Asthma in the Americas: An Update: A Joint Perspective from the Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, and American Thoracic Society

Abstract

Asthma affects a large number of people living in the Americas, a vast and diverse geographic region comprising 35 nations in the Caribbean and North, Central, and South America. The marked variability in the prevalence, morbidity, and mortality from asthma across and within nations in the Americas offers a unique opportunity to improve our understanding of the risk factors and management of asthma phenotypes and endotypes in children and adults. Moreover, a better assessment of the causes and treatment of asthma in less economically developed regions in the Americas would help diagnose and treat individuals migrating from those areas to Canada and the United States. In this focused review, we first assess the epidemiology of asthma, review known and potential risk factors, and examine commonalities and differences in asthma management across the Americas. We then discuss future directions in research and health policies to improve the prevention, diagnosis, and management of pediatric and adult asthma in the Americas, including standardized and periodic assessment of asthma burden across the region; large-scale longitudinal studies including omics and comprehensive environmental data on racially and ethnically diverse populations; and dissemination and implementation of guidelines for asthma management across the spectrum of disease severity. New initiatives should recognize differences in socioeconomic development and health care systems across the region while paying particular attention to novel or more impactful risk factors for asthma in the Americas, including indoor pollutants such as biomass fuel, tobacco use, infectious agents and the microbiome, and psychosocial stressor and chronic stress.

Over 1 billion people live in the Americas, a large area comprising 35 countries in the Caribbean and North, Central, and South America whose languages include English, Spanish, Portuguese, French, and Creole, along with multiple Native American tongues. The Americas are richly diverse with regard to geography and climate, culture, racial and ethnic composition, industrialization and urbanization, education, economic development, and health indicators.

Asthma affects over 350 million people worldwide and is the most common chronic respiratory disease of childhood. Asthma is a major public health problem across the Americas, though disease prevalence varies, and most disease-related deaths occur in low-income countries. Such variability offers a unique opportunity to improve our understanding of the risk factors and management of diverse asthma phenotypes and endotypes. Moreover, a better assessment of the causes and treatment of asthma in less economically developed regions in the Americas would help asthma management of migrants to Canada and the United States.

In this focused review, we assess the epidemiology of asthma, review known and potential risk factors, examine commonalities and differences in asthma management, and discuss challenges and future directions for research and health policy across the Americas.

Epidemiology

The prevalence, morbidity, and mortality from asthma vary considerably across and within countries in the Americas. The Global Burden of Disease (GBD) provides current estimates of annual prevalence and mortality from current asthma in most nations using vital registry data, systematic literature reviews, unpublished reports, and surveys (1). However, such estimates may lack the accuracy needed to determine whether asthma prevalence has changed since the last comprehensive review of asthma in Latin America (2), and they do not always correlate with local estimates. New efforts are underway to update regional estimates as part of the Global Asthma Network (3).

Current estimates of the prevalence of asthma in North America and the Caribbean are highest in the United States and Puerto Rico, respectively (Table 1; Figure E1 in the online supplement). Belize and Costa Rica have the highest asthma prevalence in Central America, while Argentina has the highest asthma prevalence in South America. Although deaths from asthma are uncommon, Haiti has the highest overall asthma mortality rate. By region, asthma mortality rates are highest in Mexico (for North America), Honduras (for Central America), and Uruguay (for South America). Prevalence, incidence, and mortality from asthma vary widely between regions (e.g., states or departments) within each country (Figure E2 and Table E1 show some regional estimates based on GBD data).

Table 1.

