Lung transplantation for sarcoidosis: outcome and prognostic factors.

STUDY QUESTION: In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation. PATIENTS AND METHODS: We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres. RESULTS: Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications. ANSWER TO THE STUDY QUESTION: Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.

Training Thoracic Ultrasound Skills: A Randomized Controlled Trial of Simulation-Based Training versus Training on Healthy Volunteers.

INTRODUCTION: As ultrasound becomes more accessible, the use of point-of-care ultrasound examinations performed by clinicians has increased. Sufficient theoretical and practical skills are prerequisites to integrate thoracic ultrasound into a clinical setting and to use it as supplement in the clinical decision-making. Recommendations on how to educate and train clinicians for these ultrasound examinations are debated, and simulation-based training may improve clinical performance. OBJECTIVES: The aim of this study was to explore the effect of simulation-based training in thoracic ultrasound compared to training on healthy volunteers. METHOD: A total of 66 physicians with no previous experience in thoracic ultrasound completed a training program and assessment of competences from November 2018 to May 2019. After a theoretical session in ultrasound physics, sonoanatomy, and thoracic ultrasound, the physicians were randomized into one of three groups for practical training: (1) simulation-based training, (2) training on a healthy volunteer, or (3) no training (control group). Primary outcome was difference in the clinical performance score after the training period. RESULTS: Using a multiple comparison, ANOVA with Bonferroni correction for multiplicity, there was no statistical significant difference between the two trained groups' performance score: 45.1 points versus 41.9 points (minimum 17 points, maximum 68 points; p = 0.38). The simulation-based training group scored significantly higher than the control group without hands-on training, 36.7 points (p = 0.009). CONCLUSIONS: The use of simulation-based training in thoracic ultrasound does not improve the clinical performance score compared to conventional training on healthy volunteers. As focused, thoracic ultrasound is a relatively uncomplicated practical procedure when taught; focus should mainly be on the theoretical part and the supervised clinical training in a curriculum. However, simulation can be used instead or as an add-on to training on simulated patients.

Clinical Applicability of Lung Ultrasound Methods in the Emergency Department to Detect Pulmonary Congestion on Computed Tomography.

BACKGROUND: B-lines on lung ultrasound are seen in decompensated heart failure, but their diagnostic value in consecutive patients in the acute setting is not clear. Chest CT is the superior method to evaluate interstitial lung disease, but no studies have compared lung ultrasound directly to congestion on chest CT. PURPOSE: To examine whether congestion on lung ultrasound equals congestion on a low-dose chest CT as the gold standard. MATERIALS AND METHODS: In a single-center, prospective observational study we included consecutive patients ≥ 50 years of age in the emergency department. Patients were concurrently examined by lung ultrasound and chest CT. Congestion on lung ultrasound was examined in three ways: I) the total number of B-lines, II) ≥ 3 B-lines bilaterally, III) ≥ 3 B-lines bilaterally and/or bilateral pleural effusion. Congestion on CT was assessed by two specialists blinded to all other data. RESULTS: We included 117 patients, 27 % of whom had a history of heart failure and 52 % chronic obstructive pulmonary disease. Lung ultrasound and CT were performed within a median time of 79.0 minutes. Congestion on CT was detected in 32 patients (27 %). Method I had an optimal cut-point of 7 B-lines with a sensitivity of 72 % and a specificity of 81 % for congestion. Method II had 44 % sensitivity, and 94 % specificity. Method III had a sensitivity of 88 % and a specificity of 85 %. CONCLUSION: Pulmonary congestion in consecutive dyspneic patients ≥ 50 years of age is better diagnosed if lung ultrasound evaluates both B-lines and pleural effusion instead of B-lines alone.

Lung Ultrasound in the Assessment of Pulmonary Complications After Lung Transplantation.

