Yu Kuang Lai

All Publications

• Identification of Pulmonary Arterial Hypertension Patients with Venous or Capillary Involvement. American journal of respiratory and critical care medicine Andruska, A. M., Cruz-Utrilla, A., Nossent, E. J., Celant, L. R., Yang, I. Y., Lyn, R., Lai, Y. K., Kudelko, K., Sung, Y., Spiekerkoetter, E., De Jesus Perez, V., Guo, H. H., Bogaard, H. J., Escribano-Subias, P., Zamanian, R. T., Sweatt, A. 2026

  Abstract

  While therapeutic advances have improved survival in Group 1 Pulmonary Arterial Hypertension (PAH), patients with Group 1.5 "PAH with features of venous/capillary involvement" (formerly Pulmonary Veno-Occlusive Disease or Pulmonary Capillary Hemangiomatosis, now collectively termed PVOD/PCH) remain underrecognized, develop serious complications from usual PAH therapy titrations, and suffer high mortality awaiting necessary lung transplant. Identifying PVOD/PCH early before therapy initiation could aid management and expedite transplant referral.We aimed to develop a likelihood score distinguishing PVOD/PCH from other forms of PAH using clinical variables.Due to low PVOD/PCH prevalence and no dedicated registries, we leveraged published case control/series studies to assess the ability of several clinical variables to discriminate PVOD/PCH from PAH. From pooled literature-derived data, we performed Sensitivity/Specificity and simulation-based Receiver Operator Characteristic (ROC) analyses to estimate variable performance. Top-performing variables formed a PVOD/PCH Likelihood score, which had its accuracy tested for distinguishing histopathology-confirmed PVOD/PCH cases (n = 37) from PAH controls (n = 60) in three cohorts of transplant-eligible patients from the United States, Spain, and the Netherlands.DLCO, six-minute walk desaturation, PaO2, sex, smoking history, CT septal line thickening, and CT lymphadenopathy had the highest sensitivity and specificity performance and were incorporated into the PVOD score. Across test cohorts, the score achieved a ROC area under the curve of 0.97 (95% CI 0.93-1.00) for discriminating PVOD/PCH and it retained accuracy when data were missing.This score could facilitate early PVOD/PCH identification in incident PAH, potentially helping expedite transplant referral and informing therapy initiation/titration decisions.

  View details for DOI 10.1093/ajrccm/aamag289

  View details for PubMedID 42275164

• Lung Complications after Allogeneic Hematopoietic Cell Transplant and Outcomes: Implications Beyond Bronchiolitis Obliterans Syndrome. Transplantation and cellular therapy Lai, Y. K., Sharifi, H., Arai, S., Scheck, A., Brondstetter, T., Epstein, D. J., Hsu, J. L. 2026

  Abstract

  Lung chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) comprises heterogeneous pulmonary phenotypes known as lung complications after transplantation (LCAT). While bronchiolitis obliterans syndrome (BOS) is well recognized and is associated with poor survival, restrictive phenotypes-including HCT-associated organizing pneumonia (HCT-OP) and truncal sclerosis (TS)- remain poorly defined. Prior studies often grouped restrictive phenotypes, potentially obscuring phenotype-specific risk profiles and introducing survival bias by not taking into account the variable timing of LCAT onset. Direct comparison between specific LCAT phenotypes and patients with cGVHD without lung involvement is limited, leaving uncertainty regarding the relative prognostic impact of individual LCAT phenotypes.Using dynamic time-dependent Cox regression, we hypothesized that LCAT phenotypes represent clinically and prognostically distinct entities.We conducted a longitudinal retrospective cohort study of adults with cGVHD. LCAT phenotypes were adjudicated as BOS, HCT-OP, or TS based on clinical, physiologic, and radiographic criteria. Patients with cGVHD without lung involvement served as the control group. Baseline for all survival analyses was defined as the date of cGVHD diagnosis. Multivariable Cox proportional hazards models were fit with LCAT phenotype as a time-varying exposure to account for variable onset timing and mitigate immortal-time bias; adjusted survival curves were derived using dynamic standardization. Non-relapse mortality (NRM) was analyzed using cause-specific Cox models with relapse occurring after cGVHD onset as a competing event.Of 895 patients who met inclusion criteria, LCAT was identified in 183 patients: BOS (n=85), HCT-OP (n=42), TS (n=32), and mixed phenotypes (n=24). Median time from cGVHD diagnosis to LCAT onset differed significantly: 3.3 months for HCT-OP, 9.4 months for BOS and 20.5 months for TS (p <0.001). Pulmonary function tests showed distinct patterns, with severe airflow obstruction in BOS, predominant diffusion impairment in HCT-OP; and restriction in TS. In multivariable time-dependent Cox models, BOS was independently associated with inferior OS (HR 2.14; 95% CI 1.51-3.02; p<0.001) and elevated NRM (HR 3.04; 95% CI 2.08-4.43; p<0.001) relative to controls. TS was independently associated with increased NRM (HR 2.33; 95% CI 1.12-4.86; p=0.024) but not OS (HR 1.53; 95% CI 0.78-3.05; p=0.217). HCT-OP was not significantly associated with increased OS or NRM risk relative to controls, a finding confirmed by sensitivity landmark analyses. In the LCAT burden model, mixed LCAT (≥2 phenotypes) conferred the greatest risk for both OS (HR 3.22; 95% CI 1.78-5.83; p<0.001) and NRM (HR 4.95; 95% CI 2.55-9.62; p<0.001) compared with controls, and also carried higher NRM than single LCAT (HR 2.04; 95% CI 1.03-4.02; p=0.041).LCAT phenotypes represent clinically distinct entities with divergent prognostic profiles. Accurate and granular phenotyping is essential to inform prognosis, guide surveillance strategies, and support therapeutic decision-making in patients with cGVHD.

