Joshua Mooney

All Publications

• Bexotegrast Shows Dose-dependent Integrin αvβ6 Receptor Occupancy in Lungs of Participants with Idiopathic Pulmonary Fibrosis: A Phase 2, Open-Label Clinical Trial. Annals of the American Thoracic Society Mooney, J. J., Jacobs, S., Lefebvre, É. A., Cosgrove, G. P., Clark, A., Turner, S. M., Decaris, M., Barnes, C. N., Jurek, M., Williams, B., Duan, H., Kimura, R., Rizzo, G., Searle, G., Wardak, M., Guo, H. H. 2024

  Abstract

  Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by dyspnea and loss of lung function. Transforming growth factor-beta (TGF-β) activation mediated by αv integrins is central to the pathogenesis of IPF. Bexotegrast (PLN 74809) is an oral, once-daily, dual-selective inhibitor of αvβ6 and αvβ1 integrins under investigation for the treatment of IPF. Positron emission tomography (PET) using an αvβ6-specific PET tracer could confirm target engagement of bexotegrast in the lungs of participants with IPF. Objectives: This Phase 2 study (NCT04072315) evaluated αvβ6 receptor occupancy in the lung, as assessed by changes from baseline in αvβ6 PET tracer uptake, following single dose administration of bexotegrast to participants with IPF. Methods: In this open-label, single-center, single-arm study, adults with IPF received up to 2 single doses of bexotegrast, ranging from 60 to 320 mg with or without background IPF therapy (pirfenidone or nintedanib). At baseline and approximately 4 hours after each orally administered bexotegrast dose, a 60-minute dynamic PET/CT scan was conducted following administration of an αvβ6-specific PET probe ([18F]FP-R01-MG-F2). αvβ6 receptor occupancy by bexotegrast was estimated from the changes in PET tracer uptake following bexotegrast. Pharmacokinetics, safety, and tolerability of bexotegrast were also assessed. Results: Eight participants completed the study. Total and unbound plasma bexotegrast concentrations increased in a dose-dependent manner, and regional PET volume of distribution (VT) values decreased in a dose- and concentration-dependent manner. The VT data fit a simple saturation model, producing an unbound bexotegrast EC50 estimate of 3.32 ng/mL. Estimated maximum receptor occupancy was 35%, 53%, 71%, 88%, and 92% following single 60, 80, 120, 240, and 320-mg doses of bexotegrast, respectively. No treatment-emergent adverse events related to bexotegrast were reported. Conclusions: Dose- and concentration-dependent αvβ6 receptor occupancy by bexotegrast was observed by PET imaging, supporting once-daily 160 to 320 mg dosing to evaluate efficacy in clinical trials of IPF. Trial registration number: NCT04072315 Primary source of funding: Pliant Therapeutics, Inc. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  View details for DOI 10.1513/AnnalsATS.202409-969OC

  View details for PubMedID 39499805

• Potential Delays in Diagnosis of Idiopathic Pulmonary Fibrosis in Medicare Beneficiaries. Annals of the American Thoracic Society Mooney, J. n., Chang, E. n., Lalla, D. n., Papoyan, E. n., Raimundo, K. n., Reddy, S. R., Stauffer, J. n., Yan, T. n., Broder, M. S. 2019

  View details for PubMedID 30620617

• Estimated Impact of Hepatitis C Positive Lung Donor Utilization on US Donor Lung Supply. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Mooney, J. J., Purington, N. n., Mohabir, P. n., Dhillon, G. S. 2019

  Abstract

  The availability of highly effective direct-acting antiviral agent (DAA) medications for Hepatitis C virus (HCV) has led to reports of safely transplanting HCV+ donor lungs to HCV- candidates. However, it remains unclear how the ability to use HCV+ donor lungs for lung transplant could impact the number of donor lungs available for transplant. Using Scientific Registry of Transplant Recipient data we identified all deceased organ donors within the United States from March 1, 2015 to February 28, 2018 and stratified by HCV status. A donor prediction model for lung donation was derived and validated within HCV- donors and applied to HCV+ donors to estimate the number of acceptable HCV+ lung donors. Of 29,481 eligible donors, 2,054 (7.0%) were HCV+ donors with 82 HCV+ donors' lungs being utilized for transplant during the study period. The prediction model for donor lung donation (specificity 92.6%, sensitivity 65.6%) estimated 248 HCV+ donors (75 non-viremic, 173 viremic) were acceptable for lung transplant during the study period, suggesting that 166 acceptable HCV+ lung donors were discarded. The ability to transplant lungs from HCV+ organ donors would lead to an estimated nationwide increase of at least 55 donor lungs per year, including 44 from HCV viremic donors. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ajt.15558

  View details for PubMedID 31394016

• Multiple Listing in Lung Transplant Candidates: A Cohort Study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Mooney, J. J., Yang, L., Hedlin, H., Mohabir, P., Dhillon, G. S. 2018

  Abstract

  Lung transplant candidates can be waitlisted at more than one transplant center, a practice known as multiple listing. The factors associated with multiple listing and whether multiple listing modifies waitlist mortality or likelihood of lung transplant is unknown. US lung transplant waitlist candidates were identified as either single or multiple listed using data from the Scientific Registry of Transplant Recipients. Characteristics of single and multiple listed candidates were compared and multivariable logistic regression was used to estimate associations with multiple listing. Multiple listed candidates were matched to single listed candidates using a combination of exact and propensity score matching methods. Cox proportional hazard models were used to estimate the relationship of multiple listing on waitlist mortality and receiving a transplant. Multiple listing occurred in 2.3% of lung transplant waitlist candidates. Younger age, female gender, white race, short stature, high antibody sensitization, college or post-college education, lower lung allocation score, and a cystic fibrosis diagnosis were independently associated with multiple listing. Multiple listing was associated with an increased likelihood of lung transplant (adjusted hazard ratio [aHR] 2.74, 95% CI 2.37 to 3.16) but was not associated with waitlist mortality (aHR 0.99, 95% CI 0.68 to 1.44). This article is protected by copyright. All rights reserved.

  View details for PubMedID 30253057

• Effect of broader geographic sharing of donor lungs on lung transplant waitlist outcomes. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Mooney, J. J., Bhattacharya, J. n., Dhillon, G. S. 2018

  Abstract

  The United States lung allocation system prioritizes allocation based on medical urgency and benefit but does not address a federal mandate for broader geographic organ sharing. It is unknown whether broader geographic sharing of donor lungs would improve lung transplant waitlist outcomes.A discrete event microsimulation model simulated donor lung allocation according to different geographic lung-sharing policies, including the historic local donor service area (DSA)-based policy and hypothetical policies that prioritize candidates to donors within 500-mile or 1,000-mile geographic radii. Candidate waitlist mortality, number of transplants, and 1-year survival were compared across organ allocation policies. Waitlist mortality rates were further stratified by diagnosis, Lung Allocation Score (LAS) threshold, ABO blood type, and region.Under broader geographic lung sharing, the proportion of chronic obstructive pulmonary disease transplant recipients decreased, whereas the proportion of pulmonary fibrosis recipients increased. Waitlist mortality decreased with broader geographic lung sharing with a 21.3% decrease in waitlist mortality with 500-mile lung sharing and a 31.8% decrease in waitlist mortality with 1,000-mile lung sharing. The decrease in waitlist deaths occured across all U.S. geographic regions and was greatest in candidates with pulmonary fibrosis and/or high medical urgency.Broader geographic sharing of donor lungs could reduce waitlist mortality, particularly among pulmonary fibrosis and high-medical-urgency candidates.

