Cystic fibrosis and race

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Cystic fibrosis transmembrane conductance regulatory (CFTR) protein. Protein CFTR PDB 1xmi.png
Cystic fibrosis transmembrane conductance regulatory (CFTR) protein.

Underrepresented populations, especially black and hispanic populations with cystic fibrosis are often not successfully diagnosed. [1] This is in part due to the minimal dissemination of existing data on patients from these underrepresented groups. While white populations do appear to experience a higher frequency of cystic fibrosis, other ethnicities are also affected and not always by the same biological mechanisms. [2] Thus, many healthcare and treatment options are less reliable or unavailable to underrepresented populations. This issue affects the level at which public health needs are being met across the world.

Contents

Definition

Cystic fibrosis (CF) is an autosomal recessive and monogenetic disorder. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. [3] The CFTR protein (Figure 1) serves to move chloride ions to the surface of cells to ensure proper hydration. When this protein becomes dysfunctional, the chloride ions are not present to thin out the viscous mucus that forms. This thickened mucus causes many problems in various organs of the body. [4]

Symptoms

Symptoms of CF Cystic fibrosis manifestations.png
Symptoms of CF

People with cystic fibrosis may experience salty skin, persistent coughing, lung infections such as pneumonia and bronchitis, and wheezing and shortness of breath. Cystic fibrosis can also cause poor weight gain and growth, nasal polyps, chronic sinus infections, clubbing or enlargement of fingers and toes, infertility in males, and rectal prolapse. [4] Cystic fibrosis may also lead to arthropathies. [5] These symptoms and co-morbidities can ultimately lead to nutritional deficits and highly decreased quality of life. [6]

Compared to white patients, black patients have more severe pulmonary imaging findings and display more respiratory symptoms at diagnosis. Similarly, black and hispanic patients have overall worse pulmonary function than white patients that is often present earlier in life. [7] Though this may be the case, these symptoms can be misdiagnosed as other health issues and treated as such. [8]

Diagnosis

Through symptoms

To be diagnosed with CF, patients must meet certain criteria. These criteria may include showing a combination of the signs and symptoms above and/or have a family member with CF and/or test positive for the mutation during genetic screening.

Conventional diagnostic criteria

Individuals must have at least one clinical feature: [3]

  • meconium ileus (bowel obstruction when meconium in intestine is too thick)
  • diarrhea and failure to thrive
  • recurrent respiratory infections
  • nasal polyps
  • rectal prolapse
  • male infertility
  • electrolyte depletion

Or CF diagnosis in family member, or positive newborn screening test, plus one or both of the following:

  • chloride channel dysfunction (positive sweat test or abnormal transepithelial potential difference)
  • known disease-causing mutations on chromosome 7 in trans

Though these symptoms may present themselves in underrepresented minorities, there remains the misconception among doctors that underrepresented minorities rarely have the disease. [9] This results in under-diagnosis in these populations. Also, in developing countries, such as in Africa, where HIV, protein energy malnutrition, [10] and chronic pulmonary infections are prominent, it can be difficult for clinicians to rightly diagnose patients with CF. [1] [8] Proper diagnosis can also be affected when patients show a positive test but do not display symptoms or display symptoms but do not show positive diagnostic tests. For this reason, it is very important to continue to monitor patients in both categories, especially those of the latter while treating the symptoms that may be disguised as another disease. [3]

Through screening

In many western countries, prenatal and newborn genetic screening is available. This has been correlated with decreased incidence as patients and their families are able to seek treatment early on. [3] [11] These screening methods may include measuring serum immunoreactive trypsin (iRT) and CFTR mutation analysis. [12] [13]

CFTR mutation classification systems typically include six classes [14] where classes I-III tend to have more severe symptoms than classes IV-VI. [1]

CFTR mutation classification

  1. Protein production mutations (Class I)
  2. Protein processing mutations (Class II)
  3. Gating mutations (Class III)
  4. Conduction mutations (Class IV)
  5. Insufficient CFTR transcript mutations (Class V)
  6. Reduced protein stability and increased turnover of CFTR at the cell surface (Class VI)

