Publications by authors named "Sevim Bavbek"

75 Publications

Microbiota - The Unseen Players in Adult Asthmatic Airways.

Turk Thorac J 2021 Jan 1;22(1):75-82. Epub 2021 Jan 1.

Department of Chest Diseases, Division of Allergy and Clinical Immunology, Ankara University School of Medicine, Ankara, Turkey.

Modulation of human lung airway physiology by commensal microbiota has become one of the key mechanisms involved in the pathogenesis of adult asthma. Recent evidence suggests that the composition of respiratory microbiota plays a significant role in the manifestation of adult asthma; however, scientific evidence about the relationship between airway microbial diversity and phenotypes of adult asthma is limited. Further research is needed to understand the interactions between the airway microbiota and host immune response to develop microbiota-based strategies in management of adult asthma. This study reviews the advances in culture-independent methods for detection of airway microbiome, the current data about airway microbiota in healthy individuals and in adult patients with asthma with a focus on bacterial communities, and the future research directions in airway microbiome.
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http://dx.doi.org/10.5152/TurkThoracJ.2020.19085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919442PMC
January 2021

Effect of drug desensitization on drug hypersensitivity-related quality of life.

J Allergy Clin Immunol Pract 2021 Apr 10;9(4):1738-1741.e1. Epub 2020 Nov 10.

Ankara University School of Medicine, Department of Chest Diseases, Division of Allergy and Immunology, Ankara, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.10.055DOI Listing
April 2021

Change in Allergy Practice during the COVID-19 Pandemic.

Int Arch Allergy Immunol 2021 15;182(1):49-52. Epub 2020 Oct 15.

Division of Allergy and Clinical Immunology, Department of Chest Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey,

Background: International guidelines in asthma and allergy has been updated for COVID-19 pandemic and pandemic has caused dramatic changes in allergy and immunology services. However, it is not known whether specialty-specific recommendations for COVID-19 are followed by allergists.

Objectives: By conducting this study, we aimed to determine the attitudes and experiences of adult/pediatric allergists on allergy management during COVID-19.

Method: We used a 20-question survey to elicit data from allergists (residents and pediatric and adult allergists registered to the Turkish National Society of Allergy and Clinical Immunology) across Turkey via e-mail. We analyzed the data statistically for frequency distributions and descriptive analysis.

Results: A total of 183 allergists participated in the survey. Telemedicine was used for management of asthma (73%), allergic rhinitis (53%), atopic dermatitis (51%), chronic urticaria/angioedema (59%), drug hypersensitivity (45%), food allergy (48%), venom allergy (30%), anaphylaxis (22%), and hereditary angioedema (28%). Thirty-one percent of the respondents discontinued subcutaneous immunotherapy (SCIT) during the COVID-19 pandemic. Thirty-four percent of the physicians reported interruption of systemic steroid use in asthma patients, and 25% of the respondents discontinued biological therapy.

Conclusions: Allergists in Turkey have been using telemedicine at a high rate during the COVID-19 pandemic for asthma and rhinitis. The continuation rate of SCIT was low while the discontinuation rate of biologicals and systemic steroid use in asthma was high in Turkey.Our study results and learning from the experiences of other countries and specialties may help to optimize allergy practice and compatibility with international guidelines.
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http://dx.doi.org/10.1159/000512079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649687PMC
January 2021

Rituximab Hypersensitivity: From Clinical Presentation to Management.

Front Pharmacol 2020 8;11:572863. Epub 2020 Sep 8.

Division of Immunology and Allergy, Department of Chest Diseases, Ankara University School of Medicine, Ankara, Turkey.

