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Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

ABSTRACT: Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis.Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR.1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%).We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.

SUBMITTER: Muller J

PROVIDER: S-EPMC5465537 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

Muller Julius J Parizotto Eneida E Antrobus Richard R Francis James J Bunce Campbell C Stranks Amanda A Nichols Marshall M McClain Micah M Hill Adrian V S AVS Ramasamy Adaikalavan A Gilbert Sarah C SC

Journal of translational medicine 20170608 1

<h4>Background</h4>Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis.<h4>Methods</h4>Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h pos ...[more]

PMID: 28595644

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Project description:ObjectivesTo assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms.MethodsAn observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health.ResultsOf the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness.ConclusionsResults suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.

Project description:Researchers interested in the effect of health on various life outcomes (such as employment, earnings and life satisfaction) often use self-reported health and disease status as an indicator of true, underlying health status. Self-reports appear to be reasonable measures of overall health. For example, self-assessed overall health has been found to be a reliable predictor of mortality. However, the validity of self-reports is questionable when investigating specific diseases such as diabetes and hypertension. A small and nascent body of research comparing self-reported status on certain diseases with the true status based on clinical diagnoses has found significant gaps. These validation exercises predominantly use data from high-income countries. In this paper, we use survey data from India to compare self-reports of disease prevalence to diagnostic tests conducted on the same individuals. We focus on hypertension and lung disease, two of the primary causes of death in India. We find that self-reported measures substantially understate the true disease burden for both conditions. The attenuation bias from using self-reports is over 80 percent for both diseases, and bigger than estimates from high-income countries. We test and reject the hypothesis that self-reports of the disease status are identical to the true disease status in expectation. We identify characteristics associated with false negative reporting (reporting not having the disease but testing positive for it) for both diseases. The large awareness gap between self-reports and true disease burden indicates multiple deficiencies in India's public health policy. The survey data depicts limited access to medical facilities, high levels of health illiteracy, low rates of health insurance, and other barriers related to poverty and lack of equity in the delivery of health services. These factors prevent timely intervention for managing health and controlling disease, invariably leading to morbidity and often to premature death.

Project description:Study objectivesTo investigate the association between self-reported and objective measures of sleep and wind turbine noise (WTN) exposure.MethodsThe Community Noise and Health Study, a cross-sectional epidemiological study, included an in-house computer-assisted interview and sleep pattern monitoring over a 7 d period. Outdoor WTN levels were calculated following international standards for conditions that typically approximate the highest long-term average levels at each dwelling. Study data were collected between May and September 2013 from adults, aged 18-79 y (606 males, 632 females) randomly selected from each household and living between 0.25 and 11.22 kilometers from operational wind turbines in two Canadian provinces. Self-reported sleep quality over the past 30 d was assessed using the Pittsburgh Sleep Quality Index. Additional questions assessed the prevalence of diagnosed sleep disorders and the magnitude of sleep disturbance over the previous year. Objective measures for sleep latency, sleep efficiency, total sleep time, rate of awakening bouts, and wake duration after sleep onset were recorded using the wrist worn Actiwatch2® from a subsample of 654 participants (289 males, 365 females) for a total of 3,772 sleep nights.ResultsParticipant response rate for the interview was 78.9%. Outdoor WTN levels reached 46 dB(A) with an arithmetic mean of 35.6 and a standard deviation of 7.4. Self-reported and objectively measured sleep outcomes consistently revealed no apparent pattern or statistically significant relationship to WTN levels. However, sleep was significantly influenced by other factors, including, but not limited to, the use of sleep medication, other health conditions (including sleep disorders), caffeine consumption, and annoyance with blinking lights on wind turbines.ConclusionsStudy results do not support an association between exposure to outdoor WTN up to 46 dB(A) and an increase in the prevalence of disturbed sleep. Conclusions are based on WTN levels averaged over 1 y and, in some cases, may be strengthened with an analysis that examines sleep quality in relation to WTN levels calculated during the precise sleep period time.

Dataset Information

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

Publications

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

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