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.

Geospatial-temporal analysis of the impact of ozone on asthma rescue inhaler use.

RATIONALE: Asthma is one of the most common chronic respiratory diseases in the United States. Several outdoor air pollutants have been associated with asthma morbidity. Previous studies of the effects of short-term air pollution exposure have been limited by potential exposure misclassification and limited spatial and temporal resolution of asthma outcome measures. OBJECTIVES: We aimed to assess the association of short-term air pollutant exposure with the use of short-acting beta-2 agonists (SABA) for asthma by monitoring the time and place of occurrence with electronic medication monitors. METHODS: In a cohort of adults and children with asthma (n = 287; 60% female), we deployed electronic medication monitors fitted to metered-dose inhalers to monitor SABA use, capturing the date, time and location of use. We assigned pollutant exposures based on each actuation's time and location (4-h mean measures for ozone and particulate matter of 2.5 µm or smaller (PM2.5)), assessed associations using generalized linear models and explored age-specific effects. MEASUREMENTS AND MAIN RESULTS: Ambient ozone exposure was positively associated with SABA use (p = 0.01). Age-specific associations were identified (interaction p = 0.01), with a larger increase in SABA use for children (11.3%; 95% CI: 7.0%-18.2%) than adults (8.4%; 95% CI: 6.4%-11.0%) per IQR increase of ozone (16.8 ppb). CONCLUSIONS: These findings support existing evidence that short-term exposure to ozone can cause morbidity in individuals with asthma, and suggest that ozone exposures below the current U.S. EPA standard may be associated with increased SABA use.

Passive Monitoring of Short-Acting Beta-Agonist Use via Digital Platform in Patients With Chronic Obstructive Pulmonary Disease: Quality Improvement Retrospective Analysis.

BACKGROUND: Digital health programs assist patients with chronic obstructive pulmonary disease (COPD) to better manage their disease. Technological and adoption barriers have been perceived as a limitation. OBJECTIVE: The aim of the research was to evaluate a digital quality improvement pilot in Medicare-eligible patients with COPD. METHODS: COPD patients were enrolled in a digital platform to help manage their medications and symptoms as part of their routine clinical care. Patients were provided with electronic medication monitors (EMMs) to monitor short-acting beta-agonist (SABA) use passively and a smartphone app to track use trends and receive feedback. Providers also had access to data collected via a secure website and were sent email notifications if a patient had a significant change in their prescribed inhaler use. Providers then determined if follow-up was needed. Change in SABA use and feasibility outcomes were evaluated at 3, 6, and 12 months. RESULTS: A total of 190 patients enrolled in the pilot. At 3, 6, and 12 months, patients recorded significant reductions in daily and nighttime SABA use and increases in SABA-free days (all P<.001). Patient engagement, as measured by the ratio of daily active use to monthly active use, was >90% at both 6 and 12 months. Retention at 6 months was 81% (154/190). Providers were sent on average two email notifications per patient during the 12-month program. CONCLUSIONS: A digital health program integrated as part of standard clinical practice was feasible and had low provider burden. The pilot demonstrated significant reduction in SABA use and increased SABA-free days among Medicare-eligible COPD patients. Further, patients readily adopted the digital platform and demonstrated strong engagement and retention rates at 6 and 12 months.

Impact of a digital health intervention on asthma resource utilization.

Digital health interventions have been associated with reduced rescue inhaler use and improved controller medication adherence. This quality improvement project assessed the benefit of these interventions on asthma-related healthcare utilizations, including hospitalizations, emergency department (ED) utilization and outpatient visits. The intervention consisted of electronic medication monitors (EMMs) that tracked rescue and controller inhaler medication use, and a digital health platform that presented medication use information and asthma control status to patients and providers. In 224 study patients, the number of asthma-related ED visits and combined ED and hospitalization events 365 days pre- to 365 days post-enrollment to the intervention significantly decreased from 11.6 to 5.4 visits (p < 0.05) and 13.4 to 5.8 events (p < 0.05) per 100 patient-years, respectively. This digital health intervention was successfully incorporated into routine clinical practice and was associated with lower rates of asthma-related hospitalizations and ED visits.

Digital Health Intervention for Asthma: Patient-Reported Value and Usability.

