The indoor environment contains numerous exposures with the potential to influence asthma development and morbidity. Exposures include biologics (allergens, bacteria, or fungi), pollutant gases and particulate matter from indoor (e.g. gas stoves and cigarette smoke) and outdoor sources. Infiltrating ambient particulate matter contains a heterogeneous mix of inorganic, organic, and biologic components. (1, 2) Indoor particle sampling can include collection of house dust (vacuumed or swiped from surfaces) or air samples (collected actively or by passive settling). Experience with nasal samplers and other personal monitoring devices for assessment of bioaerosol inhalation exposure is limited. (3–5)

The gold standard for measurement of exposure to individual allergens in dust or air samples has been enzyme-linked immunosorbent assays (ELISA), which have been improved with reduction of assay time and use of amplification to increase sensitivity. In the past decade, for standardized measurement of multiple allergens in epidemiologic studies, ELISA has largely been replaced by fluorescent multiplex array technology, with measurements shown to be reproducible within and between laboratories. (6–8) New laboratory approaches, advances in field sampling equipment and real-time data monitoring, including rapid tests for allergens (9–11) may contribute insight into the spectrum of indoor exposures (Table 1). (6, 7) Technologies for allergen measurement including qPCR, mass spectrometry and allergen biosensors are in development, including those supported by the NIH PRISMS (Pediatric Research using Integrated Sensor Monitoring Systems) program.(12) Mass spectrometry has been used as a high sensitivity method for detection of grass pollen allergens, and is also being evaluated for food allergen detection.(13–15) A first generation of allergen biosensors can measure Der p 1, Der p 2, Asp f 1 and Ara h 1, and advances in personal air sampling methodology have led to new insight into critical allergen exposure locations.(16–19)

For the characterization of indoor microbial communities in dust and air, prior to the availability of culture independent technology enabling metagenomics, environmental microbial taxa were measured either by culture, qPCR of select taxa, or quantification of presence or activity of bioactive indoor pathogen-associated molecular patterns (PAMPs). Gram negative bacteria endotoxin bioactivity has been quantified using both kinetic Limulus amebocyte lysate (LAL) and recombinant Factor C (rFC) assays.(20–22) Endotoxin and the gram positive PAMP biomarker, peptidoglycan (N-acetyl muramic acid) have been also measured by gas chromatography/mass spectrometry (GC/MS). These methods are now complemented by culture independent metagenomic characterization of communities of microbes originating from a multitude of sources (e. g., humans, pets, mice, cockroaches, dust mites, water, soil, plants, building materials).(23, 24) Amplification and sequencing of select regions (16S rDNA for bacteria; 18S or ITS for fungi) of ribosomal DNA (rDNA), the gene that encodes for ribosomal RNA, yields information on the taxonomic composition of the environmental microbiome.(23–32) Alternatively, rDNA microarrays can be used to characterize bacterial taxonomic abundance. Microarrays are less agnostic than rDNA sequencing, and may require larger quantities of 16S rDNA. (33) Whole genome shotgun sequencing of all DNA extracted from an environmental sample also yields information on taxonomic composition of bacteria, fungi and viruses, although depth of coverage may be less than for rDNA amplification and sequencing. It also provides characterization of potential function through metagenomics estimation of the proportion of genes detected for given microbial metabolic pathways.(34) All of these metagenomic techniques generate relative abundance data for taxonomic composition or representation of functional pathways, but do not measure total bacterial or fungal microbial load, a task that requires qPCR. Also, they do not adequately address the actual function of household bacteria, and the relevance to that function to metabolic products (including breakdown of household chemicals) that could influence human health, or to colonization of the human microbiome.

