BACKGROUND: Commonly used thresholds for staging FEV1 have not been evaluated as standalone spirometric predictors of death in older persons. Specifically, the proportion of deaths attributed to a reduced FEV1, when staged by commonly used thresholds in L, percent of predicted (% pred), and Z scores, has not been previously reported. METHODS: In 4,232 white persons ≥ 65 y old, sampled from the Cardiovascular Health Study, FEV1 was stratified as stage 1 (FEV1 ≥ 2.00 L, ≥80% pred, and Z score ≥−1.64), stage 2 (FEV1 1.50–1.99 L, 50–79%pred, and Z score −2.55 to −1.63), and stage 3 (FEV1 < 1.50 L, < 50% pred, and Z score < −2.55). Notably, a Z score threshold of −1.64 defines normal-for-age lung function as the lower limit of normal (ie, 5th percentile of distribution), and accounts for differences in age, sex, height, and ethnicity. Next, adjusted odds ratios and average attributable fractions for 10-y all-cause mortality were calculated, comparing FEV1 stages 2 and 3 against stage 1, expressed in L, % pred, and Z scores. The average attributable fraction estimates the proportion of deaths attributed to a predictor by combining the prevalence of the predictor with the relative risk of death conferred by that predictor. RESULTS: FEV1 stage 2 and 3 in L, % pred, and Z scores yielded similar adjusted odds ratios of death: 1.40–1.51 for stage 2 and 2.35–2.66 for stage 3. Conversely, FEV1 stages 2 and 3 in L, % pred, and Z scores differed in prevalence: 12.8–28.6% for stage 2 and 6.4–17.5% for stage 3, and also differed in the adjusted average attributable fraction for death: 3.2–6.4% for stage 2 and 4.5–9.1% for stage 3. CONCLUSIONS: In older persons, the proportion of deaths attributed to a reduced FEV1 is best stratified by Z score staging thresholds because these yield a similar relative risk of death but a more age- and sex-appropriate prevalence of FEV1 stage.

Background and Objectives: To assess whether medically supportive care partners modify the associations of symptomatic chronic conditions with the number of functional disabilities in a cohort of multimorbid older adults with cognitive impairment. Research Design and Methods: The research design is a prospective study of a nationally representative cohort of Medicare beneficiaries. National Health and Aging Trends Study (NHATS) data were linked with Medicare claims for years 2011-2015. Participants were aged 65 or older and had cognitive impairment with at least 2 chronic conditions (N = 1,003). Annual in-person interviews obtained sociodemographic information at baseline and time-varying variables for caregiving, hospitalization, and 6 activities of daily living (ADL); these variables were merged with Center for Medicare and Medicaid Services data to ascertain 16 time-varying chronic conditions. A care partner was defined as a person who sat with their care recipient during doctor visits in the past year and/or who helped them with prescribed medications in the last month. Chronic condition associations and their potential effect modifications by care partner status were assessed using weighted generalized estimating equations accounting for the complex survey design of the longitudinal analytical sample. Results: Chronic kidney disease, depression, and heart failure were associated with an increased number of functional disabilities. Among these, only the association of chronic kidney disease with the number of functional disabilities (interaction p value = .001) was weakened by the presence of a care partner. Discussion and Implications: The presence of care partners showed limited modification of the associations of symptomatic chronic conditions with functional disability.

Background: Clinical trials of COPD pharmacotherapy typically involve aging populations with moderate-to-severe COPD, but the latter is often diagnosed by spirometric criteria that are not age-appropriate across the continuum of lung function. We have therefore re-evaluated the clinical effect of combination therapy (salmeterol plus fluticasone) in moderate-to-severe COPD, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI) and trial data from Towards a Revolution in COPD Health (TORCH). Methods: Of the 6112 TORCH participants, 5688 (93.1%) had GLI-based moderate-to-severe COPD (mean age 64.8 years). The primary outcome was all-cause mortality and the primary comparison was combination therapy vs. placebo. Secondary outcomes included COPD and cardiovascular (CV) mortality and pneumonia. A modified intention-to-treat analysis evaluated differences in time-to-event over a three-year period, using Cox proportional hazards models with statistical significance at p < 0.010 (acknowledging repeated significance testing). Results: Relative to placebo, combination therapy yielded a statistically non-significant reduction in all-cause mortality-adjusted hazard ratio [adjHR] 0.78 (95% confidence interval [CI]: 0.64, 0.95), p=0.012. Relative to placebo, combination therapy also yielded statistically non-significant reductions in COPD and CV mortality-adjHR 0.75 (95% CI: 0.55, 1.02), p=0.068 and adjHR 0.76 (95% CI: 0.53, 1.09), p=0.135, respectively. In contrast, combination therapy yielded a statistically significant increased risk of pneumonia, relative to placebo-adjHR 1.80 (95% CI: 1.46, 2.21), p < 0.001. Conclusion: In GLI-based moderate-to-severe COPD, combination therapy yields a statistically significant increased risk of pneumonia but the reductions in mortality are not statistically significant, although could potentially be clinically meaningful.

