Table 2.
Studies of sarcopenia and frailty syndromes in chronic respiratory disease.
| Reference | Design | Sample | Key measures | Main findings | Implications |
|---|---|---|---|---|---|
| Sarcopenia | |||||
| Jones et al.65 | Cross-sectional case–control | 622 with COPD, 43 sarcopenic patients and 43 propensity score-matched controls pre–post rehabilitation | EWGSOP criteria ISWT QMVC CAT Physical activity by questionnaire and accelerometry |
Overall prevalence of sarcopenia 15%. Prevalence associated with age, breathlessness and disease severity. Sarcopenic patients had reduced exercise capacity, functional performance, physical activity and health status (p < 0.001). Outcomes to pulmonary rehabilitation were similar across patients with sarcopenia and a propensity-matched control group. Following rehabilitation, 12/43 (28%) sarcopenic patients no longer met EWGSOP criteria. |
Sarcopenia is a distinct phenotype from generalized muscle wasting or physical function alone and is associated with a worse functional and health status. Response to pulmonary rehabilitation is not impaired by sarcopenia and can lead to a reversal of the syndrome in some patients. |
| Frailty | |||||
| Akgün et al.66 | Prospective cohort | 7144 (3538 HIV positive) of whom 154 HIV positive with COPD and 182 HIV negative without COPD | 4-item adapted of Fried’s Frailty Phenotype Physical Limitation Scale |
Prevalence of frailty in patients with COPD 59% and 58% in those with HIV positive and negative status, respectively. COPD was associated with increased odds of being frail (p < 0.01) and with physical limitation (p < 0.001). COPD associated with fivefold greater odds of frailty in HIV-positive group and 3.5-fold greater odds in those with HIV-negative status. |
Optimizing COPD management may be important to minimize frailty and maintain physical function for individuals aging with HIV. |
| Valenza et al.67 | Cross-sectional | 212 with COPD (104 stable, 108 acute during exacerbation) and 100 without COPD | Fried Frailty Phenotype Physical activity questionnaire Barthel Index Charlson Index | Prevalence of frailty 63% in acute COPD and 65% in stable COPD. Cut-points to detect frailty using Baecke questionnaire 3.54 and 3.88 for acute and stable COPD. |
Measuring physical activity can help to predict the presence of frailty in acute and stable COPD. Interventions aimed at increasing physical activity may reduce or delay frailty. |
| Park et al.21 | Cross-sectional | 98 chronic bronchitis, 70 COPD, 43 chronic bronchitis and COPD | 9-item criteria of frailty (based on Tilburg Frailty Indicator) Physical activity by accelerometry Basic and instrumental ADLs | Prevalence of frailty 58% and of pre-frailty 22%. Self-reported breathlessness was the strongest predictor for frailty (odds ratio 3.98; 95% CI: 1.79–8.88; p < 0.05). Frail patients had a greater number of disabilities and poorer outcomes including difficulties in ADLs. |
Highlights the importance of recognizing Frailty is highly prevalent in COPD and may have implications for care. Knowledge of frailty determinants can help healthcare providers identify pre-frail patients and provide preventative interventions to delay frailty onset. |
| Mittal et al.16 | Prospective cohort | 120 chronic pulmonary disease (67 COPD) | Fried Frailty Phenotype Physical activity questionnaire 100-foot walk test | Prevalence of frailty 18% and pre-frailty 64%. Frailty was associated with increased number of falls (p = 0.018) and hospitalizations (p = 0.011) in the past year. Gait speed correlated with frailty status (r2 = 0.36, p < 0.001) and decreased as frailty increased (p = 0.001). |
Frailty could help predict falls and frail patients may benefit from a comprehensive geriatric assessment. Gait speed may help screen for frailty in chronic respiratory disease, but is only a single component of frailty. |
| Galizia et al.68 | Cross-sectional with mortality follow-up | 489 with COPD and 799 without COPD | Frailty Staging System Basic ADLs Charlson Index | Prevalence of frailty 49%. With increasing frailty stage, mortality at follow-up (12 years) increased from 54% to 97% in patients with COPD (p < 0.001). |
Clinical frailty stage offers prognostic information on long-term mortality risk in people with COPD. |
