End-stage Idiopathic Pulmonary Fibrosis Research Articles

Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

Idiopathic pulmonary fibrosis (IPF) affects subpleural lung, but is considered to spare small airways. Micro-CT studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. We use EB-OCT to evaluate small airways in early IPF and control subjects in vivo. EB-OCT was performed in 12 IPF and 5 control subjects (matched by age, sex, smoking-history, height, BMI). IPF subjects had early disease with mild restriction (FVC: 83.5% predicted), diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for UIP present) and less affected (some but not all criteria for UIP present) sites. Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Compared to control subjects (mean: 11.2 bronchioles/cm3; SD: 6.2), there was significant bronchiole reduction in IPF subjects (42% loss; mean: 6.5/cm3; SD: 3.4; p=0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; p<0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; p=0.024) sites. Stereology metrics showed IPF affected small airways were significantly larger and more distorted/irregular than in IPF less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (p=0.36-1.0). EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30 and 50%), even in areas minimally affected by disease, compared to matched controls. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Lung immune signatures define two groups of end-stage IPF patients

BackgroundThe role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial.MethodsTo investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters.ResultsWe identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities.ConclusionsIn end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored.

A CASE OF LUNG TRANSPLANT WITH RECENTLY INFECTED SARS-COV-2 DONOR LUNGS

A CASE OF LUNG TRANSPLANT WITH RECENTLY INFECTED SARS-COV-2 DONOR LUNGS

Comparative Analysis of Gene Expression in Fibroblastic Foci in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis.

Background: Fibroblastic foci (FF) are characteristic features of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) and one cardinal feature thought to represent a key mechanism of pathogenesis. Hence, FF have a high impact on UIP/IPF diagnosis in current guidelines. However, although less frequent, these histomorphological hallmarks also occur in other fibrotic pulmonary diseases. Currently, there is therefore a gap in knowledge regarding the underlying molecular similarities and differences of FF in different disease entities. Methods: In this work, we analyzed the compartment-specific gene expression profiles of FF in IPF and sarcoidosis in order to elucidate similarities and differences as well as shared pathomechanisms. For this purpose, we used laser capture microdissection, mRNA and protein expression analysis. Biological pathway analysis was performed using two different gene expression databases. As control samples, we used healthy lung tissue that was donated but not used for lung transplantation. Results: Based on Holm Bonferroni corrected expression data, mRNA expression analysis revealed a significantly altered expression signature for 136 out of 760 genes compared to healthy controls while half of these showed a similar regulation in both groups. Immunostaining of selected markers from each group corroborated these results. However, when comparing all differentially expressed genes with the fdr-based expression data, only 2 of these genes were differentially expressed between sarcoidosis and IPF compared to controls, i.e., calcium transport protein 1 (CAT1) and SMAD specific E3 ubiquitin protein ligase 1 (SMURF1), both in the sarcoidosis group. Direct comparison of sarcoidosis and IPF did not show any differentially regulated genes independent from the statistical methodology. Biological pathway analysis revealed a number of fibrosis-related pathways pronounced in IPF without differences in the regulatory direction. Conclusions: These results demonstrate that FF of end-stage IPF and sarcoidosis lungs, although different in initiation, are similar in gene and protein expression, encouraging further studies on the use of antifibrotic agents in sarcoidosis.

The clinical relevance of lymphocyte to monocyte ratio in patients with Idiopathic Pulmonary Fibrosis (IPF)

Disease course in Idiopathic Pulmonary Fibrosis (IPF) is highly heterogeneous and markers of disease progression would be helpful. Blood leukocyte count has been studied in cancer patients and a reduced lymphocyte to monocyte ratio (LMR) has been show to predict survival. Thus, we aimed to investigate the role of monocytes count and LMR in three distinct population of patients with IPF: 77 newly-diagnosed IPF, 40 with end-stage IPF and 17 IPF with lung cancer. In newly-diagnosed IPF patients, we observed a negative correlation between forced vital capacity (FVC) at diagnosis and both white blood cells and monocytes count (r = −0.24; p = 0.04 and r = −0.27; p = 0.01; respectively). Moreover, a high monocytes count was independently associated with functional decline (OR: 1.004, 95%CI 1.00–1.01; p = 0.03). In newly-diagnosed IPF, the LMR cut-off at diagnosis was 4.18 with an AUC of 0.67 (95%CI 0.5417–0.7960; p = 0.025), and overall survival was significantly worse in patients with a LMR<4.18 compared to patients with a LMR≥4.18 (HR: 6.88, 95%CI 2.55–18.5; p = 0.027). LMR was significantly lower in IPF patients with lung cancer compared to those newly diagnosed with IPF [2.2 (0.8–4.4), 3.5 (0.8–8.8); p < 0.0001] and those with end-stage disease [3.6 (2–6.5); p < 0.0001]. In conclusion, a LMR<4.18 is associated with significantly shorter survival in newly-diagnosed IPF patients. In addition, LMR is significantly lower in patients with IPF and lung cancer compared to patients with newly-diagnosed IPF. High monocytes count at baseline negatively correlates with FVC and is an independent predictor of disease progression in newly-diagnosed IPF patients.

