The Timed Up and Go test predicts frailty in patients with COPD.

The Timed Up and Go (TUG) is a global measure of mobility and has the ability to detect frail individuals. Frail patients with chronic obstructive pulmonary disease (COPD) are usually undiagnosed. We hypothesised that the TUG would identify frail patients with COPD. Frailty was assessed in 520 patients diagnosed with COPD and 150 controls using a Comprehensive Geriatric Assessment questionnaire and frailty index (FI) was derived. The TUG was used to assess physical mobility. All participants were assessed for lung function and body composition. A ROC curve was used to identify how well TUG discriminates between frail and non-frail patients with COPD. The patients with COPD and controls were similar in age, sex and BMI but the patients with COPD were more frail, mean ± SD FI 0.16 ± 0.08 than controls 0.05 ± 0.03, P < 0.001. Frail patients with COPD had a greater TUG time (11.55 ± 4.03 s) compared to non-frail patients (9.2 ± 1.6 sec), after controlling for age and lung function (F = 15.94, P < 0.001), and both were greater than the controls (8.3 ± 1.2 sec), P < 0.001. The TUG discriminated between frail and non-frail patients with COPD with an area under the curve of 72 (95% CI: 67-76), and a diagnostic odds ratio of 2.67 (95% CI:1.5-4.6), P < 0.001. The TUG showed the ability to discriminate between frail and non-frail patients with COPD, independent of age and severity of the airflow obstruction. The TUG is a simple, easy and quick measure that could be easily applied in restricted settings to screen for frailty in COPD.

Introduction

Patients with chronic obstructive pulmonary disease (COPD) are more prone to be frail compared to non-COPD individuals and it is not necessarily driven by age[1-4]. Frailty reflects a lack of resilience of physiological systems to abnormal stressors which can be characterised by a number of deficits including loss of musculoskeletal mass and strength, increased number of comorbidities, cognition deficit, and progressive deterioration in physical capacity[1,2,5].

Previous studies have shown that patients with COPD have an increased risk of frailty compared with non-COPD individuals, and it is associated with increased fat mass which is directly linked with physical inactivity and comorbidities[1,2,6,7]. Increased fat mass and frailty in patients with COPD have also been linked to musculoskeletal dysfunction and physical incapacity, which are features of COPD[1,2,8,9].

Frailty provides an overview of impairments and serves as a prognosticator for increased morbidity and mortality in patients with COPD[3,6,7]. A number of studies found that most patients with COPD were frail and had limited physical capacity[2,6,10-13]. However, neither frailty nor physical capacity is routinely assessed in clinical practice for several reasons, including lack of time, inappropriate space, or the requirement for the completion of lengthy questionnaires[1,6,7]. Rapid identification of a frail patient with COPD would allow early medical and rehabilitation interventions, which have been shown to reverse frailty in patients with COPD[2].

The Timed Up and Go (TUG) test is an integrated assessment tool for lower extremity muscles strength, gait speed, balance and cognition[14]. We have previously shown that it is a simple, reliable, and valid tool for assessing physical capacity in patients with COPD, and has the ability to discriminate between physically active and inactive patients with COPD[8]. TUG captures various age-related physiological changes and discriminates between frail and non-frail older individuals[15]. As TUG is a rapid standardised test of physical capacity and overcomes limitations associated with other assessment tools of frailty, this makes it a useful proxy measure of frailty in COPD[15,16]. Therefore, this study aimed to assess the ability of the TUG to discriminate between frail and non-frail patients with COPD, and the potential to predict frailty in the patients with COPD.

Methods

Study design and participants

This was a cross-sectional study in community-based patients with COPD, confirmed by post-bronchodilator spirometry at enrolment. Patients with COPD were drawn from the prospective Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) study[17]. Using the G power software, a retrospective sample size calculation was based on the longitudinal ARCADE study to detect a 25% difference in the rate of frailty progression with 95% power at P = 0.05 level, the estimated sample size was 522.

All the patients with COPD were clinically stable, not having taken antibiotics or oral corticosteroids in the previous 4 weeks prior to recruitment. The patients with COPD with inflammatory diseases such as rheumatoid arthritis, oral maintenance corticosteroids, inflammatory bowel syndrome, and long-term oxygen therapy were excluded. The patients with COPD were recruited from respiratory outpatient clinics, pulmonary rehabilitation and smoking cessation referrals and general practice databases. We aimed to recruit patients with COPD with mild, moderate, and severe disease who had more variable clinical presentations, therefore more patients with COPD were recruited than the controls. Volunteer controls free from respiratory disease and other exclusion criteria applied to the patients with COPD were recruited to explore if the relationship of TUG with frailty remained beyond the impact of respiratory impairment. Volunteer controls were recruited from smoking cessation clinics, the patients’ relatives, and previous respiratory research databases at Cardiff University. All controls who met the inclusion and exclusion criteria were contacted before their appointment and sent a questionnaire to complete about their medical, physical, occupational and psychosocial status. All participants gave written informed consent and the study had approval from the South East Wales Research Ethics Committee (Clinical Trials.gov, NCT01656421).