BACKGROUND: Although digital health tools are increasingly recognized as effective in improving clinical outcomes such as asthma control and medication adherence, few studies have assessed patient experiences and perception of value. OBJECTIVE: The aim of this study was to evaluate patient satisfaction, perception of usability and value, and desire to continue after 12 months of using a digital health intervention to support asthma management. METHODS: Participants were enrolled in a randomized controlled study evaluating the impact of a digital health platform for asthma management. Participants used electronic inhaler sensors to track medication use and accessed their information in a digital health platform. Electronic surveys were administered to intervention arm participants aged 12 years and older after 12 months of use. The survey assessed asthma control, patient satisfaction with the sensor device, and perception of the usability and value of the digital health platform through closed-ended and open-ended questions. Logistic regression models were used to assess the impact of participants' characteristics on survey completion, satisfaction, and perception of value. RESULTS: Of the 207 intervention arm participants aged 12 years and older, 89 submitted survey responses (42.9% response rate). Of these 89 participants, 70 reported being very satisfied (79%, 70/89) or somewhat satisfied (20%, 18/89) with the inhaler sensor device. Moreover, 93% (83/89) expressed satisfaction with the reports, and 90% (80/89) found the information from the reports useful for learning about their asthma. In addition, 72% (64/89) of the participants reported that they were interested in continuing to use the sensor and platform beyond the study. There were no significant differences in satisfaction with the device or the platform across participants' characteristics, including device type, age, sex, insurance type, asthma control, or syncing history; however, participants with smartphones and longer participation were more likely to take the survey. CONCLUSIONS: Electronic sensors and a digital health platform were well received by participants who reported satisfaction and perceived value. These results were consistent across multiple participants' characteristics. These findings can add to a limited literature to keep improving digital health interventions and ensure the meaningful and enduring impact on patient outcomes.

Effect of a mobile health, sensor-driven asthma management platform on asthma control.

BACKGROUND: Asthma inflicts a significant health and economic burden in the United States. Self-management approaches to monitoring and treatment can be burdensome for patients. OBJECTIVE: To assess the effect of a digital health management program on asthma outcomes. METHODS: Residents of Louisville, Kentucky, with asthma were enrolled in a single-arm pilot study. Participants received electronic inhaler sensors that tracked the time, frequency, and location of short-acting ß-agonist (SABA) use. After a 30-day baseline period during which reference medication use was recorded by the sensors, participants received access to a digital health intervention designed to enhance self-management. Changes in outcomes, including mean daily SABA use, symptom-free days, and asthma control status, were compared among the initial 30-day baseline period and all subsequent months of the intervention using mixed-model logistic regressions and χ2 tests. RESULTS: The mean number of SABA events per participant per day was 0.44 during the control period and 0.27 after the first month of the intervention, a 39% reduction. The percentage of symptom-free days was 77% during the baseline period and 86% after the first month, a 12% improvement. Improvement was observed throughout the study; each intervention month demonstrated significantly lower SABA use and higher symptom-free days than the baseline month (P < .001). Sixty-nine percent had well-controlled asthma during the baseline period, 67% during the first month of the intervention. Each intervention month demonstrated significantly higher percentages than the baseline month (P < .001), except for month 1 (P = .80). CONCLUSION: A digital health asthma management intervention demonstrated significant reductions in SABA use, increased number of symptom-free days, and improvements in asthma control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02162576.

Feasibility of Deploying Inhaler Sensors to Identify the Impacts of Environmental Triggers and Built Environment Factors on Asthma Short-Acting Bronchodilator Use.

BACKGROUND: Epidemiological asthma research has relied upon self-reported symptoms or healthcare utilization data, and used the residential address as the primary location for exposure. These data sources can be temporally limited, spatially aggregated, subjective, and burdensome for the patient to collect. OBJECTIVES: First, we aimed to test the feasibility of collecting rescue inhaler use data in space-time using electronic sensors. Second, we aimed to evaluate whether these data have the potential to identify environmental triggers and built environment factors associated with rescue inhaler use and to determine whether these findings would be consistent with the existing literature. METHODS: We utilized zero-truncated negative binomial models to identify triggers associated with inhaler use, and implemented three sensitivity analyses to validate our findings. RESULTS: Electronic sensors fitted on metered dose inhalers tracked 5,660 rescue inhaler use events in space and time for 140 participants from 13 June 2012 to 28 February 2014. We found that the inhaler sensors were feasible in passively collecting objective rescue inhaler use data. We identified several environmental triggers with a positive and significant association with inhaler use, including: AQI, PM10, weed pollen, and mold. Conversely, the spatial distribution of tree cover demonstrated a negative and significant association with inhaler use. CONCLUSIONS: Utilizing a sensor to capture the signal of rescue inhaler use in space-time offered a passive and objective signal of asthma activity. This approach enabled detailed analyses to identify environmental triggers and built environment factors that are associated with asthma symptoms beyond the residential address. The application of these new technologies has the potential to improve our surveillance and understanding of asthma. Citation: Su JG, Barrett MA, Henderson K, Humblet O, Smith T, Sublett JW, Nesbitt L, Hogg C, Van Sickle D, Sublett JL. 2017. Feasibility of deploying inhaler sensors to identify the impacts of environmental triggers and built environment factors on asthma short-acting bronchodilator use. Environ Health Perspect 125:254-261; http://dx.doi.org/10.1289/EHP266.