THE TALE OF THE TRAVELING CHEESE: SHIGELLA IN A LUNG TRANSPLANT PATIENT

TOPIC: Transplantation TYPE: Fellow Case Reports INTRODUCTION: Shigella is a common cause of gastroenteritis in areas of overcrowding and poor sanitation, but is seen less frequently in the developed world. Infection is mainly acquired through the fecal-oral route, but consumption of unpasteurized dairy remains a high risk for transmission. In this report, we describe a case of a lung transplant patient who presented with septic shock secondary to Shigella gastroenteritis after ingesting unpasteurized cheese brought back from Peru. CASE PRESENTATION: This is a case of a 62-year-old Peruvian man who underwent a bilateral lung transplant for end stage idiopathic pulmonary fibrosis in November 2018, a year prior to this presentation. Pre-transplant the patient status was CMV +/+, EBV +/+. At time of presentation his immunosuppression regimen consisted of Tacrolimus 0.5 mg, Mycophenolate 500mg twice daily and Prednisone 10mg daily.He had been progressing well until he presented to the emergency department with a reported fever of 103 degrees Fahrenheit, around 40 episodes a day of profuse non-bloody, watery diarrhea and abdominal discomfort. He did not complain of nausea or vomiting. He revealed that he had eaten soft, white, unpasteurized cheese that was brought from Peru two days prior.He was hypotensive with a blood pressure of 72/39, a heart rate of 107 beats per minute and SaO2 of 96% while breathing ambient air. A physical exam revealed mild diffuse abdominal tenderness, rest of exam was normal.Laboratory examination revealed a white blood cell count of 18,000 cells/mcl, platelet (PLT) count of 147,000 cells/mcl, creatinine 1.30 mg/dL, lactic acid 3.2 mmol/L. Computerized tomography (CT) of his abdomen showed fluid filled loops of the colon and small bowel, reflecting enteritis and diarrhea. Stool studies were sent. The patient was treated with intravenous fluids, Tacrolimus was held due to new acute kidney injury, Mycophenolate held due to leukopenia and Cefepime and Metronidazole were administered for empiric coverage for abdominal pathogens. On day 4 of admission Shigella flexneri (sensitive to Levofloxacin and Ceftriaxone, resistant to Ampicillin) was isolated and infectious disease consultation obtained. The patient had clinically recovered on Cefepime and he completed the antibiotic course. He was discharged the following day on his routine triple immunosuppressive therapy. DISCUSSION: Solid organ transplant recipients with diarrhea should be tested for shigella. Patients not responding to conventional treatment should undergo repeat culture and sensitivity testing. Bacterial culture is the gold standard for diagnosis of shigella infections. The use of antibiotics depends on the severity of illness, the age of the patient and immune status. CONCLUSIONS: This case highlights the importance of educating transplant patients on how to reduce certain harmful exposures that may be fatal in immunosuppressed individuals. REFERENCE #1: 1. GBD 2016 Diarrhoeal Disease Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis 2018. REFERENCE #2: 2. Kotloff KL, Winickoff JP, Ivanoff B, et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ 1999; 77:651–66 REFERENCE #3: 3. Livio S, Strockbine NA, Panchalingam S, et al. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis 2014; 59: 933–41. DISCLOSURES: No relevant relationships by Nikhil Madan, source=Web Response No relevant relationships by Vipul Patel, source=Web Response No relevant relationships by Safiyya Quintiliani, source=Web Response

Lung transplant after 6 months on ECMO support for SARS-CoV-2-induced ARDS complicated by severe antibody-mediated rejection

There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we...

