Electronic medication monitoring versus self-reported use of inhaled corticosteroids and short-acting beta2-agonists in uncontrolled asthma.

OBJECTIVE: Current standard of care, patient self-report and clinician estimation, overestimates true inhaled corticosteroids (ICS) adherence. We compare self-reported inhaled ICS and short-acting beta 2-agonists (SABA) use with objective data from electronic medication monitors (EMMs). METHODS: Adults with uncontrolled asthma and prescribed ICS and SABA were enrolled. At visit one, participants' ICS and SABA inhalers were fitted with EMMs to track real-time medication usage over 14 days. Participants were asked to complete paper diaries to self-report medication usage over the same period. Participant self-report of ICS adherence and SABA use versus objective ICS adherence and SABA use was compared using Wilcoxon signed-rank tests. RESULTS: One hundred participants (80% female, mean age 48.5 years, 60% completed college, 80% privately insured) had complete data. Participant self-report (median (IQR): 0.8 (0.0, 2.0)) was greater than objectively measured (median (IQR): 0.43 (0.1, 2.1)) SABA use, but the difference was not statistically significant (P = 0.64). Participant self-report (median (IQR): 97 (67, 100)) was significantly greater than objectively measured (median (IQR): 75 (54, 93)) ICS adherence (P = 0.002). CONCLUSIONS: Significant discrepancies between self-report and objective ICS usage were observed. EMM can provide clinicians with accurate data on ICS medication taking behavior, thus reducing medication regimen complexity, side effects, and costs.

Gaseous air pollutants and DNA methylation in a methylome-wide association study of an ethnically and environmentally diverse population of U.S. adults.

Epigenetic mechanisms may underlie air pollution-health outcome associations. We estimated gaseous air pollutant-DNA methylation (DNAm) associations using twelve subpopulations within Women's Health Initiative (WHI) and Atherosclerosis Risk in Communities (ARIC) cohorts (n = 8397; mean age 61.3 years; 83% female; 46% African-American, 46% European-American, 8% Hispanic/Latino). We used geocoded participant address-specific mean ambient carbon monoxide (CO), nitrogen oxides (NO2; NOx), ozone (O3), and sulfur dioxide (SO2) concentrations estimated over the 2-, 7-, 28-, and 365-day periods before collection of blood samples used to generate Illumina 450 k array leukocyte DNAm measurements. We estimated methylome-wide, subpopulation- and race/ethnicity-stratified pollutant-DNAm associations in multi-level, linear mixed-effects models adjusted for sociodemographic, behavioral, meteorological, and technical covariates. We combined stratum-specific estimates in inverse variance-weighted meta-analyses and characterized significant associations (false discovery rate; FDR<0.05) at Cytosine-phosphate-Guanine (CpG) sites without among-strata heterogeneity (PCochran's Q > 0.05). We attempted replication in the Cooperative Health Research in Region of Augsburg (KORA) study and Normative Aging Study (NAS). We observed a -0.3 (95% CI: -0.4, -0.2) unit decrease in percent DNAm per interquartile range (IQR, 7.3 ppb) increase in 28-day mean NO2 concentration at cg01885635 (chromosome 3; regulatory region 290 bp upstream from ZNF621; FDR = 0.03). At intragenic sites cg21849932 (chromosome 20; LIME1; intron 3) and cg05353869 (chromosome 11; KLHL35; exon 2), we observed a -0.3 (95% CI: -0.4, -0.2) unit decrease (FDR = 0.04) and a 1.2 (95% CI: 0.7, 1.7) unit increase (FDR = 0.04), respectively, in percent DNAm per IQR (17.6 ppb) increase in 7-day mean ozone concentration. Results were not fully replicated in KORA and NAS. We identified three CpG sites potentially susceptible to gaseous air pollution-induced DNAm changes near genes relevant for cardiovascular and lung disease. Further harmonized investigations with a range of gaseous pollutants and averaging durations are needed to determine the effect of gaseous air pollutants on DNA methylation and ultimately gene expression.