INTRODUCTION: Lung ultrasound (LUS) has a high diagnostic accuracy for identifying frequent conditions in the post-operative phase after lung transplantation (LTx). This study aimed to investigate the feasibility and clinical ability of LUS to identify pulmonary complications such as pleural effusions and pneumonias in the early postoperative phase after LTx. METHODS: A prospective cohort study of lung transplant recipients who consecutively underwent single LTx (SLTx) or double LTx (DLTx) at the National Lung Transplantation Center in Denmark from May 1 to October 31, 2015 was conducted. LUS was performed at four time points corresponding to post-transplant day 3, and weeks 2, 6, and 12 (LUS #1-4) to detect and monitor variation in pathological LUS findings over time. Concurrent with LUS #4, a high-resolution computed tomography examination of the thorax (HRCT) was also performed. RESULTS: 14 patients (1 SLTx/13 DLTx, 7 (50 %) women, mean age: 50.4 years) who had undergone the four prespecified LUS examinations were included. Pleural effusion was the most common condition and most pronounced at post-LTx week 2. Findings consistent with pneumonia increased during week 2 and subsequently decreased. Corresponding to LUS #1, 2, 3, and 4, pleural effusion occurred in 85.7 %, 92.9 %, 85.7 %, and 78.6 %, and pneumonia in 21.4 %, 28.6 %, 14.3 %, and 14.3 %, respectively. HRCT findings at post-LTx week 12 were predominantly presented by unspecific ground glass opacities. CONCLUSION: In a post-LTx setting, LUS represents a clinical novelty as a feasible diagnostic and monitoring tool to identify pathological pulmonary complications in the early post-operative phase.

An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe.

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway.After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000-1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200-1000 and 100-500 m, respectively (hazard ratio 1.085- 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations.Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides.

Long-term persistence of human donor alveolar macrophages in lung transplant recipients.

BACKGROUND: Alveolar macrophages (AMFs) are critical regulators of lung function, and may participate in graft rejection following lung transplantation. Recent studies in experimental animals suggest that most AMFs are self-maintaining cells of embryonic origin, but knowledge about the ontogeny and life span of human AMFs is scarce. METHODS: To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100 weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation for X/Y chromosomes and immunofluorescence staining for macrophage markers. Moreover, development of AMFs in humanised mice reconstituted with CD34+ umbilical cord-derived cells was assessed. RESULTS: The number of donor-derived AMFs was unchanged during the 2 year post-transplantation period. A fraction of the AMFs proliferated locally, demonstrating that at least a subset of human AMFs have the capacity to self-renew. Lungs of humanised mice were found to abundantly contain populations of human AMFs expressing markers compatible with a monocyte origin. Moreover, in patients with lung transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period. CONCLUSIONS: The finding that human AMFs are maintained in the lung parenchyma for several years indicates that pulmonary macrophage transplantation can be a feasible therapeutic option for patients with diseases caused by dysfunctional AMFs. Moreover, in a lung transplantation setting, long-term persistence of donor AMFs may be important for the development of chronic graft rejection.

Pulmonary hypertension as a risk factor of mortality after lung transplantation.

PURPOSE: Pulmonary hypertension (PH) is recognized as a risk factor in lung transplantation as reflected in the lung allocation score (LAS). We examined the impact of PH on outcome after lung transplantation, with special emphasis on pre- and post-capillary PH. METHODS: Consecutive lung transplant recipients were evaluated according to ISHLT criteria including right heart catheterization in the period from 1992 to October 2014. Post-transplant survival was assessed according to hemodynamic characteristics: post-capillary PH (mean pulmonary arterial pressure [mPAP] ≥ 25 mmHg and pulmonary arterial wedge pressure [PAWP] > 15 mmHg), pre-capillary PH (mPAP ≥ 25 mmHg, PAWP ≤ 15 mmHg) and non-PH (mPAP < 25 mmHg). RESULTS: Of 518 transplant recipients, 58 (11%) had post-capillary PH. Pre-capillary PH was present in 211 (41%) and 249 (48%) non-PH. Post-capillary PH and pre-capillary PH were associated with worse 90-d outcomes after transplantation compared to non-PH (p = 0.043 and 0.003, respectively). The negative effect persisted 1 yr post-transplantation in pre-capillary PH (p = 0.037), but not in post-capillary PH (p = 0.447). Long-term survival was unaffected by hemodynamic classification. CONCLUSION: Post-capillary PH was present in 11% and pre-capillary PH in 41% of the transplant cohort. Post-capillary PH and pre-capillary PH were associated with inferior 90-d survival, but long-term survival was unaffected.

Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial.

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.

The number of FoxP3+ cells in transbronchial lung allograft biopsies does not predict bronchiolitis obliterans syndrome within the first five years after transplantation.