  View details for PubMedID 30344025

• COUNTERPOINT: Should BAL Be Routinely Performed in the Diagnostic Evaluation of Idiopathic Pulmonary Fibrosis? No. Chest Mooney, J. J., Collard, H. R. 2017

  View details for PubMedID 28943280

• Racial and ethnic disparities in lung transplant listing and waitlist outcomes. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Mooney, J. J., Hedlin, H. n., Mohabir, P. n., Bhattacharya, J. n., Dhillon, G. S. 2017

  Abstract

  The United States lung transplant registry data demonstrate differences in adult waitlist mortality by race/ethnicity. It is unknown whether these differences persist after risk adjustment or occur secondary to disparities in disease severity at the time of listing.Adult lung transplant waitlist candidates between May 4, 2005 and March 5, 2015 were identified and compared by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and Asian race/ethnicity. A competing risk proportional hazards model was used to assess the association of race/ethnicity with the unadjusted and adjusted risk of waitlist death or removal for too sick, transplant, or removal for other reason. Disease illness severity at transplant listing was compared by race/ethnicity.There were 20,684 lung transplant candidates identified (82% NHW, 9% NHB, 6% Hispanic, 2% Asian and 1% other). Non-white candidates had higher unadjusted waitlist mortality, which was fully mitigated by adjusting for other risk factors (NHB: hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.93 to 1.18; Hispanic: HR 1.02, 95% CI 0.99 to 1.18; Asian: HR 0.90, 95% CI 0.70 to 1.16). Adjusted waitlist access to transplant was lower in non-white candidates (NHB: HR 0.88, 95% CI 0.83 to 0.94; Hispanic: HR 0.87, 95% CI 0.81 to 0.94; Asian: HR 0.83, 95% CI 0.73 to 0.96). NHW candidates with obstructive lung disease and pulmonary fibrosis were older with less illness severity at listing than non-white candidates.Within the current lung allocation system, there is no difference in risk-adjusted waitlist mortality by race/ethnicity, but non-white waitlist candidates have lower risk-adjusted access to lung transplant. Non-white candidates are generally younger with greater disease-specific illness severity at the time of lung transplant listing.

  View details for PubMedID 29129372

• Effect of Transplant Center Volume on Cost and Readmissions in Medicare Lung Transplant Recipients. Annals of the American Thoracic Society Mooney, J. J., Weill, D., Boyd, J. H., Nicolls, M. R., Bhattacharya, J., Dhillon, G. S. 2016; 13 (7): 1034-1041

  Abstract

  While lung transplant recipient survival is better at higher volume centers, the effect of center volume on admission cost and early hospital readmission is unknown.To understand the association between transplant center volume and recipient risk-adjusted transplant admission cost, in-hospital mortality, and early hospital readmission in lung transplant recipients.Medicare lung transplant recipients from May 4, 2005 to December 31, 2011 were identified through linkage of transplant registry and Medicare administrative claims. Transplant admission cost was extracted, adjusted for regional price variation, and compared across low, intermediate, and high volume centers. A multivariable hierarchical generalized linear regression model was used to assess the effect of transplant center volume on recipient adjusted cost. Modified Poisson regression models were used to assess adjusted in-hospital mortality and early hospital readmission by transplant center volume.There were 3,128 Medicare lung transplant recipients identified. Unadjusted transplant cost was lower at high volume centers (mean $131,352, SD±$106,165; median $90,177, IQR $79,165-$137,915) than intermediate (mean $138,792, SD±$106,270; median $93,024, IQR $82,700-$154,857) or low volume (mean $143,609, SD±$123,316; median $95,234, IQR $83,052-$152,149) centers (p<0.0001). After adjusting for recipient health risk, low volume centers had an 11.66% greater transplant admission cost (p=0.040), a 41% greater risk for in-hospital mortality (p=0.015), and a 14% greater risk for early hospital readmission (p=0.033) compared to high volume centers. There was no significant difference in transplant cost, in-hospital mortality, or early hospital readmission between intermediate and high volume centers.Lung transplant admission cost, in-hospital mortality, and early hospital readmission rate are lower at high volume centers compared to low volume centers.

  View details for DOI 10.1513/AnnalsATS.201601-017OC

  View details for PubMedID 27064753

• Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States AMERICAN JOURNAL OF TRANSPLANTATION Mooney, J. J., Hedlin, H., Mohabir, P. K., Vazquez, R., Nguyen, J., Ha, R., Chiu, P., Patel, K., Zamora, M. R., Weill, D., Nicolls, M. R., Dhillon, G. S. 2016; 16 (4): 1207-1215

  Abstract

  Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.

  View details for DOI 10.1111/ajt.13599

  View details for Web of Science ID 000373075400021

• Increased Resource Use in Lung Transplant Admissions in the Lung Allocation Score Era AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Maxwelll, B. G., Mooney, J. J., Lee, P. H., Levitt, J. E., Chhatwani, L., Nicolls, M. R., Zamora, M. R., Valentine, V., Weill, D., Dhillon, G. S. 2015; 191 (3): 302-308

  Abstract

  Rationale: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize one-year survival. It resulted in transplantation of older and sicker patients without changing one-year survival. Its effect on resource utilization is unknown. Objective: To determine changes in resource utilization over time in lung transplant admissions Methods: Solid organ transplant recipients were identified within the Nationwide Inpatient Sample (NIS) data from 2000 to 2011. Joinpoint regression methodology was performed to identify a time point of change in mean total hospital charges amongst lung transplant and other solid organ transplant recipients. Two temporal lung transplant recipient cohorts identified by joinpoint regression were compared for baseline characteristics and resource utilization, including total charges for index hospitalization, charges per day, length of stay, discharge disposition, tracheostomy, and need for extracorporeal membrane oxygenation (ECMO). Measurements and Main Results: A significant point of increased total hospital charges occurred for lung transplant recipients in 2005, corresponding to LAS implementation, that was not seen in other solid organ transplant recipients. Total transplant hospital charges increased by 40% in the post-LAS cohort [$569,942 ($53,229) vs. $407,489 ($28,360)] along with an increased median length of stay, daily charges, and discharge disposition other than to home. Post-LAS recipients also had higher post-transplant utilization of ECMO (OR 2.35, 95% CI 1.56, 3.55) and higher incidence of tracheostomy (OR 1.52, 95% CI 1.22, 1.89). Conclusions: LAS implementation is associated with a significant increase in resource utilization during index hospitalization for lung transplant.

