End-stage lung disease (ELD) is a clinical syndrome characterized by progressive, irreversible impairment of pulmonary function and systemic multiorgan pathophysiological disturbances (1, 2). It encompasses life-threatening respiratory conditions such as chronic obstructive pulmonary disease (COPD), pulmonary interstitial fibrosis, and pulmonary arterial hypertension (3). Notably, disease progression is accompanied by complex interacting factors, including chronic hypoxemia, systemic inflammatory cascades, disruption of metabolic homeostasis, and long-term pharmacotherapy (e.g., glucocorticoid use) (4–6), which synergistically drive the progressive depletion of skeletal muscle mass and function—a condition termed secondary sarcopenia. This complication has emerged as a critical, independent risk factor influencing clinical outcomes in ELD patients, profoundly impacting prognosis and therapeutic decision-making (7, 8).

Epidemiological investigations have revealed significant heterogeneity in the prevalence of sarcopenia among patients with ELD, ranging from 7.9 to 89% (8, 9), which is substantially higher than in age-matched healthy populations (7). Sarcopenia exacerbates the progression of primary diseases through multiple pathological mechanisms: it not only directly impairs respiratory muscle efficiency, leading to deterioration in ventilatory function (10), but also induces peripheral muscle atrophy, resulting in a precipitous decline in exercise capacity (11), while significantly increasing the risk of fall-related fractures (12). Clinical cohort studies confirm that ELD patients with comorbid sarcopenia exhibit an elevated risk of hospitalization due to acute exacerbations (13), a prolonged duration of mechanical ventilation dependence (14), and a markedly elevated all-cause mortality rate (15, 16). Given its profound impact on patients’ quality of life and prognosis, early identification and comprehensive intervention for sarcopenia have become critical priorities in multidisciplinary management frameworks for individuals with ELD, underscoring its significant clinical relevance in this field (7, 8, 10).

The diagnostic framework for sarcopenia lacks global consensus, with current diagnostic parameters primarily encompassing skeletal muscle mass quantification (assessed via dual-energy X-ray absorptiometry[DXA] or bioelectrical impedance analysis [BIA]) (17, 18), grip strength measurement, and physical performance evaluation (e.g., gait speed) (17). Recent observational studies have yielded extensive and inconsistent findings (19–21). Notably, the prevalence of sarcopenia appears to be higher in Asian populations compared to those in other regions (22). However, patients with ELD exhibit unique characteristics due to respiratory limitations, frequent acute exacerbations, and complex comorbidities. They may present with distinct phenotypic patterns (e.g., predominant proximal muscle involvement) and pathological mechanisms (e.g., systemic inflammation and hypoxia) that differ from those of other chronic disease cohorts (4, 5, 23). The heterogeneity of ELD etiology, the complexity of disease progression, and the diversity in sarcopenia diagnostic criteria contribute to significant variability in research outcomes. This, in turn, results in fragmented clinical protocols for sarcopenia identification, assessment, and management. Despite the growing body of research on sarcopenia in COPD, idiopathic pulmonary fibrosis, and pulmonary hypertension, critical clinical questions remain unanswered. This knowledge gap severely hampers the development of evidence-based practice guidelines, highlighting the urgent need to establish a multidimensional ELD-specific sarcopenia assessment framework.

Thus, this study utilizes systematic review and meta-analysis methodologies to comprehensively assess the prevalence of sarcopenia among patients with ELD and to ascertain its variability within distinct ELD subgroups. Through the synthesis of existing evidence, our goal is to establish an evidence-based framework for sarcopenia management in ELD, offering clinicians actionable insights to enhance therapeutic strategies.

ELD encompasses a range of critically debilitating conditions marked by severely impaired pulmonary function, diminished quality of life, and a poor prognosis. The presence of sarcopenia in these patients can further exacerbate their health status. However, owing to heterogeneity in study designs and patient populations, the reported prevalence of sarcopenia in patients with end-stage lung disease varied across studies included in this systematic review. To provide clinicians with robust evidence, we performed a meta-analysis of 24 studies reporting sarcopenia prevalence in this population. The pooled estimate revealed that 31.6% (95% CI: 26.5–36.8%) of end-stage lung disease patients were affected by sarcopenia, a finding that remained robust in sensitivity analyses. The pooled analysis showed a sarcopenia prevalence of 31.6% (95% CI: 26.5–36.8%) among ELD patients, with sensitivity analysis confirming the robustness of these findings. Numerous studies have reported a notably higher prevalence of sarcopenia (ranging from 10 to 39%) in patients with end-stage lung diseases, such as COPD, ILD and IPF (19–21, 45, 52). This evidence underscores the critical need to recognize and manage sarcopenia as a core comorbidity in this vulnerable population.

