Serum Progranulin Level Might Differentiate Non-IPF ILD from IPF.

Diagnosing interstitial lung disease (ILD) can be a challenging process. New biomarkers may support diagnostic decisions. Elevated serum progranulin (PGRN) levels have been reported in liver fibrosis and dermatomyositis-associated acute interstitial pneumonia. Our aim was to assess the role of PGRN in the differential diagnosis of idiopathic pulmonary fibrosis (IPF) and other ILDs. Serum levels of PGRN were measured by enzyme-linked immunosorbent assay in stable IPF (n = 40), non-IPF ILD (n = 48) and healthy controls (n = 17). Patient characteristics, lung function, CO diffusion (DLCO), arterial blood gases, 6-min walk test, laboratory parameters and high-resolution (HR)CT pattern were assessed. In stable IPF, PGRN levels did not differ from healthy controls; however, serum PGRN levels were significantly higher in non-IPF ILD patients compared to healthy subjects and IPF (53.47 ± 15.38 vs. 40.99 ± 5.33 vs. 44.66 ± 7.77 ng/mL respectively; p < 0.01). The HRCT pattern of usual interstitial pneumonia (UIP) was associated with normal PGRN level, while for non-UIP patterns, significantly elevated PGRN level was measured. Elevated serum PGRN levels may be associated with non-IPF ILD, especially non-UIP patterns and might be helpful in cases of unclear radiological patterns in the differentiation between IPF and other ILDs.

Post-COVID interstitial lung disease in symptomatic patients after COVID-19 disease.

COVID-19 is often associated with long-lasting pulmonary symptoms. Data are scarce about interstitial lung disease (ILD) in patients following COVID-19 hospitalization with persistent symptoms. We retrospectively reviewed all cases sent to pulmonary post-COVID evaluation due to persistent symptoms between February 2021 and February 2022 (N = 318). All patients with suspected ILD (N = 44) were reviewed at the multidisciplinary discussion. Patient characteristics, symptoms, time since hospitalization, detailed lung function measurements and 6-min walk test (6MWT) were evaluated. The post-COVID ILD suspected group included more men (68.2 vs. 31.8%) with significantly older age compared to the control group (64.0 ± 12.3 vs. 51.3 ± 14.9 years). Most patient needed hospital care for COVID-19 pneumonia (68.6% of all patients and 84.1% of ILD suspected group) and average time since hospitalization was 2.4 ± 2.3 months. Persisting symptoms included fatigue (34%), dyspnoea (25.2%), cough (22.6%), and sleep disorders (insomnia 13.2%; sleepiness 8.2%). Post-COVID ILD presented more often with new symptoms of cough and sleepiness. Functional impairment, especially decreased walking distance and desaturation during 6-min walk test (6MWT) were detected in the ILD-suspected group. Respiratory function test in the post-COVID ILD group showed slight restrictive ventilatory pattern (FVC: 76.7 ± 18.1%, FEV1: 83.5 ± 19.1%, TLC: 85.6 ± 28.1%) and desaturation during 6MWT were detected in 41% of patients. LDCT changes were mainly ground glass opacities (GGO) and/or reticular abnormalities in most cases affecting < 10% of the lungs. Our data indicate that suspected post-COVID ILD is affecting 13.8% of symptomatic patients. High resolution chest CT changes were mainly low extent GGO/reticulation, while long-term lung structural changes need further evaluation.

Lung Transplant Rehabilitation-A Review.