| Lahousse et al.17 | Prospective cohort | 402 with COPD and 1740 without COPD | Fried Frailty Phenotype Spirometry Exacerbation history | Prevalence of frailty 5% and pre-frailty 45% Those with COPD more than twice as likely to be frail (odds ratio 2.2; 95% CI: 1.34–3.54; p = 0.002). Prevalence of frailty in COPD associated with breathlessness, airflow limitation and frequent exacerbations. Frailty was an important determinant of mortality in COPD (hazard ratio 4.03; 95% CI: 1.22–13.30, p = 0.022) along with lung function and comorbidity count. |
Increased prevalence of frailty with COPD related to breathlessness and exacerbation frequency. For patients with COPD, frailty appears to offer prognostic information on mortality risk. |
| Vaz Fragoso et al.69 | Prospective cohort | 3578 older persons (262 with COPD) | Fried Frailty Phenotype Spirometry 15-foot walk test | Prevalence of frailty in patients with COPD 10% and pre-frailty 54%. Frailty associated with increased airflow limitation (odds ratio 1.88; 95% CI: 1.15–3.09), and restrictive lung function (odds ratio 3.05; 95% CI: 1.91–4.88). In those without respiratory impairment at baseline, frailty was associated with increased odds of developing respiratory impairment at 4 years (odds ratio 1.42; 95% CI: 1.11–1.82). In those not frail at baseline, those with respiratory impairment had increased odds of developing frailty at 3 years (odds ratio 1.58; 95% CI: 1.17–2.13). Greater mortality in those with frailty and respiratory impairment (2.5-fold increase in those with both compared to neither) during follow-up. |
Frailty and respiratory impairment increase mortality risk, especially when both are present. There may be a bidirectional relationship between frailty and respiratory impairment which could be important for therapy. Strategies targeting frailty- or respiratory-related impairment may extend to both conditions. |
| Singer et al.19 | Prospective cohort | 395 lung transplant candidates | Fried Frailty Phenotype SPPB 6MWD Blood Biomarkers (IL-6, TNFR1, IGF-1, leptin) |
Prevalence of frailty based on Fried Frailty Phenotype 28%. Prevalence was not associated with low skeletal muscle index. Frailty was associated with higher levels of plasma IL-6 and TNFR1, and lower levels of IGF-1 and leptin. Frailty was associated with greater disability and twice the incidence of delisting or death before transplantation (27% vs. 13%, p = 0.077). |
Frailty assessment could provide important morbidity and mortality risk information. Frailty assessment could be used to identify lung transplant candidates at increased risk of post-transplant disability or poorer outcomes. |
| Mittal et al.70 | Prospective cohort | 30 chronic pulmonary disease (23 COPD) | Fried Frailty Phenotype Physical activity questionnaire 100-foot walk test |
Prevalence of frailty 17% and pre-frailty 61%. Patients with frailty had frequent falls and hospitalizations within the last year. Following pulmonary rehabilitation, gait speed was improved (mean 0.88 to 1.02 m/second, p < 0.001) and 3/5 (60%) previously frail patients were no longer met case criteria for frailty. |
Pulmonary rehabilitation may improve frailty specifically through an effect on gait speed in some patients, but this effect is not consistent. |
| Maddocks et al.20 | Prospective cohort | 816 COPD | Fried Frailty Phenotype MRC dyspnoea score Physical activity questionnaire ISWT HADS CRQ CAT |
Prevalence of frailty 26% and pre-frailty 64%. Prevalence of frailty increased with age, GOLD stage, MRC score and comorbidity burden (p < 0.001) Frailty associated with over twice the odds of pulmonary rehabilitation non-completion (odds ratio 2.20; 95% CI: 1.39–3.46; p = 0.001). Patients who were frail had better treatment outcomes following rehabilitation, including better responses in MRC score, exercise capacity, physical activity and health status (p < 0.001). 71/115 (62%) previously frail patients no longer met case criteria for frailty following pulmonary rehabilitation. |
Frailty is an independent predictor for pulmonary rehabilitation non-completion. This highlights the importance of understanding frailty in the management of COPD and should prompt exploration of new ways to support frail patients through rehabilitation. |
ADLs: activities of daily living; CAT: COPD assessment test; COPD: chronic obstructive pulmonary disease; CRQ: chronic respiratory questionnaire; EWGSOP: European Working Group on Sarcopenia in Older People; GOLD: Global Initiative for Chronic Obstructive Lung Disease; HADS: Hospital Anxiety and Depression Scale; IGF-1: insulin-like growth factor 1; IL-6: interleukin 6; ISWT: incremental shuttle walk test; QMVC: quadriceps maximum voluntary contraction; SPPB: short physical performance battery; TNFR1: tumour necrosis factor receptor 1; 6MWD: 6-minute walk distance.