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Karolina Górka,1,2 Iwona Gross-Sondej,1,2 Jacek Górka,3 Tomasz Stachura,1,2 Kamil Polok,1,3 Natalia Celejewska-Wójcik,1,2 Sławomir Mikrut,4 Anna Andrychiewicz,5 Krzysztof Sładek,1,2,* Jerzy Soja1,2,* 1Department of Pulmonology and Allergology, University Hospital, Kraków, Poland; 2 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland; 3Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Kraków, Poland; 4Faculty of Mining Surveying and Environmental Engineering, AGH University of Science and Technology, Kraków, Poland; 5Department of Endoscopy, University Hospital, Kraków, Poland*These authors contributed equally to this workCorrespondence: Jerzy Soja 2nd Department of Internal Medicine, Jagiellonian University Medical College, ul Jakubowskiego 2, Kraków, 30-688, PolandTel +48 12 400 30 53Fax +48 12 400 30 67Email jerzy.soja@uj.edu.plPurpose: The aim of this study was to evaluate the structural changes of the airways using the endobronchial ultrasound (EBUS) in ACO patients compared to severe asthma and COPD patients.Patients and Methods: The study included 17 patients with ACO, 17 patients with COPD and 33 patients with severe asthma. Detailed clinical data were obtained from all participants. Basic laboratory tests were performed, including measurement of eosinophil counts in blood and serum immunoglobulin E (IgE) concentrations. All patients underwent spirometry and bronchoscopy with EBUS (a 20‑MHz ultrasound probe) to measure the total thicknesses of the bronchial walls and their particular layers in segmental bronchi of the right lower lobe. EBUS allows to distinguish five layers of the bronchial wall. Layer 1 (L1) and layer 2 (L2) were analyzed separately, while the outer layers (layers 3– 5 [L3– 5]) that correspond to cartilage were assessed together.Results: In patients with ACO the thicknesses of the L1 and L2 layers, which are mainly responsible for remodeling, were significantly greater than in patients with COPD and significantly smaller than in patients with severe asthma (median L1= 0.17 mm vs 0.16 mm vs 0.18 mm, p< 0.001; median L2= 0.18 mm vs 0.17 mm vs 0.20 mm, p< 0.001, respectively). The thicknesses of the total bronchial walls (L1+L2+L3– 5) and L3– 5 were significantly smaller in ACO and COPD patients compared to asthma patients (median L1+L2+L3– 5= 1.2 mm vs 1.14 mm vs 1.31 mm, p< 0.001; median L3– 5= 0.85 mm vs, 0.81 mm vs 0.92 mm, p=0.001, respectively).Conclusion: The process of structural changes in the airways assessed by EBUS is more advanced in individuals with ACO compared to patients with COPD, and less pronounced compared to patients with severe asthma. It seems that EBUS may provide useful information about differences in airway remodeling between ACO, COPD and severe asthma.Keywords: asthma-COPD overlap, airway remodeling, total bronchial wall, bronchial wall layers, endobronchial ultrasound

Natalia Celejewska-Wójcik,1 Aleksander Kania,1 Karolina Górka,1 Paweł Nastałek,1 Krzysztof Wójcik,2 Anna Gielicz,3 Lucyna Mastalerz,1 Marek Sanak,3 Krzysztof Sładek1 1Department of Pulmonology, 2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; 2 2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; 3Department of Molecular Biology and Clinical Genetics, Faculty of Medicine, Jagiellonian University Medical College, Kraków, PolandCorrespondence: Natalia Celejewska-Wójcik 2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, ul. Jakubowskiego 2, Krakow, 30-688, PolandTel +48 12 400 30 53Fax +48 12 400 30 67Email natalia.celejewska@gmail.comPurpose: Lipid mediators, particularly eicosanoids, are associated with airway inflammation, especially with the eosinophilic influx. This study aimed to measure lipid mediators and cells in induced sputum, that could possibly reflect the inflammatory process in the bronchial tree of COPD subjects.Patients and Methods: Eighty patients diagnosed with COPD and 37 healthy controls participated in the study. Induced sputum samples were ascertained for differential cell count and induced sputum supernatant concentrations of selected eicosanoids by the means of gas chromatography/mass spectrometry and high-performance liquid chromatography/tandem mass spectrometry.Results: Increased sputum eosinophilia was associated with higher concentrations of selected proinflammatory eicosanoids. In COPD subjects prostaglandin D2 and 11-dehydro-thromboxane B2 correlated negatively with airway obstruction measured by FEV1 and FEV1/FVC values. COPD subjects with disease exacerbations during past 12 months had significantly higher concentrations of prostaglandin D2, 12-oxo-eicosatetraenoic acid and 5-oxo-eicosatetraenoic acid.Conclusion: Stable COPD is often associated with eosinophil influx in the lower airways and elevated concentrations of eicosanoids that is reflected by some disease characteristics.Keywords: chronic obstructive pulmonary disease, eosinophils, eicosanoids

