Asthma and Chronic Obstructive Pulmonary Disease

INTRODUCTION

In the United States (U.S.), asthma and chronic obstructive pulmonary disease (COPD) disproportionately affect minorities and disadvantaged communities. In this article, we review the burden and potential risk factors for racial or ethnic disparities in asthma and COPD and briefly discuss future directions in this field.

ASTHMA

Asthma affects >300 million people worldwide, with marked variability in disease prevalence and severity^1–4. In the U.S., asthma affects >25 million people, including 5.8% of children and 8.4% of adults, but disease prevalence varies widely by racial/ethnic group, ranging from 3.5% in Asians to 12.3% in non-Hispanic (NH) Black adults (Table 1)². Similarly, the prevalence of asthma is higher in Puerto Ricans, individuals below the federal poverty level, and sexual and gender minority groups^5–6.

Table 1 –

Prevalence of asthma in the U.S.

	Children	Adults
By biological sex
• Female	6.0%	10.4%
• Male	5.7%	6.2%
By race / ethnicity
• White, non-Hispanic (NH)	7.6%	5.5%
• Black NH	10.8%	12.3%
• AI/AN NH	10.8%	9.3%
• Asian NH	3.5%	3.5%
• Multiple NH	11.5%	13.8%
• Hispanic	6.7%	6.7%
– Mexican	5.5%	5.3%
– Puerto Ricans	n/a	12.8%*
– Other Hispanic	8.7%	8.8%
By income level
• <100% of FPL	11.0%
• 100–250% of FPL	8.7%
• 250–400% of FPL	6.9%
• >400% of FPL	6.7%

Data from Network GA, The Global Asthma Report, 2018. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf. Accessed Aug 7 2022.

^*Based on 2017 CDC data.

After rising for several decades, the prevalence of asthma has plateaued in some areas, but trends differ by age, income, and region. The prevalence of current wheeze and severe asthma symptoms in children decreased from the late 1990s to the mid-2010s in South-East Asian and Western Pacific countries but increased in African and Eastern Mediterranean countries, with no significant changes in the Americas or Europe⁴.

Every year, ~40% of persons with asthma in the U.S. have ≥1 disease exacerbation², leading to >1.8 million emergency department (ED) visits and nearly 170,000 hospitalizations, with rates much higher in children than in adults (e.g., for ED visits: 108 per 10,000 children vs. 41.8 per 10,000 adults). Exacerbation rates are higher in NH Blacks and Puerto Ricans than in NH whites and Mexican Americans^7,8. Mortality from asthma increases with age –from ~2.8 per million in children to over 30 per million in those older than 64 years. While asthma mortality rates have declined, such rates are much higher in NH Blacks than in NH whites (Table 2)².

Table 2 –

Asthma mortality rates in the U.S.

	Children	Adults
Overall	2.8 (0.20)	15.4 (0.24)
By biological sex
• Female	2.3 (0.25)	18.1 (0.37)
• Male	3.3 (0.30)	12.5 (0.32)
By race / ethnicity
• White, non-Hispanic (NH)	1.4 (0.19)	13.0 (0.28)
• Black NH	10.7 (0.98)	34.9 (1.04)
• AI/AN NH	n/a*	17.0 (2.87)
• Asian NH	n/a*	12.4 (0.86)
• Hispanic	n/a*	10.0 (0.48)

Mortality rate (SE) per 1,000,000 population, listing asthma as underlying cause of death using ICD10 codes J45-J46. Data from Network GA, The Global Asthma Report, 2018. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf. Accessed Aug 7 2022.

^*Rates not calculated when deaths <20 for a given subgroup.

Risk factors for health disparities in asthma

Structural and social determinants of health

Structural and social determinants of health (SSDOH) are non-biological factors that affect the environment in which individuals live, attend school, and work, ultimately affecting health outcomes. SSDOH encompass health behaviors, socioenvironmental conditions, and other factors influenced by societal policies and structures.

