2023
McGarry ME, Huang CY, Ly NP. Ethnic differences in staphylococcus aureus acquisition in cystic fibrosis. Journal of Cystic Fibrosis. 2023 July
In this article, we did a longitudinal cohort study of people with cystic fibrosis ages 0-25 years in the CF Foundation Patient Registry compared acquisition of methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), persistent MRSA between Hispanic and non-Hispanic White people with cystic fibrosis. Of 10,640 people with cystic fibrosis, 7.5% were Hispanic and 92.5% were non-Hispanic White. Hispanic people with cystic fibrosis had a 19% higher risk of acquiring MSSA (HR 1.19, 95% CI 1.10-1.28, p<0.001) and 13% higher risk of acquiring MRSA (HR 1.13, 95% CI 1.02-1.26, p = 0.02) than non-Hispanic White people with cystic fibrosis. The difference in persistent MRSA between ethnicities did not reach statistical significance. After adjusting for confounding variables, only the risk of MSSA was significantly associated with ethnicity. Compared to non-Hispanic White people with cystic fibrosis, Hispanic people with cystic fibrosis acquired MSSA and MRSA at younger median ages (4.9 vs. 3.8 years (p<0.001), 22.4 vs. 20.8 years (p = 0.02).
In conclusion, Hispanic people with cystic fibrosis <25 years of age have an increased risk of acquiring MSSA and acquired MSSA and MRSA at an earlier age. Differences in S. aureus acquisition may contribute to increased morbidity in Hispanic people with cystic fibrosis.
Link: https://pubmed.ncbi.nlm.nih.gov/37460380/
McGarry ME, Gibb ER, Laguna TA, O'Sullivan BP, Sawicki GS, Zobell JT. How many billions is enough? Prioritizing profits over patients with cystic fibrosis. Pediatric Pulmonology. 2023 May
CFTR modulators have transformed CF but are some of the most expensive medications in the market and are over-priced compared with the value given. The high price of CFTR modulators leaves people with CF dependent on Vertex's copay assistance programs. Despite record-breaking profits, Vertex is drastically decreasing its copayment assistance programs, so people with CF will have to pay thousands of dollars monthly for CFTR modulators or discontinue therapy. Vertex continues to put profits above the lives of people with CF.
Link: https://onlinelibrary.wiley.com/doi/10.1002/ppul.26335
McGarry ME, Ren CL, Wu R, Farrell PM, McColley SA. Detection of disease-causing CFTR variants in state newborn screening programs. Pediatric Pulmonology. 2023 Feb.
In this article, we did a cross-sectional analysis of the detection rate of at least 1 CFTR variant for seven panels by race and ethnicity in genotyped people with CF (PwCF) or CFTR-related metabolic syndrome (CRMS)/CFTR-related disorders in CF Foundation Patient Registry (CFFPR) in 2020. We estimated the case detection rate of CFTR variant panels by applying the detection rate to Census data. Using data from CFFPR, we compared the rate of delayed diagnosis or false-negative NBS by race and ethnicity. We found that for all panels, detection of at least 1 CFTR variant was highest in non-Hispanic White PwCF (87.5%-97.0%), and lowest in Black, Asian, and Hispanic PwCF (41.9%-93.1%). Detection of at least 1 CFTR variant was lowest in Black and Asian people with CRMS/CFTR-related disorders (48.4%-64.8%). States with increased racial and ethnic diversity have lower detection rates for all panels. Overall, 3.8% PwCF had a false-negative NBS and 11.8% had a delayed diagnosis; Black, Hispanic, and mixed-race PwCF were overrepresented.
From this research, we conclude that CFTR variant panels have lower detection rates in minoritized racial and ethnic groups leading to false-negative NBS, delayed diagnosis, and likely health disparities.
Link: https://pubmed.ncbi.nlm.nih.gov/36237137/
2022
McGarry ME, McColley SA, Taylor-Cousar J. In response to “who are the 10%?–Non eligibility of cystic fibrosis (CF) patients for highly effective modulator therapies”. Respiratory Medicine. 2022 Oct 1;202.
In the article by Desai et al. (August 2022), we were not surprised to read that, similar to what we reported in people with cystic fibrosis (pwCF) in the U.S., the authors found that in the U.K. pwCF who are categorized as Black, Asian, and other ethnically minoritized backgrounds are less likely to be eligible for elexacaftor/tezacaftor/ivacaftor. In the authors’ discussion regarding the etiology of inequitable eligibility for CFTR modulators and worse health outcomes in pwCF from minoritized racial and ethnic backgrounds, critical aspects were missing, specifically factors known to affect the social determinants of health (SDOH) for which the social constructs of race and ethnicity are often proxies for systemic bias and structural racism.
