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.

[Pulmonary manifestations in systemic lupus erythematosus]. / A szisztémás lupus erythematosus pulmonalis manifesztációi.

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

[Epidemiological and treatment characteristics of patients with chronic obstructive pulmonary disease on maintenance inhaled therapy between 2011 and 2019 in Hungary]. / A krónikus obstruktív tüdobetegség miatt fenntartó inhalációs kezelésben részesült betegek epidemiológiai és terápiás jellemzoi 2011 és 2019 között Magyarországon.

Introduction: Morbidity and mortality due to chronic obstructive pulmonary disease (COPD) are on the rise worldwide. The cornerstone of treatment is maintenance inhaled therapy and the patients' good treatment adherence. Objective: To determine epidemiological and treatment characteristics of patients treated with COPD in Hungary. Methods: Using data from the National Health Insurance Fund, we recruited patients under maintenance inhaled therapy due to COPD between 2011 and 2019 (aged >40 years, who filled in at least one prescription of a maintenance inhaled drug for ICD (International Classification of Diseases) code J44, which was followed by two further prescriptions within 1 year). Data of patients were analysed every year after inclusion. Findings on age, sex, inhaled therapies, and the use of retard oral theophylline were compared among the years (chi2 test). Results: In total, 227,251 patients were included (2011­2019: 81,308­160,241 patients/year). In 2011, most patients were >70 years of age and males, while in 2019, most patients were 60­69 years old and females. The proportion of patients filling in a prescription for mono-bronchodilators or inhaled corticosteroids decreased in the observational period, while dual bronchodilators became available, and their use gradually increased. The adherence to maintenance inhaled therapies was good (>180 days/year) only in approximately half of the population (51.6% in 2019). The number of patients filling in prescriptions for oral theophylline did not decline in the observation period (32% in 2019). Discussion: Between 2011 and 2019, the number of COPD patients on maintenance inhaled therapy did not reach that of the registered patients. Adherence to maintenance inhaled treatment is inadequate in a significant portion of patients. The rate of patients taking oral theophylline is high. Conclusion: Improvement of adherence to maintenance inhaled therapies is essential for a better prognosis of COPD in Hungary. Orv Hetil. 2024; 165(9): 338­345.

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.

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.

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.

Worse lung cancer outcome in patients with lower respiratory tract infection confirmed at time of diagnosis.

BACKGROUND: Pulmonary malignancy is one of the most frequent and fatal cancers in older patients. As data on lower respiratory tract infection (LRTI) and the outcome of lung cancer are scarce, our objective was to determine the impact of LRTI on therapeutic possibilities and one-year mortality. METHODS: Patients undergoing bronchoscopy in 2017 who had bronchial microbial sampling at the time of the lung cancer diagnosis (n = 143) were included. Group 1 (LRTI+) included patients with confirmed infection (n = 74) while Group 2 (LRTI-) included patients without infection (n = 69). Clinical characteristics, pathogen profile and one-year survival were analyzed. RESULTS: Age, gender, TNM stage, histology type, comorbidities or underlying lung disease did not differ among groups. The most common LRTI pathogens included aerobic (n = 49), anaerobic (n = 14) and fungal (n = 26) infections. Chemo/immune/target therapy alone, or in combination with radiotherapy were significantly less frequently used, whilst palliative care was more common in Group 1 (LRTI+). Multiple pathogen LRTI patients were significantly older, less frequently diagnosed with adenocarcinoma and had worse performance status compared to solitary pathogen LRTI patients. One-year median survival was 274 days (235 vs. 305 days Group 1 vs. Group 2). Risk factors for increased one-year mortality included performance status ≥2 (OR 30.00, CI 95% 5.23-313.00), performance status 1 (OR 11.87, CI 95% 4.12-33.78), male gender (OR 4.04, CI 2.03-8.04), LRTI with multiple pathogens (OR 2.72, CI 1.01-6.81) and nonadenocarcinoma histology (OR 2.26, CI 1.15-4.56). CONCLUSION: LRTIs in lung cancer patients, especially multiple pathogen infections, are associated with less oncotherapeutic possibilities and significant risk for lower one-year median survival.

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.

Impact of wastewater on fish health: a case study at the Neckar River (Southern Germany) using biomarkers in caged brown trout as assessment tools.

The present work describes a field survey aiming at assessing the impact of a sewage treatment plant (STP) effluent on fish health by means of biomarkers. Indigenous fish were absent downstream of the STP. To elucidate the reason behind this, brown trout (Salmo trutta f. fario) were exposed in floating steel cages up- and downstream of a STP located at the Neckar River near Tübingen (Southern Germany), for 10 and 30 days. A combination of biomarker methods (histopathological investigations, analysis of the stress protein Hsp70, micronucleus test, B-esterase assays) offered the possibility to investigate endocrine, geno-, proteo- and neurotoxic effects in fish organs. Biological results were complemented with chemical analyses on 20 accumulative substances in fish tissue. Even after short-term exposure, biomarkers revealed clear evidence of water contamination at both Neckar River sites; however, physiological responses of caged brown trout were more severe downstream of the STP. According to this, similar bioaccumulation levels (low µg/kg range) of DDE and 12 polycyclic aromatic hydrocarbons (PAHs) were detected at both sampling sites, while up to fourfold higher concentrations of four PAHs, methyl-triclosan and two synthetic musks occurred in the tissues of downstream-exposed fish. The results obtained in this study suggest a constitutive background pollution at both sites investigated at the Neckar River and provided evidence for the additional negative impact of the STP Tübingen on water quality and the health condition of fish.

