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Patients with chronic obstructive pulmonary disease (COPD) who are both frail and who have poor lung function or dyspnea are at especially high risk of disability within 3 to 5 years as well as all-cause mortality years later, a prospective cohort study of community-dwelling adults has shown.

“Frailty, a widely recognized geriatric syndrome characterized by multidimensional functional decline in bio-psycho-social factors, is associated with functional disability and mortality,” senior author Tze Pin Ng, coumadin food risk MD, National University of Singapore, and colleagues explain.

“Our results…suggest that beyond traditional prognostic markers such as FEV1% (forced expiratory volume in 1 second) and dyspnea, the physical frailty phenotype provides additional useful prognostic information on future risks of disability and mortality,” the authors suggest.

The study was published online December 12 in Chest.

SLAS-1 and SLAS-2

Data from the Singapore Longitudinal Ageing Study (SLAS-1) and SLAS-2 were collected and analyzed. SLAS-1 recruited 2804 participants 55 years of age and older from September 2003 through to December 2004, while SLAS-2 recruited 3270 participants of the same age between March 2009 and June 2013. “Follow-up visits and assessments were conducted approximately 3–5 years apart,” the investigators noted.

Mortality was determined at a mean of 9.5 years of follow-up for SLAS-1 participants and a mean of 6.5 years’ follow-up for SLAS-2 participants. A total of 4627 participants were eventually included in the analysis, of whom 1162 patients had COPD and 3465 patients did not. COPD was classified as mild if FEV1% was ≥80%; moderate if FEV1% was ≥50% to <80%, and severe if FEV1% was <50%.

Frailty in turn was based on five clinical criteria, including weakness, slowness, low physical activity, exhaustion, and shrinking. Participants were classified as frail if they met three or more of these criteria and prefail if they met one or two criteria.

Adverse health outcomes were judged on the basis of instrumental or basic activities of daily living (IADL/ADL), while disability was judged by self-reported difficulties in or requiring assistance with at least one IADL or ADL.

Frail or Prefrail

Almost half of the participants were frail or prefrail, as the authors reported, while 25% had COPD. Among the participants with COPD, 30% had moderate to severe COPD, 6.4% had dyspnea, and almost half had prefraility, while approximately 7% were classified as frail.

This percentage was 86% higher than it was for participants without COPD, among whom just 3.2% were assessed as frail, at an odds ratio (OR) of 1.86 (95% CI, 1.35 – 2.56). Further adjustments for possible confounders reduced the gap between frail COPD and frail non-COPD participants, but frailty remained significantly associated with COPD, at an OR of 1.61 (95% CI, 1.15 – 2.26), the investigators note.

Furthermore, compared to those without COPD, a diagnosis of COPD without and with dyspnea was associated with a 1.5- and 4.2-fold increase in prevalent frailty (95% CI, 1.04 – 2.08; 1.84 – 9.19), respectively, although not with prefrailty. Again, adjusting for multiple confounders, FEV1%, dyspnea, and both prefrailty and frailty were associated with an approximately twofold higher prevalence of IADL/ADL disability, while the prevalence of IADL/ADL disability for participants with COPD was approximately fourfold higher in those with co-occurring FEV1% <80% with either prefraility, frailty, or dyspnea.

Furthermore, the presence of prefrailty or frailty in combination with a lower FEV1% or dyspnea was associated with a 3.7- to 3.8-fold increased risk of having an IADL or ADL disability.

Frailty and Mortality

Some 1116 participants with COPD were followed for a mean of 2981 days for mortality outcomes. Both FEV1% <50% and the presence of prefrailty and frailty almost doubled the risk of mortality, at an adjusted hazard ratio (HR) of 1.8 (95% CI, 1.24 – 2.68) compared to patients with an FEV1% ≥80%. In combination with either FEV1% <80% or prefraility/frailty, dyspnea almost more than doubled the risk of mortality, at an HR of 2.4 for both combinations.

“However, the mortality risk of participants with COPD was highest among those with FEV1% <80% and prefrailty/frailty,” the authors note, a more than tripling mortality risk at an adjusted HR of 3.25 (95% CI, 1.97 – 5.36). Interestingly, FEV1 <80% and prefrailty/frailty — both alone and in combination — were also associated with a twofold to fourfold increased risk of IADL or ADL disability in participants without COPD but were less strongly associated with mortality.

Researchers then went on to create a summary risk score containing all relevant variables with values ranging from 0 to 5. The highest risk category of 3 to 5 was associated with a 7- to 8.5-fold increased risk for IADL and ADL disability and mortality among participants with COPD, and that risk remained high after adjusting for multiple confounders.

Interestingly, frailty did not significantly predict mortality in women, while dyspnea did not significantly predict mortality in men. “Recognition and assessment of physical frailty in addition to FEV1% and dyspnea would allow for more accurate identification and targeted treatment of COPD at risk of future adverse outcomes,” the authors suggest.

Frailty Scoring System

Asked to comment on the study, Sachin Gupta, MD, a pulmonologist and critical care specialist at Alameda Health System in Oakland, California, noted that the current study adds to the body of literature that outcomes in patients with COPD depend as much on objectively measured variables as on qualitative measures. “By applying a frailty scoring system, these researchers were able to categorize frailty and study its impact on patient characteristics and outcomes,” he told Medscape Medical News in an email.

The summary risk assessment tool developed and assessed is familiar: it carries parallels to the widely utilized BODE Index, replacing body mass index and 6-minute walk distance with the frailty scale, he added. “Findings from this study support the idea that what meets the eye in face-to-face visits — frailty — can be codified and be part of a tool that is predictive of outcomes,” Gupta underscored.

The authors had no conflicts of interest to declare. Gupta disclosed he is also an employee and shareholder at Genentech.

Chest. Published December 12, 2021. Abstract

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