Rituximab is a chimeric monoclonal antibody (mAb) against CD20 molecule which is expressed on human B cells. It has been used for the treatment of various lymphoid malignancies, lymphoproliferative diseases, and rheumatologic disorders. Rituximab is generally well tolerated. However, increased use of rituximab has been associated with hypersensitivity reactions (HSRs), which can be classified as infusion-related, cytokine-release, type I (IgE/non-IgE), mixed, type III, and type IV reactions. Immediate infusion-related reactions to rituximab are quite common and decrease in frequency with subsequent infusions. However, in about 10% of patients, severe infusion-related reactions develop, which prevent its use. Some of the immediate infusion reactions are due to a cytokine-release but some reactions raise concerns for type I (IgE/non-IgE) hypersensitivity. Recent studies have shown the presence of serum anti-rituximab antibodies, either represented by the IgG or IgE isotype. In some cases, clinical manifestations of IgE-mediated reactions and cytokine-release reactions partially overlap, which is called a mixed reaction. Classified as Type III reaction, rituximab-induced serum sickness reactions have been reported in patients with autoimmune diseases and hematological malignancies. The classic serum sickness triad (fever, rash, and arthralgia) has been observed in patients mainly with an underlying rheumatologic condition. Severe delayed type IV hypersensitivity reactions including non-severe maculopapular rash to severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been rarely reported following rituximab injection. Comprehensive reviews focused on rituximab-induced HSRs are scarce. We aimed to review clinical presentations, underlying mechanisms of rituximab hypersensitivity, as well as management including rapid drug desensitization.
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http://dx.doi.org/10.3389/fphar.2020.572863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508176PMC
September 2020

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Authors:
Ludger Klimek Oliver Pfaar Margitta Worm Thomas Eiwegger Jan Hagemann Markus Ollert Eva Untersmayr Karin Hoffmann-Sommergruber Alessandra Vultaggio Ioana Agache Sevim Bavbek Apostolos Bossios Ingrid Casper Susan Chan Alexia Chatzipetrou Christian Vogelberg Davide Firinu Paula Kauppi Antonios Kolios Akash Kothari Andrea Matucci Oscar Palomares Zsolt Szépfalusi Wolfgang Pohl Wolfram Hötzenecker Alexander R Rosenkranz Karl-Christian Bergmann Thomas Bieber Roland Buhl Jeroen Buters Ulf Darsow Thomas Keil Jörg Kleine-Tebbe Susanne Lau Marcus Maurer Hans Merk Ralph Mösges Joachim Saloga Petra Staubach Uta Jappe Klaus F Rabe Uta Rabe Claus Vogelmeier Tilo Biedermann Kirsten Jung Wolfgang Schlenter Johannes Ring Adam Chaker Wolfgang Wehrmann Sven Becker Laura Freudelsperger Norbert Mülleneisen Katja Nemat Wolfgang Czech Holger Wrede Randolf Brehler Thomas Fuchs Peter-Valentin Tomazic Werner Aberer Antje-Henriette Fink-Wagner Fritz Horak Stefan Wöhrl Verena Niederberger-Leppin Isabella Pali-Schöll Wolfgang Pohl Regina Roller-Wirnsberger Otto Spranger Rudolf Valenta Mübecell Akdis Paolo M Matricardi François Spertini Nicolai Khaltaev Jean-Pierre Michel Larent Nicod Peter Schmid-Grendelmeier Marco Idzko Eckard Hamelmann Thilo Jakob Thomas Werfel Martin Wagenmann Christian Taube Erika Jensen-Jarolim Stephanie Korn Francois Hentges Jürgen Schwarze Liam O Mahony Edward F Knol Stefano Del Giacco Tomás Chivato Pérez Jean Bousquet Anna Bedbrook Torsten Zuberbier Cezmi Akdis Marek Jutel

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

European Academy of Allergy and Clinical Immunology (EAACI).

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

[Anti-IL-5 treatments in severe eosinophilic asthma: real life datas].

Tuberk Toraks 2020 Jul;68(2):148-159

Division of Allergy and Clinical Immunology, Department of Chest Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey.

