Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study

Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity

Assessment of Airway Remodeling Using Endobronchial Ultrasound in Asthma-COPD Overlap

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 [email protected]: 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 ultrasoun

Distribution and characteristics of COPD phenotypes – results from the Polish sub-cohort of the POPE study

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, phenotype

9α,11β-PGF2, a Prostaglandin D2 Metabolite, as a Marker of Mast Cell Activation in Bee Venom-Allergic Patients

Mast cell (MC) mediators, among them prostaglandin D(2) (PGD(2)) and 9α,11β-PGF(2), PGD(2)’s metabolite, play a key role in allergic reactions, including bee venom anaphylaxis (BVA). Assessment of these mediators has never been performed in BVA. The aim of the study was to assess the activation of MC during in vivo provocation with bee venom (BV) and to measure PGD(2) and 9α,11β-PGF(2) in the course of an allergen challenge. The second aim was to determine if assessment of these mediators could be useful for predicting adverse events during venom immunotherapy (VIT). In 16 BV-VIT patients and 12 healthy subjects, levels of PGD(2) and 9α,11β-PGF(2) were assessed during BV provocation by means of the skin chamber method. Chamber fluids, collected at 5 and 15 min, were analyzed for both mediators by gas chromatography mass spectrometry negative ion chemical ionization. BVA in comparison to non-allergic patients had a significantly higher ratio of 9α,11β-PGF(2) in allergen-challenged chambers to 9α,11β-PGF(2) in allergen-free chambers after 15 min of provocation (p = 0.039). Allergen challenge resulted in a significant increase of 9α,11β-PGF(2) levels between 5 and 15 min after provocation only in BVA patients (p < 0.05). Analysis of log-transformed PGD2 levels showed significant difference between changes in PGD(2) concentration between BVA and healthy subjects. No study patient developed adverse reactions during. 9α,11β-PGF(2) is actively generated during the early allergic response to BV. Skin chamber seems to be a promising, non-invasive and safe model of in vivo allergen provocation in BV-allergic patients. High or low levels of both mediators do not predict occurrence of adverse events during VIT

Biomarkers for predicting response to aspirin therapy in aspirin‐exacerbated respiratory disease

BACKGROUND: Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin‐exacerbated respiratory disease (AERD). OBJECTIVE: To assess clinical features as well as genetic, immune, cytological and biochemical biomarkers that might predict a positive response to high‐dose aspirin therapy in AERD. METHODS: We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52‐week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high‐dose aspirin were defined as patients with improvement in 5‐item Asthma Control Questionnaire score, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score and forced expiratory volume in 1 second at 52 weeks. RESULTS: There were 28 responders (82%). Positive baseline predictors of response included female sex (p = .002), higher SNOT‐22 score (p = .03), higher blood eosinophil count (p = .01), lower neutrophil percentage in induced sputum (p = .003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (p = .004) and lower expression of the proteoglycan 2 gene, PRG2 (p = .01). The best prediction model included Asthma Control Test and SNOT‐22 scores, blood eosinophils and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. CONCLUSIONS AND CLINICAL RELEVANCE: Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression and low PRG2 expression may predict a positive response to long‐term high‐dose aspirin therapy in patients with AERD