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.

A Mobile- and Web-Based Health Intervention Program for Diabetes and Prediabetes Self-Management (BetaMe/Melon): Process Evaluation Following a Randomized Controlled Trial.

BACKGROUND: Technology-assisted self-management programs are increasingly recommended to patients with long-term conditions such as diabetes. However, there are a number of personal and external factors that affect patients' abilities to engage with and effectively utilize such programs. A randomized controlled trial of a multi-modal online program for diabetes self-management (BetaMe/Melon) was conducted in a primary care setting, and a process evaluation was completed at the end of the study period. OBJECTIVE: This process evaluation aimed to examine the utilization patterns of BetaMe/Melon, identify which components participants found most (and least) useful, and identify areas of future improvement. METHODS: Process evaluation data were collected for intervention arm participants from 3 sources: (1) the mobile/web platform (to identify key usage patterns over the 16-week core program), (2) an online questionnaire completed during the final study assessment, and (3) interviews conducted with a subset of participants following the study period. Participants were classified as "actively engaged" if any usage data was recorded for the participant (in any week), and patterns were reported by age, gender, ethnicity, and diabetes/prediabetes status. The online questionnaire asked participants about the usefulness of the program and whether they would recommend BetaMe/Melon to others according to a 5-point Likert Scale. Of 23 invited participants, 18 participated in a digitally recorded, semistructured telephone interview. Interview data were thematically analyzed. RESULTS: Out of the 215 participants, 198 (92%) received an initial health coaching session, and 160 (74%) were actively engaged with the program at some point during the 16-week core program. Engagement varied by demographic, with women, younger participants, and ethnic majority populations having higher rates of engagement. Usage steadily declined from 50% at Week 0 to 23% at Week 15. Participants ranked component usefulness as education resources (63.7%), health coaches (59.2%), goal tracking (48.8%), and online peer support (42.1%). Although 53% agreed that the program was easy to use, 64% would recommend the program to others. Interview participants found BetaMe/Melon useful overall, with most identifying beneficial outcomes such as increased knowledge, behavioral changes, and weight loss. Barriers to engagement were program functionality, internet connectivity, incomplete delivery of all program components, and participant motivation. Participants suggested a range of improvements to the BetaMe/Melon program. CONCLUSIONS: The program was generally well received by participants; active engagement was initially high, although it declined steadily. Maintaining participant engagement over time, individualizing programs, and addressing technical barriers are important to maximize potential health benefits from online diabetes self-management programs. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617000549325; https://tinyurl.com/y622b27q.

Impact of a comprehensive digital health programme on HbA1c and weight after 12 months for people with diabetes and prediabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this RCT was to evaluate the effectiveness of a digital health programme (BetaMe/Melon) vs usual care in improving the control of type 2 diabetes and prediabetes in a primary care population. METHODS: We conducted a randomised parallel-group two-arm single-blinded superiority trial in the primary care setting in two regions of New Zealand. Eligible participants were identified through Primary Health Organisations and participating practices. Eligibility criteria were as follows: age 18-75 years, HbA1c 41-70 mmol/mol (5.9-8.6%), not taking insulin, and daily access to the internet. BetaMe/Melon is a 12 month mobile-device and web-based programme with four components: health coaching; evidence-based resources; peer support; and goal tracking. Participants were randomised into the intervention or control arm (1:1 allocation) based upon baseline HbA1c (prediabetes or diabetes range), stratified by practice and ethnicity. Research nurses and the study biostatistician were blind to study arm. Primary outcomes of the study were changes in HbA1c and weight at 12 months, using an intention-to-treat analysis. RESULTS: Four hundred and twenty-nine individuals were recruited between 20 June 2017 and 11 May 2018 (n = 215 intervention arm, n = 214 control arm), most of whom were included in analyses of co-primary outcomes (n = 210/215, 97.7% and n = 213/214, 99.5%). HbA1c levels at 12 months did not differ between study arms: mean difference was -0.9 mmol/mol (95% CI -2.9, 1.1) (-0.1% [95% CI -0.3, 0.1]) for the diabetes group and was 0.0 mmol/mol (95% CI -0.9, 0.9) (0.0% [95% CI -0.1, 0.1]) for the prediabetes group. Weight reduced slightly at 12 months for participants in both study arms, with no difference between arms (mean difference -0.4 kg [95% CI -1.3, 0.5]). CONCLUSIONS/INTERPRETATION: This study did not demonstrate clinical effectiveness for this particular programme. Given their high costs, technology-assisted self-management programmes need to be individually assessed for their effectiveness in improving clinical outcomes for people with diabetes. TRIAL REGISTRATION: www.anzctr.org.au ACTRN12617000549325 (universal trial number U1111-1189-9094) FUNDING: This study was funded by the Health Research Council of New Zealand, the Ministry of Health New Zealand and the Healthier Lives National Science Challenge. Graphical abstract.

