Environment and the Development of Severe Asthma in Inner City Population

Abstract

Purpose of review:

Higher asthma prevalence and morbidity are seen in inner-city areas, disproportionately affecting low-income families living in substandard housing. Children within these families experience more frequent asthma exacerbations, acute care and emergency department visits, and hospitalizations, thus characterizing severe asthma. In this review, we assess recent published literature focused on indoor and outdoor exposures that contribute to the development and morbidity of asthma.

Recent findings:

Many urban environmental exposures contribute to asthma burden, including tobacco/e-cigerette smoke, pest allergens, molds, and possibly synthetic chemicals such as phthalates and bisphenol A, radon, and volatile organic compounds. Individuals living in inner-city areas also experience higher levels of air pollutants and ambient heat, further perpetuating asthma incidence and severity.

Summary:

This article summarizes the latest advances and provides direction for future research on risk factors, interventions, and public policy to help alleviate the burden of asthma due to urban environment exposures.

Introduction

Asthma is one of the most common chronic diseases in the United States, affecting about 8.0% of the population (1). Uncontrolled asthma is characterized by frequent daytime and nighttime symptoms, activity limitation, recurrent exacerbations requiring oral corticosteroids, and hospitalizations. Difficult to treat asthma is uncontrolled asthma in spite of high intensity treatments. Severe asthma is a subset of difficult to treat asthma despite adherence to high dose inhaled corticosteroids and management of comorbidities that can worsen asthma symptoms (2). Patients with severe asthma constitute a small portion of all people with asthma, but a disproportionately high level of healthcare expenditure (1,2).

Inner city areas, often centrally located in historic cities, have higher poverty rates and concentration of racial/ethnic minorities. Children living in inner cities, in particular Black and Hispanic children, experience worse asthma morbidity (3-5). Incidence of asthma and frequency of asthma exacerbations are higher among individuals from low-income families. In addition, the rate of urgent care center and emergency department (ED) visits are greater in large urban areas compared with suburban and rural (1). The epidemiology of severe asthma is influenced by environmental, genetic, demographic, and social factors. In this current topical review, we focus on indoor and outdoor exposures affecting urban populations that may contribute to the development of severe asthma.

Indoor Exposures:

Tobacco smoke is one of the most potent exposures for asthma morbidity. Approximately 14% of children in the U.S. are exposed to second hand smoke at home; the incidence is higher in inner-city low-income households (6). In cross-sectional reviews of subjects enrolled in the the NIH/NIAID-funded School Inner-City Asthma Study (SICAS), Ruran et al. observed higher urinary cotinine levels in children of lower income homes as well as non-White race and Hispanic or Latinx groups (7). Furthermore, they found significant associations between urinary tobacco biomarkers - cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-buatnol (NNAL) - and asthma health outcomes. Every log₁₀ increase in cotinine level was linked with rise of 15.9% in maximum symptom days and 34.7% in odds of hospitalization. For every log₁₀ increase in NNAL, there was a 172% increase in odds of hospitalization (7).

Volatile organic compounds (VOCs) are pervasively found in homes, including but not limited to cleaning agents, glue, personal care products, solvents, and building materials (8). Maternal exposure to cleaning products and disinfectants starting before conception and continuing through pregnancy was associated with a 1.56 odds of developing childhood asthma. Exposure starting around the time of conception was linked with a 2.25 odds for childhood wheeze and/or asthma (9). Higher VOC concentrations were associated with increased asthma exacerbations (8). Multiple mechanisms have been proposed, including disruption of the integrity and immunoregulatory function of the bronchial epithelium, induction of allergen sensitization, and promotion of airway reactivity in individuals with pre-existing allergens sensitivities (10).

