Pseudomonas aeruginosa infection correlates with high MFI donor-specific antibody development following lung transplantation with consequential graft loss and shortened CLAD-free survival.

BACKGROUND: Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes. METHODS: A cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens. RESULTS: High MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival. CONCLUSIONS: P. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.

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 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.

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.

[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.

Seasonal changes of lower respiratory tract infections in lung transplant recipients during the first post-transplant year: The Hungarian experience.

BACKGROUND: After lung transplantation (LuTX) a high level of immunosuppression is needed to prevent rejection of the graft. Together with earlier colonization by pathogens, immunosuppression makes recipients more susceptible to infections, especially during the first postoperative year. As seasonality of lower respiratory tract infections (LRTI) is well-known in chronic lung diseases, we assessed seasonal changes of pathogen spectrum and number of infections in the first postoperative year in LuTX recipients. METHODS: LRTI were analyzed in 28 Hungarian adult LuTX patients. Incidence and spectrum of microorganism causing LRTI were evaluated according to post-transplant time and seasonal temperature and humidity changes. RESULTS: A total of 69 cases of LRTI were registered (average: 1.9 cases/patient; range: 0-14). Gram-negative=59, gram-positive=26, and fungal=31 pathogens were detected, with polymicrobial samples in 46% of all cases. Increased number of LRTI was observed in the cold season (1.68±1.54 vs 0.79±0.92 case/month/patient, P<.01) and significant negative correlations were identified between the incidence of polymicrobial and bacterial infections and temperature (r2 =0.1535, P<.05, r2 =0.3144, P<.01, respectively). In addition, positive correlation was observed between polymicrobial infections and humidity (r2 =0.1403, P<.05). Higher incidence of LRTI was also noted in the cold season, when accounting for the differences in immunosuppression. CONCLUSION: Seasons influenced the incidence of LRTI in the first postoperative year in LuTX recipients. More intensive vigilance for possible gram-negative and polymicrobial infections is needed in these patients in cold and wet seasons in the continental climate zone, regardless of underlying disease.

Circulating periostin level in asthmatic pregnancy.

OBJECTIVE: Asthma often complicates pregnancy and represents a risk for complications. Periostin is considered as a biomarker of asthma; however, as it also plays a role in normal gestation, pregnancy may influence circulating periostin levels. This is the first study assessing periostin in asthmatic pregnancy. METHODS: Plasma periostin levels were investigated in asthma (asthmatic non-pregnant, ANP; N = 19) and asthmatic pregnancy (AP; N = 14), compared to healthy non-pregnant controls (HNP; N = 12) and healthy pregnant women (HP; N = 17). The relationship between periostin levels and asthma control determinants was also evaluated. The diagnostic efficacy of periostin to detect uncontrolled asthma was analyzed using ROC analysis. RESULTS: Plasma periostin levels were similar in the HNP and ANP (55.68 [37.21-67.20] vs. 45.25 [32.67-64.55], p > 0.05), and elevated in the HP (68.81 [57.34-98.84] ng/mL, p = 0.02 vs. HNP) and AP groups (54.02 [44.30-74.94] ng/mL, p = 0.0346 vs. ANP). Periostin levels of the two pregnant groups were similar (p > 0.05). In AP women periostin correlated negatively with FEV1 (r = -0.5516) and positively with Raw (r = 0.5535; both p < 0.05). CONCLUSIONS: Pregnancy itself increases circulating periostin levels and this elevation is detectable in asthmatic pregnancy as well. Although periostin correlates with lung function in asthmatic pregnancy, periostin as a biomarker has to be handled with caution in pregnant patients due to the influence of pregnancy on its plasma level.

Circulating survivin levels in healthy and asthmatic pregnancy.

BACKGROUND: Asthma is one of the most common conditions which complicate pregnancy. Pro- and anti-apoptotic mechanisms can be modulated by asthma accompanying pregnancy. Survivin, an anti-apoptotic protein has been implicated in the pathomechanism of asthma and also in the development of pathological pregnancies; however survivin has not been studied in pregnant asthmatics. METHODS: Twenty-eight asthmatic pregnant (AP), 25 asthmatic non-pregnant (ANP), 21 healthy pregnant (HP) and 29 healthy non-pregnant (HNP) women were enrolled in this cross-sectional study. Plasma survivin concentration was determined by ELISA. RESULTS: Plasma survivin was significantly lower in HP (1.64 /0-74.9/ pg/ml) than in HNP (24.6 /0-333.3/ pg/ml, p = 0.01). However, this difference was not observed between the asthmatic groups (p = 0.64). Similarly, there was no difference either between HNP and ANP (10.5 /0-215.4/ pg/ml, p = 0.23) or between HP and AP (13.9 /0-364.1/ pg/ml, p = 0.30) groups. CONCLUSIONS: Decreased plasma survivin levels in physiological but not in asthmatic pregnancy may suggest that the normal apoptotic mechanisms are compromised in asthmatic gestation.

