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Exposures and Health Outcomes in Relation to Bioaerosol Emissions From Composting Facilities: A Systematic Review of Occupational and Community Studies

The number of composting sites in Europe is rapidly increasing, due to efforts to reduce the fraction of waste destined for landfill, but evidence on possible health impacts is limited. This article systematically reviews studies related to bioaerosol exposures within and near composting facilities and associated health effects in both community and occupational health settings. Six electronic databases and bibliographies from January 1960 to July 2014 were searched for studies reporting on health outcomes and/or bioaerosol emissions related to composting sites. Risk of bias was assessed using a customized score. Five hundred and thirty-six papers were identified and reviewed, and 66 articles met the inclusion criteria (48 exposure studies, 9 health studies, 9 health and exposure studies). Exposure information was limited, with most measurements taken in occupational settings and for limited time periods. Bioaerosol concentrations were highest on-site during agitation activities (turning, shredding, and screening). Six studies detected concentrations of either Aspergillus fumigatus or total bacteria above the English Environment Agency’s recommended threshold levels beyond 250 m from the site. Occupational studies of compost workers suggested elevated risks of respiratory illnesses with higher bioaerosol exposures. Elevated airway irritation was reported in residents near composting sites, but this may have been affected by reporting bias. The evidence base on health effects of bioaerosol emissions from composting facilities is still limited, although there is sufficient evidence to support a precautionary approach for regulatory purposes. While data to date are suggestive of possible respiratory effects, further study is needed to confirm this and to explore other health outcomes.

The number of composting sites in Europe is rapidly increasing, due to efforts to reduce the fraction of waste destined for landfill, but evidence on possible health impacts is limited. This article systematically reviews studies related to bioaerosol exposures within and near composting facilities and associated health effects in both community and occupational health settings. Six electronic databases and bibliographies from January 1960 to July 2014 were searched for studies reporting on health outcomes and/or bioaerosol emissions related to composting sites. Risk of bias was assessed using a customized score. Five hundred and thirty-six papers were identified and reviewed, and 66 articles met the inclusion criteria (48 exposure studies, 9 health studies, 9 health and exposure studies). Exposure information was limited, with most measurements taken in occupational settings and for limited time periods. Bioaerosol concentrations were highest on-site during agitation activities (turning, shredding, and screening). Six studies detected concentrations of either Aspergillus fumigatus or total bacteria above the English Environment Agency's recommended threshold levels beyond 250 m from the site. Occupational studies of compost workers suggested elevated risks of respiratory illnesses with higher bioaerosol exposures. Elevated airway irritation was reported in residents near composting sites, but this may have been affected by reporting bias. The evidence base on health effects of bioaerosol emissions from composting facilities is still limited, although there is sufficient evidence to support a precautionary approach for regulatory purposes. While data to date are suggestive of possible respiratory effects, further study is needed to confirm this and to explore other health outcomes.
Waste management policy is rapidly evolving, largely because European countries are running out of space for landfill sites. Further, poor waste management contributes to climate change and threatens environmental sustainability. It is estimated that each tonne of food waste diverted from landfill to composting (BMW) destined for landfill (Council Directive, 1999). Under the proposal, targets were set to recycle (including composting) at least 33% of household waste by 2015.
During the last decade there has been a rise in the number of large-scale composting facilities, as well as the introduction of a wide range of more advanced composting technologies. The majority of composting in the United Kingdom is completed in open windrows, and in 2007 approximately 90% of the total composting in the United Kingdom was undertaken using this method (Sykes et al., 2007). As material is in the open air, the process generates substantial potential emissions and exposures. Newer indoor facilities known as in-vessel composting facilities (IVC) still have some open-air processes, usually as part of the final maturation phase (Smith et al., 2009). Composting yields significant concentrations of bioaerosols (Wheeler et al., 2001;Taha et al., 2006). Bioaerosols are airborne biological particles, microbial fragments and constituents of cells, which may be viable or nonviable, and consist of fungi, bacteria, pollen, and fragments, constituents, particulate matter (PM 10 ), and by-products of cells (Douwes et al., 2003;Dowd and Maier, 2000;Viegas et al., 2014). A Health and Safety Executive (HSE) report in 2003 highlighted some studies where site workers demonstrated adverse health effects from occupational exposure to bioaerosols produced during composting (Swan et al., 2003). Further, there is increasing public concern regarding potential health impacts within communities surrounding the sites (Clapham, 2008;Gray, 2009).

