Description of included studies
A flow diagram detailing the literature search is provided in Figure 1. Of the 1301 abstracts identified during the search, 118 were selected for full-text reading, and 1183 were excluded because they did not relevant to the topic of the review. After reading the full text, another 98 papers were excluded for the following reasons: not fulfill study aims; duplicate/replicate data from the same study; not in English language; not an original article; lack clear definition of frailty; repeated measuring frailty at different time points and data unavailable. Twenty articles involving 11, 620 participants included in the final review. Of these, 11 were observational cohort studies, 8 adopted a cross-sectional design, and one was a randomized clinical trial. Characteristics of included studies are presented in Table 1. These studies were conducted during a diverse range of populations, including nine studies from Europe, six from Asia, four from North and South America and one from Oceania.
Methods used to assess frailty
For frailty evaluation, 10 studies10,11,13,18-24 used the criteria of FFP; frailty was also measured by using other measurements, such as the Timed “Up and Go”(TUG) test25 the comprehensive geriatric assessment (CGA)26, frailty index22,26,27, Frailty Staging System28, the Kihon Checklist 29,30, FRAIL Scale31, the Reported Edmonton Frailty Scale(REFS)32 and HFRS12.
Frailty prevalence
The prevalence of frailty ranged from 6.43% to 71.7% based on the frailty tool used. Overall sarcopenia prevalence varied from 32.07% (95% CI 26.64–37.49; Figure 2). The high statistical heterogeneity in this analysis (I2 = 98.12%) meant that individual study weighting was uniform (range 3.91-5.45%). Visual examination of asymmetrical funnel plots suggested publication bias (e-Figure1), and Egger’s test indicated strong evidence of publication bias detected in the meta-analysis of prevalence of frailty(Z=5.57,P<0.01).
Impact of frailty on clinical outcomes
Data from 15 studies involving 4,122 participants were reviewed for meta-analysis of pulmonary function, showing that those with frailty presented poorer FEV1% predicted than those without frailty [mean difference -5.06% (95%CI -6.70 to -3.42%); I2= 36.94%, Figure 3A].
Data from 10 studies involving 2,392 participants were available for meta-analysis of CAT score, showing that those with frailty presented higher CAT score than those without frailty [mean difference 6.2(95%CI 4.43 to 7.96); I2=84.95%, Figure 3B]. Similarly, the meta-analysis of mMRC grade from nine studies showed that having frailty was associated with higher mMRC grade [mean difference 0.93(95%CI 0.85 to 1.02; I2=0.00%, Figure 3C].
Seven studies evaluated the association between frailty status and 6-minute waking test13,18,20,21,25-27. Frailty was associated with shorter 6MWD [mean difference -90.23 meter (95%CI -124.70 to -55.76); I2= 83.92%, Figure 4A]. Four studies involving 2,430 participants reported data on activities of daily living via the Katz Activities of Daily Living11,27, lawton scale11,20,27, Barthel index12 was included in the meta-analysis. Having frailty was associated with poorer ADL [SMD -0.99 (95%CI -1.35 to -0.62); I2= 86.74%, Figure 4B].
The overall pooled analysis of the 7 studies 10,11,13,22,23,27,28demonstrated a 1.68-fold increase in the risk of long-term all-cause mortality for frail patients (95% CI 1.37-2.05; P < .0001) compared with non-frail patients (Figure 5). No significant heterogeneity among the 7 studies was observed (P=0.6, I2 = 0%). The results of the funnel plot suggested little publication bias for the above analyses of frailty upon clinical outcomes (e-Figure 2-6).
A summary of findings related to the rehospitalization and acute exacerbation is presented in Table 2; Quantitative meta-analysis was not possible due to lack of sufficient data. Compared with non-frail individuals, those with frailty tend to have heightened risk of rehospitalization10,11,22. Only two studies examined acute exacerbation risks for frailty COPD patients. Of them, Halon et al22 found that frailty increased the risk of hospitalized exacerbation and community exacerbation adjusting for FEV1. On the contrary, the other study showed that the frailty measured by FFP was not associated with COPD exacerbations.
Table 2 Clinical impact of the frailty in rehospitalization and acute exacerbation
|
Frailty measurement
|
Compared with individuals with COPD without frailty
|
frailty
|
Rehospitalization
|
FFP
|
Higher risk10,11,22/ N.d13
|
|
HFRS
|
N.d12
|
Acute exacerbation
|
FFP
|
Higher risk22/N.d13
|
COPD Chronic obstructive pulmonary disease, FFP Fried frailty phenotype,HFRS Hospital Frailty Risk Score, N.d not significant difference