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Gabriella Gálffy,1 Melanie Emmeluth,2 Arkady Koltun,3 Ferdinand Kopietz,2 Duc Tung Nguyen,2 Hans Christian Kuhl2 1Onco-Pulmonology Department, Pest County Pulmonology Hospital, Törökbálint, Hungary; 2Global Medical Affairs, MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany; 3Global Medical Affairs, Mylan, Inc, Canonsburg, PA, USACorrespondence: Gabriella GálffyHead of the Onco-Pulmonology Department and Research and Education Director of Pest County Pulmonology Hospital, Törökbálint 70, Munkácsy Mihály Street, Törökbálint, 2045, HungaryFax +36-23511598Email ggalffy@hotmail.comBackground: Allergic rhinitis (AR) is characterized by nasal and ocular symptoms, and substantially impacts the quality of life. Therapy selection for patients with AR depends on several factors, including symptom severity, age, patient preference, patient adherence, and cost.Methods: The purpose of this multicenter, noninterventional, cross-sectional survey was to evaluate current therapy decisions in routine clinical practice for patients with symptomatic AR, and to determine how these decisions are linked to experiences with previous treatments and current symptom severity as assessed by aVAS. The survey included patients aged 18 years or older in Spain and 12 years or older in Hungary who consulted a physician for treatment of AR symptoms. Physicians recorded AR symptom burden in the previous 7 days, previous AR treatments, and the current AR therapy decision made at the visit.Results: Overall, 72.9% of 181 patients (Spain) and 67.1% of 228 patients (Hungary) had received treatment in the previous 7 days. Among patients who had received step 3 treatment, 82.9% (Spain) and 75.8% (Hungary) received a free combination of intranasal corticosteroid (INCS) and antihistamines. Despite the high number of pretreated patients in both countries, 72.9% and 78.9% in Spain and Hungary, respectively, reported uncontrolled symptoms (VAS ≥ 50 mm). Of pretreated patients, 58.3% (Spain) and 61.4% (Hungary) received a step-up in treatment during the visit. Physicians more often prescribed a fixed combination of INCS and intranasal antihistamine than a free combination. However, of patients with uncontrolled symptoms who received previous therapy, 28.0% (Hungary) and 40.6% (Spain) did not receive a step-up as suggested by the guidelines.Conclusion: Many patients suffering from acute AR symptoms consulted with their physician because of insufficient medications. Not all patients with uncontrolled symptoms received a step-up in treatment, underscoring the need for improved physician education to enhance AR management and control in accordance with consensus treatment guidelines.Keywords: allergic rhinitis, therapy, decision-making, guidelines, intranasal corticosteroid, antihistamine, visual analog scale, noninterventional

Ranny van Weissenbruch,1 Ludger Klimek,2 Gabriella Gálffy,3 Melanie Emmeluth,4 Arkady Koltun,5 Ferdinand Kopietz,4 Duc Tung Nguyen,6 Hans Christian Kuhl,4 Wolfgang Pohl,7 Glenis K Scadding,8 David Price,9,10 Joaquim Mullol11 1Department of ENT Head and Neck Surgery, Wilhelmina Ziekenhuis, Assen, the Netherlands; 2Department of Otorhinolaryngology and Head and Neck Plastic Surgery, Zentrum für Rhinologie und Allergologie, Wiesbaden, Germany; 3Pulmonology Hospital, Torokbalint, Hungary; 4Global Medical Affairs, MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany; 5Mylan, Inc., Canonsburg, PA, USA; 6GBK Clinical Affairs, MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany; 7Department of Respiratory and Pulmonary Diseases, Karl Landsteiner Gesellschaft, Institute of Clinical and Experimental Pneumology, Vienna, Austria; 8Roy National Throat Nose and Ear Hospital, London, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 10Observational and Pragmatic Research Institute, Singapore, Singapore; 11Rhinology Unit & Smell Clinic, ENT Department, Hospital Clinic Barcelona IDIBAPS University of Barcelona, CIBERES, Barcelona, Catalonia, SpainCorrespondence: Ranny van WeissenbruchWilhelmina Ziekenhuis, Europaweg-Zuid 1, Assen 9401 RK, the NetherlandsTel +31 592 325229Fax +31 592 325226Email r.van.weissenbruch@wza.nlPurpose: Patients with poorly controlled allergic rhinitis (AR) experience nasal symptoms, sleep disturbances, activity impairment, and decreased quality-of-life (QoL). MP-AzeFlu is safe and effective for moderate-to-severe seasonal and perennial AR, but its impact on QoL requires investigation in the real-world, especially among phenotypes of immunoglobulin (Ig)E-mediated AR. This subanalysis of an observational study evaluated response to MP-AzeFlu via assessment of sleep quality and trouble with daily activities.Patients and Methods: This multicenter, prospective, non-interventional, real-life study included a convenience sample of patients with a history of moderate-to-severe AR presenting with acute AR symptoms (visual analog scale [VAS] ≥ 50 mm). Over approximately 14 days of treatment with MP-AzeFlu (137 μg azelastine HCL and 50 μg fluticasone propionate administered via single 0.137-mL spray in each nostril twice daily), changes in sleep quality and trouble with daily work, school, social, and outdoor activities were evaluated using a VAS for the entire study population and for four subgroups based on IgE response phenotype. VAS scores ranged from “not at all troubled” (0 mm) to “extremely troubled” (100 mm).Results: Following MP-AzeFlu treatment, mean VAS scores for sleep quality impairment and work or school impairment decreased from 55.2 mm at baseline to 22.1 mm and 57.6 mm at baseline to 23.0 mm, respectively, after ∼ 14 days. Similar results were observed for mean VAS scores for impairment of social activity (55.1 mm to 22.4 mm) and impairment of outdoor activity (64.4 mm to 25.0 mm). For all VAS scores, results were similar across populations, regardless of phenotype of IgE-mediated disease, comorbidity, age, and sex.Conclusion: MP-AzeFlu relieves symptoms and improves patient-reported QoL, illustrated by better sleep quality and less impairment of work, school, social, and outdoor activities after 14 days. The QoL benefits of MP-AzeFlu were consistent regardless of the phenotype of IgE-mediated disease.Registration: Clinical Trial Registration (CTR) Number: EUPAS23075. Trial Register Date: March 12, 2018. First patient visit; Last patient visit: February 2018; April 2019.Keywords: azelastine hydrochloride, daily activities, fluticasone propionate, sleep