BACKGROUND: An important limitation to the success of lung transplantation is the development of bronchiolitis obliterans syndrome (BOS). It has been hypothesized that regulatory T lymphocytes (Tregs) are related to the risk of BOS. We aim to evaluate whether the number of forkhead box P3 (FoxP3+) cells/mm(2) in lung allograft biopsies is a predictor of long-term outcome. MATERIALS AND METHODS: A total of 58 consecutive lung transplant patients were included in the study. For 233 routine surveillance biopsy samples, the numbers of FoxP3+ cells/mm(2) were assessed by immunohistochemical staining with antibodies against FoxP3. BOS scores were calculated for the first five yr after transplantation. RESULTS: We determined that acute rejection was related to the time elapsed from transplantation to BOS with hazard ratios of 3.18 (p = 0.02) and 3.73 (p = 0.04) when comparing the levels of acute rejection grade 1 and grade 2/3, respectively, to no rejection. According to a Cox regression analysis, the number of FoxP3+ cells/mm(2) was not predictive of time to BOS. DISCUSSION AND CONCLUSIONS: Our data indicate that the number of FoxP3+ cells in the lung allograft did not correlate with BOS-free survival time. Previous studies have been contradictory and included different time points. Our findings emphasize the importance of including a time factor.

The effect of focused lung ultrasonography on antibiotic prescribing in patients with acute lower respiratory tract infections in Danish general practice: study protocol for a pragmatic randomized controlled trial (PLUS-FLUS).

BACKGROUND: The use of antibiotics is a key driver of antimicrobial resistance and is considered a major threat to global health. In Denmark, approximately 75% of antibiotic prescriptions are issued in general practice, with acute lower respiratory tract infections (LRTIs) being one of the most common indications. Adults who present to general practice with symptoms of acute LRTI often suffer from self-limiting viral infections. However, some patients have bacterial community-acquired pneumonia (CAP), a potential life-threatening infection, that requires immediate antibiotic treatment. Importantly, no single symptom or specific point-of-care test can be used to discriminate the various diagnoses, and diagnostic uncertainty often leads to (over)use of antibiotics. At present, general practitioners (GPs) lack tools to better identify those patients who will benefit from antibiotic treatment. The primary aim of the PLUS-FLUS trial is to determine whether adults who present with symptoms of an acute LRTI in general practice and who have FLUS performed in addition to usual care are treated less frequently with antibiotics than those who only receive usual care. METHODS: Adults (≥ 18 years) presenting to general practice with acute cough (< 21 days) and at least one other symptom of acute LRTI, where the GP suspects a bacterial CAP, will be invited to participate in this pragmatic randomized controlled trial. All participants will receive usual care. Subsequently, participants will be randomized to either the control group (usual care) or to an additional focused lung ultrasonography performed by the GP (+ FLUS). The primary outcome is the proportion of participants with antibiotics prescribed at the index consultation (day 0). Secondary outcomes include comparisons of the clinical course for participants in groups. DISCUSSION: We will examine whether adults who present with symptoms of acute LRTI in general practice, who have FLUS performed in addition to usual care, have antibiotics prescribed less frequently than those given usual care alone. It is highly important that a possible reduction in antibiotic prescriptions does not compromise patients' recovery or clinical course, which we will assess closely. TRIAL REGISTRATION: ClinicalTrials.gov NCT06210282. Registered on January 17, 2024.

Computed tomography or chest X-ray to assess pulmonary congestion in dyspnoeic patients with acute heart failure.