Refractory Dyspnea in a Patient with End-Stage Idiopathic Pulmonary Fibrosis (Palliative Care unit Case Study)

Treating dyspnea in patients with idiopathic pulmonary fibrosis is a challenge. The foreign experience of using low doses of opioids to relieve dyspnea in patients with progressing diseases is controversial among Russian specialists. The presented clinical case is an 83-year-old patient with idiopathic pulmonary fibrosis in the terminal stage and refractory dyspnea, progressive respiratory failure of II - III degrees, and concomitant exertional angina II FC and organic anxiety disorder. The patient was offered low-dose morphine injections (2 mg 5 times a day subcutaneously) to relieve the shortness of breath. The patient, who had not previously received opioids, and his relatives gave prior consent to the use of morphine. Within a week from the moment of hospitalization, the general and psycho-emotional state of the patient improved, dyspnea decreased, and night sleep was partially normalized. However, а week later, being in a severe but relatively stable condition, the patient died from a massive nosebleed. Shown, that the traditional approach to reducing dyspnea and the associated agitation in patients with interstitial lung disease is the use of corticosteroids and psychotropic therapeutics in increasing doses. The use of low doses of opioids to relieve dyspnea in patients with non-cancer disease meets many organizational, medical, and psychological barriers. At the same time, this therapy is recognized as successful and safe in the foreign palliative practice. Overcoming the existing barriers based on the evidence from clinical trials, as well as the domestic and foreign clinical practice of the safe use of low doses of opioids would expand the arsenal of effective treatments for refractory dyspnea.

DIAPHRAGMATIC HEMIPARALYSIS AS A RARE CONSEQUENCE OF HIGH THORACIC EPIDURAL ANESTHESIA IN LUNG TRANSPLANTATION: A CASE REPORT

SESSION TITLE: Fellows Transplantation Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Thoracic epidural anesthesia is routinely placed intraoperatively for postoperative pain management in lung transplant recipients [1]. Herein, we sought to detail a rare consequence of thoracic epidural anesthesia if placed too high. CASE PRESENTATION: A 56-year-old male underwent bilateral lung transplant in April 2020 for treatment of end-stage idiopathic pulmonary fibrosis. There were no major intraoperative complications, and no phrenic nerve injury noted. Thoracic epidural anesthesia was placed in the operating room for routine postoperative pain management. The immediate postoperative period was uncomplicated, as the patient had no primary graft dysfunction at time 0 or 24 hours after transplant. The allograft was functioning well with minimal secretions and no positive cultures detected. After rapid ventilator weaning, the patient was extubated on post-transplant day one. However, the patient required two unsuspected re-intubations, and the right hemidiaphragm was found notably elevated on chest radiograph. The epidural block was weaned within six hours, and the patient was successfully extubated, without need for further re-intubation. The initial and follow-up chest radiographs after recovery are depicted in Figure 1. DISCUSSION: Upon review, it was noted that the epidural catheter was inserted high at the T2-3 intervertebral space. Although thoracic epidural block extending up to the T2 level does not normally alter ventilation significantly in healthy persons, our patient recovering from lung transplant was dyspneic and had difficulty generating adequate tidal volume, necessitating re-intubation. Importantly, large volumes of anesthetics may be necessary after a highly invasive thoracic surgery such as lung transplant. A high thoracic epidural block with significant anesthetic volume may affect the roots of the brachial plexus, some of which are responsible for the phrenic nerve and diaphragmatic contraction. CONCLUSIONS: Anesthesiologists and transplant clinicians should be aware that intraoperative high thoracic epidural anesthesia in a lung transplant recipient may have post-transplant motor repercussions of diaphragmatic hemiparalysis, resulting in changes to respiratory dynamics and pulmonary symptoms. Reference #1: Von Dossow V, Welte M, Zaune U, et al. Thoracic epidural anesthesia combined with general anesthesia: the preferred anesthetic technique for thoracic surgery. Anesth Analg. 2001;92(4):848-854. doi:10.1097/00000539-200104000-00010 DISCLOSURES: No relevant relationships by Hesham Abdelrazek, source=Web Response No relevant relationships by ASHWINI ARJUNA, source=Web Response No relevant relationships by Hesham Mohamed, source=Web Response No relevant relationships by Michael Olson, source=Web Response No relevant relationships by Josna Padiyar, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 by Rajat Walia, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 by Rajat Walia, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Grifols Please note: $5001 - $20000 by Rajat Walia, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Shire Please note: $1001 - $5000 by Rajat Walia, source=Admin input, value=Honoraria Speaker/Speaker's Bureau relationship with Astellas Please note: $5001 - $20000 by Rajat Walia, source=Admin input, value=Honoraria