Assessing asthma control: comparison of electronic-recorded short-acting beta-agonist rescue use and self-reported use utilizing the asthma control test.

Background: Question 4 (Q4) of the Asthma Control Test (ACT) asks patients to report their SABA use over the prior 4 weeks, a criterion for evaluating the impairment domain of asthma control. Biases in recall may lead to a misclassification of asthma control and has implications for asthma control determination and management strategies.Objective: To correlate objective electronic-recorded short-acting beta-agonist (SABA) use with self-reported use via Q4 of the ACT.Methods: Patients ≥18 years of age with a self-reported diagnosis of asthma were enrolled in a digital health electronic medication monitoring (EMM) platform, which recorded the date and time of SABA actuations and prompted the completion of the ACT. The correlations between ACT Q4 responses and EMM-recorded SABA use were evaluated using Spearman's rank correlation coefficients.Results: 1,062 patients (mean age: 35.4 years, mean ACT: 16.3) were included in analyses. Higher Q4 scores, indicating lower SABA use, were moderately and negatively correlated with EMM-recorded SABA use (ρ = -0.59 [95% CI: -0.63, -0.54]). Thirty-five percent of patients underreported SABA use when comparing Q4 to EMM-recorded SABA use.Conclusions: While ACT Q4 and EMM-recorded use were moderately correlated, underreported SABA use on the ACT highlights the need for objective measures of SABA use in asthma control assessments. The use of EMM-recorded SABA data has the potential for clinicians to more accurately determine asthma control, guide changes to controller therapy, and estimate imminent exacerbation risk.

Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study.

BACKGROUND: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease. MATERIALS AND METHODS: We estimated associations between monthly mean concentrations of PM < 10 µm and 2.5-10 µm in diameter (PM10; PM2.5-10) with time-domain measures of heart rate variability (HRV) and QT interval duration (QT) among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities Study (nHRV = 82,107; nQT = 76,711). Then we examined mediation of the PM-HRV and PM-QT associations by DNA methylation (DNAm) at three Cytosine-phosphate-Guanine (CpG) sites (cg19004594, cg24102420, cg12124767) with known sensitivity to monthly mean PM concentrations in a subset of the participants (nHRV = 7,169; nQT = 6,895). After multiply imputing missing PM, electrocardiographic and covariable data, we estimated associations using attrition-weighted, linear, mixed, longitudinal models adjusting for sociodemographic, behavioral, meteorological, and clinical characteristics. We assessed mediation by estimating the proportions of PM-HRV and PM-QT associations mediated by DNAm. RESULTS: We found little evidence of PM-HRV association, PM-QT association, or mediation by DNAm. CONCLUSIONS: The findings suggest that among racially/ethnically and environmentally diverse U.S. populations, sub-chronic exposures to coarser particulates may not exert appreciable, epigenetically mediated effects on cardiac autonomic function or ventricular repolarization. Further investigation in better-powered studies is warranted, with additional focus on shorter duration exposures to finer particulates and non-electrocardiographic outcomes among relatively susceptible populations.

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.

DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation.

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p < 1.6 × 10-3). The replicated methylation sites are heritable (h2 > 30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Posttransfusion purpura occurrence and potential risk factors among the inpatient US elderly, as recorded in large Medicare databases during 2011 through 2012.

