What is the prevalence and clinical implications of frailty in middle-aged people with COPD?

Problem

Frailty, a state of reduced physiological reserve, is common in people with chronic obstructive pulmonary disease (COPD). Frailty can occur at any age, however the implications in younger people (aged <65 years) with COPD is unclear. We assessed the prevalence of frailty in UK Biobank participants with COPD; explored relationships between frailty and FEV1; and quantified the association between frailty and adverse outcomes.

Approach

UK Biobank participants (n=3132, recruited 2006-2010) with COPD aged 40-70 years were analysed comparing two frailty measures (frailty phenotype and frailty index) at baseline. The frailty phenotype was based on five criteria (weakness, slow walking pace, weight loss, exhaustion and low physical activity; 0 criteria = robust, 1-2 = pre-frailty, 3 or more = frailty). The frailty index was a non-weighted count of 42 health deficits, scaled to between 0 and 1. Participants were categorized as robust (<0.12), mild (0.12-0.24), moderate (0.24-0.36) and severely (>0.36) frailty. Relationship with forced expiratory volume in 1 second (FEV1) was assessed for each measure. We assessed the relationship between frailty and mortality, Major Adverse Cardiovascular Event (MACE), all-cause hospitalization, hospitalisation with COPD exacerbation, and community COPD exacerbation over 8 years follow-up, adjusted for age, sex, socioeconomic status, smoking, alcohol and FEV1.

Findings

Frailty was common by both definitions. Using the frailty phenotype, 514 (17%) of participants with COPD were classified as frail, 1518 (48%) were pre-frail. Using the frailty index 872 (28%) had moderate frailty and 121 (4%) had severe frailty. The frailty phenotype, but not the frailty index, was associated with lower FEV1. Frailty phenotype [frail vs robust] was associated with mortality (hazard ratio 2.33; 95%CI 1.84-2.96), MACE (2.73; 1.66-4.49), hospitalisation (incidence rate ratio 3.39; 2.77-4.14), hospitalised exacerbation (5.19; 3.80-7.09), and community exacerbation (2.15; 1.81-2.54). The frailty index [severe vs robust] was also associated with each of these outcomes (mortality (2.65; 95%CI 1.75-4.02), MACE (6.76; 2.68-17.04), hospitalisation (3.69; 2.52-5.42), hospitalised exacerbation (4.26; 2.37-7.68), and community exacerbation (2.39; 1.74-3.28). Associations between frailty and each outcome were similar before and after adjusting for FEV1.

Consequences

Frailty, regardless of age or measure, identifies people with COPD at risk of adverse clinical outcomes. Associations between frailty and clinical outcomes also appear to be independent of COPD severity assessed using FEV1. Frailty assessment may aid risk stratification and guide targeted intervention in COPD and should not be limited to people aged >65 years.