Frailty: A global measure of the multisystem impact of COPD.
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ABSTRACT:
SUBMITTER: Gale NS
PROVIDER: S-EPMC6234567 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Frailty: A global measure of the multisystem impact of COPD.
Gale Nichola S NS Albarrati Ali M AM Munnery Margaret M MM Hubbard Ruth E RE Tal-Singer Ruth R Cockcroft John R JR Shale Dennis J DJ
Chronic respiratory disease 20180116 4
Chronic obstructive pulmonary disease (COPD) is a multisystem disease that resembles the accumulation of multiple impairments seen in aging. A comprehensive geriatric assessment (CGA) captures multisystem deficits, from which a frailty index (FI) can be derived. We hypothesized that patients with COPD would be frailer than a comparator group free from respiratory disease. In this cross-sectional analysis, the CGA questionnaire was completed and used to derive an FI in 520 patients diagnosed with ...[more]
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Project description:BackgroundAdvanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication. Aspergillus sensitisation may worsen symptoms in COPD.MethodsWe identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC < 70% and FEV1 < 80%) using standardised criteria in multiple countries, to re-estimate the prevalence of COPD. Hospitalised COPD patients develop IA in 1.3-3.9%, based on positive cultures of Aspergillus spp. and radiological findings. Given limited data on per-patient annual hospitalisation rates, we assumed a conservative 10.5% estimate. Annual IA mortality in COPD was estimated using the literature rates of 43-72%. A separate literature search assessed the impact of Aspergillus sensitisation on severity of COPD (by FEV1).ResultsWe re-estimated the global prevalence of COPD GOLD stages II-IV at 552,300,599 people (7.39% of the population) with 339,206,893 (8.58%) in Asia, 85,278,783 (8.52%) in the Americas, 64,298,051 (5.37%) in Africa, 59,484,329 (7.77%) in Europe and 4,032,543 (10.86%) in Oceania. An estimated 57,991,563 (10.5%) people with COPD are admitted to hospital annually and of these 753,073 (1.3%) - 2,272,322 (3.9%) develop IA and 540,451-977,082 deaths are predicted annually. Aspergillus sensitisation prevalence in COPD was 13.6% (7.0-18.3%) and not related to lower predicted FEV1% (P > 0.05).ConclusionsThe prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality.
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Project description:"Frailty" is a term used to refer to a state characterized by enhanced vulnerability to, and impaired recovery from, stressors compared with a nonfrail state, which is increasingly viewed as a loss of resilience. With increasing life expectancy and the associated rise in years spent with physical frailty, there is a need to understand the clinical and physiological features of frailty and the factors driving it. We describe the clinical definitions of age-related frailty and their limitations in allowing us to understand the pathogenesis of this prevalent condition. Given that age-related frailty manifests in the form of functional declines such as poor balance, falls, and immobility, as an alternative we view frailty from a physiological viewpoint and describe what is known of the organ-based components of frailty, including adiposity, the brain, and neuromuscular, skeletal muscle, immune, and cardiovascular systems, as individual systems and as components in multisystem dysregulation. By doing so we aim to highlight current understanding of the physiological phenotype of frailty and reveal key knowledge gaps and potential mechanistic drivers of the trajectory to frailty. We also review the studies in humans that have intervened with exercise to reduce frailty. We conclude that more longitudinal and interventional clinical studies are required in older adults. Such observational studies should interrogate the progression from a nonfrail to a frail state, assessing individual elements of frailty to produce a deep physiological phenotype of the syndrome. The findings will identify mechanistic drivers of frailty and allow targeted interventions to diminish frailty progression.
