Aiming to Improve Equity in Pulmonary Health: Cystic Fibrosis

INTRODUCTION

Cystic fibrosis (CF), the second most common life-shortening autosomal recessive genetic disorder in the United States, is characterized by abnormal secretions in multiple organ systems and progression to eventual respiratory failure.¹ Although the disease is caused by mutations in a single gene—the CF transmembrane conductance regulator (CFTR)—there is a substantial variation in disease progression and outcomes among individuals with identical CFTR genotypes.^2–4 This variability is due to multiple factors, both genetic and nongenetic.^2,5–7 The nongenetic factors—social,economic, environmental, and behavioral–contribute substantially to observed disparities in health and well-being among people with CF.^2,8–12

EVIDENCE OF HEALTH DISPARITIES IN CYSTIC FIBROSIS

Disparities in CF health outcomes are observed across all categories of disadvantage, including race, ethnicity, socioeconomic status (SES), geographic location, sexuality, and gender identity.¹³ Below, we summarize the current evidence of disparities based on these factors.

Disparities by Race and Ethnicity

Members of racial or ethnic minorities make up a growing proportion of US patients with CF, currently more than 18%.¹ Between 2005 and 2020, the CF Foundation Patient Registry (CFFPR), a national registry that collects longitudinal demographic, clinical, and treatment information about people with CF in the United States, reported an increase from 4.0% to 4.7% for Black or African Americans, from 6.3% to 9.6% for Hispanics/Latinos, and from 2.1% to 3.9% for other designations.¹ Patients with CF from racial and ethnic minority backgrounds experience greater disease burden and worse outcomes than their counterparts. For example, Black individuals with CF have lower lung function (percent predicted FEV₁, ppFEV₁) than White counterparts,^14,15 and in the Southern United States, which has the highest proportion of Black population, Black individuals also have a higher risk of future hospitalization.¹⁶ Similarly, Hispanics/Latinos with CF have approximately 6% lower ppFEV₁ than non-Hispanic/Latino counterparts after adjusting for demographic and clinical covariates,^15,17 and in the Western Unites States, which has the highest proportion of Hispanic/Latino population, Hispanic/Latino individuals with CF have on average 9.0% lower ppFEV₁.¹⁸ Significant increases in CF mortality among Black and Hispanic/Latino patients, as compared with their White non-Hispanic counterparts, have also been reported.^19,20

As the social aspects of race and ethnicity far outweigh any genetic basis,^21–23 the association of minority race and ethnicity with worse outcomes in populations with CF is greatly attributable to unequal social conditions and long-standing structural inequalities. For example, both Black and Hispanic/Latino individuals with CF reside in neighborhoods with lower household income and have Medicaid insurance at higher rates (52.2% and 41.8%, respectively) than their non-Hispanic White counterparts.¹⁹ It is notable that the worse CF outcomes among Hispanics/Latinos occur in spite of documented CF protective factors in this population, such as higher body mass index (BMI) and a larger proportion of residual function pancreatic sufficient CFTR mutations.^17,24

Disparities by Socioeconomic Status

Assessed with indicators such as income, education, occupation, health insurance type, and SES has been linked to a host of differential CF outcomes during the last 2 decades. Studies report up to 10% lower lung function (ppFEV₁),^25–27 twice the odds of chronic Pseudomonas aeruginosa infection (which is generally associated with a more rapid long-term decline in lung function),²⁷ and 44% increased mortality risk²⁶ between people with CF who reside in low-income versus high-income areas. The disparity exists not only at the extremes of the socioeconomic gradient. A longitudinal analysis of 2006 to 2016 data from the CFFPR shows a dose–response relationship between annual household income and lung function, where every additional US$10,000 is associated with a 0.2% increase in ppFEV₁ after controlling for demographic and clinical covariates.²⁸

Similar disparities in lung function are reported by educational status. Lower maternal education was associated with 4.2% lower ppFEV1 at the age of 6 to 7 years in the Early Pseudomonas Infection Control (EPIC) Observational Study,²⁹ whereas lower paternal education was associated with 4.9% lower ppFEV₁ at the age of 6 years through 18 years in the CFFPR (2006–2016), after adjusting for demographic and clinical covariates.²⁸ Analysis of data from the Danish CF patient registry (1969–2010) showed that low parental education was associated with a 0.5% greater annual decline in ppFEV₁ after adjusting for demographic, genetic, and clinical factors, resulting in approximately 4% gap between the most and least disadvantaged by 17 years of age.³⁰ In addition, adolescents and young adults with sufficient interactive health literacy skills, an aspect of higher educational attainment, report better CF outcomes, including fewer hospitalizations and days on intravenous and oral antibiotics as well as better quality of life.³¹

