Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials of Pharmacotherapy.

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.

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in Aging Populations.

Current epidemiologic practice evaluates COPD based on self-reported symptoms of chronic bronchitis, self-reported physician-diagnosed COPD, spirometry confirmed airflow obstruction, or emphysema diagnosed by volumetric computed chest tomography (CT). Because the highest risk population for having COPD includes a predominance of middle-aged or older persons, aging related changes must also be considered, including: 1) increased multimorbidity, polypharmacy, and severe deconditioning, as these identify mechanisms that underlie respiratory symptoms and can impart a complex differential diagnosis; 2) increased airflow limitation, as this impacts the interpretation of spirometry confirmed airflow obstruction; and 3) "senile" emphysema, as this impacts the specificity of CT-diagnosed emphysema. Accordingly, in an era of rapidly aging populations worldwide, the use of epidemiologic criteria that do not rigorously consider aging related changes will result in increased misidentification of COPD and may, in turn, misinform public health policy and patient care.

Insomnia in Community-Living Persons with Advanced Age.

OBJECTIVE: To evaluate the epidemiology of insomnia, including demographic and clinical correlates, in older adults. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: Yale Precipitating Events Project participants (N=379; mean age 84.3; 67.8% female; 11.9% African American). MEASUREMENTS: Insomnia Severity Index (ISI), with scores of 8 and higher indicating insomnia, which was further stratified according to ISI score as mild (8-14), moderate (15-21), or severe (22-28). Baseline characteristics included age, sex, race, education, smoking, obesity, medical conditions, depressive symptoms (Center for Epidemiologic Studies Depression score ≥16), cognitive impairment (Mini-Mental State Examination score <24), restless legs syndrome (RLS), self-reported sleep-disordered breathing (SDB), medications, and daytime sleepiness (Epworth Sleepiness Scale (ESS), range 0-24). RESULTS: Insomnia was established in 163 (43.0%) participants (average ISI score 12.3 (mild)). For the entire sample, average baseline characteristics were as follows: 30.1% did not complete high school, 5% were current smokers, 19.2% were obese, 28.2% had cardiovascular disease, 19.3% had chronic lung disease, 27.2% had depressive symptoms, 16.1% had cognitive impairment, 36.8% had RLS, and 3.4% had self-reported SDB; mean number of medications was 9.2, and mean ESS was 6.4. In multivariable regression models, only depressive symptoms (adjusted odds ratio (aOR)=8.34, 95% confidence interval (CI)=4.49, 15.47) and RLS (aOR=2.49, 95% CI=1.48, 4.21) were significantly associated with insomnia. CONCLUSION: In a sample of older adults with high medical burden and polypharmacy, insomnia was highly prevalent but unexpectedly mild and associated only with depressive symptoms and RLS. The discordance of high prevalence but mild severity of insomnia in the oldest adults highlights the need for diagnostic confirmation with objective measures of sleep disturbances, whereas the strong associations with depressive symptoms and RLS inform priorities in managing insomnia.

Dopamine-Related Genotypes and Physical Activity Change During an Intervention: The Lifestyle Interventions and Independence for Elders Study.

OBJECTIVES: To determine whether intervention-induced physical activity (PA) changes in sedentary older adults differed according to dopamine-related genotype. DESIGN: Randomized clinical trial (Lifestyle Interventions and Independence for Elders Trial (2010-13)). SETTING: Multicenter study, 8 U.S. PARTICIPANTS: Volunteer sample of sedentary adults aged 70 to 89 at risk of disability (N=1635). INTERVENTIONS: Structured PA versus health education (HE) for an average of 2.6 years. MEASUREMENTS: Single-nucleotide polymorphisms of dopamine-related genes (dopamine receptor (DR) D1, DRD2, DRD3, and catechol-O-methyltransferase (COMT)) were assessed. Average moderate to vigorous PA (MVPA) was calculated using accelerometry (min/d) at baseline and 6, 12, and 24 months. Between-arm MVPA differences according to genotype and genotype with square root-transformed MVPA separately according to arm were tested, stratified according to race, and adjusted for multiple comparisons. RESULTS: White participants in the PA arm (n=513) had higher average square root transformed MVPA (4.91±1.91)than those in the HE arm (n=538) (4.51±1.82) (p=.001). Between-arm differences were greater for DRD2 Met/Met (high dopamine; HE: 4.76±1.80, PA: 5.53±1.60, p=.03) than Val/Val (low dopamine; HE: 4.58±1.92, PA: 4.81±1.83, p=.16); results were similar for COMT. In the PA arm, DRD2 Met/Met was associated with higher average MVPA (5.39±2.00) than Met/Val (4.46±2.51) (p=.01) and Val/Val (4.65±2.71) (p=.01). There were no associations for other genes. Associations were not significant in blacks but followed similar trends. CONCLUSION: Higher dopamine signaling may support changes in PA during an intervention. The role of dopamine-related pathways in promoting PA participation and enhancing response to interventions in sedentary older adults should be studied. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01072500.