Aleksander Kania,1 Rafał Krenke,2 Krzysztof Kuziemski,3 Małgorzata Czajkowska-Malinowska,4 Natalia Celejewska-Wójcik,1 Barbara Kuźnar-Kamińska,5 Małgorzata Farnik,6 Juliusz Bokiej,7 Marta Miszczuk,2 Iwona Damps-Konstańska,3 Marcin Grabicki,5 Marzena Trzaska-Sobczak,6 Krzysztof Sładek,1 Halina Batura-Gabryel,5 Adam Barczyk6 1Department of Pulmonology, II Chair of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; 2Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Warsaw, Poland; 3Department of Allergology and Pneumonology, Medical University of Gdańsk, Gdańsk, Poland; 4Department of Lung Diseases and Respiratory Failure, Regional Center of Pulmonology, Bydgoszcz, Poland; 5Department of Pulmonology, Allergology and Respiratory Oncology, Poznań University of Medical Sciences, Poznań, Poland; 6Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 7Department of Lung Diseases, Regional Hospital Center Jelenia Góra, Jelenia Góra, Poland Background: This study aimed to examine the distribution of predefined phenotypes, demographic data, clinical outcomes, and treatment of patients who were included in the Polish cohort of the Phenotypes of COPD in Central and Eastern Europe (POPE) study. Patients and methods: This was a sub-analysis of the data from the Polish cohort of the POPE study, an international, multicenter, observational cross-sectional survey of COPD patients in Central and Eastern European countries. The study included patients aged .40 years, with a confirmed diagnosis of COPD, and absence of exacerbation for at least 4 weeks before study inclusion. A total of seven Polish centers participated in the study. Results: Among the 430 Polish COPD patients enrolled in the study, 61.6% were non-exacerbators (NON-AE), 25.3% were frequent exacerbators with chronic bronchitis (AE CB), 7.9% were frequent exacerbators without chronic bronchitis (AE NON-CB), and 5.1% met the definition of asthma-COPD overlap syndrome (ACOS). There were statistically significant differences among these phenotypes in terms of symptom load, lung function, comorbidities, and treatment. Patients with the AE CB phenotype were most symptomatic with worse lung function, and more frequently reported anxiety and depression. Patients with the ACOS phenotype were significantly younger and were diagnosed with COPD earlier than those with other COPD phenotypes; those with the ACOS phenotype were also more often atopic and obese. Conclusion: There is significant heterogeneity among COPD patients in the Polish population in terms of phenotype and clinical outcome. The non-exacerbator phenotype is observed most frequently in Poland, while the frequent exacerbator with chronic bronchitis phenotype is the most symptomatic. Keywords: chronic obstructive pulmonary disease, asthma-COPD overlap syndrome, phenotypes