In vitro and in vivo evaluation of orthopedic interface repair using a tissue scaffold with a continuous hard tissue-soft tissue transition.

Tendon tears produce pain and decrease joint stability; each year, over 1.1 million rotator cuff tendon surgical procedures are performed worldwide. However, surgical success is highly variable, and the inability of the procedure to drive the regeneration of the normal tendon-bone interface has been identified as a key factor in surgical failure. This study focuses on the development, in vitro evaluation, and in vivo assessment of a tissue scaffold derived from bovine cancellous bone with the potential to direct regeneration of a bone-soft tissue interface. The scaffold is a highly porous scaffold with a continuous hard tissue-soft tissue transition that facilitates load transfer across the interface and contains all of the extracellular matrix components of the orthopedic interface. This study demonstrated the in vitro characterization of the mechanical properties and successful in vivo assessment using an ovine model.

Variability in the labeling of asthma among pediatricians.

OBJECTIVE: Few studies have examined variability among physicians in the perception and interpretation of asthma symptoms. We report the results of a pilot study to investigate the variability of symptom description and diagnostic labeling and nomenclature among a group of clinicians using standardized audiovisual presentations of asthma. METHODS: Practicing pediatricians in Wisconsin recruited from an electronic mailing list were shown the International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire online, and asked to describe the symptoms and signs they observed and suggest possible diagnostic labels for each presentation. RESULTS: A total of 113 pediatricians (mean age = 43 years; 56% female) responded to ≥1 of the 5 video scenes. The number of practitioners who described the principal symptom(s) of asthma depicted in the 5 sequences ranged from 5.5% for Scene 5 (featuring both dyspnea and wheeze), to 100% for Scene 4 (featuring cough). The number who suggested label of 'asthma' as a possible cause of the presentations ranged from 69.7% for Scene 3 (featuring nocturnal wheeze), to 92.7% for Scene 2 (featuring exercise induced wheeze). CONCLUSION: There is important unexplained variation in the perceptions and labeling of asthma symptoms among pediatricians. These differences may influence the likelihood of diagnosis and the apparent prevalence of asthma. Many participants suggested that the ISAAC video be used in the education and training of pediatricians.

Remote monitoring of inhaled bronchodilator use and weekly feedback about asthma management: an open-group, short-term pilot study of the impact on asthma control.

OBJECTIVE: Adequate symptom control is a problem for many people with asthma. We asked whether weekly email reports on monitored use of inhaled, short-acting bronchodilators might improve scores on composite asthma-control measures. METHODS: Through an investigational electronic medication sensor attached to each participant's inhaler, we monitored 4 months' use of inhaled, short-acting bronchodilators. Participants completed surveys, including the Asthma Control Test(TM) (ACT), to assess asthma control at entry and monthly thereafter. After the first month, participants received weekly email reports for 3 months. The reports summarized inhaled bronchodilator use during the preceding week and provided suggestions derived from National Asthma Education and Prevention Program (NAEPP) guidelines. Paired t-tests and random-effects mixed models were implemented to assess changes in primary asthma endpoints. RESULTS: Thirty individuals participated in the 4-month study; 29 provided complete asthma control information. Mean age was 36.8 years (range: 19-74 years); 52% of respondents were female. Mean ACT scores were 17.6 (Standard Deviation [SD]  = 3.35) at entry and 18.4 (SD = 3.60) at completion of the first month. No significant difference appeared between ACT values at entry and completion of the first month (p = 0.66); however, after participants began receiving email reports and online information about their inhaler use, mean ACT scores increased 1.40 points (95% CI: 0.61, 2.18) for each subsequent study month. Significant decreases occurred in 2-week histories of daytime symptoms (ß = -1.35, 95% CI: -2.65, -0.04) and nighttime symptoms (ß = -0.84, 95% CI: -1.25, -0.44); no significant change in activity limitation (ß = -0.21, 95% CI: -0.69, 0.26) was observed. Participants reported increased awareness and understanding of asthma patterns, level of control, bronchodilator use (timing, location) and triggers, and improved preventive practices. CONCLUSIONS: Weekly email reports and access to online charts summarizing remote monitoring of inhaled bronchodilator frequency and location were associated with improved asthma control and a decline in day-to-day asthma symptoms.

