Elizabeth D. Hilborn

Particulate matter in cigarette smoke alters iron homeostasis to produce a biological effect.

RATIONALE Lung injury after cigarette smoking is related to particle retention. Iron accumulates with the deposition of these particles. OBJECTIVES We tested the postulate that (1) injury after smoking correlates with exposure to the particulate fraction of cigarette smoke, (2) these particles alter iron homeostasis, triggering metal accumulation, and (3) this alteration in iron homeostasis affects oxidative stress and inflammation. METHODS Rats and human respiratory epithelial cells were exposed to cigarette smoke, filtered cigarette smoke, and cigarette smoke condensate (the particulate fraction of smoke), and indices of iron homeostasis, oxidative stress, and inflammatory injury were determined. Comparable measures were also evaluated in nonsmokers and smokers. MEASUREMENTS AND MAIN RESULTS After exposure of rats to cigarette smoke, increased lavage concentrations of iron and ferritin, serum ferritin levels, and nonheme iron concentrations in the lung and liver tissue all increased. Lavage ascorbate concentrations were decreased, supporting an oxidative stress. After filtering of the cigarette smoke to remove particles, most of these changes were reversed. Exposure of cultured respiratory epithelial cells to cigarette smoke condensate caused a similar accumulation of iron, metal-dependent oxidative stress, and increased IL-8 release. Lavage samples in healthy smokers and smoking patients with chronic obstructive pulmonary disease revealed elevated concentrations of both iron and ferritin relative to healthy nonsmokers. Lavage ascorbate decreased with cigarette smoking. Serum iron and ferritin levels among smokers were increased, supporting systemic accumulation of this metal after cigarette smoke exposure. CONCLUSIONS We conclude that cigarette smoke particles alter iron homeostasis, both in the lung and systemically.

Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa.

Background Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexisting risk factors and frequently require hospitalization. Objectives The objectives of this report are to alert professionals of the impact of OPPPs, the fact that 30% of the population may be exposed to OPPPs, and the need to develop means to reduce OPPP exposure. We herein present a review of the epidemiology and ecology of these three bacterial OPPPs, specifically to identify common and unique features. Methods A Water Research Foundation–sponsored workshop gathered experts from across the United States to review the characteristics of OPPPs, identify problems, and develop a list of research priorities to address critical knowledge gaps with respect to increasing OPPP-associated disease. Discussion OPPPs share the common characteristics of disinfectant resistance and growth in biofilms in water distribution systems or premise plumbing. Thus, they share a number of habitats with humans (e.g., showers) that can lead to exposure and infection. The frequency of OPPP-infected individuals is rising and will likely continue to rise as the number of at-risk individuals is increasing. Improved reporting of OPPP disease and increased understanding of the genetic, physiologic, and structural characteristics governing the persistence and growth of OPPPs in drinking water distribution systems and premise plumbing is needed. Conclusions Because broadly effective community-level engineering interventions for the control of OPPPs have yet to be identified, and because the number of at-risk individuals will continue to rise, it is likely that OPPP-related infections will continue to increase. However, it is possible that individuals can take measures (e.g., raise hot water heater temperatures and filter water) to reduce home exposures. Citation Falkinham JO III, Hilborn ED, Arduino MJ, Pruden A, Edwards MA. 2015. Epidemiology and ecology of opportunistic premise plumbing pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa. Environ Health Perspect 123:749–758; http://dx.doi.org/10.1289/ehp.1408692

Structural analysis of biofilm formation by rapidly and slowly growing nontuberculous mycobacteria.

ABSTRACT Mycobacterium avium complex (MAC) and rapidly growing mycobacteria (RGM) such as M. abscessus, M. mucogenicum, M. chelonae, and M. fortuitum, implicated in health care-associated infections, are often isolated from potable water supplies as part of the microbial flora. To understand factors that influence growth in their environmental source, clinical RGM and slowly growing MAC isolates were grown as biofilm in a laboratory batch system. High and low nutrient levels were compared, as well as stainless steel and polycarbonate surfaces. Biofilm growth was measured after 72 h of incubation by enumeration of bacteria from disrupted biofilms and by direct quantitative image analysis of biofilm microcolony structure. RGM biofilm development was influenced more by nutrient level than by substrate material, though both affected biofilm growth for most of the isolates tested. Microcolony structure revealed that RGM develop several different biofilm structures under high-nutrient growth conditions, including pillars of various shapes (M. abscessus and M. fortuitum) and extensive cording (M. abscessus and M. chelonae). Although it is a slowly growing species in the laboratory, a clinical isolate of M. avium developed more culturable biofilm in potable water in 72 h than any of the 10 RGM examined. This indicates that M. avium is better adapted for growth in potable water systems than in laboratory incubation conditions and suggests some advantage that MAC has over RGM in low-nutrient environments.