BACKGROUND: Both lung transplant recipients and candidates are characterised by reduced training capacity and low average quality of life (QoL). This review investigates the impact of training on exercise ability and QoL in patients before and after lung transplant. METHODS: Searches were conducted from the beginning to 7 March 2022 using the terms "exercise," "rehabilitation," "lung transplant," "exercise ability," "survival," "quality of life" and "telerehabilitation" in six databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, CINAHL, Nursing and Allied Health, and Scopus. The inclusion criteria were studies evaluating the effects of an exercise training programme concurrent with lung transplantation as well as patients and candidates (>18 years old) through any lung diseases. The term "lung transplant rehabilitation" was used to refer to all carefully thought-out physical activities with the ultimate or intermediate objective of improving or maintaining physical health. RESULTS: Out of 1422 articles, 10 clinical- and 3 telerehabilitation studies, candidates (n = 420) and recipients (n = 116) were related to the criteria and included in this review. The main outcome significantly improved in all studies. The 6-min walk distance, maximum exercise capacity, peak oxygen uptake, or endurance for constant load rate cycling improved measuring physical activity [aerobic exercises, breathing training, and aerobic and inspiratory muscle training sessions (IMT)]. Overall scores for dyspnoea improved after exercise training. Furthermore, health-related quality of life (HRQOL) also improved after aerobic exercise training, which was performed unsupervised or accompanied by breathing sessions. Aerobic training alone rather than combined with inspiratory muscle- (IMT) or breathing training enhanced exercise capacity. CONCLUSION: In conclusion, rehabilitation programmes seem to be beneficial to patients both preceding and following lung transplantation. More studies are required to determine the best training settings in terms of time scale, frequency, and work intensity in terms of improving exercise ability, dyspnoea, and HRQOL.

Remdesivir in Solid Organ Recipients for COVID-19 Pneumonia.

Solid organ transplant (SOT) recipients represent a vulnerable patient population and are of high risk for airborne viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Treatment of COVID-19 is still challenging, as no proven therapeutic regimen is available for immunocompromised patients. Our aim was to evaluate the efficacy and safety of remdesivir (RDV) therapy in infected hospitalized SOT patients. All transplanted recipients (N = 25; lung: 19; kidney: 3, liver: 2, heart: 1) who needed hospital care were reviewed in the time period between September 2020 and May 2021 out of the 945 patients treated at the Department. Case control matched patients receiving RDV (all in need of supplementary oxygen) and standard of care (SOC) were included as controls. Among the 25 SOT patients (female:male = 11:14; average age = 53.2 ± 12.7 years), 15 received RDV medication (RDV-TX), and in 10 cases SOC treatment was used (SOC-TX). Significantly worse clinical score was noted in RDV patients compared with RDV-TX; however, transfer to a higher intensity care unit as well as 60-day survival of RDV-TX patients were significantly worse. All SOT fatalities within 60 days of follow-up were lung transplant recipients (6 out of 19 lung transplant patients). No adverse events were noted related to RDV therapy. In SOT patients, especially lung transplant recipients, with severe COVID-19 needing supplementary oxygen, RDV treatment was safe; however, outcome was significantly worse as compared with nontransplanted individuals with initially worse clinical parameters.

Post-COVID Subacute Thyroiditis and Bronchiolitis in a Lung Transplant Recipient: A Case Report.

Lung transplant recipients are at risk for life-threatening infections including severe acute respiratory syndrome coronavirus 2-associated COVID-19. Several viral infections have been associated with the development of chronic lung allograft dysfunction. Long-term outcomes of COVID-19 on graft function are not known. A 53-year-old female patient, who underwent bilateral lung transplantation 3 years before because of stage IV sarcoidosis and secondary pulmonary hypertension was admitted in the second wave of the pandemic because of COVID-19 with symptoms including dry cough. Chest computed tomography showed ground glass opacities affecting 25% to 50% of the lung parenchyma. She was admitted to the COVID-19 Unit of our clinic. She received oxygen via nasal cannula, remdesivir, and low-dose methylprednisolone while mycofenolate acid administration was stopped. Her clinical condition improved. The first follow-up visit 1 month after the infection demonstrated deterioration in lung function. Computed tomography scan showed almost complete resolution; transbronchial biopsy was performed and proved acute allograft rejection. During the hospitalization a new onset atrial fibrillation was confirmed. In the background of atrial fibrillation and simultaneous neck pain, severe hyperthyroidism was proven. Because of thyroiditis and lung allograft rejection, high-dose steroid treatment was initiated and everolimus was added to the immunosuppressive therapy. Donor specific antibodies were also detected, hence plasmapheresis was indicated and continued with photoferesis. On the follow-up spirometry the values were stable; however, they did not reach pre-COVID levels. In lung transplant recipients COVID-19 might trigger allograft rejection in addition to virus-related thyroid disease.

Clinical Predictors of Lung-Function Decline in Systemic-Sclerosis-Associated Interstitial Lung Disease Patients with Normal Spirometry.

Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = −67.5 and IPF = −65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of −153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline.

Serological findings following the second and third SARS-CoV-2 vaccines in lung transplant recipients.

INTRODUCTION: Lung transplant recipients (LuTX) represent a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though many vaccines are already developed, more clinical data need to support effective immunological response in immunocompromised patients. METHODS: Stable LuTX recipients with no medical history of coronavirus disease (COVID-19) were enrolled. Currently available messenger RNA (mRNA) (BNT162b2-mRNA, mRNA-1273) and non-mRNA (ChAdOx1, BBIBP-CorV) vaccines were given according to availability, boosters were all mRNA-based. SARS-CoV-2 Spike1 immunoglobulin G (IgG) antibody titer was evaluated before and 2 weeks after second and third dose. Difference between mRNA versus non-mRNA vaccines was assessed. RESULTS: Forty-one patients (49% men, age 48.4 ± 13.8 years) received two doses of SARS-CoV-2 vaccines: 23 of mRNA, 18 of non-mRNA, and 24/41 (58%) received a third dose. Median 92 months passed since transplantation, and serum level of tacrolimus was median 5.5 ng/ml. Positive serology was found in 37% of all patients after the second dose, 86% had mRNA vaccine. After the third dose, 29% became positive who had no antibody before. Significantly higher level of antibody was found after the second mRNA than non-mRNA vaccines (2.2 vs. 1568.8 U/ml, respectively, p = .002). 6/23 (26%) patients received two doses of mRNA vaccine developed COVID-19 after the second injection in an average of 178 days, half of them recovered, half of them died in intensive care unit (ICU). 3/6 (50%) patients with two doses mRNA and recovered from COVID-19 had significantly higher level of antibody (average 20847.3 U/ml) than without infection. After the booster vaccine, 1/24 (4%) developed infection. CONCLUSION: Immunosuppression therapy may induce a weaker SARS-CoV-2 response in LuTX recipients; therefore, third dose is a priority in transplanted patients. The highest antibody level was measured recovering from COVID after two doses. Our data confirm that booster mRNA vaccine could increase antibody levels, even if immunization was started with non-mRNA vaccine.

Peripheral blood and bronchoalveolar leukocyte profile in lung transplant recipients and their changes according to immunosuppressive regimen: A single-center experience.

BACKGROUND: After lung transplantation (LuTX), lower respiratory tract infections (LRTI) and acute cellular rejection (ACR) are associated with changes in peripheral blood and bronchoalveolar lavage fluid mononuclear cell profile (PBMC and BALIC). PBMC is also influenced by immunosuppressive regimen and its changes with postoperative time. First-year PBMC and BALIC changes were evaluated in this study with rabbit anti-thymocyte globulin (ATG) and alemtuzumab (AL) induction therapy. METHODS: In total, 64 LuTX recipients were included, 53 of them received AL and 11 ATG as induction therapy. PBMC and BALIC were examined routinely and in cases suspicious of infection and/or rejection. A PBMC- and BALIC-based algorithm for infection and rejection prediction was also tested. RESULTS: In the AL group, peripheral blood lymphocyte and basophil cell numbers were significantly reduced, while the neutrophil cell number elevation during LRTI was significantly higher compared to the control. Early postoperative measurements showed a lower BALIC lymphocyte count. The algorithm had 17% sensitivity and 94% specificity for ACR in all patients and 33% sensitivity and 95% specificity for ACR with coexisting LRTI. CONCLUSION: BALIC is not significantly influenced by the immunosuppressive regimen. PBMC- and BALIC-based algorithm may improve the differential diagnosis of ACR.

Treatment and Systemic Sclerosis Interstitial Lung Disease Outcome: The Overweight Paradox.