Randomized controlled studies have shown that anti-IL-5 treatments reduce the need for oral corticosteroids, annual asthma exacerbation and hospitalization rates, blood eosinophil count and increase FEV1 values, asthma control, and quality of life in patients with eosinophilic severe asthma. Although the number of real-life studies with anti-IL-5 is limited, there are 10 real life studies with mepolizumab, one real life study with benralizumab and one real life study with reslizumab in the current literature. Similar to randomized controlled trials, real-life studies reported that a reduction in the need for oral corticosteroids, annual asthma exacerbation and hospitalization rates, and blood eosinophil counts and increase FEV1 values, asthma control test and quality of life scores, Response criteria were defined in some of the real-life studies and although different response rates were given according to these criteria, most of the patients with severe eosinophilic asthma showed high response rates to anti-IL-5 treatments. In real-life studies evaluating the safety of anti-IL-5 treatments, the most common adverse effect is mild local injection site reaction that does not require treatment, in conclusion, real-life studies suggest that all three anti-IL-5 treatments in clinical practice are effective and well tolerated.
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http://dx.doi.org/10.5578/tt.69416DOI Listing
July 2020

Economic Burden of Pediatric Asthma in Turkey: A Cost of Illness Study from Payer Perspective.

Turk Thorac J 2020 Jul;21(4):248-254

Department of Health Care Management, Başkent University Faculty of Health Sciences, Ankara, Turkey.

Objectives: To estimate economic burden of pediatric asthma in Turkey from payer perspective.

Materials And Methods: This cost of illness study was based on identification of per patient annual direct medical costs for the management of pediatric asthma in Turkey from payer perspective. Average per patient direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations and interventions, drug treatment and equipment, and co-morbidities/complications.

Results: Based on total annual per patient costs calculated for outpatient admission ($113.14), laboratory-radiological tests ($35.94), hospitalizations ($725.92), drug treatment/equipment ($212.90) and co-morbidities/complications ($144.62) cost items, total per patient annual direct medical cost related to management of pediatric asthma was calculated to be $1,232.53 from payer perspective. Hospitalizations and interventions (58.9%) was the main cost driver. Direct cost for managing controlled and uncontrolled pediatric asthma were calculated to be $530.17 [key cost driver: drugs/equipment (40.0%)] and $1,023.16 [key cost driver: hospitalization/interventions (59.0%)], respectively.

Conclusion: Our findings indicate that managing patients with pediatric asthma pose a considerable burden to health economics in Turkey, with hospitalizations identified as the main cost driver and two-fold cost increment in case of uncontrolled disease.
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http://dx.doi.org/10.5152/TurkThoracJ.2019.19025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371397PMC
July 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

Allergy 2020 11;75(11):2764-2774

Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON, Canada.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
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http://dx.doi.org/10.1111/all.14407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300800PMC
November 2020

Intradermal Tests With Drugs: An Approach to Standardization.

Front Med (Lausanne) 2020 15;7:156. Epub 2020 May 15.

Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.

Intradermal tests (IDTs) are performed and interpreted differently in drug allergy centers making valid comparison of results difficult. To reduce method-related and intercenter variability of IDTs by the introduction of a standardized method. In 11 centers of the European Network for Drug Allergy, IDTs were prospectively performed with saline and with amoxicillin (20 mg/ml) using (1) the local method and (2) the standardized European Network in Drug Allergy (ENDA) method (0.02 ml). The diameters of the initial injection wheal (Wi) for the different volumes and sites injected obtained from each center were analyzed. The most reproducible method was to fill a syringe with test solution, then expel the excess fluid to obtain exactly 0.02 ml. The median Wi diameter with 0.02 ml injection using the standardized method was 5 mm [range 2-10 mm; interquartile range (IQR) 5-5 mm; = 1,096] for saline and 5 mm (range 2-9 mm; IQR = 4.5-5 mm; = 240) for amoxicillin. IDT injection sites did not affect the Wi diameter. Training improved precision and reduced the variability of Wi diameters. Using the standardized IDT method described in this multicenter study helped to reduce variability, enabling more reliable comparison of results between individuals and centers.
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http://dx.doi.org/10.3389/fmed.2020.00156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243670PMC
May 2020

Validity and Reliability of the Assessment Tool for Asthma (ATA) Questionnaire: the ATA Study.