Changes in exhaled breath condensate pH in healthy and asthmatic pregnant women.

OBJECTIVE: Asthma is a common chronic disease complicating pregnancy with a risk for perinatal complications. Control of airway inflammation in the asthmatic pregnancy improves pregnancy outcomes. Our aim was to evaluate pH of exhaled breath condensate (EBC), a non-invasive method for the assessment of asthmatic airway inflammation, in healthy and asthmatic pregnancies. DESIGN: Cross-sectional study. SETTING: Hungarian university clinics. POPULATION: Seventeen healthy pregnant women, 21 asthmatic pregnant women, 23 healthy non-pregnant women and 22 asthmatic non-pregnant women. METHODS: EBC samples were collected using a portable condenser, EBC pH was measured after argon deaeration. MAIN OUTCOME MEASURE: EBC pH. RESULTS: EBC pH (mean ± SD) of healthy non-pregnant and asthmatic non-pregnant women was similar (7.75 ± 0.27 vs. 7.54 ± 0.57; p = 0.118), probably indicating an optimal control of airway inflammation in asthmatic women. On the other hand, EBC pH was higher in healthy pregnant women compared with healthy non-pregnant women (8.02 ± 0.43 vs. 7.75 ± 0.27; p = 0.017). Higher EBC pH accompanying healthy pregnancy was absent in asthmatic pregnant patients whose EBC pH was lower (7.65 ± 0.38) than that of healthy pregnant women (p = 0.006), and it was similar to that in asthmatic and healthy non-pregnant women (p = 0.470 and p = 0.300, respectively). The EBC pH in asthmatic pregnant women correlated positively with birthweight (r = 0.49, p = 0.047) and negatively with forced vital capacity (r = 0.45, p = 0.039). EBC pH was not related to blood pH. CONCLUSIONS: EBC pH is higher in healthy pregnant women but not in asthmatic pregnant women compared with data from healthy non-pregnant women, indicating that oxidative inflammatory processes induced by asthma may compromise the regulatory mechanisms causing alkaline pH in the airways during pregnancy.

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.

Peripheral T(h)1/T(h)2/T(h)17/regulatory T-cell balance in asthmatic pregnancy.

Asthma is a common chronic disease that may complicate pregnancy and a risk factor for complications; however, immunological mechanisms of the bilateral interactions between asthma and pregnancy are not fully understood. Healthy gestation is characterized by a sensitive balance of T(h)1/T(h)2/T(h)17/regulatory T (Treg) cells that may be altered in asthmatic pregnancy. The aim of this study was to describe the prevalence of these cell subsets in asthmatic compared with healthy pregnancy. The prevalence of T(h)1, T(h)2, T(h)17 and Treg lymphocytes was identified by cell surface and intracellular marker staining in blood samples of 24 healthy non-pregnant (HNP), 23 healthy pregnant (HP), 15 asthmatic non-pregnant (ANP) and 15 asthmatic pregnant (AP) women using flow cytometry. The T(h)1/T(h)2 cell ratio was decreased in both HP and ANP compared with HNP women; however, no further decrease was observed in the AP group. The T(h)17/Treg ratio was decreased in HP, but not in AP women, compared with HNP data. Healthy pregnancy increased Treg cell prevalence compared with HNP data (4.64% versus 2.98%; P < 0.05), and this pregnancy-induced elevation was absent in AP women (2.52% versus 4.64%; P < 0.05). T(h)17 cell prevalence was similar in the HP and HNP groups (2.78% versus 3.17%; P > 0.05). Asthma increased T(h)17 prevalence in non-pregnant patients (3.81% versus 3.17%; P < 0.05), and this asthma-specific increase of T(h)17 cell prevalence was also observed in AP patients (AP versus HP: 3.44% versus 2.78%; P < 0.05). The abnormal asthma-dependent T(h)17 elevation together with blunted Treg increase may play a role in the compromised immune tolerance characterizing asthmatic pregnancy.

Circulating and exhaled vascular endothelial growth factor in asthmatic pregnancy.

CONTEXT: Vascular endothelial growth factor (VEGF) plays a role in asthma and pathological pregnancies. OBJECTIVE: This is the first study assessing plasma and exhaled breath condensate VEGF levels in asthmatic pregnancy. MATERIAL AND METHODS: Thirty-one asthmatic pregnant, 29 asthmatic nonpregnant, 28 healthy pregnant and 22 healthy nonpregnant women were enrolled. Plasma was collected in all subjects, EBC in 57 volunteers for VEGF measurements. RESULTS: Plasma VEGF decreased in both pregnant groups (p < 0.01), without any differences between the asthmatic and the respective nonasthmatic groups (p > 0.05). VEGF was undetectable in EBC. CONCLUSION: Concomitant asthma does not affect plasma VEGF during pregnancy.

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.

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.

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.

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.

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.