IRT and CFTR mutation analyses are always confirmed with what is known as a sweat test which will show elevated levels of chloride in sweat of CF patients. [3] [15] However, this is not a perfect system and many children end up with an inconclusive diagnosis and need to be monitored for symptoms that may not show up until much later in life. [16] Also, in some states such as New Jersey, there is only one mutation on the CFTR screening panel (F508del). Because 12.9% of CF patients in the United States do not have this specific mutation, they cannot be diagnosed using this particular screening method. This value can be even larger when narrowing in on minority populations (see race and ethnicity). [8] [17] Upon analysis of the 2020 Cystic Fibrosis Foundation Patient Registry, the detection rate of CFTR mutation variants in known CF patients was highest in white patients at a false negative rate of only 3–5%. [11]

CFTR Mutation Detection Rate 2020 Cystic Fibrosis Foundation Patient Registry [11]
Race / ethnicityDetection rate (%)Detection failure rate (%)
Asian56-7723-44
Black73-8614-27
American Indian and Alaskan Natives84-919-16
Hispanic81-946-19
White95-973-5

Risk factors, incidence, and prevalence

Genetics, sex, and age

Since the CFTR mutation is autosomal recessive, the most significant risk factor is family history. The disease only manifests itself when a child inherits CFTR mutations from both parents. Children who inherit a mutation from one parent are considered carriers and can pass it on to their children. [4] With this being the case, mutations may be family and region specific (See Race, ethnicity, and geographic location). [17] In regard to sex, CF occurs in occurs in males and females; however, women are more likely to display worse symptoms and outcomes. [18] This is particularly relevant in regard to Peudomonas aeruginosa [19] respiratory infections. [20] Age-wise, most people are diagnosed by the age of 2; however, the Cystic Fibrosis Foundation Patient Registry shows that more than half of the CF population is age 18 or older in the United States. [4]

Race, ethnicity, and geographic location

Cystic fibrosis occurs in all races, but may be most prevalent in white people of Northern European ancestry. [21] CF incidence in other populations may be underreported as there are hundreds of CFTR mutations that can manifest the disease and not all have been identified. Though there has been a decrease in incidence in more developed countries due to prenatal genetic screening, [22] [23] the prevalence is expected to increase as people are able to live longer with the disease. [3]

F508del is the most common mutation across all cystic fibrosis patients. [24] However, it is not the most common mutation found in specific geographical locations.

CFTR mutation F508del frequency by geographical location [17]
Frequency (%)Location
70central, northern, western, and northeastern Europe
100Faroe Islands of Denmark
20Turkey
60Argentina and Uruguay
40Brazil, Chile, Colombia, Mexico, and Venezuela
20-30Puerto Rico, Cuba, Ecuador, and Costa Rica
10Dominican Republic
60Pakistan
20India
10Japan

Since a popular method of identification is genetic testing for this particular mutation, the identification frequency is lower in underrepresented population.

CFTR mutation identification frequency by race in the United States [17]
Identification categoryFrequency (%)Race
Unclassified25Black, Hispanic, and other races
11non-Hispanic White
One unidentified8-10Black, Hispanic, and other races
3non-Hispanic White people

African descendants display the most genetic diversity across the human population. For CF patients of African descent, this means that they are more likely to harbor less common CFTR mutations. [1] Some mutations that are unique to Africa are 2766del8, 1670delC, Y1109x, and A204T.

Cystic fibrosis and race
Map of Mutations Identified in African countries.
CFTR mutations on the African continent. Mutations in bold text are unique to Africa. [1]
CountryMutations
MoroccoΔF508, 5T, 12TG, 11TG, 711+1G>T, R74W, R1070W, D1270N, 3849+10kbC>T, S549R, G1244E, U
AlgeriaΔF508, 1609delCA, N1303K, 711+1G>T, 1812-1G>A, 5T, E1104X, U
TunisiaΔF508, W1282X, 711+1G>T, E1104X, R74W, Y122X, V201M, R1158X, 4016insT, U, G542X, N1303K, 405+1G>A, G85E, D1270N, R1066C, I1203V, R785X, 5T, 2766del8, F1166C, 3729delAinsTCT, 1811+5A>G, T665S, L1043R, 4268+2T>G
Libya1670delC, ΔF508, E1104X, N1303K, U
EgyptΔF508, N1303K, U, 1838+3A>C, T665S, 5T, 7T, 9T
SudanD579G, R1102K
SenegalU, 4136+1G>A, EX17a-EX18del
CameroonY1109x, 405+4A>G
RwandaF693L, T854T, M470V, P1290P, E527E, U, 3120+1G>A, Q1463Q, 1898+152T>A, 1001+11C>T, 2752-15C>G, A204T, 3041-71A>G, 4575+2G>A, 3272-32T>C
NamibiaΔF508
Zimbabwe3120+1G>A, c.54-1161_c.164+1603del2875
South AfricaΔF508, G1249E, D1270N, 394deITT, R553X, N1303K, R117H, S549N, 1717-1G>A, 3659deIC, 2183delAA, 3120+1G>A, 3196de154, 3272-26A>G, G542X, W1282X, G5510, 0493X, 621+1G>T, 278945G>A, R1162X, U, -94G>T, c.54-1161_c.164+1603del2875

