Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients.

BACKGROUND: Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. METHODS: We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. RESULTS: A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. CONCLUSIONS: In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Quantitative computed tomography assessment of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a clinical manifestation of chronic allograft rejection following lung transplantation. We examined the quantitative measurements of the proximal airway and vessels and pathologic correlations in subjects with BOS. METHODS: Patients who received a lung transplant at the Brigham and Women's Hospital between December 1, 2002 and December 31, 2010 were included in this study. We characterized the quantitative CT measures of proximal airways and vessels and pathological changes. RESULTS: Ninety-four (46.1%) of the 204 subjects were included in the study. There was a significant increase in the airway vessel ratio in subjects who developed progressive BOS compared to controls and non-progressors. There was a significant increase in airway lumen area and decrease in vessel cross-sectional area in patients with BOS compared to controls. Patients with BOS had a significant increase in proximal airway fibrosis compared to controls. CONCLUSIONS: BOS is characterized by central airway dilation and vascular remodeling, the degree of which is correlated to decrements in lung function. Our data suggest that progressive BOS is a pathologic process that affects both the central and distal airways.

Predictors and outcomes of unplanned early rehospitalization in the first year following lung transplantation.

Unplanned early rehospitalization (UER), defined as an unscheduled admission within 30 days of a hospital discharge, is associated with graft loss and recipient mortality in some solid organ transplants but has not been investigated in lung transplant. In this retrospective study, we collected socio-demographic and clinical factors to determine predictors and outcomes of UER in the first year following lung transplantation. There were 193 patients who underwent lung transplantation and survived to discharge during the 7.9-year study period. There were 116 (60.1%) patients with at least one UER. Infections (32.8%) and post-surgical complications (11.8%) were the most common reasons for UER. On multivariate analysis, the strongest predictor of having an UER was discharge to a long-term acute care facility (odds ratio: 3.01, 95% confidence interval [CI] 1.46-6.20; P=.003). Patients with any UER in the first year following transplantation had worse adjusted survival (hazard ratio: 1.89, 95% CI 1.02-3.50; P=.04). It is unclear, however, to what extent UERs reflect preventable outcomes. Further large-scale, prospective research is needed to identify the extent to which certain types of UER are modifiable and to define patients at high-risk for preventable UER.

Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates.

RATIONALE: The prevalence of anti-HLA antibodies in lung transplant candidates and their impact on waitlist and transplant outcomes is not known. OBJECTIVES: We examined the prevalence of pretransplant anti-HLA antibodies at varying thresholds and evaluated their impact on outcomes before and after lung transplantation. METHODS: We performed a single-center retrospective cohort study including all patients listed for lung transplantation between January 2008 and August 2012. Per protocol, transplant candidates were assessed by solid phase LABscreen mixed Class I and II and LABscreen Single Antigen assays. MEASUREMENTS AND MAIN RESULTS: Among 224 patients, 34% had anti-HLA antibodies at mean fluorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24% had antibodies at MFI 1,000 to 3,000 (group II). Ninety percent of the patients with pretransplant anti-HLA antibodies had class I antibodies, whereas only seven patients developed class II alone. Patients in group III were less likely to receive transplants than patients without any anti-HLA antibodies (group I) (45.5 vs. 67.7%, P = 0.005). Wait time to transplant was longer in group III than group I, although this difference did not meet statistical significance, and waitlist mortality was similar. Among transplant recipients, antibody-mediated rejection (AMR) was more frequent in group III than in group II (20% vs. 0%, P = 0.01) or group I (6.3%, P = 0.05). CONCLUSIONS: The presence of anti-HLA antibodies at the high MFI threshold (>3,000) was associated with lower transplant rate and higher rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may be important in managing transplant candidates and recipients.

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Interaction of tau protein with model lipid membranes induces tau structural compaction and membrane disruption.

The misfolding and aggregation of the intrinsically disordered, microtubule-associated tau protein into neurofibrillary tangles is implicated in the pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation and toxicity remain unknown. Recent work has shown that anionic lipid membranes can induce tau aggregation and that membrane permeabilization may serve as a pathway by which protein aggregates exert toxicity, suggesting that the plasma membrane may play dual roles in tau pathology. This prompted our investigation to assess tau's propensity to interact with membranes and to elucidate the mutually disruptive structural perturbations the interactions induce in both tau and the membrane. We show that although highly charged and soluble, the full-length tau (hTau40) is also highly surface active, selectively inserts into anionic DMPG lipid monolayers and induces membrane morphological changes. To resolve molecular-scale structural details of hTau40 associated with lipid membranes, X-ray and neutron scattering techniques are utilized. X-ray reflectivity indicates hTau40s presence underneath a DMPG monolayer and penetration into the lipid headgroups and tailgroups, whereas grazing incidence X-ray diffraction shows that hTau40 insertion disrupts lipid packing. Moreover, both air/water and DMPG lipid membrane interfaces induce the disordered hTau40 to partially adopt a more compact conformation with density similar to that of a folded protein. Neutron reflectivity shows that tau completely disrupts supported DMPG bilayers while leaving the neutral DPPC bilayer intact. Our results show that hTau40s strong interaction with anionic lipids induces tau structural compaction and membrane disruption, suggesting possible membrane-based mechanisms of tau aggregation and toxicity in neurodegenerative diseases.