OBJECTIVE To examine the epidemiology and key demographic and clinical correlates of patient‐reported hypersomnia in persons with advanced age. DESIGN Cross‐sectional design. SETTING Community. PARTICIPANTS A total of 357 community‐dwelling persons from the Yale Precipitating Events Project with a mean age of 84.2 years (range = 78‐102 years). MEASUREMENTS We studied patient‐reported hypersomnia, defined categorically by an Epworth Sleepiness Scale (ESS) score of 10 or greater; as well as the severity of hypersomnia symptoms, defined continuously by an ESS score range of 0 to 24 (higher scores denote greater sleepiness). In multivariable regression models, we examined cross‐sectional associations between key correlates and ESS score, expressed as categorical and continuous variables. Key correlates included: demographics, education, smoking status, body mass index, self‐reported medical conditions, Center for Epidemiologic Studies Depression score, Mini‐Mental State Examination score, Physical Activity Scale for the Elderly, restless legs syndrome (RLS), self‐reported sleep‐disordered breathing (SDB), medications, and Insomnia Severity Index. RESULTS Mean ESS score for all participants was 6.4. Patient‐reported hypersomnia (ESS score ≥10) was established in 82 participants (23.0%)—their mean ESS score was 13.0. In multivariable models, male sex, nonwhite race, arthritis, depressive symptoms, low physical activity, RLS, SDB, central nervous system depressant medications, and insomnia severity were cross‐sectionally associated with patient‐reported hypersomnia (higher adjusted odds ratios, ranging from 1.93‐2.86) and/or with the severity of hypersomnia symptoms (higher ESS scores, ranging from 0.11‐2.86 points). CONCLUSION Patient‐reported hypersomnia was prevalent in a sample of community‐dwelling persons with advanced age. In addition, based on cross‐sectional associations with the ESS score, key demographic and clinical characteristics were identified that may inform screening strategies for hypersomnia in advanced age. J Am Geriatr Soc 67:2545–2552, 2019

Rationale: Psychiatric conditions are often falsely considered inherent to aging. We examined whether negative age stereotypes, which older individuals tend to assimilate from the environment across their lifespan, contributed to an increased risk of developing four psychiatric conditions, and, if so, whether this risk was reduced through active coping. Method: The sample consisted of participants aged 55 years and older, free of the psychiatric conditions at baseline, drawn from the National Health and Resilience in Veterans Study, a nationally representative sample. New cases of posttraumatic stress disorder, suicidal ideation, generalized anxiety disorder, and major depressive disorder were assessed during three waves spanning a four-year period. Results: As predicted, participants holding more-negative age stereotypes were more likely to develop the psychiatric conditions, and their engagement in active coping reduced the risk of their developing these conditions. Conclusion: Our findings suggest that prevention and treatment efforts designed to reduce psychiatric conditions in later life may benefit from bolstering active coping as well as positive age stereotypes.

Polypharmacy and potentially inappropriate medications (PIMs) are increasingly common and associated with adverse health effects. However, post-graduate education in polypharmacy and complex medication management for older adults remain limited. The Initiative to Minimize Pharmaceutical Risk in Older Veterans (IMPROVE) polypharmacy clinic was created to provide a platform for teaching internal medicine (IM) and nurse practitioner (NP) residents about outpatient medication management and deprescribing for older adults. We aimed to assess residents’ knowledge of polypharmacy and perceptions of this interprofessional education intervention. A prospective cohort study with an internal comparison group. IM residents and NP residents; Veterans ≥ 65 years and taking ≥ 10 medications. IMPROVE consists of a pre-clinic conference, shared medical appointment, individual appointment, and interprofessional precepting model. We assessed residents’ performance on a pre-post knowledge test, residents’ qualitative assessment of the educational impact of IMPROVE, and the number and type of medications discontinued or decreased. The IMPROVE intervention group (n = 18) had a significantly greater improvement in test scores than the control group (n = 18) (14% ± 15% versus − 1.3% ± 16%) over a period of 6 months (Wilcoxon rank sum, p = 0.019). In focus groups, residents (n = 17) reported perceived improvements in knowledge and skills, noting that the experience changed their practice in other clinical settings. In addition, residents valued the unique interprofessional experience. Veterans (n = 71) had a median of 15 medications (IQR 12–19), and a median of 2 medications (IQR 1–3) was discontinued. Vitamins, supplements, and cardiovascular medications were the most commonly discontinued medications, and cardiovascular medications were the most commonly decreased in dose or frequency. Overall, IMPROVE is an effective model of post-graduate primary care training in complex medication management and deprescribing that improves residents’ knowledge and skills, and is perceived by residents to influence their practice outside the program.