Using occupation as a measure of SES, a 2008 study of mortality data from England and Wales reported 2.5 higher odds of dying above the median age of death from CF among people with CF working in manual versus nonmanual occupations.³² CF disease progression is known to limit occupational opportunities and functioning; a significant proportion of adults with CF are employed part-time, in less physically demanding occupations, or report work-related disability.^33–36 However, deprivation amplifies the harmful effect of CF disease severity on employment and is an independent risk factor for unemployment.³⁷

When health insurance is used as an indicator of SES, multiple disparities emerge. Patients on Medicaid have 9% lower lung function (ppFEV₁)³⁸ and 3.65 times higher adjusted risk of death^38,39 compared with counterparts not on Medicaid. Children with exclusively public and intermittently private insurance have 6.6% and 3.3% lower ppFEV₁ at the age of 6 years, respectively, compared with those with exclusively private insurance.⁴⁰ During the transition to adulthood, public insurance coverage is associated with accelerated ppFEV₁ decline at the rate of 3.1% and 2.4% per year for patients with exclusive and intermittent public insurance, respectively, compared with 2.1% per year for those with exclusively private coverage.⁴¹

Disparities by Geographic Location

The United States has significant regional variations in CF pathogens, clinical outcomes, and comorbidities.⁴² For example, the South has the highest proportion of patients with methicillin-resistant Staphylococcus aureus (41.9%), P aeruginosa (71.2%), and nontuberculous mycobacterium (10.0%), as well as the lowest mean BMI and FEV₁. Although mean regional CF mortality rates are not statistically different among regions, the South has the highest mortality rates in each age grouping,⁴² which parallels the higher mortality and morbidity among the general population in the Southeast region.⁴³ There is also evidence of disparities between rural and urban CF populations, both in the United States and globally, with rural patients having worse outcomes likely due to travel distance that limits access to specialized CF care.⁴⁴ For example, adult patients with CF in British Columbia who lived more than 2.5 hours from a CF center were less likely to attend quarterly clinic visits than those within 45-minutes travel distance.⁴⁵

Disparities by Gender, Gender Identity, or Sexual Orientation

Female sex is associated with worse CF outcomes than male sex. Women with CF acquire P aeruginosa and other pathogens at an earlier age,⁴⁶ have more pulmonary exacerbations,⁴⁷ worse pulmonary function,⁴⁸ and ultimately shorter life expectancy.⁴⁶ Although there is some biological basis for the observed differences in outcomes by sex,^49,50 the evidence for the role of gendered social norms (eg, life attitudes, body image, treatment adherence) is compelling. For example, men with CF are less reflective or concerned than women about the disease’s impact on their future, including career and longevity,⁵¹ whereas women with CF are more content with being thin than their male counterparts.^52–54 These attitudinal differences associate with behavior differences: for example, men with CF are more likely than women to exercise regularly, to eat better and more frequently, to use nutritional supplements, and to follow prescribed treatment regimens.^51,52,55

Kidd and colleagues estimate upward of 300 gender diverse youth with CF in the United States alone.⁵⁶ Data about disparities in CF outcomes by gender identity or sexual orientation is sparse. A small study reports similar negative mental health outcomes among transgender people with CF.⁵⁷ In addition, chest binding may be associated with reduction in pulmonary function.^58,59 The implications of gender-affirming hormone therapy in patients with CF are unclear but data suggest that estrogen may have proinflammatory qualities, resulting in inhibited mucociliary clearance and suppressed response to P aeruginosa infection.^60–62

DETERMINANTS OF HEALTH DISPARITIES IN CYSTIC FIBROSIS

Social Determinants of Health

The described disparities in CF outcomes are multifactorial and exist across multiple domains. Table 1 summarizes social risk factors, along with additional, CF-specific challenges, in the 5 social determinants of health domains outlined in Healthy People 2030: economic stability, education access and quality, health-care access and quality, neighborhood and built environment, and social and community context.⁶³ The basic terminology around social determinants of health⁶⁴ is illustrated in Fig. 1.

Table 1.