Turk Thorac J 2020 03 1;21(2):93-99. Epub 2020 Mar 1.

Department of Pulmonary Diseases, Division of Allerrgy and Immunology, Ankara University School of Medicine, Ankara, Turkey.

Objectives: A multicenter trial was designed to validate the "Assessment Tools for Asthma (ATA)" questionnaire, a newly developed questionnaire, which evaluates both asthma control and risk factors associated with asthma control with a single instrument.

Materials And Methods: This cross-sectional study involved 810 cases from 14 clinics in 9 Turkish cities. The ATA questionnaire and Asthma Control Test (ACT) were administered. The Visual Analog Scale (VAS) was used to evaluate the control status of 100 randomized cases. ATA is an eight-item physician-administered questionnaire. It comprises the following two sections-ATA1, assesses symptomatic control criteria, and the remaining section, queries the flare-up of asthma, control of comorbidities, treatment adherence, and inhaler technique.

Results: The mean scores for ATA1, ATA total, VAS, and ACT were 24.7±14.8, 53.8±19, 7.1±3, and 18.8±5.5, respectively. According to the ATA questionnaire, among all patients, 34.3% had controlled, 18.8% had partly controlled, and 46.9% had uncontrolled asthma. Furthermore, 16.6% patients had flare-ups between visits, 96.4% patients had uncontrolled comorbidity, 17% patients had irregular asthma treatment, and only 8.4% patients used the incorrect inhaler technique. The ATA questionnaire showed internal consistency (Cronbach's alpha coefficient=0.683). ACT, ATA1, and two specialists' evaluations using VAS correlated strongly with the ATA total scores (Spearman correlation coefficient (r) values: 0.776, 0.783, and 0.909, respectively; p-values: p<0.001, p<0.001, and p<0.001, respectively). According to Receiver Operating Characteristic analysis, the cut-off value of ATA was 50 (sensitivity=84.4%, specificity=82.40%).

Conclusion: The validated ATA questionnaire may be a practical tool for physicians in asthma management.
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http://dx.doi.org/10.5152/TurkThoracJ.2019.180186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089703PMC
March 2020

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Allergy 2021 01;76(1):71-89

Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Hospital for Sick Children, Toronto, ON, Canada.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
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http://dx.doi.org/10.1111/all.14282DOI Listing
January 2021

Anti-IL-5 Biologicals Targeting Severe Late Onset Eosinophilic Asthma.

Turk Thorac J 2020 Jan 1;21(1):61-68. Epub 2020 Jan 1.

Department of Pulmonary Disease, Division of Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey.

Improved knowledge about the pathogenesis of asthma has facilitated the development of novel drugs and provided hope for patients with severe asthma. After the short- and long-term success of omalizumab in severe allergic phenotype, researchers have targeted patients with severe eosinophilic asthma who comprise up to 45% of adult severe asthma. Interleukin (IL)-5 and IL-5 receptor subunit α play crucial roles in the development, maturation, and operation of eosinophils. Currently, patients treated with anti-IL-5 biologicals depleting eosinophils experience the positive efficacy of these drugs, especially with regard to the reduction of exacerbation rate. The aim of this review was to shed light on severe eosinophilic asthma treatment with these new currently available agents selectively targeting IL-5 or its receptor, discussing their usage including pre-treatment concerns, such as selecting the target population and choosing the right agent among them, and subsequent assessment of relevant effect and safety issues.
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http://dx.doi.org/10.5152/TurkThoracJ.2019.180204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020889PMC
January 2020

Hypersensitivity reactions to proton-pump inhibitors: Clinical presentation, diagnosis, and management.

Allergy Asthma Proc 2020 03;41(2):e37-e44

Division of Allergy and Immunology, Department of Chest Diseases, Ankara University School of Medicine, Ankara, Turkey.