BIOAEROSOLS EMITTED DURING COMPOSTING
The process of composting is often divided into three major stages (sanitization, stabilization, and maturation) and involves the interrelated activities of a diverse range of microorganisms (Searl, 2008;Taha et al., 2007). These microorganisms become airborne, giving rise to fugitive emissions during the composting process, particularly during agitation activities, such as shredding, turning, and screening (Taha et al., 2006). The bioaerosol components studied and identified as potentially harmful (Searl, 2008;Swan et al., 2003) are: • Fungi and fungal spores-including the thermotolerant species Aspergillus fumigatus. • Bacteria-including gram-negative bacteria and the spore-producing gram-positive bacteria actinomycetes. • Endotoxin-structural components of some bacteria released through cell wall damage, including lipopolysaccharides (LPS) or lipooligo-saccharides (LOS). • Dust or particulate matter (PM) containing microbial fragments. • Beta (1→3) glucans-polysaccharides found in the cell walls of certain fungi, particularly Aspergillus species.
It is possible that mycotoxins, which are toxic secondary metabolites of fungi (one of the most potent of these is aflatoxin, which is mainly produced by Aspergillus flavus) (Searl, 2008;Swan et al., 2003), may also be emitted during the composting process. However, there is no firm evidence to suggest this. The main routes of exposure to bioaerosols are through ingestion and inhalation. The risk of occupational exposure to bioaerosols via ingestion may be controlled by application of good hygiene practices (Swan et al., 2003). Exposure to bioaerosols through inhalation is of most concern. Once airborne, bioaerosols may travel considerable distances and be potentially inhaled by workers at the composting sites, as well as nearby residents.
The Environment Agency for England (and Wales until 2013; now referred to as the Environment Agency) published a position statement with provisional guidance for composting operators when applying for an operating permit (Environment Agency, 2010). It states that acceptable levels of bioaerosols, measured using the standardized sampling protocol (Association for Organics Recycling [AfOR], 2009), above upwind background concentrations, need to be maintained at 250 m or at the nearest sensitive receptor (such as a dwelling or place of work), whichever is closer, to protect public health, as bioaerosol concentrations are considered to generally reduce to nearbackground levels within 250 m (Wheeler et al., 2001). The acceptable levels are: • 1000 cfu/m 3 for total bacteria.
These levels are guidelines and are not based upon dose-response relationships or health measures. There are no current guideline levels for endotoxins in the United Kingdom.
There are no apparent existing guidelines for community levels in other countries to our knowledge, but a number of countries published occupational limit values. The Federal Ministry for Environment, Nature Conservation and Nuclear Safety (BUNR) in Germany suggest a minimum distance of 300 m for enclosed installations, and 500 m for open-windrow composting for facilities processing 3000 kg or more, but do not provide any acceptable limits for bioaerosol components (BUNR, 2002). In 2010 the Dutch Expert Committee on Occupational Safety (DECOS) proposed an occupational exposure limit for airborne endotoxin of 90 Endotoxin per cubic meter (EU/m 3 ) (8-h time-weighted average) (DECOS, 2010). The Federal Institute for Occupational Safety and Health (BAUA) in Germany have a regulatory occupational limit for mesophilic fungus (includes Aspergillus sp.) of 50,000 cfu/m 3 in breathable air in the workplace (BAUA, 2013). In the United Kingdom, there are no regulatory occupational limits for endotoxins or fungi, but the Health and Safety Executive (HSE) do provide composting facility employers with guidance on how to comply with the Control of Substances Hazardous to Health (COSHH) regulations to control exposure and protect workers' health (HSE, 2011), with guidance on respiratory protective equipment (HSE, 2013).

POTENTIAL HEALTH EFFECTS OF BIOAEROSOLS FROM COMPOSTING FACILITIES
Dependent on particle size, bioaerosols may penetrate deep into the lungs and become embedded in alveoli (Douwes et al., 2003;Ivens, 1999). For the species of bioaerosols emitted from composting facilities, principal types of health effects in humans have been identified (Lacey and Dutkiewicz, 1994). These include but are not limited to: 1. Allergic asthma, rhinitis, hypersensitivity pneumonitis (HP)/extrinsic allergic alveolitis, allergic bronchopulmonary aspergillosis (ABPA), eye and skin irritations 2. Toxic non-allergic asthma, rhinitis, mucous membrane irritations (MMI), chronic bronchitis, chronic airway obstruction such as chronic obstructive pulmonary disease (COPD), organic dust toxic syndrome (ODTS), toxic pneumonitis. 3. Infectious aspergillosis, zygomycosis; immunocompromised individuals are more susceptible at lower concentrations of the relevant pathogens.
Further animal studies suggested high levels of endotoxin exposure may result in elevated inflammatory response in pregnant rats (Huffman et al., 2004) and may also be damaging to an animal fetus (Duncan et al., 2002(Duncan et al., , 2003Ando et al.1988). Elevated inflammatory responses have also been found in humans working in agricultural settings (May et al., 2012;Poole et al., 2010).
There are currently no apparent published systematic reviews available of health impacts from exposure to bioaerosols specific to composting, but a comprehensive report on health risks was conducted by the UK Institute of Occupational Medicine (IOM), published in 2008 (Searl, 2008). This reviewed literature on exposure and associated health effects from bioaerosol emissions from the waste management industry, including but not limited to waste composting (Searl, 2008). The report identified few studies of health impacts of bioaerosols, with most evidence derived from studies not specific to waste composting. More recently, a literature review by Wéry (2014) on bioaerosols from composting facilities has been published, which provides a broad overview of the issues in this subject area. The aim of this study was to provide an up-to-date systematic review of occupational and community studies measuring concentrations of bioaerosols and/or assessing health effects associated with bioaerosol emissions within and nearby composting plants.