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Project description:BackgroundSarcopenia, cachexia and frailty have overlapping features and clinical consequences, but often go unrecognized. The objective was to detect patients described by clinicians as having sarcopenia, cachexia or frailty within electronic health records (EHR) and compare clinical variables between cases and matched controls.MethodsWe conducted a case-control study using retrospective data from the Indiana Network for Patient Care multi-health system database from 2016 to 2017. The computable phenotype combined ICD codes for sarcopenia, cachexia and frailty, with clinical note text terms for sarcopenia, cachexia and frailty detected using natural language processing. Cases with these codes or text terms were matched to controls without these codes or text terms matched on birth year, sex and race. Two physicians reviewed EHR for all cases and a subset of controls. Comorbidity codes, laboratory values, and other coded clinical variables were compared between groups using Wilcoxon matched-pair sign-rank test for continuous variables and conditional logistic regression for binary variables.ResultsCohorts of 9594 cases and 9594 matched controls were generated. Cases were 59% female, 69% white, and a median (1st, 3rd quartiles) age 74.9 (62.2, 84.8) years. Most cases were detected by text terms without ICD codes n = 8285 (86.4%). All cases detected by ICD codes (total n = 1309) also had supportive text terms. Overall 1496 (15.6%) had concurrent terms or codes for two or more of the three conditions (sarcopenia, cachexia or frailty). Of text term occurrence, 97% were used positively for sarcopenia, 90% for cachexia, and 95% for frailty. The remaining occurrences were negative uses of the terms or applied to someone other than the patient. Cases had lower body mass index, albumin and prealbumin, and significantly higher odds ratios for diabetes, hypertension, cardiovascular and peripheral vascular diseases, chronic kidney disease, liver disease, malignancy, osteoporosis and fractures (all p < 0.05). Cases were more likely to be prescribed appetite stimulants and caloric supplements.ConclusionsPatients detected with a computable phenotype for sarcopenia, cachexia and frailty differed from controls in several important clinical variables. Potential uses include detection among clinical cohorts for targeting recruitment for research and interventions.
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Project description:IntroductionMultifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically tested for measurement differences by key characteristics.MethodsWe used the Women's Health and Aging Studies (WHAS) I and II (N = 649), and the Health ABC study (N = 1515). Twelve biomarkers representing multiple systems including stress response (e.g., inflammation), endocrine system, and energy regulation were identified. A series of confirmatory factor analyses (CFA) were conducted to evaluate the interplay between physiological systems and underlying multisystem dysregulation. We evaluated convergent criterion validity of a score for multisystem dysregulation against the physical frailty phenotype, and predictive criterion validity with incidence of walking difficulty and mortality.ResultsA bifactor CFA, a model in which dysregulation of individual systems proceeds independently of generalized dysregulation, fit data well in WHAS (RMSEA: 0.019; CFI: 0.977; TLI: 0.961) and Health ABC (RMSEA: 0.047; CFI: 0.874; TLI: 0.787). The general dysregulation factor was associated with frailty (OR: 2.2, 95 % CI: 1.4, 3.5), and elevated risk of incident walking difficulty and mortality. Findings were replicated in Health ABC.DiscussionBiomarker data from two epidemiologic studies support the construct of multisystem physiological dysregulation. Results further suggest system-specific and system-wide processes have unique and non-overlapping contributions to dysregulation in biological markers.
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Project description:BackgroundFrailty remains an elusive concept despite many efforts to define and measure it. The difficulty in translating the clinical profile of frail elderly people into a quantifiable assessment tool is due to the complex and heterogeneous nature of their health problems. Viewing frailty as a 'latent vulnerability' in older people this study aims to derive a model based measurement of frailty and examines its internal reliability in community dwelling elderly.MethodThe British Women's Heart and Health Study (BWHHS) cohort of 4286 women aged 60-79 years from 23 towns in Britain provided 35 frailty indicators expressed as binary categorical variables. These indicators were corrected for measurement error and assigned relative weights in its association with frailty. Exploratory factor analysis (EFA) reduced the data to a smaller number of factors and was subjected to confirmatory factor analysis (CFA) which restricted the model by fitting the EFA-driven structure to observed data. Cox regression analysis compared the hazard ratios for adverse outcomes of the newly developed British frailty index (FI) with a widely known FI. This process was replicated in the MRC Assessment study of older people, a larger cohort drawn from 106 general practices in Britain.ResultsSeven factors explained the association between frailty indicators: physical ability, cardiac symptoms/disease, respiratory symptoms/disease, physiological measures, psychological problems, co-morbidities and visual impairment. Based on existing concepts and statistical indices of fit, frailty was best described using a General Specific Model. The British FI would serve as a better population metric than the FI as it enables people with varying degrees of frailty to be better distinguished over a wider range of scores. The British FI was a better independent predictor of all-cause mortality, hospitalization and institutionalization than the FI in both cohorts.ConclusionsFrailty is a multidimensional concept represented by a wide range of latent (not directly observed) attributes. This new measure provides more precise information than is currently recognized, of which cluster of frailty indicators are important in older people. This study could potentially improve quality of life among older people through targeted efforts in early prevention and treatment of frailty.