Asthma prevalence and mortality in the Americas

	Population (Millions)*	Asthma Prevalence (%)†		Mortality (per 100,000)	GDP per Capita ($)‡	GDP on Healthcare (%)§	Education Index‖	HAQ Index¶
		Adults	Children
North America
United States	329	10.9	18.5	1.24	65,544	16.9	0.900	81.3
Canada	37.4	4.81	9.9	0.82	43,242	10.8	0.894	87.6
Mexico	127.6	2.85	6.8	1.32	8,347	5.4	0.703	62.6
Central America
Belize	0.4	6.2	10.8	2.06	4,436	5.7	0.695	58.3
Costa Rica	5	5.5	10.5	1.08	12,077	7.6	0.726	72.9
El Salvador	6.4	5.7	9.9	2.78	3,799	7.1	0.555	64.4
Guatemala	17.5	3.2	6.1	1.84	4,603	5.7	0.519	55.7
Honduras	9.7	4.3	7.9	3.79	2,405	7.1	0.499	53.9
Nicaragua	6.5	4.2	7.8	1.55	1,905	8.6	0.573	64.3
Panama	4.2	4.7	9.7	2.46	12,269	7.3	0.700	64.4
South America
Argentina	44.7	7.3	9.3	1.09	8,441	9.6	0.855	68.4
Bolivia	11.5	4.9	10.8	1.62	3,143	6.3	0.695	59.2
Brazil	211	4.6	12.1	1.32	6,799	9.5	0.694	64.9
Chile	18.9	5.8	6.9	1.48	13,232	9.1	0.810	76.0
Colombia	50.3	3.4	7.3	0.55	5,332	7.6	0.682	67.8
Ecuador	17.3	4.4	10.1	0.54	5,600	8.1	0.702	61.2
Paraguay	7	5.7	12.2	1.3	4,950	6.7	0.638	60.4
Perú	32.5	4.4	10.8	0.67	6,127	5.2	0.740	69.6
Uruguay	3.4	6.3	8.4	3.57	15,438	9.2	0.765	72.0
Venezuela	28.5	3.9	7.9	1.48	16,056**	3.6	0.700	64.7
Caribbean
Cuba	11.3	5.9	13	2.3	9,099	11.2	0.790	73.5
Dominican Republic	10.7	4.4	7.7	4.4	7,268	5.7	0.666	62.5
Haiti	11.2	8.4	11.4	8.8	1,177	7.7	0.456	38.5
Puerto Rico	2.9	7.8	15.3	2.65	32,291	N/A	N/A	76.7

Definition of abbreviations: GDP = gross domestic product; HAQ = healthcare access and quality; N/A = not applicable.

^*Population based on United Nations estimates and projections (https://worldpopulationreview.com/countries).

^† Asthma prevalence from Global Burden of Disease data (https://www.healthdata.org/research-article/global-regional-and-national-deaths-prevalence-disability-adjusted-life-years-and and https://vizhub.healthdata.org/gbd-compare/).

^‡ Gross domestic product (GDP) in U.S. dollars, 2020 (https://data.worldbank.org/indicator/NY.GDP.PCAP.CD, accessed 2021 Aug 27).

^§ Healthcare expenditure, 2018 (https://data.worldbank.org/indicator/SH.XPD.CHEX.GD.ZS).

^‖ The education index (http://hdr.undp.org/en/indicators/103706) is the average of mean years of schooling (of adults) and expected years of schooling (of children), both expressed as an index; the maximum is 1.0, which means 100% of citizens in that country attained 15 years of education by age 25.

^¶ Healthcare Access and Quality (HAQ) index, 2015 (https://ourworldindata.org/grapher/healthcare-access-and-quality-index).

^**GDP data for Venezuela as reported for 2014.

The disparities in asthma prevalence across countries in the Americas are predominantly due to variability in socioeconomic status (SES) and related environmental risk factors (4–6), though reporting bias may somewhat overestimate such disparities. Several studies in Cuba, Brazil, Perú, and the United States demonstrate within-country variability in asthma prevalence linked to low SES (7, 8).

Asthma morbidity and mortality are strongly linked to poverty and its correlates, including healthcare access and environmental exposures such as air pollution (8). For example, Canadian citizens have universal access to health coverage (9) and thus reduced use of urgent health care for asthma among lower-income families (10), yet asthma burden varies across Canadian cities along with SES and air quality (11–13). The remarkably high mortality rates in Haiti, the Dominican Republic, and Honduras are largely due to poverty, as impoverished individuals have limited access to controllers such as inhaled corticosteroids (ICS) (14).

Risk Factors

The variable asthma burden across the Americas is likely explained by underlying differences in environmental risk factors, often coexisting in various combinations and interacting with genetic variants. Such environmental risk factors include SES, pollutants and tobacco smoke, diet and obesity, infections and the microbiome, and psychosocial stress.