Purpose: Obstructive sleep apnea (OSA) is associated with many long-term health consequences. We hypothesized that previously unrecognized and untreated OSA may be associated with more severe respiratory failure in hospitalized patients with COVID-19., Methods: Patients hospitalized in the Pulmonology Department with confirmed COVID-19, University Hospital in Kraków, Poland, between September 2020 and April 2021 were enrolled. OSA screening questionnaires including Epworth Sleepiness Scale (ESS), STOP-BANG, Berlin questionaire (BQ), OSA-50, and No-SAS were completed. Polygraphy was performed after > 24 h without requirement for supplemental oxygen., Results: Of 125 patients with median age of 61.0 years, 71% of whom were male. OSA was diagnosed in 103 patients (82%) and was categorized as mild, moderate, and severe in 41 (33%), 30 (24%), and 32 (26%), respectively. Advanced respiratory support was introduced in 85 patients (68%), and 8 (7%) patients eventually required intubation. Multivariable analysis revealed that increased risk of requirement for advanced respiratory support was associated with higher respiratory event index (OR 1.03, 95%CI 1.00 to 1.07), oxygen desaturation index (OR 1.05, 95%CI 1.02 to 1.10), and hypoxic burden (1.02 95% CI 1.00 to 1.03) and lower minimal SpO 2 (OR 0.89, 95%CI 0.81 to 0.98), but not with results of OSA screening tools like BQ score (OR 0.66, 95%CI 0.38 to 1.16), STOP-BANG score (OR 0.73, 95%CI 0.51 to 1.01), NoSAS score (OR 1.01, 95%CI 0.87 to 1.18), or OSA50 score (OR 0.84, 95%CI 0.70 to 1.01)., Conclusion: Previously undiagnosed OSA was common among hospitalized patients who survived the acute phase of COVID-19. The degree of OSA was associated with the severity of respiratory failure., (© 2023. The Author(s).)

Introduction: Hemostatic abnormalities play an important role in the pathogenesis of COVID‑19 and are considered determinants of the patients' outcomes. Less is known about the dynamics of these abnormalities in a short‑term observation., Objectives: The aim of the study was to evaluate hemostatic activity markers in patients hospitalized for COVID‑19 depending on the severity of respiratory failure., Patients and Methods: This was a prospective observational study enrolling adult patients hospitalized for COVID‑19 in a tertiary center in Poland, from January to May 2021. Blood samples were drawn upon admission and 28 days after the admission to measure the markers of coagulation, fibrinolysis, and endothelial dysfunction, and to evaluate whether there are significant differences between these 2 time points. All analyses were performed in the entire cohort and after stratification into 3 groups depending on the degree of respiratory support., Results: We recruited 245 patients at the median age of 63 years (interquartile range, 52-69), among whom 158 (64.5%) were men. The analysis of hemostatic markers on admission revealed that hypercoagulability, hypofibrinolysis, and endothelial dysfunction are related to the degree of respiratory support. We found significant differences between the admission and 28‑day follow‑up in all markers except for plasminogen activity. Interestingly, the markers of endothelial dysfunction remained the highest in the advanced respiratory support group after 28 days, while differences in the other markers diminished., Conclusion: Hemostatic abnormalities are significantly attenuated within a month after a hospital admission due to COVID‑19. The initially observed association between severity of the disease and hemostatic derangements persists only for the markers of endotheliopathy.