SSDOH and unequal environmental exposures are key contributors to asthma disparities⁹. American Indians and Alaska Natives have a higher prevalence of chronic respiratory disease – including asthma– than NH whites, but such risk is largely due to education, marital status, income, smoking, and obesity¹⁰. Lower SES and parental education, neighborhood violent crime, poor healthcare access, and discrimination have been linked to ED visits and hospitalizations for asthma in children^11–13. Conversely, adequate health insurance is associated with better asthma outcomes through reduced cost barriers and access to physician visits¹⁴.

Multipronged approaches could best address SSDOH while improving asthma outcomes¹⁵, as single interventions may be insufficient. The Affordable Care Act markedly reduced the proportion of U.S. residents without health insurance but lacked a similar impact on use of asthma medications or regular access to care, due to uncovered costs¹⁶. Recent reviews on SSDOH and asthma may be of interest^17,18.

Psychosocial stress

As recently reviewed¹⁹, psychosocial stressors and chronic stress are associated with asthma across life stages²⁰. Maternal stress during pregnancy has been linked to asthma in the offspring and could potentiate detrimental effects of air pollutants²¹. Living in unsafe neighborhoods has also been linked to worse asthma outcomes in children^22,23.

Psychosocial stressors and related distress could affect asthma through mechanisms including reduced response to treatment¹⁹. Violence-related distress may reduce response to inhaled corticosteroids (ICS), a key controller medication²⁴. In Puerto Rican children, exposure to violence was associated with asthma via methylation of ADCYAP1R1, a gene implicated in childhood anxiety and post-traumatic stress disorder (PTSD)²⁵. Follow-up studies showed that an ADCYAP1R1 polymorphism was associated with reduced bronchodilator response in youth and with a radiologic marker of anxiety in traumatized adults²⁶. Further, World Trade Center rescue and recovery workers with probable PTSD after 9/11 were at higher risk of new-onset asthma, independently of smoking²⁷.

Environmental exposures

Indoor and outdoor pollution contribute to asthma disparities. In the U.S., NO₂ exposure may account for ~18% of pediatric asthma cases per year²⁸, and NO₂ and other pollutants disproportionately affect vulnerable populations. Greater exposure to PM_2.5, NO₂, and ozone is associated with asthma hospitalizations among U.S. residents on Medicaid²⁹, and such associations happened at concentrations below reference standards, highlighting no ‘safe’ levels of pollution. Further, the effects of PM_2.5 and ozone on asthma hospitalizations were more pronounced in persons with obesity and those living in disadvantaged neighborhoods²⁹.

“Redlining” started in the 1930s, when neighborhoods predominantly inhabited by NH Blacks and immigrants were graded as high risk for mortgage defaults and marked in red. Redlining determined where highways, factories, and toxic waste sites were built, perpetuating high exposure to pollutants and other risk factors for asthma. In Pittsburgh, lower neighborhood “mortgage lending desirability” is associated with higher exposure to PM_2.5, SO₂, carbon monoxide, and volatile organic compounds (VOC), which was in turn correlated with uncontrolled asthma³⁰. Similarly, historically redlined census tracts in California have persistently higher rates of ED visits for asthma³¹.

Indoor exposure to allergens and other pollutants such as VOC or PM from heating or cooking have been associated with symptoms and exacerbations of asthma^32,33. Such exposures can also exist at schools but reducing school allergen levels has no proven long-term beneficial effects on asthma³⁴.

Genetic susceptibility and comorbidities may worsen the effects of pollutants on asthma morbidity^35,36. Further, multiple allergens and pollutants may have synergistic effects^37,38, and thus multi-pronged interventions may have greater beneficial effects on asthma than single-target interventions³⁹.