(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated in a real-world setting. (2) Methods: All SSc-ILD cases previously confirmed by rheumatologists and a multidisciplinary ILD team between January 2017 and June 2019 were included (n = 54). The detailed medical history, clinical parameters and HRCT were analyzed. The longitudinal follow-up for pulmonary symptoms, functional parameters and treatment were performed for at least 2 years in no treatment, immunosuppression and biological treatment subgroups. (3) Results: In SSc-ILD patients (age 58.7 ± 13.3 years, 87.0% women), the main symptoms included dyspnea, cough, crackles and the Raynaud's phenomenon. The functional decline was most prominent in untreated patients, and a normal body mass index (BMI < 25 kg/m2) was associated with a significant risk of deterioration. The majority of patients improved or were stable during follow-up. The progressive fibrosing-ILD criteria were met by 15 patients, the highest proportion being in the untreated subgroup. (4) Conclusions: SSc-ILD patients who are overweight are at a lower risk of the functional decline and progressive phenotype especially affecting untreated patients. The close monitoring of lung involvement and a regular BMI measurement are advised and early treatment interventions are encouraged.

The effectiveness of pulmonary rehabilitation in connection with lung transplantation in Hungary.

BACKGROUND: The role of pre- and post-lung transplant rehabilitation is to maintain or improve exercise tolerance, lung mechanics, peripheral and respiratory muscle function. Our aim was to measure the effectiveness of pre- and post-transplant rehabilitation in terms of the changes of functional and quality of life markers. METHODS: Sixty-three patients (40 COPD FEV1: 21±5%pred, 18 IPF TLC: 42±13%pred, 4 bronchiectasis FEV1: 28±4%pred and 1 alveolitis fibrotisans TLC: 31%pred) participated in a pre- and 14 took part in a post-transplant rehabilitation program (more than 2 months after lung transplantation (LTx), primary diagnoses: 9 COPD, 4 IPF). The rehabilitation program consisted of chest-wall stretching, controlled breathing techniques and personalized exercise of 20-30 minutes by cycling and treadmill 2-3 times per day for 4 weeks. Seven functional and quality of life markers, like lung function, chest wall expansion (CWE), 6-minute walking distance (6MWD), modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), breath holding time (BHT) and hand grip strength (HGS) were measured at the onset and the end of the rehabilitation program. The safety profile of the rehabilitation program was followed-up. RESULTS: Pre-transplant pulmonary rehabilitation resulted in significant improvement in CWE (3.24±1.49 vs. 4.48±1.62 cm), CAT IQR {19 [13-25] vs. 15 [11-21]}, 6MWD (315±118 vs. 375±114 m), P<0.05. FEV1, FVC, mMRC, BHT and HGS did not change significantly. Post-transplant rehabilitation resulted in significant improvement in CWE (3.7±2.1 vs. 6.2±1.8 cm), CAT IQR {17 [11-23] vs. 10 [6-14], BHT (22±14 vs. 35±16 s), FEV1 (73±8 vs. 86±9%pred) and FVC (70±12 vs. 85±14%pred), P<0.05. The 6MWD, mMRC and HGS did not change significantly. No cardiovascular or other side effects were detected during the rehabilitation program. CONCLUSIONS: Our results underline the importance of perioperative pulmonary rehabilitation in the complex treatment of lung transplant patients in Hungary, as well. There was a limitation because no control group was evaluated without rehabilitation.

Autoimmune Progressive Fibrosing Interstitial Lung Disease: Predictors of Fast Decline.

A subset of interstitial lung diseases (ILDs) with autoimmune traits-including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)-develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.

Impact of interstitial lung disease and simultaneous lung cancer on therapeutic possibilities and survival.

BACKGROUND: Fibrosing interstitial lung diseases (ILDs) are associated with poor survival and an increased risk of developing lung cancer (LC). Patient and LC characteristics, therapeutic possibilities and survival in this rare patient population are not well established. METHODS: Fibrosing ILD patients treated at the Department of Pulmonology Semmelweis University were reviewed retrospectively between 2012-2018 (N = 160). All patients with concomitant LC (N = 23) underwent detailed pulmonary evaluation. Cancer characteristics including driver mutation data, as well as therapy and survival were analyzed. RESULTS: ILD-LC patients (56% men, mean age 73 ± 6 years) had mild-moderate lung functional impairment (forced vital capacity [FVC]: 80 ± 24%ref., forced expiratory volume in one second [FEV1]: 76 ± 27%ref.; transfer factor of the lung for carbon monoxide [TLCO]: 62 ± 25% reference). In 56% of cases histology confirmed adenocarcinoma followed by squamous cell carcinoma in 26%. Lobectomy could only be performed in one case; driver mutation was present in one patient. Chemotherapy was most commonly administered; however, 26% could only receive supportive palliative care. Four idiopathic pulmonary fibrosis patients received concomitant nintedanib to their LC treatment. Median survival of ILD-LC patients was only 321 days. CONCLUSIONS: Diagnosis and therapy of ILD-LC is challenging and patients have a very limited survival. A significant proportion of patients could only receive palliative care indicating the need for better management strategies in this special patient population. The evaluation of the effect of cotreatment with antifibrotics needs further study. KEY POINTS: Interstitial lung diseases are often associated with lung cancer Diagnosis is challenging and therapy often limited due to underlying lung disease. Patients received platinum based chemotherapy or only supportive care.