The Immediate Pulmonary Disease Pattern following Exposure to High Concentrations of Chlorine Gas.

Background. Classification of pulmonary disease into obstructive, restrictive, and mixed patterns is based on 2005 ATS/ERS guidelines and modified GOLD criteria by Mannino et al. (2003), but these guidelines are of limited use for simple spirometry in situations involving mass casualties. Aim. The purpose of this study was to apply these guidelines to patients who underwent simple spirometry following high concentration of chlorine gas inhalation after a train derailment in Graniteville, South Carolina. Methods. We retrospectively investigated lung functions in ten patients. In order to classify pulmonary disease pattern, we used 2005 ATS/ERS guidelines and modified GOLD criteria along with our own criteria developed using available simple spirometry data. Results. We found predominant restrictive pattern in our patients with both modified GOLD and our criteria, which is in contrast to other chlorine exposure studies where obstructive pattern was more common. When compared to modified GOLD and our criteria, 2005 ATS/ERS guidelines underestimated the frequency of restrictive disease. Conclusion. Diagnosis of pulmonary disease patterns is of importance after irritant gas inhalation. Acceptable criteria need to be developed to evaluate pulmonary disease through simple spirometry in events leading to mass casualty and patient surge in hospitals.

Understanding socioeconomic and racial differences in adult lung function.

RATIONALE: The contribution of socioeconomic factors to racial differences in the distribution of lung function is not well understood. OBJECTIVES: We investigated the contribution of socioeconomic factors to racial differences in FEV1 using statistical tools that allow for examination across the population distribution of FEV1. METHODS: We compared FEV1 for white and African-American participants (aged 20-80 yr) in NHANES III with greater than or equal to two acceptable maneuvers to a restricted sample following the routine exclusion criteria used to derive population reference equations. Ordinary least squares and quantile regression analyses using spirometric, anthropometric, and socioeconomic data (high school completion) were performed separately by sex for both data sets. MEASUREMENTS AND MAIN RESULTS: In the entire sample with acceptable spirometry (n » 9,658), high school completion was associated with a mean 69.13-ml increase in FEV1 for males (P , 0.05) and a mean 50.75-ml increase in FEV1 for females (P , 0.01). In quantile regression analysis, we observed a significant racial difference in the association of high school completion with FEV1 among both sexes that varied across the distribution; college completion was associated with an additional increase in FEV1 for white males (70.36-250.76 ml) and white females (57.87-317.77 ml). Routine exclusion criteria differentially excluded individuals by age, race, and education. In the restricted sample (n » 2,638), the association with high school completion was not significant. CONCLUSIONS: High school completion is associated with racially patterned improvements in the FEV1 of adults in the general population. The application of routine exclusion criteria leads to underestimates of the role of high school completion on FEV1.

Follow-up assessment of health consequences after a chlorine release from a train derailment--Graniteville, SC, 2005.

INTRODUCTION: After a train derailment released chlorine gas in Graniteville, South Carolina, in 2005, a multiagency team performed an epidemiologic assessment of chlorine exposure and resulting health effects. Five months later, participants were resurveyed to determine their health status and needs and to assist in planning additional interventions in the community. METHODS: Questionnaires were mailed to 279 patients interviewed in the initial assessment; follow-up telephone calls were made to nonresponders. The questionnaire included questions regarding duration of symptoms experienced after exposure and a posttraumatic stress disorder (PTSD) assessment tool. RESULTS: Ninety-four questionnaires were returned. Seventy-six persons reported chronic symptoms related to the chlorine exposure, 47 were still under a doctor's care, and 49 were still taking medication for chlorine-related problems. Agreement was poor between the first and second questionnaires regarding symptoms experienced after exposure to the chlorine (κ=0.30). Forty-four respondents screened positive for PTSD. PTSD was associated with post-exposure hospitalization for three or more nights [relative risk (RR) = 1.7; 95% confidence interval (CI)=1.1-2.6] and chronic symptoms (RR=9.1; 95% CI=1.3-61.2), but not with a moderate-to-extreme level of chlorine exposure (RR=1.2; 95% CI=0.8-1.8). CONCLUSIONS: Some victims of this chlorine exposure event continued to experience physical symptoms and continued to require medical care 5 months later. Chronic mental health symptoms were prevalent, especially among persons experiencing the most severe or persistent physical health effects. Patients should be interviewed as soon as possible after an incident because recall of acute symptoms experienced can diminish within months.

