Frailty in Chronic Obstructive Pulmonary Disease and Risk of Exacerbations and Hospitalizations

Figures & data

Figure 1 Prevalence of frailty measures at baseline. (A) Prevalence of individual frailty measures: Exhaustion (Short Form Health Survey 36 scale score <50); Weakness (low handgrip strength); Slowness (Cadence <30 steps per minute); Low activity (total daily steps <2500); Undernutrition (body mass index ≤21). (B) Prevalence of frailty phenotypes: non-frail (0 frailty measures); pre-frail (1–2 frailty measures); Frail (≥3 frailty measures).

Table 1 Participant Characteristics (N=280)

	Not Frail n=40	Pre-Frail n=176	Frail n=64	P-value*
Age, yr, mean (SD)	69.4 (8.0)	66.9 (8.4)	68.6 (9.2)	0.14
Sex, female (%)	10 (25.0)	34 (19.3)	12 (18.2)	0.67
Race, non-White (%)	0	23 (13.1)	10 (15.2)	0.04^b
BMI
Mean (SD)	28.5 (3.9)	28.0 (5.9)	28.0 (7.9)	0.82
Low BMI (≤21)	0	12 (6.8)	17 (25.8)	<0.001^a,b,c
Current smoker (%)	8 (20.0)	47 (26.7)	21 (31.8)	0.41
COPD Disease severity
FEV1% predicted mean (SD)	49.5 (15.1)	46.9 (15.4)	36.9 (14.5)	<0.001^b,c
GOLD severity category				0.002^b,c
Moderate (50–80%)	20 (50.0)	78 (44.3)	14 (21.2)
Severe (30–49%)	14 (35.0)	71 (40.3)	30 (45.5)
Very severe (<30%)	6 (15.0)	27 (15.3)	22 (33.3)
mMRC, mean (SD)	1.3 (0.8)	1.9 (1.1)	2.6 (1.0)	<0.001^a,b,c
Home supplemental oxygen (%)	9 (22.5)	51 (29.0)	36 (54.6)	<0.001^b,c
≥ 1 COPD hospitalization prior yr (%)	14 (35)	75 (43)	35 (52)	0.23
Comorbidity
Charlson Comorbidity Index, ≥1 (%)	18 (45.0)	85 (48.3)	35 (53.0)	0.70
Non-metastatic cancer**	7 (17.5)	19 (10.8)	9 (13.6)	0.48
Neurologic disease^#	3(7.5)	3 (1.7)	1 (1.5)	0.09
Physical Function
6MWT, mean (SD), feet	1301 (277)	1136 (343)	844(377)	<0.001^a,b,c
Physical Activity Data
Total Daily Steps, mean (SD)	7943 (2978)	6675 (3139)	3030 (1981)	<0.001^b,c
Low physical activity (<2500 steps/day)	0	3 (1.7)	36 (54.6)	<0.001^a,b,c
Slowness (cadence <30 steps/minute)	0	85 (48.3)	64 (97.0)	<0.001^a,b,c
Peak Performance, mean (SD)^##	36.1 (5.0)	31.6 (7.5)	20.8 (6.8)	<0.001^a,b,c
SF-36 Vitality Score
Mean Vitality Score (SD)	60.9 (5.4)	46.2 (11.7)	39.2 (9.9)	<0.001^a,b,c
Low Vitality Score (≤55)	0	124 (70.5)	62 (93.9)	<0.001^a,b,c
Handgrip strength, Kg
Mean Handgrip strength (SD)	35.2 (8.3)	33.9 (9.6)	26.2 (7.8)	<0.001^b,c
Low handgrip strength by Fried criteria	0	38 (21.6)	48 (72.7)	<0.001^a,b,c
Low handgrip strength by Dodd criteria	3 (7.5)	52 (29.6)	50 (75.8)	<0.001^a,b,c

Notes: *P-value for Wald test with robust standard errors of linear regression models for continuous variables, and Wald chi-square test for categorical variables. **Non-skin cancer, no lymphoma or leukemia. ^#Multiple sclerosis or Parkinson’s. ##Peak performance is defined as the top steps/minute during the top 30 one-minute periods each day. ^ap<0.0167 comparing not frail and pre-frail participants. ^bp<0.0167 comparing not frail and frail participants. ^cp<0.0167 comparing pre-frail and frail participants.

Abbreviations: SD, standard deviation; BMI, body mass index; mMRC, Modified Medical Research Council Dyspnea Scale; SF-36, Short Form Health Survey 36.

Table 2 Mean Annual Exacerbation, Hospitalization Rates and Mortality by Frailty Category

Outcome	Not Frail n=40	Pre-Frail n=176	Frail n=64	P-value*
Moderate-to-severe exacerbations per year, mean (SD)	0.59 (0.70)	0.75 (0.89)	0.87 (1.16)	0.27
All-cause hospitalizations per year, mean (SD)	0.20 (0.41)	0.34 (0.65)	0.49 (0.68)	0.02^b
Non-COPD hospitalizations per year, mean (SD)	0.10 (0.23)	0.17 (0.41)	0.22 (0.37)	0.12
Mortality, n (%)	3 (7.5)	8 (4.6)	10 (15.2)	0.02^c

Notes: *P-value for Wald test with robust standard errors of linear regression models for continuous outcome variables and Wald chi-square test for mortality frequency. ^bp<0.0167 comparing not frail and frail participants. ^cp<0.0167 comparing pre-frail and frail participants.