Social risk factors for cystic fibrosis disparities across 5 domains

	Economic Stability	Education Access and Quality	Health-Care Access and Quality	Neighborhood and Built Environment	Social and Community Context
Social risk factors	• Unemployment • Low-earning occupation • Low income • Limited assets • Debt • Food insecurity • Housing insecurity • Utilities insecurity • Internet access	• Limited education • Low health literacy • Low digital literacy • Language barriers	• Underinsurance • Policy restrictions • High copays or deductibles • Lack of access to specialist care • Suboptimal health-care quality	• Area deprivation • Schooling options • Food deserts • Lack of transport • Air pollution • Toxic exposures • Unhealthy living conditions • Limited green space and walkability • Crime • Residential segregation	• Racism • Homophobia • Discrimination • Stigma • Lack of social support • Family structure
Additional, CF-specific challenges	• Limited employment opportunities • Fewer suitable occupations • Limited flexibility to get time off from work to attend to health-care needs • High cost of CF care • Increased nutrition needs • Financial readiness for transplant • Financial planning for the future	• Access to educational opportunities and suitable schooling options • Need for schooling accommodations • Issues with school attendance policies • Understanding of CF care, including transplant care • CF disease self-management skills • Adherence to therapy • Self-advocacy with providers	• Consistent access to care, medication, equipment, pharmacies • Managing medications from multiple pharmacies • Aging out of parental policies • Transplant access • Fewer home caregivers • Limited coverage of nutritional supplements • Access to CFTR modulators • Newborn screening for less common genotypes	• Distance to care center and other providers • Access to reliable transportation • Infectious agents • Smoke exposure	• Treatment burden

Fig. 1.

Social determinants of health: concepts and terminology.

Mechanisms of Health Disparities in Cystic Fibrosis

Social and economic policies

An analysis of the CFFPR data showed that both area-level socioeconomic characteristics and state-level child health are impactful for the health of children with CF. The residual association of state child health with CF outcomes after controlling for area-level socioeconomic deprivation points to the potential of state policies and programs, such as the Supplemental Nutrition Assistant Program, the Special Supplemental Nutrition Program for Women, Infants, and Children, medical nutrition assistance programs, and the expansion of Medicaid eligibility under the Affordable Care Act, to mitigate the effect of poverty.^65,66 Globally, analysis of data from 13 European countries showed that, after adjusting for confounders, countries with higher health-care spending had a 46% lower hazard of CF-related mortality than countries with lowest health-care spending.⁶⁷

Neighborhood characteristics

Neighborhoods are often characterized by socioeconomic and racial or ethnic distributions.⁶⁸ Lower income neighborhoods, and those with a greater proportion of racial or ethnic minority members, often have less access to healthy foods, green spaces, and other health-promoting resources^69–72 and may experience higher rates of crime and violence.^73–76 There are also regional disparities: for example, states with the highest share of neighborhoods that are both low-income and have low access to food are most prevalent in the Southern United States.⁷⁷

There is a paucity of research on the effect of neighborhood characteristics for CF respiratory outcomes. Area socioeconomic deprivation has been associated with worse respiratory outcomes in pediatric patients with CF in the CFFPR, including lower lung function, more intravenous treatment nights annually, and higher odds of pulmonary exacerbations.⁶⁵ However, the effect of specific neighborhood characteristics, both individually and jointly, is yet to be investigated.

Food access and insecurity

Limited access to full-service supermarkets and farmers markets, as well as difficulty getting to grocery stores due to lack of transportation or unsafe neighborhoods are important environmental correlates of nutritional intake and food insecurity.^78,79 About 30% of people with CF are food insecure, compared with approximately 12% of the general US population.⁸⁰ The reasons for this disparity are multifactorial, from higher caloric needs, to disrupted educational opportunities, to limited occupational choices and unstable employment, which affect earning potential. There is ample evidence that the nutritional status of people with CF is closely associated with their SES,^{27,38,81–84} as well as emerging evidence that food insecurity is linked to suboptimal CF health outcomes.⁸⁵

Housing and living conditions

Housing is an important social determinant of health, and housing quality is associated with a wide range of health outcomes, including incidence, prevalence, and morbidity from infectious and chronic diseases including respiratory disease. Molds, particularly the filamentous fungus Aspergillus fumigatus, have been implicated in the pathogenesis of allergic bronchopulmonary aspergillosis and CF bronchiectasis.^86,87 In general, however, the role of housing and living conditions for CF respiratory outcomes remains underexplored.

Environmental exposures

Environmental exposures, such as outdoor and indoor air quality, allergens, and infectious agents, are important determinants on CF lung health.⁸⁸ Potential mechanisms include both direct damage to the lung tissue and indirect pathways via reactive oxygen species and systemic inflammation.^89,90

Tobacco smoke exposure.