Subgroup analyses have revealed significant variability in the prevalence of sarcopenia across various age groups, genders, diagnostic criteria, measurement tools, geographic regions, and disease categories. Consistent with previous findings (53), the incidence of sarcopenia increases with age, reflecting the interplay of multiple physiological and disease-specific mechanisms. Chronic hypoxia and systemic inflammation in ELD patients activate the ubiquitin-proteasome system (UPS), accelerating muscle protein degradation and inducing an “accelerated aging” phenotype (54, 55). Studies indicate (19) that ELD patients, especially those with COPD, experience a shift in muscle fiber composition from type I to type II fibers (56), which likely contributes to dyspnea symptoms and impaired exercise performance (e.g., reduced endurance and exercise capacity) (57). Further clarification of the molecular and cellular mechanisms underlying sarcopenia pathogenesis in ELD populations will aid in the development of optimized assessment tools, allowing for more precise diagnosis, severity stratification, and personalized intervention strategies for this condition.

A significant sex difference in the prevalence of sarcopenia among ELD patients was observed in the overall population, with males exhibiting a higher rate than females (33% vs. 11%, p < 0.05). Research indicates (58) that ELD predominantly affects males due to factors such as smoking and occupational/environmental exposures. Previous studies (59) similarly report notable heterogeneity in sarcopenia incidence between genders across ELD populations. However, investigations by Awano (60) and Li (21) demonstrate that while male patients constitute the majority of ELD cohorts, no statistically significant difference in sarcopenia prevalence exists between male and female ELD patients. These findings underscore the need for further research to comprehensively characterize gender-specific epidemiological patterns and elucidate potential mechanistic pathways underlying observed sex-related disparities.

Assessment of sarcopenia prevalence in ELD populations is significantly influenced by variations in diagnostic criteria and musculoskeletal measurement tools. All included studies in this review adhered to existing sarcopenia consensus definitions, including EWGSOP 2010, EWGSOP2, AWGS 2014, and AWGS 2019. Firstly, discrepancies exist in the selection of definitions and core indicators, particularly regarding muscle mass assessment, where various criteria employ different measurement methodologies and thresholds. Inconsistencies may arise between measurements obtained via DXA and BIA, as BIA results are susceptible to fluctuations in hydration status, whereas DXA offers greater precision albeit at a higher cost. Regarding threshold settings: The Asian criteria (AWGS) (17) may establish stricter muscle mass thresholds (e.g., <7.0 kg/m² for males, <5.7 kg/m² for females), whereas European criteria (18) (EWGSOP) adopt slightly more lenient thresholds. Regarding muscle strength: Handgrip strength thresholds vary across different criteria. For example, AWGS defines abnormal handgrip strength as <28 kg for males and <18 kg for females, while EWGSOP may employ sex-stratified thresholds. Regarding physical performance: The inclusion or exclusion of gait speed tests (e.g., 6-meter walk) or balance assessments directly impacts diagnostic outcomes. Secondly, diagnostic algorithm complexity varies: EWGSOP requires concurrent abnormalities in muscle mass reduction plus either strength or functional decline for confirmation, whereas AWGS categorizes sarcopenia into “probable,” “confirmed,” and “severe” stages. Finally, heterogeneity exists in measurement tools and methodologies. While DXA measures total-body muscle mass, it cannot differentiate intramuscular fat infiltration. Variations in dynamometer models and testing protocols (e.g., seated vs. standing posture) may introduce measurement biases. For instance, Yogesh et al.’s study (42) (AWGS 2019) reported a 52.3% sarcopenia prevalence in ELD patients using BIA, whereas Jiang et al.’s research (35) (EWGSOP2) found a 17.2% prevalence using DXA. The lack of uniformity in diagnostic criteria and musculoskeletal assessment tools contributes to significant variability in sarcopenia prevalence estimates. Future efforts should prioritize the development of standardized definitions (e.g., disease-specific consensus guidelines) and more precise evaluation tools (e.g., AI-assisted muscle imaging analytics) to enhance interstudy comparability and diagnostic accuracy.