Author(s): P. Horváth [sup.1] , Z. Lázár [sup.1] , G. Gálffy [sup.1] , R. Puskás [sup.1] , L. Kunos [sup.1] , Gy. Losonczy [sup.1] , M. Mészáros [sup.1] , Á. [...], Purpose Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia which induces inflammation in blood vessels leading to the development of cardiovascular comorbidities. Several studies implicated the role of P-selectin in vascular inflammation of OSA. P-selectin glycoprotein ligand 1 (PSGL-1) is the main activator for P-selectin and is involved in immune cell trafficking. However, PSGL-1 has not been analyzed in OSA. The aim of the study was to investigate plasma PSGL-1 and P-selectin levels to have a deeper understanding on their interaction in obstructive sleep apnea. Methods Fifty-one untreated patients with OSA and 42 non-OSA controls were recruited. Plasma PSGL-1 levels were determined in evening and morning samples, P-selectin levels were analyzed in morning samples using commercially available ELISA kits. Polysomnography was performed in all participants. OSA was defined by an apnea-hypopnea index [greater than or equal to] 5/h. Results PSGL-1 levels did not differ between controls and OSA patients either in the evening or in the morning. Although, there was no difference between controls (16.9/6.8-40.8 ng/ml) and patients with OSA (19.6/8.4-56.8, p = 0.24), patients with severe OSA had increased plasma P-selectin levels (25.6/8.4-56.8 ng/ml) compared to mild OSA patients (14.1/8.5-35.3 ng/ml, p = 0.006) and controls (p = 0.03). Conclusions P-selectin expression relates to disease severity suggesting a pathophysiological role in endothelial cell activation. PSGL-1 levels are unaltered in OSA, suggesting an alternative activation pathway for P-selectin in OSA.

Veronika Müller,1 Gabriella Gálffy,1 Márta Orosz,1 Zsuzsanna Kováts,1 Balázs Odler,1 Olof Selroos,2 Lilla Tamási1 1Department of Pulmonology, Semmelweis University, Budapest, Hungary; 2Semeco AB, Ängelholm, Sweden Abstract: The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio

Balázs Odler,1 István Ivancsó,1 Vivien Somogyi,1 Kálmán Benke,2 Lilla Tamási,1 Gabriella Gálffy,1 Balázs Szalay,3 Veronika Müller11Department of Pulmonology, 2Heart and Vascular Centre, 3Department of Laboratory Medicine, Semmelweis University, Budapest, HungaryIntroduction: The association between vitamin D and clinical parameters in obstructive lung diseases (OLDs), including COPD and bronchial asthma, was previously investigated. As asthma–COPD overlap syndrome (ACOS) is a new clinical entity, the prevalence of vitamin D levels in ACOS is unknown.Aim: Our aim was to assess the levels of circulating vitamin D (25-hydroxyvitamin D [25(OH)D]) in different OLDs, including ACOS patients, and its correlation with clinical parameters.Methods: A total of 106 men and women (control, n=21; asthma, n=44; COPD, n=21; and ACOS, n=20) were involved in the study. All patients underwent detailed clinical examinations; disease control and severity was assessed by disease-specific questionnaires (COPD assessment test, asthma control test, and modified Medical Research Council); furthermore, 25(OH)D levels were measured in all patients.Results: The 25(OH)D level was significantly lower in ACOS and COPD groups compared to asthma group (16.86±1.79 ng/mL and 14.27±1.88 ng/mL vs 25.66±1.91 ng/mL). A positive correlation was found between 25(OH)D level and forced expiratory volume in 1 second (r=0.4433; P

The aim of this study was to analyse the effect of breathing parameters, age, gender and disease status on the lung doses of the two ICS + LABA fixed combination dry powder drugs. Breathing parameters of 113 COPD patients were measured while inhaling through emptied NEXThaler® and Ellipta® inhalers and the corresponding lung doses were calculated. Lung dose of Foster® NEXThaler® was superior to the lung dose of Relvar® Ellipta® in around 85 % of the patients. The average value of the ratio of bronchiolar to bronchial deposition fractions was 5.0 for Foster® NEXThaler® and 2.6 for Relvar® Ellipta®. Lung dose was sensitive to the inhalation parameters, such as peak inhalation flow, inhaled volume and breath-hold time. For both studied drugs the dose to the lungs was relatively high for moderate PIF values, but it declined for low (<35 L/min) and high (>95 L/min) PIFs. The lung dose increased by the increase of the inhaled volume, but saturated over 1.0 L of inhaled air. Longer breath-hold time led to higher lung deposition, but the dependence was drug-specific. FEV 1 (%) and FEV 1 /FVC (%) did not influence the lung dose significantly (p = 0.05). Exacerbating patients had lower lung doses (28.8 ± 5.8 % for Foster® NEXThaler® and 23.7 ± 3.8 % for Relvar® Ellipta®) than their non-exacerbating counterparts (33.7 ± 6.1 % for Foster® NEXThaler® and for 24.9 ± 3.9 % for Relvar® Ellipta®). The exact clinical consequences of the differences between the deposition distributions of the two drugs could be assessed only by systematic clinical trials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Balázs Sánta reports a relationship with Chiesi Hungary Kft that includes: employment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The nationwide HUN-CANCER EPI study examined cancer incidence and mortality rates in Hungary from 2011 to 2019., Methods: Using data from the National Health Insurance Fund (NHIF) and Hungarian Central Statistical Office (HCSO), our retrospective study analyzed newly diagnosed malignancies between Jan 1, 2011, and Dec 31, 2019. Age-standardized incidence and mortality rates were calculated for all and for different tumor types using both the 1976 and 2013 European Standard Populations (ESP)., Findings: The number of newly diagnosed cancer cases decreased from 60,554 to 56,675 between 2011-2019. Age-standardized incidence rates were much lower in 2018, than previously estimated (475.5 vs. 580.5/100,000 person-years [PYs] in males and 383.6 vs. 438.5/100,000 PYs in females; ESP 1976). All-site cancer incidence showed a mean annual decrease of 1.9% (95% CI: 2.4%-1.4%) in men and 1.0% (95% CI:1.42%-0.66%) in women, parallel to mortality trends (-1.6% in males and -0.6% in females; ESP 2013). In 2018, the highest age-standardized incidence rates were found for lung (88.3), colorectal (82.2), and prostate cancer (62.3) in men, and breast (104.6), lung (47.7), and colorectal cancer (45.8) in women. The most significant decreases in incidence rates were observed for stomach (4.7%), laryngeal (4.4%), and gallbladder cancers (3.5%), with parallel decreases in mortality rates (3.9%, 2.7% and 3.2%, respectively)., Interpretation: We found a lower incidence of newly diagnosed cancer cases for Hungary compared to previous estimates, and decreasing trends in cancer incidence and mortality, in line with global findings and the declining prevalence of smoking., Competing Interests: Authors ZKi, ZP, EG, MV, AB, TS, EK and KK were employed by the company MSD Pharma Hungary. ZV is an employee of Semmelweis University. Semmelweis University received a grant from MSD Pharma Hungary to contribute to this research. GR, VK, AB-T and IF are employees of RxTarget Ltd. and ZB is employed by Syntesia Ltd. where their contribution to this project was financially compensated. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study received funding from MSD Pharma Hungary. The funder had the following involvement with the study: study design, data collection and analysis, decision to publish, and preparation of the manuscript., (Copyright © 2024 Kiss, Szabó, Polgár, Horváth, Nagy, Fábián, Kovács, Surján, Barcza, Kenessey, Wéber, Wittmann, Molnár, Gyöngyösi, Benedek, Karamousouli, Abonyi-Tóth, Bertókné Tamás, Fürtős, Bogos, Moldvay, Gálffy, Tamási, Müller, Krasznai, Ostoros, Pápai-Székely, Maráz, Branyiczkiné Géczy, Hilbert, Tamás Berki, Rokszin and Vokó.)

