M. Patricia Fabian

Influenza Virus Aerosols in Human Exhaled Breath: Particle Size, Culturability, and Effect of Surgical Masks

The CDC recommends that healthcare settings provide influenza patients with facemasks as a means of reducing transmission to staff and other patients, and a recent report suggested that surgical masks can capture influenza virus in large droplet spray. However, there is minimal data on influenza virus aerosol shedding, the infectiousness of exhaled aerosols, and none on the impact of facemasks on viral aerosol shedding from patients with seasonal influenza. We collected samples of exhaled particles (one with and one without a facemask) in two size fractions (“coarse”>5 µm, “fine”≤5 µm) from 37 volunteers within 5 days of seasonal influenza onset, measured viral copy number using quantitative RT-PCR, and tested the fine-particle fraction for culturable virus. Fine particles contained 8.8 (95% CI 4.1 to 19) fold more viral copies than did coarse particles. Surgical masks reduced viral copy numbers in the fine fraction by 2.8 fold (95% CI 1.5 to 5.2) and in the coarse fraction by 25 fold (95% CI 3.5 to 180). Overall, masks produced a 3.4 fold (95% CI 1.8 to 6.3) reduction in viral aerosol shedding. Correlations between nasopharyngeal swab and the aerosol fraction copy numbers were weak (r = 0.17, coarse; r = 0.29, fine fraction). Copy numbers in exhaled breath declined rapidly with day after onset of illness. Two subjects with the highest copy numbers gave culture positive fine particle samples. Surgical masks worn by patients reduce aerosols shedding of virus. The abundance of viral copies in fine particle aerosols and evidence for their infectiousness suggests an important role in seasonal influenza transmission. Monitoring exhaled virus aerosols will be important for validation of experimental transmission studies in humans.

Research findings from nonpharmaceutical intervention studies for pandemic influenza and current gaps in the research.

In June 2006, the Centers for Disease Control and Prevention released a request for applications to identify, improve, and evaluate the effectiveness of nonpharmaceutical interventions (NPIs)-strategies other than vaccines and antiviral medications-to mitigate the spread of pandemic influenza within communities and across international borders (RFA-CI06-010). These studies have provided major contributions to seasonal and pandemic influenza knowledge. Nonetheless, key concerns were identified related to the acceptability and protective efficacy of NPIs. Large-scale intervention studies conducted over multiple influenza epidemics, as well as smaller studies in controlled laboratory settings, are needed to address the gaps in the research on transmission and mitigation of influenza in the community setting. The current novel influenza A (H1N1) pandemic underscores the importance of influenza research.

Development and Performance Evaluation of an Exhaled-Breath Bioaerosol Collector for Influenza Virus.

The importance of the aerosol mode for transmission of influenza is unknown. Understanding the role of aerosols is essential to developing public health interventions such as the use of surgical masks as a source control to prevent the release of infectious aerosols. Little information is available on the number and size of particles generated by infected persons, which is partly due to the limitations of conventional air samplers, which do not efficiently capture fine particles or maintain microorganism viability. We designed and built a new sampler, called the G-II, that collects exhaled-breath particles that can be used in infectivity analyses. The G-II allows test subjects to perform various respiratory maneuvers (i.e., tidal breathing, coughing, and talking) and allows subjects to wear a mask or respirator during testing. A conventional slit impactor collects particles greater than 5.0 μm. Condensation of water vapor is used to grow remaining particles, including fine particles, to a size large enough to be efficiently collected by a 1.0 μm slit impactor and be deposited into a buffer-containing collector. We evaluated the G-II for fine particle collection efficiency with inert particle aerosols and evaluated infective virus collection using influenza A virus aerosols. Testing results showed greater than 85% collection efficiency for particles greater than 50 nm and influenza virus collection comparable with a reference SKC BioSampler®. The new design will enable determination of exhaled infectious virus generation rate and evaluate control strategies such as wearing a surgical-type mask to prevent the release of viruses from infected persons. Copyright 2013 American Association for Aerosol Research

Combined impact of lead, cadmium, polychlorinated biphenyls and non-chemical risk factors on blood pressure in NHANES

High blood pressure is associated with exposure to multiple chemical and non-chemical risk factors, but epidemiological analyses to date have not assessed the combined effects of both chemical and non-chemical stressors on human populations in the context of cumulative risk assessment. We developed a novel modeling approach to evaluate the combined impact of lead, cadmium, polychlorinated biphenyls (PCBs), and multiple non-chemical risk factors on four blood pressure measures using data for adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (1999-2008). We developed predictive models for chemical and other stressors. Structural equation models were applied to account for complex associations among predictors of stressors as well as blood pressure. Models showed that blood lead, serum PCBs, and established non-chemical stressors were significantly associated with blood pressure. Lead was the chemical stressor most predictive of diastolic blood pressure and mean arterial pressure, while PCBs had a greater influence on systolic blood pressure and pulse pressure, and blood cadmium was not a significant predictor of blood pressure. The simultaneously fit exposure models explained 34%, 43% and 52% of the variance for lead, cadmium and PCBs, respectively. The structural equation models were developed using predictors available from public data streams (e.g., U.S. Census), which would allow the models to be applied to any U.S. population exposed to these multiple stressors in order to identify high risk subpopulations, direct intervention strategies, and inform public policy.