Proton-pump inhibitors (PPI) are one of the most commonly prescribed drugs, and they are generally well tolerated. However, several immediate and delayed hypersensitivity reactions due to PPIs have been reported. To review the clinical characteristics and management of immune-mediated immediate and delayed hypersensitivity reactions to PPIs. We performed a search of a medical literature data base from January 1980 to October 2019 by using keywords that included "proton-pump inhibitors" and "hypersensitivity." Anaphylaxis is the most-common clinical presentation in patients with immediate hypersensitivity reactions to PPIs, followed by urticaria and/or angioedema. Occupational contact dermatitis, maculopapular eruption, fixed drug eruption, symmetrical drug-related intertriginous and flexural exanthema, and severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have also been reported with PPIs. The current knowledge and severity of the reported reactions indicated the importance of consideration of a causal relationship between hypersensitivity reactions and PPIs, and awareness of the existence of cross-reactivity among PPIs.
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http://dx.doi.org/10.2500/aap.2020.41.190033DOI Listing
March 2020

Rapid Drug Desensitization with Chemotherapeutics (Platins, Taxanes, and Others): A Single-Center Retrospective Study.

Int Arch Allergy Immunol 2019 20;179(2):114-122. Epub 2019 Mar 20.

Department of Chest Disease, Division of Allergy and Clinical Immunology, Ankara University School of Medicine, Ankara, Turkey,

Background: Rapid drug desensitization (RDD) induces a temporary tolerance to chemotherapeutics that induce hypersensitivity reactions (HSRs).

Purpose: Our objective is to report our experience with RDD to platins, taxanes, etoposide, doxorubicin, and irinotecan.

Methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to chemotherapeutics. HSRs were classified as grade I, II, or III, based on their severity. Skin prick/intradermal tests were performed with implicated chemotherapeutics. A 12-step RDD protocol was used.

Results: The study consisted of 38 women and 3 men (mean age 53.3 ± 11.6 years). Patients had ovarian (n = 13, 31.8%), breast (n = 10, 24.4%), colon (n = 7, 17%), lung (n = 4, 9.8%), and other cancers (n = 7; endometrial sarcoma, testicular cancer, uterine cancer, ampulla of Vater tumor, choledochal tumor, peritonitis carcinomatosa, and Merkel cell carcinoma, n = 1, respectively). Twenty-two patients experienced HSRs to platins, 15 to taxanes, and 4 to other chemotherapeutics (doxorubicin, irinotecan, and etoposide). A total of 122 RDDs (47 to platins, 52 to taxanes, 23 to other chemotherapeutics) were performed. In 25 (61%) patients no reactions occurred during RDD, but breakthrough reactions developed in 16 patients (39%) with platins (n = 11), taxanes (n = 3), doxorubicin (n = 1), and irinotecan (n = 1). RDD procedures could not be completed in only 2 patients with grade II breakthrough reactions to carboplatin and oxaliplatin.

Conclusion: In our experience, 98.3% of 122 RDDs were completed. We found that RDD was safe and effective in this the largest series of RDD with chemotherapeutics in our country.
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http://dx.doi.org/10.1159/000496745DOI Listing
July 2019

Analysis of the factors associated with diagnostic skin test positivity in immediate-type hypersensitivity reactions due to proton pump inhibitors.

Allergy 2019 06 29;74(6):1187-1190. Epub 2019 Jan 29.

Department of Chest Diseases, Division of Allergy and Immunology, Ankara University School of Medicine, Ankara, Turkey.

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http://dx.doi.org/10.1111/all.13715DOI Listing
June 2019

Omalizumab in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA): single-center experience in 18 cases.

World Allergy Organ J 2018 3;11(1):39. Epub 2018 Dec 3.

1Department of Chest Diseases, Division of Immunology and Allergy, School of Medicine, Ankara University, Ankara, Turkey.

Background: Data are limited regarding the effectiveness of omalizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Our aim was to evaluate the clinical and functional effectiveness of omalizumab in patients with EGPA in long-term follow-up.

Methods: This study was a retrospective chart review of patients with EGPA who were treated with omalizumab injections between May 2012 and April 2018. Once treatment with omalizumab was started, data were collected at various time points: baseline, the 16th week, 1st year, and annually until the last evaluation.