OBJECTIVE:Little is known about the cardiovascular effects of mutual emotional spousal support given for health concerns. We examined the hypotheses that: (a) mutual support (both spouses giving and receiving support) compared to one-sided or no support, would decrease blood pressure and heart rate in both spouses during a recovery period; and (b) wives would benefit more from mutual support than would husbands. A second aim was to examine gender differences in cardiovascular reactivity, distress, and closeness in response to receiving support regardless of mutuality. METHOD:In 98 married couples (Age 50+), spouses discussed health concerns and were assigned randomly to one of four conditions: neither spouse received support (n = 26), only the wife received support from the husband (n = 22), only the husband received support from the wife (n = 23), or both received support (n = 27). Systolic and diastolic blood pressure and heart rate were measured during baseline, the discussions, and recovery. Distress, closeness, and support were self-reported. Support quality was observationally coded. RESULTS:Mutual support did not affect cardiovascular reactivity. When husbands received support from wives, husbands' blood pressure and distress decreased, and both partners' closeness increased. When wives received support, husbands and wives felt closer, but both partners' heart rate remained elevated and wives felt more distressed. CONCLUSIONS:Receiving support individually may be more important than receiving support mutually for older adult spouses coping with their health concerns. Also, support interventions for couples coping with health conditions should take into account that husbands receive greater benefits from spousal support than wives. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Both aging and HIV infection are associated with an enhanced pro-inflammatory environment that contributes to impaired immune responses and is mediated in part by innate immune pattern-recognition receptors. MINCLE is a C-type lectin receptor that recognizes trehalose-6,6'-dimycolate or "cord factor," the most abundant glycolipid in Mycobacterium tuberculosis. Here, we evaluated MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21-35 years) and older adults (≥60 years) via stimulation of peripheral blood mononuclear cells with trehalose-6,6-dibehenate, a synthetic analog of trehalose-6,6'-dimycolate and measurement of cytokine production (interleukin [IL]-10, IL-12, IL-6, tumor necrosis factor-α) by multicolor flow cytometry. Our studies show an age- and HIV-associated increase in cytokine multifunctionality of monocytes both at the population and single cell level that was dominated by IL-12, IL-10, and IL-6. These findings provide insight into the host response to M. tuberculosis and possible sources for the pro-inflammatory environment seen in aging and HIV infection.

INTRODUCTION:Older minority individuals are less likely to receive adequate health care than their white counterparts. This study investigates whether perceived racism is associated with delayed/forgone care among minority older adults, and whether poor doctor communication mediates this relationship.METHODS:Study cohort consisted of minority participants, aged ≥65 years, in the 2015 California Health Interview Survey (N=1,756). Authors obtained data in November 2017, and statistical analyses were performed from February to April 2018. Multivariable logistic regression analyses were conducted with relevant covariates, including insurance coverage, years living in the U.S., and language. A mediation analysis was also performed.RESULTS:Among minority older individuals, perceived racism was significantly associated with delayed/forgone care (AOR=3.92, 95% CI=1.38, 11.15, p=0.010). Poor doctor communication significantly and partially mediated the relationship (AOR=3.64, 95% CI=1.30, 10.21, p=0.014), accounting for 9.9% of the total effect.CONCLUSIONS:Perceived racism may contribute to health disparities for older minority individuals in part through doctors communicating messages that discourage adequate utilization of health care. Future research should explore culturally sensitive communication skills that reduce this barrier to receiving adequate health care.

This letter comments on the letter by Buck et al.