METHODOS
Methods were developed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria (Moher et al., 2009), and also informed by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria (Stroup et al., 2000).

Search Strategy
A literature search was conducted across six electronic databases, (Medline, Embase, PubMed, Science Direct, Web of Science, and Springerlink). Gray literature was identified using Internet-wide search engines (Google and Google Scholar) and one university database (Cranfield University, UK, included as the institution has conducted a number of relevant studies). Two searches were performed, to identify both health-based and exposure-based studies; example search strings used are supplied in Appendices 1 and 2, respectively. The search strings were inputted within the title and abstract fields of the electronic databases. Hand searching of bibliographies of the papers identified was also conducted.
Search strategies were developed with assistance from an academic librarian for health and exposure studies relating to bioaerosols from composting, adapted to each of the individual databases. Search terms for general health and specific health outcomes (e.g., asthma, aspergillosis) were employed. References were downloaded into Endnote X7, a referencing software program, and duplicates were removed.

Study Selection
After excluding duplicates, the records identified by the searches were assessed for inclusion in two steps. All retrieved references were first screened for relevance on title and abstract using predefined inclusion and exclusion criteria. Full texts of potentially relevant articles were then retrieved and reassessed for eligibility. Each step was conducted by an independent reviewer (CP, EL, PD), and any uncertainties or disputes were resolved through discussion, or with an additional reviewer (AH).
Studies included in the review had to meet all of the following criteria: • The study was published in English between January 1960 and July 2014. • The study concerned exposure or health effects relating to bioaerosols (organisms and their cellular constituents) emitted from composting sites. • The study contained results that could be extracted into one or both an exposure measurements table or a health effects table relating to monitored bioaerosol components. • The study was either peer reviewed or was published by a recognized institution.
Studies were excluded if: • They did not concern waste composting.
• They did not concern bioaerosols. • They did not include any original data.
• They were review papers, although the reference list was still searched to identify any other potential relevant studies. • They were unavailable in English.
• They were toxicological studies in animals.
• Full texts were unavailable.
• If the paper only concerned microbial volatile organic compounds (MVOCs).

Quantitative Quality Assessment
In order to evaluate quality and highlight biases in the cross-sectional and cohort health studies, a detailed quality assessment scoring tool suitable for environmental epidemiology was developed based on Shah and Balkhair (2011) (see Appendix 3 for details). Two reviewers (CP, EL) assessed each study with reported health effects for eight potential sources of bias: study design, selection, responder, confounder, exposure assessment, outcome assessment, sample size, and analytical. A third reviewer resolved any disputes. Scores were provided on a scale of 1 to 4; a score of 4 was given where there was low bias. Prospective cohort studies were scored as very low risk of study design bias; exposure assessment was scored at very low risk of bias if direct sampling involving measurement was conducted.

RESULTS
The study selection process is represented in Figure 1. Five hundred and thirty-six articles were identified through the electronic searches and either the abstracts or entire articles were fully examined by two of the reviewers (involving EL, CP, PD); 470 papers were excluded. This review first considered studies with measured exposures of bioaerosols and then health studies; occupational and community studies were considered separately for both categories. Figure 1 details how many articles fit into each category. Almost all health studies included corresponding exposure data, but data were not always supplied within the publication in an  extractable form (e.g., data were not provided in the paper, or had to be extracted from figures). Most of the 66 studies included were occupation based (n = 51). Figure 2 shows the number of exposure and health studies where measurements were taken of different bioaerosols. Many bioaerosol components were monitored, of which total fungi, Aspergillus fumigatus, total bacteria, actinomycetes, and endotoxins are the most common, and the figure highlights how most studies occurred in occupational settings.