Results: Eighteen patients (16F/2M) with a mean age of 48.61 ± 11.94 years were included. Data were available for all patients for the first year, 12 patients for the second year, 10 patients for the third  year, 8 patients for the fourth  year and 5 patients for the fifth year. All patients were on mean dosage of 15.77 ± 7.6 mg/day oral corticosteroid (OCS) as daily bases for mean 8.61 ± 4 years besides high-dose inhaler corticosteroid/long-acting beta agonist. Antineutrophil cytoplasmic antibodies (ANCA) were positive in 2  patients, and 8 patients were diagnosed as having vasculitis by skin biopsy, one patient had polyneuropathy, and one patient had cardiac involvement.By considering the individual responses of patients and the level of improvement at the last evalulation, 10 (55.6%) patients responded completely, 1 responded partially, and 7 (38.9%) had no improvement. Omalizumab worked as a steroid-sparing agent in all patients and the daily OCS dose was reduced with a mean dosage of 6.28 mg/day at the end of the first year. The mean OCS reduction time for the whole group was 4 months. A reduction in asthma exacerbations/hospitalizations, improvement in forced expiratory volume in 1 second, and no decrease in the eosinophil count during treatment with omalizumab were also observed.

Conclusions: Omalizumab improved asthma control in some patients with EGPA with uncontrolled asthma by reducing asthma exacerbations and oral steroid requirement. However, more data are needed before recommending widespread use of omalizumab in patients with EGPA.
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http://dx.doi.org/10.1186/s40413-018-0217-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276141PMC
December 2018

Role of Skin Tests in the Diagnosis of Immediate Hypersensitivity Reactions to Taxanes: Results of a Multicenter Study.

J Allergy Clin Immunol Pract 2019 03 5;7(3):990-997. Epub 2018 Oct 5.

Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

Background: Immediate hypersensitivity reactions (HSRs) to taxanes have been increasing in recent years, but the importance of skin tests in allergological workup has not been established.

Objective: In our study we tried to evaluate the role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and docetaxel.

Methods: In this multicenter prospective study, we enrolled patients with immediate HSRs to the aforesaid agents. Skin tests were performed on these subjects and if results were negative, intradermal tests with the culprit drug were conducted. Patients with grade 1 reactions subsequently underwent graded challenge; in cases of grade 2 or 3 reactions and/or positive test results, the culprit drug was administered with a desensitization schedule. Skin tests were also performed in 30 control subjects exposed to the taxanes without HSRs.

Results: A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel) were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients (69%) developed grade 2 or 3 reactions. Prick test results were negative in all the cases, whereas intradermal test results were positive in 14 patients (10 with paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests significantly correlated with grade 3 reactions and cutaneous involvement during HSRs. Graded challenge was performed in 16 patients without problems and 58 subjects underwent desensitization, which was well tolerated in all but 2 cases. In the control group, skin test results were negative in all the patients.

Conclusions: Skin tests for taxanes seem useful and can be performed in the allergological workup of subjects with HSRs to these agents, especially in cases of severe reactions with cutaneous involvement.
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http://dx.doi.org/10.1016/j.jaip.2018.09.018DOI Listing
March 2019

[Alarmins and anti-alarmin biologics in asthma].

Tuberk Toraks 2018 Jun;66(2):166-175

Division of Allergy and Immulogy, Faculty of Medicine, Ankara University, Ankara, Turkey.