  View details for DOI 10.1164/rccm.201408-1562OC

  View details for Web of Science ID 000348827000014

  View details for PubMedID 25517213

• Impact of the lung allocation score on survival beyond 1 year. American journal of transplantation Maxwell, B. G., Levitt, J. E., Goldstein, B. A., Mooney, J. J., Nicolls, M. R., Zamora, M., Valentine, V., Weill, D., Dhillon, G. S. 2014; 14 (10): 2288-2294

  Abstract

  Implementation of the lung allocation score (LAS) in 2005 led to transplantation of older and sicker patients without altering 1-year survival. However, long-term survival has not been assessed and emphasizing the 1-year survival metric may actually sustain 1-year survival while not reflecting worsening longer-term survival. Therefore, we assessed overall and conditional 1-year survival; and the effect of crossing the 1-year threshold on hazard of death in three temporal cohorts: historical (1995-2000), pre-LAS (2001-2005) and post-LAS (2005-2010). One-year survival post-LAS remained similar to pre-LAS (83.1% vs. 82.1%) and better than historical controls (75%). Overall survival in the pre- and post-LAS cohorts was also similar. However, long-term survival among patients surviving beyond 1 year was worse than pre-LAS and similar to historical controls. Also, the hazard of death increased significantly in months 13 (1.44, 95% CI 1.10-1.87) and 14 (1.43, 95% CI 1.09-1.87) post-LAS but not in the other cohorts. While implementation of the LAS has not reduced overall survival, decreased survival among patients surviving beyond 1 year in the post-LAS cohort and the increased mortality occurring immediately after 1 year suggest a potential negative long-term effect of the LAS and an unintended consequence of increased emphasis on the 1-year survival metric.

  View details for DOI 10.1111/ajt.12903

  View details for PubMedID 25208599

• Radiographic Fibrosis Score Predicts Survival in Hypersensitivity Pneumonitis CHEST Mooney, J. J., Elicker, B. M., Urbania, T. H., Agarwal, M. R., Ryerson, C. J., Nguyen, M. L., Woodruff, P. G., Jones, K. D., Collard, H. R., King, T. E., Koth, L. L. 2013; 144 (2): 586-592

  Abstract

  It is unknown if the radiographic fibrosis score predicts mortality in persistent hypersensitivity pneumonitis (HP) and if survival is similar to that observed in idiopathic pulmonary fibrosis (IPF) when adjusting for the extent of radiographic fibrosis.We reviewed records from 177 patients with HP and 224 patients with IPF whose diagnoses were established by multidisciplinary consensus. Two thoracic radiologists scored high-resolution CT (HRCT) scan lung images. Independent predictors of transplant-free survival were determined using a Cox proportional hazards analysis. Kaplan-Meier survival curves were constructed, stratified by disease as well as fibrosis score.HRCT scan fibrosis score and radiographic reticulation independently predicted time to death or lung transplantation. Clinical predictors included a history of cigarette smoking, auscultatory crackles on lung examination, baseline FVC, and FEV1/FVC ratio. The majority of HP deaths occurred in patients with both radiographic reticulation and auscultatory crackles on examination, compared with patients with only one of these manifestations (P < .0001). Patients with IPF had worse survival than those with HP at any given degree of radiographic fibrosis (hazard ratio 2.31; P < .01).Survival in patients with HP was superior to that of those with IPF with similar degrees of radiographic fibrosis. The combination of auscultatory crackles and radiographic reticulation identified patients with HP who had a particularly poor outcome.

  View details for DOI 10.1378/chest.12-2623

  View details for Web of Science ID 000323021400035

  View details for PubMedID 23392130

• Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial. JAMA Raghu, G., Richeldi, L., Fernández Pérez, E. R., De Salvo, M. C., Silva, R. S., Song, J. W., Ogura, T., Xu, Z. J., Belloli, E. A., Zhang, X., Seid, L. L., Poole, L. 2024

  Abstract

  Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events.To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis.Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023.Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks.The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported.Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group).Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48.ClinicalTrials.gov Identifier: NCT03955146.

  View details for DOI 10.1001/jama.2024.8693

  View details for PubMedID 38762797

• A Machine Learning System to Indicate Diagnosis of Idiopathic Pulmonary Fibrosis Non-Invasively in Challenging Cases. Diagnostics (Basel, Switzerland) Ahmad, Y., Mooney, J., Allen, I. E., Seaman, J., Kalra, A., Muelly, M., Reicher, J. 2024; 14 (8)

  Abstract

  Radiologic usual interstitial pneumonia (UIP) patterns and concordant clinical characteristics define a diagnosis of idiopathic pulmonary fibrosis (IPF). However, limited expert access and high inter-clinician variability challenge early and pre-invasive diagnostic sensitivity and differentiation of IPF from other interstitial lung diseases (ILDs). We investigated a machine learning-driven software system, Fibresolve, to indicate IPF diagnosis in a heterogeneous group of 300 patients with interstitial lung disease work-up in a retrospective analysis of previously and prospectively collected registry data from two US clinical sites. Fibresolve analyzed cases at the initial pre-invasive assessment. An Expert Clinical Panel (ECP) and three panels of clinicians with varying experience analyzed the cases for comparison. Ground Truth was defined by separate multi-disciplinary discussion (MDD) with the benefit of surgical pathology results and follow-up. Fibresolve met both pre-specified co-primary endpoints of sensitivity superior to ECP and significantly greater specificity (p = 0.0007) than the non-inferior boundary of 80.0%. In the key subgroup of cases with thin-slice CT and atypical UIP patterns (n = 124), Fibresolve's diagnostic yield was 53.1% [CI: 41.3-64.9] (versus 0% pre-invasive clinician diagnostic yield in this group), and its specificity was 85.9% [CI: 76.7-92.6%]. Overall, Fibresolve was found to increase the sensitivity and diagnostic yield for IPF among cases of patients undergoing ILD work-up. These results demonstrate that in combination with standard clinical assessment, Fibresolve may serve as an adjunct in the diagnosis of IPF in a pre-invasive setting.

  View details for DOI 10.3390/diagnostics14080830

  View details for PubMedID 38667475

• Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease. Rheumatology (Oxford, England) Allanore, Y., Khanna, D., Smith, V., Aringer, M., Hoffmann-Vold, A. M., Kuwana, M., Merkel, P. A., Stock, C., Sambevski, S., Denton, C. P. 2024; 63 (3): 639-647

  Abstract

  To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc).In the SENSCIS trial, patients with SSc-ILD were randomized to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib.Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (s.e.) of decline in forced vital capacity (FVC; ml/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (s.e.) change in FVC at week 52 was -86.4 (21.1) ml in the placebo group and -39.1 (22.2) ml in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (s.e.) change in FVC from baseline to week 52 of SENSCIS-ON was -41.5 (24.0) ml in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) ml in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON.Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD.ClinicalTrials.gov (https://clinicaltrials.gov), NCT02597933 and NCT03313180.