Frailty

A modified version of the comprehensive geriatric assessment (CGA) questionnaire[1,18], specific to community-dwelling individuals was administered by a researcher to all participants, and a frailty index (FI) was derived. The FI is a reliable and valid tool for quantifying health status, stratifying patients’ risk of institutionalisation and death[18]. The FI was calculated by dividing the total number of CGA deficits by the maximum possible score of 61. The upper 90th centile FI for controls (0.09) was used as a cutoff for frailty based on a previous study by Gale and coauthors[1].

Lung function

All participants performed spirometry (Vitalograph Alpha, using the global lung initiative (GLI) reference equations, to determine forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the FEV1:FVC ratio[19]. A diagnosis of COPD was confirmed as post-bronchodilator spirometry FEV1:FVC < 0.70[20]. The patients with COPD were classified according to the Global Initiative of Obstructive Lung Disease (GOLD) combined assessment, GOLD A-D based on the COPD assessment test (CAT) score[20].

Body composition

Body compositions were measured barefoot in lightweight indoor clothing. Fat percentage, fat-free mass[21] and body mass index (BMI kg/m2) were determined using a segmental bio-electrical impedance analyser (BC418 Tanita Corp, Tokyo). Waist circumference was measured using stretch-resistant tape.

Timed Up and Go

All participants undertook the TUG test using a standard chair (seat height 45 cm high) and standardised instructions[22]. Participants were seated with their backs supported against the chair. They were instructed to stand up, walk three metres to a mark on the floor, cross the mark, turn around, walk back to the chair and sit down. The task was performed at their normal comfortable pace. A stopwatch was started on the word “go” and stopped as the subject sat down and the time recorded in seconds. The TUG of 8.42 sec has been previously a validated cutoff value for normal physical capacity in patients with COPD[8].

Handgrip measurement

Maximal right and left handgrip strength (HGS) was determined twice and the mean was calculated for each hand using a hand dynamometer (T.K.K. 5401 grip-D, Takei, Japan).

COPD health status questionnaire

The patients with COPD completed the St George’s Respiratory Questionnaire (SGRQ) and the CAT, both validated to assess the impact of COPD on health status[23,24].

The patients with COPD reported the number of chest exacerbations (defined as worsening of respiratory symptoms requiring antibiotic or oral corticosteroid therapy) per year[20]. Breathlessness score was recorded using the modified Medical Research Council (mMRC). The number of previously diagnosed comorbidities in the patients with COPD and controls were also recorded.

Statistical analysis

Data analysis was performed using IBM SPSS Statistics for Windows, Version 27.0 (IBM Corp., Armonk, NY, USA). Interval ratio data were checked for normality prior to analysis. Data that were normally distributed were presented as mean and standard deviation (SD) or median (range) for non-normal and percentage for categorical data. Comparisons between the patients with COPD and controls were performed using analysis of variance. Categorical data were analysed using the Chi-square test. Relationships between variables were explored using Pearson’s and Spearman correlation coefficients. The receiver operating characteristics (ROC) curve was performed to determine the diagnostic ability of the TUG test for discrimination between frail and non-frail patients with COPD. For all analyses a P value < 0.05 was considered significant. The 90th percentile of FI in the controls was used as a cutoff for frailty based on a previous study, which used the same tool to detect frailty in the patients with COPD[1]. The cutoff for frailty was 10 sec as reported in a recent systematic review[25].

Table 1

Participants physical and clinical characteristics.

	COPD (n = 520)	Control (n = 150)	P
Gender male: female	270:250	76:74	0.451
Age (years)	66.1 ± 7.6	65 ± 7.4	0.109
FEV1/FVC (%)	0.53 ± 0.11	0.78 ± 0.05	0.001
FEV1 (% predicted)	58 ± 19	105 ± 14	0.001
FVC (% predicted)	87 ± 21	109 ± 15	0.001
Smoking (pack years)	41 ± 25	22 ± 18	0.001
BMI (kg/m2)	28.0 ± 5.5	28.1 ± 4.1	0.951
Waist circumference (cm)	99.6 ± 15.0	94.7 ± 10.2	0.001
Handgrip (kg)	27.1 ± 9.7	31.3 ± 10.3	0.001
TUG (sec)	11.5 ± 4	8.3 ± 1.2	0.001
CGA total	9 (6–13)	2.25 (1–4)	0.001
Frailty index	0.16 ± 0.08	0.05 ± 0.03	0.001
mMRC	2.0 ± 1	-	-
SGRQ Total	53 (36–68)	-	-
CAT score	21 (14–27)	-	-

All data mean ± SD or Median (IQR), #=Geometric mean, - not assessed.

P < 0.05 significant difference between patients with COPD and controls

BMI body mass index; CAT COPD assessment test; CGA comprehensive geriatric assessment; FEV forced expiratory volume in 1 sec; FFMI fat-free mass index; FVC forced vital capacity; mMRC modified Medical Research Council; SGRQ St George’s Respiratory Questionnaire; TUG Timed Up and Go.