Alarmins are endogenous, constitutively expressed, chemotactic, and immune activating proteins/peptides that are released as a result of degranulation, cell injury or death, or in response to immune induction. Alarmins are involved in a variety of processes including antimicrobial gene expression regulation, cellular homeostasis, wound healing, inflammation, allergy, autoimmunity and oncogenesis. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) are airway epithelial-derived alarmins and the characteristics of alarmins are that they are rapidly released after nonprogrammed cell death, they activate the immune cells. It is thought that the inhibition of the effects of alarmin on the immune system may be useful in the treatment of asthma. The effects of anti-IL-25 (Brodalumab) and anti-TSLP (Tezepelumab) treatments on asthmatic patients were investigated for that purpose. Brodalumab provided limited benefit only in the asthmatic group with high reversibility. Tezepelumab was found to be the first biological drug to have significant positive effect on two important indicators of asthmatic inflammation such as blood eosinophils and nitric oxide fraction in exhaled air. The effect of anti-IL-33 on airway inflammation was shown in animal experiments and anti-IL-33 was found to be protective by reducing eosinophilia, inflammatory cytokines, airway hypersensitivity. In this review, we aimed to summarize the role of alarmines in the pathogenesis of asthma and the results of studies with anti-alarmin biologics.
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http://dx.doi.org/10.5578/tt.66695DOI Listing
June 2018

Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper.

Allergy 2019 01 2;74(1):28-39. Epub 2018 Oct 2.

Department of Immunology and Allergy, Medical University, Lodz, Poland.

NSAID-exacerbated respiratory disease (N-ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence-based recommendations for the diagnosis and management of N-ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N-ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N-ERD. Recommendations for the most effective management of a patient with N-ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub-phenotypes and emerging sub-endotypes of N-ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N-ERD and unmet needs, which should be addressed in the future.
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http://dx.doi.org/10.1111/all.13599DOI Listing
January 2019

Subcutaneous Injectable Drugs Hypersensitivity and Desensitization: Insulin and Monoclonal Antibodies.

Immunol Allergy Clin North Am 2017 11 18;37(4):761-771. Epub 2017 Aug 18.

Division of Allergy and Immunology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.

Injectable drugs, including monoclonal antibodies, are becoming crucial components in the management of chronic diseases. The most common side effects are local reactions at the site of administration. With the increased and prolonged use of these medications, we are seeing increased reports of hypersensitivity reactions. The aim of this article is to discuss the signs and symptoms of these reactions as well as management, which may involve desensitization for 3 commonly encountered injectable drugs: tumor necrosis factor-α inhibitors (etanercept and adalimumab), insulin, and omalizumab.
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http://dx.doi.org/10.1016/j.iac.2017.06.001DOI Listing
November 2017

Physicians' preference for controller medication in mild persistent asthma.

Respir Med 2017 10 1;131:236-240. Epub 2017 Sep 1.

Turkish National Society of Allergy and Clinical Immunology, Turkey.

Background: Although the asthma guidelines recommend inhaled corticosteroids(ICS) or leukotriene receptor antagonists-(LTRAs) for the treatment of mild persistent asthma, factors governing the physicians' preference are unknown. We aimed to investigate the preference of physicians for the controller medication and the factors governing their choice.

Methods: A self-administered questionnaire composed of 16 questions that aimed to determine the preference of the physicians for the first choice controller medication in mild persistent asthma and physician and patient related factors that may be associated with this selection was e-mailed to the members of the Turkish National Society of Allergy and Clinical Immunology and distributed to participants in the 21st congress.

Results: Of the 670 questionnaires, there were 51% participants and 336 of them were complete enough to be included in the analysis. Low dose ICS was preferred as the first choice controller medication for mild persistent asthma by 84.5% of the physicians. The reasons for physicians' preference were different for ICS and LTRA. In the logistic regression analysis, use of asthma guidelines (OR:3.5, 95%CI:1.3-9.3, p = 0.01), alignment in guidelines (OR:2.9, 95%CI:1.4-5.8, p = 0.002) and the opinion that it is a more effective (OR:2.3, 95%CI:1.1-4.8, p = 0.02) were independently associated with ICS preference. Being a pediatrician (OR:5.4, 95%CI: 2.7-10.5, p < 0.001) and the opinion that it has better patient compliance (OR:4.4, 95%CI: 1.6-12.0, p = 0.004) were independently associated with LTRA preference.

