Critical Review pubs.acs.org/est
Factors Shaping the Human Exposome in the Built Environment: Opportunities for Engineering Control Dongjuan Dai, Aaron J. Prussin, II, Linsey C. Marr,* Peter J. Vikesland,* Marc A. Edwards,* and Amy Pruden* Via Department of Civil and Environmental Engineering, Virginia Polytechnic Institute and State University, Blacksburg Virginia 24061, United States ABSTRACT: The “exposome” is a term describing the summation of one’s lifetime exposure to microbes and chemicals. Such exposures are now recognized as major drivers of human health and disease. Because humans spend ∼90% of their time indoors, the built environment exposome merits particular attention. Herein we utilize an engineering perspective to advance understanding of the factors that shape the built environment exposome and its influence on human wellness and disease, while simultaneously informing development of a framework for intentionally controlling the exposome to protect public health. Historically, engineers have been focused on controlling chemical and physical contaminants and on eradicating microbes; however, there is a growing awareness of the role of “beneficial” microbes. Here we consider the potential to selectively control the materials and chemistry of the built environment to positively influence the microbial and chemical components of the indoor exposome. Finally, we discuss research gaps that must be addressed to enable intentional engineering design, including the need to define a “healthy” built environment exposome and how to control it.
1. EXPOSOME: CAUSE OF A MAJORITY OF HUMAN ILLNESS It is widely accepted that the genetic model has failed to explain the majority of human disease or to provide many anticipated cures; rather, evidence now points to environmental factors as being responsible for approximately 90% of human illness.1 The term “exposome” has been recently introduced to describe one’s lifetime exposures to general external influences (e.g., climate, social status), specific external factors (e.g., chemical contaminants, environmental microbes, diet), and internal conditions (e.g., host metabolism, inflammation).2−10 To date, specific external exposures have been the primary focus of studies aimed at identifying risk factors for human disease, whereas general exposures to global and regional environmental factors have also been shown to influence health.11,12 Both increased urbanization (from 30% in 1950 to 54% in 2015 globally and from 64% to 83% in the U.S. over the same period)13 and the increased amount of time spent indoors (from 80% to >90% over the last 20 years in the U.S.)14 in the built environment (residences, workplaces, public buildings, etc.) point to the need to characterize the built environment exposome and the factors that shape it, especially within the context of its influence on human health and disease. Within the built environment, exposure to physical and chemical external factors, such as lead in water, gaseous and particulate pollutants in indoor air, and dust on surfaces is widely recognized for its effects on human health.15−17 Exposure to biological agents, including mold, pollen, © XXXX American Chemical Society
pathogens, insects, and their associated biochemicals can trigger various diseases, allergies, asthma, and sick building syndrome.18−21 Recently, the broad community of microbes that inhabit the built environment have gained attention as a fundamental component of indoor exposures.22,23 Highly diverse and complex microbial communities, known as “microbiomes”, inhabit all aspects of the built environment, including food, tap water, indoor air, and various surfaces (e.g., floors, mattresses, door knobs, keyboards).24−26 These microbial constituents are continually being ingested, inhaled, and subject to colonization of skin and mucous membranes. A revolution is underway conceptualizing the relationship between microbes and human health and we are rapidly moving from the simplistic assumption that microbes are “bad”, to the discovery of the coevolutionary, codependent, and beneficial roles many microbes play in preventing modern diseases, such as digestive disorders,27 obesity,28,29 cancer,30 diabetes,31 autism,32 heart disease,33 and mental disease.34 As the field of exposome science is still being conceptualized, it is critical that microbial aspects of the exposome be considered, both in terms of the microbial components themselves as well as their collective influence on other aspects of the exposome. Received: March 1, 2017 Revised: May 18, 2017 Accepted: June 7, 2017
A
DOI: 10.1021/acs.est.7b01097 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
Critical Review
Environmental Science & Technology