  View details for DOI 10.1093/rheumatology/kead280

  View details for PubMedID 37294870

  View details for PubMedCentralID PMC10907814

• Associations of Plasma Omega-3 Fatty Acids with Progression and Survival in Pulmonary Fibrosis. Chest Kim, J. S., Ma, S. F., Ma, J. Z., Huang, Y., Bonham, C. A., Oldham, J. M., Adegunsoye, A., Strek, M. E., Flaherty, K. R., Strickland, E., Udofia, I., Mooney, J. J., Ghosh, S., Maddipati, K., Noth, I. 2023

  Abstract

  Pre-clinical experiments suggest protective effects of omega-3 fatty acids and their metabolites in lung injury and fibrosis. Whether higher intake of omega-3 fatty acids is associated with disease progression and survival in humans with pulmonary fibrosis is unknown.What are the associations of plasma omega-3 fatty acid levels (a validated marker of omega-3 nutritional intake) with disease progression and transplant-free survival in pulmonary fibrosis?Omega-3 fatty acid levels were measured from plasma samples of patients with clinically-diagnosed pulmonary fibrosis from the Pulmonary Fibrosis Foundation (PFF) Patient Registry (n=150), University of Virginia (UVA) (n=58), and University of Chicago (UC) (n=101) cohorts. The N-3 index (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]) was the primary exposure variable of interest. Linear-mixed effects models with random intercept and slope were used to examine associations of plasma omega-3 fatty acid levels with changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) over a period of 12 months. Cox proportional hazards models were used to examine transplant-free survival. Stratified analyses by telomere length were performed in the UC cohort.Majority of the cohort were patients with IPF (88%) and men (74%). One-unit increment in log-transformed N-3 index plasma level was associated with a change in DLCO of 1.43 ml/min/mmHg per 12 months (95% CI 0.46-2.41) and a hazard ratio for transplant-free survival of 0.44 (95% CI 0.24-0.83). Cardiovascular disease history, smoking, and antifibrotic usage did not significantly modify associations. Omega-3 fatty acid levels were not significantly associated with changes in FVC. Higher EPA plasma levels were associated with longer transplant-free survival among UC participants with shorter telomere length (p-value for interaction=0.02).Further research is needed to investigate underlying biological mechanisms and whether omega-3 fatty acids are a potential disease-modifying therapy.

  View details for DOI 10.1016/j.chest.2023.09.035

  View details for PubMedID 37866772

• Factors associated with listing for lung transplantation in IPF patients: An analysis of the pulmonary fibrosis foundation registry. Heliyon King, C. S., White, E., Aryal, S., Shlobin, O. A., Singhal, A., Brown, A. W., Thomas, C., Khangoora, V., Nyquist, A., Flaherty, K. R., Nathan, S. D., Mooney, J. J. 2023; 9 (8): e18618

  Abstract

  Lung transplantation is a potentially life-saving treatment option for patients with idiopathic pulmonary fibrosis (IPF); however, not all eligible candidates get referred and listed for transplantation. Amongst IPF patients within the Pulmonary Fibrosis Foundation Patient Registry (PFF-R), we sought to determine the proportion of patients who undergo lung transplant listing and the characteristics associated with transplant listing.An analysis of IPF patients with at least six months of follow-up data was performed. Patients with well-established contraindications to lung transplantation were excluded. Two complementary analyses were performed. The "prevalent" population included all patients with IPF at time of enrollment into the registry. The "incident severe" population included all patients with IPF who progressed to GAP Stage 3.Of the 2003 patients in the PFF-R, 475 patients were included in the "prevalent" population. Of this group, only 42 (8.8%) were either listed for or underwent lung transplant. Univariable analysis of the "prevalent" population found age (per 10 year increase, OR 0.531, p = 0.0025), percent predicted FVC (OR 0.572, p=<0.0001), percent predicted DLCO (OR 0.606, p < 0.0001), 6-min walk distance (per 50 m, OR 0.831, p = 0.019), and oxygen use at rest (OR 5.157, p < 0.0001) were predictive of listing. On multivariable analysis, age (per 10 year increase, OR 0.558, p = 0.0088), percent predicted FVC (OR 0.728, p = 0.0161), and oxygen use at rest (OR 3.264, p = 0.0029) remained significant predictors for lung transplant listing. The "incident severe" group consisted of 176 patients (8.8%). 24 patients (13.6%) from this cohort were either listed for or received a transplant. Only age (per 10 year increase, OR 0.0286, p = 0.0465) was associated with transplant listing on univariable analysis in the Incident severe population.Only a small proportion of potentially eligible patients with IPF are listed for lung transplantation, even when seen at pulmonary fibrosis centers of excellence. Advanced age appears to be the primary factor associated with failure to be listed. Further refinement of future registry data is required to more clearly delineate exact reasons for low rates of listing.

  View details for DOI 10.1016/j.heliyon.2023.e18618

  View details for PubMedID 37600402

  View details for PubMedCentralID PMC10432603

• A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis. Rheumatology (Oxford, England) Baker, M. C., Horomanski, A., Wang, Y., Yuhan, L., Parsafar, S., Fairchild, R., Mooney, J. J., Raj, R., Witteles, R., Genovese, M. C. 2023

  Abstract

  Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; interleukin-6 (IL-6) antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis.This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In Period 1, subjects were treated with open-label sarilumab 200mg subcutaneously every two weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed Period 1 without a sarcoidosis flare entered Period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. Endpoints included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient reported outcomes, and laboratory values.Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed Period 1. During Period 1, 4 of 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of 15 subjects (35.7%). During Period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis.In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal for improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn.ClinicalTrials.gov Identifier: NCT04008069.

  View details for DOI 10.1093/rheumatology/kead373

  View details for PubMedID 37471590

• Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial. BMC pulmonary medicine Podolanczuk, A. J., Kim, J. S., Cooper, C. B., Lasky, J. A., Murray, S., Oldham, J. M., Raghu, G., Flaherty, K. R., Spino, C., Noth, I., Martinez, F. J. 2022; 22 (1): 475

  Abstract

  Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. N-acetylcysteine (NAC) is a well-tolerated, inexpensive treatment with antioxidant and anti-fibrotic properties. The National Heart, Lung, and Blood Institute (NHLBI)-sponsored PANTHER (Prednisone Azathioprine and NAC therapy in IPF) trial confirmed the harmful effects of immunosuppression in IPF, and did not show a benefit to treatment with NAC. However, a post hoc analysis revealed a potential beneficial effect of NAC in a subgroup of individuals carrying a specific genetic variant, TOLLIP rs3750920 TT genotype, present in about 25% of patients with IPF. Here, we present the design and rationale for the Phase III, multi-center, randomized, double-blind, placebo-controlled Prospective Treatment Efficacy in IPF Using Genotype for NAC Selection (PRECISIONS) clinical trial.The PRECISIONS trial will randomize 200 patients with IPF and the TOLLIP rs3750920 TT genotype 1:1 to oral N-acetylcysteine (600 mg tablets taken three times a day) or placebo for a 24-month duration. The primary endpoint is the composite of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or death from any cause. Secondary endpoints include change in patient-reported outcome scores and proportion of participants with treatment-emergent adverse events. Biospecimens, including blood, buccal, and fecal will be collected longitudinally for future research purposes. Study participants will be offered enrollment in a home spirometry substudy, which explores time to 10% relative FVC decline measured at home, and its comparison with study visit FVC.The sentinel observation of a potential pharmacogenetic interaction between NAC and TOLLIP polymorphism highlights the urgent, unmet need for better, molecularly focused, and precise therapeutic strategies in IPF. The PRECISIONS clinical trial is the first study to use molecularly-focused techniques to identify patients with IPF most likely to benefit from treatment. PRECISIONS has the potential to shift the paradigm in how trials in this condition are designed and executed, and is the first step toward personalized medicine for patients with IPF. Trial Registration ClinicalTrials.gov identifier: NCT04300920. Registered March 9, 2020. https://clinicaltrials.gov/ct2/show/NCT04300920.