Children living in inner-city housing are exposed to higher levels of pest allergens compared to those living in suburban homes. Some studies have shown that greater contact in early life to cockroach and mouse allergens was inversely associated with the incidence of wheeze and atopy (5), suggesting tolerance to allergen exposures may occur. Yet pest exposure in individuals with pest allergen sensitization have also been repeatedly linked with decreased asthma symptom control (4,11). Additionally, inner city school exposure to mouse was significantly associated with asthma morbidity, independent of mouse allergen sensitivity (12). The mechanism behind the relationship between allergen sensitization and asthma may be immune mediated. Children with allergen sensitivities, wheeze, and low lung function have increased Type 2 (T2) inflammatory response. The T2 immune feedback leads to persistent up-regulation of genes for Interleukin (IL)-9, IL-13, and IL-31. These three markers are significantly associated with the development of cockroach-allergen sensitization and asthma by age 7 years old (13).

Children living in inner-cities encounter high mold exposure at home and in schools (4,14). Prior studies have demonstrated that mold sensitization was more common in patients with severe asthma, poor symptom control, and more frequent exacerbations. An analysis of dust samples collected as part of the Asthma Phenotypes in the Inner City (APIC) study revealed that the species Mucor was seen in significantly greater concentrations in homes of children with difficult to treat asthma compared to easy to treat asthma. Mucor is found ubiquitously and generally aggregates around air-conditioners (AC). Children living in homes with window AC systems were more likely to have difficult to treat asthma than children in homes without such units (15).

Emerging indoor exposures

In recent years, phthalate exposures have gained more attention as a risk factor for asthma, allergy, and eczema development. Phthalates are synthetic chemicals used as solvents and plasticizers in personal hygiene products, cosmetics, toys, medical equipment, building materials, and medications, as well as, plastic food and drink containers (16). Children’s exposure to phthalates are primarily through ingestion, particularly of fast food, a practice that is more common in non-White populations (16,17). Mean concentrations of high molecular weight phthalate biomarkers are greater in children of low-income families compared to children in the general U.S. population (16). Phthalates cause airway inflammation through oxidative stress and via the Th2 pathway, possibly leading to airway remodeling and the emergence of obstructive physiology (16). High and low molecular weight phthalates are strongly associated with worsened asthma symptoms and greater healthcare utilization via ED, acute care, and unscheduled doctor visits (18).

Bisphenol A (BPA) is another synthetic chemical found in toys, building materials, canned foods, beverage containers, and consumer goods that has been linked to increased asthma morbidity in children of low-income urban settings. Higher BPA concentrations are seen in children of low-income and Black communities compared to children in the general U.S. population (18). This has been attributed to differences in dietary and consumer good consumption practices, which is perpetuated by food deserts and poor access to fresh produce resulting in greater ingestion of canned foods and beverages contained in polycarbonate bottles. BPA may heighten the allergic immune response though multiple mechanisms: 1) production of proallergic cytokine IL-4, and antigen-specific IgE, 2) reduction of regulatory T cell, interferon (IFN)-gamma, and IL-10, and 3) up-regulation of the T_H2 pathway, which has been associated with eosinophilic airway inflammation, asthma development, frequent asthma exacerbations, and corticosteroid insensitivity. Thus, with higher BPA exposures, patients may experience more symptom days, acute care visits and ED visits for asthma (18). Further investigation is needed to identify the modes of exposure – inhalation, ingestion, transdermal – that contribute to health outcomes.

Radon is a noble gas formed from the radioactive decay of uranium that accumulates in poorly ventilated and enclosed spaces. It is known to cause cancer. Recent evidence suggests it may influence non-cancer mortality, especially in patients with COPD (19). Mukharesh et al. reported short-term exposure to higher modeled residential radon levels was associated with increased frequency of asthma diagnosis and twice the odds of school absenteeism among inner-city children (20), suggesting radioactivity inhalation even at low levels may affect respiratory health in children.

