Loneliness and its predictors among older adults prior to and during the COVID-19 pandemic: Cross-sectional and longitudinal survey findings from participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort in the USA

Objectives We aimed to ascertain the prevalence of perceived loneliness among older adults following the onset of the COVID-19 pandemic and to examine factors contributing to the perception of loneliness. Design Cross-sectional and longitudinal data from the Atherosclerosis Risk in Communities (ARIC) Study cohort. Setting The ARIC Study cohort, a prospective cohort that recruited (1987-1989) participants from four distinct communities in the USA. Participants 2984 ARIC cohort members. Primary and secondary outcomes Perceived loneliness assessed using the University of California at Los Angeles (UCLA) UCLA three-item Loneliness Scale telephone interviews conducted May-October 2020 and prior to March 2020. Results Of the total 5037 participants alive in 2020, 2984 (56.2%) responded to the UCLA three-item questionnaire (mean age 82.6 (SD 4.6) years, 586 (19.6%) black participants, 1081 (36.2%) men), of which 66 (2.2%) reported having had a COVID-19 infection during the observation period. The proportion of participants reporting feeling lonely was 56.3% (n=1680). Among participants with repeat measures of loneliness (n=516), 35.2% (n=182) reported feeling more lonely following pandemic onset. Self-rated health and emotional resilience were strongly associated with self-perceived loneliness. The burden of COVID-19 infections, concern about the pandemic and decreased self-reported physical activity were greater among black as compared with white participants and among those with an educational attainment of less than high school as compared with high school or more. Conclusion Findings from this study document the increase in perceived loneliness among older adults during the COVID-19 pandemic in the USA

Mapping alveolar oxygen partial pressure in COPD using hyperpolarized helium-3: the multi-ethnic study of atherosclerosis (MESA) COPD study

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) 3He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP 3He MRI measuring pAO2, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm2/s) correlated with emphysema and heterogeneity in pAO2 measurements. Strong correlations were found between the heterogeneity of global pAO2 as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic pAO2 values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between pAO2 SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas pAO2 heterogeneity and the fraction of non-physiological pAO2 results increase in mild to moderate COPD. Measurements of pAO2 are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation

Marijuana use associations with pulmonary symptoms and function in Tobacco smokers enrolled in the Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS)

Background: Marijuana is often smoked via a filterless cigarette and contains similar chemical makeup as smoked tobacco. There are few publications describing usage patterns and respiratory risks in older adults or in those with chronic obstructive pulmonary disease (COPD). Methods: A cross-sectional analysis of current and former tobacco smokers from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) study assessed associations between marijuana use and pulmonary outcomes. Marijuana use was defined as never, former (use over 30 days ago), or current (use within 30 days). Respiratory health was assessed using quantitative high-resolution computed tomography (HRCT) scans, pulmonary function tests and questionnaire responses about respiratory symptoms. Results: Of the total 2304 participants, 1130 (49%) never, 982 (43%) former, and 192 (8%) current marijuana users were included. Neither current nor former marijuana use was associated with increased odds of wheeze (odds ratio [OR] 0.87, OR 0.97), cough (OR 1.22; OR 0.93) or chronic bronchitis (OR 0.87; OR 1.00) when compared to never users. Current and former marijuana users had lower quantitative emphysema (P=0.004, P=0.03), higher percent predicted forced expiratory volume in 1 second (FEV1%) (P < 0.001, P < 0.001), and percent predicted forced vital capacity (FVC%) (p < 0.001, P < 0.001). Current marijuana users exhibited higher total tissue volume (P=0.003) while former users had higher air trapping (P < 0.001) when compared to never marijuana users. Conclusions: Marijuana use was found to have little to no association with poor pulmonary health in older current and former tobacco smokers after adjusting for covariates. Higher forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was observed among current marijuana users. However, higher joint years was associated with more chronic bronchitis symptoms (e.g., wheeze), and this study cannot determine if long-term heavy marijuana smoking in the absence of tobacco smoking is associated with lung symptoms, airflow obstruction, or emphysema, particularly in those who have never smoked tobacco cigarettes

