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Browsing by Author "Chan, Kevin M."
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Item Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction(Wiley, 2021) EPI Study Group; Hage, Chadi A.; Klesney-Tait, Julia; Wille, Keith; Arcasoy, Selim; Yung, Gordon; Hertz, Marshall; Chan, Kevin M.; Morrell, Matt; Goldberg, Hilary; Vedantham, Suresh; Derfler, Mary Clare; Commean, Paul; Berman, Keith; Spitznagel, Ed; Atkinson, Jeff; Despotis, George; Medicine, School of MedicineBackground: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV1 in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed. Study design and methods: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV1 decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint. Results: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV1 decline that were reduced by 93% in evaluable ECP-treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV1 decline were observed in the non-survivors (-212 ± 177 ml/month) when compared to the survivors (-95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment. Conclusions: These analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.Item Histopathology of Explanted Lungs From Patients With a Diagnosis of Pulmonary Sarcoidosis(Elsevier, 2016-02) Zhang, Chen; Chan, Kevin M.; Schmidt, Lindsay A.; Myers, Jeffrey L.; Department of Pathology & Laboratory Medicine, IU School of MedicineBackground Pathologic features of end-stage pulmonary sarcoidosis (ESPS) are not well defined; anecdotal reports have suggested that ESPS may mimic usual interstitial pneumonia (UIP). We hypothesized that ESPS has distinct histologic features. Methods Twelve patients who received a diagnosis of pulmonary sarcoidosis and underwent lung transplantation were included. Control subjects were 10 age- and sex-matched lung transplant patients with UIP. Hematoxylin and eosin-stained tissue sections were examined for the following features: extent/pattern of fibrosis; presence and quantity (per 10 high-power fields) of fibroblast foci and granulomas; distribution and morphology of granulomas; and presence and extent of honeycomb change. Extent of fibrosis and honeycomb change in lung parenchyma was scored as follows: 1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%; 4 = 76% to 100% of lung parenchyma. Results Eight of 12 cases demonstrated histologic findings typical of ESPS. All showed well-formed granulomas with associated fibrosis distributed in a distinct lymphangitic fashion. Granulomas were present in hilar or mediastinal lymph nodes from six of six patients with ESPS and none of eight control subjects. The extent of fibrosis, honeycomb change, and fibroblast foci was significantly lower in ESPS cases compared with control cases. Two patients with remote histories of sarcoidosis showed histologic features of diseases other than ESPS (UIP and emphysema) without granulomas. Two patients with atypical clinical findings demonstrated nonnecrotizing granulomas combined with either severe chronic venous hypertension or UIP. Conclusions ESPS and UIP have distinct histopathologic features in the lungs. Patients with a pretransplant diagnosis of sarcoidosis may develop other lung diseases that account for their end-stage fibrosis.Item Lung Transplantation for Bronchopulmonary Dysplasia in Adults: A Clinical and Pathological Study of Three Cases(Wolters Kluwer, 2020-04) Liu, Natalia; Cummings, Oscar W.; Lagstein, Amir; Hage, Chadi A.; Chan, Kevin M.; Zhang, Chen; Pathology and Laboratory Medicine, School of MedicineBronchopulmonary dysplasia (BPD) is usually seen in premature infants who require mechanical ventilation and oxygen therapy for acute respiratory distress. Although most patients wean from oxygen therapy by the ages of 2 to 3, rehospitalization for respiratory problems is common in these patients in adulthood. There have been few studies that document the long-term outcomes of BPD survivors and information about the pulmonary function and radiographic findings of adult BPD are limited. Data on pathologic features of adult BPD are scarce. Three adult patients who underwent recent lung transplantation for BPD from 2 institutions were identified. Clinical data including clinical presentation, chest radiographic images, pulmonary function tests, cardiac catheterization, and echocardiography were retrieved from the electronic medical records. Hematoxylin and eosin and selective elastic stained sections of the explant lungs were examined. CD31 immunohistochemical stain is performed on representative sections. All 3 cases had similar clinical and radiologic features including the history of prematurity and long-term mechanical ventilation after birth, hyperexpanded lungs with air trapping and mosaic attenuation on chest computed tomographic scan, severe obstructive changes on pulmonary function test, and pulmonary hypertension. Pathologic examination showed common features including enlarged and simplified alveoli, peribronchial, subpleural, and interlobular septal fibrosis, narrowing/obliteration of the small airways by elastosis and muscular hypertrophy, thickening of venous walls by fibromuscular hyperplasia, and bronchitis/bronchiolitis. Cholesterol granulomas were seen in 2 cases. The common pathologic findings in the lungs explain the clinical and radiologic findings. Future studies are warranted to further characterize the clinical and pathologic features of adult BPD to develop optimal management strategies for these patients.