Vibrio cholerae, Salmonella enterica, Escherichia coli O157:H7). Exposure to these organisms can result in acute or chronic waterborne diseases and epidemics such as cholera, other forms of diarrhea, or gastroenteritis that remain as pervasive public health threats in many lesser developed countries.43,44 In recent decades, especially in more highly developed countries, a new generation of nonfecally derived, or “opportunistic” pathogens (e.g., Legionella pneumophila, Mycobacterium avium, Pseudomonas aeruginosa) has emerged as the primary source of drinking water related illness and deaths.45 Opportunistic pathogens are harbored by and grow within the biofilms of the water distribution system and the building plumbing environment itself (e.g., water heaters and shower heads), which makes their control particularly challenging.46−50 Exposure to opportunistic pathogens can lead to infections, particularly of the respiratory system, urinary tract, and skin and can result in pneumonia, pulmonary disease, as well as eye and skin irritations, especially among immunocompromised populations.40,51,52 In the U.S., L. pneumophila is now a primary cause of many water-related disease outbreaks,53 with the recent Legionnaire’s disease outbreak in Flint, Michigan illustrating the critical role that water chemistry and infrastructure play in its spread.54 The microbial ecology of the distribution system plays a key role in the proliferation of opportunistic pathogens, especially the presence of free-living amoebae that can protect, transport, and aid the survival, replication, and virulence of L. pneumophila and other opportunistic pathogens.55 Some free-living amoebae, such as Naegleria fowleri, are themselves pathogens and can have a high mortality rate (>97% for N. fowleri).56,57 Beyond explicit consideration of pathogens, exposure to the broader waterborne microbial community is beginning to gain attention. Interestingly, as far back as 1991, it was observed that the consumption of tap water that met drinking water standards correlated with higher incidence of gastrointestinal illness than the consumption of tap water subjected to treatment by reverse-osmosis, which eliminates virtually all microbes and chemicals.58 This result illustrates the likely influence of the drinking water exposome on the human gut microbiome, something that has been shown to be an important factor in gastrointestinal health as well as other diseases.59 Recently, Lee et al. observed a direct linkage between the drinking water microbiome and the gut microbiome in controlled studies conducted using germ-free mice.60 The co-occurrence of several bacterial lineages (Ralstonia, Sphingopyxis, Bacillus, E. coli, and Bosea) in the drinking water and the guts of the mice suggests direct transmission of bacteria from the water to the intestinal tract. A simple comparison of bacteria identified in drinking water with those reported in human microbiome databases reveals significant overlap (35 lineages belonging to five phyla) and is thus suggestive of a link between the two.61 It stands to reason that exposure to the broad microbial community present within drinking water results in inoculum of the human microbiome of the gut, skin, mouth, and possibly the lungs via aspiration. Exposure to particles in water can also elicit health impacts. Drinking water typically contains some quantity of submicrometer particles, including inorganics (e.g., clays, asbestos, carbonate salts, and metal rusts) and organic colloidal material (e.g., natural organic matter) that pass though the treatment process or are generated by pipe corrosion during distribution.42,62,63 Such particles can result in aesthetically displeasing water and may also pose real health concerns. For example, particulate lead in drinking water can lodge in the digestive
The physical, chemical, and microbial components of the exposome are highly interrelated. For example, inhalation of house dust is accompanied by exposure to microorganisms and allergens associated with the dust particles.35,36 Another example is free chlorine, a strong oxidizing chemical routinely added to municipal water systems as a biocide to kill pathogens and limit microbial growth, but which also produces a range of unwanted disinfection byproducts (DBPs).37−39 Several chlorination byproducts are known to be toxic and carcinogenic, while some opportunistic pathogens, such as certain Mycobacteria, can actually be selected for, rather than inactivated, by the use of free chlorine.40 Here we seek a holistic and comprehensive understanding of the exposome in the built environment, including the summation of all physical, chemical, and microbial components and their interrelationships, with a specific emphasis on developing a framework for informing design and control in a manner that promotes human health and well-being. Herein we discuss the indoor exposome by considering three distinct, yet highly interrelated exposure media: water, air, and surfaces (Figure 1). The surface-borne exposome is closely
Figure 1. Critical components of the built environment exposome. The built environmental exposome includes physical, chemical, and microbial exposures from highly interrelated components: water, air, and surfaces.