Racial Ancestry and Omics

Studies of racially admixed Hispanic populations in the United States, Puerto Rico, and Costa Rica have shown that the global proportion of Native American ancestry is associated with reduced asthma risk and higher lung function, while the reverse is reported for African ancestry (15). Such data must be cautiously interpreted, as racial ancestry is correlated not only with genetic variation but also with social and structural determinants of health (SDOH) that affect lung health and growth. Indeed, the burden of asthma varies across ancestral Native American populations, with lower asthma prevalence in Native Americans living in rural areas of South and Central America than in North America (16, 17). While Puerto Ricans and African Americans bear a high asthma burden, other populations with substantial African ancestry (e.g., Dominicans and Afro-Colombians in the Caribbean) are less commonly affected with asthma. Taken together, this suggests that environmental exposures, perhaps as early as in utero, may explain previous findings for ancestry in racially admixed Hispanics and African Americans.

While genomic studies continue to predominantly include populations of European ancestry, admixture mapping and whole-genome sequencing studies have confirmed loci reported in other populations while identifying novel loci in Hispanics (18–20). A recent genome-wide association study, including four cohorts of Latinx youth from the United States, Costa Rica, and Brazil, reported that single-nucleotide polymorphism (SNP) rs2253681 in FLJ22447 is associated with severe asthma exacerbations, a major cause of morbidity (21). In other genome-wide association studies, a Peruvian study identified a novel locus for lung function that may be specific to children with indigenous ancestry (22), while the 6p21.3 locus was associated with asthma hospitalizations in the United Kingdom Biobank and then replicated in two Latinx cohorts (23). A deletion at 6p22.1 was associated with asthma symptom burden in Brazilian children (24), and a Chilean study reported filaggrin loss-of-function variants R501X and 2282del4 associated with asthma but not atopic dermatitis (25). Finally, a recent study in Brazil described SNPs associated with asthma only among subjects with seropositivity for varicella-zoster (26).

“Omics” research has expanded beyond genotypes. Epigenome- and transcriptome-wide analyses of nasal (airway) epithelial samples from Puerto Rican youth recently identified CpG markers and genes associated with atopic asthma (27, 28). Most top results replicated in separate cohorts of African American and European children, implying that most epigenomic pathways contributing to asthma are universal rather than specific to Latinx subjects.

Socioeconomic Factors

Low SES is broadly correlated with environmental and behavioral factors that vary across communities. Low SES is often but not always associated with asthma prevalence, likely due to interactions among SES-correlated risk or protective factors. Poverty, on the other hand, is consistently associated with morbidity and healthcare use for asthma.

A meta-analysis of 68 studies (including some conducted in the Americas) identified poverty as a moderate risk factor for asthma (29). In a nationwide study of U.S. preschoolers, neighborhood disorder was associated with asthma (30), while an observational study including 16.8 million children showed that being enrolled in Medicaid and living in impoverished areas were associated with asthma-related emergency department visits and hospitalizations (31). Many studies across the Americas have shown that living in deprived neighborhoods is associated with higher asthma risk (32–34). However, low SES has been linked to lower risk of asthma in Mexican Americans (who have low asthma prevalence despite being disproportionately represented among the poor) (35), while a survey of U.S. children demonstrated that Black race, Puerto Rican ethnicity, and lower household income (but not residence in poor or urban areas) were independent risk factors for asthma (36). Indeed, recent data further suggest that the effects of SDOH (including poverty, food and housing insecurity, residence in poor neighborhoods, and structural racism) (37, 38) and environmental exposures (39) on asthma are often entangled.

Indoor/Outdoor Pollutants and Tobacco Smoke

Exposure to industrial pollutants or traffic-related air pollution is associated with childhood asthma (40–42). Air pollutants (including particulate matter ⩽2.5 microns [PM_2.5], nitrogen dioxide [NO₂], ozone, and carbon monoxide) are causal or “likely to cause” respiratory conditions such as asthma (43) or trigger asthma exacerbations (44). In the United States, NO₂ exposure may account for 17.6% of incident asthma in children, and second-trimester exposures may be associated with childhood asthma (45, 46). In a recent study evaluating the burden of new asthma cases associated with traffic-related air pollution, Lima and Bogotá occupied two of the top three places in the list (47).