  View details for DOI 10.1186/s12890-022-02281-8

  View details for PubMedID 36514019

  View details for PubMedCentralID PMC9746571

• Phase 2 drug target engagement study of PLN-74809 in patients with idiopathic pulmonary fibrosis using a novel av beta 6 cystine knot PET imaging tracer Wardak, M., Turner, S., Mooney, J., Rizzo, G., Morris, K., Jacobs, S., Duan, H., Lefebvre, E., Cosgrove, G., Wong, S., Bellini, J., Jurek, M., Decaris, M., Williams, B., Kimura, R., Gunn, R., Wu, J., Coulie, B., Guo, H. SOC NUCLEAR MEDICINE INC. 2022

  View details for Web of Science ID 000893739700004

• ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part II: Cardiac, surgical, perioperative, operative, and post-operative challenges and management statements. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Bermudez, C. A., Crespo, M. M., Shlobin, O. A., Cantu, E., Mazurek, J. A., Levine, D., Gutsche, J., Kanwar, M., Dellgren, G., Bush, E. L., Heresi, G. A., Cypel, M., Hadler, R., Kolatis, N., Franco, V., Benvenuto, L., Mooney, J., Pipeling, M., King, C., Mannem, H., Raman, S., Knoop, C., Douglas, A., Mercier, O. 2021

  Abstract

  Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD.

  View details for DOI 10.1016/j.healun.2021.07.016

  View details for PubMedID 34404570

• The Role of Surgical Lung Biopsy in the Diagnosis of Fibrotic Interstitial Lung Disease: Perspective from the Pulmonary Fibrosis Foundation. Annals of the American Thoracic Society Hariri, L. P., Roden, A. C., Chung, J. H., Danoff, S. K., Gomez Manjarres, D. C., Hartwig, M., Kheir, F., King, C., Kreider, M., Lynch, D. A., Mooney, J., Muniappan, A., Myers, J. L., Paoletti, L., Raj, R., Safdar, Z., Suliman, S., Thavarajah, K., Lederer, D. J., Rudell, F. L., Bianchi, P., Shea, B. S., Ley, B. 2021

  Abstract

  Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary diagnosis (MDD) approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathological specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in ILD patients. This document was developed by the Surgical Lung Biopsy Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD, outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD, and provide practical information to maximize the yield and safety of SLB.

  View details for DOI 10.1513/AnnalsATS.202009-1179FR

  View details for PubMedID 34004127

• Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial. JAMA Martinez, F. J., Yow, E., Flaherty, K. R., Snyder, L. D., Durheim, M. T., Wisniewski, S. R., Sciurba, F. C., Raghu, G., Brooks, M. M., Kim, D. Y., Dilling, D. F., Criner, G. J., Kim, H., Belloli, E. A., Nambiar, A. M., Scholand, M. B., Anstrom, K. J., Noth, I. 2021; 325 (18): 1841-1851

  Abstract

  Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis.To assess the effect of antimicrobial therapy on clinical outcomes.Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020).Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group.The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality.Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%).Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease.ClinicalTrials.gov Identifier: NCT02759120.

  View details for DOI 10.1001/jama.2021.4956

  View details for PubMedID 33974018

  View details for PubMedCentralID PMC8114133

• Essential Components of an Interstitial Lung Disease Clinic: Results From a Delphi Survey and Patient Focus Group Analysis. Chest Graney, B. A., He, C., Marll, M., Matson, S., Bianchi, P., Cosgrove, G. P., Lee, J. S. 2021; 159 (4): 1517-1530

  Abstract

  Management of patients with interstitial lung disease (ILD) requires subspecialized, comprehensive, multidisciplinary care. The Pulmonary Fibrosis Foundation established the Care Center Network (CCN) in 2013 with identified criteria to become a designated CCN site. Despite these criteria, the essential components of an ILD clinic remain unknown.How are ILD clinics within the CCN structured? What are the essential components of an ILD clinic according to ILD physician experts, patients, and caregivers?This study had three components. First, all 68 CCN sites were surveyed to determine the characteristics of their current ILD clinics. Second, an online, three-round modified Delphi survey was conducted between October and December 2019 with 48 ILD experts participating in total. Items for round 1 were generated using expert interviews. During rounds 1 and 2, experts rated the importance of each item on a 5-point Likert scale. The a priori threshold for consensus was more than 75% of experts rating an item as important or very important. In round 3, experts graded items that met consensus and ranked items deemed essential for an ILD clinic. Third, ILD patient and caregiver focus groups were conducted and analyzed for content to determine their perspectives of an ideal ILD clinic.Forty items across four categories (members, infrastructure, resources, and multidisciplinary conference) achieved consensus as essential to an ILD clinic. Patient and caregiver focus groups identified three major themes: comprehensive, patient-centered medical care; expanded access to care; and comprehensive support for living and coping with ILD.The essential components of an ILD clinic are well-aligned between physician experts and patients. Future research can use these findings to evaluate the impact of these components on patient outcomes and to inform best practices for ILD clinics throughout the world.

  View details for DOI 10.1016/j.chest.2020.09.256

  View details for PubMedID 33031832

  View details for PubMedCentralID PMC7534733

• First lung and kidney multi-organ transplant following COVID-19 Infection. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Guenthart, B. A., Krishnan, A., Alassar, A., Madhok, J., Kakol, M., Miller, S., Cole, S. P., Rao, V. K., Acero, N. M., Hill, C. C., Cheung, C., Jackson, E. C., Feinstein, I., Tsai, A. H., Mooney, J. J., Pham, T., Elliott, I. A., Liou, D. Z., La Francesca, S., Shudo, Y., Hiesinger, W., MacArthur, J. W., Brar, N., Berry, G. J., McCarra, M. B., Desai, T. J., Dhillon, G. S., Woo, Y. J. 2021

  Abstract

  As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

  View details for DOI 10.1016/j.healun.2021.02.015

  View details for PubMedID 34059432

• Antifibrotic therapies reduce mortality and hospitalization among Medicare beneficiaries with idiopathic pulmonary fibrosis. Journal of managed care & specialty pharmacy Mooney, J., Reddy, S. R., Chang, E., Broder, M. S., Gokhale, S., Corral, M. 2021; 27 (12): 1724-1733