BACKGROUND: Posttransfusion purpura (PTP) is a serious transfusion complication resulting in sudden thrombocytopenia with bleeding. The study's objective was to assess PTP occurrence and potential risk factors among the inpatient US elderly, ages 65 and older, during 2011 through 2012. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized large Medicare databases for calendar years 2011 and 2012. Transfusions of blood and blood components were identified by recorded ICD-9-CM procedure codes and revenue center codes, and PTP was ascertained via ICD-9-CM diagnosis code. Our study evaluated PTP rates (per 100,000 inpatient transfusion stays) among elderly Medicare beneficiaries, overall and by age, sex, race, number of units, and blood components transfused. Multivariate regression analyses were used to assess potential risk factors. RESULTS: Among 4,336,338 inpatient transfusion stays for elderly beneficiaries during the study period, 78 had a PTP diagnosis code recorded, an overall rate of 1.8 per 100,000 stays. PTP occurrence varied by the blood components, units transfused, and other characteristics. Significantly higher odds of PTP were found for platelet (PLT)-containing transfusions, with greater number of units transfused, as well as for elderly with histories of cardiac arrhythmias (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.43-4.93), coagulopathy (OR, 1.79; 95% CI, 1.01-3.21), leukemia (OR, 2.37; 95% CI, 1.07-5.26), transplant (OR, 2.68; 95% CI, 1.41-5.09), and other conditions. CONCLUSION: Our population-based study suggests a substantially higher PTP risk with PLT-containing transfusions. The study also suggests increased PTP risk with greater number of units transfused as well as the importance of underlying health conditions and prior recipient alloimmunization for PTP occurrence among the elderly.

Transfusion-related acute lung injury and potential risk factors among the inpatient US elderly as recorded in Medicare claims data, during 2007 through 2011.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication leading to pulmonary edema and respiratory failure. This study's objective was to assess TRALI occurrence and potential risk factors among inpatient US elderly Medicare beneficiaries, ages 65 and older, during 2007 through 2011. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized large Medicare administrative databases. Transfusions were identified by recorded procedure and revenue center codes. TRALI was ascertained via ICD-9-CM diagnosis code. The study evaluated TRALI rates among the inpatient elderly overall and by calendar year, age, sex, race, blood components, and units transfused. Logistic regression analyses were used to assess potential risk factors. RESULTS: Of 11,378,264 inpatient transfusion stays for elderly Medicare beneficiaries, 2556 had a recorded TRALI diagnosis code, an overall rate of 22.46 per 100,000 stays. TRALI rates were higher for platelet (PLT)- and plasma-containing transfusions and increased by year and number of units transfused (p < 0.0001). Significantly higher odds of TRALI were also found for persons ages 65 to 79 years versus more than 79 years (OR, 1.19; 95% confidence interval CI, 1.09-1.29), females versus males (OR, 1.26; 95% CI, 1.16-1.38), white versus nonwhite (OR, 1.43; 95% CI, 1.27-1.66), and with 6-month histories of postinflammatory pulmonary fibrosis (OR, 1.89; 95% CI, 1.52-2.20), tobacco use (OR, 1.16; 95% CI, 1.00-1.26), and other diseases. CONCLUSION: Our study among the elderly suggests TRALI to be a severe event and identifies a substantially increased TRALI occurrence with greater number of units and with PLT- or plasma-containing transfusions. The study also suggests importance of underlying health conditions, prior recipient alloimmunization, and nonimmune mechanism in TRALI development among the elderly.

Epidemiology of Injuries Among National Basketball Association Players: 2013-2014 Through 2018-2019.