Extended post-ex vivo lung perfusion cold preservation predicts primary graft dysfunction and mortality: Results from a multicentric study.

BACKGROUND: Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes. METHODS: A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics. RESULTS: Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes. CONCLUSIONS: Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.

MDCT evaluation of central airway and vascular complications of lung transplantation.

OBJECTIVE: The purpose of this article is to illustrate the spectrum of central airway and vascular complications in lung transplantation using MDCT, with an emphasis on the usefulness of advanced postprocessing techniques. CONCLUSION: MDCT is an invaluable tool in the diagnosis, evaluation, and posttreatment assessment of central airway and vascular complications in lung transplant recipients. Advanced postprocessing techniques provide complementary information that is visually accessible and anatomically meaningful for the clinician.

Comparison of extracorporeal photopheresis and alemtuzumab for the treatment of chronic lung allograft dysfunction.

BACKGROUND: Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD). Immunomodulatory therapies such as extracorporeal photopheresis (ECP) and alemtuzumab (AL) have been described for refractory CLAD, but comparative outcomes are not well defined. METHODS: We retrospectively reviewed spirometric values and clinical outcomes after therapy with ECP, AL, or no treatment (NT) in patients with CLAD who underwent transplant between January 2005 and December 2014. We used inverse probability-weighted regression adjustment (IPWRA) to adjust for potential confounders affecting treatment choice. RESULTS: Of 267 patients, 31 received immunomodulatory therapies for CLAD, and 78 received NT. The slope of forced expiratory volume in 1 second (FEV1) decline significantly improved after treatment with AL and with ECP compared with pre-treatment FEV1 slope; however, there was no significant change in slope of forced vital capacity (FVC). Comparison with NT was limited because of clinical differences in treatment groups. After IPWRA, we found no significant difference in mean difference of FEV1 slope (ml/month) when comparing treatment with NT, suggesting stabilization of lung function in the treatment group. We found no difference between the 2 immunomodulatory therapies 1, 3, and 6 months post-treatment (-49.9 [95% CI -581.8, +482.0], p = 0.85; +27.7 [95% CI -167.6, +223.0], p = 0.78; -9.6 [95% CI -167.5, +148.2], p = 0.91). We found no difference in mean FVC slope or differences between ECP and AL in infection rates or survival after treatment. CONCLUSIONS: Immunomodulatory therapy for CLAD with ECP or AL was associated with a significant change in FEV1 slope post-treatment compared with pre-treatment slope, with minimal effect on FVC. There was no difference between the 2 therapies in their effect on pulmonary function.

Posttransplant Lymphoproliferative Disorders in Epstein-Barr Virus Donor Positive/Recipient Negative Lung Transplant Recipients.

BACKGROUND: Epstein-Barr virus (EBV) donor positive/recipient negative (D+/R-) status is a significant risk factor for posttransplant lymphoproliferative disorder (PTLD) in lung transplant. There are, however, no studies that identify the risk factors for PTLD in the EBV D+/R- lung transplant population to guide the decision to proceed with an EBV-positive donor. METHODS: This was a retrospective cohort study of adults listed in the Scientific Registry of Transplant Recipients between May 5, 2005, and August 31, 2016. Cox proportional hazards models were used to assess the impact of EBV D+/R- status on the development of PTLD, the impact of PTLD on survival, and survival differences between EBV D+/R- and EBV D-/R- recipients. RESULTS: The incidence of PTLD was 6.2% (79 of 1,281) versus 1.4% (145 of 10,352) in EBV D+/R- versus all other recipients (adjusted odds ratio 4.0; 95% confidence interval: 2.8 to 5.9, p < 0.001). Among EBV D+/R- recipients, age less than 40 years and white race were associated with PTLD. The EBV D+/R- patients who had PTLD had increased adjusted risk of death (hazard ratio 1.91; 95% confidence interval: 1.35 to 2.71; p < 0.001). Compared with EBV D+/R- recipients, EBV D-/R- recipients did not have improved adjusted survival (hazard ratio 0.82; 95% confidence interval: 0.57 to 1.18; p = 0.30). CONCLUSIONS: Despite increased rates of PTLD and associated mortality in the EBV D+/R- population, EBV seronegative patients did not have worse mortality when transplanted with lungs from EBV seropositive donors compared with lungs from EBV seronegative donors. Consideration should be given for close monitoring for PTLD among EBV D+/R- recipients, particularly those who are white and less than 40 years of age.

