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Rationale: Survivors of critical illness have multiple symptoms, but how restricting symptoms change after critical illness and whether these changes differ among vulnerable subgroups is unknown. Objectives: To evaluate changes in restricting symptoms over the six months after critical illness among older adults and to determine whether these changes differ by sex, multimorbidity, and individual- and neighborhood-level socioeconomic disadvantage. Methods: From a prospective longitudinal study of 754 community-living adults ⩾70 years old interviewed monthly (1998-2018), we identified 233 admissions from 193 participants to the ICU. The occurrence of 15 restricting symptoms, defined as those leading to restricted activity, were ascertained during interviews in the month before ICU admission (baseline) and each of the six months after hospital discharge. Measurements and Main Results: The occurrence and number of restricting symptoms increased more than threefold in the six months after a critical illness hospitalization (adjusted rate ratio [95% confidence interval], 3.1 [2.1-4.6] and 3.3 [2.1-5.3], respectively), relative to baseline. These increases were largest in the first month after hospitalization (adjusted rate ratio [95% confidence interval], 5.3 [3.8-7.3] and 5.4 [3.9-7.5], respectively] before declining and becoming nonsignificant in the third month. Increases in restricting symptoms did not differ significantly by sex, multimorbidity, or individual- or neighborhood-level socioeconomic disadvantage. Conclusions: Restricting symptoms increase substantially after a critical illness before returning to baseline three months after hospital discharge. Our findings highlight the need to incorporate symptom management into post-ICU care and for further investigation into whether addressing restricting symptoms can improve quality of life and functional recovery among older ICU survivors.

Rationale: The prevalence of frailty (diminished physiologic reserve) and its effect on outcomes for those aged 18 years and older with critical illness is unclear., Objectives: We hypothesized greater frailty would be associated with subsequent mortality, disability, and cognitive impairment, regardless of age., Methods: At enrollment, we measured frailty using the Clinical Frailty Scale (range, 1 [very fit] to 7 [severely frail]). At 3 and 12 months post-discharge, we assessed vital status, instrumental activities of daily living, basic activities of daily living, and cognition. We used multivariable regression to analyze associations between Clinical Frailty Scale scores and outcomes, adjusting for age, sex, education, comorbidities, baseline disability, baseline cognition, severity of illness, delirium, coma, sepsis, mechanical ventilation, and sedatives/opiates., Measurements and Main Results: We enrolled 1,040 patients who were a median (interquartile range) of 62 (53-72) years old and who had a median Clinical Frailty Scale score of 3 (3-5). Half of those with clinical frailty (i.e., Clinical Frailty Scale score ≥5) were younger than 65 years old. Greater Clinical Frailty Scale scores were independently associated with greater mortality (P = 0.01 at 3 mo and P < 0.001 at 12 mo) and with greater odds of disability in instrumental activities of daily living (P = 0.04 at 3 mo and P = 0.002 at 12 mo). Clinical Frailty Scale scores were not associated with disability in basic activities of daily living or with cognition., Conclusions: Frailty is common in critically ill adults aged 18 years and older and is independently associated with increased mortality and greater disability. Future studies should explore routine screening for clinical frailty in critically ill patients of all ages. Interventions to reduce mortality and disability among patients with heightened vulnerability should be developed and tested. Clinical trial registered with www.clinicaltrials.gov (NCT 00392795 and NCT 00400062).