BACKGROUND: Understanding the epidemiology of injuries to athletes is essential to informing injury prevention efforts. HYPOTHESIS: The incidence and impact of basketball-related injuries among National Basketball Association (NBA) players from 2013-2014 through 2018-2019 is relatively stable over time. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 3. METHODS: Injuries from 2013-2014 through 2018-2019 were analyzed using the NBA Injury and Illness Database from an electronic medical record system. Descriptive statistics were calculated for injuries by season, game-loss, and onset. Incidence rates were estimated using Poisson models and linear trend tests. RESULTS: Between 552 and 606 players participated in ≥1 game per season during the study. Annual injury incidence ranged from 1550 to 1892, with 33.6% to 38.5% resulting in a missed NBA game. Game-loss injury rates ranged from 5.6 to 7.0 injuries per 10,000 player-minutes from 2014-2015 through 2018-2019 (P = 0.19); the rate was lower in 2013-2014 (5.0 injuries per 10,000 player-minutes), partly due to increased preseason injury rates and transition of reporting processes. The 6-year game-loss injury rate in preseason and regular season games was 6.9 (95% CI 6.0, 8.0) and 6.2 (95% CI 6.0, 6.5) injuries per 10,000 player-minutes; the rate in playoff games was lower (P < 0.01) at 2.8 (95% CI 2.2, 3.6). Most (73%) game-loss injuries had acute onset; 44.4% to 52.5% of these involved contact with another player. CONCLUSION: From 2013-2014 through 2018-2019, over one-third of injuries resulted in missed NBA games, with highest rates of game-loss injuries in preseason games and lowest rates in playoff games. Most game-loss injuries had acute onset, and half of those involved contact with another player. CLINICAL RELEVANCE: These findings - through reliable data reporting by team medical staff in an audited system - can guide evidence-based injury reduction strategies and inform player health priorities.

Radon Exposure and Incident Stroke Risk in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States. METHODS: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics. RESULTS: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L (p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses. DISCUSSION: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

Individual and Neighborhood-level Socioeconomic Status and Somatic Mutations Associated With Increased Risk of Cardiovascular Disease and Mortality: A Cross-Sectional Analysis in the Women's Health Initiative.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of leukemogenic mutations in white blood cells, has been associated with increased risk of atherosclerotic cardiovascular diseases, cancer, and mortality. OBJECTIVE: We examined the relationship between individual- and neighborhood-level socioeconomic status (SES) and CHIP and evaluated effect modification by interpersonal and intrapersonal resources. METHODS: The study population included 10,799 postmenopausal women from the Women's Health Initiative without hematologic malignancy or antineoplastic medication use. Individual- and neighborhood (Census tract)-level SES were assessed across several domains including education, income, and occupation, and a neighborhood-level SES summary z-score, which captures multiple dimensions of SES, was generated. Interpersonal and intrapersonal resources were self-reports. CHIP was ascertained based on a prespecified list of leukemogenic driver mutations. Weighted logistic regression models adjusted for covariates were used to estimate risk of CHIP as an odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The interval-scale neighborhood-level SES summary z-score was associated with a 3% increased risk of CHIP: OR (95% CI) = 1.03 (1.00-1.05), p = .038. Optimism significantly modified that estimate, such that among women with low/medium and high levels of optimism, the corresponding ORs (95% CIs) were 1.03 (1.02-1.04) and 0.95 (0.94-0.96), pInteraction < .001. CONCLUSIONS: Our findings suggest that reduced risk of somatic mutation may represent a biological pathway by which optimism protects contextually advantaged but at-risk women against age-related chronic disease and highlight potential benefits of long-term, positive psychological interventions.

Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. METHODS: We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. RESULTS: The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. DISCUSSION: The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

Retrospective assessment of a collaborative digital asthma program for Medicaid-enrolled children in southwest Detroit: reductions in short-acting beta-agonist (SABA) medication use.

BACKGROUND: Real-world evidence for digitally-supported asthma programs among Medicaid-enrolled children remains limited. Using data from a collaborative quality improvement program, we evaluated the impact of a digital intervention on asthma inhaler use among children in southwest Detroit. METHODS: Children (6-13 years) enrolled with Kids Health Connection (KHC), a program involving home visits with an asthma educator, were invited to participate in a digital self-management asthma program (Propeller Health). Patients were provided with a sensor to capture short-acting beta-agonist (SABA) medication use, and given access to a paired mobile app to track usage. Patients' healthcare providers and caregivers ("followers") were invited to view data as well. Retrospective paired t-tests assessed change in mean SABA use and SABA-free days (SFD) over time, and regressions explored the relationship between followers and medication use. RESULTS: Fifty-one patients were assessed. Mean program participation was nine months, and patients had on average 3 followers. From the first to last participation month, mean SABA use decreased from 0.68 to 0.25 puffs/day (p < 0.001), and mean SFD increased from 25.2 to 28.1 days/month (p < 0.001). 76% of patients had an increase in the number of SFD. There was a positive, but non-significant, relationship between the number of followers and reductions in SABA inhaler use. CONCLUSIONS: We observed a significant reduction in SABA inhaler use and an increase in the number of SABA-free days among Medicaid-enrolled children enrolled in a multi-modal digital asthma program.