Purpose: The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC)., Patients and Methods: Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was the objective response rate. Prespecified exploratory biomarker analyses were conducted in arms A and C., Results: In arm A (n = 41), arm B (n = 10), and arm C (n = 21), the confirmed objective response rates were 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells or immune cells) ≥1% seemed to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (tumor cells and immune cells) <1%, and lower baseline ctDNA and reduction in the on-treatment ctDNA level were both associated with longer overall survival. Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers., Conclusions: In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer overall survival suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account., Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex., Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes)., Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future., Competing Interests: GS, GH, ÉB, and KK are employees of MSD Pharma Hungary Ltd. ZV is an employee of Semmelweis University where his contribution to this project was financially compensated. ZKis is also an employee of MSD Pharma Hungary Ltd. and has an affiliation at the Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. The project was financed by MSD Pharma Hungary Ltd. VM has received consultation fees from AstraZeneca, Boehringer Ingelheim, Roche, Berlin-Chemie, Chiesi, BMS, Novartis, Actelion, Gilead, Pfizer, Richter, Lilly, Orion Pharma and Ipsen and served as PI for over 10 LC studies. LT is an employee of Semmelweis University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gálffy, Szabó, Tamási, Müller, Moldvay, Sárosi, Kerpel-Fronius, Kardos, Csada, Pápai-Székely, Szász, Király, Hódi, Kovács, Balogh, Kovács, Darida, Buga, Rokszin, Abonyi-Tóth, Kiss, Vokó and Bogos.)

Surgical resection of pulmonary adenocarcinoma is considered to be curative but progression-free survival (PFS) has remained highly variable. Antitumor immune response may be important, however, the prognostic significance of tumor-infiltrating natural killer (NK) and regulatory T (Treg) lymphocytes is uncertain. Resected pulmonary adenocarcinoma tissues (n = 115) were studied by immunohistochemical detection of NKp46 and FoxP3 positivity to identify NK and Treg cells, respectively. Association of cell densities with clinicopathological features and progression-free survival (PFS) as well as overall survival (OS) were analyzed with a follow-up time of 60 months. Both types of immune cells were accumulated predominantly in tumor stroma. NK cell density showed association with female gender, non-smoking and KRAS wild-type status. According to Kaplan-Meier analysis, PFS and OS proved to be longer in patients with high NK or Treg cell densities (p = 0.0293 and p = 0.0375 for PFS, p = 0.0310 and p = 0.0448 for OS, respectively). Evaluating the prognostic effect of the combination of NK and Treg cell density values revealed that PFS and OS were significantly longer in NK high /Treg high cases compared to the other groups combined (p = 0.0223 and p = 0.0325, respectively). Multivariate Cox regression analysis indicated that high NK cell density was independent predictor of longer PFS while high NK and high Treg cell densities both proved significant predictors of longer OS. The NK high /Treg high combination also proved to be an independent prognostic factor for both PFS and OS. In conclusion, NK and Treg cells can be components of the innate and adaptive immune response at action against progression of pulmonary adenocarcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases., Methods: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients., Results: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001)., Conclusions: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary., Clinical Relevance Statement: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region., Key Points: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The deposition of dry powder aerosol drugs depends on the inhalation parameters of the patients through the inhaler. These data are not directly measured in clinical practice. Their prediction based on the routinely measured spirometric data could help in choosing the appropriate device and optimizing the therapy. The aim of this study was to perform inhalation experiments to find correlations between inhalation parameters of COPD patients through two DPI devices and their native spirometric data, gender, age and disease severity. Another goal was to establish relationships between peak inspiratory flows through NEXThaler® and Ellipta® inhalers and their statistical determinants. Breathing parameters of 113 COPD patients were measured by normal spirometry and while inhaling through the two DPIs. Statistical analysis of the measured data was performed. The average values of peak inspiratory flow through the devices (PIF dev ) were 68.4 L/min and 78.0 L/min for NEXThaler® and Ellipta®, respectively. PIF dev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant. PIF dev values correlated best with their native spirometric counterparts (PIF) and linear relationships between them were revealed. Current results may be used in the future to predict the success of inhalation of COPD patients through DPI devices, which may help in the inhaler choice. By choosing the appropriate device-drug pair for each patient the lung dose can be increased and the efficiency of the therapy improved. Further results of the clinical study will be the subject of a next publication., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alpár Horváth, Gábor Tomisa, Balázs Sánta report a relationship with Chiesi Hungary Kft that includes: employment., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in ∼15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gálffy, Morócz, Korompay, Hécz, Bujdosó, Puskás, Lovas, Gáspár, Yahya, Király and Lohinai.)