Smoke exposure reduces CFTR functional expression^91–94 and inhibits anion transport by the CFTR.^95–99 It also increases airway inflammation and impairs pathogen clearance in people with CF.^100–102 In the US Cystic Fibrosis Twin and Sibling Study, children had a 0.6% annual decrease in ppFEV₁ attributable to smoke exposure,¹⁰³ or 6.1% decrease in mean ppFEV₁ at the age of 20 years,⁴ whereas adults had 42% increased annual risk of hospitalization compared with unexposed counterparts.¹⁰³ The EPIC Observational Study found significant 4-year decreases in mean ppFEV₁ associated with smoke exposure: 6.0% if the mother smoked after birth, 4.6% if the mother smoked during pregnancy, 3.2% if the child was ever around smokers, and 2.6% if a household member smoked, as compared with no smoke exposure during pregnancy or after birth.¹⁰⁴ Similarly, a longitudinal analysis of CFFPR data (2006–2016) demonstrated that at the age of 6 years, ppFEV₁ of smoke-exposed children was nearly 5% lower than among unexposed, a deficit that persisted through age of 18 years.²⁸ Because tobacco use is more prevalent among people with lower SES, smoke exposure is a potential mechanism by which SES influences CF lung health.^4,105

There is also evidence that smoke exposure may affect the efficacy of highly effective modulator therapies for CF. Analysis of CFFPR data (2016–2018) showed that tezacaftor/ivacaftor provided no benefit to smoke-exposed individuals with CF aged 12 to 20 years but was associated with improved ppFEV₁ among their unexposed counterparts.¹⁰⁶ Smoke exposure was also associated with significantly less improvement in sweat chloride levels in the G551D Observational Trial of ivacaftor.¹⁰⁷ The health benefits of removing smoke exposure were highlighted in a CFFPR data analysis (2006–2018). Cessation of smoke exposure among children and adolescents with CF reduced their odds of a pulmonary exacerbation in 12 months by 17% in the first year of cessation, with an additional 6% decrease on odds of exacerbation for each additional year of cessation; 3 years of cessation were associated with 2% higher ppFEV₁ and BMI.¹⁰⁸

Indoor air pollution.

Beyond smoke exposure, other sources of indoor air pollution, such as forced hot air and wood stove/fireplace, also increase morbidity in people with CF. For example, forced hot air was associated with a 0.5% annual decrease in ppFEV₁ in the US Cystic Fibrosis Twin and Sibling Study.¹⁰³

Outdoor air pollution.

People living in disadvantaged communities are commonly exposed to higher levels of environmental pollution,^109–112 which compromises lung growth in children¹¹³ and leads to increased mortality in adults.^112,114 These effects are ever stronger among people with CF and other lung diseases.¹¹⁵ A Belgian study reported a significant correlation between ambient concentrations of particulate matter, nitrogen dioxide, and ozone and prescriptions of IV antibiotics for pulmonary exacerbations among people with CF.¹¹⁶ Similarly, a Brazilian study showed that exposure of patients with CF to short-term air pollution nearly doubles the risk of a pulmonary exacerbation. In CFFPR data, higher exposure to ambient ozone and particulate matter, specifically PM_2.5. and PM₁₀, was associated with increased pulmonary exacerbations and decreased lung function.¹¹⁷ Exposure to fine particulate matter has also been associated with an increased risk of P aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) acquisition in young children with CF.^118,119

Infectious agents.

UK patients with CF residing in the most deprived geographic areas are nearly twice as likely to have chronic P aeruginosa infection than comparators in the most affluent areas.²⁷ The likelihood of P aeruginosa acquisition is also increased in US children with low maternal education.¹²⁰ Socioeconomic disparities have also been reported in MRSA infection.¹²¹ For example, neighborhood deprivation has been linked to more than 2-fold increase in the odds of having MRSA after adjusting for demographic and clinical covariates.¹²² Multiple mechanisms may contribute to this association, including indoor and outdoor air quality and exposure to pathogens, and further study of potential mediators is warranted.

Psychosocial factors

Family structure.

Closely related to SES, family structure is implicated in a range of health-related outcomes. For example, children with CF who are cared for by a single caregiver have worse respiratory and nutritional outcomes and lower adherence to treatment than children with dual caregivers, after adjusting for income and education.^123,124 Relatedly, mothers of children with CF report higher levels of stress associated with decision-making and responsibility for parenting.^125,126

Chronic stress.

Socioeconomic position is associated with differential exposure to chronic stressors,¹²⁷ a primary mechanism of socioeconomic disparities in health outcomes.¹²⁸ In addition, low SES is a potential risk factor for the disproportionate prevalence of anxiety among CF families.^129,130 People with CF are also affected by stress indirectly through the toll it takes on their caregivers in the form of humanistic and economic burden.^131–133 A third of parents of children with CF are clinically depressed, likely related to caregiving burden or giving up career opportunities to fulfill their caregiving role.¹³⁴ Low SES is also associated with a higher prevalence of depressive symptoms.¹³⁵ Depression is linked to worse health outcomes, including lower lung function^131,136,137 and increased mortality.¹³⁸

Social support.