  View details for DOI 10.1016/j.jtct.2026.06.010

  View details for PubMedID 42259420

• Successful GH Treatment of Hepatopulmonary Syndrome in Panhypopituitarism-related Advanced Liver Disease. JCEM case reports Chen, S., Diaz-Lankenau, R., Kwong, A., Chang, J., McAvoy, J., Lai, Y. K. 2026; 4 (4): luaf307

  Abstract

  Hepatopulmonary syndrome (HPS) is a known pulmonary vascular complication of chronic liver disease. In rare circumstances, HPS has been described in the context of panhypopituitarism. An underlying mechanism of panhypopituitarism-related liver injury is thought to stem from GH deficiency, leading to steatohepatitis from augmented lipid deposition within hepatocytes. Although liver transplantation remains the definitive treatment for HPS, resolution of panhypopituitarism-related HPS following GH replacement therapy has been occasionally described. These successful cases uniformly showed hepatic steatosis on biopsy that resolved after GH replacement, suggesting GH may effectively reverse the pathological process before permanent damage occurs. We present the first reported case of panhypopituitarism-related HPS successfully treated with GH replacement in the presence of significant liver fibrosis without steatosis. This case highlights the sustained therapeutic efficacy of GH even in advanced liver disease and adds to the limited literature regarding successful treatment of HPS, especially in the context of panhypopituitarism, without liver transplantation.

  View details for DOI 10.1210/jcemcr/luaf307

  View details for PubMedID 41909159

  View details for PubMedCentralID PMC13019524

• Lung Complications after Allogeneic Hematopoietic Cell Transplant and Outcomes: Implications Beyond BOS Lai, Y., Shari, H., Arai, S., Scheck, A., Hsu, J. L. ELSEVIER SCIENCE INC. 2026

  View details for Web of Science ID 001708754600010

• Noninfectious pulmonary complications after hematopoietic cell transplantation: a comprehensive review. Respiratory medicine Bertini, C., Soto, F., Brown, R., Bashoura, L., Cheng, G. S., Hensley, M. K., Hsu, J., Lai, Y. K., Sharifi, H., Sturek, J. M., Yanik, G. A., Yadav, H., Faiz, S. A., Sheshadri, A. 2025: 108336

  Abstract

  Hematopoietic stem cell transplant (HSCT) is a cornerstone for the treatment of high-risk hematologic malignancies. The efficacy of HSCT is limited by transplant-related complications, particularly pulmonary complications. Broadly speaking, the myriads of non-infectious complications that occur after HSCT are less completely understood than infectious complications despite contributing to significant morbidity and mortality. This review covers all major non-infectious pulmonary complications (NIPCs), offering clinical context regarding NIPCs presentation and provoking events while highlighting pathogenesis, knowledge gaps, and emerging therapies.