Introduction: Asthma is the most prevalent obstructive pulmonary disease, with drastically improved treatment options over the past decades. However, there is still a proportion of patients with suboptimal level of asthma control, leading to multiple hospitalisation due to severe acute exacerbation (SAE) and earlier death. In our study, we aimed to assess the risk of SAEs and mortality in patients who suffered an SAE., Methods: The database of the National Health Insurance Fund was used to retrospectively analyse the data of all asthmatic patients who had been hospitalised for an SAE between 2009 and 2019. We used a competing risk model to analyse the effect of each exacerbation on the risk of further SAEs with age, sex, Charlson index and the number of severe and moderate exacerbations included as covariates., Result: Altogether, 9257 asthmatic patients suffered at least one exacerbation leading to hospitalisation during the study time. The majority (75.8%) were women, and the average age was 58.24 years. Most patients had at least one comorbidity. 3492 patients suffered at least one further exacerbation and 1193 patients died of any cause. In the competing risk model, each SAE increased the risk of further exacerbations (HR=2.078-7.026; p<0.0001 for each case) but not death. The risk of SAEs was also increased by age (HR=1.008) female sex (HR=1.102) and with the number of days of the first SAE (HR=1.007)., Conclusions: Even though asthma is generally a well-manageable disease, there still are many patients who suffer SAEs that significantly increase the risk of further similar SAEs., Competing Interests: Competing interests: The authors report that they have no conflicts of interest related to the submitted work. LT has received lecture or consultancy fees and/or support for conference attendance from Berlin-Chemie, Orion Corporation, Novartis, Chiesi, Teva Pharmaceutical and AstraZeneca. NE has received lecture or consultancy fees and/or support for conference attendance from Berlin-Chemie, Orion Corporation, Novartis, Chiesi, Teva Pharmaceutical and AstraZeneca. GG has accepted reports personal fees from Astra-Zeneca, Chiesi, BMS, MSD, Berlin Chemie, Boehringer Ingelheim, Roche, Novartis, Pfizer, Ipsen, Mylen, Orion outside the submitted workB. Santa, G. Tomisa and A. Horváth are all employees of Chiesi Hungary., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Increased DNA damage triggered through poly (ADP-ribose) polymerase inhibition may modify tumor immunogenicity, sensitizing tumors to immunotherapy. ORION (NCT03775486) evaluated the combination of olaparib with durvalumab as maintenance therapy in patients with metastatic NSCLC., Methods: ORION is a phase 2, randomized, multicenter, double-blind, international study. Patients with metastatic NSCLC (without activating EGFR or ALK aberrations) and Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled to receive initial therapy with durvalumab (1500 mg intravenously; every 3 wk) plus platinum-based chemotherapy for four cycles. Patients without disease progression were then randomized (1:1) to maintenance durvalumab (1500 mg; every 4 wk) plus either olaparib (300 mg orally) or placebo (both twice daily); randomization was stratified by objective response during initial therapy and tumor histologic type. The primary end point was investigator-assessed progression-free survival (PFS) (Response Evaluation Criteria in Solid Tumors version 1.1)., Results: Between January 2019 and February 2020, 269 of 401 patients who received initial therapy were randomized. As of January 11, 2021 (median follow-up: 9.6 mo), median PFS was 7.2 months (95% confidence interval: 5.3-7.9) with durvalumab plus olaparib versus 5.3 months (3.7-5.8) with durvalumab plus placebo (hazard ratio = 0.76, 95% confidence interval: 0.57-1.02, p = 0.074). Safety findings were consistent with the known profiles of durvalumab and olaparib. Anemia was the most common adverse event (AE) with durvalumab plus olaparib (26.1% versus 8.2% with durvalumab plus placebo). The incidence of grade 3 or 4 AEs (34.3% versus 17.9%) and AEs leading to treatment discontinuation (10.4% versus 4.5%) was numerically higher with durvalumab plus olaparib versus durvalumab plus placebo., Conclusions: Maintenance therapy with durvalumab in combination with olaparib was not associated with a statistically significant improvement in PFS versus durvalumab alone, although numerical improvement was observed., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database., Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology., Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period., Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic., Competing Interests: GH, KKn, TS, ZP and KKo are employees of MSD Pharma Hungary Ltd. ZV is an employee of Semmelweis University where their contribution to this project was financially compensated. ZKis is also employee of MSD Pharma Hungary Ltd., and has affiliation at Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The program is financed by MSD Pharma Hungary Ltd. VM has received consultation fees from Astraeneca, Boehringer Ingelheim, Roche, Berlin-Chemie, Chiesi, BMS, Novartis, Actelion, Gilead, Pfizer, Richter, Lilly, Orion Pharma and Ipsen and served as PI for over 10 LC studies. LT is employee of Semmelweis University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kiss, Gálffy, Müller, Moldvay, Sárosi, Pápai-Székely, Csada, Kerpel-Fronius, Király, Szász, Hódi, Polányi, Kovács, Karamousouli, Knollmajer, Szabó, Berta, Vokó, Rokszin, Abonyi-Tóth, Barcza, Tamási and Bogos.)