Use of the Reversible Myogenic to Lipogenic Transdifferentiation Switch for the Design of Pre-clinical Drug Screening in Idiopathic Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is an end-stage lung disease characterized by excessive extracellular matrix (ECM) deposition from activated myofibroblasts (MYFs) and tissue scarring. Eventually leading to stiffening of the lung, capable of assuming only limited gas exchange function. So far two drugs, pirfenidone [acting via TGF-β (transforming growth factor beta) inhibition] and nintedanib (a pan-tyrosine kinase receptor inhibitor) have been approved for IPF patients. They both act on the activated MYF by reducing the expression of fibrotic markers. Unfortunately, these drugs are only slowing down fibrosis formation and as such do not represent a cure for this lethal, devastating disease. We previously reported that activated MYF originate, at least in part, from lung fibroblast resident cells called lipofibroblasts (LIF). During resolution, these activated MYF can transdifferentiate into LIF. We propose that this reversible myogenic/lipogenic transdifferentiation switch paradigm can be used to screen for drugs capable of triggering the lipogenic differentiation of activated MYFs. Ideally, these drugs should also induce the reduction of pro-fibrotic markers alpha smooth muscle actin2 (ACTA2) and collagen 1A1 (COL1A1) in activated MYF and as such would represent important alternatives to the approved drugs. The goal of this review is to summarize the current knowledge and limitations of the current strategies aiming to carry out methodical pre-clinical drug screening in pertinent in vitro, ex vivo, and in vivo models of IPF. These models include (1) in vitro culture of primary fibroblasts from IPF patients, (2) ex vivo culture of precision cut lung slices from end-stage IPF lungs obtained from transplant patients, and (3) bleomycin-induced fibrosis mouse models in the context of lineage tracing of activated MYF during resolution. For all these assays, we propose the innovative use of lipogenic read outs for the LIFs.

CA 19-9 serum levels in patients with end-stage idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs): Correlation with functional decline.

Idiopathic pulmonary fibrosis presents a progressive and heterogeneous functional decline. CA 19-9 has been proposed as biomarker to predict disease course, but its role remains unclear. We assessed CA 19-9 levels and clinical data in end-stage ILD patients (48 IPF and 20 non-IPF ILD) evaluated for lung transplant, to correlate these levels with functional decline. Patients were categorized based on their rate of functional decline as slow (n = 20; ΔFVC%pred ≤ 10%/year) or rapid progressors (n = 28; ΔFVC%pred ≥ 10%/year). Nearly half of the entire patients (n = 32; 47%) had CA 19-9 levels ≥37kU/L. CA 19-9 levels in IPF were not different from non-IPF ILD populations, however, the latter group had a median CA 19-9 level above the normal cut-off value of 37 KU/l (60 [17–247] kU/L). Among IPF patients, CA 19-9 was higher in slow than in rapid progressors with a trend toward significance (33vs17kU/L; p = 0.055). In the whole population, CA19-9 levels were inversely related with ΔFVC/year (r = −0.261; p = 0.03), this correlation remained in IPF patients, particularly in rapid progressors (r = −0.51; p = 0.005), but not in non. Moreover, IPF rapid progressors with normal CA 19-9 levels showed the greater ΔFVC/year compared to those with abnormal CA 19-9 (0.95 vs. 0.65 L/year; p = 0.03). In patients with end-stage ILD, CA 19-9 may represent a marker of disease severity, whereas its level is inversely correlated with functional decline, particularly among IPF rapid progressors.

RNA sequencing of transplant-stage idiopathic pulmonary fibrosis lung reveals unique pathway regulation

Idiopathic pulmonary fibrosis (IPF), the scarring of lung parenchyma resulting in the loss of lung function, remains a fatal disease with a significant unmet medical need. Patients with severe IPF often develop acute exacerbations resulting in the rapid deterioration of lung function, requiring transplantation. Understanding the pathophysiological mechanisms contributing to IPF is key to develop novel therapeutic approaches for end-stage disease.We report here RNA-sequencing analyses of lung tissues from a cohort of patients with transplant-stage IPF (n=36), compared with acute lung injury (ALI) (n=11) and nondisease controls (n=19), that reveal a robust gene expression signature unique to end-stage IPF. In addition to extracellular matrix remodelling pathways, we identified pathways associated with T-cell infiltration/activation, tumour development, and cholesterol homeostasis, as well as novel alternatively spliced transcripts that are differentially regulated in the advanced IPF lung versus ALI or nondisease controls. Additionally, we show a subset of genes that are correlated with percent predicted forced vital capacity and could reflect disease severity.Our results establish a robust transcriptomic fingerprint of an advanced IPF lung that is distinct from previously reported microarray signatures of moderate, stable or progressive IPF and identifies hitherto unknown candidate targets and pathways for therapeutic intervention in late-stage IPF as well as biomarkers to characterise disease progression and enable patient stratification.

