Comparative Study of Frailty Phenotype and Short Physical Performance Battery for Frailty Assessment in Chronic Obstructive Pulmonary Disease

ABBREVIATIONS USED IN THIS ARTICLE

ATS = American Thoracic Society; CAT = COPD assessment test; CI = Confidence intervals; CFS = Clinical frailty scale; CRP = C-reactive protein; FFP = Fried frailty phenotype; FP = Frailty phenotype; mMRC = Modified medical research council; OPD = Outpatient department; OR = Odds ratios; SPPB = Short physical performance battery; TNF = Tumor necrosis factor; UCSD SOBQ = University of California San Diego shortness of breath questionnaire; 6MWT = Six-minute walk test.

INTRODUCTION

Frailty is a syndrome characterized by an aggregation of physiologic deficits across different interconnected body systems, leading to functional limitations and heightened vulnerability to new stressors that would otherwise be inconsequential.¹ The pathways contributing to frailty involve chronic systemic inflammation, marked by elevated serum levels of proinflammatory cytokines such as interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP). Chronic obstructive pulmonary disease (COPD) impairs peripheral muscle performance and reduces functional capacity, making patients more prone to frailty, with a prevalence ranging from 6 to 57.8%.^2,3 Additionally, acute exacerbations of COPD are associated with impaired lung function, reduced muscle strength, and physical inactivity.^3–6 Valenza MC conducted a study on adult COPD patients and found that more frequent exacerbations of lung disease, hospitalizations, functional status decline, and all-cause mortality are all independently associated with frailty.⁷

Numerous measures have been devised for the assessment of frailty including the fried frailty phenotype (FFP),⁸ short physical performance battery (SPPB),⁹ Frailty Index,¹⁰ Clinical Frailty Scale (CFS),¹¹ and Reported Edmonton Frail Scale.¹² Limpawattana et al. conducted a study that reported a 10.2% prevalence of frailty in elderly COPD patients, as determined by the FFP method.¹³ In the study by Patel et al., determinants of frailty in COPD by SPPB were quadriceps strength and functional exercise capacity rather than lung function.¹⁴ Research on frailty in COPD patients is limited, especially in Southeast Asia, where lifestyle and ethnic factors differ from those in other regions. Given the limited availability of Indian studies on the prevalence of frailty in COPD, this study was conducted to assess frailty among COPD patients in India using two distinct methods: FP and SPPB. The prevalence obtained by each method was correlated with other predictors of disease severity and quality of life followed by a comparative assessment of the two methods.

MATERIALS AND METHODS

This was a prospective descriptive cross-sectional study. In the study, we recruited 150 patients visiting the outpatient department (OPD) at Vallabhbhai Patel Chest Institute, Delhi, India during 2021–2022. The ethical clearance for the study was taken from the Institutional Ethics Committee. Patients diagnosed with COPD as per the GOLD 2021 guidelines and giving their informed consent, were included in the study.¹⁵ Patients with significant cognitive impairment or with any physical disability or unable to maintain SpO₂ > 90% on room air were excluded. Patients who did not give full voluntary informed consent were also excluded from the study. The sample size was based on the reported average mean prevalence of frailty in COPD by using formula n = [Z² × p(1–p)]/d² where “n” is the sample size, prevalence “p” was 5%, “z” was 1.96 (for a level of confidence of 95% according to the standard normal distribution) and “d” was precision (tolerated margin of error), i.e., 0.05. The computed minimal sample size was 64. To improve the power of our study, we have taken a sample size of 150 patients.

The methodology followed is as depicted in Figure 1. All baseline characteristics, such as age, gender, body mass index (BMI), and smoking status including pack-years of smoking, were recorded. Pulmonary function tests were conducted in accordance with the 2019 guidelines of the American Thoracic Society (ATS) and European Respiratory Society guidelines of 2021.^16,17 All the recruited patients were assessed for frailty by the following two methods:

RESULTS

The baseline characteristics of the study population are depicted in Table 1. The mean SD age of the participants was 60.59 (5.91) years. Out of these, there were 133 males (88.67%). Among them, 47 individuals (31.33%) were current smokers. Upon evaluation by the FP method, the prevalence of frailty was found to be 51.33% whereas, the prevalence of frailty by the SPPB method was found to be 20%. Patients identified as Frail by the FP measure had a higher number of exacerbations as compared to the frail patients by SPPB. By the FP measure, 51 (66.23%) frail patients were in GOLD group D whereas 21 (65.63%) frail patients by the SPPB method had similar severity of disease. Eighty-two patients (54.67%) experienced at least one exacerbation in the past 12 months. The majority of participants had cardiometabolic conditions, such as hypertension (44, 29.33%), type 2 diabetes mellitus (18, 12%), and coronary artery disease (15, 10%).

The total St. George's Respiratory Questionnaire (SGRQ) score was comparable in both Frail groups (43.21 vs 42.78) whereas the Frail group by SPPB measure had slightly better symptoms’ score (43.01 ± 14.86 vs 45.71 ± 14.77) (p = 0.1156; 6.066–0.666) and activity score (44.19 vs 45.5). Participants classified as frail by either the FFP or SPPB did not show a significant difference in forced expiratory volume in 1 second (FEV1)% predicted [FP {40(36–47)} vs SPPB {40(33–47.25)}] or BMI [FP (21.84 ± 4.11) vs SPPB (22.65 ± 3.68)] (p = 0.0732; 1.6964–0.0764).