The harmful health effects of stress can be buffered by stress-mitigating resources such as social support.¹²⁸ Relatively few studies focus on the importance of social support in CF, however.^139,140 A study of 250 adults with CF showed that greater social support was associated with fewer self-reported mental and physical health symptoms, lower treatment burden, better body image, and higher emotional, social, and role functioning.¹⁴¹ Social support has also been protective against lung function decline¹⁴² and hospitalizations¹⁴³ after transfer from pediatric to adult care.

Behavioral factors

Maintenance of daily therapies is a challenge for all people with CF,¹⁴⁴ and suboptimal adherence has been reported across the CF population, with negative implications for a range of outcomes.^145,146 Studies suggest that lower educational attainment is associated with worse treatment adherence.¹²⁴ Relatedly, understanding of the treatment regimen and its rationale are a prerequisite for adherence in CF.^147–149 For example, maternal nutritional knowledge specific to CF is a predictor of caloric intake and growth in children with CF.¹⁵⁰ CF treatment adherence also correlates with optimism, family functioning, and parental stress.^151,152 Thus, worse adherence is a likely contributor to poorer outcomes among disadvantaged children and adults with CF.^153,154

Health system factors

Telehealth.

The coronavirus disease 2019 pandemic resulted in a widespread implementation of telehealth in CF care delivery. However, people with CF from racial or ethnic minority background, especially Hispanic/Latino patients, were less likely to have had a telehealth visit as compared with phone visit or no visit.¹⁵⁵ In addition, people who reported financial difficulties found telehealth more difficult to use and were less satisfied with their telehealth visit.¹⁵⁵ Lack of broadband Internet access, mobile technology, digital literacy, language barriers, and suboptimal home conditions may be barriers to telehealth use in vulnerable people with CF.¹⁵⁶

Lung transplantation.

Although access to care, including appropriate treatments and medications, is typically found to be associated with health disparities in most conditions, the multidisciplinary CF Center model of care delivery seems to mitigate this problem. Several studies demonstrate that the socioeconomic disparities in CF health cannot be attributed to differences in standard medical treatment, such as prescription of chronic medications and therapies, treatment of pulmonary exacerbations, or the use of health services as documented in CF patient registries.^157–160 However, significant disparities have been observed in access to lung transplantation. Low SES, measured by zip-code income, education level, and/or Medicaid insurance, has been associated with non-referral to evaluation¹⁶¹ or nonacceptance for lung transplantation¹⁶² despite meeting eligibility criteria. In addition, individuals who undergo lung transplant at non-CF Foundation accredited care centers are disproportionately of Hispanic origin, whereas Black transplant patients with CF have an increased risk of mortality, pointing to racial and ethnic disparities in transplant access and outcomes.¹⁶³ Furthermore, a case-control study of linked CFFPR/Scientific Registry of Transplant Recipients found that the accumulation of socioeconomic barriers (minority race, education, health insurance, zip-code income, and distance to transplant program) limits access to lung transplant irrespective of disease severity.¹⁶⁴ As a result, individuals with greater socioeconomic barriers accessed transplant about half as often as those with less barriers at the same level of medical severity,¹⁶⁴ have higher risk of death while awaiting lung transplantation,¹⁶⁵ and worse survival after lung transplantation.¹⁶⁶

CFTR modulator therapies.

CFTR modulators, genomic-specific medications that target the malfunctioning protein made by the CFTR gene, have revolutionized the treatment of CF for most people with the disease. However, CFTR therapeutics are mutation-specific, and racial and ethnic minority groups are less likely to have CFTR mutations responsive to currently available CFTR modulators.^167,168 As a result, there are large racial and ethnic disparities in access to CFTR modulators. Although more than 90% of non-Hispanic Whites with CF in the United States have CFTR mutations that qualify for a CFTR modulator therapy, only 70% of American Blacks, 75% of Hispanics, and 80% of other racial minorities with diagnosed CF have qualifying mutations.¹⁶⁸ This lack of applicable lifesaving drugs can only exacerbate the already existing racial and ethnic disparities in CF outcomes.