Exposure Studies
There were 58 exposure studies examined (Figure 1), of which 49 examined worker and occupational exposure, some in addition to community exposures (see Appendix 4). The majority of the studies were located in Europe and North America. The full study characteristics of occupational and community exposure studies are listed in Appendix 5 and Appendix 6, respectively. There were 10 components of bioaerosols commonly measured in exposure studies: viable total bacteria, gramnegative bacteria, actinomycetes, total fungi, and Aspergillus fumigatus, and also endotoxin, beta (1→3) glucans, organic dust, particulates, and total microbes.
The studies were heterogeneous in design, which may have affected concentrations detected; however, the majority of investigations provided the following information: • Type and size of site (e.g., whether the site was open-windrow, IVC, or mixed). • Whether agitation activities, such as shredding, turning, and screening, were taking place. • Air sampling instrument used (e.g., filtration, liquid impingement and direct impaction). • Sampling methodology (e.g., sample location and height, sampling time, laboratory culture methods). • Meteorological variability, especially wind speed and direction.
Some studies also provided the following information, although this was less common: • The age of compost (the amount and the microbiological composition of the composting material changes throughout the process) . Most studies provided measurements of colonyforming units (CFU/M 3 ) per cubic meter. Exposure sampling studies are reported here in two categories: occupational (including personal sampling for the assessment of workers exposure), and community exposure near composting facilities. Occupational Exposure Studies Occupational median or mean concentrations (depending on what was reported in the original papers) from on-site locations at composting sites extracted from the reviewed literature were in the following ranges: • Fungi, 10 1 to 10 7 cfu/m 3 .
The highest bioaerosol concentrations were generally observed during compost agitation activities such as turning, shredding, and screening, but only around half of the studies specifically stated that measurements were taken during different compost site activities. Thirteen occupational studies measured personal exposure of compost workers to different bioaerosol components (Bünger et al., 2007;Crook et al., 2008;Drew et al., 2007;Douwes et al., 1997;Epstein et al., 2001;Krajewski et al., 2002;Schlosser et al., 2009;Sigsgaard et al., 1994;Stagg et al., 2010;Sykes et al., 2011;Taha et al., 2007;Wheeler et al., 2001), detecting significantly high concentrations of actinomycetes, Aspergillus fumigatus, fungi, and endotoxin (Stagg et al., 2010), and elevated personal exposure levels of endotoxin in workers, particularly during composting agitation activities (Sykes et al., 2011). Four occupational studies measured mesophilic mould/fungi (Reinthaler et al., 2004;Schlosser et al., 2009;Tolvanen et al., 2005;van Kampen et al., 2014). All mean/median (depending on metric reported) onsite measurements completed by Reinthaler et al. (2004) and Schlosser et al. (2009) exceeded the 50,000 cfu/m 3 occupational limit set by BAUA in Germany in 2006(BAUA, 2006. Median on-site measurements by van Kampen et al. (2014) at sorting cabins, delivery places, and during processing also exceeded the BAUA limit. The mean/median values reported at the remainder of the on-site sampling locations in van Kampen et al. (2014) and the values reported in Tolvanen et al. (2005) did not exceed the BAUA limit, but the upper range did.
Total bacteria and Aspergillus fumigatus were the most consistently measured bioaerosol components, and their mean/ medians (depending on metric reported, with range if provided) from occupational studies at selected sampling locations are shown in Figures 3 and 4, respectively. Both had wide variability in measured concentrations. Highest bioaerosol concentrations were experienced on-site during agitation activities, with lower bioaerosol concentrations upwind. Measured Aspergillus fumigatus concentrations were more varied than total bacteria, ranging over eight orders of magnitude, compared to five orders of magnitude for total bacteria. Measured concentrations of total bacteria and Aspergillus fumigatus at the remaining sampling locations (such as at sorting areas and during periods of no activity) are provided in Appendices 7 and 8, respectively.
Community Exposure Studies The studies monitored bioaerosols at different distances from composting facilities, usually comparing concentrations measured downwind to the composting site with upwind concentrations, but also at points of interest, for example, at a sensitive receptor. There were wide ranges in measured concentrations of bioaerosol components in the studies, but this is difficult to interpret as studies were heterogeneous in design and presentation of results (some studies presented ranges and some presented medians or means). Figures 5 and 6 show the median or mean (as reported) exposure values by distance upwind and downwind from the composting sites for total bacteria (nine studies) and Aspergillus fumigatus (eight studies), respectively, the most commonly measured bacterial and fungal components across the included studies. The solid line denotes the 250m boundary recommended by the Environment Agency (Environment Agency, 2010). Figures 5 and 6 show that, as expected, generally the bioaerosol concentrations markedly increased immediately downwind of the composting facilities with concentrations gradually reducing on dispersion. However, it is important to recognize that not all studies measured concentrations at an upwind position, and therefore it is difficult to determine when concentrations returned back to background levels or to acceptable levels above background suggested by the Enviornment Agency.
In Figure 5, three (Herr et al., 2003b;Reinthaler et al., 2004;Williams et al., 2013) of nine studies presented have measurements of total bacteria that exceed the  Chang et al., 2014Coccia et al., 2010Duquenne et al., 2012Fischer et al., 2007Heida et al., 1995Hryhoczuk et al., 2001Nadal et al., 2009Nikaeen et al., 2009* Persoons et al., 2010Reinthaler et al., 1997Reinthaler et al., 1999Reinthaler et al., 2004Stagg et al., 2010Wheeler et al., 2001 Background/Upwind/Control Indoor composting areas Shredding Turning Screening/Sieving Downwind   Concentrations that appear to have been measured at 0m were taken on-site or on the site boundary. Please refer to Appendix 6 for study characteristics. * Crook, Stagg, and Uwagboe (2008) stated that one of their measurements was collected at 120-150m downwind. These measurements are presented at 135m downwind on the graph. * * Reinthaler et al. (1999) stated that measurements were taken at different distances from compass points around the site. It was not clear whether these measurements represented upwind or downwind measurements, and have been assumed to have been downwind within this graph. * * * Results from Williams et al. (2013) were estimated from graphs, and therefore the exact locations and concentrations has not been replicated.  Concentrations that appear to have been measured at 0m were taken on-site or on the site boundary. Please refer to Appendix 6 for study characteristics. * The results in Syzdek and Haines (1995) were presented as spores/m 3 . * * Crook, Stagg, and Uwagboe (2008) stated that two of their measurements was collected at 120-150m downwind. These measurements are presented at 135m downwind on the graph. * * * Results from Williams et al. (2013) were estimated from graphs, and therefore the exact locations and concentrations has not been replicated.
acceptable level of 500 cfu/m 3 above background concentrations beyond 250 m downwind (Environment Agency, 2010). Measurements by Pankhurst et al. (2011) and Reinthaler et al. (1999) may also have exceeded the Environment Agency's acceptable levels beyond 250 m, but background values are not provided in these studies.