The Surgeon General Report suggests a causal link between cigarette smoking and asthma incidence and exacerbations in children and adults (48). Smoking is common among Latin American adolescents, and active and passive smoking have been associated with asthma in aboriginal populations in Brazil and Canada (49, 50). The use of e-cigarettes, particularly among young persons, has increased alarmingly over the past five years (51). In the United States, e-cigarettes have been associated with asthma in adolescents (52, 53). The effects of pollutants and tobacco smoke on asthma may be modified by other factors, including synoptic weather conditions, aero-allergens, and SES (54).

Diet and Obesity

Obesity has been associated with asthma and greater asthma severity in children and adults (55) worldwide (including those in the Americas) (56–61), with some studies showing a stronger association between obesity and asthma outcomes in females (62). Maternal obesity and diet have also been associated with asthma in the offspring (63, 64), and leptin levels in cord blood are associated with asthma in Chilean infants born to obese mothers (65). However, not all studies have found significant associations between obesity and asthma (66), suggesting a complex and multifactorial relationship.

High intake of fruits and vegetables has been linked to lower asthma risk, while higher consumption of fried/fast food or sweets/dairy has been associated with higher asthma risk in Mexico, Brazil, and Puerto Rico (67–70). A proinflammatory diet has been linked to wheeze, asthma, and lower lung function in Hispanics and the overall U.S. population (71, 72), while the Mediterranean diet has been associated with lower asthma risk in Mexican children (73). A healthier overall diet and higher folate levels have been linked to lower odds of asthma in Peruvian youth (74, 75). In contrast to data for whole diet or dietary patterns, supplementation of individual nutrients such as vitamin D has not been shown to reduce incidence or exacerbations of asthma (76, 77).

Very few studies have examined the impact of weight loss (78) or dietary interventions (at the individual or population level) on asthma or asthma severity in the Americas.

Infections and the Microbiome

Recent findings have improved our understanding of infections and asthma in Latin America (2, 15). A Brazilian study showed an association between the number of helminthic infections (Ascaris lumbricoides, Trichuris trichiura, and Toxocara spp) and eosinophilia, total immunoglobulin E (IgE), increased production of interleukin-10 (IL-10) from unstimulated leukocytes, and reduced skin test reactivity to allergens (79). This further supports a dose-response relationship between helminth infections and atopy through upregulation of IL-10 despite an increased total IgE. However, in that study helminth infections were not associated with asthma (79).

Viral infections commonly trigger asthma exacerbations. In Mexico, viral infections were detected in approximately 60% of children younger than 15 years hospitalized with acute respiratory disease. Human rhinovirus was the most frequent etiology, and human rhinovirus-C was associated with asthma (80). Subsequent work using whole-genome sequencing reported differences in the virome and bacteriome of the upper respiratory tract between children hospitalized with asthma exacerbations and those hospitalized for pneumonia (81). There is no convincing evidence of a link between tuberculosis and atopy or asthma, as shown in a negative Peruvian study (82).

Providing indirect evidence for a role of the microbiome in asthma, a study of school-aged children in Córdoba, Argentina, reported that antibiotic use in the first year of life was associated with an approximately 2.4-fold increased odds of current wheeze and allergic rhinoconjunctivitis among children who lived in an urban area in early life, but not among those who lived in a rural area (83). Further, preschoolers with recurrent wheezing living in rural areas had lower odds of having a positive Asthma Predictive Index than their peers from urban areas (84), and a study within the ECUAVIDA birth cohort in rural Ecuador reported that microbial dysbiosis at age three months was associated with atopic wheeze by age five years (85). Metagenomic analysis found differences in genes involved in carbohydrate and taurine metabolism in the children who developed atopic wheeze. Even in the absence of marked dysbiosis, children with asthma may have altered IgA responses to gut bacteria compared with healthy controls (86).