Lung Function Changes are More Common in Marfan Patients Who Need Major Thoracic Surgery.

INTRODUCTION: Marfan syndrome is a genetic disorder affecting the connective tissue. Changes in lung tissue might influence respiratory function; however, a detailed respiratory functional assessment according to the need for major thoracic surgery is missing. METHODS: Comprehensive pulmonary examinations were performed in 55 Marfan patients including respiratory symptoms, lung function (LF) testing using European Coal and Steel Community (ECSC) reference values, TLCO and quality of life measurements. Groups included patients who did not need surgery (Mf, n = 32) and those who underwent major thoracic surgery (Mfop, n = 23). RESULTS: Respiratory symptoms affected 20% of patients. Scoliosis was significantly more frequent in the Mfop group. LF demonstrated in all Marfan patients a tendency towards airway obstruction (FEV1/FVC = 0.77 ± 0.10), more prominent in Mfop patients (0.74 ± 0.08 vs. Mf: 0.80 ± 0.11; p = 0.03). Correction of LF values using a standing height modification by arm span (Hcorrected) revealed additional changes in FVC and FEV1. TLCO and quality of life did not differ between groups. CONCLUSIONS: Marfan syndrome is associated with airway obstruction, especially in patients who have undergone major thoracic surgery, indicative of more severe connective tissue malfunction. The use of arm span for height correction is suitable to evaluate LF changes in this special patient group including patients with significant scoliosis.

First 3 Years of the Hungarian Lung Transplantation Program.

In this article we summarize the results of the first 3 years after launching the Hungarian Lung Transplantation Program. PATIENTS AND METHODS: The first lung transplant in Hungary was carried out on December 12, 2015, with the collaboration of the National Institute of Oncology and the Semmelweis University. Up to December 31, 2018, a total of 62 lung transplants were performed. Data were analyzed retrospectively. Patients were listed for lung transplant after the indication was established by the National Lung Transplantation Committee. Donor lungs were procured from brain-dead donors only. RESULTS: Within this period our team was involved in 87 lung procurements, 61 of which resulted in bilateral lung transplant and 1 in single-sided transplant. The operative approach was unilateral thoracotomy (n = 1), bilateral thoracotomy (n = 1), or clamshell incision (n = 60) with venoarterial extracorporeal membrane oxygenation support. The underlying disease of the recipients was obstructive lung disease (n = 30), lung fibrosis (n = 11), cystic fibrosis (n = 18), primary pulmonary hypertension (n = 2), histiocytosis-X syndrome (n = 1), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and retransplant because of bronchiolitis obliterans syndrome (n = 1). The youngest patient was 13 years of age, while the oldest was 65 years. Three patients died in the early postoperative phase. One-year survival was 80%. DISCUSSION: The number of cases rises steadily in the Hungarian Lung Transplantation Program, which is exceptional compared with the start of other centrums. The incidence of complications and mortality is comparable with those of other experienced centers around the world. Our future goal is to broaden our waiting list, thus increasing the number of lung transplants carried out.

Testicular Cancer in a Lung Transplant Patient With Cystic Fibrosis: A Case Report.

BACKGROUND: Cystic fibrosis (CF) is one of the most common genetic disorders that develops from a mutation of the cystic fibrosis transmembrane regulator gene. Patients with CF are known to be at risk for malignancies, and lung transplantation-associated immunosuppression further increases this risk. CASE REPORT: We describe a case of a 29-year-old male patient with CF who developed testicular cancer 14 months after a lung transplantation. Immunosuppressive therapy included antithymocyte globulin induction and tacrolimus, mycophenolate, and prednisolone maintenance therapy as compared to standard alemtuzumab induction, followed by tacrolimus and prednisolone, as used in our center. He underwent semicastration and refused chemotherapy. Immunosuppressive treatment was changed to tacrolimus, everolimus, and prednisolone, which did not influence excellent graft function. This case report highlights the importance of uro-oncological observation of patients with CF following lung transplantations.