Systems for screening, diagnosing, and treating CF are designed to favor non-Hispanic White pwCF. Genetic panels and newborn screening programs favor the identification of CFTR variants in non-Hispanic White people over those more commonly found in pwCF of non-European genetic ancestry. For the same reasons, variants in non-Hispanic White people are more often well characterized. PwCF of minoritized racial and ethnic backgrounds are more likely to have false negative newborn screening tests and to be diagnosed at an older age as a result of bias by clinicians regarding the epidemiology of CF taught in medical training; CF has long been characterized as a White, “Caucasian”, or Northern European disease6. While the adverse effects of lower socioeconomic status (SES) are well characterized in CF and other chronic diseases, many pwCF of minoritized ethnic backgrounds experience poor health outcomes regardless of SES as there are multiple drivers of lower pulmonary function in Black and Hispanic pwCF that can be addressed in clinical care and research. Trials of CF therapies, including CFTR modulators, include almost exclusively non-Hispanic White participants, creating gaps in early access to highly effective therapies (via open-label access to trial participants)10, and leaving a lack of knowledge about how the social determinants of health affecting pwCF influence outcomes. The eligibility for CFTR modulators was designed in a way that favors non-Hispanic White pwCF and leaves pwCF from minoritized racial and ethnic groups without the same access to disease-altering drugs. While social determinants of health have long-impacted equity in CF care, eligibility, and access to CFTR modulators has created a wide chasm in care between those able to benefit from CFTR modulators and those unable to benefit. Based on our work and that of Desai et al., pwCF of minoritized racial and ethnic backgrounds are clearly overrepresented in the group of pwCF not benefiting from CFTR modulators.
None of us desire worse outcomes for our patients of minoritized racial and ethnic backgrounds. However, health equity efforts require that differences in access and outcomes are not simply described by race/ethnicity but that more attention is given to the social, economic, and environmental factors that differentially put those of minoritized ethnic and racial backgrounds at risk for worse outcomes. Following the appropriate identification of risk factors, those of us invested in research and entrusted with clinical care must redouble our efforts to assure timely diagnosis, research engagement and inclusion, and support for pwCF who are minoritized by structural racism not only in society but in CF diagnosis and treatment.
Link: https://www.resmedjournal.com/article/S0954-6111(22)00218-9/fulltext
2021
McGarry ME, Gibb ER, Oates GR, Schechter MS. Left behind: the potential impact of CFTR modulators on racial and ethnic disparities in cystic fibrosis. Paediatric Respiratory Reviews. 2021 Dec 22.
The advent of CFTR modulators, a genomic specific medication, revolutionized the treatment of CF for many patients. However, given that these therapeutics were only developed for specific CFTR mutations, not all people with CF have access to such disease-modifying drugs. Racial and ethnic minority groups are less likely to have CFTR mutations that are approved for CFTR modulators. This exclusion has the potential to widen existing health disparities.
Link: https://pubmed.ncbi.nlm.nih.gov/35277357/
McGarry ME, McColley SA. Cystic fibrosis patients of minority race and ethnicity less likely eligible for CFTR modulators based on CFTR genotype. Pediatric pulmonology. 2021 Jun;56(6):1496-503.
In this article, we conducted a cross-sectional study of patients in the 2018 CF Foundation Patient Registry. to analyze the percentage of patients in each US Census defined racial and ethnic group eligible for CFTR modulators based on CFTR mutations approved by the US FDA and then based on both mutations and FDA approval by age. We compared lung function based on CFTR modulator eligibility and prescription. Based on CFTR mutations alone, 92.4% of non-Hispanic White patients, 69.7% of Black/African American patients, 75.6% of Hispanic patients, and 80.5% of other race patients eligible for CFTR modulators. For each CFTR modulator, Black/African American patients were least likely to have eligible mutations, and non-Hispanic White patients were most likely. There was no difference in the disparity between racial and/or ethnic groups with the addition of current FDA approval by age. The lowest pulmonary function in the cohort was seen in non-Hispanic White, Black/African American, and Hispanic patients not eligible for CFTR modulators.
Link: https://pubmed.ncbi.nlm.nih.gov/33470563/
McGarry ME, Huang CY, Nielson DW, Ly NP. Early acquisition and conversion of Pseudomonas aeruginosa in Hispanic youth with cystic fibrosis in the United States. Journal of Cystic Fibrosis. 2021 May 1;20(3):424-31.