Modeling the airborne survival of influenza virus in a residential setting: the impacts of home humidification

BackgroundLaboratory research studies indicate that aerosolized influenza viruses survive for longer periods at low relative humidity (RH) conditions. Further analysis has shown that absolute humidity (AH) may be an improved predictor of virus survival in the environment. Maintaining airborne moisture levels that reduce survival of the virus in the air and on surfaces could be another tool for managing public health risks of influenza.MethodsA multi-zone indoor air quality model was used to evaluate the ability of portable humidifiers to control moisture content of the air and the potential related benefit of decreasing survival of influenza viruses in single-family residences. We modeled indoor AH and influenza virus concentrations during winter months (Northeast US) using the CONTAM multi-zone indoor air quality model. A two-story residential template was used under two different ventilation conditions - forced hot air and radiant heating. Humidity was evaluated on a room-specific and whole house basis. Estimates of emission rates for influenza virus were particle-size specific and derived from published studies and included emissions during both tidal breathing and coughing events. The survival of the influenza virus was determined based on the established relationship between AH and virus survival.ResultsThe presence of a portable humidifier with an output of 0.16 kg water per hour in the bedroom resulted in an increase in median sleeping hours AH/RH levels of 11 to 19% compared to periods without a humidifier present. The associated percent decrease in influenza virus survival was 17.5 - 31.6%. Distribution of water vapor through a residence was estimated to yield 3 to 12% increases in AH/RH and 7.8-13.9% reductions in influenza virus survival.ConclusionThis modeling analysis demonstrates the potential benefit of portable residential humidifiers in reducing the survival of aerosolized influenza virus by controlling humidity indoors.

The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model

BackgroundIn the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date.MethodsWe designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%), which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold.ResultsModel design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates.ConclusionsWe describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens), medication compliance, seasonality, and medical history on asthma outcomes (symptom-days, medication use, hospitalizations, and emergency room visits). The model can be used to evaluate building interventions and green building construction practices on pollutant concentrations, energy savings, and asthma healthcare utilization costs, and demonstrates the value of a simulation approach for studying complex diseases such as asthma.

Meta-Analytic Approaches for Multistressor Dose-Response Function Development: Strengths, Limitations, and Case Studies

For many policy analyses, including but not limited to cumulative risk assessments, it is important to characterize the individual and joint health effects of multiple stressors. With an increasing focus on psychosocial and other nonchemical stressors, this often includes epidemiological meta-analysis. Meta-analysis has limitations if epidemiological studies do not include all of the stressors of interest or do not provide multivariable outputs in a format necessary for risk assessment. Given these limitations, novel analytical methods are often needed to synthesize the published literature or to build upon available evidence. In this article, we discuss three recent case studies that highlight the strengths and limitations of meta-analytic approaches and other research synthesis techniques for human health risk assessment applications. First, a literature-based meta-analysis within a risk assessment context informed the design of a new epidemiological investigation of the differential toxicity of fine particulate matter constituents. Second, a literature synthesis for an effects-based cumulative risk assessment of hypertension risk factors led to a decision to develop new epidemiological associations using structural equation modeling. Third, discrete event simulation modeling was used to simulate the impact of changes in the built environment on environmental exposures and associated asthma outcomes, linking literature meta-analyses for key associations with a simulation model to synthesize all of the model components. These case studies emphasize the importance of conducting epidemiology with a risk assessment application in mind, the need for interdisciplinary collaboration, and the value of advanced analytical methods to synthesize epidemiological and other evidence for risk assessment applications.