Modeling of Fibrotic Lung Disease Using 3D Organoids Derived from Human Pluripotent Stem Cells

The pathogenesis of idiopathic pulmonary fibrosis (IPF), an intractable interstitial lung disease, is unclear. Recessive mutations in some genes implicated in Hermansky-Pudlak syndrome (HPS) cause HPS-associated interstitial pneumonia (HPSIP), a clinical entity that is similar to IPF. We previously reported that HPS1-/- embryonic stem cell-derived 3D lung organoids showed fibrotic changes. Here, we show that the introduction of all HPS mutations associated with HPSIP promotes fibrotic changes in lung organoids, while the deletion of HPS8, which is not associated with HPSIP, does not. Genome-wide expression analysis revealed the upregulation of interleukin-11 (IL-11) in epithelial cells from HPS mutant fibrotic organoids. IL-11 was detected predominantly in type 2 alveolar epithelial cells in end-stage IPF, but was expressed more broadly in HPSIP. Finally, IL-11 induced fibrosis in WT organoids, while its deletion prevented fibrosis in HPS4-/- organoids, suggesting IL-11 as a therapeutic target. hPSC-derived 3D lung organoids are, therefore, a valuable resource to model fibrotic lung disease.

Fibrocytes are increased in lung and peripheral blood of patients with idiopathic pulmonary fibrosis

BackgroundFibrocytes are implicated in Idiopathic Pulmonary Fibrosis (IPF) pathogenesis and increased proportions in the circulation are associated with poor prognosis. Upon tissue injury, fibrocytes migrate to the affected organ. In IPF patients, circulating fibrocytes are increased especially during exacerbations, however fibrocytes in the lungs have not been examined.Therefore, we sought to evaluate if fibrocytes can be detected in IPF lungs and we compare percentages and phenotypic characteristics of lung fibrocytes with circulating fibrocytes in IPF.MethodsFirst we optimized flow cytometric detection circulating fibrocytes using a unique combination of intra- and extra-cellular markers to establish a solid gating strategy. Next we analyzed lung fibrocytes in single cell suspensions of explanted IPF and control lungs and compared characteristics and numbers with circulating fibrocytes of IPF.ResultsUsing a gating strategy for both circulating and lung fibrocytes, which excludes potentially contaminating cell populations (e.g. neutrophils and different leukocyte subsets), we show that patients with IPF have increased proportions of fibrocytes, not only in the circulation, but also in explanted end-stage IPF lungs. These lung fibrocytes have increased surface expression of HLA-DR, increased intracellular collagen-1 expression, and also altered forward and side scatter characteristics compared with their circulating counterparts.ConclusionsThese findings demonstrate that lung fibrocytes in IPF patients can be quantified and characterized by flow cytometry. Lung fibrocytes have different characteristics than circulating fibrocytes and represent an intermediate cell population between circulating fibrocytes and lung fibroblast. Therefore, more insight in their phenotype might lead to specific therapeutic targeting in fibrotic lung diseases.

Access to Palliative Care for Patients Undergoing Mechanical Ventilation With Idiopathic Pulmonary Fibrosis in the United States.

The utilization of palliative care (PC) in patients with end-stage idiopathic pulmonary fibrosis (IPF) is not well understood. The Nationwide Inpatient Sample (NIS) was utilized to examine the use of PC in mechanically ventilated (MV) patients with IPF. The NIS captures 20% of all US inpatient hospitalizations and is weighted to estimate 95% of all inpatient care. A total of 55 208 382 hospital admissions from the 2006 to 2012 NIS samples were examined. There were 21 808 patients identified with pulmonary fibrosis, of which 3166 underwent mechanical ventilation and were included in the analysis. Of the 3166 patients in the main cohort, 408 (12.9%) had an encounter with PC, whereas 2758 (87.1%) did not. After multivariate logistic regression modeling, variables associated with increased access to PC referral were age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P < .01), treatment in an urban teaching hospital (OR: 1.49, 95% CI: 1.27-3.58, P < .01), and do-not-resuscitate status (OR: 9.86, 95% CI: 7.48-13.00, P < .01). Factors associated with less access to PC were Hispanic race (OR: 0.64, 95% CI: 0.41-0.99, P = .04) and missing race (OR: 0.52, 95% CI: 0.34-0.79, P < .01), with white race serving as the reference. The use of PC has increased almost 10-fold from 2.3% in 2006 to 21.6% in 2012 ( P < .01). The utilization of PC in patients with IPF who undergo MV has increased dramatically between 2006 and 2012.