Airway deposition of aerosol drugs is highly dependent on the breathing manoeuvre of the patients. Though incorrect exhalation before the inhalation of the drug is one of the most common mistakes, its effect on the rest of the manoeuvre and on the airway deposition distribution of aerosol drugs is not explored in the open literature. The aim of the present work was to conduct inhalation experiments using six dry powder inhalers in order to quantify the effect of the degree of lung emptying on the inhalation time, inhaled volume and peak inhalation flow. Another goal of the research was to determine the effect of the exhalation on the aerodynamic properties of the drugs emitted by the same inhalers. According to the measurements, deep exhalation before drug inhalation increased the volume of the inhaled air and the average and maximum values of the inhalation flow rate, but the extent of the increase was patient and inhaler specific. For different inhalers, the mean value of the relative increase in peak inhalation flow due to forceful exhalation was between 15.3 and 38.4% (min: Easyhaler®, max: Breezhaler®), compared to the case of normal (tidal) exhalation before the drug inhalation. The relative increase in the inhaled volume was between 36.4 and 57.1% (min: NEXThaler®, max: Turbuhaler®). By the same token, forceful exhalation resulted in higher emitted doses and smaller emitted particles, depending on the individual breathing ability of the patient, the inhalation device and the drug metered in it. The relative increase in the emitted dose varied between 0.2 and 8.0% (min: Foster® NEXThaler®, max: Bufomix® Easyhaler®), while the relative enhancement of fine particle dose ranged between 1.9 and 30.8% (min: Foster® NEXThaler®, max: Symbicort® Turbuhaler®), depending on the inhaler. All these effects and parameter values point toward higher airway doses due to forceful exhalation before the inhalation of the drug. At the same time, the present findings highlight the necessity of proper patient education on the importance of lung emptying, but also the importance of patient-specific inhaler-drug pair choice in the future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arpad Farkas reports financial support was provided by Centre for Energy Research. Gabor Tomisa, Alpar Horvath, Georgina Szenasi reports a relationship with Chiesi Hungary Kft that includes: employment., (© 2023 The Authors.)

Introduction: We present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC., Methods: Patients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mg/m 2 (d 1) and 500 mg/m 2 (d 8), cisplatin 75 mg/m 2 (d 1), and gemcitabine 1250 mg/m 2 (d 1 and 8) for four 3-week cycles, followed by avelumab 800 mg and cetuximab 500 mg/m 2 every 2 weeks. The primary end point was the best overall response; the secondary end points were progression-free survival, duration of response, overall survival, and safety. Efficacy analyses were reported from an updated data cutoff., Results: A total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% [95% confidence interval: 21.0%-50.9%]), and the median duration of response was 7.1 months (95% confidence interval: 4.2-12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event., Conclusions: The combination of avelumab + cetuximab and chemotherapy showed antitumor activity and tolerable safety; however, the ORR was not improved compared with those reported for current standards of care (NCT03717155)., (© 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.)

Objective: The Hungarian Undiagnosed Lung Cancer (HULC) study aimed to explore the potential reasons for missed LC (lung cancer) diagnosis by comparing healthcare and socio-economic data among patients with post-mortem diagnosed LC with those who were diagnosed with LC during their lives., Methods: This nationwide, retrospective study used the databases of the Hungarian Central Statistical Office (HCSO) and National Health Insurance Fund (NHIF) to identify patients who died between January 1, 2019 and December 31, 2019 and were diagnosed with lung cancer post-mortem (population A) or during their lifetime (population B). Patient characteristics, socio-economic factors, and healthcare resource utilization (HCRU) data were compared between the diagnosed and undiagnosed patient population., Results: During the study period, 8,435 patients were identified from the HCSO database with LC as the cause of death, of whom 1,203 (14.24%) had no LC-related ICD (International Classification of Diseases) code records in the NHIF database during their lives (post-mortem diagnosed LC population). Post-mortem diagnosed LC patients were significantly older than patients diagnosed while still alive (mean age 71.20 vs. 68.69 years, p<0.001), with a more pronounced age difference among female patients (difference: 4.57 years, p<0.001), and had significantly fewer GP (General Practitioner) and specialist visits, X-ray and CT scans within 7 to 24 months and 6 months before death, although the differences in GP and specialist visits within 7-24 months did not seem clinically relevant. Patients diagnosed with LC while still alive were more likely to be married (47.62% vs. 33.49%), had higher educational attainment, and had more children, than patients diagnosed with LC post-mortem., Conclusions: Post-mortem diagnosed lung cancer accounts for 14.24% of total lung cancer mortality in Hungary. This study provides valuable insights into patient characteristics, socio-economic factors, and HCRU data potentially associated with a high risk of lung cancer misdiagnosis., Competing Interests: Authors ZK, AV, KKn, MV, KKo, AB, IKö, EK and ZP are employed by MSD Pharma Hungary Ltd. ZV is employed by Semmelweis University where his contribution to this project was financially compensated. KB, JM and GyO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GabG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. ZsB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The programme is financed by MSD Pharma Hungary Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kiss, Bogos, Tamási, Ostoros, Müller, Bittner, Sárosi, Vastag, Knollmajer, Várnai, Kovács, Berta, Köveskuti, Karamousouli, Rokszin, Abonyi-Tóth, Barcza, Kenessey, Weber, Nagy, Freyler-Fadgyas, Szócska, Szegner, Hilbert, Géczy, Surján, Moldvay, Vokó, Gálffy and Polányi.)

During oncological treatments, body mass index (BMI) and weight loss (WL) are important prognostic factors, but can be influenced by nutrition therapy. The aim of the study was to collect data on BMI and WL of patients with lung cancer and on the nutritional therapy influencing malnutrition. In our multicenter, retrospective study involving 1616 patients, data were collected using a questionnaire with 51 questions, and statistical analysis was performed with descriptive, and multivariate analysis methods with IBM SPSS 20 software. According to the method of Martin, based on BMI and WL, patients were ranked on a scale of 0 to 4 (grade 0 24.9%; grade 1 20.7%; grade 2 14.9%; grade 3 22.4%; grade 4 17.0%). Based on this data low BMI and WL may affect survival in 75.1%. In contrast, only 37.6% of patients received nutritional therapy, based on 47 different strategies. The data substituted into the prognostic matrix highlights that weight loss may shorten patients' survival. The 47 strategies indicate that the use of nutritional therapy is inconsistent throughout this patient cohort.