As depicted in Figure 2, our study demonstrated a significant positive correlation between frailty, assessed using the FP method, and factors such as age (p-value = 0.009), mMRC score, CAT score, and SGRQ scores. Pack-years of smoking, duration of dyspnea, and number of exacerbations in the past year. On the contrary, frailty evaluated through the SPPB method showed a significant negative correlation with the same factors. A significant negative correlation was found between frailty by either measure with post-bronchodilator FEV1(%), FVC(%), FEV1/FVC, 6MWT distance, and dyspnea severity.

Table 2 is representative of the association between FP and SPPB, which was significant but with a poor inter-rater kappa agreement of 0.196 (p-value = 0.0001). Among the 51.33% (n = 77) patients classified into the Frail group by the FP method, only 20% (n = 30) were categorized as Frail by SPPB. The rest 28.67% (n = 43) and 2.67% (n = 4) were categorized as pre-frail and not frail, respectively. This could possibly be due to the three objective measures in the SPPB method as compared to the four subjective and one objective parameter of FP method.

The univariate regression analysis for the FP measure, as presented in Table 3, revealed that the risk of frailty significantly increased with a history of ≥1 exacerbation in the past year, use of oral corticosteroid, pack-years of smoking, co-morbidities, CAT score, UCSD-SOBQ score, GOLD stages moderate and severe, GOLD group B and GOLD group D. The risk of frailty was significantly lower in patients with higher post-bronchodilator FEV1 (%), FVC (%), and greater distance covered during the 6MWT. In the multivariate regression analysis shown in Table 4, the only significant independent risk factors for frailty based on the FP measure were 6MWT distance and GOLD group B.

For frailty assessed using the SPPB method, univariate analysis identified symptom scores, impact scores, and total scores from the SGRQ as significant risk factors. However, multivariate logistic regression revealed that the 6MWT distance and severity of dyspnea were the significant independent predictors of frailty by the SPPB measure after adjusting for confounding factors.

DISCUSSION

This study evaluated frailty in stable COPD patients by comparing the FP and SPPB frailty assessment methods. We found a significant association between FP and SPPB methods but with poor inter-rater kappa agreement, including an overlap of frailty classification in only 20% of cases. This finding contrasts with the study by Brighton et al., which reported approximately 80% agreement between the two measures.⁴

Participants classified as frail by either method showed significant differences from those categorized as non-frail or pre-frail. Frail subjects were predominantly male, exhibited lower post-bronchodilator FEV1, demonstrated poorer functional exercise capacity (6MWD), had a higher number of comorbidities, and experienced higher dyspnea severity. Our findings align with those of Singer et al., who reported that 28% of participants were identified as frail by the FFP and 10% by the SPPB, with higher frailty scores in both assessments independently associated with greater disability and a higher risk of mortality.⁵

The two measures showed significant differences in their associations with the duration of dyspnea, exacerbations in the past year, mMRC score, CAT score, SGRQ score, and pack-years of smoking. Frailty by FP measure showed a significant positive correlation with these characteristics in contrast to a significant negative correlation demonstrated by the SPPB measure. This could possibly be due to the objective measures of SPPB as compared to a rather subjective assessment by FP. This implies that FP and SPPB could not be used interchangeably in assessing frailty status in COPD patients.

A common predictor of frailty by both the methods was distance covered in a 6MWT test. The distance covered in this self-paced test (6MWT) is a tool for assessing response to therapy and assessing symptom burden. In our study, the 6MWT distance was significantly lower in patients in the Frail group than those classified as Not Frail or Pre-frail. The negative correlation between 6MWT distance and frailty was also a notable finding in the study by Gale et al.²⁵ This signifies that frailty predisposes COPD patients to have poor functional capacity due to limb muscle dysfunction and reduced gait speed.

The assessment of frailty in respiratory care is gaining importance with the increasing availability of resources and equipment across various settings (e.g., handgrip dynamometers) highlighting the need to understand the utilities of different measures when deciding on a screening approach.¹⁸ For instance, the FP might focus more on identifying individuals with subjective symptoms, placing less emphasis on balance and gait issues which the SPPB method addresses, while being less sensitive to parameters such as exhaustion and weight loss. Wherever physical tests are not feasible, self-reported screening tools, (e.g., frail scale) are necessitated.^26–28 Comprehensive geriatric assessment is considered the gold standard for identifying frailty syndrome.⁶

The absence of follow-up in our study limited the ability to use frailty assessments to foretell risks of exacerbations, time to first hospitalization, or mortality, while the single-center design and limited number of participants may affect the external validity of the results. Although both measures were performed by the patients and the sequence of the tests was allotted randomly to reduce the learning effect, parameters like gait speed test, chair stand test, or hand grip strength might have been impacted.

CONCLUSION

In conclusion, in Indian patients with stable COPD, we found the prevalence of frailty to be 51.33% by FP and 21.33% by short performance physical battery. We found that both these methods of frailty assessment cannot be used interchangeably. 6MWT distance was found to be the most important predictor of frailty and it correlated with frailty by both methods.

ORCID

Sharmistha Dutta https://orcid.org/0009-0006-0721-3887

Nitin Goel https://orcid.org/0000-0001-5155-8985

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