The next generation of public health approaches to asthma in Asia and the Middle East.

Chronic respiratory diseases now affect more than half a billion people worldwide and their importance as a global health problem has risen dramatically in recent years, prompting intense epidemiological investigation and the launch of numerous initiatives. Across Asia and the Middle East, a variety of environmental exposures increase the risk for the onset or exacerbation of chronic respiratory disease, resulting in a considerable burden of morbidity and mortality. This article outlines new possibilities for public health surveillance of environmental exposures and chronic respiratory disease built around an emerging model of participatory public health: a decentralized approach that involves citizens in the collection and analysis of data, harnesses pervasive technology such as mobile phones and distributed sensors, and provides an open platform for public-private collaboration.

Medical devices for developing countries: design constraints and approaches.

Medical devices intended for use in developing countries have certain differences compared to those used in developed countries. Thus, many of the medical devices built for developed countries may not be compatible with the environment in developing countries. In this specific case study we consider the respiratory problems in India and elucidate design constraints and approaches for the development of medical devices to diagnose them.

Acute health effects after exposure to chlorine gas released after a train derailment.

In January 2005, a train derailment on the premises of a textile mill in South Carolina released 42 to 60 tons of chlorine gas in the middle of a small town. Medical records and autopsy reports were reviewed to describe the clinical presentation, hospital course, and pathology observed in persons hospitalized or deceased as a result of chlorine gas exposure. Eight persons died before reaching medical care; of the 71 persons hospitalized for acute health effects as a result of chlorine exposure, 1 died in the hospital. The mean age of the hospitalized persons was 40 years (range, 4 months-76 years); 87% were male. The median duration of hospitalization was 4 days (range, 1-29 days). Twenty-five (35%) persons were admitted to the intensive care unit; the median length of stay was 3 days. Many surviving victims developed significant pulmonary signs and severe airway inflammation; 41 (58%) hospitalized persons met PO2/FiO2 criteria for acute respiratory distress syndrome or acute lung injury. During their hospitalization, 40 (57%) developed abnormal x-ray findings, 74% of those within the first day. Hypoxia on room air and PO2/FiO2 ratio predicted severity of outcome as assessed by the duration of hospitalization and the need for intensive care support. This community release of chlorine gas caused widespread exposure and resulted in significant acute health effects and substantial health care requirements. Pulse oximetry and arterial blood gas analysis provided early indications of outcome severity.

Breath acidification in adolescent runners exposed to atmospheric pollution: a prospective, repeated measures observational study.

BACKGROUND: Vigorous outdoors exercise during an episode of air pollution might cause airway inflammation. The purpose of this study was to examine the effects of vigorous outdoor exercise during peak smog season on breath pH, a biomarker of airway inflammation, in adolescent athletes. METHODS: We measured breath pH both pre- and post-exercise on ten days during peak smog season in 16 high school athletes engaged in daily long-distance running in a downwind suburb of Atlanta. The association of post-exercise breath pH with ambient ozone and particulate matter concentrations was tested with linear regression. RESULTS: We collected 144 pre-exercise and 146 post-exercise breath samples from 16 runners (mean age 14.9 years, 56% male). Median pre-exercise breath pH was 7.58 (interquartile range: 6.90 to 7.86) and did not change significantly after exercise. We observed no significant association between ambient ozone or particulate matter and post-exercise breath pH. However both pre- and post-exercise breath pH were strikingly low in these athletes when compared to a control sample of 14 relatively sedentary healthy adults and to published values of breath pH in healthy subjects. CONCLUSION: Although we did not observe an acute effect of air pollution exposure during exercise on breath pH, breath pH was surprisingly low in this sample of otherwise healthy long-distance runners. We speculate that repetitive vigorous exercise may induce airway acidification.