Treatment

Treatment is most effective with early diagnosis. As CF is a complicated ailment, patients must often use a combination of therapies. [4]

Airway clearance

Clearing the airways of mucus can help decrease the incidence of infection in the lung and improve lung function. The most common airway clearance techniques include deep coughing, active breathing therapy, autogenic drainage, and positive expiratory pressure.[ citation needed ]

Inhaled medications

There are several available inhaled medications such as bronchodilators and mucus thinners. These are medications that are delivered as a mist or aerosol and inhaled through a nebulizer. They may also include antibiotics.[ citation needed ]

Figure 3. Bronchodilators are a type of inhaled medication used to treat symptoms of CF. Bronchodilators.png
Figure 3. Bronchodilators are a type of inhaled medication used to treat symptoms of CF.

Antibiotics

Antibiotics are used to fight bacterial infections which CF patients are very likely to develop due to thickened mucus. They are often taken daily by CF patients. It is recommended that inhaled antibiotics be taken only when the airway has been clear so that the drug can reach the affected area easily.[ citation needed ]

Pancreatic enzyme supplements

Pancreatic enzyme supplements serve to improve pancreatic function by increasing the absorption of essential nutrients. They are taken with meals. Multivitamins as supplements are also recommended for CF patients. [25]

Mechanism of action of Elexacaftor/tezacaftor/ivacaftor. Elexacaftor tezacaftor ivacaftor mechanism of action.png
Mechanism of action of Elexacaftor/tezacaftor/ivacaftor.

Fitness plans

A personalized fitness plan can aid in airway clearance, improve energy, increase lung function, and help the overall health of the patient. [26]

CFTR modulators

CFTR modulators target the mutated CFTR protein. [27] [28] Thus far, there are some approved CFTR modulators for specific mutations. One such drug is elexacaftor/tezacaftor/ivacaftor. However, the cost of CFTR modulators is high. [29] In addition to the high cost, the available CFTR modulators may not be as effective in minority populations. [30] In fact, while 92.4% of white patients are eligible for treatment with CFTR modulators, only 69.7% and 75.6% of Hispanic patients are eligible. [30]

Global impact

Healthcare access

Communities with large black and hispanic populations are also most likely to have lower quality/less available healthcare. [31] This means that the risk of mistakes being made in screening and diagnosis are more likely to happen in these areas. The clinics and hospitals are often understaffed and rushing through samples can cause inaccurate screening results. [8] Furthermore, the cystic fibrosis screening tests for CFTR present false negative results most often in black and hispanic babies. [11] [32] This happens because the CFTR variants most tested for are those that are largely found in white populations. [11] Also, as previously mentioned, one of the most common methods of diagnosis is using the sweat test. However, this test has a disproportionate rate of false negatives in areas with less healthcare access. [11] [30] The presence of implicit biases in healthcare also contribute to this. [7] [33] Additionally, availability of genetic screening options in developing countries and areas of lower socioeconomic status has proven to be difficult both because of financial and resource burden. [34] Altogether, this means that black and hispanic families are more likely to be diagnosed later on and therefore do not receive timely and as effective treatment.[ citation needed ]

Prognosis and quality of life in underrepresented populations

It is still up for debate on whether the overall prognosis of CF is improving. In areas where genetic screening is available, clinicians are able to identify and provide treatment for CF early on. In areas where this is not available, many patients are not diagnosed until later in life and display worse symptoms and poorer management of symptoms. [35] This is often in areas where there is a high density of underrepresented groups. [36] With the reduced access to healthcare, minority populations experience worse outcomes, even after taking low socioeconomic status into account. [7] Although hispanic patients are more likely than white patients to have milder CFTR mutations (those from Classes IV-VI), they suffer worse outcomes.

