Impact of Frailty on the Risk of Exacerbations and All-Cause Mortality in Elderly Patients with Stable Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Baseline Characteristics of Elderly Patients with Stable Chronic Obstructive Pulmonary Disease (COPD), Classified According to Frailty

	Total Cohort	Non-Frail	Frail^†	P-value
N (%)	309	155 (50.2)	154 (49.8)
Age, yr, median (IQR)	86 (80, 90)	82 (77, 88)	89 (85, 92)	<0.001*
Sex, female n (%)	68 (22.0)	29 (18.7)	39 (25.3)	0.205
Smoking Status, n (%)				0.031*
Never	143 (46.3)	68 (43.9)	75 (48.7)
Previous	99 (32.0)	44 (28.4)	55 (35.7)
Current	67 (21.7)	43 (27.7)	24 (15.6)
Smoking Index (pack yr), median (IQR)	5 (0, 30)	10 (0, 30)	3 (0, 30)	0.942
BMI (kg/m^2), mean (SD)	24.1 (3.8)	25.1 (3.2)	23.2 (4.1)	<0.001*
CCI, median (IQR)	4 (3, 5)	3 (2, 4)	5 (3, 6)	<0.001*
MNA-SF, median (IQR)	12 (9, 14)	13 (12, 14)	10 (8, 12)	<0.001*
Malnutrition, n (%)	32 (10.5)	6 (3.9)	26 (17.1)	<0.001*
COPD Disease Severity
FEV1% predicted, median (IQR)	74.2 (60.4, 85.3)	76.3 (63.8, 87.5)	71.0 (57.0, 83.4)	0.028*
GOLD severity category, n (%)				0.090
Mild (≥80%)	114 (36.9)	63 (40.6)	51 (33.1)
Moderate (50–80%)	162 (52.4)	81 (52.3)	81 (52.6)
Severe (30–49%)	30 (9.7)	11 (7.1)	19 (12.3)
Very severe (<30%)	3 (1.0)	0 (0)	3 (1.9)
mMRC, median (IQR)	2.0 (1.0, 3.0)	1.0 (1.0, 2.0)	2.0 (2.0, 3.0)	<0.001*
mMRC ≥ 2, n (%)	85 (27.5)	9 (5.8)	76 (49.4)	<0.001*
CAT, median (IQR)	8 (3, 13)	5 (2, 9)	12 (6, 15)	<0.001*
CAT ≥ 10, n (%)	131 (42.4)	36 (23.2)	95 (61.7)	<0.001*
≥ 1 COPD moderate-to-severe exacerbations prior yr, n (%)	95 (30.7)	26 (16.8)	69 (44.8)	<0.001*
GOLD stage				<0.001*
GOLD A, n (%)	129 (41.7)	107 (69.0)	22 (14.3)
GOLD B, n (%)	132 (42.7)	40 (25.8)	92 (59.7)
GOLD C, n (%)	7 (2.3)	2 (1.3)	5 (3.2)
GOLD D, n (%)	41 (13.3)	6 (3.9)	35 (22.7)
ADL, median (IQR)	5 (3, 6)	6 (5, 6)	3 (2, 5)	<0.001*
IADL, median (IQR)	5 (2, 8)	8 (6, 8)	3 (1, 5)	<0.001*
Physical Function
Pace, m/s, median (IQR)	0.57 (0.27, 0.88)	0.88 (0.67, 1.09)	0.30 (0, 0.45)	<0.001*
Handgrip strength, kg, mean (SD)	20 (13, 26)	25 (20, 32)	14 (8, 20)	<0.001*
Medication				0.009*
LAMA/LABA, n (%)	127 (41.1)	66 (42.9)	61 (39.4)
2BD/BD+ICS, n (%)	24 (7.8)	6 (3.9)	18 (11.6)
LAMA+LABA+ICS, n (%)	43 (13.9)	16 (10.4)	27 (17.4)
None, n (%)	115 (37.2)	66 (42.9)	49 (31.6)

Notes: ^†Frailty was defined as Fried phenotype scores ≥ 3. *P < 0.05.

