Browsing by Author "Cheng, Pi Chun"

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    Elexacaftor/Tezacaftor/Ivacaftor Supports Treatment for CF with ΔI1023-V1024-CFTR
    (MDPI, 2025-05-31) Huang, Yunjie; Gonzales Cordova, Jorge Moises; Penrod, Sarah; Bendy, Lisa Lynn; Cheng, Pi Chun; Sanders, Don B.; Denning Davis, Michael; Gaston, Benjamin; Chmiel, James Francis; Pediatrics, School of Medicine
    Cystic Fibrosis (CF) is a common genetic disease in the United States, resulting from mutations in the Cystic Fibrosis transmembrane conductance regulator (cftr) gene. CFTR modulators, particularly Elexacaftor/Tezacaftor/Ivacaftor (ETI), have significantly improved clinical outcomes for patients with CF. However, many CFTR mutations are not eligible for CFTR modulator therapy due to their rarity. In this study, we report that a patient carrying rare complex CFTR mutations, c.1680-877G>T and c.3067_3072delATAGTG, showed positive clinical outcomes after ETI treatment. We demonstrate that ETI was able to increase the expression of CFTR harboring c.3067_3072delATAGTG in a heterologous system. Importantly, patient-derived nasal epithelial cells in an air-liquid interface (ALI) culture showed improved CFTR function following ETI treatment. These findings supported the initiation of ETI with the patient. Retrospective studies have suggested that the patient has shown small but steady improvement over the past two years in several clinical metrics, including lung function, body mass index (BMI), and sweat chloride levels. Our studies suggest that ETI could be beneficial for patients carrying c.3067_3072delATAGTG.
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    Pediatric Pulmonology 2024 Year in Review: Rare and Diffuse Lung Disease
    (Wiley, 2025) Cheng, Pi Chun; Liptzin, Deborah R.; Garagozlo, Katiana; Barber, Andrew T.; Pediatrics, School of Medicine
    The field of pediatric rare and diffuse lung diseases continues to advance, with ongoing research deepening our understanding of the diagnosis and treatment of conditions such as children's interstitial and diffuse lung disease (chILD), non-cystic fibrosis (CF) bronchiectasis, and pulmonary complications of childhood cancer. Recent publications in Pediatric Pulmonology and other journals in 2024 have highlighted new insights into the pathophysiology, disease progression, and emerging diagnostic tools for these rare lung conditions, as well as innovative therapeutic approaches. This review features these important advancements within the context of current diagnostic practices and clinical care for pediatric patients with rare and diffuse lung diseases.
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    Primary Graft Dysfunction Grade 3 following Pediatric Lung Transplantation is Associated with Chronic Lung Allograft Dysfunction
    (Elsevier, 2023) Wong, Wai; Johnson, Brandy; Cheng, Pi Chun; Josephson, Maureen B.; Maeda, Katsuhide; Berg, Robert A.; Kawut, Steven M.; Harhay, Michael O.; Goldfarb, Samuel B.; Yehya, Nadir; Himebauch, Adam S.; Pediatrics, School of Medicine
    Background: Severe primary graft dysfunction (PGD) is associated with the development of bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), in adults. However, PGD associations with long-term outcomes following pediatric lung transplantation are unknown. We hypothesized that PGD grade 3 (PGD 3) at 48- or 72-hours would be associated with shorter CLAD-free survival following pediatric lung transplantation. Methods: This was a single center retrospective cohort study of patients ≤ 21 years of age who underwent bilateral lung transplantation between 2005 and 2019 with ≥ 1 year of follow-up. PGD and CLAD were defined by published criteria. We evaluated the association of PGD 3 at 48- or 72-hours with CLAD-free survival by using time-to-event analyses. Results: Fifty-one patients were included (median age 12.7 years; 51% female). The most common transplant indications were cystic fibrosis (29%) and pulmonary hypertension (20%). Seventeen patients (33%) had PGD 3 at either 48- or 72-hours. In unadjusted analysis, PGD 3 was associated with an increased risk of CLAD or mortality (HR 2.10, 95% CI 1.01-4.37, p=0.047). This association remained when adjusting individually for multiple potential confounders. There was evidence of effect modification by sex (interaction p = 0.055) with the association of PGD 3 and shorter CLAD-free survival driven predominantly by males (HR 4.73, 95% CI 1.44-15.6) rather than females (HR 1.23, 95% CI 0.47-3.20). Conclusions: PGD 3 at 48- or 72-hours following pediatric lung transplantation was associated with shorter CLAD-free survival. Sex may be a modifier of this association.
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    Pulmonary function testing in pediatric allogeneic stem cell transplant recipients to monitor for Bronchiolitis obliterans syndrome: a systematic review
    (Springer Nature, 2025-03-28) Gower, William A.; Tamae-Kakazu, Maximiliano; Shanthikumar, Shivanthan; Srinivasan, Saumini; Reardon, Erin E.; Barochia, Amisha V.; Charbek, Edward; Calvo, Charlotte; Cheng, Pi Chun; Das, Shailendra; Davies, Stella M.; Gross, Jessica; Sheshadri, Ajay; Towe, Christoper T.; Goldfarb, Samuel B.; Iyer, Narayan P.; Pediatrics, School of Medicine
    Background: Bronchiolitis obliterans syndrome (BOS) represents a significant source of morbidity and non-relapse mortality among children and young adults treated with allogeneic hematopoietic stem cell transplantation (aHSCT). Pulmonary function testing (PFT) pre- and post-aHSCT may allow for pre-symptomatic detection of BOS, and thus early intervention. Current guidelines and practices vary regarding which tests to perform and timing relative to transplant. A systematic review evaluating PFT before and after pediatric aHSCT was conducted to inform American Thoracic Society clinical practice guidelines on detection of BOS. Objective: To determine the optimal approach to conducting PFT prior to and after pediatric aHSCT. Study design: We performed a systematic review of the literature to identify studies of PFT in human aHSCT recipients < 25 years of age to address two questions: (1) Should pre-transplant screening PFT be performed in pediatric patients who will undergo aHSCT? (2) At what frequency should pediatric patients who have had aHSCT undergo PFT? We searched in Medline through August 2022 for studies that enrolled patients < 25 years of age being treated with aHSCT for whom PFT data were reported before or after transplant. Results: The 30 studies with pre-transplant PFT data showed a wide range of findings, with the majority demonstrating abnormalities. In studies reporting respiratory symptoms, 85-100% of patients were asymptomatic. In the 21 studies reporting post-transplant PFT, 11 used a surveillance strategy where at least one test was performed in the first year post-transplant. Median time to BOS diagnosis was 6-12 months in the regular surveillance studies, and 6-24 months in the others. Forced expiratory volume in one second at the time of BOS diagnosis was 38-84% predicted in studies with regular surveillance versus 44-57% predicted in studies with no surveillance. In the surveillance group, BOS was identified in some patients who were asymptomatic. Data quality in studies reviewed was moderate to very low. Conclusions: Abnormalities in PFT are common in children prior to aHSCT. Regular monitoring in the first 1-2 years post-aHSCT may improve early and/or pre-symptomatic identification of BOS, but significant limitations may still be seen at the time of diagnosis. Higher quality data are needed.