  View details for DOI 10.1016/j.rmed.2025.108336

  View details for PubMedID 40902833

• Bronchiectasis in bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Transplantation and cellular therapy Epstein, D. J., Rodriguez-Ormaza, N., Sharifi, H., Lai, Y. K., Guo, H. H., Borges, C. H., Omar, S. H., Sahota, A., Dhillon, E. S., Musa, Z. M., Moss, C. T., Chatterjee, P., Hofmann, G. H., Johnston, L., Arai, S., Hsu, J. L. 2025

  Abstract

  Bronchiectasis-bronchial dilatation accompanied by impaired mucociliary clearance, chronic infection, and chronic inflammation-may contribute to poor outcomes in bronchiolitis obliterans syndrome (BOS) complicating hematopoietic cell transplantation, though its epidemiology and impact are poorly understood.We assessed factors associated with bronchiectasis in BOS. We also assessed relationships between bronchiectasis and survival, respiratory infections, and percent predicted forced expiratory volume in one second (FEV1%).This single-center retrospective cohort study included adults who underwent allogeneic hematopoietic cell transplantation from 2010-2023 who subsequently developed BOS. Bronchiectasis was defined based on validated radiographic and clinical criteria. We used multivariable logistic and linear regression, extended Cox regression models, negative binomial regression, and generalized estimating equation to determine relationships between pre-BOS events and subsequent bronchiectasis, and between bronchiectasis and death, infections, and FEV1%.Among the 87 patients included for analysis, 54% developed bronchiectasis over a median follow-up of 2.2 years (IQR, 1.0-5.8) after BOS diagnosis. Thirty-three patients (37.9%) died. None of the prespecified risk factors were associated with bronchiectasis. Bronchiectasis was associated with an increased risk of death (HR, 3.10; 95% CI, 1.40-6.48; P = .0048) and an increased incidence rate of respiratory infections (IRR, 1.93; 95% CI, 1.23-3.02; P = .0040), controlling for confounders. Among those with bronchiectasis, chronic infection with Pseudomonas aeruginosa occurred in 8 (17.0%) and nontuberculous mycobacteria in 11 (23.4%). FEV1% was lower and declined more rapidly in those with bronchiectasis.Bronchiectasis frequently accompanies BOS and is associated with 2 poorer outcomes, though its causes in this population are not known.

  View details for DOI 10.1016/j.jtct.2025.08.013

  View details for PubMedID 40818827

• A Call for a Better PoPH Risk Assessment Model, and Treatment Direction. Pulmonary circulation Lai, Y. K. 2025; 15 (3): e70147

  View details for DOI 10.1002/pul2.70147

  View details for PubMedID 40766202

• How I diagnose and treat organizing pneumonia in hematopoietic cell transplant recipients. Blood Lai, Y. K., Sharifi, H., Hsu, J. L. 2024

  Abstract

  Organizing pneumonia (OP) is a known non-infectious pulmonary complication following allogeneic hematopoietic cell transplant (HCT) and represents a significant risk factor for non-relapse mortality in HCT recipients. Unlike bronchiolitis obliterans syndrome, it is not universally acknowledged as a distinctive pulmonary manifestation of chronic-graft-versus-host disease (cGVHD) and therefore, its diagnostic criteria and management approach is lacking. Given it shared similar clinical features, radiological and histological findings to OP in non-HCT population, the diagnostic approach and treatment strategy for OP in HCT recipient is largely adapted from the non-HCT population. In this paper, we aim to enhance the understanding of OP within the context of cGVHD following HCT, distinguish its clinical features and treatment strategy from non-HCT counterpart, thereby reinforcing its recognition as a pulmonary manifestation of GVHD. We will propose the diagnostic criteria and outline our approach in diagnosis and treatment strategy, highlighting the potential challenges that may arise in each process. Finally, we will discuss knowledge gaps in this field and identify the area of need for future research.

  View details for DOI 10.1182/blood.2023023249

  View details for PubMedID 38864640

• Portopulmonary Hypertension. Clinics in liver disease Lai, Y. K., Kwo, P. Y. 2023; 27 (1): 71-84

  Abstract

  PoPH is a well-recognized complication of portal hypertension with or without cirrhosis and is classified as a subset of PAH. Identification of PoPH is crucial as it has a major impact on prognosis and liver transplant candidacy. Echocardiogram is the initial screening tool of choice and the patient should proceed to RHC for confirmation. PAH-directed therapy is the treatment of choice, allowing the patient to achieve a hemodynamic threshold to undergo a liver transplant safely.

