could be closely linked to handgrip strength, considering both measures simultaneously is important when evaluating clinical risks in COPD.¹⁴ Therefore, we classified patients into four groups: presarcopenia, dynapenia, sarcopenia and control.^{15 34}

In this study, despite a significant reduction in fat-free mass similar to sarcopenia, the presarcopenia group had clinical outcomes comparable to the control group. This finding aligns with previous reports, showing similar falling risk and functional capacity between presarcopenia and non-sarcopenic groups, with markedly greater impairment in sarcopenia.^{15 45} Notably, the presarcopenia group showed a tendency towards reduced 6 min walk distance compared with controls, and severe exercise-induced desaturation was more prevalent (table 2). This may be attributed to the close link between low fat-free mass index and airway obstruction: during exertion, dynamic hyperinflation can particularly develop in patients with COPD and low chest wall muscle mass, resulting in reduced elastic recoil.¹⁷ In addition, previous studies have reported elevated inflammatory markers and reduced antioxidant activity in presarcopenia compared with non-sarcopenia.^{45 46} These observations highlight the importance of assessing fat-free mass even when handgrip strength is preserved in patients with COPD.

Based on our findings, dynapenia appears distinct from sarcopenia. Although patients with dynapenia had reduced strength, their dyspnoea severity and prognosis were similar to controls. However, on the 6 min walk test, the dynapenia group appeared frailer than controls. Impaired four-metre gait speed, similar to sarcopenia, was more prevalent in dynapenia than in controls. This is consistent with a nationwide Korean study showing a negative correlation between physical activity and dynapenia and with reports of higher disability prevalence in dynapenia compared with controls.^{23 47 48} Notably, patients with sarcopenia in this study experienced more pronounced deterioration in 6 min walk distance over 1 year than those with dynapenia, highlighting the importance of confirming sarcopenia in patients with muscle weakness, as it is associated with significantly worse functional outcomes.¹⁴

In this study, the risk of AE was similar in the presarcopenia, dynapenia and control groups, but tended to be higher in the sarcopenia group. After adjusting for confounders, however, sarcopenia was not a significant risk factor for severe AE. The occurrence of severe AE is multifactorial and variable in nature.^{49 50} Prediction cannot rely on a single factor; for example, the Acute COPD Exacerbation Prediction Tool (ACCEPT) incorporates nine clinically relevant factors in its model.⁴⁰ Furthermore, because all participants in this study were enrolled in a pay-for-performance programme and received comprehensive multidisciplinary care, the natural course of disease may have been altered, reducing the predictive value of anthropometric factors.²⁶ Nonetheless, the ACCEPT model identifies baseline BMI as an important predictor and a multi-hospital study of elderly patients found nutritional status to be a significant risk factor for 30-day readmission after AE.^{40 41} Taken together, we consider sarcopenia in patients with COPD a high-risk factor for severe AE that warrants clinical attention.

In our study, mortality rates were higher in the sarcopenia group than in the presarcopenia or dynapenia groups. Although all three groups were characterised by low handgrip strength or low muscle mass, both established predictors of poor prognosis, they showed different clinical outcomes.^{17 42 43} The higher mortality in sarcopenia may be explained by the greater degree of airway obstruction compared with dynapenia and presarcopenia.³⁹ In dynapenia, the obesity paradox in COPD may play a role, as a significantly higher proportion of patients were obese compared with those in the sarcopenia group.⁴⁴ For presarcopenia, the generally preserved functional capacity likely accounts for the lower mortality compared with sarcopenia.^{16 39}

The underlying mechanisms may differ. In presarcopenia and sarcopenia, muscle loss is attributed to a shift from type II to type I muscle fibres and intramyocellular fat deposition.^{21 51} In contrast, dynapenia is characterised by muscle mass preservation with progressive central fat accumulation, mimicking the occurrence of obesity rather than the changes seen in sarcopenia.⁵² These distinctions highlight dynapenia, presarcopenia and sarcopenia as separate phenotypes, particularly in COPD. Further studies are required to elucidate the detailed pathogenesis.

We propose that identifying these phenotypes is crucial because their clinical management may differ. Most patients with presarcopenia do not present with obesity, disability or poor prognosis; thus, intervention should focus on identifying underlying causes of malnutrition. Conversely, while most patients with sarcopenia are undernourished and advised to have nutritional and caloric supplementation, dynapenia management may emphasise moderate restriction of energy intake to address obesity.^{8 52 53} Although high protein intake is recommended for older adults, the target may vary: increasing muscle mass in presarcopenia and sarcopenia, but maintaining it in dynapenia.⁵³ Similarly, regarding physical training, different training intensities may be recommended due to the varying degrees of frailty between presarcopenia, dynapenia and sarcopenia.^{54 55}

This study has several limitations. First, participants were enrolled from a tertiary hospital, and most were men; therefore, the findings may not be generalisable to the global COPD population. However, the predominance of male participants is typical of the COPD population in Taiwan and parts of Asia, representing a natural limitation.^{12 13 23 56 57} Second, dynapenia was determined using handgrip strength without evaluating knee extensor strength, which Manini and Clark proposed as a more advanced method.²⁰ Knee extensor strength, however, is not included in the Asian Working Group for Sarcopenia Consensus.¹⁴ In addition, it is much simpler to perform a standardised handgrip strength measurement in daily practice than the knee extensor strength measurement. As handgrip strength has been extensively researched and is considered a reliable indicator of frailty and prognosis, we believe that the use of handgrip strength criteria can be commonly adopted in many clinical settings.^{47 58 59} Third, the definition of dynapenia used in this study is another concern. It was more restricted than that used in previous studies, most of which did not consider fat-free mass.^{23 47 48} Nonetheless, by adhering to the latest Asian Working Group for Sarcopenia Consensus, this study provides an operational definition that distinctly reflects loss of strength without loss of mass.¹⁴ Finally, body composition is dynamic, and phenotypes may shift, particularly after intervention.⁶⁰ Longer longitudinal studies are needed to clarify the consistency of the phenotypes and their clinical utility.

Conclusions

Patients with COPD in the presarcopenia and dynapenia groups had lower mortality risk than those with sarcopenia. However, the dynapenia group demonstrated a significant decline in functional capacity, while the presarcopenia group was notable for exercise-induced desaturation. Assessing handgrip strength and fat-free mass is essential to identify these phenotypes and enable timely phenotype-based interventions in the holistic care of COPD.

The funders did not influence the results/outcomes of the study despite author affiliations with the funder.

Data availability statement

Data are available on reasonable request.