The lower use of CFTR modulator therapy among people with CF from racial and ethnic minority backgrounds is not simply a function of differences in CFTR mutations. Even among those with a copy of G551D, uptake of ivacaftor was significantly slower in US adults from racial and ethnic minority backgrounds compared with non-Hispanic Whites.¹⁶⁹ Similarly, in the 18 months following Food and Drug Administration (FDA) approval of lumacaftor-ivacaftor, the drug was prescribed more frequently to patients with private insurance and previous clinical trial participation; racial and ethnic minorities in the United States are less likely to be in either of those groups.¹⁷⁰ The differential rate of initial uptake of new therapies such as CFTR modulators is likely due, in part, to several factors including education and race-based differences in self-advocacy during medical encounters,¹⁷¹‘¹⁷² lack of racial and ethnic diversity in clinical trial populations,¹⁷³ implicit bias,^174,175 and patient reluctance due to earlier experiences of discrimination leading to mistrust, lower health literacy, or competing needs.¹⁷⁶ Anticipated changes in modulator coverage may further widen access disparities in low-income populations, including low-income minority populations.

Newborn screening and CF diagnosis.

In the United States, almost 75% of non-Hispanic Whites with CF have Class I to III mutations, compared with approximately 50% of Blacks, Hispanics, and other races with CF.¹⁶⁸ Approximately 25% of Blacks, Hispanics, and other races with CF have unclassified CFTR mutations, compared with only 11% of non-Hispanic Whites with CF.¹⁶⁸ Although only 3% of non-Hispanic Whites with CF do not have 2 identified CFTR mutations, 8% to 10% of Blacks, Hispanics, and people of other races with CF have at least 1 unidentified CFTR mutation.¹⁶⁸ As a result, non-Hispanic White newborns with CF are more likely to be missed on state newborn screening for CF,¹⁷⁷ delaying diagnosis and potentially impairing outcomes,¹⁷⁸ especially growth.^178–181 However, newborn screening is not the only reason for racial and ethnic disparities in CF diagnosis. There are examples of decades-long delays in diagnosis of CF among Black people due to lack of awareness that the disease exists in non-White populations and implicit bias among health-care providers.¹⁸²

Clinical trial participation.

Significant racial, ethnic, and socioeconomic disparities in clinical trial participation have been observed.¹⁷³ Very few pharmacology clinical trials in CF and clinical trials of CFTR modulators included patients from racial or ethnic minority background.¹⁷³ In the United States, clinical trial participants are more likely to be White and to have private health insurance.¹⁸³ Inadequate inclusion of all population subgroups in clinical research may bias trial results and inhibit understanding of factors that influence drug response.

In summary, multiple studies report disparities in CF outcomes from early childhood throughout the life course. Determinants and mechanisms are multifactorial and complex. Improved understanding of the various pathways generating and sustaining such disparities is critical for policy, social, and health-care strategies that advance equity.

STRATEGIES FOR HEALTH EQUITY IN CYSTIC FIBROSIS

A strategy to achieve health equity is most effective when it includes steps moving systematically from identifying health disparities to action to eliminate them.¹⁸⁴ Multilevel strategies are particularly needed.

Policy-Level Strategies

Strategies and interventions for health equity must include policies that tackle the social mechanisms that systematically generate an inequitable distribution of health-related resources among population groups. Although population-level policy, system, and environmental interventions are more difficult, they are decidedly more impactful than individual, patient-level interventions to improve CF health.^185,186 Table 2 provides examples of policy strategies for the general population and specifically for people with CF across the 5 domains outlined in Healthy People 2030.⁶³

Table 2.

Policy strategies for cystic fibrosis health equity across 5 domains

	Economic Stability	Education Access and Quality	Health-Care Access and Quality	Neighborhood and Built Environment	Social and Community Context
General	• Labor policies to ensure adequate wages • Employment protection and unemployment insurance • Progressive taxation • Subsidized housing and transportation • Public broadband access • Parental leave policies • Social protection of single mothers	• High-quality public education • Early childhood education • Free school lunches	• Universal health coverage • Access to primary and specialty care	• Guaranteed access to basic services (water, plumbing) • Healthy living conditions (lead, molds, pests) • Emission reduction and climate change policies • Tobacco control policies • Land use, urban planning policies • Neighborhood crime and safety	• Equal opportunity policies for gender, racial, and other minorities
Additional, CF-specific	• Social security schemes and supplemental income for care and rehabilitation • Career counseling and workforce development programs • Financial planning programs • Food assistance programs	• Educational support programs • Schooling accommodations	• Quality improvement programs to promote consistency of care and lessen dependence on self-advocacy • Programs that target improving self-efficacy and disease self-management in vulnerable populations • Medical nutrition assistance programs • Access to CFTR modulators • Newborn screening for less common genotypes	• Tobacco-free living and working conditions • Clean indoor air policies	• Disability protections

Community-Level Strategies

Several interventions developed specifically for the CF community have been particularly successful. For example, the CF Foundation-sponsored patient assistance program (CF Compass) offers personalized service to help with insurance, financial, legal, and other issues faced by people with CF, their families, or their care teams.¹⁸⁷ Compass’s team of case managers provide free expert advice and connect individuals to resources offered by community organizations, local and state governments, foundations, or other groups. In addition, the CF Foundation has made a commitment to the CF community regarding equity, racial justice, diversity, and inclusion (Box 1) and has taken key steps to deliver on these promises (for more details, see https://www.cff.org/about-us/our-commitment-equity-racial-justice-diversity-and-inclusion).