Global Burden of Chronic Obstructive Pulmonary Disease Through 2050.

Importance: Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies assessed the global current-day prevalence of COPD, but to better facilitate resource planning and intervention development, long-term projections are needed. Objective: To assess the global burden of COPD through 2050, considering COPD risk factors. Design, Setting, and Participants: In this modeling study, historical data on COPD prevalence was extracted from a recent meta-analysis on 2019 global COPD prevalence, and 2010 to 2018 historical prevalence was estimated using random-effects meta-analytical models. COPD risk factor data were obtained from the Global Burden of Disease database. Main Outcomes and Measures: To project global COPD prevalence to 2050, generalized additive models were developed, including smoking prevalence, indoor and outdoor air pollution, and development indices as predictors, and stratified by age, sex, and World Bank region. Results: The models estimated that the number of COPD cases globally among those aged 25 years and older will increase by 23% from 2020 to 2050, approaching 600 million patients with COPD globally by 2050. Growth in the burden of COPD was projected to be the largest among women and in low- and middle-income regions. The number of female cases was projected to increase by 47.1% (vs a 9.4% increase for males), and the number of cases in low- and middle-income regions was expected to be more than double that of high-income regions by 2050. Conclusions and Relevance: In this modeling study of future COPD burden, projections indicated that COPD would continue to affect hundreds of millions of people globally, with disproportionate growth among females and in low-middle income regions through 2050. Further research, prevention, and advocacy are needed to address these issues so that adequate preparation and resource allocation can take place.

Perceptions of Environmental Influence and Environmental Information-Seeking Behavior Among People With Asthma and COPD.

Environmental exposures and socioeconomic status (SES) are associated with asthma and chronic obstructive pulmonary disease (COPD) morbidity and mortality. Despite efforts to reduce the impact of environmental exposures through regulation and education, knowledge gaps remain. We sought to understand how adults with asthma and COPD perceive and seek information about environmental factors, and how these responses varied by disease or socioeconomic characteristics. Participants with self-reported asthma or COPD enrolled in a digital platform for respiratory disease self-management, consisting of sensors to track medication use and a companion smartphone app, completed an electronic survey exploring perceptions of environmental factors. Using mixed-method analyses, we evaluated differences in responses by disease (asthma vs. COPD), education (≤ vs. > some college), annual household income (< vs. ≥ $50,000), and mean annual residential air pollutant exposure (> vs. ≤80th percentile). Survey responses from 698 participants [500 asthma (72%) and 198 COPD (28%)] were analyzed. A high percentage of participants perceived that environmental factors could influence their symptoms, including: pollen (93% for asthma vs. 86% for COPD), mold (89 vs. 85%), second-hand smoke (89 vs. 83%), and air pollution (84% for both). Participants reported seeking environmental information daily from an average of three sources, preferring mobile apps and television (TV) programs. Significant differences were identified by disease. Conclusion: Participants with asthma and COPD perceive a relationship between their respiratory symptoms and their environment and regularly seek out environmental information. This information can help inform digital health development for respiratory education and self-management.

Identifying impacts of air pollution on subacute asthma symptoms using digital medication sensors.