Surgical interventions for emphysema.

Three surgical procedures are pertinent to the treatment of end-stage emphysema: giant bullectomy, lung volume reduction surgery (LVRS), and lung transplantation. Patients with localized disease manifesting as a giant bulla that compresses adjacent healthy lung tissues can be offered bullectomy. Patients with diffuse disease can be offered LVRS, lung transplantation, or staged LVRS/lung transplant, depending on multiple factors including age, lung function parameters, lobar predominance, and whether the disease is uni- or bilateral. Since end-stage emphysema is refractory to most medical treatment, surgery is often the only remaining option.

The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD-Related Death.

BACKGROUND: Development of donor-specific antibodies (DSA) after lung transplantation is associated with antibody mediated rejection, acute cellular rejection, and bronchiolitis obliterans syndrome; however, the significance of circulating antibodies before transplant remains unclear. METHODS: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012. We assessed the impact of circulating HLA and noncytotoxic DSA detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD-related death. RESULTS: 30% of subjects had circulating class I antibodies alone, 4% Class II, and 14.4% class I and class II at mean fluorescent intensity greater than 1000. Nine percent of the subjects had DSA class I, 9% class II, and 2.4% both DSA classes 1 and 2. Neither the presence of circulating antibodies (adjusted hazard ratio, 0.87; 95% confidence interval, 0.50-1.54) nor the presence of DSA (adjusted hazard ratio, 1.56; 95% confidence interval, 0.77-3.18) before transplant at mean fluorescent intensity greater than 1000 was associated with the development of CLAD or CLAD-related death. CONCLUSIONS: Although in previous studies we have shown an increased incidence of antibody-mediated rejection in patients with pretransplant DSA, neither the presence of HLA antibodies nor DSA translated to an increased risk of allograft dysfunction or death if prospective crossmatch testing was negative. Prospective studies are needed to define the impact of pretransplant sensitization on lung transplant recipients.

Interventions to improve guideline compliance following coronary artery bypass grafting.

BACKGROUND: Lifestyle modification and appropriate medical therapy improve long-term outcomes following coronary artery bypass grafting (CABG). Our institutional experience suggested that evidence-based recommendations were not being followed postdischarge after CABG. We undertook this study to document our rate of compliance with evidence-based guidelines and to correct deficiencies in our discharge practices. METHODS: Seven evidence-based interventions were studied after CABG: (1) institution of beta-blocker therapy, (2) angiotensin-converting enzyme (ACE) inhibitor therapy, (3) aspirin, (4) lipid-lowering therapy, (5) smoking cessation intervention, (6) heart-healthy diet therapy, and (7) physical activity recommendations. The rate of compliance with guidelines in 50 control patients was measured at discharge. A multidisciplinary team including cardiac surgeons, nurses, dieticians, physical therapists, and clinical pharmacists evaluated the guideline compliance in the control group and developed interventions to assure guideline compliance at the time of discharge. A subsequent study group of 50 patients was then assessed prospectively to measure the guideline compliance after institution of intervention programs. The multidisciplinary team agreed on predefined acceptable compliance limits as follows: (1) >80% of patients receive ACE inhibitors at discharge, (2) 100% of patients receive beta-blockers, aspirin, and lipid-lowering agents at discharge, and (3) 100% of patients receive lifestyle modification counseling at discharge. Compliance with guidelines was defined as documentation in the medical record of provision of medications and lifestyle counseling at the time of discharge. RESULTS: In the control group, the rate of guideline compliance was surprisingly low. Rates of compliance with guidelines increased significantly after the multidisciplinary interventions were undertaken. CONCLUSIONS: We conclude that compliance with guidelines known to improve long-term outcome is suboptimal after CABG. A multidisciplinary intervention program can improve compliance with currently accepted guidelines and quality indicators in patients following CABG.

The association between mood, anxiety and adjustment disorders and hospitalization following lung transplantation.