Soluble Urokinase-Type Plasminogen Activator Receptor and Arterial Stiffness in Patients with COPD.

INTRODUCTION: Soluble urokinase-type plasminogen activator receptor (suPAR) is upregulated by inflammation and plays a role in the pathogenesis of atherosclerosis. Chronic obstructive pulmonary disease (COPD) is associated with enhanced systemic inflammation and increased risk for atherosclerosis, however, studies analysing the circulating suPAR levels in COPD are contradictory. The aim of the study was to investigate plasma suPAR concentrations together with markers of arterial stiffness in COPD. MATERIALS AND METHODS: Twenty-four patients with COPD and 18 non-COPD, control subjects participated in the study. Plasma suPAR was measured, together with lung volumes, symptom burden, exacerbation history, markers of arterial stiffness and soluble inflammatory biomarkers, such as endothelin-1, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6). RESULTS: Plasma suPAR levels were higher in COPD (2.84 ± 0.67 ng/ml vs. 2.41 ± 0.57 ng/ml, p = 0.03) and were related to lung function measured with FEV1 (r = - 0.65, p < 0.01) and symptom burden determined with the modified Medical Research Council questionnaire (r = 0.55, p < 0.05). Plasma suPAR concentrations correlated with various measures of arterial stiffness in all subjects, but only with ejection duration in COPD (r = - 0.44, p = 0.03). CONCLUSIONS: Plasma suPAR levels are elevated in COPD and relate to arterial stiffness. Our results suggest that suPAR may be a potential link between COPD and atherosclerosis.

Long-Term Effects and Adverse Events of Nintedanib Therapy in Idiopathic Pulmonary Fibrosis Patients with Functionally Advanced Disease.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is one of the most common interstitial lung diseases with limited survival. The effect of IPF therapy in patients with severely impaired lung function is not well established. The aim of this study was to characterize IPF patients with a forced vital capacity (FVC) < 50% (group 1) and FVC 50-60% predicted (group 2) and analyze the effect and adverse events of nintedanib in Hungarian patients diagnosed between April 2015 and July 2017. METHODS: The impact of nintedanib therapy on lung function, survival, and adverse events was analyzed longitudinally. RESULTS: Twenty-two out of 103 patients were included in the analysis (group 1: N = 10; male/female = 6:4, age 62.6 ± 10.8 years and group 2: N = 12; male/female = 3:9, age 65.7 ± 11.6 years). Eighteen patients were treated with nintedanib (8 in group 1, 10 in group 2); treatment stabilized lung function in 42% and 50%, respectively, in the two groups. Median survival was 444 days for group 1 and 476 days for group 2. Adverse events were less common than in clinical trials; dose reduction was necessary in three cases, drug discontinuation in two cases. No differences between groups were identified regarding clinical parameters and radiological pattern; however, hypertension as comorbidity was more common in group 1 patients. CONCLUSIONS: Nintedanib therapy was effective and well tolerated even among patients with severely impaired lung function. Longitudinal follow-up confirmed high mortality in patients with very severe and severe IPF; however, median survival was meaningful as it exceeded 1 year in both groups.

[The start of the Hungarian lung transplantation program and the first results]. / A magyar tüdotranszplantációs program indulása és elso eredményei.