Active smoking and second-hand smoke can cause or worsen asthma, and both are more common in individuals of lower SES. Use of e-cigarettes has disturbingly increased in the past decade⁴⁰, jeopardizing gains in the fight against tobacco. E-cigarettes and other electronic nicotine delivery systems (ENDS) have been associated with asthma in youth^{41, 42}. Moreover, combined use of e-cigarettes with traditional cigarettes or marijuana further increases asthma risk⁴¹. Inhaled substance use is also higher among sexual minority youth⁴³.

NH Blacks and Puerto Ricans are heavily affected with obesity, which may affect asthma risk directly or through interactions with other risk factors^44,45. Similarly, a pro-inflammatory diet has been linked to worse asthma outcomes, but little is known about diet and asthma disparities⁴⁶.

Genetics

Recent genetic studies have better represented racial and ethnic minorities. Such studies have shown that while many asthma risk loci are “cosmopolitan” (affecting most groups), some are race- or ethnic-specific⁴⁷. A recent genome-wide association study (GWAS) of over 4,000 Latinx youth identified a novel polymorphism in FNJ22447 that was associated with severe asthma exacerbations⁴⁸, and another GWAS in African American and Hispanic children identified DNAH5 polymorphisms associated with bronchodilator response⁴⁹. Conversely, a recent analysis of ICS response identified risk polymorphisms in ROBO2 that were replicated in Europeans but not in racially admixed subjects⁵⁰.

Epigenetic regulation of gene expression provides a link between environment and asthma. In a recent study, DNA methylation markers in nasal epithelium that were associated with maternal stress and gun violence exposure were also associated with asthma⁵¹. In a small proof-of-concept study, low SES in children with asthma was associated with a negative family emotional climate, which in turn predicted lower expression of NR3C1, a glucocorticoid receptor gene linked to ICS response in asthma⁵². These and other studies illustrate the potential of “omics” to improve our understanding of asthma disparities.

Disparities in diagnosis, morbidity, and management

Affordable access to healthcare is a SSDOH. Minorities and individuals of lower SES are more likely to require ED visits and hospitalizations for asthma⁵³, often due to inadequate access to primary care. A database-driven study from a pediatric hospital showed that, compared to NH whites, Hispanics were ~50% less likely to have sufficient electronic health record data to determine asthma severity, while NH Blacks were ~50% less likely to have spirometry data⁵⁴.

Disparities are particularly concerning for severe asthma. In the U.S., NH Black children with severe asthma have worse asthma control and quality of life than NH white children⁵⁵. In the U.K., non-white adults suffer higher asthma burden than white adults yet are less likely to be prescribed systemic corticosteroids⁵⁶. Access to a subspecialist’s care for severe asthma can improve outcomes, but patients facing social and health inequities may lack such access, even in countries with universal healthcare⁵⁷.

Tele-health solutions could improve healthcare access for underserved patients with asthma. However, technology-based solutions may not adequately serve disadvantaged populations lacking connectivity or technological savviness. Other non-hospital-based solutions, such as school-based clinics have improved asthma management for marginalized populations⁵⁸ and could be models for future interventions. Similarly, incorporating a subspecialty asthma clinic into prenatal care led to improved asthma symptoms and quality of life in inner-city women⁵⁹. Ongoing studies are evaluating interventions such as home visits and clinic navigators in low-income populations with poorly controlled asthma⁶⁰ while others have described interventions to mitigate the deleterious impact of poor housing on asthma⁶¹.

Developing novel interventions to reduce health disparities in asthma will require increased representation of historically excluded populations in research studies⁶².

COPD

COPD, a progressive respiratory illness including chronic bronchitis and emphysema, affects 11 million people and is the third leading cause of death in the U.S.⁶³. The burden of COPD varies across racial and ethnic groups, along with differing SSDOH, environmental, and heritable factors (Figure 1).

Figure 1. Genetic and Environmental Factors Influencing COPD.

COPD is due to interactions between genetic and environmental risk factors. Racial or ethnic disparities in COPD are largely due to unequal exposure to tobacco smoke and other environmental risk factors in genetically susceptible individuals.