Cyanotoxins in inland lakes of the United States: Occurrence and potential recreational health risks in the EPA National Lakes Assessment 2007

A large nation-wide survey of cyanotoxins (1161 lakes) in the United States (U.S.) was conducted during the EPA National Lakes Assessment 2007. Cyanotoxin data were compared with cyanobacteria abundance- and chlorophyll-based World Health Organization (WHO) thresholds and mouse toxicity data to evaluate potential recreational risks. Cylindrospermopsins, microcystins, and saxitoxins were detected (ELISA) in 4.0, 32, and 7.7% of samples with mean concentrations of 0.56, 3.0, and 0.061μg/L, respectively (detections only). Co-occurrence of the three cyanotoxin classes was rare (0.32%) when at least one toxin was detected. Cyanobacteria were present and dominant in 98 and 76% of samples, respectively. Potential anatoxin-, cylindrospermopsin-, microcystin-, and saxitoxin-producing cyanobacteria occurred in 81, 67, 95, and 79% of samples, respectively. Anatoxin-a and nodularin-R were detected (LC/MS/MS) in 15 and 3.7% samples (n=27). The WHO moderate and high risk thresholds for microcystins, cyanobacteria abundance, and total chlorophyll were exceeded in 1.1, 27, and 44% of samples, respectively. Complete agreement by all three WHO microcystin metrics occurred in 27% of samples. This suggests that WHO microcystin metrics based on total chlorophyll and cyanobacterial abundance can overestimate microcystin risk when compared to WHO microcystin thresholds. The lack of parity among the WHO thresholds was expected since chlorophyll is common amongst all phytoplankton and not all cyanobacteria produce microcystins.

A pilot study of global positioning system/geographical information system measurement of residential proximity to agricultural fields and urinary organophosphate metabolite concentrations in toddlers

This pilot study enrolled 20 children between the ages of 11 and 17 months in Imperial County, California to assess childrens pesticide exposure and residential proximity to agricultural fields. We compared parental self-report of residential proximity to agricultural fields to measurements using global positioning system/geographical information system (GPS/GIS) technology, and we assessed the relationship between residential proximity to agricultural fields and a biomarker of organophosphate (OP) pesticide exposure. Questionnaires were administered twice, 4 weeks apart, to determine self-reported residential proximity to agricultural fields. Urine samples were collected at each contact to measure OP metabolites. Actual residential proximity to the closest agricultural field and number of fields was within 1 mile to the west were measured using GPS/GIS. Self-report of living proximity to agricultural fields agreed with GPS/GIS measurement 75% of the time during the initial interview, compared to 66% agreement during the second interview. Presence of urinary metabolites suggests that OP exposure was ubiquitous: creatinine-adjusted total urinary dimethyl values ranged from 1.60 to 516.00 μg/g creatinine, and total diethyl ranged from 2.70 to 134.84 μg/g creatinine. No association was found between urinary OP metabolites and residential to field proximity. These results suggest that initial self-report of living proximity to agricultural fields may be more accurate than follow-up self-report. Limitations in this pilot study prevent determination of whether self-report is an accurate measure of proximity.

One health and cyanobacteria in freshwater systems: Animal illnesses and deaths are sentinel events for human health risks

Harmful cyanobacterial blooms have adversely impacted human and animal health for thousands of years. Recently, the health impacts of harmful cyanobacteria blooms are becoming more frequently detected and reported. However, reports of human and animal illnesses or deaths associated with harmful cyanobacteria blooms tend to be investigated and reported separately. Consequently, professionals working in human or in animal health do not always communicate findings related to these events with one another. Using the One Health concept of integration and collaboration among health disciplines, we systematically review the existing literature to discover where harmful cyanobacteria-associated animal illnesses and deaths have served as sentinel events to warn of potential human health risks. We find that illnesses or deaths among livestock, dogs and fish are all potentially useful as sentinel events for the presence of harmful cyanobacteria that may impact human health. We also describe ways to enhance the value of reports of cyanobacteria-associated illnesses and deaths in animals to protect human health. Efficient monitoring of environmental and animal health in a One Health collaborative framework can provide vital warnings of cyanobacteria-associated human health risks.

Improving waterborne disease outbreak investigations

This article is a summary of discussions held and recommendations made at a workshop for the investigation of waterborne disease outbreaks in Chapel Hill, North Carolina, December 7‐8, 1998. Suspected waterborne outbreaks in the United States are primarily investigated by state and local public health officials who may infrequently conduct enteric disease outbreak investigations. Thus, it is important that officials have a formal plan to ensure that epidemiological studies are methodologically sound and that effective collaboration occurs among the epidemiologists, scientists, and engineers who will conduct the investigations. Laboratory support to analyze water samples and clinical specimens should be arranged well in advance of when services may be needed. Enhanced surveillance activities can help officials recognize additional outbreaks and initiate investigations in a timely manner. Epidemiologists should pay more attention early in the investigation to study design, questionnaire development, and sources of bias, especially recall bias, that may affect the interpretation of observed associations. Improved investigations can increase our knowledge about important etiological agents, water systems deficiencies, and sources of water contamination so that waterborne outbreaks can be more effectively prevented.