Table 3 Associations Between Frailty Measures and Acute COPD Exacerbations and All-Cause Hospitalizations Using Handgrip Strength Based on Fried et al Criteria

Frailty Measures*	Moderate-Severe COPD Exacerbations		All-Cause Hospitalizations		Non-COPD Hospitalizations
	Adj. IRR (CI)**	p-value	Adj. IRR (CI)**	p-value	Adj. IRR (CI)**	p-value
Number of frailty measures
Non-frail (0)	ref		ref		ref
Pre-frail (1–2)	1.13 (0.74–1.72)	0.57	1.36 (0.70–2.64)	0.36	1.58 (0.68–3.70)	0.29
Frail (≥3)	1.14 (0.69–1.89)	0.62	1.96 (0.92–4.19)	0.08	2.62 (1.00–6.84)	0.05
Individual frailty components
Exhaustion (SF 36-vitality score <55)	1.25 (0.93–1.69)	0.14	1.49 (0.95–2.33)	0.09	1.51 (0.86–2.66)	0.15
Weakness (Low HGS based per Fried)	1.46 (1.09–1.97)	0.01	1.27 (0.81–2.01)	0.30	1.23 (0.70–2.18)	0.47
Slowness (Cadence <30 steps/min)	0.86 (0.64–1.16)	0.32	1.14 (0.74–1.76)	0.55	1.96 (1.13–3.38)	0.02
Low activity (Total daily steps <2500)	0.55 (0.35–0.88)	0.01	1.03 (0.56–1.91)	0.93	1.33 (0.61–2.90)	0.48
Undernutrition (BMI ≤21)	0.95 (0.61–1.47)	0.80	0.93 (0.47–1.85)	0.84	0.83 (0.34–2.04)	0.69

Notes: *Each frailty measure represents an independent model. **Adjusted for Age, Sex, Charlson comorbidity index ≥ 1, FEV1, nMRC, Home O2, Prior COPD hospitalizations in the past year.

Abbreviations: IRR, incidence rate ratio; CI, confidence interval; SF-36, Short Form Health Survey 36; HGS, handgrip strength; BMI, body mass index.

Table 4 Sensitivity Analysis: Associations Between Frailty Measures and Acute COPD Exacerbations and All-Cause Hospitalizations Using Handgrip Strength Based on Dodd et al Criteria

Frailty Measures*	Mod-Severe COPD Exacerbations		All-Cause Hospitalizations		Non-COPD Hospitalizations
	Adj. IRR (CI)**	p-value	Adj. IRR (CI)**	p-value	Adj. IRR (CI)**	p-value
Number of frailty measures
Non-frail (0)	Ref		Ref		Ref
Pre-frail (1–2)	1.13 (0.73–1.75)	0.59	1.16 (0.59–2.27)	0.67	1.30 (0.55–3.08)	0.54
Frail (≥3)	1.12 (0.67–1.87)	0.65	1.83 (0.86–3.88)	0.12	2.62 (1.02–6.74)	0.05
Weakness (Low HGS based per Fried)	1.40 (1.05–1.85)	0.02	1.27 (0.83–1.96)	0.27	1.47 (0.87–2.49)	0.15

Notes: *Each frailty measure represents an independent model. **Adjusted for Age, Sex, Charlson comorbidity index ≥ 1, FEV1, mMRC, Home O2, Prior COPD hospitalizations in the past year.

Abbreviations: IRR, incidence rate ratio, CI, confidence interval HGS, handgrip strength.

Table 5 Associations Between Frailty Measures and Mortality

Frailty Measures*	Adjusted HR (CI)**	P-value
Number of frailty measures
0	Ref
1–2	0.58 (0.15–2.29)	0.43
≥3	1.47 (0.34–6.38)	0.61
Individual frailty components
Exhaustion (SF 36-vitality scale score <55)	0.83 (0.34–1.99)	0.67
Weakness (Low HGS per Fried)	1.31 (0.33–1.96)	0.30
Weakness (Low HGS per Dodd)	1.49 (0.61–3.61)	0.38
Slowness (Cadence <30 steps/min)	1.93 (0.67–5.53)	0.22
Low activity (Total daily steps <2500)	1.16 (0.36–3.76)	0.81
Undernutrition (Low weight BMI ≤21)	1.87 (0.58–6.01)	0.29

Notes: *Each frailty measure represents an independent model. **Adjusted for Age, Sex, Charlson comorbidity index ≥ 1, FEV1, MMRC, Home O2, Prior COPD hospitalizations in the past year.

Abbreviations: HR, hazard ratio; SF-36, Short Form Health Survey 36; HGS, handgrip strength; BMI, body mass index.