Outdoor Exposures

Air pollution plays an indisputable role in asthma health outcomes. Higher air pollutant concentrations are found in urban settings. Multiple longitudinal cohort and epidemiologic studies have demonstrated increased asthma prevalence and symptoms, decreased lung function, and increased airway inflammation in individuals living in areas of lower air quality, cumulating in higher numbers of ED visits (10,21). Particulate matter (PM) is a mixture of solid and liquid particles that are suspended in the air. PM_2.5 are molecules smaller than 2.5μm in size that, when inhaled, can deposit in the distal airways as far as the alveolar space. About 25% of urban ambient PM_2.5 is from traffic, 15% from industrial activities, and 20% from domestic fuel burning (22). PM_2.5 is the most important indicator for air polluation affecting asthma in all seasons (23).

PM_2.5 and nitrogen dioxide (NO₂), a gaseous air pollutant, have been linked with greater asthma prevalence. High maternal exposure to PM_2.5 during weeks 6-26 of pregnancy (the pseudo-glandular and canalicular stages of embryology during which the tracheobronchial tree elongates and develops smooth muscles, connective tissue, and respiratory bronchioles) was significantly associated with increased incidence of childhood asthma (24). Increased PM_2.5 exposure in childhood was associated with a greater risk for developing asthma (10,24). High environmental NO₂ levels during prenatal period and in the first year of life was associated with greater asthma prevalence in pre-school children (25).

Air pollution leads to greater asthma morbidity. Due to historic societal inequity, Black persons and people living in low-income areas with inadequate access to social supports and minimal job availability are generally exposed to higher PM_2.5 concentrations (26). Elevated ambient PM_2.5 levels are associated with greater asthma symptoms and outpatient visits (27). Children who reside in areas with more air pollution experience higher numbers of ED visits compared to children living in areas with low levels of PM_2.5 (10,21). Komisarow and Pakhtigian (28) found that a 1 μg/m³ increase in average annual PM_2.5 concentrations was associated with around an 11% increase in ED visits for asthma-related conditions. Children who live in close proximity to coal-plants, which emit PM_2.5, NO₂, and many other compounds, also suffer worse asthma control. Although coal-consumption declined in the past decade, approximately 7% of all children between 0 and 4 years of age in the U.S. still live within 10-kilometers of an active coal-fired power plant. After the closure of 3 coal-fired powerplants in the Chicago area, there was a 12%-18% reduction in ED visits for asthma exacerbations (28). A case-crossover study investigating the association between air pollution and asthma exacerbation in Philadelphia (n=54,632) found average PM_2.5 levels to be higher during the cold seasons than warm (11.29 μg/m³ and 9.43 μg/m³, respectively). The exposure-response relationship during cold months was essentially linear with no lag time, while during the warm months, the exposure-response curve indicates thresholds of effect at around 8 μg/m³ (29). The current U.S. Environmental Protection Agency (EPA)’s standards for PM_2.5 is set at 12-15 μg/m³ for the annual average (30). Simply summarized, higher levels of air pollution worsen asthma morbidity, and improved air quality can lead to fewer symptoms and better outcomes.

In the U.S., the most widely used resource for air quality information is the EPA’s Air Quality Index (AQI, airnow.gov). The AQI reflects the single highest pollutant for a network area. AQI categories are denoted Good (0-50), Moderate (51-100), Unhealthy for Sensitive Groups (101-150), Unhealthy (151-200), Very Unhealthy (201-300), and Hazardous (301-500). The EPA releases air quality alerts beginning at AQI greater than 100. However, Rosser et al. found that increasing AQI is correlated with higher rates of asthma exacerbations even at AQI below 100, particularly for Black children. A two-day lag time existed between the AQI category and ED presentation (31).

Emerging outdoor exposures

Recent literature implicates increasing ambient temperatures in asthma development and morbidity. A retrospective cohort study of 39,782 children in cities throughout China found that prenatal and postnatal heat exposure was associated with greater risk of childhood asthma. Extreme heat days (in which temperatures were ≥86°F) within a child’s first year of life also increased their lifetime risk for asthma diagnosis (25). With regards to temperature, individuals living in inner-city areas are again at a disadvantage. Low-income neighborhoods have low to no tree canopy, and are comparably hotter than wealthier communities even within the same city (32). A study conducted at the Children’s Hospital of Philadelphia examining 7,637 encounters for asthma found higher daily temperatures increased the risk for asthma exacerbations in preschool-aged children. Notably, this study population was composed of predominantly Black children (81%) on Medicaid and State Children’s Health Insurance Program (33). Mechanistically, heat may trigger bronchoconstriction, promote growth and release of mold and pollens that can worsen asthma symptoms, or catalyze photochemical reactions of nitrogen and VOCs to create O₃, an air pollutant well linked with asthma morbidty (33). These data raise specific concern for asthmatic patients as the effects of climate change build.