The Association between Dust Storms and Daily Non-Accidental Mortality in the United States, 1993–2005

Background: The impact of dust storms on human health has been studied in the context of Asian, Saharan, Arabian, and Australian storms, but there has been no recent population-level epidemiological research on the dust storms in North America. The relevance of dust storms to public health is likely to increase as extreme weather events are predicted to become more frequent with anticipated changes in climate through the 21st century. Objectives: We examined the association between dust storms and county-level non-accidental mortality in the United States from 1993 through 2005. Methods: Dust storm incidence data, including date and approximate location, are taken from the U.S. National Weather Service storm database. County-level mortality data for the years 1993–2005 were acquired from the National Center for Health Statistics. Distributed lag conditional logistic regression models under a time-stratified case-crossover design were used to study the relationship between dust storms and daily mortality counts over the whole United States and in Arizona and California specifically. End points included total non-accidental mortality and three mortality subgroups (cardiovascular, respiratory, and other non-accidental). Results: We estimated that for the United States as a whole, total non-accidental mortality increased by 7.4% (95% CI: 1.6, 13.5; p = 0.011) and 6.7% (95% CI: 1.1, 12.6; p = 0.018) at 2- and 3-day lags, respectively, and by an average of 2.7% (95% CI: 0.4, 5.1; p = 0.023) over lags 0–5 compared with referent days. Significant associations with non-accidental mortality were estimated for California (lag 2 and 0–5 day) and Arizona (lag 3), for cardiovascular mortality in the United States (lag 2) and Arizona (lag 3), and for other non-accidental mortality in California (lags 1–3 and 0–5). Conclusions: Dust storms are associated with increases in lagged non-accidental and cardiovascular mortality. Citation: Crooks JL, Cascio WE, Percy MS, Reyes J, Neas LM, Hilborn ED. 2016. The association between dust storms and daily non-accidental mortality in the United States, 1993–2005. Environ Health Perspect 124:1735–1743; http://dx.doi.org/10.1289/EHP216

Extreme Precipitation and Emergency Room Visits for Gastrointestinal Illness in Areas with and without Combined Sewer Systems: An Analysis of Massachusetts Data, 2003-2007.

Background Combined sewer overflows (CSOs) occur in combined sewer systems when sewage and stormwater runoff are released into water bodies, potentially contaminating water sources. CSOs are often caused by heavy precipitation and are expected to increase with increasing extreme precipitation associated with climate change. Objectives The aim of this study was to assess whether the association between heavy rainfall and rate of emergency room (ER) visits for gastrointestinal (GI) illness differed in the presence of CSOs. Methods For the study period 2003–2007, time series of daily rate of ER visits for GI illness and meteorological data were organized for three exposure regions: a) CSOs impacting drinking water sources, b) CSOs impacting recreational waters, c) no CSOs. A distributed lag Poisson regression assessed cumulative effects for an 8-day lag period following heavy (≥ 90th and ≥ 95th percentile) and extreme (≥ 99th percentile) precipitation events, controlling for temperature and long-term time trends. Results The association between extreme rainfall and rate of ER visits for GI illness differed among regions. Only the region with drinking water exposed to CSOs demonstrated a significant increased cumulative risk for rate (CRR) of ER visits for GI for all ages in the 8-day period following extreme rainfall: CRR: 1.13 (95% CI: 1.00, 1.28) compared with no rainfall. Conclusions The rate of ER visits for GI illness was associated with extreme precipitation in the area with CSO discharges to a drinking water source. Our findings suggest an increased risk for GI illness among consumers whose drinking water source may be impacted by CSOs after extreme precipitation. Citation Jagai JS, Li Q, Wang S, Messier KP, Wade TJ, Hilborn ED. 2015. Extreme precipitation and emergency room visits for gastrointestinal illness in areas with and without combined sewer systems: an analysis of Massachusetts data, 2003–2007. Environ Health Perspect 123:873–879; http://dx.doi.org/10.1289/ehp.1408971

Molecular Comparison of Mycobacterium avium Isolates from Clinical and Environmental Sources

ABSTRACT We collected Mycobacterium avium isolates from clinical and drinking-water sources and compared isolates among themselves and to each other using molecular methods. Four clinical isolates were related to water isolates. Groups of indistinguishable clinical isolates were identified. The groups of identical clinical isolates suggest a common source of exposure.