Collection of Aerosolized Human Cytokines Using Teflon® Filters

Background Collection of exhaled breath samples for the analysis of inflammatory biomarkers is an important area of research aimed at improving our ability to diagnose, treat and understand the mechanisms of chronic pulmonary disease. Current collection methods based on condensation of water vapor from exhaled breath yield biomarker levels at or near the detection limits of immunoassays contributing to problems with reproducibility and validity of biomarker measurements. In this study, we compare the collection efficiency of two aerosol-to-liquid sampling devices to a filter-based collection method for recovery of dilute laboratory generated aerosols of human cytokines so as to identify potential alternatives to exhaled breath condensate collection. Methodology/Principal Findings Two aerosol-to-liquid sampling devices, the SKC® Biosampler and Omni 3000™, as well as Teflon® filters were used to collect aerosols of human cytokines generated using a HEART nebulizer and single-pass aerosol chamber setup in order to compare the collection efficiencies of these sampling methods. Additionally, methods for the use of Teflon® filters to collect and measure cytokines recovered from aerosols were developed and evaluated through use of a high-sensitivity multiplex immunoassay. Our results show successful collection of cytokines from pg/m3 aerosol concentrations using Teflon® filters and measurement of cytokine levels in the sub-picogram/mL concentration range using a multiplex immunoassay with sampling times less than 30 minutes. Significant degradation of cytokines was observed due to storage of cytokines in concentrated filter extract solutions as compared to storage of dry filters. Conclusions Use of filter collection methods resulted in significantly higher efficiency of collection than the two aerosol-to-liquid samplers evaluated in our study. The results of this study provide the foundation for a potential new technique to evaluate biomarkers of inflammation in exhaled breath samples.

Temporal trends in air pollution exposure inequality in Massachusetts

ABSTRACT Mounting evidence over the past several decades has demonstrated inequitable distribution of pollutants of ambient origin between sociodemographic groups in the United States. Most environmental inequality studies to date are cross‐sectional and used proximity‐based methods rather than modeled air pollution concentrations, limiting the ability to examine trends over time or the factors that drive exposure inequalities. In this paper, we use 1 km2 modeled PM2.5 and NO2 concentrations in Massachusetts over an 8‐year period and Census demographic data to quantify inequality between sociodemographic groups and to develop a more nuanced understanding of the drivers and trends in longitudinal air pollution inequality. Annual‐average population‐weighted PM2.5 and NO2 concentrations were highest for urban non‐Hispanic black populations (11.8 &mgr;g/m3 in 2003 and 8.4 &mgr;g/m3 in 2010, vs. 11.3 &mgr;g/m3 and 8.1 &mgr;g/m3 for urban non‐Hispanic whites) and urban Hispanic populations (15.9 ppb in 2005 and 13.0 ppb in 2010, vs. 13.0 ppb and 10.2 ppb for urban non‐Hispanic whites), respectively. While population groups experienced similar absolute decreases in exposure over time, disparities in population‐weighted concentrations increased over time when quantified by the Atkinson Index, a relative inequality measure. Exposure inequalities were approximately one order of magnitude greater for NO2 compared to PM2.5, were more pronounced in urban compared to rural geographies, and between racial/ethnic groups compared to income and educational attainment groups. Our results also revealed similar longitudinal PM2.5 and NO2 inequality trends using Census 2000 and Census 2010 data, indicating that spatio‐temporal shifts in air pollution may best explain observed trends in inequality. These findings enhance our understanding of factors that contribute to persistent inequalities and underscore the importance of targeted exposure reduction strategies aimed at vulnerable populations and neighborhoods. HIGHLIGHTSWe characterized longitudinal PM2.5 and NO2 inequality trends across Massachusetts.Exposure inequality increased in urban, but not rural areas.NO2 exposure inequality was greater in magnitude than PM2.5 inequality.Observed inequality trends likely driven by spatiotemporal pollution shifts.

Spatial Variability in ADHD-Related Behaviors Among Children Born to Mothers Residing Near the New Bedford Harbor Superfund Site

Abstract Attention-deficit/hyperactivity disorder (ADHD) has an uncertain etiology, with potential contributions from different risk factors such as prenatal environmental exposure to organochlorines and metals, social risk factors, and genetics. The degree to which geographic variability in ADHD is independent of, or explained by, risk factors may provide etiological insight. We investigated determinants of geographic variation in ADHD-related behaviors among children living near the polychlorinated biphenyl–contaminated New Bedford Harbor (NBH) Superfund site in Massachusetts. Participants were 573 children recruited at birth (1993–1998) who were born to mothers residing near the NBH site. We assessed ADHD-related behaviors at age 8 years using Conners’ Teacher Rating Scale–Revised: Long Version. Adjusted generalized additive models were used to smooth the association of pregnancy residence with ADHD-related behaviors and assess whether prenatal organochlorine or metal exposures, sociodemographic factors, or other factors explained spatial patterns. Models that adjusted for childs age and sex displayed significantly increased ADHD-related behavior among children whose mothers resided west of the NBH site during pregnancy. These spatial patterns persisted after adjusting for prenatal exposure to organochlorines and metals but were no longer significant after controlling for sociodemographic factors. The findings underscore the value of spatial analysis in identifying high-risk subpopulations and evaluating candidate risk factors.