Box 1. The Cystic Fibrosis Foundation’s commitment to equity, racial justice, diversity, and inclusion.

• At the Cystic Fibrosis Foundation, we commit to equity, racial justice, diversity, and inclusion as core principles guiding our efforts to provide all people with CF the opportunity to live long, fulfilling lives.

• We commit to helping address the systemic barriers that have led to health disparities for many in the CF community, particularly Black, Hispanic, and other communities of color. We will work toward ensuring all individuals with CF have the opportunity for optimal health outcomes.

• This commitment guides our work to engage and support the CF community, and to work in partnership with individuals in the CF community to best inform and enact these efforts.

• This commitment guides us as Foundation staff work together to build an inclusive and respectful environment where everyone is welcomed, and where talented individuals from all backgrounds, identities, and lived experiences have opportunity to thrive.

• Our commitment to these principles makes us stronger as an organization, enables us to better serve all members of the CF community, and ultimately speeds the advancement of our work to find a cure for CF.

Further interventions that will benefit people with CF include urban planning that promotes physical separation from pollution sources, complete streets that facilitate active transportation, efforts to increase walkability and access to parks and recreational facilities, and mobile markets to increase access to healthy foods.

Health System–Level Strategies

Screening for social needs

Identifying unmet social needs can inform providers that a patient needs more support to manage their condition or could benefit from referrals to social services.¹⁸⁸ For example, the CF Foundation recommends screening for food insecurity due to the profound health implications of food insecurity for people with CF.¹⁸⁹ Preliminary evidence exists that screening for unmet social needs in CF care is feasible.¹⁹⁰ However, such screening can detect adverse social circumstances that require resources beyond the scope of clinical care. Referring families to nonmedical organizations to resolve social needs requires specialized training and dedicated staff that few clinicians.^191–193 Garg and colleagues warn about the unintended consequences of screening for social needs in health-care settings, especially when referral resources are unavailable for addressing identified needs,¹⁹⁴ and calls for enhanced social infrastructure in these circumstances.

Referrals to community organizations

Screening in clinical settings has limited impact unless it is followed by an action to help alleviate the identified social needs. One common intervention is the referral of patients to community organizations that provide such assistance. However, the availability of such community resources is often limited. For example, in 2019 there were nearly 600 requests to CFF Compass program for assistance with food, housing, transportation, or utilities. In 19% of these cases, there was not an existing community resource to meet the caller’s needs, highlighting the urgency of creating a social safety net through policy changes and investing in community infrastructure.

Screening for tobacco smoke exposure and delivery of tobacco treatment services

CF care teams can screen for smoke exposure and deploy evidence-based tobacco treatment approaches tailored to the needs of people with CF and their families.^195,196 Determining what cessation strategies are most effective for CF families will be critical to improving CF lung health and maximizing the benefit from CFTR modulator therapies. Clinical barriers to such efforts include limited staff trained to provide tobacco counseling, inadequate health system support and reimbursement for tobacco treatment services, and a general lack of enthusiasm about undertaking an arduous effort with a perceived low level of success.¹⁹⁷ Still, tobacco use is one of few modifiable risk factors for CF lung health, and most parents of children with CF have welcomed advice regarding smoking cessation from their child’s physician.¹⁹⁸

Screening for and treatment of anxiety and depression

International CF care guidelines recommend universal screening and treatment of anxiety and depression in people with CF,¹⁹⁹ yet the diagnosis and treatment of mental health disorders vary considerably across care centers.²⁰⁰ Improvements in the rate of screening through QI efforts and ensuring access to mental health services to those in need could have a positive effect on socially vulnerable people with CF and reduce disparities.

Ensuring equitable access to transplantation

The differential referral for and acceptance into organ transplantation program by SES was previously noted.^{161,162,164–166} For the most part, the disparity stems from a perception that the resources and social support needed to successfully undergo organ transplantation are beyond the reach of people with limited finances and education.¹⁶² It is essential that transplant programs focus additional resources to make the process more equitable.

