Current Research at the McGarry Lab
Pulmonary Disease Severity
Latino children with cystic fibrosis suffer a greater burden from their disease with more severe pulmonary disease compared to non-Latino white children. Over the past decade, Dr. McGarry’s research has developed the field and directly led to our better understanding of health disparities research in cystic fibrosis (CF). Our focus is to understand the clinical, microbiology, environmental and social factors that may be differentially contributing to more severe disease in Latino children with CF.
Prior findings
We have found that Latino children with CF have worse pulmonary disease than non-Latino white children with CF. Additionally, there are regional differences in this ethnic gap in lung function, as Latino children with CF in the West have twice as large a disparity in lung function compared to the other U.S. Census regions. This disparity is not modified by socioeconomic factors and occurs even in children with the same CFTR variants. Latino children with CF acquired all forms of Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus at a younger age than non-Hispanic children with CF. Compared to non-Hispanic children with CF, Latino children are also at an increased risk of acquiring all forms of Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus.
Key publications
- Pulmonary Function Disparities Exist and Persist in Hispanic Patients With Cystic Fibrosis: A Longitudinal Analysis
- Regional variations in longitudinal pulmonary function: A comparison of Hispanic and non-Hispanic subjects with cystic fibrosis in the United States
Pulmonary Pathogens and Microbiome
In cystic fibrosis (CF), respiratory infections increase inflammation leading to lung damage and lower lung function. Certain pathogens (such as Pseudomonas aeruginosa) lead to a steeper decline in lung function, more severe lung function and higher mortality. We are investigating how these pulmonary pathogens are contributing to more severe lung disease in Latino people with CF. We are also investigating how the pulmonary environment or microbiome may be different and contributing to health disparities.
Prior findings
We have found that Latino people with CF are more likely to acquire severe pathogens (Pseudomonas aeruginosa and Staphylococcus aureus). Latino people with CF are more likely to convert to severe forms of these pathogens, such as mucoid. Latino people with CF also acquire these pathogens at a younger age than non-Latino white people.
Key publications
- Ethnic differences in staphylococcus aureus acquisition in cystic fibrosis.
- Early acquisition and conversion of Pseudomonas aeruginosa in Hispanic youth with cystic fibrosis in the United States
Equality in Diagnosis for All
People with cystic fibrosis (CF) who are Asian, Black, Indigenous or Latino are less likely to have known, well-described CFTR gene variants. Race and ethnicity are social constructs, but the frequency of gene variants or mutations reflects a person’s ancestry or where their family/ancestors originate from. Genetic panels for diagnosis often only include CFTR variants or mutations that occur in white or European populations. This creates barriers to people being diagnosed with CF in a timely manner.
Prior findings
We have shown how commonly used CFTR variant panels miss many people with CF who are Asian, Black, Indigenous or Latino. Dr. McGarry advocates for improved screening to reduce disparities in diagnosis. Dr. McGarry is the lead author of the new Cystic Fibrosis Foundation Newborn Screening Guideline which will bring equality to newborn screening.
Previously, we have genetically sequenced the CFTR gene in people with cystic fibrosis who live in the Dominican Republic and Puerto Rico. Despite these two countries being close geographically, we found the variant frequency was quite different.
Key publications
- Detection of disease-causing CFTR variants in state newborn screening programs
- Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico
- CFTR Variant Frequencies and Newborn Screening Panel Performance in the Diverse CF Population Receiving Care in the State of Georgia
- Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation
- Refining CFTR-Related Metabolic Syndrome (CRMS)/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Diagnosis: Impact of CFTR2 Variant Classifications
- The Newborn Screening Experience of Caregivers of Children With Cystic Fibrosis in the United States: A Cross-Sectional Survey
Disparities in Access to Medications
Cystic fibrosis is at the forefront of precision medicine with a new class of drug called CFTR modulators. However, CFTR modulators are only approved for a limited number of CFTR variants leaving some people with CF without access. People who are Asian, Black, Indigenous or Latino are less likely to qualify for and be prescribed CFTR modulators.
Prior findings
We have found that people with CF who are Asian, Black, or Latino 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. We found that people with CF who are Asian, Black or Latino are less likely to qualify for CFTR modulators which are disease altering and greatly improve outcomes.
We previously 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.
Dr. McGarry continues to advocate that people with CF all over the world should have access to CFTR modulator therapy that is affordable.
Key publications
- In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies
- Left behind: The potential impact of CFTR modulators on racial and ethnic disparities in cystic fibrosis
- Minorities Are Underrepresented in Clinical Trials of Pharmaceutical Agents for Cystic Fibrosis
- In response to “who are the 10%? – Non eligibility of cystic fibrosis (CF) patients for highly effective modulator therapies”
- Triple Therapy for Cystic Fibrosis with a Phe508del CFTR Mutation
- Normalization of sweat chloride concentration and clinical improvement with ivacaftor in a patient with cystic fibrosis with mutation S549N