CFTR class I-III mutation frequency by race in the United States [17]
Frequency (%)Race
75non-Hispanic White
50Black, Hispanic, and other races

Current programs and research

In addition to focusing on improving detection and diagnosis, understanding CF microorganisms, and developing new treatments, optimizing current treatments, and evaluating long-term antimicrobial use, the Cystic Fibrosis Foundation is currently[ when? ] striving for more equity and timeliness in cystic fibrosis newborn screening. [37] Cystic Fibrosis Research Institute has implemented strategies to increase awareness in underrepresented populations. [38] Though there is ongoing research about cystic fibrosis in underrepresented populations, many of the studies leave much to be desired and are not performed to the standards of studies conducted in white patients.[ citation needed ][ editorializing ]

Related Research Articles

<span class="mw-page-title-main">Cystic fibrosis</span> Autosomal recessive disease mostly affecting the lungs

Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. The hallmark feature of CF is the accumulation of thick mucus in different organs. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.

<span class="mw-page-title-main">Bronchiectasis</span> Disease of the lungs

Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest pain. Wheezing and nail clubbing may also occur. Those with the disease often get lung infections.

<span class="mw-page-title-main">Primary ciliary dyskinesia</span> Medical condition

Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, fallopian tube, and flagella of sperm cells. The alternative name of "immotile ciliary syndrome" is no longer favored as the cilia do have movement, but are merely inefficient or unsynchronized. When accompanied by situs inversus the condition is known as Kartagener syndrome.

In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a nonsense codon, or a premature stop codon in the transcribed mRNA, and leads to a truncated, incomplete, and possibly nonfunctional protein product. Nonsense mutation is not always harmful, the functional effect of a nonsense mutation depends on many aspects, such as the location of the stop codon within the coding DNA. For example, the effect of a nonsense mutation depends on the proximity of the nonsense mutation to the original stop codon, and the degree to which functional subdomains of the protein are affected. As nonsense mutations leads to premature termination of polypeptide chains; they are also called chain termination mutations.

<span class="mw-page-title-main">Cystic fibrosis transmembrane conductance regulator</span> Mammalian protein found in humans

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the CFTR gene.

<span class="mw-page-title-main">Allergic bronchopulmonary aspergillosis</span> Medical condition

Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system to the fungus Aspergillus. It occurs most often in people with asthma or cystic fibrosis. Aspergillus spores are ubiquitous in soil and are commonly found in the sputum of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses.

Congenital absence of the vas deferens (CAVD) is a condition in which the vasa deferentia reproductive organs fail to form properly prior to birth. It may either be unilateral (CUAVD) or bilateral (CBAVD).

Wilson–Mikity syndrome, a form of chronic lung disease (CLD) that exists only in premature infants, leads to progressive or immediate development of respiratory distress. This rare condition affects low birth babies and is characterized by rapid development of lung emphysema after birth, requiring prolonged ventilation and oxygen supplementation. It is closely related to bronchopulmonary dysplasia (BPD), differing mainly in the lack of prior ventilatory support. All the initial patients described with Wilson–Mikity syndrome were very low birth weight infants that had no history of mechanical ventilation, yet developed a syndrome that clinically resembled BPD. Upon the death of some of these infants, autopsies showed histologic changes similar to those seen in BPD.

Williams–Campbell syndrome (WCS) is a disease of the airways where cartilage in the bronchi is defective. It is a form of congenital cystic bronchiectasis. This leads to collapse of the airways and bronchiectasis. It acts as one of the differential to allergic bronchopulmonary aspergillosis. WCS is a deficiency of the bronchial cartilage distally.

Transepithelial potential difference (TEPD) is the voltage across an epithelium, and is the sum of the membrane potentials for the outer and inner cell membranes.

<span class="mw-page-title-main">Ivacaftor</span> Pharmaceutical medication used to treat cystic fibrosis

Ivacaftor is a medication used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis. It is also included in combination medications, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor which are used to treat people with cystic fibrosis.

Inquilinus limosus is a bacterium first isolated from cystic fibrosis patients' lungs, and is rarely observed elsewhere, prompting extensive research into its biology.

Claire E. Wainwright is a paediatric respiratory physician and professor of pediatrics, residing and working in Queensland. She commenced her medical training in London and completed her specialist training at the Royal Children's Hospital, Brisbane. She is now head of the Cystic Fibrosis Service at the Queensland Children's Hospital and a professor of pediatric medicine at the University of Queensland, Australia. Wainwright has published numerous academic papers focusing upon her main area of interest; the impacts of fungal infections upon children with cystic fibrosis. However, her interests also expand to include other airway complications within children.