  View details for DOI 10.1016/j.cld.2022.08.002

  View details for PubMedID 36400468

• Epidemiology of lower respiratory tract infections and community-acquired respiratory viruses in patients with bronchiolitis obliterans syndrome after hematopoietic cell transplant: a retrospective cohort study. Transplantation and cellular therapy Epstein, D. J., Liang, E. C., Sharifi, H., Lai, Y. K., Arai, S., Graber-Naidich, A., Sundaram, V., Nelson, J., Hsu, J. L. 2022

  Abstract

  Among 55 patients with bronchiolitis obliterans syndrome, 34 (61.8%) developed lower respiratory tract infections, which were associated with impaired lung function and a trend toward increased mortality. Rhinovirus/enterovirus and Pseudomonas aeruginosa infections predominated; 10 (18.2%) patients developed non-tuberculous mycobacterial infections.

  View details for DOI 10.1016/j.jtct.2022.07.016

  View details for PubMedID 35872303

• Machine learning algorithms to differentiate among pulmonary complications after hematopoietic cell transplant. Chest Sharifi, H. n., Lai, Y. K., Guo, H. n., Hoppenfeld, M. n., Guenther, Z. D., Johnston, L. n., Brondstetter, T. n., Chhatwani, L. n., Nicolls, M. R., Hsu, J. L. 2020

  Abstract

  Pulmonary complications, including infections, are highly prevalent in patients after hematopoietic cell transplant with chronic graft-versus-host disease. These comorbid diseases can make the diagnosis of early lung graft-versus-host disease (bronchiolitis obliterans syndrome) challenging. A quantitative method to differentiate among these pulmonary diseases can address diagnostic challenges and facilitate earlier and more targeted therapy.We conducted a single center study of 66 patients with computed tomography chest scans analyzed with a quantitative imaging tool known as parametric response mapping. Parametric response mapping results were correlated with pulmonary function tests and clinical characteristics. Five parametric response mapping metrics were applied to K-means clustering and support vector machine models to distinguish among post-transplant lung complications solely from quantitative output.Compared to parametric response mapping, spirometry showed a moderate correlation with radiographic air trapping, and total lung capacity and residual volume showed a strong correlation with radiographic lung volumes. K-means clustering analysis distinguished 4 unique clusters. Clusters 2 and 3 represented obstructive physiology (encompassing 81% of patients with bronchiolitis obliterans syndrome) in increasing severity (percent air trapping 15.6% and 43.0%, respectively). Cluster 1 was dominated by normal lung, and cluster 4 was characterized by patients with parenchymal opacities. A support vector machine algorithm differentiated bronchiolitis obliterans syndrome with specificity of 88%, sensitivity of 83%, accuracy of 86% and an area under the receiver operating characteristic curve of 0.85.Our machine learning models offer a quantitative approach for the identification of bronchiolitis obliterans syndrome versus other lung diseases, including late pulmonary complications after hematopoietic cell transplant.

  View details for DOI 10.1016/j.chest.2020.02.076

  View details for PubMedID 32343962

• A Young Woman With a Rapidly GrowingThoracic Tumor. Chest Lai, Y. K., Holmes, B., Guo, H. H. 2019; 155 (5): e145–e148

  Abstract

  CASE PRESENTATION: A 38-year-old woman presented with 2months of dry cough, progressiveshortness of breath, central chest pain, nausea, vomiting, and dizziness. She was previously healthy and was not taking any medications. She denied fever, night sweats, or weight loss. She had a two pack-year smoking history and had quit smoking at 27 years of age. She denied drug use and had no recent travel history. Family history was pertinent for ovarian cancer, breast cancer, and colon cancer.

  View details for DOI 10.1016/j.chest.2018.12.014

  View details for PubMedID 31060712

• The Intralobular Gradient as Seen in Re-Expansion Pulmonary Edema. Radiology. Cardiothoracic imaging Lai, Y. K., Lindholm, P. n., Guo, H. H. 2019; 1 (5): e190084

  View details for DOI 10.1148/ryct.2019190084

  View details for PubMedID 33778531

  View details for PubMedCentralID PMC7977743