Health Studies
Eighteen health studies relating to bioaerosols from composting facilities were reviewed, the majority of which were conducted in Europe (Appendix 4). The full characteristics for both occupational and community based studies are displayed in Tables 1 and 2, respectively.
For each study, only a small number of conditions of those examined showed statistically significant associations as reported in Tables 3 and 4 for occupational and community-based health studies, respectively (nonsignificant health effects are presented in Appendix 9). As the majority of health studies were cross-sectional in design and too diverse to permit a quantitative meta-analysis, a narrative synthesis and table of significant health effects from occupational and communitybased health studies are presented. Table 5 presents results of bias assessment for health studies. The risk of bias was assessed using the tool presented in Appendix 3, based on Shah and Balkhair (2011). Sample sizes were generally low, introducing the possibility of statistical power issues. Many studies were also assessed as being at high risk of response bias, usually due to lack of explanation of follow-up of initial nonresponders. In addition, earlier published occupation-based studies were less likely to have taken relevant confounders into account (such as age, gender, and deprivation).

Bias Assessment
Occupational Health Studies There were two occupational case reports (of two patients in total) reviewed, both of which were of HP in compost workers (Vincken and Roels, 1984;Brown et al., 1995). Ten further occupational studies. . . . . (quasi-experimental design, i.e., a nonrandomized pre-post intervention study; Harris et al., 2004), one lab based study, one experimental study, and one was a cohort study (see Appendix 4 for details). Studies generally reported upper respiratory symptoms, eye and nose irritation, and skin and intestinal symptoms in exposed workers (see Table 3 for statistically significant health effects and Appendix 9 for all non-statistically significant health effects). This was supported by evidence from studies examining inflammatory markers and two further lab studies of human airway cells.
Three small studies examined inflammatory markers using experimental and quasiexperimental designs. Two were occupational studies, with nasal lavage measurements preand postshift (Douwes et al., 2000) or three days of work (Heldal, 2003) on 25 and 31 composting workers, respectively, while a third examined peripheral blood pre and post 2h exposure in 17 healthy young adult volunteers (Müller et al., 2006). Both occupational studies found elevations in neutrophils and inflammatory markers of myeloperoxidase and interleukin-8 (IL-8) in nasal lavage fluid post shift; one of the studies (Heldal, 2003) also noted a rise in eosinophil cationic protein (ECP). Both studies reported some evidence for associations between exposures to endotoxin, beta (1→3) glucan and fungal spores (Heldal et al., 2003), but inflammatory responses were not specific to measured components of the bioaerosol dust. Müller et al. (2006), found elevated levels of blood neutrophils postexposure, but not inflammatory cytokines of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), or interleukin-6 (IL-6).
Two lab studies of inflammatory markers were identified. Chang et al. (2014) examined expression of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to airborne bioaerosols from sampling filters used in a composting plant. Postexposure there were elevations in IL-6, transforming N/A. Those exposed worked almost exclusively in the compost hall and therefore exposed to organic dusts.  growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1(p21 WAF1/CIP1 ) but not matrix metallopeptidase (MMP)-9. Liu et al (2011) showed elevated inflammatory cytokine production in cultured human D562 pharyngeal epithelial and MM6 monocytic cell cultures exposed to airborne endotoxin samples from active on-site areas, but not where samples displayed low endotoxin levels, including those collected upwind, downwind at 100 m or more from composting site boundary, or when composting sites were inactive. Liu et al. (2011) suggested that airborne endotoxin levels of >50 EU/m 3 may have the potential to induce proinflammatory responses in airway epithelial cells.   Eye/nose/throat irritation Bunger Germany As above Watering eyes; itching eyes; conjunctivitis reported more frequently in compost workers than in control subjects (p < .05) Van Kampen (2012) Germany As above Watering eyes; foreign body sensation in eyes reported more frequently in compost workers than in control subjects (p = .008 and .013, respectively) Hambach (2012)