Association of Nonobstructive Chronic Bronchitis with Respiratory Health Outcomes in Adults

Importance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain. Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers. Design, Setting, and Participants: This prospective cohort study included 22325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of &lt;0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018. Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years. Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis. Results: Among 22325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11082 ever smokers with 99869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11243 never smokers with 120004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes. Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies

Albuminuria, lung function decline, and risk of incident chronic obstructive pulmonary disease the NHLBI pooled cohorts study

Rationale: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD. Objectives: To test whether albuminuria was associated with lung function decline and incident CLRDs. Methods: Six U.S. population–based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications. Measurements and Main Results: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV 1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV 1 decline (95% confidence interval [CI], 0.86–4.76%; P = 0.0047), 11.02% greater FEV 1 /FVC decline (95% CI, 4.43–17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2–31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18–34%, P, 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease. Conclusions: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population–based sample

Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study

Background: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease. Methods: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV1 decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV1 decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption. Findings: 25 352 participants (ages 17–93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3–20), FEV1 decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66–31·37) in sustained never-smokers, 34·97 mL per year (34·36–35·57) in former smokers, and 39·92 mL per year (38·92–40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV1 decline of 1·82 mL per year (95% CI 1·24–2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35–10·08). Compared to never-smokers, accelerated FEV1 decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (&lt;10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV1 decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21–9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86–12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00–2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results. Interpretation: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage. Funding: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency

Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study

Aims: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). Methods and results: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking. Conclusion: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors

Harmonization of Respiratory Data from 9 US Population-Based Cohorts

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRDrelated or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD

Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

Background Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. Methods In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40–80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1–4) on the basis of post-bronchodilator FEV1. Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. Findings 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations. Interpretation Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations. Funding National Institutes of Health, and National Heart, Lung, and Blood Institute

Rural residence and chronic obstructive pulmonary disease exacerbations: Analysis of the SPIROMICS cohort

Rationale: Rural residence is associated with poor outcomes in several chronic diseases. The association between rural residence and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. Objectives: In this work, we sought to determine the independent association between rural residence and COPD-related outcomes, including COPD exacerbations, airflow obstruction, and symptom burden. Methods: A total of 1,684 SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) participants with forced expiratory volume in 1 second/forced vital capacity <, 0.70 had geocoding-defined rural-urban residence status determined (N = 204 rural and N = 1,480 urban). Univariate and multivariate logistic and negative binomial regressions were performed to assess the independent association between rurality and COPD outcomes, including exacerbations, lung function, and symptom burden. The primary exposure of interest was rural residence, determined by geocoding of the home address to the block level at the time of study enrollment. Additional covariates of interest included demographic and clinical characteristics, occupation, and occupational exposures. The primary outcome measures were exacerbations determined over a 1-year course after enrollment by quarterly telephone calls and at an annual research clinic visit. The odds ratio (OR) and incidence rate ratio (IRR) of exacerbations that required treatment with medications, including steroids or antibiotics (total exacerbations), and exacerbations leading to hospitalization (severe exacerbations) were determined after adjusting for relevant covariates. Results: Rural residence was independently associated with a 70% increase in the odds of total exacerbations (OR, 1.70 [95% confidence interval (CI), 1.13-2.56]; P = 0.012) and a 46% higher incidence rate of total exacerbations (IRR 1.46 [95% CI, 1.02-2.10]; P = 0.039). There was no association between rural residence and severe exacerbations. Agricultural occupation was independently associated with increased odds and incidence of total and severe exacerbations. Inclusion of agricultural occupation in the analysis attenuated the association between rural residence and the odds and incidence rate of total exacerbations (OR, 1.52 [95% CI, 1.00-2.32]; P = 0.05 and IRR 1.39 [95% CI, 0.97-1.99]; P = 0.07). There was no difference in symptoms or airflow obstruction between rural and urban participants. Conclusions: Rural residence is independently associated with increased odds and incidence of total, but not severe, COPD exacerbations. These associations are not fully explained by agriculture-related exposures, highlighting the need for future research into potential mechanisms of the increased risk of COPD exacerbations in the rural population