  Abstract

  BACKGROUND: Additional real-world studies are needed to more fully elucidate the effectiveness of antifibrotic treatment in slowing the progression of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To compare mortality and hospitalization between Medicare beneficiaries with IPF who initiate antifibrotic therapy and those who did not receive treatment. METHODS: A retrospective observational study of Medicare beneficiaries using the 100% Medicare Research Identifiable File was conducted. We included patients aged 67 years and over diagnosed with IPF (≥ 1 inpatient or ≥ 2 outpatient claims with IPF diagnosis, J84.112]) during the study period (January 1, 2010-December 31, 2017). Patients who initiated antifibrotic treatment (pirfenidone or nintedanib) between October 15, 2014 (FDA approval date) and December 31, 2017 (ie, treated patients) were compared with those who did not receive treatment during a historical period (January 1, 2012-October 14, 2014) before the availability of antifibrotics (ie, untreated historical controls). Patients were matched by propensity score, and the outcomes, mortality, and hospitalization (all cause and respiratory related) were compared using a Cox proportional hazards model. RESULTS: We identified 4,641 treated patients and 4,641 propensity score-matched controls who met all study criteria; 352 treated patients who lacked matches were excluded from the study. Cox regression analysis of treated patients vs matched controls showed a significantly lower risk of mortality (HR = 0.62, 95% CI = 0.57-0.68); lower risk of hospitalization (HR = 0.71, 95% CI = 0.67-0.76; HR = 0.70, 95% CI = 0.64-0.76); and lower rate in number of hospitalizations per month (incident rate ratio [IRR] = 0.65, 95% CI = 0.60-0.71; IRR = 0.65, 95% CI = 0.58-0.73). CONCLUSIONS: This study suggests that treatment with antifibrotics may confer a survival benefit and protection against all-cause and respiratory-related hospitalization for IPF patients. DISCLOSURES: This work was sponsored by F. Hoffmann-La Roche/Genentech, Inc. Corral is employed by Genentech, Inc. Reddy, Chang, Broder, and Gokhale are employed by Partnership for Health Analytic Research LLC, a health services research company, which was hired by Genentech to conduct this research. Mooney has received advisory board/consulting fees and research support from Genentech, unrelated to this work. Mooney also reports advisory board/consulting fees and research support from Boehringer Ingelheim; personal fees from Imvaria; and grants from Celgene and Pliant, unrelated to this work. Through their employment with Partnership for Health Analytic Research, Reddy, Chang, Broder, and Gokhale have been compensated to conduct research for AbbVie, Akcea, ASPC, Amgen, AstraZeneca, BMS, Boston Scientific Corporation, Celgene, Eisai, Ethicon, GRAIL, Helsinn, Illumina, Innovation and Value Initiative, Ionis, Jazz, Kite, Novartis, Otsuka, Pathnostics, PhRMA, Prothena, Sage, Verde Technologies, Genentech, Inc., Greenwich Biosciences, Inc., Mirum Pharmaceuticals, Inc., Sanofi US Services, Inc., Sunovion Pharmaceuticals, Inc., and Dompe US, Inc., unrelated to this work. This research was presented as an abstract at CHEST 2020 Annual Meeting (virtual), October 18-21, 2020, and American Thoracic Society 2020 Virtual Meeting, June 2020.

  View details for DOI 10.18553/jmcp.2021.27.12.1724

  View details for PubMedID 34818092

• Gastric per-oral endoscopic myotomy for severe post-lung transplant gastroparesis: A single-center experience. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Podboy, A. J., Clarke, J. O., Nguyen, L. A., Mooney, J. J., Dhillon, G. S., Hwang, J. H. 2020

  View details for DOI 10.1016/j.healun.2020.06.019

  View details for PubMedID 32711933

• Utilization of hepatitis C virus-infected organ donors in cardiothoracic transplantation: An ISHLT expert consensus statement. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Aslam, S., Grossi, P., Schlendorf, K. H., Holm, A. M., Woolley, A. E., Blumberg, E., Mehra, M. R. 2020; 39 (5): 418-432

  Abstract

  The advent of therapies for successful treatment of hepatitis C virus has allowed the heart and lung transplant community to re-explore the use of hepatitis C virus-positive donors for organ transplantation, with a benefit for many terminally ill patients. The consensus statements provided herein represent the current state of knowledge and expertise in this area, which we expect will continue to rapidly evolve over the next few years.

  View details for DOI 10.1016/j.healun.2020.03.004

  View details for PubMedID 32362393

• Rituximab Versus Mycophenolate in the Treatment of Recalcitrant Connective Tissue Disease-Associated Interstitial Lung Disease. ACR open rheumatology Zhu, L. n., Chung, M. P., Gagne, L. n., Guo, H. H., Guenther, Z. n., Li, S. n., Jacobs, S. n., Morisset, J. n., Mooney, J. J., Raj, R. n., Chung, L. n. 2020

  Abstract

  Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue diseases (CTDs). We aimed to assess the effect of rituximab ± mycophenolate mofetil (MMF) compared with MMF on pulmonary function and prednisone dosage in patients with CTD-related ILD (CTD-ILD).This retrospective study included 83 patients from Stanford and Centre Hospitalier de l'Universite de Montreal. Fifteen patients received rituximab ± MMF (rituximab group), and 68 patients received MMF only (control group).Median ILD duration at the start of treatment was longer in the rituximab group at 47 months (range: 4-170) versus 6.5 months (range: 0-164) in controls. Forced vital capacity (FVC) decreased by 3.0% (range: 11%-21%) after treatment in the rituximab group, whereas it increased by 2.0% (range: 14%-25%) in the control group (p = 0.025). Diffusing capacity of carbon monoxide (DLCO) decreased by 3.0% (range: 10%-12%) after treatment in the rituximab group, whereas it increased by 4.5% (range: 30%-36%) in the control group (p = 0.046). Mixed model analysis controlling for ILD duration, baseline DLCO, systemic sclerosis, pulmonary hypertension, and prednisone use showed no significant difference in FVC or DLCO between groups at 6 months or 1 year. The average daily prednisone dose score decreased after treatment in the rituximab group, whereas it remained unchanged in the control group (p = 0.017).Rituximab ± MMF did not significantly change pulmonary function compared with MMF alone, but it did result in a relative decrease in average daily prednisone dose in a population with recalcitrant CTD-ILD.

  View details for DOI 10.1002/acr2.11210

  View details for PubMedID 33274857

• Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nature communications Kimura, R. H., Wang, L., Shen, B., Huo, L., Tummers, W., Filipp, F. V., Guo, H. H., Haywood, T., Abou-Elkacem, L., Baratto, L., Habte, F., Devulapally, R., Witney, T. H., Cheng, Y., Tikole, S., Chakraborti, S., Nix, J., Bonagura, C. A., Hatami, N., Mooney, J. J., Desai, T., Turner, S., Gaster, R. S., Otte, A., Visser, B. C., Poultsides, G. A., Norton, J., Park, W., Stolowitz, M., Lau, K., Yang, E., Natarajan, A., Ilovich, O., Srinivas, S., Srinivasan, A., Paulmurugan, R., Willmann, J., Chin, F. T., Cheng, Z., Iagaru, A., Li, F., Gambhir, S. S. 2019; 10 (1): 4673

  Abstract

  Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6.

  View details for DOI 10.1038/s41467-019-11863-w

  View details for PubMedID 31611594

• Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. The New England journal of medicine Distler, O., Highland, K. B., Gahlemann, M., Azuma, A., Fischer, A., Mayes, M. D., Raghu, G., Sauter, W., Girard, M., Alves, M., Clerisme-Beaty, E., Stowasser, S., Tetzlaff, K., Kuwana, M., Maher, T. M. 2019; 380 (26): 2518-2528

  Abstract

  Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52.A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group.Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).

  View details for DOI 10.1056/NEJMoa1903076

  View details for PubMedID 31112379

• Successful Heart-Lung Transplant for a Patient on Continuous-Flow Left Ventricular Assist Device Support Complicated With Amiodarone-Induced Pulmonary Fibrosis. Transplantation proceedings Currie, M. E., Shudo, Y., Mooney, J., Woo, Y. J. 2019; 51 (2): 593–94

  Abstract

  In this case report, we present a successful case of en bloc heart-lung transplant in a patient with advanced cardiopulmonary respiratory failure from amiodarone-associated pulmonary fibrosis that occurred post-left ventricular assist device implantation.