Rationale: Most of the 1.4 million older adults who survive the intensive care unit (ICU) annually in the United States face increased disability, but little is known about those who achieve functional recovery., Objectives: Our objectives were twofold: to evaluate the incidence and time to recovery of premorbid function within 6 months of a critical illness and to identify independent predictors of functional recovery among older ICU survivors., Methods: Potential participants included 754 persons aged 70 years or older who were evaluated monthly in 13 functional activities (1998-2012). The analytic sample included 218 ICU admissions from 186 ICU survivors. Functional recovery was defined as returning to a disability count less than or equal to the pre-ICU disability count within 6 months. Twenty-one potential predictors were evaluated for their associations with recovery., Measurements and Main Results: Functional recovery was observed for 114 (52.3%) of the 218 admissions. In multivariable analysis, higher body mass index (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.12) and greater functional self-efficacy (HR, 1.05; 95% CI, 1.02-1.08), a measure of confidence in performing various activities, were associated with recovery, whereas pre-ICU impairment in hearing (HR, 0.38; 95% CI, 0.22-0.66) and vision (HR, 0.59; 95% CI, 0.37-0.95) were associated with a lack of recovery., Conclusions: Among older adults who survived an ICU admission with increased disability, pre-ICU hearing and vision impairment were strongly associated with poor functional recovery within 6 months, whereas higher body mass index and functional self-efficacy were associated with recovery. Future research is needed to evaluate whether interventions targeting these factors improve functional outcomes among older ICU survivors.

Rationale: The Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated., Objectives: To evaluate respiratory-related phenotypes in GLI-defined spirometric impairment., Methods: In COPDGene (N = 10,131 patients; age range, 45-81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, ≥2), poor respiratory health-related quality of life (St. George's Respiratory Questionnaire total score, ≥25), poor exercise performance (6-minute-walk distance, <391 m), bronchodilator reversibility (FEV1 change, >12% and ≥200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively)., Measurements and Main Results: GLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea-1.31 (1.10-1.56), 2.20 (1.81-2.68), and 10.73 (8.04-14.33); poor respiratory health-related quality of life-1.49 (1.28-1.75), 2.69 (2.08-3.47), and 14.61 (10.09-21.17); poor exercise performance-1.11 (0.94-1.31), 1.58 (1.33-1.88), and 4.58 (3.42-6.12); bronchodilator reversibility-2.76 (2.24-3.40), 5.18 (4.29-6.27), and 6.21 (5.06-7.62); emphysema-4.86 (3.16-7.47), 6.41 (4.09-10.05), and 17.79 (10.79-29.32); and gas trapping-3.92 (3.12-4.93), 5.20 (3.82-7.07), and 16.28 (9.71-27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60-1.32]) or gas trapping (1.15 [0.92-1.42])., Conclusions: GLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.

Rationale: In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD])., Objectives: To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories., Methods: Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm)., Measurements and Main Results: Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories., Conclusions: GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the normal range for multiple phenotypes. These results suggest that among adults with GLI-defined normal spirometry, GOLD may misclassify normal phenotypes as having respiratory impairment.

Rationale: The lambda-mu-sigma (LMS) method is a novel approach that defines the lower limit of normal (LLN) for the ratio of FEV1/FVC as the fifth percentile of the distribution of Z scores. The clinical validity of this threshold as a basis for establishing chronic obstructive pulmonary disease is unknown., Objective: To evaluate the association between the LMS method of determining the LLN for the FEV1/FVC, set at successively higher thresholds, and clinically meaningful outcomes., Methods: Using data from a nationally representative sample of 3,502 white Americans aged 40-80 years, we stratified the FEV1/FVC according to the LMS-LLN, with thresholds set at the 5th, 10th, 15th, 20th, and 25th percentiles (i.e., LMS-LLN5, LMS-LLN10, etc.). We then evaluated whether these thresholds were associated with an increased risk of death or prevalence of respiratory symptoms. Spirometry was not specifically completed after a bronchodilator., Measurements and Main Results: Relative to an FEV1/FVC greater than or equal to LMS-LLN25 (reference group), the risk of death and the odds of having respiratory symptoms were elevated only in participants who had an FEV1/FVC less than LMS-LLN(5), with an adjusted hazard ratio of 1.68 (95% confidence interval, 1.34-2.12) and an adjusted odds ratio of 2.46 (95% confidence interval, 2.01-3.02), respectively, representing 13.8% of the cohort. Results were similar for persons aged 40-64 years and those aged 65-80 years., Conclusions: In white persons aged 40-80 years, an FEV1/FVC less than LMS-LLN5 identifies persons with an increased risk of death and prevalence of respiratory symptoms. These results support the use of the LMS-LLN5 threshold for establishing chronic obstructive pulmonary disease.