Germany
As above Irritation + (work related) = 4.7 (1.8-25.3) + runny eyes, blocking of nose, runny nose, sore throat, ticking nose or sneeze aggregated Note. Nonsignificant health results are presented in Appendix 9. * The study information from Sigsgaard, Hansen, and Malmros (1997) is from a conference paper, as the results were not reported in Sigsgaard et al. (1994).

Respiratory system
Browne (    Note. The scores are provided on a scale of 1 to 4; the maximum score is 32 (best quality study) and the minimum score is 8 (lowest quality study).

Community Health Studies
One case report of allergic bronchopulmonary aspergillosis (ABPA) produced by Aspergillus fumigatus in a patient with a history of asthma was identified (Kramer et al., 1989). The patient lived 250 ft from a municipal leaf composting site. There were no reported cases of invasive aspergillosis of residents living near compost plants (Kramer et al., 1989).
Three cross-sectional community-based studies, two of which also measured exposure (Herr et al., 2003a(Herr et al., , 2003b, examined health effects in residents of communities at various distances to composting facilities (see Table 4 for statistically significant health effects and Appendix 9 for all non-statistically significant health effects). Three studies used questionnaires to assess symptoms, one in Finland (Aatamila et al., 2011) and two in Germany (Herr et al., 2003a(Herr et al., , 2003b, also assessing odor (Aatamila et al., 2011;Herr et al., 2003aHerr et al., , 2003b and bioaerosol concentrations (Herr et al., 2003a(Herr et al., , 2003b. A fourth study in the United States used daily symptom diaries (Browne et al., 2001) in relation to Aspergillus fumigatus spore counts, comparing residents (oversampling those with allergic rhinitis and asthma) near a composting facility with those from a reference area. The three questionnairebased studies reported adverse health effects, predominantly respiratory and irritated eye and nose symptoms, but may have been prone to reporting and selection biases (Table 5). However, the symptom diary study did not find marked associations between allergy and asthma symptom symptoms and A. fumigatus spore counts (Browne et al., 2001).
The community-based health effect studies provided limited evidence of increased exposure levels at distances greater than 200 m to 300 m. The zone widths (1.5 km) in Aatamila et al. (2011) were most likely too large for this type of stratification, and distance zones in the study were not consistently associated with the observed symptoms (although symptoms were with reported odor annoyance).

DISCUSSION
The aim of this systematic review was to evaluate the current evidence relating to possible health impacts associated with bioaerosol emissions from composting facilities, and this is the first systematic review to focus entirely on bioaerosol emissions from composting facilities. The exposure studies were heterogeneous in design and analysis, with limited details provided in many studies, but did identify a wide range of possible exposures to bioaerosol components. Highest bioaerosol concentrations were reported most frequently during agitation activities, such as turning, screening, and shredding. Most of the health studies were occupational. These studies provided qualitative evidence linking occupational exposure to bioaerosols to gastrointestinal (GI), skin, and respiratory-tract symptoms, supported by objective evidence from occupational and lab studies showing small decrements in lung function and elevation in inflammatory markers, but there were too few studies and designs were too heterogeneous to determine exposureresponse relationships. There were four community health studies, three of which were prone to response bias. As with any review, some studies may have not been retrieved, but a comprehensive search strategy was employed that also incorporated gray literature to attempt to include all evidence currently available.