The first lung transplantation in Hungary was performed on 12th of December, 2015. It was a joint effort of the National Institute of Oncology and the Semmelweis University. Hereby we summarise the results and experiences from the first three years. Until August, 2018, 55 lung transplantations were performed in Hungary. This was a retrospective analysis. All patients were listed according to the recommendation of the Lung Transplantation Committee. All implanted lungs have been procured from brain dead donors. Postoperative treatment and rehabilitation of the patients were continued at the Semmelweis University. Between 12. 12. 2015 and 31. 07. 2018, our team performed 76 organ retrievals: out of 45 Hungarian offers, 23 came from Eurotransplant countries and 8 outside of the Eurotransplant region. From these donations, 54 double and 1 single side transplantations were successfully performed. The surgical approach was single side thoracotomy (n = 1), bilateral thoracotomy (n = 1) and in the majority of the cases clamshell incision (n = 53). For the intraoperative veno-arterial extracorporeal membrane oxygenation support was used. The extracorporeal membrane oxygenation support had to be prolonged in 3 patients into the early postoperative period, two other recipients were bridged to transplant with extracorporeal membrane oxygenation. In the same time period, one combined lung-kidney transplantation was also performed. The distribution of recipients according to the underlying disease was: chronic obstructive pulmonary disease (n = 28); idiopathic pulmonary fibrosis (n = 8); cystic fibrosis (n = 12); primary pulmonary hypertension (n = 2); hystiocytosis-X (n = 1); bronchiectasis (n = 2); lymphangioleiomyomatosis (n = 1); and re-transplantation following bronchiolitis obliterans syndrome (n = 1), respectively. The mean age of recipients was 47.5 ± 15.18 years. The youngest recipient was 13 years old. We unfortunately lost 12 patients on our waiting list. The mean intensive care unit stay was 24.6 ± 18.18 days. Two patients were lost in the early postoperative phase. Tracheostomy was necessary in 13 cases due to the need of prolonged ventilation. 1-year survival of the recipients was 82.96% (until 31. 07. 2018). When looking at the first three years of the program, the case numbers elevated quickly throughout the years which is rather unique when compared to other centres in their starting period. Perioperative mortality and morbidity is comparable with high-volume lung transplantation centres. In the future we would like to increase the number of patients on the waiting list, thus increasing the total number of transplantations performed, and we are also planning to implement the use of the ex vivo lung perfusion system (EVLP) in our program. Orv Hetil. 2018; 159(46): 1859-1868.

Peripheral CD4+ T-cell changes in connective tissue diseases.

Connective tissue diseases (CTDs) are all characterized by changes in the adaptive immune system. In the last few decades several CD4 + T lymphocytes and their products have been associated with the development, progression, organ involvement, or therapeutic response of different CTDs. The T helper (Th) T-cell subsets are easy to measure in the peripheral blood, however changes are difficult to interpret. This review summarizes data about Th1/Th2/Th17 and regulatory T-cell (Treg) changes in the most common CTDs. Concordance and divergence of data might help in the better understanding of the common processes of these different systemic autoimmune disorders and might give future clues for differences in disease behavior and treatment response.

Circulating Clusterin and Osteopontin Levels in Asthma and Asthmatic Pregnancy.

Asthma in pregnancy poses a risk of adverse outcomes. Osteopontin and clusterin emerged as asthma biomarkers; however, their circulating levels during pregnancy are unknown yet. This cross-sectional study investigated peripheral osteopontin and clusterin levels and their relationship to disease control in 26 asthmatic pregnant (AP), 22 asthmatic nonpregnant (ANP), and 25 healthy pregnant (HP) women and 12 healthy controls (HNP). Osteopontin levels of ANP and HNP were similar (2.142 [1.483-2.701] versus 2.075 [1.680-2.331] ng/mL, p = 0.7331). Pregnancy caused a marked elevation in both healthy (HP: 3.037 [2.439-4.015] ng/ml, p = 0.003 versus HNP) and asthmatic (AP: 2.693 [1.581-3.620] ng/ml) patients; thus the pregnant groups did not differ (p = 0.3541). Circulating clusterin levels were comparable in ANP and HNP (109.2 [95.59-116.3] versus 108.8 [97.94-115.3] µg/mL, p = 0.8730) and the level was lower in HP (98.80 [84.26-105.5] µg/mL, p = 0.0344 versus HNP). In contrast, the level was higher in AP (111.7 [98.84-125.6] µg/mL, p = 0.0091 versus HP). In ANP, a positive correlation of PEF (r = 0.3405; p = 0.0221) and a negative correlation of Raw (r = -0.3723; p = 0.0128) to clusterin level were detected. Circulating osteopontin level increases in pregnancy regardless of concomitant well-controlled asthma, indicating its gestational role. Clusterin level decreases in healthy but not in asthmatic pregnancy and correlates directly with lung function.