Models of preclinical Alzheimer's disease (AD) propose that cerebral amyloidosis leads to neuro-degeneration and subsequent cognitive decline. This study investigated whether APOE genotype is related to beta-amyloid (A beta) burden in brain regions preferentially affected by AD and whether A beta burden is associated with gray-matter (GM) fraction (as a marker of neurodegeneration) and episodic memory performance in cognitively normal middle-aged individuals at varying genetic risk for AD. Three groups of cognitively normal participants aged 50-65 years with a first-degree family history of AD (APOE genotype epsilon 4 epsilon 4 [n = 15], epsilon 3 epsilon 4 [n = 15], and epsilon 3 epsilon 3 [n = 15]) underwent [C-11]PiB positron emission tomography scans to quantify cortical A beta, brain magnetic resonance imaging, and neuropsychological testing. APOE epsilon 4 epsilon 4 participants demonstrated significantly higher cortical A beta burden than APOE epsilon 3 epsilon 3 (p < 0.001). Furthermore, cortical A beta burden was inversely associated with cortical GM fraction (p = 0.017) but not episodic memory performance. In cognitively normal, middle-aged individuals, A beta burden is significantly associated with GM fraction but not episodic memory performance. These findings are consistent with models of preclinical AD in which neurodegeneration occurs before manifest cognitive decline. (C) 2017 The Authors. Published by Elsevier Inc.

Abstract Background Patient sharing between hospitals and long-term care facilities (LTCF) is widespread. However, surveillance criteria for noncatheter associated urinary tract infection (UTI) vary by healthcare setting. Consequently, patients with identical features of UTI may meet criteria in LTCF but not in hospitals. A common definition that spans hospitals and LTCF may inform UTI surveillance efforts across healthcare facilities. Methods We performed a cohort analysis of all suspected UTI cases in women ≥65 years from 21 LTCF enrolled in a clinical trial evaluating cranberry capsules to reduce bacteriuria plus pyuria from August 2012 to October 2015. We applied 2017 hospital National Healthcare Safety Network (NSHN), 2012 LTCF NSHN, and proposed criteria (Figure 1) to all suspected UTI cases. Proposed criteria were derived a priori. Differences in the correlated proportions of UTI detected per criteria were assessed using McNemar’s test. Results Of 350 suspected UTI cases, LTCF NSHN criteria detected more UTI (22/350, 6.3%) compared with hospital NHSN (15/350, 4.3%; P = 0.04) and proposed (15/350, 4.3%; P = 0.02) criteria (Table 1). Half (11/22) of LTCF NHSN UTI included ≥102 CFU/mL of organisms from a catheterized urine as the microbiological criterion. Four UTI meeting LTCF NHSN or proposed criteria did not meet the hospital NHSN criteria because fever is only a listed clinical feature for patients ≤65 years.Table 1. UTI Detection by Surveillance Criteria. Criteria P value LTCF NHSN Hospital NHSN Present Absent Present 13 2 Absent 9 326 0.04 LTCF NHSN Proposed Present Absent Present 15 0 Absent 7 328 0.02 Conclusion Current hospital and LTCF NHSN criteria both have limitations. The hospital NHSN criteria exclude fever in older adults as a clinical feature. The LTCF NHSN criteria include insensitive microbiological criteria. Our proposed surveillance criteria address these limitations and may be generalizable to both hospitals and LTCF. Disclosures M. Juthani-Mehta, Iterum Therapeutics: Scientific Advisor, Consulting fee.

PurposeCritically ill patients experience significant sleep disruption. In this study of ICU patients with delirium, we evaluated associations between the loss of stage N2 features (K-complexes, sleep spindles), grade of encephalopathy based on electroencephalography (EEG), and intensive care unit (ICU) outcomes. We hypothesized that loss of stage N2 features is associated with more severe grades of encephalopathy and worse ICU outcomes including death.Materials and methodsThis was an observational cohort study of 93 medical ICU patients without primary acute brain injury who underwent continuous EEG. Type and severity of critical illness, sedative-hypnotic use, length of stay, modified Rankin Scale at hospital discharge, and death during hospitalization were abstracted from the medical record. EEG was evaluated for grade of encephalopathy and sleep features.ResultsPatients without K-complexes or without sleep spindles had more severe encephalopathy and higher odds of death. The odds ratio for patients without K-complexes was 18.8 (p = .046). The odds ratio for patients without sleep spindles was 6.3 (p = .036).ConclusionsLoss of stage N2 features is common and associated with more severe encephalopathy and higher odds of death. The absence of either Stage N2 feature, K complexes or sleep spindles, may have important prognostic value.