Background: The cellular inflammatory pattern of nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous. However, data on the heterogeneity of non-eosinophilic asthma (NEA) with aspirin hypersensitivity are scanty. By examination of N-ERD patients based on clinical data and eicosanoid biomarkers we aimed to identify NEA endotypes potentially guiding clinical management., Methods: Induced sputum was collected from patients with N-ERD. Sixty six patients (49.6% of 133 N-ERD) with NEA were included in the hierarchical cluster analysis based on clinical and laboratory data. The quality of clustering was evaluated using internal cluster validation with different indices and a practical decision tree was proposed to simplify stratification of patients., Results: The most frequent NEA pattern was paucigranulocytic (PGA; 75.8%), remaining was neutrophilic asthma (NA; 24.2%). Four clusters were identified. Cluster #3 included the highest number of NEA patients (37.9%) with severe asthma and PGA pattern (96.0%). Cluster #1 (24.2%) included severe only asthma, with a higher prevalence of NA (50%). Cluster #2 (25.8%) comprised well-controlled mild or severe asthma (PGA; 76.5%). Cluster #4 contained only 12.1% patients with well-controlled moderate asthma (PGA; 62.5%). Sputum prostaglandin D 2 levels distinguished cluster #1 from the remaining clusters with an area under the curve of 0.94., Conclusions: Among identified four NEA subtypes, clusters #3 and #1 represented N-ERD patients with severe asthma but a different inflammatory signatures. All the clusters were discriminated by sputum PGD 2 levels, asthma severity, and age of patients. The heterogeneity of non-eosinophilic N-ERD suggests a need for novel targeted interventions., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Introduction: COVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown., Patients and Methods: In 118 adult Caucasian severe but non-critically ill COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram [CAT assay]) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications., Results: COVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE., Conclusions: In COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: During the coronavirus disease 2019 (COVID-19) pandemic, it has become a pressing need to be able to diagnose aspirin hypersensitivity in patients with asthma without the need to use oral aspirin challenge (OAC) testing. OAC is time consuming and is associated with the risk of severe hypersensitive reactions. In this study, we sought to investigate whether machine learning (ML) based on some clinical and laboratory procedures performed during the pandemic might be used for discriminating between patients with aspirin hypersensitivity and those with aspirin-tolerant asthma., Methods: We used a prospective database of 135 patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) and 81 NSAID-tolerant (NTA) patients with asthma who underwent OAC. Clinical characteristics, inflammatory phenotypes based on sputum cells, as well as eicosanoid levels in induced sputum supernatant and urine were extracted for the purpose of applying ML techniques., Results: The overall best ML model, neural network (NN), trained on a set of best features, achieved a sensitivity of 95% and a specificity of 76% for diagnosing NERD. The 3 promising models (i.e., multiple logistic regression, support vector machine, and NN) trained on a set of easy-to-obtain features including only clinical characteristics and laboratory data achieved a sensitivity of 97% and a specificity of 67%., Conclusions: ML techniques are becoming a promising tool for discriminating between patients with NERD and NTA. The models are easy to use, safe, and achieve very good results, which is particularly important during the COVID-19 pandemic., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Introduction: Health‑related quality of life in patients with chronic obstructive pulmonary disease (COPD) can be measured by the Clinical COPD Questionnaire (CCQ). In this study, the CCQ was used to assess the therapeutic success of a fixed‑dose tiotropium / olodaterol combination treatment in Polish COPD patients., Objectives: We aimed to evaluate the changes in the CCQ score in Polish patients with COPD after 6 weeks of treatment with tiotropium / olodaterol and to assess the predictors of response to this treatment., Patients and Methods: Data of the Polish subgroup of the NIS‑CCQ observational study (NCT03663569) were extracted. COPD patients who had received a new tiotropium / olodaterol prescription were included. The primary end point was therapeutic success predefined as a 0.4‑point reduction in the CCQ score after 6 weeks of tiotropium / olodaterol treatment. Post‑hoc logistic regression analysis was performed to identify the predictors of response to the treatment., Results: After 6 weeks of treatment, 72.4% of patients achieved therapeutic success. The therapy was successful in 83.4% of treatment‑naïve patients, as compared with 62.6% and 73.3% of those previously treated with long‑acting muscarinic antagonists or long‑acting β2 agonists in monotherapy and in combination with inhaled corticosteroids, respectively. Therapeutic success was achieved by at least 50% of patients regardless of the COPD severity and exacerbation history but it was more frequent in patients with more severe disease. The airflow limitation severity grades 2 to 4, modified Medical Research Council Dyspnea Scale classes 2 to 4, exacerbations within the last year before the study, and treatment‑naïve status predicted a better response to tiotropium / olodaterol., Conclusions: Tiotropium / olodaterol treatment improved clinical control in Polish COPD patients. Therapeutic success was the most pronounced in individuals with more severe COPD and in the treatment‑naïve group but occurred also in those with moderate disease and in previously treated participants.