Air pollutants found indoors, that can trigger asthma symptoms, originate from outdoor (e.g., traffic) and indoor sources (e.g., secondhand smoke (SHS), gas stove emissions). Elimination of SHS through smoking cessation and home smoking bans should always be considered a first-line indoor environmental intervention for children with asthma. Technologic improvements have been made in the efficacy of High Efficiency Particulate Air (HEPA) particle filtration designed to remove targeted indoor air pollutants such as fine particulate matter (PM_2.5).(61) Other than replacement of gas stoves with electric stoves, fewer methods are currently available for indoor NO₂ reduction of indoor or outdoor origin.(62, 63) In homes with smokers, recent home and school-based intervention trials in children report significant reductions in particulate matter with HEPA filter use, (64–66) but without reduction in indoor gases, without consistent reductions in markers of cigarette smoke, and with mixed success in improving child asthma symptoms. The efficacy in reducing indoor pollutants is dependent on room dimensions and building structure and conditions. While air cleaners have been also been used as adjunct interventions in multipronged environmental intervention trials (67) successful in reducing asthma symptoms, their independent contributions to health is uncertain, and the physical settings in which they may reduce exposure sufficiently to contribute to asthma control are also not well defined.

Indoor fungi originate through penetration from outdoors as well as from indoor sources, especially in damp and water damaged buildings.(68–70) They have a multitude of forms, properties and components. Fungi and their irritant or toxicant components can have adverse airway irritant as well as allergenic properties, and asthma symptoms can occur in individuals not sensitized, as well as in those sensitized to fungi.(71, 72) The mechanisms for effects of individual fungal components and interactive effects with other indoor exposures on airway and immune responses are not well-understood. Paradoxically, some observational birth cohort studies suggest that specific microbial communities or early life diversity of microbial agents, including fungi, may protect against allergy development,(73) but this is not a justification for discouraging fungal remediation in water damaged homes or poorly maintained moldy homes.

In symptomatic patients with asthma, fungal prevention and remediation strategies and their success in reducing exposures or improving health in damp or water damaged buildings can vary by housing stock, climatic region, and resident behaviors. New building materials, ventilation systems, and home furnishings, particularly those harboring humidity, may introduce new challenges requiring novel strategies to minimize fungal growth. While a review of studies to reduce mold in buildings and assess health outcomes recommended “better research, preferably with a randomized controlled study design and with more validated outcome measures,” (74–76) imaginative study designs are needed to fit extreme situations investigators and communities are at times confronted with. In disasters with clear-cut mold damage the health risks can be obvious, but building remediation solutions may be challenging. The post-Hurricane Katrina HEAL study reported improvement of asthma symptoms with implementation of a hybrid intervention with asthma counselors and environmental remediation, but in the midst of post-disaster changes, investigators could not disentangle the extent to which the active study environmental interventions were responsible for the observed fungal reduction or symptom improvement.(77)

A variety of multi-pronged community-based strategies have been used to decrease indoor allergen exposures (78, 79) with varying success in reducing exposure and in improving asthma control. This inconsistency may be due to variable levels of intensity of the intervention, provided resources, participant education, social resources or adherence. More confounders include other changes in environmental exposures, differences in tailoring the interventions to individual sensitivities of the participants, baseline levels of allergens, and effect modification of the intervention health effect by the presence of co-exposures like stress or ETS (i.e., SHS).

While many studies have sampled and tested efficacy of interventions in individual indoor homes, effects of the structure and building components of housing, including multi-unit structures, on exposure are less well studied. In Northeastern and mid-Atlantic cities, asthma prevalence is often high in multifamily low-income housing sites where multiple and interrelated housing-related exposures are present. A few studies have evaluated indoor environmental and respiratory health before and after alterations in single or multifamily homes that undergo ‘green’ construction, renovation or weatherization under construction guidelines aimed to conserve energy while maintaining adequate ventilation, using “environmentally friendly” materials. Such studies take advantage of costly interventions already taking place but have the potential limitations of uncontrolled observational study designs.(80) In one Boston-based study, asthmatic children living in green homes experienced substantially lower risk of asthma symptoms, hospital visits, and asthma-related school absences than children living in conventional public housing.(80) A study of green housing in the South Bronx (81) showed improvements in asthma symptoms and urgent care visits for asthma and a Chicago-based study showed self-reported asthma symptom improvements.(82) However, given the variable application of “green” construction approaches, the potential risks of responding to financial pressures by reduction of air exchange or inadequate maintenance even in new buildings, and study design limitations, uncertainty remains about which aspects of new construction may improve asthma.

Table 2 offers a summary of selected published studies on exposure reduction and on associations between exposure reduction with asthma control.