related to the waterborne and airborne exposomes because of transfer between the different media. Gases, liquids, and particles may be emitted from water or resuspended from surfaces into air. The reverse process of deposition from air or water onto surfaces also occurs. Standing water may allow for transfer directly between water and surfaces.22 While we discuss each exposure medium individually, we recognize that altering one dimension of the exposome will likely affect the others. 1.1. Waterborne Exposome and Human Health. The wonder and modern necessity of indoor plumbing is a bulwark of civilization, with access to clean water for drinking and personal hygiene having been credited for wide declines in waterborne sickness and disease.41 Even the highest standards of treatment still result in water containing particles, chemicals, and microorganisms. These constituents can originate in the source water, form during treatment, or be generated in the pipe networks used to distribute the water.26,42 Thus, drinking water represents an often underappreciated and unavoidable source of exposure to microbes and chemicals. Consideration of drinking water based microbial exposures has historically focused on fecally derived pathogens (e.g., B
DOI: 10.1021/acs.est.7b01097 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
Critical Review
Environmental Science & Technology tract and pose a long-term source of lead poisoning.62 There is also indirect evidence that other particulates, such as manganese and asbestos fibers present in aerosols,64 can be inhaled and potentially result in neurotoxicity and carcinoma.65−67 Engineered nanoparticles (e.g., silver and titanium dioxide) from consumer products can pass though the water treatment process and reach finished water at concentrations up to tens of ng/L.68 Furthermore, nanoparticles and microplastics released from clothing and paint can also end up in drinking water.69 The adverse impacts of nanoparticles on immune and digestive systems (e.g., toxicity, cell death, inflammation, oxidative stress disorders) have been reported in both in vitro and animal studies.70 Both water chemistry and chemical contaminants can significantly impact human health. Researchers have found that drinking acidified rather than pH-neutral water significantly altered the gut microbiome of mice, thus resulting in a reduced risk of diabetes.71,72 This is direct evidence that fundamental aspects of water chemistry may influence at least one prevalent modern human disease, diabetes. Disinfectants, their byproducts, and trace metals, are perhaps the best-studied chemicals in drinking water with respect to human health.73,74 Free chlorine, chloramines, and other disinfectants are widely used in drinking water treatment and distribution systems to limit the downstream growth of microbes. Several DBPs, including four trihalomethanes, five haloacetic acids, bromate, and chlorite, are regulated in drinking water in many countries, including the U.S.75 In addition to these regulated DBPs, there are hundreds of others, many of which remain unidentified and have lesser-known toxicities.76 Trace metals are commonly detected in drinking water, resulting from the source water, water mains or building pipe materials.77 Lead and arsenic are two notorious examples.78 Lead in drinking water results in increased adverse health impacts, such as high organ toxicity, developmental neurotoxicity, and reproductive dysfunction.79,80 Arsenic in drinking water causes numerous well-known adverse health effects, such as skin lesions, lung and bladder cancer, neurological issues, high blood pressure, and cardiovascular disease,81 while it has also recently been found to perturb the gut microbiome and metabolism.81 Biotoxins represent a class of harmful constituents at the biological-chemical interface. A recent example that gained widespread attention are the algal toxins produced by algal blooms in some source waters used for drinking water supply.82 Algal blooms typically result from excess nutrients in source water as a result of nonpoint source pollution. The algal biotoxins of greatest concern include the microcystin group, cylindrospermopsin, and anatoxin-a, each of which exhibits different toxicity mechanisms (e.g., neurotoxicity, protein phosphatase inhibition).83 Ingestion or skin contact with drinking water containing sufficiently high levels of these biotoxins can result in acute reactions, such as the poisoning of neural systems and the liver, abdominal pain, diarrhea, vomiting, and pneumonia.84,85 Further, long-term exposure to low levels of microcystins and cylindrospermopsin may result in chronic liver injury and promote tumor growth.86 Several cyanotoxins are regulated in drinking water in some countries and states (e.g., Australia, Canada, New Zealand, and four U.S. states: Minnesota, Ohio, Oregon, and Vermont) and there is an increased likelihood of expanded monitoring of public water systems in the U.S. in the near future.83 The recent shut down of the municipal drinking water supply in Toledo, Ohio in