Background Empirical data regarding the frequency of infection during fever episodes among women in long-term care facilities are lacking. Methods We conducted a case-series analysis of women long-term care residents enrolled in a randomized trial evaluating cranberry capsules to reduce bacteriuria plus pyuria across twenty-one long-term care facilities in CT, USA. Fever episodes identified during adverse event surveillance were assessed using established guidelines for older adults. Among fever episodes, infections were classified using standardized infection surveillance definitions in long-term care residents. Results We identified 123 fever episodes among 80 women long-term care residents. Median age was 88 years (range, 65–101), and 81% (N=65) had dementia. Among 123 fever episodes, 79 (64%) met criteria for 86 total infections (lower respiratory tract, N=43; pneumonia, N=27; gastroenteritis, N=9; urinary tract, N=7). Conclusion Data from this study suggest that approximately two-thirds of fever episodes involve infection among women in long-term care facilities. These data may guide provider assessments of fever in older adult women in long-term care facilities.

OBJECTIVES: To examine factors associated with caregiver burden from a multifactorial perspective by examining caregiver and care recipient characteristics and a full range of caregiving tasks. DESIGN: Nationally representative surveys of community-dwelling older adults and their family caregivers residing in the United States. SETTING: 2011 National Health and Aging Trends Study and National Study of Caregiving. PARTICIPANTS: Community-dwelling older adults and their family caregivers. MEASUREMENTS: Caregiver burden, comprising emotional, physical, and financial difficulties associated with caregiving. RESULTS: An estimated 14.9 million caregivers assisted 7.6 million care recipients. More than half of caregivers reported burden related to caregiving. In a multivariable regression model, caregivers who assisted with more activities of daily living and instrumental activities of daily living, health management tasks, and health system logistics were more likely to experience burden, as were female caregivers, adult child caregivers, caregivers in poor health, caregivers with anxiety symptoms, and those using respite care. Dementia was the only care recipient characteristic associated with burden. CONCLUSION: Caregiver characteristics and provision of caregiving tasks determine caregiver burden more than care recipient characteristics. Absence of an association between type of a care recipient's chronic conditions and burden, except for dementia, suggests that the tasks that caregivers who assist older adults with a variety of health conditions undertake shape the experience of caregiving.

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age.

Objective: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time. Design: Longitudinal, dyadic path analysis with the actor-partner interdependence model. Setting: Data were from visit 5 (1992/1993), visit 8 (1995/1996), and visit 11 (1998/1999) of the Cardiovascular Health Study, a multisite, longitudinal, observational study of risk factors for cardiovascular disease in adults 65 years or older. Demographic information was from the 1989/1990 original and 1992/1993 African American cohort baseline visits. Participants: Husbands and wives from 1,028 community-dwelling married couples (N = 2,065). Measurements: Cognitive functioning was measured with the Modified Mini-Mental State Exam. Depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale. Age, education, and disability (activities of daily living and instrumental activities of daily living) were included as covariates. Results: Cross-partner associations (partner effects) revealed that one spouse's greater depressive symptoms predicted the other spouse's lower cognitive functioning, but a spouse's lower cognitive functioning did not predict the other spouse's greater depressive symptoms over time. Within-individual associations (actor effects) revealed that an individual's lower cognitive functioning predicted the individual's greater depressive symptoms over time, but greater depressive symptoms did not predict lower cognitive functioning over time. Effects did not differ for husbands and wives. Conclusion: Having a spouse who is depressed may increase one's risk of cognitive decline as well as one's risk of depression. Interventions for preventing cognitive decline and depression among older adults may be enhanced by considering the marital context.

Suspected urinary tract infection is a common indication for antimicrobial therapy in long-term care residents. We sought to characterize antimicrobial susceptibilities among urine isolates collected from women long-term care residents enrolled in a clinical trial across 21 long-term care facilities in Connecticut, United States of America between August 2012 and October 2015. Among 967 urine cultures collected from 175 women long-term care residents with and without suspected urinary tract infection, we identified 456 bacterial isolates. Escherichia coli (55.3%), Klebsiella (13.8%) and Enterococcus (8.3%) species were the predominant organisms identified. Among all 456 urine isolates, 68.1% were ciprofloxacin-susceptible, 77.2% were trimethoprim/sulfamethoxazole-susceptible, 86.3% were cefazolin-susceptible, and 72.6% were nitrofurantoin-susceptible. Among 252 Escherichia coli urine isolates, 60.2% were ciprofloxacin-susceptible, 73.7% were trimethoprim/ sulfamethoxazole-susceptible, 84.5% were cefazolin-susceptible, and 86.5% were nitrofurantoin-susceptible. These findings suggest that trimethoprim/sulfamethoxazole may be favorable empiric therapy while the urinary isolate is unknown, and nitrofurantoin may be optimal therapy for uncomplicated urinary tract infection due to Escherichia coli in women long-term care residents.

Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial-N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.