Primary prevention of asthma is an enviable goal that, if achieved, could reduce the prevalence of the disease. Of a large number of potentially modifiable risk factors for asthma development identified in the literature, (104) allergen exposure is one that has attracted considerable attention.(105, 106) Observational epidemiologic studies have identified early life allergen exposures as risk factors for subsequent allergic sensitization, and early allergic sensitization is a major risk factor for asthma.(107) However, the concept of allergen avoidance for primary prevention of asthma has been challenged by investigators who argue that this approach is limited by a) the ubiquitous nature of aeroallergens in some ecologic and cultural settings; b) the dominance of genetic factors in influencing the course of asthma; c) the importance of early priming by other factors (microbes or microbial components, in utero smoking, vitamin D, etc.) or, most recently d) the benefits from early allergen exposure as manifested by studies in food allergy and e) the protective effect against wheezing of high aeroallergen exposure in the first years of life. Evidence for potential benefits of early exposure to allergens or their sources for allergic sensitization, wheeze or asthma have been reported by observational birth cohort studies including the Massachusetts-based Epidemiology of Home Allergens and Asthma Study (EHAAS), the Wisconsin Childhood Origins of Asthma Study (COAST), the Detroit Childhood Allergy Study (CAS) and the Urban Environment and Childhood Asthma (URECA) Study. (24, 56, 58, 108) Most of these observational studies report protective associations with early-life mammalian exposures, especially dogs and associated allergens or microbes. The URECA data indicated that early-life multiple exposures including cockroach and mouse are protective, (24) whereas EHAAS found these two exposures to be risk factors. Multiple differences in cofactors and exposure levels may be responsible for the contrasts in these observational studies.

Although indoor environmental interventions aimed at reducing asthma morbidity have been more successful than those aimed at primary prevention of asthma, questions remain about their role in asthma management. Table 2 provides an overview of the most recent environmental intervention trials and highlights their findings and limitations in influencing exposure reduction and asthma control. Effective environmental interventions are typically multi-faceted, tailored to the specific exposures and sensitivities of the target subject, and intensive.(84, 150) Publication bias leads to less publication of unsuccessful intervention trials, but the few that have been published suggest that single-allergen interventions and low-intensity efforts are ineffective. One such negative publication (151) exemplifies the challenge of translating an efficacious intervention from a tightly controlled clinical trial setting to a broader population: when the provision of allergen-proof mattress/pillow encasements to adults with asthma was tested in primary care, no effect was found with this untailored intervention. Although the study population was adults, the notion that health benefits observed in tightly controlled RCTs may not easily translate to more “real-world” settings is applicable to environmental interventions in children, too. In addition, families face a number of barriers to remediating environmental exposures, including costs, preferences, home ownership status, life-long behavioral practices, and education. For example, low-income urban populations are highly mobile and have limited resources with which to address environmental concerns. Also, residents often do not control the structure of their buildings since they rent, rather than those who own their homes.

The Inner-City Asthma Study (ICAS) may be the most successful environmental intervention study conducted to date; the intervention was targeted at specific allergen reduction in asthmatic children who were both sensitized and exposed to those allergens, but the intervention was also multi-facetted including integrated pest management targeted to specific allergen sensitivities, provision of HEPA vacuum cleaners, free standing bedroom HEPA filter air cleaners, and allergen-impermeable mattress and pillow covers. Primary trial results reported in 2004 found that the environmental intervention group experienced significant and clinically meaningful reductions in a range of asthma outcomes compared to controls.(84) Benefits were seen up to 12 months after the environmental intervention and cost-effectiveness analysis derived a cost of $750 to $1000 per year per family to implement, a cost they estimated was equivalent to cost of mid-range inhaled corticosteroid and albuterol for a child with moderately severe asthma. This translated to almost $28 per gained symptom-free day.(152) Because a multi-faceted, patient-tailored, intervention was tested in ICAS, and direct measures of environmental tobacco smoke exposure reduction were not made, it is not possible to determine the relative contribution of individual components of the environmental intervention and exposure reduction to the successful outcome. Notably, both arms of the ICAS (environmental intervention and physician feedback) were successful without other interaction with the health care systems, but optimally environmental control trials should be designed in the context of optimal access to health care, access to medications, and appropriate clinical asthma management.