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.

Optimizing Advances in Nanoparticle Delivery for Cancer Immunotherapy.

Cancer immunotherapy is one of the fastest growing and most promising fields in clinical oncology. T-cell checkpoint inhibitors are revolutionizing the management of advanced cancers including non-small cell lung cancer and melanoma. Unfortunately, many common cancers are not responsive to these drugs and resistance remains problematic. A growing number of novel cancer immunotherapies have been discovered but their clinical translation has been limited by shortcomings of conventional drug delivery. Immune signaling is tightly-regulated and often requires simultaneous or near-simultaneous activation of multiple signals in specific subpopulations of immune cells. Nucleic acid therapies, which require intact intracellular delivery, are among the most promising approaches to modulate the tumor microenvironment to a pro-immunogenic phenotype. Advanced nanomedicines can be precisely engineered to overcome many of these limitations and appear well-poised to enable the clinical translation of promising cancer immunotherapies.

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.

AIR Louisville: Addressing Asthma With Technology, Crowdsourcing, Cross-Sector Collaboration, And Policy.

Cross-sector partnerships benefit public health by leveraging ideas, resources, and expertise from a wide range of partners. In this study we documented the process and impact of AIR Louisville (a collaboration forged among the Louisville Metro Government, a nonprofit institute, and a technology company) in successfully tackling a complex public health challenge: asthma. We enrolled residents of Louisville, Kentucky, with asthma and used electronic inhaler sensors to monitor where and when they used medication. We found that the use of the digital health platform achieved positive clinical outcomes, including a 78 percent reduction in rescue inhaler use and a 48 percent improvement in symptom-free days. Moreover, the crowdsourced real-world data on inhaler use, combined with environmental data, led to policy recommendations including enhancing tree canopy, tree removal mitigation, zoning for air pollution emission buffers, recommended truck routes, and developing a community asthma notification system. AIR Louisville represents a model that can be replicated to address many public health challenges by simultaneously guiding individual, clinical, and policy decisions.

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.

Self-compassionate reactions to health threats.

Four studies investigated the relationship between self-compassion, health behaviors, and reactions to illness. Participants completed measures of self-compassion, health-related thoughts and feelings, reactions to actual and hypothetical illnesses, and self-regulation. Study 1 revealed that self-compassion was related to health-related cognitions and affect for healthy and unhealthy participants. In Study 2, self-compassion predicted participants' reactions to actual illnesses beyond the influence of illness severity and other predictors of health behaviors. Self-compassionate people also indicated they would seek medical attention sooner when experiencing symptoms than people lower in self-compassion. Study 3 demonstrated that self-compassion is related to health-promoting behaviors even after accounting for self-regulatory capabilities and illness cognitions. Study 4 revealed that the relationship between self-compassion and health reactions is partially explained by a proactive approach to health, benevolent self-talk, and a motivation toward self-kindness. Overall, these studies demonstrate that self-compassion has important implications for health-promoting behaviors and reactions to illness.

Thymomegaly, microsplenia, and defective homeostatic proliferation of peripheral lymphocytes in p51-Ets1 isoform-specific null mice.

Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1(DeltaVII) (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1(DeltaVII) isoform. Ets1(DeltaVII) homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8(+) and CD8(+)CD4(+) thymocytes were observed. Lymphoid cell (CD19(+), CD4(+), and CD8(+)) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1(DeltaVII) mutants demonstrate lymphocyte maturation defects associated with misregulation of p16(Ink4a), p27(Kip1), and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis.

slc26a3 (dra)-deficient mice display chloride-losing diarrhea, enhanced colonic proliferation, and distinct up-regulation of ion transporters in the colon.