Objective: This study aimed to examine the characteristics of the lung cancer (LC) patient pathway in Hungary during a 6-years period. Methods: This nationwide, retrospective study included patients newly diagnosed with LC (ICD-10 C34) between January 1, 2011, and December 31, 2016, using data from the National Health Insurance Fund (NHIF) of Hungary. The following patient pathway intervals were examined: system, diagnostic and treatment interval by age, gender, tumor type, study year and first-line LC therapy. Results: During the 6-years study period, 17,386 patients had at least one type of imaging (X-ray or CT/MRI) prior to diagnosis, and 12,063 had records of both X-ray and CT/MRI. The median system interval was 64.5 days, and it was 5 days longer among women, than in men (68.0 vs. 63.0 days). The median system interval was significantly longer in patients with adenocarcinoma compared to those with squamous cell carcinoma or small cell lung cancer (70.4 vs. 64.0 vs. 48.0 days, respectively). Patients who received surgery as first-line treatment had significantly longer median system intervals compared to those receiving chemotherapy (81.4 vs. 62.0 days). The median system interval significantly increased from 62.0 to 66.0 days during the 6-years study period. Conclusion: The LC patient pathway significantly increased in Hungary over the 6-years study period. There were no significant differences in the length of the whole LC patient pathway according to age, however, female sex, surgery as first-line treatment, and adenocarcinoma were associated with longer system intervals., Competing Interests: ZK, AV, ZP, ZN-E, KK, and MV are employees of MSD Pharma Hungary Ltd. MV is a research fellow at Semmelweis University. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees at Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The programme is financed by MSD Pharma Hungary Ltd. JM was supported by the Hungarian Brain research Program (grant 2017-1.2.1-NKP-2017-00002), and the Hungarian NRDI Office (grant K-129065). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study: development of study design, data collection, data analysis, interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2021 Kiss, Bogos, Tamási, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Knollmajer, Várnai, Nagy, Horváth, Rokszin, Abonyi-Tóth, Barcza, Moldvay, Gálffy and Vokó.)

We aimed to evaluate the prevalence of asthma and its associating environmental factors within a 6-12-year-old population. A cross-sectional, questionnaire-based study was conducted in primary schools located in the capital of Hungary; 3836 eligible parent-reported questionnaires were evaluated. Besides the International Study of Asthma and Allergies in Childhood (ISAAC) phase three core questions for asthma, the survey also assessed various potential risk factors. We introduced the umbrella term cumulative asthma as the union of physician-diagnosed asthma and current wheezing to estimate the lifetime prevalence of asthma. Current wheezing and physician-diagnosed asthma showed a frequency of 9.5% and 6.3%, respectively. They contributed to a cumulative asthma prevalence of 12.6% among the sampled population, with a girl-boy percentage of 37.4% to 62.6%. Air-pollution and weedy areas were associated with greater risk for asthma, while a suburban residence showed lesser odds. Indoor smoking, visible mold, and keeping a dog were defined as risk factors for asthma, while the presence of plants in the bedroom and pet rodents were associated with lower odds ratios. The consumption of fast food, beverages containing additives and margarine were significantly higher in asthmatics, while we found frequent sport activity and cereal intake associated with lower odds ratios for asthma. In this urban environment, we identified an increased asthma prevalence compared to some previously published studies, but the cross-sectional design and the different methodology did not permit us to draw timeframe-dependent conclusions.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler ® device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. Enhanced feature (slides, video, animation) (MP4 43768 kb)., (© 2021. The Author(s).)

Objective: Hungary has one of the highest incidences and mortality rates of lung cancer (LC), therefore the objective of this study was to analyse and compare LC incidence and mortality rates between the main Hungarian regions. Methods: This nationwide, retrospective study used data from the National Health Insurance Fund and included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between Jan 1, 2011 and Dec 31, 2016. Age-standardized incidence and mortality rates were calculated and compared for the main regions. Results: The highest incidence rate in males was recorded in Northern Hungary (146.8/100,000 person-years [PY]), while the lowest rate was found in Western Transdanubia (94.7/100,000 PY in 2011). All rates showed a declining trend between 2011 and 2016, with the largest decrease in the Northern Great Plain (-20.0%; p = 0.008). LC incidence and mortality rates in women both showed a rising tendency in all regions of Hungary, reaching the highest in Central Hungary (59.86/100,000 PY in 2016). Lung cancer incidence and mortality rates in males correlated with the level of education and smoking prevalence ( p = 0.006 and p = 0.01, respectively) in the regions. A correlation with GDP per capita and Health Development Index (HDI) index could also be observed in the Hungarian regions, although these associations were not statistically significant. No correlations could be detected between these parameters among females. Conclusion: This analysis revealed considerable differences in the epidemiology of LC between the 7 main Hungarian regions. LC incidence and mortality rates significantly correlated with smoking and certain socioeconomic factors in men, but not in women. Further research is needed to explain the regional differences., Competing Interests: ZB was employed by the company Syntesia Medical Communications Ltd. AV, ZK, ZP, ZN-E, AD and KK are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University, employed in the framework of a joint research programme of Eötvös Loránd and MSD Pharma Hungary Ltd. MV and PS are research fellows at Semmelweis University, employed in the framework of a joint research programme of Semmelweis University and MSD Pharma Hungary Ltd. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB, JM and GO are employees of National Korányi Institute of Pulmonology, GG is an employee of Oncology Center of Törökbálint, LT and VM are employees of Semmelweis University, LU is an employee of Gyógyintézet, NB is an employee of University of Debrecen, VS is an employee of University of Pécs, where their contribution to this project was not financially compensated. GR and ZA-T are employees of RxTarget Ltd where their contribution to this project was financially compensated. The programme is financed by MSD Pharma Hungary Ltd. JM was supported by the Hungarian Brain Research Program (grant 2017-1.2.1-NKP-2017-00002), and the Hungarian NRDI Office (grant K-129065). The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study: development of study design, data collection, data analysis, interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2021 Gálffy, Vastag, Bogos, Kiss, Ostoros, Müller, Urbán, Bittner, Sárosi, Polányi, Nagy-Erdei, Daniel, Knollmajer, Várnai, Szegner, Vokó, Nagy, Horváth, Rokszin, Abonyi-Tóth, Pozsgai, Barcza, Moldvay and Tamási.)