Background and Objectives: Poor sleep quality in patients with obstructive sleep apnea (OSA) may be associated with different clinical and polysomnographic features. The aim of this study was to identify features associated with poor sleep quality in OSA patients. Materials and Methods: This was a cross-sectional study enrolling patients with OSA confirmed by polysomnography (PSG). In addition to gathering clinical data, patients were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Clinical Global Impression Scale. Univariate and multivariable analyses were performed to identify factors associated with an increased risk of poor sleep quality in this population. Results: Among 505 enrolled patients (mean age of 57.1 years, 69.7% male) poor quality of sleep (PSQI score ≥ 5) was confirmed in 68.9% of them. Multivariable analysis revealed the following factors associated with poor sleep quality: chronic heart failure (OR 3.111; 95% CI, 1.083−8.941, p = 0.035), male sex (OR 0.396; 95% CI, 0.199−0.787, p = 0.008), total ESS score (OR 1.193; 95% CI, 1.124−1.266, p < 0.001), minimal saturation during sleep (OR 1.034; 95% CI, 1.002−1.066, p = 0.036), and N3 percentage of total sleep time (OR 1.110; 95% CI, 1.027−1.200, p = 0.009). Conclusions: Our study suggests that both the female sex and coexistence of heart failure are independent risk factors for poor sleep quality. Moreover, we hypothesize that nocturnal hypoxia may lead to a misperception of sleep quality and may explain the counterintuitive association between a higher proportion of deep sleep and poor sleep quality.

Aim: To assess the association between discharge policy and hospital stay length, and to evaluate the factors related to duration of viral clearance among patients with coronavirus disease 2019 (COVID-19)., Methods: This cross-sectional study enrolled consecutive patients aged ≥18 years with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test who were admitted to hospital. The participants were divided into the test-based (TB) policy group or symptom-based (SB) group depending on the policy valid at their hospital discharge. Multivariable analyses were performed to assess the factors related to the duration of hospital stay and viral clearance., Results: The study involved 305 patients (66.6% men). The mean age was 60.9 (15.2) years. TB and SB policy groups consisted of 145 (47.5%) and 160 patients (52.5%), respectively. The TB group had significantly longer duration of hospital stay (21.0 vs 16.0, P=0.003). In multivariable analysis, SB policy was associated with significantly shorter hospital stay (β-coefficient -5.87, 95% confidence interval [CI] -9.78 to -1.96, P=0.003). Longer viral clearance was associated with older age (β-coefficient 0.33, 95% CI 0.15 to 0.51, P<0.001) and history of cough in the pre-hospital phase of the disease (5.96, 95% CI 0.64 to 11.29, P = 0.028)., Conclusion: SB discharge policy is preferable in the context of limited resources during the COVID-19 pandemic.

Introduction: A significant proportion of patients with COVID‑19 present with a rapidly progressing severe acute respiratory failure., Objectives: We aimed to assess the efficacy of high‑flow nasal oxygen (HFNO) therapy in severe acute respiratory failure in the course of COVID‑19 in a noncritical care setting as well as to identify predictors of HFNO failure., Patients and Methods: This prospective observational study was conducted between March and December 2020. We enrolled all consecutive patients hospitalized with confirmed SARS‑CoV‑2 infection in whom HFNO therapy was used. The primary outcome was death or endotracheal intubation within 30 days from admission., Results: Of the 380 patients with COVID‑19 hospitalized at our tertiary center, 116 individuals (30.5%) requiring HFNO due to severe pneumonia were analyzed. The primary outcome occurred in 54 patients (46.6%). The overall 30‑day mortality rates were 30.2% (35 out of 116 patients) in the entire cohort and 64.7% (34 out of 51 patients) among individuals requiring endotracheal intubation. A multivariable analysis revealed that the ROX index (the ratio of oxygen saturation / fraction of inspired oxygen to respiratory rate) below 3.85 measured within the first 12 hours of therapy was related to increased mortality (hazard ratio, 5.86; 95% CI, 3.03-11.35) compared with the ROX index of 4.88 or higher., Conclusions: The results of our study suggest that nearly half of patients treated with HFNO due to severe COVID‑19 pneumonia will require mechanical ventilation. The ROX index is a useful tool for predicting HFNO failure in this population.