  View details for PubMedID 30879597

• Identification of Diagnostic Criteria for Chronic Hypersensitivity Pneumonitis: An International Modified Delphi Survey. American journal of respiratory and critical care medicine Morisset, J., Johannson, K. A., Jones, K. D., Wolters, P. J., Collard, H. R., Walsh, S. L., Ley, B. 2017

  Abstract

  Current diagnosis of chronic hypersensitivity pneumonitis (cHP) involves considering a combination of clinical, radiological, and pathological information in multidisciplinary team discussions. However, this approach is highly variable with poor agreement between centers.We aimed to identify diagnostic criteria for cHP that reach consensus among international experts.A 3-round modified Delphi survey was conducted between April and August 2017. Forty-five experts in interstitial lung disease from 14 countries participated in the online survey. Diagnostic items included in round 1 were generated using expert interviews and literature review. During rounds 1 and 2, experts rated the importance of each diagnostic item on a 5-point Likert scale. The a priori threshold of consensus was ≥ 75% of experts rating a diagnostic item as very important or important. In the third round, experts graded the items that met consensus as important and provided their level of diagnostic confidence for a series of clinical scenarios.Consensus was achieved on 18 of the 40 diagnostic items. Among these, experts gave the highest level of importance to the identification of a causative antigen, time relation between exposure and disease, mosaic attenuation on chest imaging, and poorly formed non-necrotizing granulomas on pathology. In clinical scenarios, the diagnostic confidence of experts in cHP was heightened by the presence of these diagnostic items.This consensus-based approach for the diagnosis of cHP represents a first step towards the development of international guidelines for the diagnosis of cHP.

  View details for DOI 10.1164/rccm.201710-1986OC

  View details for PubMedID 29172641

• Hospital cost and length of stay in idiopathic pulmonary fibrosis JOURNAL OF MEDICAL ECONOMICS Mooney, J. J., Raimundo, K., Chang, E., Broder, M. S. 2017; 20 (5): 518-524

  Abstract

  To provide a detailed picture of the economic impact of hospitalization in idiopathic pulmonary fibrosis (IPF) and to identify factors associated with cost and length of stay (LOS).In this retrospective cross-sectional study using the Nationwide Inpatient Sample (NIS), we included hospitalizations for IPF (ICD-9-CM 516.3) with a principal diagnosis of respiratory disease (ICD-9-CM 460-519) from 2009-2011; lung transplant admissions were excluded. Total inpatient cost, LOS, in-hospital death, and discharge disposition were reported. Linear regression models were used to determine variables predictive of LOS and cost.From 2009-2011, 22,350 non-transplant IPF patients with a principal diagnosis of respiratory disease were admitted: mean (+/-SE) age was 70.0 (0.32), and 49.1% were female. While in-hospital, 11.4% of patients received mechanical ventilation and 8.9% received non-invasive ventilation. Mean (+/-SE) LOS was 7.4 (0.15) days overall (p < 0.001). The mean (+/-SD) admission cost was $16,042 (+/-631). Of hospitalized patients, 14.1% died, 20.6% transferred facilities, and 46.4% were routinely discharged. The adjusted LOS (95%CI) for patients with and without mechanical ventilation was 16.1 days (15 - 17.5) versus 6.3 (6 - 6.5); adjusted costs were $48,772 (43,979 - 53,565) versus $11,861 (11,292 - 12,431).The positive predictive value of the algorithm used to identify IPF is not optimal. The NIS database does not follow patients longitudinally and claims after admission are not available. Claims do not indicate whether listed diagnoses were present on admission or developed during hospitalization. The exclusion of transplant-related expenditures lead to underestimation of cost.Using a nationally-representative database, we found IPF respiratory-related hospitalizations represent a significant economic burden with approximately 7,000 non-transplant IPF admissions per year, at a mean cost of $16,000 per admission. Mechanical ventilation is associated with statistically significant increases in LOS and cost. Therapeutic advances that reduce rates and costs of IPF hospitalizations are needed.

  View details for DOI 10.1080/13696998.2017.1282864

  View details for Web of Science ID 000399655000010

  View details for PubMedID 28092235

• Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality. Clinical transplantation Sher, Y., Mooney, J., Dhillon, G., Lee, R., Maldonado, J. R. 2017; 31 (5)

  Abstract

  Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized.The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS and one-year mortality.Thirty six % developed early-onset and 44% - ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first post-operative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (p=0.001), ICU LOS (p<0.001), and hospital LOS (p=0.005). Ever-onset delirium was associated with longer ICU (p<0.001) and hospital LOS (p<0.001). After adjusting for clinical variables, delirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55).Delirium is common after lung transplant surgery and associated with increased hospital resources. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.12966

  View details for PubMedID 28314081

• Mechanical ventilation in idiopathic pulmonary fibrosis: a nationwide analysis of ventilator use, outcomes, and resource burden. BMC pulmonary medicine Mooney, J. J., Raimundo, K. n., Chang, E. n., Broder, M. S. 2017; 17 (1): 84

  Abstract

  Idiopathic pulmonary fibrosis (IPF) is associated with increased risk of respiratory-related hospitalizations. Studies suggest mechanical ventilation (MV) use in IPF does not improve outcomes and guidelines recommend against its general use. Our objective was to investigate MV use and association with cost and mortality in IPF.This retrospective study, using a nationwide sample, included claims with IPF (ICD-9-CM: 516.3) in 2009-2011 and principal respiratory disease diagnosis (ICD-9-CM: 460-519); excluding lung transplant. Regression models were used to determine predictors of MV and association with cost, LOS, and mortality. Domain analysis was used to account for use of subpopulation. Costs were adjusted to 2011. Data on patient severity not available.Twenty two thousand three hundred fifty non-transplant IPF patients were admitted with principal respiratory disease diagnosis: Mean age 70.0 (SD 13.9), 49.1% female, mean LOS 7.4 (SD 8.2). MV was used in 11.4% of patients with a non-significant decline over time. In regression models, MV was associated with an increased stay of 9.78 days (95% CI 8.38-11.18) and increased cost of $36,583 (95% CI $32,021-41,147). MV users had significantly increased mortality (OR 15.55, 95% CI 12.13-19.95) versus nonusers.Mechanical ventilation use has not significantly changed over time and is mostly used in younger patients and those admitted for non-IPF respiratory conditions. MV was associated with a 4-fold admission cost increase ($49,924 versus $11,742) and a 7-fold mortality increase (56% versus 7.5%), although patients who receive MV may differ from those who do not. Advances in treatment and decision aids are needed to improve outcomes in IPF.