Objective: Lung cancer is one of the most common cancers worldwide and its survival is still poor. The objective of our study was to estimate long-term survival of Hungarian lung cancer patients at first time based on a nationwide review of the National Health Insurance Fund database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between January 1, 2011 and December 31, 2016. Survival rates were evaluated by year of diagnosis, patient gender and age, and morphology of lung cancer. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.7 and 65.9 years during study period. One- and 5-year overall survival rates for the total population were 42.2 and 17.9%, respectively. Survival was statistically associated with gender, age and type of lung cancer. Female patients ( n = 16,362) had 23% better survival (HR: 0.77, 95% confidence interval (CI): 0.75-0.79; p < 0.001) than males ( n = 25,492). The highest survival rates were found in the 20-49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.5%). We measured 5.3% improvement (9.2% adjusted) in lung cancer survival comparing the period 2015-2016 to 2011-2012 (HR: 0.95 95% CI: 0.92-0.97; p = 0.003), the highest at females <60 year (0.86 (adjusted HR was 0.79), interaction analysis was significant for age and histology types. Conclusion: Our study provided long-term Lung cancer survival data in Hungary for the first time. We found a 5.3% improvement in 5-year survival in 4 years. Women and young patients had better survival. Survival rates were comparable to-and at the higher end of-rates registered in other East-Central European countries (7.7%-15.7%)., Competing Interests: ZK, AV, ZN-E, and AD are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. LT and VM are employees of Semmelweis University. LU is employee of Mátra Gyógyintézet. NB is employee of University of Debrecen. VS is employee of University of Pécs. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bogos, Kiss, Tamási, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Daniel, Vokó, Nagy, Horváth, Rokszin, Abonyi-Tóth, Barcza, Gálffy and Moldvay.)

Objective: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between January 1, 2011 and December 31, 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any cancer treatment other than lung cancer protocols were excluded. Results: Lung cancer incidence and mortality increased with age, peaking in the 70-79 age group (375.0/100,000 person-years) among males, while at 60-69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46-3.01 ( p < 0.0001) among the 70-79 age group. We found 2-11% decrease in male incidence rate at most age groups, while a significant 1-3% increase was observed in older females (>60) annually during the study period. Conclusion: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary decreased in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population., Competing Interests: ZK, AV, and ZN-E, and AD are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary, LT and VM are employees of Semmelweis University and they declare have no conflict of interest, LU is employee of MG and he declares have no conflict of interest, NB is employee of University of Debrecen and she declares have no conflict of interest, VS is employee of University of Pécs and she declares have no conflict of interest. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employees of Synthesia Ltd. And her contribution to this project was financially compensated. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study: study design, data collection and analysis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tamási, Horváth, Kiss, Bogos, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Daniel, Nagy, Rokszin, Abonyi-Tóth, Moldvay, Vokó and Gálffy.)

Background: The study aimed to determine the prevalence and risk factors of allergic rhinitis and related comorbidities in school-age children in Budapest, capital of Hungary. Data and epidemiological studies on this disease are still limited., Methods: A cross sectional study was conducted in 21 representative and randomly selected primary schools in 2019. International Study of Asthma and Allergies in Childhood-based questionnaires (n = 6869) inquiring about prevalence and related risk factors of allergic rhinitis were distributed to all parents. The data were characterised with standard descriptive statistics: frequencies (percentages) and means for categorical and quantitative data, respectively., Results: 3836 of the questionnaires (1857 M/1979F) were completed. The prevalence of current allergic rhinitis was 29.3% (1043), physician-diagnosed allergic rhinitis was 9.7% (373), cumulative allergic rhinitis was 36.2% (1289) and current allergic rhinoconjunctivitis was 16.2% (577). The presence of physician diagnosed atopic disease-asthma (p < 0.0001, OR = 4.398, 95% CI 3.356-5.807), food allergy (p < 0.0001, OR = 2.594, 95% CI 1.995-3.378), and eczema (p < 0.0001, OR = 1.899, 95% CI 1.568-2.300)-were significantly related to an increased risk of cumulative allergic rhinitis. Significant factors associated with allergic rhinitis include male gender (p < 0.0001), family history of atopy (p < 0.0001), frequent upper respiratory tract infections (p < 0.0001), tonsillectomy (p = 0.0054), antibiotics given in the first year of life (p < 0.0001), paracetamol given in the first year of life (p = 0.0038), long-lasting common infections caused by viruses and/or bacteria before the appearance of the allergy (p < 0.0001), consumption of drinks containing preservatives or colourants (p = 0.0023), duration of living in Budapest (p = 0.0386), smoking at home (p = 0.0218), smoking at home in the first year of life (p = 0.0048), birds at home (p = 0.0119), birds at home in the first year of life (p = 0.0052), visible mould in the bedroom (p = 0.0139), featherbedding (p = 0.0126), frequent or constant heavy-vehicle traffic (p = 0.0039), living in a weedy area (p < 0.0001) and living in the vicinity of an air-polluting factory or mine (p = 0.0128)., Conclusions: The prevalence of allergic rhinoconjunctivitis in 6-12-year-old children in Budapest is higher than reported for most of the surrounding European countries. While asthma (OR = 4.398) is the most significant comorbidity, environmental factors such as birds at home in the first year of life (OR = 2.394) and living in a weedy area (OR = 1.640) seem to be the most important factors associated with AR. Strategies for preventive measures should be implemented., Trial Registration Number: KUT-19/2019. The study was approved by the Ethics Committee at Heim Pál National Pediatric Institute.