To evaluate association between bariatric surgery and changes in obstructive sleep apnea (OSA) severity and sleep architecture was as well as to asses continuous positive airway pressure (CPAP) effectiveness and compliance. We enrolled patients undergoing bariatric surgery. Polysomnography was performed in each patient preoperatively and 12 months after the procedure in a subgroup of patients diagnosed with OSA. STOP-BANG, Epworth Sleepiness Scale (ESS) and Berlin questionnaire scores were obtained pre- and postoperatively. CPAP compliance data was recorded during follow-up hospitalization. Among 44 patients with median age of 49.5 years, predominantly women (68.2%) pre- and postoperative polysomnography was performed. We observed significant improvement in STOP-BANG (6.0 vs. 3.0, p < 0.001) and ESS (12.0 vs. 5.0, p < 0.001) scores, apnea-hypopnea index (44.9 vs. 29.2, p < 0.001), oxygen desaturation index (43.6 vs. 18.3, p < 0.001) and sleep architecture parameters. CPAP compliance was poor with a median percentage of days with CPAP use accounting to 49.3%. Bariatric surgery is associated with a significant decrease in the number of sleep-related respiratory disturbances, as well as improvement of sleep efficiency. Postoperative CPAP therapy compliance was poor despite low rate of OSA resolution. This study suggests that patients with OSA undergoing bariatric surgery require postoperative reassessment.

Introduction: The coronavirus disease 2019 (COVID-19) is one of the greatest clinical challenges of the last decades. Clinical factors associated with severity of the disease remain unclear. The aim of the study was to characterize Polish patients hospitalized due to COVID-19 and to evaluate potential prognostic factors of severe course of the disease., Material and Methods: An observational study was conducted from March to July 2020 in the Pulmonology and Allergology Department of the University Hospital in Kraków, Poland. Consecutive patients with confirmed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection were enrolled, and data about past medical history, signs and symptoms, laboratory results, imaging studies results, in-hospital management and outcomes was prospectively gathered., Results: The study sample comprised 100 patients at the mean age of 59.2 (SD 16.1) years among whom 63 (63.0%) were male. Among them 10 (10.0%) died, 47 (47%) presented respiratory failure, 15 (15.0%) were transferred to the intensive care unit, 17 (17.0%) developed acute kidney injury, 7 (7.0%) had sepsis and 10 (10.0%) were diagnosed with pulmonary embolism. Multivariable analysis revealed age (OR 1.1; 95% CI 1.01-1.15), body mass index (BMI; OR 1.24; 95% CI 1.01-1.53), modified early warning score (MEWS; OR 3.95; 95% CI 1.48-12), the highest d-dimer value (OR 1.73; 95% CI 1.03-2.9) and lactate dehydrogenase (LDH; OR 1.16; 95% CI 1.03-1.3) to be associated with severe course of COVID-19., Conclusion: This observational study showed that almost half of hospitalized patients with COVID-19 developed respiratory failure in the course of the disease. Increasing age, BMI, MEWS, d-dimer value and LDH concentration were associated with the severity of COVID-19.

Background: To date, there has been no reliable in vitro test to either diagnose or differentiate nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD). The aim of the present study was to develop and validate an artificial neural network (ANN) for the prediction of N-ERD in patients with asthma., Methods: This study used a prospective database of patients with N-ERD (n = 121) and aspirin-tolerant (n = 82) who underwent aspirin challenge from May 2014 to May 2018. Eighteen parameters, including clinical characteristics, inflammatory phenotypes based on sputum cells, as well as eicosanoid levels in induced sputum supernatant (ISS) and urine were extracted for the ANN., Results: The validation sensitivity of ANN was 94.12% (80.32%-99.28%), specificity was 73.08% (52.21%-88.43%), and accuracy was 85.00% (77.43%-92.90%) for the prediction of N-ERD. The area under the receiver operating curve was 0.83 (0.71-0.90)., Conclusions: The designed ANN model seems to have powerful prediction capabilities to provide diagnosis of N-ERD. Although it cannot replace the gold-standard aspirin challenge test, the implementation of the ANN might provide an added value for identification of patients with N-ERD. External validation in a large cohort is needed to confirm our results., (© 2020 The Authors. Allergy published by John Wiley & Sons Ltd.)