Mutations in the SLC26A3 (DRA (down-regulated in adenoma)) gene constitute the molecular etiology of congenital chloride-losing diarrhea in humans. To ascertain its role in intestinal physiology, gene targeting was used to prepare mice lacking slc26a3. slc26a3-deficient animals displayed postpartum lethality at low penetrance. Surviving dra-deficient mice exhibited high chloride content diarrhea, volume depletion, and growth retardation. In addition, the large intestinal loops were distended, with colonic mucosa exhibiting an aberrant growth pattern and the colonic crypt proliferative zone being greatly expanded in slc26a3-null mice. Apical membrane chloride/base exchange activity was sharply reduced, and luminal content was more acidic in slc26a3-null mouse colon. The epithelial cells in the colon displayed unique adaptive regulation of ion transporters; NHE3 expression was enhanced in the proximal and distal colon, whereas colonic H,K-ATPase and the epithelial sodium channel showed massive up-regulation in the distal colon. Plasma aldosterone was increased in slc26a3-null mice. We conclude that slc26a3 is the major apical chloride/base exchanger and is essential for the absorption of chloride in the colon. In addition, slc26a3 regulates colonic crypt proliferation. Deletion of slc26a3 results in chloride-rich diarrhea and is associated with compensatory adaptive up-regulation of ion-absorbing transporters.

Alterations in PMS2, MSH2 and MLH1 expression in human prostate cancer.

DNA mismatch repair (MMR) is involved in the post-replication correction of errors due to misincorporated nucleotides or DNA slippage during DNA synthesis. We previously reported the reduction or loss of MMR protein expression in human prostate cancer cell lines and some primary tumors. In the present report, we further demonstrate the involvement of defects of MMR in the pathogenesis of prostate cancer. Immunohistochemical analysis of 39 formalin-fixed, paraffin-embedded human prostate tumors, showed reduction or absence of MMR protein expression (MLH1, MSH2, PMS2) in the epithelium of prostate tumor foci compared to normal adjacent prostate tissue. The reduction or absence of the PMS2 and MSH2 (but not MLH1) protein was correlated to the differentiation of the tumor. Poorly differentiated tumors showed greater loss of these two proteins than the well differentiated tumors (P<0.05). We previously reported that microsatellite instability was detectable by a beta-galactosidase restoration mutation assay in the prostate cancer cell lines DU145, PC3, LNCaP, p67SV40T, M2182, and M12. In this study, we detected the insertion or deletion of one nucleotide in the mononucleotide repeats located within the coding regions of BAX gene in DU145, and TGFbetaRII in M12 cells. In addition, we used an in vitro model of defective MMR to demonstrate that microsatellite instability can be induced in an otherwise stable cancer cell line by transfection with a dominant negative fragment of PMS2. These results suggest that defects in MMR may result in MSI in the secondary genes in prostate cancer. From these results, we conclude that loss of MMR function can produce MSI and target some secondary genes containing microsatellites in their coding regions. These series of events may play important roles in the development of human prostate cancer.

The colon anion transporter, down-regulated in adenoma, induces growth suppression that is abrogated by E1A.

The down-regulated in adenoma (DRA) gene is significantly down-regulated in adenomas and adenocarcinomas of the colon as well as in colon cancer cell lines. It is also mutated in the disease congenital chloride diarrhea, which is characterized by loss of chloride transport and diarrhea. We now show a second function for DRA relevant to colon tumorigenesis, i.e., growth suppression. Transfection of full-length DRA into various cell lines (DLD-1, HT-29, HCT-15, SW837, SW480, MCF-7, NIH3T3, CaSki, and HeLa) that lack endogenous DRA expression results in a reduced number of drug-resistant colonies compared with vector control, suggesting growth suppression by DRA. In addition, expression of DRA under the control of an inducible promoter reduced the growth rate of DLD-1 cells compared with cells not expressing DRA. The COOH-terminal cytoplasmic domain of DRA is required for growth suppression, but an in-frame deletion (DeltaVal317) that causes congenital chloride diarrhea and results in a loss of anion transport had no effect on growth suppression, indicating that anion transport and growth suppression are independent functions of DRA. One cell line, adenovirus-transformed HEK293, exhibited significant resistance to DRA-induced growth suppression, whereas the human papillomavirus-transformed cell lines, CaSki and HeLa, did not. E1A is an adenoviral protein required to transform HEK293 cells. DLD-1 cells that stably express 12S E1A are resistant to growth suppression by DRA, similar to HEK293 cells.