In this article, we did a longitudinal study comparing the timing and risk of acquisition of different forms of P. aeruginosa between Hispanic and non-Hispanic white patients aged 0-21 years old with CF in the CF Foundation Patient Registry (CFFPR) in 2008-2013. Hispanic patients acquired all forms of P. aeruginosa at a younger age than non-Hispanic white patients. Hispanic patients had a higher risk of acquiring P. aeruginosa than non-Hispanic white patients: the hazard ratio (HR) was 1.26 (95% CI 1.16-1.38, p<0.001) for initial P. aeruginosa, 1.59 (95% CI 1.43-1.77, p<0.001) for mucoid P. aeruginosa, 1.91 (95% CI 1.64-2.23, p<0.001) for multidrug-resistant P. aeruginosa, and 1.39 (95% CI 1.25-1.55, p<0.001) for chronic P. aeruginosa.
Link: https://pubmed.ncbi.nlm.nih.gov/33162303/
2020
McGarry ME. Triple therapy for cystic fibrosis with a Phe508del CFTR mutation. The New England Journal of Medicine. 2020 Feb 13;382(7):684.
In this article, we comment on the lack of description of subjects’ race and ethnicity.
Link: https://pubmed.ncbi.nlm.nih.gov/32053310/
2019
McGarry ME, Williams WA, McColley SA. The Demographics of Adverse Outcomes in Cystic Fibrosis. Pediatric Pulmonology. 2019 Nov. 54(53):S74-S83.
In this article, we review demographic factors associated with poorer health outcomes in CF, known and postulated biological mechanisms of these outcomes, and interventions that healthcare teams can implement that may reduce outcome disparities.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31715087
Zeiger, A.M.*, McGarry, M.E.*, Mak, A.C., Medina, V., Salazar, S., Eng, C., Liu, A.K., Oh, S.S., Nuckton, T.J., Jain, D. and Blackwell, T.W., 2019. Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico. Pediatric Pulmonology. 2019.
We conducted the first CFTR sequencing of CF patients in Puerto Rico and the Dominican Republic. We found that only 10% of Dominican patients had two CFTR mutations identified compared with 81% of Puerto Rican patients. No CFTR mutations were identified in 69% of Dominican patients and 10% of Puerto Rican patients. The spectrum of mutations is different from other Hispanic populations.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31665830
2017
McGarry ME, Neuhaus JM, Nielson DW, Burchard EG, Ly NP. Regional Variations In Longitudinal Pulmonary Function: A Comparison of Hispanic and Non-Hispanic Subjects With Cystic Fibrosis In the United States. Pediatric Pulmonology. 2019 May 29. 54(9):1382-1390.
Using CFF Registry data, we found that the gap in lung function between Hispanics and whites is twice as big in the West compared to the rest of the United States.
Link: https://www.ncbi.nlm.nih.gov/pubmed/31144477/
McGarry ME, Neuhaus JM, Nielson DW, Burchard EG, Ly NP. Pulmonary function disparities exist and persist in Hispanic patients with cystic fibrosis: A longitudinal analysis. Pediatric Pulmonology. 2017 Oct 30. 52(12):1550-1557.
Using CFF Registry data, we found that Hispanics had worse lung function compared to non-Hispanic whites. FEV1 percent predicted was 5.8% lower but no difference in decline.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29082671
McGarry ME, Illek B, Ly NP, Zlock L, Olshansky S, Moreno C, Finkbeiner WE, Nielson DW. In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies. Pediatric Pulmonology. 2017 Jan 09.
We conducted a N-of-1 clinical trial of ivacaftor versus placebo in patients with CF and clinical signs of residual CFTR function. Some CF patients with residual CFTR function have decreased sweat chloride concentration with ivacaftor. Increased chloride current in HNE cultures among subjects with decreased sweat chloride concentrations may predict clinical response to ivacaftor.
Link: https://www.ncbi.nlm.nih.gov/pubmed/28068001
2016
McGarry ME, McColley SA. Minorities Are Underrepresented In Clinical Trials of Pharmaceutical Agents for Cystic Fibrosis. Ann Am Thorac Soc. 2016 Jul 13.
We investigated and found that minorities are proportionally underrepresented in CF pharmacology clinical trials compared to the CF population. Over 80% of CF pharmacology clinical trials did not even report subjects’ race and ethnicity.
Link: https://www.ncbi.nlm.nih.gov/pubmed/27410177
2013
McGarry ME, Nielson DW. Normalization of Sweat Chloride Concentration and Clinical Improvement With Ivacaftor in a Patient with Cystic Fibrosis with Mutation S549N. Chest. 2013 Oct; 144(4):1376-8.
In this case report, we discuss the first use of ivacaftor, a CFTR potentiator, in a patient without a G511D CFTR mutation. Her response in sweat chloride concentration and lung function was greater than reported in clinical trials.
Link: https://www.ncbi.nlm.nih.gov/pubmed/24081349
Link to Dr. McGarry’s Pubmed list: https://www.ncbi.nlm.nih.gov/myncbi/1xQFivt8tihQD/bibliography/public/