Background: Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID-exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro-inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous., Objective: We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA)., Methods: A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA., Results: Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild-to-moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE 4 /logPGE 2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro-inflammatory LTE 4 in ISS and the highest logLTE 4 /logPGE 2 ratio. Class 3 subjects had mild-to-moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro- (LTE 4 , PGD 2 and 11-dehydro-TBX 2 ) was balanced by anti-inflammatory PGE 2 . The value of logLTE 4 /logPGE 2 was between values calculated for classes 1 and 3, similarly to disease control and severity., Conclusions: LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Road accidents are among the main fatalities worldwide and drowsy driving is a significant cause of road deaths where drivers are at fault. There are well known diseases which impair sensory and cognitive functions and can cause sleepiness during driving. Such diseases can be an important contraindication to driving because they may have an adverse effect on its safety. Thus, medical examinations for drivers should also be directed at identifying any possible conditions posing risks for driving safety. Occupational medicine specialists should look for symptoms of locomotor and sleep-related breathing disorders as these are medical conditions which could preclude a person from driving. In this case report, the authors describe a professional driver with chest deformity and present a pioneering attempt at assessing his medical fitness to drive. It is also explained why scoliosis can impair driving ability and how it should be diagnosed and treated. Finally, the authors describe how they used driving simulator tests as part of their diagnosis and suggest a relevant treatment regimen. Int J Occup Med Environ Health. 2019;32(5):735-45., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Introduction: The COPD Assessment Test (CAT) is a standardized patient-completed tool dedicated to assessment of symptom severity. While the Polish CAT version has been used for a few years, it has not been validated so far., Objectives: The aim of the study was to validate the Polish‑language version of the CAT questionnaire by assessing its reproducibility and reliability., Patients and Methods: Validation of the Polish‑language version of the CAT questionnaire was a substudy of the international multicenter observational cross‑sectional POPE survey of patients with chronic obstructive pulmonary disease (COPD) in Central and Eastern European countries. The study was completed in 395 outpatients with stable disease at least 4 weeks before the survey. Validation was performed with the use of the Spearman correlation and Cronbach α coefficients, Cohen κ test, and the Bland-Altman procedure., Results: The internal consistency assessed by the Cronbach α coefficient was 0.87 for the questionnaire and 0.84 to 0.86 for its separate items. The repeatability of the questionnaire was good to very good (Cohen κ, 0.76-0.85; P <0.01). The Spearman coefficient for the sum of scores of test-retest responses was 0.95 (P <0.01). The Bland-Altman analysis revealed very good test-retest and interrater reliability, with the mean difference between test I and test II results of -0.556 (95% CI, -0.345 to 0.767)., Conclusions: The Polish version of the CAT questionnaire is a reproducible and reliable instrument for evaluation of patients with COPD and should be recommended for use in clinical practice.

Background: The concordance between asthma-chronic obstructive pulmonary disease overlap (ACO) defined according to Global Inititative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) and other diagnostic criteria is unknown., Objective: To assess the concordance between different ACO definitions and to estimate the definition-based ACO prevalence and characteristics., Methods: A prospective, real-life study based on a 32-item data set was performed in a mixed population of patients with asthma and chronic obstructive pulmonary disease (COPD). Five different definitions of ACO, including the GINA/GOLD criteria, were analyzed., Results: A total of 1609 patients were included in the final analysis. Application of Venn diagram for ACO populations resulted in 31 ACO subpopulations, which were further reduced to 6 separate populations by introducing a rank order for the analyzed definitions to classify patients from intersecting groups. Overall, the level of agreement between different ACO definitions was poor. Cohen kappa coefficient for the agreement between ACO GINA/GOLD definition and other ACO definitions varied from 0.06 to 0.21. Only 2 patients (0.12%) met all the ACO definitions. Definition-based ACO prevalence ranged between 3.8% (Spanish criteria) and 18.4% (clinician's diagnosis). A total of 573 (33.4%) patients met the criteria from at least 1 ACO definition. Patients who could not be classified as suffering from "pure" asthma, "pure" COPD, or ACO accounted for as much as 27.5% of the whole investigated group. The most severe symptoms were observed in patients with ACO defined as COPD and asthma diagnosed at age less than 40 years., Conclusions: The current ACO definitions identify distinct populations that share only a small number of common features and present with different disease phenotypes. ACO prevalence is highly variable, depending on the definition applied., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: M. Szołkowska declares paid lectures for Roche Polska. The authors have no conflicts of interest to declare.