AIMS: While computed tomography (CT) is widely acknowledged as superior to chest radiographs for acute diagnostics, its efficacy in diagnosing acute heart failure (AHF) remains unexplored. This prospective study included consecutive patients with dyspnoea undergoing simultaneous low-dose chest CT (LDCT) and chest radiographs. Here, we aimed to determine if LDCT is superior to chest radiographs to confirm pulmonary congestion in dyspnoeic patients with suspected AHF. METHODS AND RESULTS: An observational, prospective study, including dyspnoeic patients from the emergency department. All patients underwent concurrent clinical examination, laboratory tests, echocardiogram, chest radiographs, and LDCT. The primary efficacy measure to compare the two radiological methods was conditional odds ratio (cOR). The primary outcome was adjudicated AHF, ascertained by comprehensive expert consensus. The secondary outcome, echo-bnp AHF, was an objective AHF diagnosis based on echocardiographic cardiac dysfunction, elevated cardiac filling pressure, loop diuretic administration, and NT-pro brain natriuretic peptide > 300 pg/mL. Of 228 dyspnoeic patients, 64 patients (28%) had adjudicated AHF, and 79 patients (35%) had echo-bnp AHF. Patients with AHF were older (78 years vs. 73 years), had lower left ventricular ejection fraction (36% vs. 55%), had higher elevated left ventricular filling pressures (98% vs. 18%), and had higher NT-pro brain natriuretic peptide levels (3628 pg/mL vs. 470 pg/mL). The odds to diagnose adjudicated AHF and echo-bnp AHF were up to four times greater using LDCT (cOR: 3.89 [2.15, 7.06] and cOR: 2.52 [1.45, 4.38], respectively). For each radiologic sign of pulmonary congestion, the LDCT provided superior or equivalent results as the chest radiographs, and the interrater agreement was higher using LDCT (kappa 0.88 [95% CI: 0.81, 0.95] vs. 0.73 [95% CI: 0.63, 0.82]). As first-line imaging modality, LDCT will find one additional adjudicated AHF in 12.5 patients and prevent one false-positive in 20 patients. Similar results were demonstrated for echo-bnp AHF. CONCLUSIONS: In consecutive dyspnoeic patients admitted to the emergency department, LDCT is significantly better than chest radiographs in detecting pulmonary congestion.

Thoracic Ultrasound in Lung Transplantation-Insights in the Field.

The use of thoracic ultrasound (TUS) is a novel and dynamic diagnostic and monitoring modality that has shown remarkable advances within the last decade, with several published papers investigating its role within the field of lung transplantation. The aim of this current opinion review is to review the existing literature on the role of TUS in all stages of LTx, from in-donor lung evaluation to graft assessment on ex vivo lung perfusion and in the short- and long-term follow-up after LTx.

Achromobacter spp. in a Cohort of Non-Selected Pre- and Post-Lung Transplant Recipients.

Achromobacter is an opportunistic pathogen that mainly causes chronic lung infections in cystic fibrosis (CF) patients and is associated with increased mortality. Little is known about Achromobacter spp. in the lung transplant recipient (LTXr) population. We aimed at describing rates of Achromobacter spp. infection in LTXr prior to, in relation to, and after transplantation, as well as all-cause mortality proportion in infected and uninfected LTXr. We included 288 adult LTXr who underwent lung transplantation (LTX) between 1 January 2010 and 31 December 2019 in Denmark. Bronchoalveolar lavage was performed at regular intervals starting two weeks after transplantation. Positive cultures of Achromobacter spp. were identified in nationwide microbiology registries, and infections were categorized as persistent or transient, according to the proportion of positive cultures. A total of 11 of the 288 LTXr had transient (n = 7) or persistent (n = 4) Achromobacter spp. infection after LTX; CF was the underlying disease in 9 out of 11 LTXr. Three out of the four patients, with persistent infection after LTX, also had persistent infection before LTX. The cumulative incidence of the first episode of infection one year after LTX was 3.8% (95% CI: 1.6-6.0). The incidence rates of transient and persistent infection in the first year after LTX were 27 (12-53) and 15 (5-37) per 1000 person-years of follow-up, respectively. The all-cause mortality proportion one year after LTX was 27% in the Achromobacter spp. infected patients and 12% in the uninfected patients (p = 0.114). Achromobacter spp. mainly affected LTXr with CF as the underlying disease and was rare in non-CF LTXr. Larger studies are needed to assess long-term outcomes of Achromobacter spp. in LTXr.

Chest computed tomography features of heart failure: A prospective observational study in patients with acute dyspnea.