Concomitant Single Vessel Coronary Revascularization and Single Lung Transplant in an Elderly Patient with End-Stage Idiopathic Pulmonary Fibrosis and Reduced Ejection Fraction

Concomitant Single Vessel Coronary Revascularization and Single Lung Transplant in an Elderly Patient with End-Stage Idiopathic Pulmonary Fibrosis and Reduced Ejection Fraction

Pulmonary Hypertension in End-Stage Pulmonary Fibrosis: Prevalence, Predictors and Survival before and after Lung Transplantation

Purpose The prevalence, prognosis and factors that predict the presence and degree of pulmonary hypertension (PH) in patients with end-stage idiopathic pulmonary fibrosis (IPF) remain unclear. Methods and Materials This retrospective study analyzed the occurrence and degree of PH (mPAP ≥25mmHg and PCWP ≤15mmHg) with right heart catheterization (RHC), in a consecutive cohort of patients with end-stage IPF at Rigshospitalet, Denmark. A total of 100 patients with end-stage IPF were evaluated for lung transplantation and had available RHC data. The analysis excluded 10 patients with PVH (mPAP ≥25 mm Hg, PCWP >15 mmHg). Prediction of PH was assessed using regression analysis and prognosis was determined using Kaplan-Meier statistics. Results The analysis included 90 patients, of whom 44 had PH (21 transplanted), and the remaining 46 patients had normal pulmonary pressures (21 transplanted). The group mPAP showed a skewed distribution towards high mPAPs with a median of 24.5mmHg (range 10-59mmHg). The mean age at evaluation was 53.7±10.2 years (32% women). All patients were in NYHA function class III-IV with FEV 1 46±18%, FVC 45±17%, DL CO 24±14% and total lung capacity 51±17% of predicted. Predictors of PH were confined to PaO 2 , DL CO and 6-minute walk distance. Median survival in non-transplanted patients was less than 1 year. 20 patients died with PH, (median survival 129 days, range 22-1959 days) and 17 died without PH (median 291 days, range 12-3992 days (p=0.45). The 5-year survival in IPF patients was 35% with PH vs 40% without PH (p=0.26), in multivariable analysis, PH was associated with a HR of 0.83 (p=0.68). Similarly, no difference was observed in survival after lung transplantation (p=0.23). Conclusions PH was present in 49% of patients with end-stage IPF. Hypoxemia, DL CO and 6-minute walk distance were predictive factors. PH appears to have no significant effect on survival in end-stage IPF, either before or after lung transplantation; but IPF itself determines survival.

Lung 26S and 20S proteasomes are increased in patients with end-stage idiopathic pulmonary fibrosis

Lung 26S and 20S proteasomes are increased in patients with end-stage idiopathic pulmonary fibrosis

Year in review 2010: Interstitial lung diseases, acute lung injury, sleep, physiology, imaging, bronchoscopic intervention and lung cancer

Year in review 2010: Interstitial lung diseases, acute lung injury, sleep, physiology, imaging, bronchoscopic intervention and lung cancer

Pulmonary Vein Stenosis After Lung Transplantation Successfully Treated With Stent Implantation

A 31-year-old white woman with end stage idiopathic pulmonary fibrosis underwent left lung transplantation in our institution in January 2010. Oxygenation could be preserved by the native right lung, so surgery was performed without cardiopulmonary bypass. The procedure was uneventful and a bronchoscopic assessment of the graft showed only mild edema of the mucosa. In the early postoperative course gas exchange was difficult to maintain, requiring high FiO2 and positive end-expiratory pressure. Chest x-ray demonstrated alveolar infiltrates in the graft (Figure 1A). Due to the suspicion of reperfusion edema, an infusion of furosemide was initiated, although only a partial resolution of the congestion was achieved. The patient was successfully extubated 5 days after intervention, however reintubation was needed within 24 hours due to desaturation and inadequate response to noninvasive ventilation. At this time point a bronchoscopic evaluation was carried …