Psychosocial Stress and Related Factors

Chronic distress due to mental illness or violence exposure has been linked to asthma or asthma morbidity across life stages. For example, a large cross-sectional study of U.S. adolescents showed that victimization, suicidal behavior, and feeling sad or hopeless were each associated with asthma (87). In other U.S. studies, mild to moderate distress was associated with emergency department visits and hospitalizations (88), with neighborhood- and school-related stress linked to emergency department visits for asthma in adolescents (89). In Perú, women who reported more episodes of childhood abuse had higher odds of adult-onset asthma (90). Similarly, an ecological study in Brazil showed a direct correlation between indicators of violence and asthma hospitalizations (91).

There is emerging evidence on the underlying mechanisms for this association. A mechanistic modeling study examining the hypothalamic-pituitary axis in children born to women who reported intimate partner violence showed that intimate partner violence predicted incident asthma and that this association was modified by hypothalamic-pituitary axis reactivity (92). In another study, child or maternal stress and an SNP in a gene that regulates anxiety were associated with reduced bronchodilator responsiveness in diverse children with asthma in Puerto Rico and the United States (93). A recent review may be of interest to readers seeking a broader overview of stress and asthma (94).

Overall Impact of SDOH

There has been increased attention to the role of SDOH in asthma over the past few years. Racial/ethnic and SES inequities that affect asthma morbidity include environmental exposures, housing conditions, health care access and quality, chronic psychosocial stress, competing priorities, and other features associated with structural racism and population injustice. Excellent reviews on SDOH in asthma (95, 96) have recently summarized several of these factors, and Table E2 lists several recent studies on the topic. Most studies directly evaluating SDOH have focused on pediatric asthma in the United States, although these inequities and injustices likely exist throughout the Americas (97).

Management

Guidelines and strategies for asthma management across the Americas have recently been updated (98–103). ICS continue to be the pharmacologic cornerstone of asthma management, but guidelines diverge concerning daily versus intermittent use of ICS. Since 2019, the Genetic Information Nondiscrimination Act has recommended that no patient >12 years with asthma be prescribed an as-needed (pro re nata or PRN) short-acting β-agonist regimen, a recommendation adopted in some but not all guidelines (98, 99, 101, 102) (Table 2).

Table 2.

Comparison of guideline recommendations for step 1 and 2 treatment^*

	Spain (101)	Canada (99)	United States (98)	GINA (100)†
Criteria for step 1	Daytime symptoms <2 per month, 0 exacerbations	Daytime symptoms <2 per week, 0 exacerbations	Daytime symptoms <2 per week, <2 exacerbations per year	Daytime symptoms <2 per month, 0 exacerbations
Step 1 treatment	PRN SABA; PRN ICS/formoterol	PRN SABA; PRN ICS/formoterol; or daily ICS	PRN SABA; PRN SABA with ICS course (for 0–4 yr)	PRN ICS/formoterol; or PRN ICS and SABA
Step 2 treatment	Daily ICS	Daily ICS	Daily ICS plus PRN SABA; PRN ICS and SABA	PRN ICS/formoterol; or daily ICS plus PRN SABA

Definition of abbreviations: GINA = Global Initiative for Asthma; ICS = inhaled corticosteroids; PRN = as needed (pro re nata); SABA = short-acting β-agonist.

Spanish guidelines are used in certain Latin American countries such as Argentina and Brazil and are therefore included here.

^*Recommendations for patients 12 years of age and older unless otherwise noted.

^† Brazil and Argentina recently published national guidelines based on GINA recommendations (102, 103).

Improving Asthma Control and Exacerbation Rates

Misperceptions about asthma control and controller medications are common in the Americas. The AIMS study found that 60–77% of patients rated their asthma as well-controlled, despite only 8–29% having well-controlled disease (104) (Table 2). Compared with North American patients, Latin American patients are less likely to agree on the need for controller medications (64–74% versus 41%), which may partly explain high hospitalization rates in Latin America (Table 3). A U.S. study showed that subjects with lower income or education and present unemployment were less likely to use antiinflammatory medications for asthma (105).

Table 3.

