Browsing by Author "Weiner, Daniel J."

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    Historic Use of Race-Based Spirometry Values Lowered Transplant Priority for Black Patients
    (Elsevier, 2024) Colon Hidalgo, Daniel; Ramos, Kathleen J.; Harlan, Emily A.; Holguin, Fernando; Forno, Erick; Weiner, Daniel J.; Griffith, Matthew F.; Medicine, School of Medicine
    Background: The lung allocation score (LAS) is a tool used to prioritize patients for lung transplantation. For patients with interstitial lung diseases (ILDs), spirometry data are used for the LAS calculation. Spirometry values such as a FVC are subjected to race-specific equations that determine expected values. The effect of race-specific equations in LAS score remains unknown. Research question: Did the use of a race-based spirometry equation lead to longer waitlist times for Black patients? Study design and methods: We performed a retrospective analysis of patients listed for lung transplantation from 2005 through 2020 using publicly available data from the United Network for Organ Sharing. We recalculated LAS scores for Black patients using White-specific equations with the available variables. The primary objective was to evaluate the effect of race-specific equations on LAS scores and time on the transplant waitlist. Results: A total of 33,845 patients listed for lung transplantation were included in the analysis. White patients were listed at lower LAS scores, a higher proportion of White patients underwent transplantation, and White patients died on the waitlist at lower rates. When recalculating LAS scores using White-specific equations, Black patients with ILD had up to a 1.9-point higher score, which resulted in additional waitlist time. Interpretation: Race-specific equations led to longer wait times in Black patients listed for lung transplantation. The use of race-based equations widened already known disparities in pulmonary transplantation.
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    Nasal Epithelium Transcriptomics Predict Clinical Response to Elexacaftor/Tezacaftor/Ivacaftor
    (American Thoracic Society, 2024) Yue, Molin; Weiner, Daniel J.; Gaietto, Kristina M.; Rosser, Franziska J.; Qoyawayma, Christopher M.; Manni, Michelle L.; Myerburg, Michael M.; Pilewski, Joseph M.; Celedón, Juan C.; Chen, Wei; Forno, Erick; Pediatrics, School of Medicine
    Elexacaftor/tezacaftor/ivacaftor (ETI) has had a substantial positive impact for people living with cystic fibrosis (pwCF). However, there can be substantial variability in efficacy, and we lack adequate biomarkers to predict individual response. We thus aimed to identify transcriptomic profiles in nasal respiratory epithelium that predict clinical response to ETI treatment. We obtained nasal epithelial samples from pwCF before ETI initiation and performed a transcriptome-wide analysis of baseline gene expression to predict changes in forced expiratory volume in 1 second (ΔFEV1), year's best FEV1 (ΔybFEV1), and body mass index (ΔBMI). Using the top differentially expressed genes, we generated transcriptomic risk scores (TRSs) and evaluated their predictive performance. The study included 40 pwCF ≥6 years of age (mean, 27.7 [SD, 15.1] years; 40% female). After ETI initiation, FEV1 improved by ≥5% in 22 (61.1%) participants, and ybFEV1 improved by ≥5% in 19 (50%). TRSs were constructed using top overexpressed and underexpressed genes for each outcome. Adding the ΔFEV1 TRS to a model with age, sex, and baseline FEV1 increased the area under the receiver operating characteristic curve (AUC) from 0.41 to 0.88, the ΔybFEV1 TRS increased the AUC from 0.51 to 0.88, and the ΔBMI TRS increased the AUC from 0.46 to 0.92. Average accuracy was thus ∼85% in predicting the response to the three outcomes. Results were similar in models further adjusted for F508del zygosity and previous CFTR modulator use. In conclusion, we identified nasal epithelial transcriptomic profiles that help accurately predict changes in FEV1 and BMI with ETI treatment. These novel TRSs could serve as predictive biomarkers for clinical response to modulator treatment in pwCF.
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    Nutritional Status and Lung Function in Children with Pancreatic-Sufficient Cystic Fibrosis
    (Elsevier, 2022) Madde, Ankitha; Okoniewski, Will; Sanders, Don B.; Ren, Clement L.; Weiner, Daniel J.; Forno, Erick; Pediatrics, School of Medicine
    Background: There is a strong association between nutrition and long-term FEV1 in cystic fibrosis (CF), but studies have been driven by data from subjects with pancreatic insufficiency (PI-CF). We thus evaluated the association between body mass index (BMI) and FEV1 percent-predicted (FEV1pp) in children with pancreatic sufficiency (PS-CF) and contrasted it with the association in PI-CF. Methods: We utilized data from the CF Foundation Patient Registry. The cohort included children born 1995-2010, diagnosed <2 years of age, and who had annualized data on BMI percentile and FEV1pp at ages 6-16 years. Pancreatic status was defined based on pancreatic enzyme replacement therapy. The association between BMI and FEV1 was evaluated using linear and mixed-effects longitudinal regression. Results: There were 424 children with PS-CF and 7,849 with PI-CF. The association between BMI and FEV1 differed significantly by pancreatic status: each 10-pct higher BMI was associated with 2% [95%CI = 1.9-2.1] higher FEV1pp in PI-CF, compared to just 0.9% [0.5-1.3] in PS-CF (PINTERACTION < 0.001). Within the at-risk nutritional category (BMI <25pct), each 10-pct higher BMI was associated with 5% higher FEV1pp in PI-CF, but no significant increase in PS-CF. Moreover, in PS-CF, overweight/obesity (BMI ≥85pct) was associated with decreasing FEV1pp. In addition, FEV1pp decline through age 20 years in youth with PS-CF was modest (-0.6% per year) and independent of BMI (BMI*age PINTERACTION = 0.37). Conclusions: In children with PS-CF, BMI remains an important determinant of lung function. However, it may be less critical to attain a BMI >50th percentile; and BMI ≥85th percentile may be detrimental.