BACKGROUND: Objective tracking of asthma medication use and exposure in real-time and space has not been feasible previously. Exposure assessments have typically been tied to residential locations, which ignore exposure within patterns of daily activities. METHODS: We investigated the associations of exposure to multiple air pollutants, derived from nearest air quality monitors, with space-time asthma rescue inhaler use captured by digital sensors, in Jefferson County, Kentucky. A generalized linear mixed model, capable of accounting for repeated measures, over-dispersion and excessive zeros, was used in our analysis. A secondary analysis was done through the random forest machine learning technique. RESULTS: The 1039 participants enrolled were 63.4% female, 77.3% adult (>18) and 46.8% White. Digital sensors monitored the time and location of over 286 980 asthma rescue medication uses and associated air pollution exposures over 193 697 patient-days, creating a rich spatiotemporal dataset of over 10 905 240 data elements. In the generalized linear mixed model, an interquartile range (IQR) increase in pollutant exposure was associated with a mean rescue medication use increase per person per day of 0.201 [95% confidence interval (CI): 0.189-0.214], 0.153 (95% CI: 0.136-0.171), 0.131 (95% CI: 0.115-0.147) and 0.113 (95% CI: 0.097-0.129), for sulphur dioxide (SO2), nitrogen dioxide (NO2), fine particulate matter (PM2.5) and ozone (O3), respectively. Similar effect sizes were identified with the random forest model. Time-lagged exposure effects of 0-3 days were observed. CONCLUSIONS: Daily exposure to multiple pollutants was associated with increases in daily asthma rescue medication use for same day and lagged exposures up to 3 days. Associations were consistent when evaluated with the random forest modelling approach.

Concurrent Improvement Observed in Patient-Reported Burden and Sensor-Collected Medication Use Among Patients Enrolled in a COPD Digital Health Program.

Background: The COPD assessment test (CAT) is an 8-item questionnaire widely used in clinical practice to assess patient burden of disease. Digital health platforms that leverage electronic medication monitors (EMMs) are used to track the time and date of maintenance and short-acting beta-agonist (SABA) inhaler medication use and record patient-reported outcomes. The study examined changes in CAT and SABA inhaler use in COPD to determine whether passively collected SABA and CAT scores changed in a parallel manner. Methods: Patients with self-reported COPD enrolled in a digital health program, which provided EMMs to track SABA and maintenance inhaler use, and a companion smartphone application ("app") to provide medication feedback and reminders. Patients completing the CAT questionnaire in the app at enrollment and at 6 months were included in the analysis. Changes in CAT burden category [by the minimally important difference (MID)] and changes in EMM-recorded mean SABA inhaler use per day were quantified at baseline and 6 months. Results: The analysis included 611 patients. At 6 months, mean CAT improved by -0.9 (95% CI: -1.4, -0.4; p < 0.001) points, and mean SABA use decreased by -0.6 (-0.8, -0.4; p < 0.001) puffs/day. Among patients with higher burden (CAT ≥ 21) at enrollment, CAT improved by -2.0 (-2.6, -1.4; p < 0.001) points, and SABA use decreased by -0.8 (-1.1, -0.6; p < 0.001) puffs/day. Conclusion: Significant and parallel improvement in CAT scores and SABA use at 6 months were noted among patients enrolled in a digital health program, with greater improvement for patients with higher disease burden.

The relationship between objective app engagement and medication adherence in asthma and COPD: a retrospective analysis.

Digital health tools can promote disease self-management, but the association of smartphone app engagement and medication adherence is unclear. We assessed the relationship between objective smartphone app engagement and controller medication use in adults with asthma and COPD. We retrospectively analyzed data from participants enrolled in a digital self-management platform for asthma and COPD. Eligible adults had a smartphone and a paired electronic medication monitor (EMM). Longitudinal, mixed-effects logistic regressions estimated the relationship between daily app engagement (app opens, session duration) and daily controller medication use. Data from 2309 participants (71% asthma; 29% COPD) was analyzed. Opening the app (vs. not opening the app) was associated with significantly greater odds (OR (95% CI)) of using controller medications in asthma (2.08 (1.98, 2.19)) and COPD (1.61 (1.49, 1.75). Longer session duration was also associated with greater odds of using controller medications in asthma and COPD, but the odds of use attenuated with longer session duration in COPD. This study presents a novel assessment of the relationship between objectively-measured smartphone app engagement and controller medication use in asthma and COPD. Such insights may help develop targeted digital health tools and interventions.