Abbreviations: SD, standard deviation; IQR, inter-quartile range; BMI, body mass index; ADL, activity of daily living; IADL, instrumental activity of daily living; CCI, Charlson’s comorbidity index; MNA-SF, Mini Nutritional Assessment-Short Form; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for COPD; mMRC, modified Medical Research Council; CAT, COPD Assessment Test; BD, bronchodilator; ICS, inhaled corticosteroids; LABA, long-acting beta-agonists; LAMA, long-acting muscarinic antagonists.

Figure 1 Distribution of frailty phenotypic characteristics assessed using Fried frailty phenotypes in older patients with stable chronic obstructive pulmonary disease (COPD).

Table 2 Results for 1-Year Acute Exacerbation of COPD, All-Cause Hospitalization, and Mortality in Frail and Non-Frail Elderly Patients with Stable COPD

Outcome	Total Cohort (n=309)	Non-Frail (n= 155)	Frail^† (n=154)	Crude IRR/HR (95% CI)	P-value
Moderate-to-severe exacerbations per year, median (min, max)	0 (0, 5)	0 (0, 2)	0 (0, 5)	4.48 (3.03–6.85)	<0.001*
All-cause hospitalizations per year, median (min, max)	1 (0, 6)	0 (0, 3)	1 (0, 6)	2.45 (1.92–3.12)	<0.001*
All-cause 1-year death, n (%)	28 (9.1)	3 (1.9)	25 (16.2)	9.00 (2.72,29.83)	<0.001*
All-cause death during follow-up, n (%)	50 (16.2)	7 (4.5)	43 (27.9)	6.94 (3.12,15.42)	<0.001*

Notes: ^†Frailty was defined as Fried phenotype scores ≥ 3. *P < 0.05.

Abbreviations: IRR, incidence rate ratio; HR, hazard ratios; CI, confidence intervals.

Table 3 Effects of Frailty and Its Characteristics on 1-Year Acute Exacerbation, All-Cause Hospitalization, and All-Cause Mortality in Older Patients with Stable COPD

	Moderate-Severe COPD Exacerbations		All-Cause Hospitalizations		All-Cause Mortality
	IRR (95% CI)	P-value	IRR (95% CI)	P-value	HR (95% CI)	P-value
Non-frail	ref		ref		ref
Frail (≥3) ^†	1.75 (1.09–2.82)	0.021*	1.39 (1.04–1.87)	0.028*	2.54 (1.01–6.36)	0.047*
Individual frailty characteristics
Exhaustion	1.29 (0.88–1.89)	0.193	1.11 (0.87–1.43)	0.401	1.33 (0.66–2.66)	0.418
Weakness	1.92 (0.99–3.73)	0.055	1.53 (1.04–2.25)	0.029*	6.39 (0.77–52.98)	0.084
Slowness	1.77 (1.03–3.03)	0.038*	1.17 (0.85–1.59)	0.334	2.11 (0.74–6.02)	0.156
Low physical activity	1.35 (0.88–2.09)	0.172	1.00 (0.76–1.32)	0.996	2.66 (1.17–6.05)	0.021*
Weight loss	1.07 (0.68–1.70)	0.768	0.96 (0.67–1.35)	0.798	2.15 (1.02–4.51)	0.044*

Notes: Data were estimated incidence rate ratios and 95% confidence intervals of the explanatory variables in the 1-year acute exacerbation and all-cause hospitalization, and hazard ratios and 95% confidence intervals of the explanatory variables in the all-cause mortality. IRR and HR were both adjusted for age, gender, CCI, medication, GOLD severity, moderate-to-severe exacerbation history, and CAT. ^†Frailty was defined as Fried Phenotype scores ≥ 3. *P < 0.05.

Abbreviations: IRR, incidence rate ratio; HR, hazard ratios; CI, confidence intervals.

Figure 2 Comparison of unadjusted and adjusted survival curves of patients age ≥ 65 years with stable COPD stratified according to frailty (Fried phenotype score ≥ 3). (A) Unadjusted Kaplan–Meier curve. (B) Survival curves adjusted by age, gender, CCI, medication, GOLD severity, moderate-to-severe exacerbation history, and CAT. Frail patients had a higher mortality.