Our analysis revealed regional disparities in the prevalence of eldery sarcopenia, with the highest rate reported in North America (42%), followed by Asia (34%) and Europe (23%). These estimates contrast with those from two prior studies conducted in North America (61) and Europe (62), which reported rates of 7 and 48%, respectively. The heterogeneity in prevalence may be attributed to several factors. In North America, the high prevalence might be linked to the high burden of metabolic disorders—such as obesity, diabetes, and cardiovascular disease—where the co-occurrence of low physical activity and obesity (sarcopenic obesity) may exacerbate muscle loss and metabolic dysfunction (63). Conversely, several European countries (e.g., the Netherlands, Sweden, Belgium) have implemented early screening and intervention systems targeting geriatric health, including community-based programs combining nutrition and exercise, which may help mitigate sarcopenia progression (64). Although Asian countries (e.g., China, Japan) are experiencing the most rapid population aging globally, systematic screening and prevention strategies for sarcopenia remain underdeveloped in the region (65). Notably, the geographic distribution of included studies was highly uneven, with most evidence originating from Asian and European populations. The body of evidence for North America derives solely from a single study conducted in Mexico (40), constituting a significant gap in geographic representation. Given the considerable heterogeneity in ethnic background, lifestyle, and dietary habits among North American countries (e.g., Mexico, the United States, and Canada), findings from one study cannot be generalized to the entire region. This imbalance may introduce selection bias and limits the external validity of our geographic comparisons. Therefore, further high-quality studies from diverse geographic settings are needed to validate the observed regional differences in sarcopenia prevalence and clarify their underlying causes. Such efforts will be crucial for developing targeted prevention and management strategies globally.

This study also demonstrated significant differences in the prevalence of sarcopenia across various types of ELD. IPF had the highest prevalence rate at 38%, followed by COPD at 31%, both figures exceeding previously reported rates of 26 and 27%, respectively (21, 53). ILD exhibited the lowest prevalence at 28%. Potential reasons for these disparities include the following: IPF is characterized by the persistent overexpression of pro-inflammatory cytokines, such as IL-6, TNF-α, and TGF-β. These not only promote pulmonary fibrosis but also accelerate muscle protein degradation by activating the ubiquitin-proteasome system (UPS) and inhibiting the mTOR signaling pathway, thereby suppressing protein synthesis (66). On the other hand, inflammation associated with COPD predominantly involves neutrophilic infiltration (67), whereas ILD presents with heterogeneous inflammatory profiles depending on the subtype (e.g., sarcoidosis, hypersensitivity pneumonitis) (68), generally with lower systemic inflammatory intensity compared to IPF. Patients with IPF experience earlier and more prolonged hypoxemia, especially during exertion (69), whereas COPD patients typically show intermittent hypoxia (4). Chronic hypoxia suppresses mitochondrial oxidative phosphorylation, leading to muscle lactate accumulation, insufficient ATP synthesis, and accelerated muscle fiber atrophy (70).

Beyond the factors analyzed in subgroup analyses, this systematic review revealed that body mass index (BMI), systemic inflammatory markers, the dietary inflammatory index (DII), physical activity levels, and related psychological factors are all associated with sarcopenia in patients with ELD. The relationship between BMI and the prevalence of sarcopenia presents conflicting research findings, indicating a “dual effect” of BMI. A low BMI, associated with malnutrition, is directly linked to sarcopenia (29), reflecting muscle wasting due to insufficient energy-protein intake. On the other hand, a high BMI, related to obesity, also elevates the risk (22), possibly due to pro-inflammatory cytokines derived from adipocytes (e.g., IL-6) that induce muscle insulin resistance and contribute to a “sarcopenic obesity” phenotype. Elevated DII scores correlate with increased levels of pro-inflammatory cytokines (e.g., IL-6, TNF-α, CRP) and elevated hsTNF-α (29, 35), suggesting that chronic inflammation may accelerate muscle protein degradation through the activation of the (Ubiquitin-Proteasome System, UPS) and inhibit muscle stem cell proliferation.