Patient perception of asthma control, asthma management, and indicators of symptom control

	Canada, %	United States, %	Latin America, % (Range)*
Patients’ perception of asthma control
Patients rated their asthma as well-controlled	77	71	60
Patients agreeing that asthma was well-controlled with these criteria
Urgent care 2 visits/year	50	67	2 urgent care visits/year or 3 to 4 exacerbations/year or 1 emergency department visit/year: 44–51
Emergency department 1 visit/year	60	60
Reliever required 3 times a week	42	46
Fear of exacerbation keeps them from doing what they want	25	29	43 (35–57)
Indicators of asthma control
Asthma symptoms daily or on most days	26	27	24 (Mexico: 12; Argentina: 35)
Asthma control (GINA or NHLBI criteria)
Well-controlled	18	29	8 (Venezuela: 3; Brazil/Mexico: 9)
Uncontrolled	24	47	35 (Venezuela: 32; Argentina: 57)
Systemic steroids in last year	30	35	43 (29–53)
Hospitalization in last year	5	6	23 (Venezuela: 14; Brazil: 27)
Medication use
Controller used daily	52	80	38
Use of controller interrupted >1 mo	30	24	61 (Argentina: 49; Brazil: 71)
Beliefs about asthma medications
Maintenance medication should be used daily	64	74	41 (Venezuela: 26; Argentina/Puerto Rico: 61)
Worry about use of systemic steroids	54	57	61
Worry about use of inhaled steroids	Not reported	Not reported	60

Definition of abbreviations: GINA = Global Initiative for Asthma; NHLBI = National Heart, Lung, and Blood Institute.

Adapted from Nathan and colleagues (104).

^*Countries surveyed: Argentina, Brazil, Mexico, Venezuela, Puerto Rico (range includes country-specific data where provided).

Increased access to guideline-based care can improve asthma management in the Americas. In Brazil, government provision of free ICS increased medication use, decreased hospitalizations, and was cost-effective (106). Similarly, asthma programs integrating education with access to healthcare providers and asthma medications decreased severe asthma exacerbations in Colombian children from 25.1 to 3 per hundred people per year (107).

Diagnosing Treatment-Resistant Severe Asthma

The approach to identifying patients with treatment-resistant severe asthma is similar across the Americas and requires access to guideline-based asthma care (100, 104, 108). Ongoing follow-up is particularly important, as asthma severity is dynamic and changing. Over a 10-year follow-up, 8% of adults with mild asthma progressed to either moderate or severe asthma (109), while only 17% of those initially classified with severe asthma persisted with severe disease (110). In children, 50% of those with severe asthma improved when assessed over three years and were reclassified as nonsevere (111).

After asthma is confirmed and comorbidities are excluded or adequately treated, treatment-resistant severe asthma is defined as asthma that requires treatment with high-dose ICS and a second controller to maintain control or remains uncontrolled despite this treatment (108). The prevalence of severe asthma is difficult to determine and is estimated to be approximately 5% of adult patients, with a Dutch study identifying a prevalence of 3.6% using population-based pharmaceutical data (112). Yet, in clinic-based samples in Latin America, 31% of adults (113) and 12% of children (114) were identified as having treatment-resistant severe asthma; these patients had higher rates of some comorbidities and high healthcare utilization. In North America, similar patterns of increased healthcare utilization and high per-patient costs for those with severe asthma have been reported.

Management of Treatment-Resistant Severe Asthma

Current guidelines for treating severe asthma are similar across the Americas. While most medications target Th2 pathways (Figure 1), a long-acting inhaled muscarinic antagonist can be safely used in children and adults with uncontrolled disease, regardless of endotype (100, 115). Data for tiotropium accessibility is scarce, with broad differences in use among countries (e.g., 4.5% in the United States [116] versus 18.5% in some Latin American countries [113]). This may be due to differential access to treatment options and/or considerations of cost-effectiveness (117). While the use of theophylline is now less frequent in the United States, it may be higher in other countries (118).

Figure 1.