The Impact of Patient Self-Monitoring Via Electronic Medication Monitor and Mobile App Plus Remote Clinician Feedback on Adherence to Inhaled Corticosteroids: A Randomized Controlled Trial.

BACKGROUND: Poor adherence to inhaled corticosteroids (ICSs) and overuse of short-acting beta2-agonists (SABAs) are associated with increased asthma morbidity. OBJECTIVE: To assess whether patient self-monitoring via electronic medication monitoring and smartphone application plus remote clinician feedback influences ICS and SABA use. METHODS: Adults with uncontrolled asthma and prescribed ICS and SABA were enrolled in this 14-week study. Inhalers were fitted with electronic medication monitoring to track real-time usage. After a 14-day baseline, participants were randomly assigned to the treatment group where they received reminders and feedback on ICS and SABA use via a smartphone application and clinician phone calls, or control group without feedback. Linear mixed models compared the baseline percentage of SABA-free days and ICS adherence to the last 14 study days. RESULTS: Participants (n = 100) had a mean age of 48.5 years, 80% were female, 68% white, and 80% privately insured. The percentage of SABA-free days increased significantly in the treatment group (19%; 95% CI, 12 to 26; P < .01) and nonsignificantly in the control group (6%, 95% CI, -3 to 16; P = .18), representing a 13% (95% CI, 1-26; P = .04) difference. ICS adherence changed minimally in the treatment group (-2%; 95% CI, -7 to 3; P = .40), but decreased significantly (-17%; 95% CI, -26 to -8; P < .01) in the control group, representing a 15% (95% CI, 4 to 25; P < .01) difference. CONCLUSIONS: Patient self-monitoring via a digital platform plus remote clinician feedback maintained high baseline ICS adherence and decreased SABA use.

Pilot Study of a Patient Experience with an ELLIPTA Inhaler Electronic Medication Monitor and Associated Integrated System: A Prospective Observational Study Using the COPD Patient-Powered Research Network.

BACKGROUND: Electronic medication monitors (EMMs) are associated with decreased rescue inhaler use, symptom burden, and increased medication adherence in asthma. However, the use of EMMs in people with chronic obstructive pulmonary disease (COPD) using the ELLIPTA dry powder inhaler has not been studied. METHODS: This was an open-label, single-arm, prospective observational study of EMMs and associated application (app) use over 12 weeks and up to 24 weeks (April-October 2019) in people with self-reported COPD aged ≥40 years enrolled in the COPD Patient-Powered Research Network, using an ELLIPTA inhaler. The primary outcome was daily active use of the app over 12 weeks. Treatment adherence, rescue inhaler use, and participant satisfaction were assessed over the same period. RESULTS: Among the 122 participants, mean (standard deviation [SD]) proportion of days participants opened the app was 59.5% (31.4), 51.1% (33.5) and 41.3% (34.2) for Days 1-30, 31-60 and 61-90, respectively. Mean (SD) adherence to maintenance medication remained stable: 80.2% (22.7) and 79.9% (26.7) for Days 1-30 and 61-90, respectively. In participants using a rescue inhaler and EMM, mean (SD) rescue-free days increased from 18.5 (10.0; Days 1-30, n=51) to 21.4 (9.6; Days 61-90, n=48). Participants reported high levels of confidence in using the EMM, valued app reminders highly and reported high system satisfaction (mean [SD] scale: 1=low, 5=high; 4.6 [1.1], 4.3 [1.1] and 4.1 [1.1], respectively). CONCLUSIONS: Use of an ELLIPTA EMM with frequent app engagement, high participant satisfaction and decreased rescue medication use may aid COPD management.