A study (36) included in this analysis revealed that patients with sarcopenia exhibited significantly lower levels of physical activity compared to those without sarcopenia (p < 0.01). One potential mechanism underlying this association may be that physical activity reduces levels of pro-inflammatory cytokines such as IL-6 and TNF-α, while elevating anti-inflammatory factors like IL-10, thereby attenuating inflammation-mediated muscle proteolysis (4, 71). Consequently, increasing physical activity is essential for ameliorating sarcopenia. In support of this, Constantin et al. (72) demonstrated that an 8-week resistance training program led to improvements in both muscle mass and strength. Additionally, patients with anxiety and depression often exhibit hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, resulting in chronically elevated cortisol levels (73). Elevated cortisol may contribute directly to muscle loss by suppressing insulin-like growth factor-1 (IGF-1) signaling and activating proteolytic pathways in skeletal muscle (74).

It must be acknowledged that this study did not include smoking—a critical exposure factor for ELD. Despite the fact that smoking is a major risk factor for ELD, research findings regarding its association with sarcopenia are inconsistent. One study confirmed a significant correlation between smoking and sarcopenia (32), whereas two other studies found no statistically significant association (22, 75). Jone et al. (36) further reported that there were no significant differences in smoking status (current, former, or never smokers) between COPD patients with and without sarcopenia, suggesting that smoking may indirectly affect muscle function through alternative mechanisms, such as exacerbating pulmonary dysfunction (19).

Sarcopenia significantly contributes to adverse clinical outcomes in patients with end-stage lung disease, increasing mortality, reducing quality of life, and accelerating respiratory functional decline. Corticosteroids, frequently prescribed during acute exacerbations of COPD, ILD, and IPF, can aggravate muscle atrophy (62, 76–78). Studies demonstrate that even brief glucocorticoid exposure enhances proteolytic pathways via activation of the UPS and suppression of the mTOR signaling axis, while concurrently impairing protein synthesis—collectively hastening the progression of sarcopenia (54, 79). This effect is particularly detrimental in patients with pre-existing malnutrition, systemic inflammation, and physical inactivity, further compromising muscle function and long-term prognosis (6). The pathophysiological interplay between sarcopenia and ELD is characterized by a self-perpetuating systemic-organ vicious cycle. Consequently, early screening and multimodal intervention for sarcopenia represent a pivotal therapeutic target to attenuate disease progression in ELD.

This review has several potential limitations. Firstly, all the included studies were cross-sectional in design, which precludes causal inferences and results in less rigorous exploration of influencing factors. Secondly, due to variations in measurement tools, diagnostic criteria, sampling methods, and sample sources across studies, significant heterogeneity persisted despite subgroup analyses. This may compromise the accuracy of the findings and warrants further investigation. Additionally, in this review, the diagnostic criteria adopted by each included study were independently defined by the respective authors, potentially referencing different guidelines without considering cultural and population-specific adaptations, further contributing to heterogeneity. Finally, due to resource constraints, we were unable to include unpublished literature or data. Therefore, more in-depth research is needed to investigate sarcopenia in patients with ELD.

Sarcopenia is highly prevalent in patients with end-stage lung disease (ELD), with a pooled prevalence of 31.6% (95% CI: 26.5–36.8), underscoring its considerable burden in this population and calling for heightened clinical attention. Our analysis reveals marked heterogeneity in sarcopenia manifestations among ELD patients, influenced by multiple factors including divergent assessment methods, lack of diagnostic standardization, and age-related physiological decline.

This systematic review synthesizes current evidence to inform screening and management strategies for sarcopenia in ELD, while highlighting the critical challenge posed by inconsistent diagnostic criteria. To address this issue, we propose the development of structured and standardized disease-specific diagnostic algorithms that integrate functional and morphological measures to improve accuracy in identification and targeting of interventions. Furthermore, we emphasize the urgent need for harmonized definitions and evaluation frameworks to enhance comparability across studies. Moving forward, priority should be given to prospective clinical trials designed to evaluate integrated care pathways that concurrently target sarcopenia and respiratory function. Such studies will be essential for generating robust evidence to guide future clinical practice recommendations.