Pathophysiologic pathways in Th2-high severe asthma. Shown are asthma pathways relevant to currently approved biologics or those being currently evaluated. Reprinted from Reference 120, under Creative Commons Attribution License (CC BY); original figure created by the authors using Biorender. IgE = immunoglobulin E; IL = interleukin; ILC2 = innate lymphoid cell group 2; PGD₂ = prostaglandin D2; Th2 = T-helper cell type 2; TSLP = thymic stromal lymphopoietin.

Monoclonal antibodies or “biologics” for Th2-high severe asthma aim to inhibit high-affinity IgE receptors or IL pathways (IL-5 or its receptor IL-5Rα; or IL-4Rα, which binds both IL-4 and IL-13) (Figure 1). Data on efficacy and safety of approved biologics for clinical use (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) support the use of these drugs as add-on therapy for patients with severe uncontrolled asthma (100, 116), as they decrease exacerbations, reduce oral corticosteroid use (mepolizumab, benralizumab, and dupilumab), and improve lung function (mepolizumab, benralizumab, and dupilumab) and asthma control (115).

Biologics are more broadly available in high-income countries across the Americas than in low- and middle-income countries (Figure 2); omalizumab is the most accessible, while reslizumab is only available in North America. While 75.3% of insured severe asthmatics in the United States were on biologics and 24.7% on oral corticosteroids (116), the exact proportion of patients on biologics in Latin America and Canada, or among the uninsured in the United States, is unknown and equitable access to such therapies remains a barrier to advanced care, particularly in low- and middle-income countries. Moreover, it will be important to consider local realities when allocating limited resources; for instance, a recent study from Colombia reported that omalizumab may not be cost-effective for treating children with uncontrolled severe allergic asthma (119).

Figure 2.

Monoclonal antibodies approved for the treatment of severe asthma across the Americas. Data for the United States obtained from https://www.accessdata.fda.gov/scripts/cder/daf/​index.cfm; for Canada from https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html; and for other countries in the Americas directly from practicing physicians and/or pharmaceutical companies as of August 2021. Map created using https://mapchart.net under CC BY-SA license. BE = benralizumab; DU = dupilumab; ME = mepolizumab; OM = omalizumab; RE = reslizumab.

Conclusions and Future Directions

Studying asthma across the Americas presents unique opportunities to improve our understanding of risk factors and challenges to improve disease control. Although not addressed in the GBD report, asthma prevalence is changing across the region, increasing in some countries while remaining stable in others. Regional studies with standardized methodology and frequent, longitudinal sampling are needed to understand what drives changes over time and, more importantly, implement effective public health policies for prevention and management.

Representation of non-White racial and ethnic groups should be an explicit aim of large-scale genomics studies with adequate data on sociodemographic factors and environmental exposures across groups with different ancestries. Dynamic “omics,” such as studies of epigenomics, transcriptomics, and metabolomics, can help us understand how different and changing conditions lead to contrasts in asthma prevalence and severity. In particular, comparative studies aiming to identify risk or protective factors correlated with underlying racial or ethnic ancestry in different environments, including dietary patterns, the virome and the microbiome, infectious agents, and psychosocial stressors and chronic distress, should yield novel insights into the pathogenesis and progression of asthma endotypes and phenotypes across the Americas.

It will also be crucial to better understand the impact of SDOH on asthma disparities in the continent, as well as the most impactful and effective approaches to mitigate and eliminate such injustices, both at the individual and systems levels. Professional societies such as the American Thoracic Society (ATS), the Asociación Latinoamericana de Tórax (ALAT), the Canadian Thoracic Society (CTS), and the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) are uniquely positioned to champion these goals across the region.

In parallel with furthering our understanding of asthma causation, Pan-American collaborations could help improve disease management and outcomes across the region. Barriers to treatment are rarely unique to individual countries, and thus common policy approaches could be implemented across the region. Among these barriers are existing inequities in access to healthcare, predominant in low-income countries but also common in otherwise developed countries like the United States. Disseminating evidence-based guidelines will help improve and standardize asthma management, but this should be done while addressing misperceptions about asthma medications, particularly ICS. Finally, patients with severe treatment-resistant asthma, a relatively small group with very high healthcare utilization and at high risk of mortality, would benefit from wider access to monoclonal antibodies or “biologics.”