Over the past two decades, the prevalence of COPD has become similar between NH whites and African Americans^64,65. Recent estimates of the prevalence of self-reported physician-diagnosed COPD were 6.9% in NH whites and 6.5% in African Americans⁶⁴. Similarly, spirometry-based estimates of COPD prevalence (which are unaffected by healthcare access) were 15% in NH whites and 14.1% in African Americans (Figure 2)⁶⁵.

Figure 2. Self-Reported COPD, Spirometry-Confirmed COPD, and Current Smoking Prevalence Across Racial and Ethnic Groups.

Data for self-reported COPD from references 64 and 66, those for spirometry-defined COPD from references 65 and 67 and those for current smoking from references 76 and 79.

COPD prevalence varies across Hispanic subgroups. From 2007 to 2009, U.S. estimates of the prevalence of self-reported COPD were highest in Puerto Ricans (6.9%) and lowest in Mexican Americans (2.6%)⁶⁶. In the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), age- and sex-adjusted estimates of the prevalence of spirometry-defined COPD were highest in Puerto Ricans (14.1%) and lowest in Mexicans (4.6%), with intermediate values in Central and South Americans (5.2–5.9%), Dominicans (5.6%), and Cubans (9.8%)(Figure 2)⁶⁷. Additional adjustment for asthma onset before age 45 years resulted in non-significant differences in COPD prevalence across subgroups, suggesting that asthma contributes to the pathogenesis of COPD or Asthma-COPD Overlap in Puerto Ricans⁶⁷.

NH whites have a higher prevalence of self-reported COPD than Mexican Americans, even after accounting for smoking, occupation, and country of birth⁶⁸. This could be due to lower susceptibility to COPD in Mexican Americans or unmeasured confounders such as depth of smoking inhalation^{68, 69}.

Compared with NH whites, African Americans and Mexican Americans have greater COPD severity but no increased mortality. In COPDGene, the proportion of participants with early-onset COPD was higher in African Americans (42%) than in NH whites (14%)⁷⁰. Moreover, African Americans with prior COPD exacerbations reported worse quality of life than NH whites⁷¹. Other studies have shown that, compared with NH whites, African Americans were younger and had fewer pack-years of smoking when presenting with advanced emphysema and COPD⁷². Similarly, Mexican Americans with COPD are more likely to report poor quality of life than NH whites, partly because of worse healthcare access⁷³.

In the U.S., mortality rates from COPD decreased from 1999 to 2013⁷⁴. In 2013, COPD mortality rates (per 100,000 individuals) were lower in African Americans than in NH whites ((22.7 vs. 54.8)⁷⁵. Similarly, 2013 mortality rates from chronic lower respiratory diseases (per 100,000 individuals) were lower in Mexican Americans (18.3), Puerto Ricans (26.9), and Cubans (28.0) than in NH whites (46.7)⁷⁶. Although longitudinal studies have shown similar mortality rates from COPD in NH whites, Mexican American, and African Americans⁷⁷, those studies included never smokers and lacked comprehensive information on tobacco use.

Risk factors for health disparities in COPD

The strongest risk factor for COPD is tobacco smoking, but genetic variants, biomass smoke, and occupational hazards can cause COPD in ever and never smokers⁷⁸.