Background: In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases., Methods: In the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD. In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma. It was evaluated whether these lncRNAs can be used as diagnostic biomarkers for any studied disease. With systems biology analysis the biological functions of the selected lncRNAs were predicted., Results: In the discovery cohort, the mean expression of 27 lncRNAs showed nominally significant differences in at least one comparison. OIP5-AS1, HNRNPU, RP11-325K4.3, JPX, RP11-282O18.3, MZF1-AS1 were selected for measurement in the replication cohort. Three lncRNAs (HNRNPU, RP11-325K4.3, JPX) expressed significantly higher in healthy children than in adult controls. All the mean expression level of the 6 lncRNAs differed significantly between adult allergic rhinitis patients and controls. RP11-325K4.3, HNRNPU and OIP5-AS1 expressed higher in allergic asthma than in non-allergic asthma. COPD and asthma differed in the expression of RP11-325K4.3 from each other. In examining of the lncRNAs as biomarkers the weighted accuracy (WA) values were especially high in the comparison of healthy controls and patients with allergic rhinitis. OIP5-AS1 and JPX achieved 0.98 and 0.9 WA values, respectively, and the combination of the selected lncRNAs also resulted in a high performance (WA = 0.98). Altogether, OIP5-AS1 had the highest discriminative power in case of three out of six comparisons., Conclusion: Differences were detected in the expression of circulating lncRNAs in chronic respiratory diseases. Some of these differences might be utilized as biomarkers and also suggest a possible role of these lncRNAs in the pathomechanism of these diseases. The lncRNAs and the associated pathways are potential therapeutic targets in these diseases, but naturally additional studies are needed for the confirmation of these results.

The effect of breathing parameters on the airway deposition of the inhaled aerosols with known size was intensively studied in the literature. However, in the case of dry powder aerosol drugs both the quantity and quality of the particles emitted by the inhaler and inhaled by the patients is a complex function of the patient's breathing parameters, which in turn depend also on the disease severity and current status of the patient. The aim of this study was to evaluate the impact of breathing parameters, gender, age, symptoms and exacerbation history related disease severity (GOLD groups) of chronic obstructive pulmonary disease (COPD) patients on the lung dose of four different drugs emitted by three DPIs (dry powder inhalers). Breathing profiles of 47 COPD patients were recorded while they inhaled through Turbuhaler®, Breezhaler® and Genuair® inhalers. Patient specific emitted doses and particle size distributions were determined for Symbicort® Turbuhaler®, Onbrez® Breezhaler®, Seebri® Breezhaler® and Bretaris® Genuair® aerosol drugs. Airway deposition was quantified by a validated whole respiratory tract particle deposition model. Correlation analysis of the lung doses with breathing parameters through the devices and with standard spirometric parameters was performed. The effects of gender, age and degree of disease severity (GOLD groups) on the lung doses were also studied by statistical analysis. Mean values and distributions of the deposited lung doses proved to be both drug and device specific, yielding 24.2 (±7.8), 22.6 (±3.6), 34.2 (±4.8) and 23.9 (±5.4) % values for Symbicort®, Onbrez®, Seebri® and Bretaris®, respectively. Drugs with flow rate sensitive emitted dose and emitted particle size distribution exhibited higher intersubject variability of the lung doses. The degree of correlation of lung doses with breathing parameters through the devices was also drug specific. Correlation with flow rate was the strongest for Symbicort® Turbuhaler®. Longer breath-hold increased the lung dose of all the studied drugs. Correlations of lung dose with standard spirometric parameters was generally weaker than its correlation with the parameters measured when inhaling through the devices. Men had higher lung deposition than women, younger patients had higher deposition than older ones and patients with less severe disease higher doses than those with more severe COPD, but the differences were statistically significant only upon gender and only in case of Symbicort® and Seebri®. Patients with better inhalation parameters are likely to have higher lung deposition when inhaling a drug with emitted dose and particle size distribution sensitive to the inhalation flow rate. At the same time, patients with lower lung capacity show better deposition results when inhaling from inhalers emitting a more constant amount of drug and particles with more stable aerodynamic characteristics. A more powerful inhalation significantly increases the lung dose for the drug emitted by Turbuhaler®, while long breath-hold is likely to yield significantly higher deposition for drugs emitted by Breezhaler® and Genuair®. Lung doses of two different drugs dispensed in the same inhaler can be significantly different., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Small cell lung cancer (SCLC; comprising approximately 14% of all lung cancer cases in Hungary) is an aggressive tumor type characterized by rapid growth and early metastasis. Although SCLC is a particularly malignant form of cancer, targeted therapies in its treatment have remained largely unsuccessful and thus there were no major therapeutic advances in the last three decades. SCLC was once considered a molecularly homogeneous malignancy. However, recent analyses led to the classification of neuroendocrine and molecular subtypes, based on the dominant expression of one of the following four transcriptional regulator genes: ASCL1, NEUROD1, YAP1 and POU2F3. Because these genetically and biologically distinct subtypes might contribute to therapeutic resistance, the better understanding of their biological and clinicopathological characteristics may help in the development of more effective SCLC therapies.

In the international publications, in the last decades, incidence and mortality of lung cancer was the highest in Hungary in the ranking of European countries and even worldwide, despite the fact that no lung cancer incidence data were reported from Hungary until 2019. In the studies published by our working group at the end of 2019 and in the first half of 2020, we were the first to publish Hungarian lung cancer incidence and mortality data based on research on the NEAK database. The results of this study showed a significant, 25-30% lower incidence of lung cancer in Hungary than the previously reported data. Based on these findings, it was determined that the previously reported Hungarian lung cancer incidence and mortality data can be compiled due to different methodological applications of inadequately calculated results, and Hungarian lung cancer incidence and mortality are equally high, but not higher than the average in Central European countries. In addition, a decrease in the incidence and mortality of male lung cancer was measured between 2011 and 2016, while increasing values were found for women.

Lung cancer is the leading cause of cancer deaths not only in Hungary but also in the world. Within this, women's lung cancer morbidity and mortality have increased significantly in recent years. For many years, we only had a chemotherapy option to treat lung cancer. The year 2005 was a major breakthrough in the treatment of non-small cell lung cancer with the advent of a new treatment strategy, targeted treatments, EGFR-TKI treatments. Since then, we have several years of experience with first-, second-, and even third-generation TKI treatments in lung adenocarcinoma. The second major step in targeted therapy for lung cancer was to learn about ALK mutant lung cancer and the emergence of ALK inhibitor therapies on the therapeutic palette with the advent of first, second and third generation formulations. In recent years, the range of options for targeted therapeutic targets has expanded to include personalized therapeutic options. By recognizing and targeting the ROS1, BRAF, MET, RET, NTRK, HER2 mutations, we can tailor the most optimal treatment to more and more patients.