<span class="mw-page-title-main">Tezacaftor</span> Chemical compound

Tezacaftor is a drug used for the treatment of cystic fibrosis (CF) in people six years and older, who have a F508del mutation, the most common type of mutation in the CFTR gene. It is sold as a fixed-dose combination with ivacaftor under the brand name Symdeko. It was approved by the U.S. FDA in 2018. The combination of elexacaftor, tezacaftor, and ivacaftor is being sold as Trikafta.

Jane C. Davies is a British physician who is Professor of Paediatric Respirology at Imperial College School of Medicine. She is an Honorary Consultant at the Royal Brompton and Harefield NHS Foundation Trust.

Elexacaftor/tezacaftor/ivacaftor, sold under the brand names Trikafta (US) and Kaftrio (EU), is a fixed-dose combination medication used to treat cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor is composed of a combination of ivacaftor, a chloride channel opener, and elexacaftor and tezacaftor, CFTR modulators.

Peter Grootenhuis was a Dutch-American Medicinal Chemist. Grootenhuis was the Project Leader and Co-Inventor of Ivacaftor (VX-770), the first CFTR potentiator FDA approved drug to treat the underlying cause of Cystic Fibrosis (CF) in patients with certain mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, who account for 4-5% of CF cases. Grootenhuis also led the Vertex team to subsequent discovery of Orkambi, the combination of Ivacaftor and Lumacaftor(VX-809), approved to treat CF in people with two copies of the F508del mutation. Most recently, Grootenhuis's team discovered Tezacaftor (VX-661) and Elexacaftor (VX-445), which in combination with Ivacaftor are the components of Trikafta, a drug approved by the FDA in 2019 to treat CF in more than 90% of CF patients. For Grootenhuis’ contributions to the discovery of these compounds, he was awarded the 2018 IUPAC Richter Prize, the American Chemical Society’s 2013 Heroes of Chemistry Award, and inducted into the American Chemical Society Division of Medicinal Chemistry Hall of Fame. Grootenhuis has contributed to the discovery of over 11 clinical candidates, co-authored more than 100 peer reviewed papers and is inventor of 65 + U.S Patents, and more than 50 EU Patents.

Johanna Rommens is a Canadian geneticist who was on the research team which identified and cloned the CFTR gene, which when mutated, is responsible for causing cystic fibrosis (CF). She later discovered the gene responsible for Shwachman-Diamond syndrome, a rare genetic disorder that causes pancreatic and hematologic problems. She is a Senior Scientist Emeritus at SickKids Research Institute and a professor in the Department of Molecular Genetics at the University of Toronto.

Batsheva Kerem is an Israeli geneticist who was on the research team that identified and cloned the CFTR gene, which when mutated, is responsible for causing cystic fibrosis (CF). She later established the Israel National Center for CF Genetic Research. She discovered the most prevalent cystic fibrosis-causing mutations among the Israeli population, allowing for the establishment of nationwide genetic screening programs to identify carriers of these mutations and enabling prenatal diagnoses. She researches how some CF mutations prevent CFTR protein production by causing nonsense-mediated decay and abnormal mRNA splicing, and how therapies might be able to counteract those problems. She also studies the role of genetic instability in cancer. She is currently a professor at the Hebrew University.

Paul Adrian Negulescu is an American–Romanian cell biologist. He is the Senior Vice President and Site Head of the San Diego Research Center of American pharmaceutical company Vertex Pharmaceuticals. He received the 2022 Shaw Prize in Life science and medicine, together with Michael J. Welsh, for their work that uncovered the etiology of cystic fibrosis and developed effective medications.