Exposure Studies
The exposure studies included in the review demonstrated a wide variation in the types of bioaerosols sampled and concentrations measured both on-site and at various distances from sites in community studies. The variability in measured concentrations is likely due, in part, to different methods of sampling and measurement.
Several countries have issued recommendations for sampling methods and equipment, but these all differ, which affects study comparisons. In the United Kingdom, the Association for Organics Recycling (AfOR), now the Organics Recycling Group (ORG), published a standardized protocol for monitoring bioaerosols at open (but not IVC) composting facilities in 1999composting facilities in , updated in 2009composting facilities in (AfOR, 2009. The protocol recommends the use of Andersen impaction samplers and IOM filter samplers enumerate colonies of total bacteria and Aspergillus fumigatus only. However, a comparison of different sampling techniques, including Andersen impaction samplers and IOM filter samplers (as well as others), found that there was no consistent relationship between the concentrations of bioaerosols measured with the AfOR standard sampling methods (Williams et al., 2013). In Germany, BAUA published recommendations of how to sample airborne biological particles in an occupational setting, covering but not specific to composting processes (BAUA, 2006;Meffert and Blome, 2011), and recommended the sampling equipment to be used. The National Institute for Occupational Safety and Health (NIOSH) produced a sampling method when measuring bioaerosols in indoor air (Lonon, 1998), which is different again. In 2013, The European Intergovernmental Panel on Climate Change (IPCC) called for a technical working group to review the biowaste industry's best available techniques (BAT) reference document (BREF) (Collins, 2013, ORG, 2013. A BREF for biowaste is underway, but not yet available, although a BREF for waste treatment industries is (European Commission, 2006).
Analysis of total microbial cell numbers is also an area of differences in bioaerosol concentrations reported between studies. Only a proportion of microbial cells within a bioaerosol are capable of being cultured, with the remainder being either dead but intact cells, or "viable but non culturable" (VBNC)-live cells not capable of being cultured either because they have entered a metabolically dormant state or because the agar medium used does not support their growth. However, these microorganisms may also pose a health risk and need to be taken into consideration in human health impact assessment. Sampling techniques that rely on microbiological cultures are also subject to upper and lower limits of detection. Impaction samplers are capable of capturing lower concentrations of bioaerosols, but become overloaded when sampling in areas where higher concentrations are expected (such as on-site or during agitation activities) (Williams et al., 2013). Therefore, the sampling technique used needs to be carefully considered and be appropriate for the study needs. The weaknesses in the sampling techniques also provide challenges for dispersion modellers attempting to predict bioaerosol exposure.
Perhaps most importantly, the current sampling regimes do not provide information on long-term exposures, which is particularly important for community health studies. The AfOR protocol has short sampling times (up to 45 min, but usually 10-30 min, depending on the location and sampler used) (AfOR, 2009) that provide only a short snapshot of emissions at the time of sampling. However, recently continuous sampling techniques have become available, for example, Wideband Integrated Bioaerosol Sensors (WIBS) (Droplet Measurement Technologies [DMT], 2014), which operate using light scattering and fluorescence detection. These bioaerosol sensors are capable of operating over long periods of time and detect VBNC cells, providing the potential to complete chronic exposure studies. Measurement of PM 10 (particulate matter 10 μm in diameter; the diameter of a bioaerosol may also be 10 μm, as they range in size from 0.02 to 100 μm [Dowd and Maier, 2000]) may also allow an estimation of continuous bioaerosol concentrations (Brown et al., 2009, Williams et al., 2013. However, Williams et al. (2013) demonstrated a poor correlation between PM 10 and bioaerosol concentrations, and therefore additional research needs to be completed before PM 10 measurements can be used solely as a proxy for bioaerosol concentrations.
Many of the exposure studies included in this review did not measure a background concentration. Further, where a background concentration was measured it was not clear whether concentrations determined downwind of the composting site had taken into account the background levels. This lack in reporting of background concentrations may, in part, reflect difficulties in obtaining background measurements. For example, the site might be located in an area where there are many sources of bioaerosols. As bioaerosols are ubiquitous and highly variable, defining a "true" background concentration is problematic. In addition, in areas where the site is located near multiple sources of bioaerosols, downwind measurements may be influenced by other sources. This causes difficulties when defining exposure levels and apportioning bioaerosol exposure to a source.