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Project description:ObjectivesDevelop and validate a modified frailty phenotype measure for older Mexican Americans participating in the Hispanic Established Populations for the Epidemiological Study of the Elderly (H-EPESE) and related studies.DesignExpert-based panel evaluation of content validity, cross-sectional analysis of construct validity, and longitudinal analysis of criterion validity for a modified version of the frailty phenotype measure.SettingFive southwestern states.ParticipantsA total of 1833 community-dwelling Mexican Americans aged 67 years or older.MeasurementsFrailty was assessed using the frailty phenotype measure (weight loss, weakness, exhaustion, slowness, and low physical activity) and a modified frailty phenotype measure (replacing "low physical activity" with "limitations in walking half a mile"). Each individual was classified as non-frail, pre-frail, or frail based on both frailty measures (original vs modified). Expert panel consensus was used to examine content validity. Spearman correlation, κ, weighted κ, and bootstrapping κ examined construct validity (n = 1833). Generalized linear mixed models, odds ratios, Cox proportional regression models, hazard ratios, and C statistics were used to analyze criterion validity (n = 1446) across four outcomes: hospitalization, physician visits, disability, and mortality from wave 3 (1998-99) through wave 8 (2012-13).ResultsThe original and modified frailty phenotype measures had a strong correlation (r = .89; P < .000) and agreement (κ = .84; 95% confidence interval [CI] = .81-.86; weighted κ = .86; 95% CI = .84-.88; bootstrap κ = .84; 95% CI = .81-.86; bootstrap-weighted κ = .86; 95% CI = .84-.88 with 1000 bootstrapping samples). Four outcome models showed similar risk predictions for both frailty measures, with the exception of physician visits for frail participants.Conclusion"Limitations in walking half a mile" can be used as a substitute criterion for "low physical activity" in assessing frailty. The modified frailty phenotype measure was comparable with the original frailty phenotype measure in H-EPESE participants over time. Our results indicate the modified frailty phenotype is a useful longitudinally frailty measure for community-dwelling older Mexican Americans. J Am Geriatr Soc 67:2393-2397, 2019.
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Project description:BackgroundIn chronic obstructive pulmonary disease, both smaller and larger airways are affected. FEV1 mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow. In this study, the objective was to evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6 seconds (FEV3/FEV6), and small airways measures and gas trapping at quantitative chest CT scanning, and clinical outcomes in the Genetic Epidemiology of COPD (COPDGene) cohort.MethodsSeven thousand eight hundred fifty-three current and ex-smokers were evaluated for airflow obstruction by using recently defined linear iteratively derived equations of Hansen et al to determine lower limit of normal (LLN) equations for prebronchodilator FEV1/FVC, FEV1/FEV6, FEV3/FEV6, and FEV3/FVC. General linear and ordinal regression models were applied to the relationship between prebronchodilator spirometric and radiologic and clinical data.ResultsOf the 10,311 participants included in the COPDGene phase I study, participants with incomplete quantitative CT scanning or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with FEV1/FVC greater than or equal to the LLN, 15.4% had abnormal FEV3/FEV6. Compared with normal FEV3/FEV6 and FEV1/FVC, abnormal FEV3/FEV6 was associated with significantly greater gas trapping; St. George's Respiratory Questionnaire score; modified Medical Research Council dyspnea score; and BMI, airflow obstruction, dyspnea, and exercise index and with shorter 6-min walking distance (all P < .0001) but not with CT scanning evidence of emphysema.ConclusionsCurrent and ex-smokers with prebronchodilator FEV3/FEV6 less than the LLN as the sole abnormality identifies a distinct population with evidence of small airways disease in quantitative CT scanning, impaired indexes of physical function and quality of life otherwise deemed normal by using the current spirometric definition.
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Project description: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.
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Project description:In deciding on the treatment plan for patients with chronic obstructive pulmonary disease (COPD), the burden of COPD as experienced by patients should be the core focus. It is therefore important for daily practice to develop a tool that can both assess the burden of COPD and facilitate communication with patients in clinical practice. This paper describes the development of an integrated tool to assess the burden of COPD in daily practice. A definition of the burden of COPD was formulated by a Dutch expert team. Interviews showed that patients and health-care providers agreed on this definition. We found no existing instruments that fully measured burden of disease according to this definition. However, the Clinical COPD Questionnaire meets most requirements, and was therefore used and adapted. The adapted questionnaire is called the Assessment of Burden of COPD (ABC) scale. In addition, the ABC tool was developed, of which the ABC scale is the core part. The ABC tool is a computer program with an algorithm that visualises outcomes and provides treatment advice. The next step in the development of the tool is to test the validity and effectiveness of both the ABC scale and tool in daily practice.
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