References

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  23. ↑ Scotet, Virginie; L'Hostis, Carine; Férec, Claude (2020-05-26). "The Changing Epidemiology of Cystic Fibrosis: Incidence, Survival and Impact of the CFTR Gene Discovery". Genes. 11 (6): 589. doi: 10.3390/genes11060589 . ISSN   2073-4425. PMC   7348877 . PMID   32466381.
  24. ↑ "Featured Review: Drugs for correcting the basic defect in the most common cystic fibrosis-causing gene variant". Cochrane. Retrieved 2022-11-18.
  25. ↑ Borowitz, Drucy; Wegman, Theresa; Harris, Margaret (December 1994). "Preventive Care for Patients With Chronic Illness: Multivitamin Use in Patients With Cystic Fibrosis". Clinical Pediatrics. 33 (12): 720–725. doi:10.1177/000992289403301203. ISSN   0009-9228. PMID   7874824. S2CID   43047336 . Retrieved 10 December 2022.
  26. ↑ Ward, Nathan; Morrow, Scott; Stiller, Kathy; Holland, Anne E. (1 August 2021). "Exercise as a substitute for traditional airway clearance in cystic fibrosis: a systematic review". Thorax. 76 (8): 763–771. doi: 10.1136/thoraxjnl-2020-215836 . ISSN   0040-6376. PMID   33443204. S2CID   229357310 . Retrieved 10 December 2022.
  27. ↑ Habib, Al-Rahim R.; Kajbafzadeh, Majid; Desai, Sameer; Yang, Connie L.; Skolnik, Kate; Quon, Bradley S. (2019-05-10). "A Systematic Review of the Clinical Efficacy and Safety of CFTR Modulators in Cystic Fibrosis". Scientific Reports. 9 (1): 7234. Bibcode:2019NatSR...9.7234H. doi:10.1038/s41598-019-43652-2. ISSN   2045-2322. PMC   6510767 . PMID   31076617.
  28. ↑ Lopes-Pacheco, Miquéias (2020). "CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine". Frontiers in Pharmacology. 10: 1662. doi: 10.3389/fphar.2019.01662 . ISSN   1663-9812. PMC   7046560 . PMID   32153386.
  29. ↑ Goetz, Danielle M.; Savant, Adrienne P. (December 2021). "Review of CFTR modulators 2020". Pediatric Pulmonology. 56 (12): 3595–3606. doi:10.1002/ppul.25627. ISSN   8755-6863. PMID   34407318. S2CID   237216168.
  30. 1 2 3 McGarry, Meghan E.; McColley, Susanna A. (June 2021). "Cystic Fibrosis Patients of Minority Race and Ethnicity Less Likely Eligible for CFTR Modulators Based on CFTR Genotype". Pediatric Pulmonology. 56 (6): 1496–1503. doi:10.1002/ppul.25285. ISSN   8755-6863. PMC   8137541 . PMID   33470563.
  31. ↑ "Racism, Inequality, and Health Care for African Americans". The Century Foundation. 2019-12-19. Retrieved 2022-12-09.
  32. ↑ Rho, Jason; Ahn, Chul; Gao, Ang; Sawicki, Gregory S.; Keller, Ashley; Jain, Raksha (2018-10-15). "Disparities in Mortality of Hispanic Patients with Cystic Fibrosis in the United States. A National and Regional Cohort Study". American Journal of Respiratory and Critical Care Medicine. 198 (8): 1055–1063. doi:10.1164/rccm.201711-2357OC. ISSN   1073-449X. PMC   6221571 . PMID   29742360.
  33. ↑ "Implicit Bias and Racial Disparities in Health Care". www.americanbar.org. Retrieved 2022-11-18.
  34. ↑ da Silva Filho, Luiz Vicente Ribeiro Ferreira; Zampoli, Marco; Cohen-Cymberknoh, Malena; Kabra, Sushil K. (2021-06-01). "Cystic fibrosis in low and middle-income countries (LMIC): A view from four different regions of the world". Paediatric Respiratory Reviews. 38: 37–44. doi:10.1016/j.prrv.2020.07.004. ISSN   1526-0542. PMID   32826173. S2CID   221240158.
  35. ↑ DiMango, Emily; Simpson, Kaitlyn; Menten, Elizabeth; Keating, Claire; Fan, Weijia; Leu, Cheng-Shiun (2021-07-31). "Health Disparities among adults cared for at an urban cystic fibrosis program". Orphanet Journal of Rare Diseases. 16 (1): 332. doi: 10.1186/s13023-021-01965-4 . ISSN   1750-1172. PMC   8325847 . PMID   34332588.
  36. ↑ McBennett, Kimberly A.; Davis, Pamela B.; Konstan, Michael W. (February 2022). "Increasing life expectancy in cystic fibrosis: Advances and challenges". Pediatric Pulmonology. 57 (Suppl 1): S5–S12. doi:10.1002/ppul.25733. ISSN   8755-6863. PMC   9004282 . PMID   34672432.
  37. ↑ "CF Foundation Continues Working Toward Equity and Timeliness in Cystic Fibrosis Newborn Screening". Cystic Fibrosis Foundation. 29 September 2022. Retrieved 2022-11-18.
  38. ↑ "Diversity and Inclusion". Cystic Fibrosis Research Institute. Retrieved 2022-11-18.
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