BACKGROUND: Pulmonary congestion is a key component of heart failure (HF) that chest computed tomography (CT) can detect. However, no guideline describes which of many anticipated CT signs are most associated with HF in patients with undifferentiated dyspnea. METHODS: In a prospective observational single-center study, we included consecutive patients ≥ 50 years admitted with acute dyspnea to the emergency department. Patients underwent immediate clinical examination, blood sampling, echocardiography, and CT. Two radiologists independently evaluated all images. Acute HF (AHF) was adjudicated by an expert panel blinded to radiology images. LASSO and logistic regression identified the independent CT signs of AHF. RESULTS: Among 232 patients, 102 (44%) had AHF. Of 18 examined CT signs, 5 were associated with AHF (multivariate odds ratio, 95% confidence interval): enlarged heart (20.38, 6.86-76.16), bilateral interlobular thickening (11.67, 1.78-230.99), bilateral pleural effusion (6.39, 1.98-22.85), and increased vascular diameter (4.49, 1.08-33.92). Bilateral ground-glass opacification (2.07, 0.95-4.52) was a consistent fifth essential sign, although it was only significant in univariate analysis. Eighty-eight (38%) patients had none of the five CT signs corresponding to a 68% specificity and 86% sensitivity for AHF, while two or more of the five CT signs occurred in 68 (29%) patients, corresponding to 97% specificity and 67% sensitivity. A weighted score based on these five CT signs had an 0.88 area under the curve to detect AHF. CONCLUSIONS: Five CT signs seem sufficient to assess the risk of AHF in the acute setting. The absence of these signs indicates a low probability, one sign makes AHF highly probable, and two or more CT signs mean almost certain AHF.

Post-Transplantation Anemia and Risk of Death Following Lung Transplantation.

BACKGROUND: Post-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated. METHODS: We performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models. RESULTS: A total of 278 patients were included. At one and three years post-lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P = 0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P = 0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07). DISCUSSION: Post-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed.

Remote dielectric sensing to detect acute heart failure in patients with dyspnoea: a prospective observational study in the emergency department.

Aims: Remote dielectric sensing (ReDS) enables quick estimation of lung fluid content. To examine if ReDS is superior to other methods in detecting acute heart failure. Methods and results: We included consecutive patients with dyspnoea from the emergency departments at Bispebjerg Hospital, Copenhagen, and performed ReDS, low-dose chest computed tomography (CT), echocardiogram, lung ultrasound, NT-Pro-brain natriuretic peptide (NT-proBNP), and a Boston score evaluation (chest X-ray and clinical signs). ReDS values >35% were used as a cut-off to diagnose pulmonary congestion. Acute heart failure was adjudicated by experts' review of health records but independently of ReDS values. Sub-analyses investigated ReDS in acute heart failure patients with congestion on CT. We included 97 patients within a median of 4.8 h from admittance: 25 patients (26%) were ReDS-positive and 39 (40%) had adjudicated acute heart failure (21 with and 18 without CT congestion). Heart failure patients had median ReDS 33%, left ventricular ejection fraction 48%, and NT-proBNP 2935 ng/L. A positive ReDS detected heart failure with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS was like the Boston score (P = 0.88) and the lung ultrasound score (P = 0.74). CT-congested heart failure patients had higher ReDS values than patients without heart failure (median 38 vs. 28%, P < 0.001). Heart failure patients without CT-congestion had ReDS values like patients without heart failure (mean 30 vs. 28%, P = 0.07). Conclusion: ReDS detects acute heart failure similarly to the Boston score and lung ultrasound score, and ReDS primarily identifies the acute heart failure patients who have congestion on a chest CT.

Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients.

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1-91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

Lung Ultrasound to Phenotype Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. A Prospective Observational Study.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) are two distinct phenotypes of chronic lung allograft dysfunction (CLAD) in lung transplant (LTx) recipients. Contrary to BOS, RAS can radiologically present with a pleuroparenchymal fibroelastosis (PPFE) pattern. This study investigates lung ultrasound (LUS) to identify potential surrogate markers of PPFE in order to distinguish CLAD phenotype RAS from BOS. METHODS: A prospective cohort study performed at a National Lung Transplantation Center during June 2016 to December 2017. Patients were examined with LUS and high-resolution computed tomography of the thorax (HRCT). RESULTS: Twenty-five CLAD patients (72% males, median age of 54 years) were included, corresponding to 19/6 BOS/RAS patients. LUS-identified pleural thickening was more pronounced in RAS vs. BOS patients (5.6 vs. 2.9 mm) compatible with PPFE on HRCT. LUS-identified pleural thickening as an indicator of PPFE in RAS patients' upper lobes showed a sensitivity of 100% (95% CI; 54-100%), specificity of 100% (95% CI; 82-100%), PPV of 100% (95% CI; 54-100%), and NPV of 100% (95% CI; 82-100%). CONCLUSION: Apical pleural thickening detected by LUS and compatible with PPFE on HRCT separates RAS from BOS in patients with CLAD. We propose LUS as a supplementary tool for initial CLAD phenotyping.