Tobacco smoking

Disparities in tobacco use are determined by marketing strategies targeting marginalized groups. In 2016, 15.5% of all adults in the U.S. reported current smoking but adults who were uninsured or insured by Medicaid and those below the poverty line were more likely to be current smokers⁷⁹. Further, current smoking is more common in American Indians or Alaska Natives (31.8%) than in African Americans and NH whites (16.5–16.6%)⁷⁹. Among Hispanic subgroups, current smoking is highest in Puerto Ricans (21.6%) and Cubans (18.2%) and lowest in Mexican Americans (13%), with intermediate values in Central and South Americans (9.2%)(Figure 2)⁷⁶. Such differences can be explained or modified by sex (because of higher smoking prevalence in males than in females) and nativity (because of higher smoking prevalence in U.S.-born than in foreign-born Hispanics.⁷⁶

While the low prevalence of COPD in Mexican Americans is mostly attributable to low rates of smoking⁷⁶, factors other than smoking (e.g., healthcare access) likely explain why African Americans have more severe COPD despite lower smoking intensity than NH whites^70,72,80,81. Smoking cessation services should be pursued and are beneficial in African Americans despite a greater tendency towards nicotine dependence and lower cessation rates than NH whites^82,83.

Outdoor pollutants, biomass fuel, and occupational hazards

Outdoor pollutants increase the risk of COPD and related morbidity^84,85. In SPIROMICS, levels of particulate matter with a diameter <2.5μm (PM_2.5) were higher while ozone levels were lower in medium-to-high poverty areas. Despite lower ozone levels, residents in medium-to-high poverty areas experienced greater adverse effects of ozone on COPD symptoms and exacerbations⁸⁶. African Americans residing in segregated neighborhoods have higher ozone exposure, lower lung function, and more exacerbations and emphysema on CT scans than those in non-segregated neighborhoods⁸⁷. The risk of COPD in vulnerable populations may be further increased through interactions between pollutants and other factors (e.g., non-access to healthy foods)⁸⁸. Further, immigrants from low-to-middle income countries, particularly women, may have been exposed to household combustion of biomass fuels, a risk factor for COPD^89,90.

The fraction of COPD cases attributable to workplace exposure to hazardous chemical gases, fumes, and dusts may be as high as 31%⁹¹. In NHANES III, such attributable fraction was much higher in Mexican Americans (49.6%) than in African Americans (23.4%) or NH whites (22.2%)⁹¹. African Americans and Hispanics are more likely to work in hazardous settings than NH whites, which could contribute to COPD disparities^92,93.

Genetics of lung function and COPD

GWAS of lung function and COPD have identified both overlapping and distinct risk loci in the general population and at-risk smokers. This is expected, as COPD is often defined by airflow obstruction on spirometry. GWAS of lung function in general populations have identified loci that regulate lung development and inflammatory and proteolytic pathways, while COPD GWAS in ever smokers identified distinct loci related to nicotine addiction and proteolytic pathways, including SERPINA, the alpha₁-antitrypsin gene^94–97.

The largest lung function GWAS to date identified 279 risk loci in over 400,000 Europeans, but those loci had weaker associations with COPD in African Americans than in NH whites in independent cohorts⁹⁶. COPD genetic risk scores developed from GWAS data were associated with a smaller number of distal airways, more emphysema, thinner airway walls, and smaller airway lumen sizes in NH whites, but those associations were not all found in African Americans or Hispanics, likely because of ancestry-specific differences in allelic frequencies of GRS loci⁹⁸. Consistent with “cosmopolitan” and “ethnic-specific” susceptibility loci, a GWAS of lung function in Hispanic adults replicated loci reported in NH whites while identifying eight novel susceptibility loci, including ZSWIM7, a gene involved in DNA repair⁹⁹. Ancestry-specific variation has been reported for SERPINA1, the strongest genetic risk factor for COPD¹⁰⁰.

Genetic ancestry, lung function, and COPD

Genetic markers can be used to estimate an individual’s genome-wide (global) continental ancestry. In cross-sectional studies of African Americans and Puerto Ricans, African ancestry was associated with lower FEV₁ and FVC, but not FEV₁/FVC, independent of SES, health insurance, sitting height, and other covariates^101,102. In contrast, higher Native American ancestry has been associated with higher lung function measures, including FEV1/FVC, and reduced risk for COPD in Costa Ricans and New Mexico Hispanics^103,104. The trends observed for Native American ancestry align with the lower prevalence of COPD in Mexican Americans.