  View details for PubMedID 28532459

  View details for PubMedCentralID PMC5441011

• Hypersensitivity Pneumonitis: Lessons from the Great Imitator in Interstitial Lung Disease. Annals of the American Thoracic Society Mooney, J. J. 2017; 14 (10): 1506–7

  View details for PubMedID 28961032

• Rebuttal from Drs Mooney and Collard. Chest Mooney, J. J., Collard, H. R. 2017

  View details for PubMedID 28943278

• Changing the curve in chronic lung allograft dysfunction: Implications of chronic lung allograft dysfunction phenotypes in assessing treatment interventions. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Mooney, J. J. 2017

  View details for PubMedID 28720212

• Lung transplantation following death by drowning: a review of the current literature. Clinical transplantation Pasupneti, S., Patel, K., Mooney, J. J., Chhatwani, L., Dhillon, G., Weill, D. 2016; 30 (10): 1195-1197

  Abstract

  While multiple donor characteristics have been cited as ideal for lung transplantation, there are minimal widely accepted exclusion criteria. One criterion that many centers view with hesitation is death by drowning. However, recent literature suggests such donors may result in acceptable outcomes following transplation. This review highlights a case of a patient who underwent successful bilateral lung transplant from a donor following a drowning event. A review of the current literature is presented, concluding with a new proposed set of favorable donor criteria following death by drowning. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ctr.12822

  View details for PubMedID 27447443

• Invasive mold infections in lung and heart-lung transplant recipients: Stanford University experience TRANSPLANT INFECTIOUS DISEASE Vazquez, R., Vazquez-Guillamet, M. C., Suarez, J., Mooney, J., Montoya, J. G., Dhillon, G. S. 2015; 17 (2): 259-266

  Abstract

  Recipients of lung transplantation (LT) and heart-lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non-Aspergillus IMIs in this population have not been well documented.LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non-Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis.During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non-Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non-Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non-Aspergillus group, with dissemination occurring only within the non-Aspergillus group (12.5%). Overall 90-day and 1-year mortality following IMI was 24% and 44%. One-year mortality was increased in the non-Aspergillus group (39.5% vs. 60.5%, P = 0.03).There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non-Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1-year mortality. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/tid.12362

  View details for Web of Science ID 000352219400011

  View details for PubMedID 25648194

• Understanding the lung allocation score for the non-transplant pulmonologist Current Pulmonology Reports Mooney, J. J., Gries, C. J. 2015

  View details for DOI 10.1007/s13665-015-0113-9

• Predicting Survival Across Chronic Interstitial Lung Disease The ILD-GAP Model CHEST Ryerson, C. J., Vittinghoff, E., Ley, B., Lee, J. S., Mooney, J. J., Jones, K. D., Elicker, B. M., Wolters, P. J., Koth, L. L., King, T. E., Collard, H. R. 2014; 145 (4): 723-728

  Abstract

  Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis.Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated ILD (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from an ongoing database (N=1,012). Performance of the previously validated GAP model was compared with novel prediction models in each ILD subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation.The GAP model had good performance in all ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared with alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia.The GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.

  View details for DOI 10.1378/chest.13-1474

  View details for Web of Science ID 000334097700014

  View details for PubMedID 24114524

• Surgical lung biopsy over bronchoalveolar lavage in chronic hypersensitivity pneumonitis. American journal of respiratory and critical care medicine Mooney, J. J., Koth, L. L. 2014; 189 (3): 371-372

  View details for DOI 10.1164/rccm.201309-1736LE

  View details for PubMedID 24484347

• Lung Transplantation for Hypersensitivity Pneumonitis. Chest Kern, R. M., Singer, J. P., Koth, L. n., Mooney, J. n., Golden, J. n., Hays, S. n., Greenland, J. n., Wolters, P. n., Ghio, E. n., Jones, K. D., Leard, L. n., Kukreja, J. n., Blanc, P. D. 2014

  Abstract

  Background:Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may lead to lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared to referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). Methods:To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000-2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to IPF referents. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. Results:We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared to IPF was 96%, 89% and 89% vs. 86%, 67%, and 49%, respectively. HP subjects manifested a reduced adjusted risk of death compared to IPF subjects (HR 0.25, 95% CI 0.08-0.74; p=0.013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in 5 (16%). Two subjects developed recurrent HP in their allografts. Conclusions:Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk of death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may lead to lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared to referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF).To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000-2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to IPF referents. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling.We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared to IPF was 96%, 89% and 89% vs. 86%, 67%, and 49%, respectively. HP subjects manifested a reduced adjusted risk of death compared to IPF subjects (HR 0.25, 95% CI 0.08-0.74; p=0.013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in 5 (16%). Two subjects developed recurrent HP in their allografts.Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk of death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.

  View details for PubMedID 25412059

• Prevalence and prognosis of unclassifiable interstitial lung disease EUROPEAN RESPIRATORY JOURNAL Ryerson, C. J., Urbania, T. H., Richeldi, L., Mooney, J. J., Lee, J. S., Jones, K. D., Elicker, B. M., Koth, L. L., King, T. E., Wolters, P. J., Collard, H. R. 2013; 42 (3): 750-757

  Abstract

  The aim of this study was to determine the prevalence, characteristics and outcomes of patients with unclassifiable interstitial lung disease (ILD) and to develop a simple method of predicting disease behaviour. Unclassifiable ILD patients were identified from an ongoing longitudinal cohort. Unclassifiable ILD was diagnosed after a multidisciplinary review did not secure a specific ILD diagnosis. Clinical characteristics and outcomes were compared with idiopathic pulmonary fibrosis (IPF) and non-IPF ILDs. Independent predictors of mortality were determined using Cox proportional-hazards analysis to identify subgroups with distinct disease behaviour. Unclassifiable ILD was diagnosed in 10% of the ILD cohort (132 out of 1370 patients). The most common reason for being unclassifiable was missing histopathological assessment due to a high risk of surgical lung biopsy. Demographic and physiological features of unclassifiable ILD were intermediate between IPF and non-IPF disease controls. Unclassifiable ILD had longer survival rates when compared to IPF on adjusted analysis (hazard ratio 0.62, p = 0.04) and similar survival compared to non-IPF ILDs (hazard ratio 1.54, p = 0.12). Independent predictors of survival in unclassifiable ILD included diffusion capacity of the lung for carbon monoxide (p = 0.001) and a radiological fibrosis score (p = 0.02). Unclassifiable ILD represents approximately 10% of ILD cases and has a heterogeneous clinical course, which can be predicted using clinical and radiological variables.

  View details for DOI 10.1183/09031936.00131912

  View details for Web of Science ID 000326160500025

  View details for PubMedID 23222877

• Ninety-day mortality and major complications are not affected by use of lung allocation score JOURNAL OF HEART AND LUNG TRANSPLANTATION McCue, J. D., Mooney, J., Quail, J., Arrington, A., Herrington, C., Dahlberg, P. S. 2008; 27 (2): 192-196

  Abstract

  In May 2005 the Organ Procurement Transplant Network (OPTN) and United Network for Organ Sharing (UNOS) implemented the donor lung allocation score (LAS) system to prioritize organ allocation among prospective transplant recipients. The purpose of our study was to determine the impact of LAS implementation on 90-day survival, early complications and incidence of severe primary graft dysfunction (PGD) after the transplant procedure.Early outcomes among 78 patients receiving transplants after the initiation of the scoring system were compared with those of the 78 previous patients. Survival rates at 90 days and 1 year were the primary end-points of the study. Arterial blood-gas measurements were collected for all patients at the time of ICU arrival and at 12, 24 and 48 hours after surgery to determine the distribution of International Society of Heart and Lung Transplant (ISHLT) PGD grade. Major complications within 30 days post-transplant were recorded.We found a small but significant 1-year survival advantage among post-LAS implementation patients, which was largely due to decreased early mortality in comparison to the control cohort. The incidence of ISHLT Grade 3 PGD measured within the first 24 hours after transplant did not differ between groups, nor was there an increase in the rate of major post-operative complications.Implementation of the LAS system has not been associated with an increase in early mortality, immediate PGD or major complications.

  View details for DOI 10.1016/j.healun.2007.11.001

  View details for Web of Science ID 000253258800008

  View details for PubMedID 18267226