Health Studies
Our review suggests that information in relation to health risks from compost facilities has expanded in recent years, but is still limited. The evidence base is not sufficient to provide quantitative dose-response estimatesand is limited by lack of evidence base relating to dose.
Workers at compost sites are those exposed to the highest levels of bioaerosol components. Health studies provide some evidence of potential short-term respiratory, gastrointestinal, and proinflammatory effects at high levels of exposure, but respiratory protection is recommended for compost site workers to minimize impacts on health (HSE, 2013). The strength of inferences that may be drawn from the available studies was weakened by the small sample sizes and short-term nature of the investigations. Only one occupational cohort study was identified, and this was suggestive of higher risks of chronic bronchitis and reduced lung function with ongoing bioaerosol exposure. There were no studies identified that would enable the estimation of incidence rates of occupational allergic disease, one of the most frequent occupational respiratory disorders. However, respiratory and allergic disease following elevated exposures to some bioaerosols, such as endotoxin and Aspergillus fumigatus (Rautiala et al., 2003), was noted in other occupations including agricultural workers (May et al., 2012;Poole et al., 2010) and domestic waste collectors that were not considered in this review. The lack of longitudinal studies is most likely due to the practical difficulties of longitudinal studies in these settings, and the difficulty in obtaining historical data due to the relatively recent development of the composting industry. More studies are needed to determine if chronic effects can be confirmed, particularly if respiratory protection has been used.
Only five community health studies were identified; one was a case report and four were cross-sectional studies (therefore limiting interpretation of causality) and reliant on self-reported symptoms (which may be prone to recall and reporting bias). There are as yet no large-scale longitudinal investigations of adverse health impacts on residents of bioaerosols emitted from composting facilities. None of the community studies provided information on the relationship between emission rates of bioaerosols on site and resulting concentration of bioaerosols at distances from source. The potentially harmful microbes identified in this review and diseases associated with them are tabulated in Appendix 10, but of the nine health studies that also measured exposure, Apergillus fumigatus, endotoxin, and gram-negative bacteria were the only specific organisms for which exposure sampling measurements were conducted. Selection of participants in the community studies is also a potential source of bias, and the chosen distance bands (0-<1500, 1500-<3000, and 3000-<5000 m) in Aatimila et al. (2011) are too large, given that exposure studies demonstrated that most bioaerosol concentrations fall to nearbackground levels at 250 m.
No studies provided direct evidence relevant to vulnerable members of the population such as the immunocompromised, who are potentially at risk of invasive respiratory fungal infection from Aspergillus fumigatus at lower concentrations than are healthy individuals (Stagg et al., 2010), or asthmatics, who occasionally were reported to suffer increased risk of hypersensitivity to fungi at concentrations found in ambient air (Searl, 2008). The developing fetus may also be considered potentially sensitive to environmental exposures, but no apparent studies of reproductive outcomes were found.

CONCLUSIONS
Overall, the results reported in this systematic review endorse those previously noted by Searl (2008). Current evidence on both exposure to bioaerosol emissions from composting facilities and potential for associated health effects remains limited. All of the exposure studies included in this review have involved shortterm sampling, which provides little insight into long-term exposures. The health studies have design limitations, generally involving small numbers of subjects and, in the community studies, reliant on self-reported outcomes that may be prone to bias. Further, with the exception of one cohort study that was undertaken over the course of 5 years (Bünger et al., 2007), studies were either of short time scales or cross-sectional in design, which limits interpretation.
The health studies provide no quantitative dose-response estimates, and therefore evidence to date is insufficient to inform risk-based regulation. However, occupational and community health studies do provide qualitative evidence of adverse health outcomes that is sufficient to justify the current approach to prevent community exposures to elevated bioaerosol levels. This is the current position adopted by the Environment Agency (Environment Agency, 2010). Results from studies to date do not provide clear guidance as to where the distance boundaries from site should be placed, or what elevation in bioaerosol levels is harmful. Three studies have detected concentrations of total bacteria, and two investigations detected concentrations of Aspergillus fumigatus above the Environment Agency's recommended threshold levels above background beyond 250 m from the site, which might potentially be of concern to susceptible individuals and argues against reducing the current boundary, although studies certainly indicate lower exposures beyond 250 m compared with closer to the site. An additional problem is that background levels of bioaerosols are not well defined and are likely to vary both spatially and temporally.
To address current limitations in the evidence base, more detailed and longer term monitoring of various components of bioaerosols, better characterization of background bioaerosol levels, examination of the health effects over longer time scales and in larger numbers of individuals, use of objective measures of health outcomes (such as biomarkers, functional assessments such as lung function, and outcomes validated by examination of health records), and investigation of impacts in potentially sensitive groups (children, elderly, those with chronic illness, and reproductive health) is suggested. An initial research focus on respiratory and allergic disease is supported by the literature. Our paper summarizes available information on bioaerosol exposure profiles in relation to composting, and this may facilitiate comparisons with health studies in other settings (such as intensive agriculture) when exposure profiles are found to be comparable.

FUNDING
The work of the UK Small Area Health Statistics Unit is funded by Public Health England as part of the MRC-PHE Centre for Environment and Health, funded also by the UK Medical Research Council. This research also received funding from the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Health Impact of Environmental Hazards at King's College London, in partnership with Public Health England and collaboration with Imperial College London. We thank Tim Reeves at Imperial College library for his assistance with the literature search, and Daniela Fecht for her assistance with translating German documents. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, the Department of Health, or Public Health England.