Tobacco smoking may interact with ancestry-correlated factors to influence COPD risk and progression. In Costa Ricans, 31% of the estimated effect of Native American ancestry on COPD was mediated by smoking intensity¹⁰³. Similar interactions could partly explain greater COPD severity in African Americans^70,105.

Disparities in diagnosis, severity, and management

COPD diagnosis and severity are based on how an individual’s lung function measures compare to population-based reference values. Reference equations quantify racial differences through correction factors resulting in predicted lung function estimates biased by considering race as a biologic variable but not as a marker of SSDOH and environmental exposures^106–108. The Global Lung Function Initiative (GLI) Network has developed reference equations to predict lung function in NH whites and African Americans, but not for Africans or Hispanics (categorized as “others”)¹⁰⁹. Race- or ethnicity-based NHANES III lung function estimates can result in African Americans having better predicted lung function than NH whites, while GLI equations for “others” led to the opposite phenomenon¹¹⁰. GLI equations were also better correlated with COPD symptoms and quality of life in African Americans¹¹⁰. Race-specific approaches to estimating lung function perpetuates the false assumption that lower lung function is a “normal” attribute in non-whites and obscures true causes of disparities, resulting in a lower likelihood that society will identify and act upon modifiable causes for impaired lung function.

Ancestral differences in lung function have implications for race and ethnicity-based spirometry reference equations¹¹¹, which can misclassify COPD severity. Such misclassification becomes increasingly complex in Puerto Ricans, Dominicans, and Cubans with variable inter-individual proportions of African, Native American, and European ancestry^102,112. Studying racially admixed Hispanic subgroups could improve reference equations and understanding ancestry-correlated variability in lung function.

Disparities exist for beneficial COPD interventions. African Americans and Hispanics with COPD are less likely to engage in smoking cessation interventions, be vaccinated against influenza, or use supplemental oxygen^113–116. Compared with NH whites, African Americans are less likely to have health insurance or a primary care provider, but more likely to use the emergency department for primary care^117,118. Cumulative differences in access may contribute to greater COPD severity in African Americans¹¹⁹.

CONCLUSION

In the U.S., the burden of asthma and COPD varies across racial or ethnic groups, largely because of unequal exposure to environmental exposures such as tobacco smoke and pollutants, which is in turn determined by SSDOH that affect education, housing, occupation, and healthcare access for marginalized communities. Governmental and health policies that promote clean air (free from tobacco smoke and pollution), occupational safety, and universal healthcare have the greatest potential to mitigate disparities in asthma and COPD. More inclusive and diverse research studies of well-characterized populations are necessary to fully understand the genetic and environmental determinants of asthma and COPD in all people.

Key points:

• In the United States, the burden of asthma and COPD vary across racial or ethnic groups.

• Racial or ethnic disparities in asthma and COPD are largely due to correlated disparities in environmental exposures such as tobacco smoke and air pollution, which are in turn rooted in longstanding inequities determined by structural and social determinants of health (e.g., racism, redlining) that affect education, housing, occupation, and healthcare access.

• Long-term policies to reduce the negative impact of structural and socioeconomic barriers, including those promoting clean air and universal healthcare, have the greatest potential to mitigate health disparities in asthma and COPD.

Synopsis.

In the United States, asthma and chronic obstructive pulmonary disease (COPD) disproportionately affect African Americans, Puerto Ricans, and other minority groups. Compared with non-Hispanic whites, minorities have been marginalized and more frequently exposed to environmental risk factors such as tobacco smoke and outdoor and indoor pollutants. Such divergent environmental exposures, alone or interacting with heredity, lead to disparities in the prevalence, morbidity, and mortality of asthma and COPD, which are worsened by lack of access to healthcare. In this article, we review the burden and risk factors for racial or ethnic disparities in asthma and COPD and discuss future directions in this field.