201487 exemplified a proactive measure to warn the public when the microcystin levels were higher than the advisory value (1.6 μg/L for adults and school-age children) and brought attention to the need for improved policy to address algal toxins in drinking water. 1.2. Airborne Exposome and Human Health. While pollutants in outdoor air can contribute to exposures within the built environment, there are also sources that produce distinct concerns indoors. Pollutants of traditional concern indoors include carbon monoxide, radon, volatile organic compounds (VOCs), and particulate matter (PM).88−90 Carbon monoxide is produced by incomplete combustion, such as from a fireplace or malfunctioning gas burners, and causes acute effects, ranging from headache at low levels to coma and death at high concentrations.91 Radon gas occurs naturally in soil in some regions and can infiltrate into buildings through cracks in the foundation and basement. On average, radon accounts for the plurality of an individual’s total exposure to radioactivity when considering background, medical, and other sources.92 VOCs are a large class of compounds, including many of those designated to characterize toxic air by the U.S. Environmental Protection Agency.93 Formaldehyde is a wellknown example that is commonly emitted in the built environment by the off-gassing of building materials, furniture, and carpets.94−96 Formaldehyde exposure can induce acute poisoning, increase the risk of cancer, cause reproductive problems, decrease pulmonary function, and increase the risk of asthma and allergies.94,97 Cleaning products, personal care products, paint, adhesives, and pesticides can be additional sources of VOCs.98 Certain metabolites produced by microbes are also VOCs.89,99 Exposure to VOCs, especially during the early postnatal stage, can affect neurodevelopment and growth, and increase the risks of childhood respiratory diseases, such as asthma and wheezing.100,101 Occurring over a large size range of ∼0.001 to ∼100 μm, PM is a complex chemical mixture that may include acidic substances, organic compounds, oxidative species, pesticides, herbicides, and metals.102,103 Exposure to PM via inhalation, especially the fraction smaller than 10 μm (PM10) and 2.5 μm (PM2.5), is correlated with an array of adverse health effects, such as respiratory irritation, decreased lung function, lung cancer, cardiovascular disease, cerebrovascular disease, and mortality.88,90 Besides outdoor sources, dust that is resuspended from indoor surfaces, such as flooring, furniture, and clothing, contributes to indoor PM. Exposure to house dust is highly correlated with an increased risk of allergies, asthma, and wheezing.20,36 Herbicides in house dust, most notably chlorthal, are associated with increased risk of childhood acute lymphoblastic leukemia.104 Furthermore, heavy metals in house dust can result in increased risk of cancer and severe disturbance to the cardiovascular and central nervous systems.105,106 Some indoor PM may be of biological origin, such as pollen, dust mites, pet and human dander, or microbes. The dust mite has long been considered a menace in the indoor environment, as its feces act as allergens in house dust, causing allergic rhinitis and asthma. 21 Inhalation of pathogenic bacteria (e.g., Streptococcus agalactiae) and viruses (e.g., rhinovirus, influenza) can result in acute infection and disease outbreaks. A large body of work has recently been devoted to documenting the composition of the indoor air microbiome, the factors shaping it, its interrelationship with human occupants, and its influence on the human microbiome.107−111 For example, inhalation of C
DOI: 10.1021/acs.est.7b01097 Environ. Sci. Technol. XXXX, XXX, XXX−XXX
Critical Review
Environmental Science & Technology
2. BUILT ENVIRONMENT EXPOSOME CHARACTERISTICS AND CONTROLLING FACTORS Recognizing the close relationships between the built environment exposome and human health effects, as described above, we now describe the characteristics of the exposome in the built environment and specifically outline critical factors that affect and control the exposome in water, in air, and on surfaces. 2.1. Waterborne Exposome. Exposure to constituents in drinking water results from complex interactions among several factors, including global/regional influences (e.g., climate, source water, season), treatment technology (e.g., biofiltration, disinfectant use), water distribution infrastructure (e.g., age, type, pipe maintenance history), building plumbing (e.g., pipe material, configuration), point-of-use treatment (e.g., on-site disinfection, whole-house filtration), and water use patterns (e.g., use frequency, type, setting of water heaters).26,133−136 DBPs represent an important category of chemicals in water. More than 600 DBPs have been identified in disinfected drinking water, but only a small number of them have been quantified and evaluated for toxicity.38 Some commonly monitored DBPs, such as trihalomethanes (THMs) and bromate, are under strict regulation in many countries (e.g., in the U.S. total THMs < 0.08 mg/L, bromate