OBJECTIVES: Psychiatric comorbidities such as mood, anxiety and adjustment disorders are common among individuals seeking lung transplantation. The objective of this study is to describe the association between these disorders and length of initial hospitalization and number of hospitalizations in the first year following transplantation. METHODS: This was a retrospective cohort study of all lung transplantation patients between January 1, 2008 and July 1, 2014 at a large academic center. We evaluated whether pretransplantation mood, anxiety or adjustment disorders were associated with length and number of hospitalizations after transplant, adjusting for age, sex, native disease, forced expiratory volume in 1 s prior to transplantation, wait list time and lung allocation score. RESULTS: There were 185 patients who underwent transplantation during the 7.5-year study period of whom 125 (67.6%) had a mood, anxiety or adjustment disorder. Patients with an adjustment disorder had decreased length of initial hospitalization [B coefficient=-5.76; 95% confidence interval (CI)=-11.40 to -0.13; P=.04]. Patients with anxiety disorders had an increased number of hospitalizations in the first year following transplantation (rate ratio=1.41; 95% CI=1.06-1.88; P=.02). There was no association between mood disorders and length or number of hospitalizations. Mood, adjustment and anxiety disorders were not associated with time to initial rehospitalization. CONCLUSIONS: Among the three most common pretransplantation psychiatric disorders, only anxiety disorders are associated with increased hospitalization in the first year following lung transplant. Interventions designed to better control pretransplantation and posttransplantation anxiety may be associated with less frequent hospitalization.

Donor-acquired fat embolism syndrome after lung transplantation.

OBJECTIVES: Fat embolism is a known complication of severe trauma and closed chest cardiac resuscitation both of which are more common in the lung transplant donor population and can lead to donor-acquired fat embolism syndrome (DAFES). The objective was to review the diagnosis and management of DAFES in the lung transplantation literature and at our centre. METHODS: We performed a literature review on DAFES using the Medline database. We then reviewed the transplant record of Brigham and Women's Hospital, a large academic hospital with an active lung transplant programme, for cases of DAFES. RESULTS: We identified 2 cases of DAFES in our centre, one of which required extracorporeal membrane oxygenation (ECMO) for successful management. In contrast to the broader literature on DAFES, which emphasizes unsuccessfully treated cases, both patients survived. CONCLUSION: DAFES is a rare but likely underappreciated early complication of lung transplant as it can mimic primary graft dysfunction. Aggressive interventions, including ECMO, may be necessary to achieve a good clinical outcome following DAFES.

Aminocaproic acid for the management of bleeding in patients on extracorporeal membrane oxygenation: Four adult case reports and a review of the literature.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is associated with a significant risk of bleeding and thrombosis. Despite high rates of bleeding and bleeding-related mortality in patients on ECMO, there is little evidence available to guide clinicians in the management of ECMO-associated bleeding. METHODS: We report the use of aminocaproic acid in four patients with bleeding on ECMO and a review of the literature. RESULTS: High D-dimer levels and low fibrinogen levels suggested that an antifibrinolytic agent may be effective as an adjunct to control bleeding. After aminocaproic acid administration, bleeding was controlled in each patient as evidenced by clinical and laboratory parameters. One patient suffered a cardiac arrest and care was withdrawn. CONCLUSIONS: In patients on ECMO with evidence of fibrinolysis, aminocaproic acid may be an effective option to control bleeding and to stabilize clot formation.

Thin-filament-based modulation of contractile performance in human heart failure.

BACKGROUND: The contribution of the sarcomere's thin filament to the contractile dysfunction of human cardiomyopathy is not well understood. METHODS AND RESULTS: We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms alpha, beta1, and beta2 was increased in failing human myocardium and reduced after left ventricular assist device support. CONCLUSIONS: These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and (3) the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C.

Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease.

BACKGROUND: Human telomere disease consists of a wide spectrum of disorders, including pulmonary, hepatic, and bone marrow abnormalities. The extent of bone marrow and liver abnormalities in patients with interstitial lung disease (ILD) and short telomeres is unknown. METHODS: The lung transplant clinic established a prospective protocol to identify short telomeres in patients with ILD not related to connective tissue disease or sarcoidosis. Patients with short telomeres underwent bone marrow biopsies, liver biopsies, or both as part of the evaluation for transplant candidacy. RESULTS: One hundred twenty-seven patients met ILD categorization for inclusion. Thirty were suspected to have short telomeres, and 15 had the diagnosis confirmed. Eight of 13 (53%) patients had bone marrow abnormalities. Four patients had hypocellular marrow associated with macrocytosis and relatively normal blood counts, which resulted in changes to planned immunosuppression at the time of transplant. Four patients with more severe hematologic abnormalities were not listed because of myelodysplastic syndrome (two); monoclonal gammopathy of unclear significance (one); and hypocellular marrow, decreased megakaryocyte lineage associated with thrombocytopenia (one). Seven patients underwent liver biopsies, and six had abnormal liver pathology. These abnormalities did not affect listing for lung transplant, and liver biopsies are no longer routinely obtained. CONCLUSIONS: Subclinical bone marrow and liver abnormalities can be seen in patients with ILD and short telomeres, in some cases in the absence of clinically significant abnormalities in peripheral blood counts and liver function tests. A larger study examining the implication of these findings on the outcome of patients with ILD and short telomeres is needed.