Obstructive sleep apnea (OSA) is the most common manifestation of sleep-related breathing disorders that are often accompanied by dysfunction of the autonomic nervous system. The main objective of the study was to assess the usefulness of heart rate variability (HRV) analysis in the diagnosis of patients with severe OSA and in the assessment of the effects of 3-month treatment with continuous positive airway pressure (CPAP). There were 54 patients enrolled in the study. The OSA group consisted of 39 patients suffering from severe OSA (apnea/hypopnea index >30/h), and the control group included 15 non-OSA patients with matched demographic characteristics and comorbidities. All patients underwent 24-h Holter electrocardiographic monitoring. HRV was analyzed using the time- and frequency-domains. We found that OSA patients had decreases in time-domains and increases in frequency-domains of HRV, compared to non-OSA controls, which strongly suggested a clinically disadvantageous shift in the balance of parasympathetic/sympathetic activity toward the latter. Further, CPAP treatment, partly, albeit significantly, reversed the OSA-induced changes in HRV. We conclude that HRV analysis may be of help in the diagnosis of OSA and in the monitoring of the effectiveness of treatment.

The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear.

Background: Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC)., Methods: EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge., Results: Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027)., Conclusion: A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A case of a 49-year-old male with exacerbation of eosinophilic granulomatosis with polyangiitis (EGPA) with heart involvement mimicking acute coronary syndrome is presented. Institution of intensive immunosupresive treatment resulted in the improvement of clinical condition and systolic left ventricular function. Coronary angiography excluded atherosclerosis as a primary cause of heart damage.

Introduction: Chronic rhinosinusitis (CRS) with nasal polyposis (NP) may be associated with hypersensitivity to nonsteroidal anti-inflammatory drugs, representing a syndrome of aspirin-exacerbated respiratory disease (AERD)., Objectives: The aim of the study was to validate a simple measurement of urinary leukotriene E4 (uLTE4) excretion for the diagnosis of AERD in patients with CRS and indication for surgery., Patients and Methods: Subjects requiring functional endoscopic sinus surgery (FESS) were recruited from the Department of Otolaryngology (n = 24). Before surgery, a standard oral placebo-controlled aspirin challenge was performed to diagnose aspirin hypersensitivity. Urine samples were collected on the placebo day and both before and within 2 to 4 hours after aspirin challenge for uLTE4 measurement., Results: All patients with CRS had sinusitis confirmed by computed tomography. Previous ear, nose, and throat surgery was performed in 70% of the patients, NP was present in 86%, and asthma was diagnosed in 62.5%. AERD was diagnosed in 8 subjects (7 women and 1 man). Five of those patients had bronchoconstriction. At baseline, median uLTE4 was 7.5-times higher in AERD subjects than in the remaining patients. It increased almost 6-fold following the challenge, while remained unchanged in patients without aspirin hypersensitivity. Pretest uLTE4 had a sensitivity of 87.5% and specificity of 93.75% to diagnose aspirin hypersensitivity in patients with CRS. After the challenge, the values improved to 100% sensitivity and 93% specificity., Conclusions: Among CRS subjects requiring FESS, as many as 33.3% may have AERD and respond to a small provocative dose of aspirin with bronchoconstriction and/or mucosal and skin edema. A simple and inexpensive measurement of uLTE4 can help diagnose AERD in patients with CRS with sensitivity of 87.5%, but its specificity is limited and depends on the arbitrary threshold of uLTE4.