Environmental interventions

Children living in urban low-income neighborhoods face many risks for the development of asthma and asthma morbidity. Exposure to higher levels of environmental toxins, allergens, and heat play an important role (Figure 1). Specific environmental interventions have met with mixed results (34-39). In the Mouse Allergen and Asthma Intervention Trial (38) comprised of predominantly Black and Hispanic low-income households, families were provided pest management education, with the intervention group receiving additional professional integrated pest management support. Regardless of whether they were enrolled in the control or intervention group, more than 40% all participating homes had at least a 90% reduction in mouse allergen at some point during the study; this improvement was associated with 0.8 fewer acute care visits and 0.07 fewer hospitalizations per person-year, a reduction greater than seen in some trials of inhaled corticosteroids. Regardless of treatment arm, decreasing mouse allergen levels in bedroom floors by 50% was linked to fewer asthma symptoms, short-acting beta-agonist use, and acute care and ED visits for asthma (38). Lowering home mouse allergen from higher baseline levels was also associated with greater improvements in number of asthma symptom days, less frequent short-acting beta-agonist use, and better exercise tolerance (40). Within the school setting, Phipatanakul et al. (35) found that while throughout the school year school wide integrated pest management did not overall improve asthma symptoms, the intervention did reduce asthma symptoms by 63% in the fall/winter seasons compared to control. Although classroom HEPA filters significantly reduced PM 2.5 and airborne mouse and dog allergen levels, these reducations were not enough to significantly decrease symptoms. Secondarily, IPM did reduce overall school-days missed due to asthma (35). We recently found that mouse allergen levels in the schools has been decreasing over the past decade (41), highlighting the need for continued research into changing environmental exposures in urban homes and schools. In a subsequent sub-analysis of students with higher mold exposure at school (pre-intervention) compared to home, HEPA filtration systems reduced the concentration of molds associated with indoor moisture damage in classrooms and was associated with a 4.2% improvement in FEV1 (42).

Figure 1:

Urban environmental exposures associated with the development of severe asthma. Indoor exposures, including tobacco/e-cigarette smoke, volatile organic compounds, pests, molds, phthalates, bisphenol A, and radon, as well as outdoor air pollution and high ambient temperatures contribute to the development of severe asthma in inner-city populations. Created with BioRender.com

Conclusion

Allergen and toxin exposure may vary over time and effective measures to evaluate the total exposure environment, the interaction between exposures, and the optimal intervention to remediate exposures to optimize health are still significant challenges. Societal structural inequities lay at the core of many of the environmental insults to children and affects the development and morbidity of childhood asthma. Novel discoveries of phthalates, BPA, and radon in relation to asthma need to be further explored, as well as the mode of exposure-outcome relationship. Are the chemicals just in the air or can ingestion and transdermal exposures be harmful? Tackling these questions will lead to impactful scientific discovery and powerful evidence to inform public policy.

Key Points:

1. Children living in inner-cities experience higher levels of indoor and outdoor exposures that increases risk of asthma development and morbidity.

2. Indoor exposures shown to worsen asthma outcomes include pest tobacco/e-cigarette smoke, VOCs, allergens, molds, phthalates, BPA, and radon.

3. Outdoor air pollution and ambient heat has been linked with increased asthma incidence as well as poor asthma control.

4. Pest control measures in homes can help decrease allergen exposures and improve asthma outcomes.

5. Within the school setting, non-sustained health improvements were found with integrated pest management interventions, but not with High Efficiency Particulate Air (HEPA) air purification.