Ensuring equitable access to CFTR modulators

Shemie and colleagues identified 3 mitigating strategies regarding the use of CFTR modulators: (1) improved diagnostic testing, diversified genetic databases, and increased participation of ethnic and racial minorities in clinical trials; (2) regulatory oversight to ensure long-term drug access for all; and (3) health-care system implementation, including alternative provision models.²⁰¹ Approval of CFTR modulators to rare CFTR mutations based on in vitro data alone²⁰² as well as off-label use of CFTR modulators can also mitigate the racial and ethnic disparities in CF outcomes.²⁰³ In addition, better characterization of variants occurring in non-White patients as well as theratyping efforts can help expand access.

Ensuring timely cystic fibrosis diagnosis for all

Correcting the misconception of CF as a disease only found in White persons is central to this effort. Delayed or missed diagnosis of CF in racial and ethnic minorities has long-lasting health implications. It is also important to keep exploring faster, comprehensive, and reliable newborn screening testing to improve the timely diagnosis of babies from racial and ethnic backgrounds with unidentified CFTR mutations.

Improving diversity in clinical trials

To ensure adequate representation of all population groups, CF clinical trials should oversample vulnerable populations and report the sociodemographic characteristics of all study participants. Study sponsors must consider the racial and ethnic diversity of study sites, provide adequate training to study coordinators to prevent racial and ethnic bias in recruitment, ensure translated study materials or interpreters, and review compensation guidelines and other study benefits. Significant efforts should be devoted not only to recruit subjects that reflect the actual diversity of the CF population but also to recruit enough subjects from racial/ethnic minority backgrounds so differences in adverse events, drug metabolism, or therapeutic benefit could be detected.

Improving the diversity of cystic fibrosis clinical and research teams

To reach health equity, it is essential to grow a CF workforce that represents diverse socioeconomic, racial, ethnic, and cultural backgrounds. Specifically, strategies are needed for recruitment, training, and career development support of individuals historically underrepresented in CF clinical care and research.

Quality improvement efforts that ensure consistency of care

Variations in care processes and inconsistencies in following care guidelines, which are well documented in the CF literature,²⁰⁴ are associated with corresponding differences in disease outcomes,^205,206 and can be mitigated in part by patient self-advocacy.^31,207–209 Efforts to promote participation in care decisions by patients and families with less confidence in their interactions with health-care providers are one avenue to reduce social disparities. Another is to develop structures that ensure more consistent adherence to effective care patterns so that there is less dependence on patient self-advocacy. One such effort, designed to improve the consistency of response to acute drops in lung function and deficits in nutritional status in children with CF,²¹⁰ had a disproportionately positive impact on Medicaid compared with privately insured patients.²¹¹ Encouraging participation in care and ensuring consistent care patterns are important complementary strategies to improve the quality of CF care.

SUMMARY

With advancements in early diagnosis and medical treatment, survival in CF has improved rapidly, yet variations in disease progression persist. People with CF from disadvantaged racial, ethnic, socioeconomic, geographic, and other marginalized backgrounds have worse health and survival than those in more advantaged positions. Multiple mechanisms operating across levels and domains of influence are responsible for these disparities; therefore, multiple strategies are needed to overcome them. Policy-level and community-level strategies to reduce disparities may include (1) interventions that support children with CF to reach their full educational potential; (2) expanded career counseling, vocational rehabilitation guidance, and workplace risk assessment and management strategies; and (3) expanded support to meet health-related needs for food, housing, transportation, and other services for people with CF. Healthcare strategies may include screening for and addressing social risk factors, smoke exposure, anxiety, and depression; providing equitable access to CFTR modulators, transplantation services, and timely CF diagnosis to all; quality improvement efforts that ensure consistency of care; and diversifying clinical trials as well as the CF workforce.

KEY POINTS.

• Disparities in cystic fibrosis (CF) health outcomes are observed across all categories of social disadvantage, including race, ethnicity, socioeconomic status, geographic location, sexuality, and gender identity.

• Risk factors contributing to health disparities in CF exist across multiple domains: economic stability, education access and quality, health-care access and quality, neighborhood and built environment, and social and community context.

• The mechanisms that generate and sustain CF disparities throughout the life course are complex and operate on multiple levels. Examples include social and economic policies, neighborhood characteristics, food access, housing and living conditions, environmental exposures, health system factors, as well as psychosocial and behavioral factors.

• Improved understanding of the pathways leading to disparities in CF health is critical for policy-level, community-level, and health system–level strategies to reduce disparities. Health-care strategies, specifically, may include screening for social risk factors and assisting with unmet basic needs; screening for and addressing smoke exposure as well as anxiety and depression; providing equitable access to CF transmembrane conductance regulator modulators, transplantation services, and timely CF diagnosis to all; supporting quality improvement efforts that ensure consistency of care; and diversifying clinical trials as well as the CF workforce.