Staging the severity of chronic obstructive pulmonary disease in older persons based on spirometric Z-scores.

OBJECTIVES: Among older persons, the use of spirometric Z-scores as calculated by the Lambda-Mu-Sigma (LMS) method has a strong scientific rationale for establishing a diagnosis of chronic obstructive pulmonary disease (COPD), but its clinical validity in staging COPD severity is not yet known. The current study has therefore evaluated the association between LMS-staged COPD and health outcomes, in two separate cohorts of older persons. DESIGN: Longitudinal cohort study. SETTING: The Cardiovascular Health Study (CHS, N = 3,248) and the Third National Health and Nutrition Examination Survey (NHANES-III, N = 1,354). PARTICIPANTS: Community-living white participants aged 65 to 80. MEASUREMENTS: Using spirometric data, COPD was staged as mild, moderate, or severe based on LMS-derived Z-scores. Clinical validity was then evaluated according to all-cause mortality, respiratory symptoms (chronic bronchitis, dyspnea, or wheezing), and moderate to severe dyspnea (available in CHS only). RESULTS: In CHS, the LMS staging of COPD as mild, moderate, and severe was associated with mortality (adjusted HR (aHR) = 1.50, 95% confidence interval (CI) = 1.15-1.94; aHR = 1.31, 95% CI = 1.03-1.67; and aHR = 2.00, 95% CI = 1.70-2.36, respectively) and with respiratory symptoms (adjusted OR (aOR)  = 1.69, 95% CI = 1.12-2.56; aOR = 1.87, 95% CI = 1.28-2.73; and aOR = 3.99, 95% CI = 2.91-5.48, respectively). Also in CHS, moderate and severe, but not mild, LMS-staged COPD was associated with moderate to severe dyspnea (aOR = 2.16, 95% CI = 1.24-3.75; aOR = 3.98, 95% CI = 2.77-5.74; and aOR = 0.84, 95% CI = 0.35-2.01, respectively). Similar associations were found for mortality and respiratory symptoms in NHANES-III, except mild severity was not associated with mortality (aHR = 0.93, 95% CI = 0.62-1.40). CONCLUSION: In white older persons, the spirometric staging of COPD severity based on LMS-derived Z-scores was associated with several clinically relevant health outcomes. These results support the use of the LMS method for staging the severity of COPD in older populations.

Peak expiratory flow as a predictor of subsequent disability and death in community-living older persons.

OBJECTIVES: To determine whether peak expiratory flow (PEF), when expressed by a validated method using standardized residual (SR) percentile, is associated with subsequent disability and death in older persons. DESIGN: Prospective cohort study. SETTING: New Haven, Connecticut. PARTICIPANTS: Seven hundred fifty-four initially nondisabled, community-living persons aged 70 and older. MEASUREMENTS: PEF was assessed at baseline along with chronic conditions and smoking history. The onset of persistent disability in activities of daily living (ADLs), continuous mobility disability, and death were ascertained during monthly interviews over a 5-year period. RESULTS: Participants' mean age was 78.4, 63.7% had a smoking history, and 17.4% reported chronic lung disease. The incidence rates per 100 person-months were 1.00 (95% confidence interval (CI)=0.90-1.12) for ADL disability, 0.80 (95% CI=0.70-0.93) for mobility disability, and 0.44 (95% CI=0.38-0.51) for death. At a PEF less than 10(th) SR percentile, identifying nearly one-quarter of the cohort, hazard ratios (HRs) adjusted for multiple confounders, including age, smoking, and chronic lung disease, demonstrated a greater risk of ADL disability (HR=1.79, 95% CI=1.23-2.62), mobility disability (HR=1.89, 95% CI=1.15-3.10), and death (HR=2.31, 95% CI=1.29-4.12). CONCLUSION: In an elderly cohort, it was found that low PEF, when expressed as an SR percentile, is independently associated with subsequent disability and death. These results support the use of PEF as a potentially valuable risk assessment tool in community-living older persons.