(Eco)toxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) in zebrafish (Danio rerio) and permanent fish cell cultures.

2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a high-production volume chemical used in paper, ink, pesticide, and adhesive industries as a wetting and anti-foaming agent. The physicochemical properties and slow biodegradation rate of TMDD indicate a low bioaccumulation potential but a high prevalence in the environment. As a consequence, TMDD has been detected in several European rivers in the nanogram per liter and lower microgram per liter range; however, its environmental risk to aquatic organisms is considered low. Recent studies almost exclusively focused on acute effects by TMDD, little is known about cytotoxic and genotoxic effects, reproduction and developmental toxicity, endocrine disruption, and any kind of long-term toxicity and carcinogenicity so far. The present study aims to provide more specific baseline information on the ecotoxicological effects of TMDD in fish. For this end, cyto- and genotoxicity assays were carried out in vitro with the permanent fish cell line RTL-W1; in addition, in vivo studies were conducted with the early life stages of zebrafish (Danio rerio) in order to fill the data gaps in developmental toxicity and endocrine disruption. TMDD showed a cytotoxic and slight genotoxic potential in fish cell lines; moreover, various sublethal and lethal effects could be detected in developing zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD; however, mortality following prolonged exposure to TMDD during fish sexual development test was clearly higher than mortality in the fish embryo test after 96-h exposure. Our results thus confirmed previous findings of laboratory screening tests, suggesting short-term toxic effects of TMDD in the intermediate, and long-term effects in the lower milligram per liter range.

Peripheral CD4+ cell prevalence and pleuropulmonary manifestations in systemic lupus erythematosus patients.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease involving several organs, including the lungs. Previous results confirmed changes of peripheral T cell subsets in lupus patients; however no data are available about their possible relationship with pulmonary involvement. OBJECTIVE: To determine pulmonary manifestations and potential relationship in changes of peripheral CD4+ T cell subsets. METHODS: Patients with SLE (N = 28) were enrolled in complex pulmonary examination. Patients were divided into groups with pleuropulmonary manifestations (SLEpulm N = 13 age: 44.9 ± 3.3 years, female: male = 11:2) or without (SLEc N = 15 age: 27.2 ± 3.7 years, female: male = 12:3). Peripheral blood was taken for T helper (Th)1, Th2, Th17, CD4+CD25hi+ and regulatory T (Treg: CD4+CD25hi+ CD127-) cell analysis from SLE patients and healthy volunteers (controls, N = 40). RESULTS: SLEpulm patients were older, had more pulmonary symptoms and significantly decreased pO2 as compared to SLEc group. Ventilatory disorder was present in 92% of SLEpulm patients, with significantly decreased lung volumes, signs of airway involvement and decrease in DLco. Significant increase in Th1/Th2, while decrease in Th17/Treg ratios was present in all SLE compared to controls. In SLEpulm CD4+CD25hi+ subset without changes in Treg number was significantly increased as compared to SLEc and this subgroup of T cell showed significant positive correlation with dynamic lung function parameters and DLco (p < 0.05). CONCLUSION: In lupus patients pleuropulmonary manifestations are prevalent and lung function and blood gas measurements should be regularly performed in the daily clinical assessment. Significant increase of activated CD4+CD25hi+ T cells, but not Treg is associated with decreased lung function parameters in SLEpulm patients.

Patterns of erythropoiesis-stimulating agent use for chemotherapy-induced anemia in lung cancer: results of a retrospective Hungarian real-life clinical data analysis.

OBJECTIVE: Lung cancer carries a relatively high risk of chemotherapy-induced anemia, one of the most frequent hematological complications. Previous data show a lack of optimal anemia correction in patients with chemotherapy-induced anemia. This paper analyzes real-life data considering the prevalence and severity of chemotherapy-induced anemia, together with the frequency and efficacy of erythropoietin treatment of anemia in Hungarian lung cancer patients. RESEARCH DESIGN AND METHODS: Data of 482 patients with histological or cytological confirmed lung cancer receiving chemotherapy were collected retrospectively between 1 January and 31 December, 2008. In all, 83 (17%) of them developed chemotherapy-induced moderate to severe anemia (44.6% male, 55.4% female; mean age 70 ± 8.6 years; NSCLC 67.5%, small cell lung cancer 32.5%). RESULTS: More than 50% of the patients suffering from moderate to severe chemotherapy-induced anemia (hemoglobin below 10 g/dl) did not receive erythropoietin treatment. Chemotherapy had to be postponed due to anemia in 32.26% of the patients receiving erythropoietin supplementation, while this was seen in 41.94% of the group without erythropoietin treatment (p < 0.05). In patients not receiving erythropoietin, the severity of anemia increased, while erythropoietin treated patients maintained acceptable hemoglobin levels after the end of the chemotherapy. CONCLUSIONS: The data draws attention to the fact that nowadays chemotherapy-induced anemia is not treated according to current guidelines in many lung cancer cases in Hungary.