Conclusion: Surveyed Turkish physicians, the majority of whom were specialists, preferred ICS over LTRA as controller medication in mild persistent asthma. Asthma guidelines, training background (pediatrician versus not) and perceived efficacy and patient compliance appeared to influence their preferences.
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http://dx.doi.org/10.1016/j.rmed.2017.08.029DOI Listing
October 2017

Omalizumab in non-allergic Asthma: A report of 13 cases.

J Asthma 2018 07 12;55(7):756-763. Epub 2017 Sep 12.

a Division of Immunology and Allergy, Department of Chest Diseases, School of Medicine , Ankara University , Ankara , Turkey.

Background: There are limited data regarding the effectiveness of omalizumab in patients with non-allergic asthma.

Objective: To evaluate the clinical and functional effectiveness of omalizumab in patients with non-allergic asthma.

Methods: The study was a single-center, retrospective chart review of patients with non-allergic asthma who were treated with add-on omalizumab between February 2014 and March 2016. After omalizumab was started, data of the asthma control test (ACT), pulmonary function test, and daily oral corticosteroid (OCS) dosage were collected at baseline, 16 weeks, 1 year, 2 and 3 years (if available). The number of exacerbations/hospitalizations were collected 1 year prior to and 6 months/1 year after omalizumab. To calculate the total daily dosage of OCS in milligrams, data for 6 months/1 year prior and after omalizumab treatment were recorded.

Results: Thirteen patients were included. After omalizumab, the mean ACT was significantly increased at 16 weeks (n = 13, p = 0.002), 1 year (n = 7, p = 0.006), and 2 years (n = 5, p = 0.006). The mean daily OCS dose was significantly decreased at 16 weeks (n = 13, p = 0.001), 1 year (n = 7, p = 0.006), and 2 years (n = 5, p = 0.04). The mean number of exacerbations and hospitalizations were decreased at the 6th month (n = 13; p = 0.001, p = 0.005) and 1st year (n = 7; p = 0.01, p = 0.02). The mean total quantity of OCS decreased 42% from 1.4 to 0.8 g in the six-month period prior to and post-omalizumab treatment (n = 6, p = 0.02) and decreased 76% from 3.8 to 0.9 g at 1 year in the pre vs. post-omalizumab treatment comparison (n = 7, p = 0.01). Six (46.2%) patients responded perfectly and seven (53.8%) partially responded to treatment.

Conclusion: Omalizumab can be effective in non-atopic severe asthma.
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http://dx.doi.org/10.1080/02770903.2017.1362427DOI Listing
July 2018

A Case of Pantoprazole Anaphylaxis with Cross Reactivity to All Proton Pump Inhibitors: Finding a Safe Alternative.

Curr Drug Saf 2017 ;12(3):198-200

Department of Clinical Immunology and Allergy, Ankara University, School of Medicine, Ankara. Turkey.

Background: Hypersensitivity reactions due to Proton pump inhibitors (PPIs ) are rare, and further anaphylaxis to a PPI with cross-reactivity to all commercially available PPIs is very rare.

Objective: To present a case of anaphylaxis to pantoprazole with cross-reactivity to all commercially available PPIs.

Methods: Skin prick tests (SPTs), intradermal tests (IDTs) and oral provocation tests (OPTs) were performed with available PPIs according to the method described in previous studies.

Results: All tested PPIs except lansoprazole were positive on skin tests either SPT or IDT. The patient was challenged with lansoprazole at increasing doses (7.5 mg, 15 mg, 30 mg capsule) every 60 minutes and she reacted with urticaria to 52.5 mg cumulative dose of lansoprazole. She could tolerate ranitidine and famotidine tablets via OPT.

Conclusion: In our best knowledge, our case was the first case in this regard and that points the possibility of all cross-reactive pattern in patients with pantoprazole anaphylaxis and the importance of a thorough drug allergy work-up for finding safe alternatives. H2 receptor antagonists are used as safe alternatives in cases with PPI hypersensitivity.
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http://dx.doi.org/10.2174/1574886312666170711122341DOI Listing
June 2018

Prospects for new and emerging therapeutics in severe asthma: the role of biologics.

Expert Rev Respir Med 2017 06 10;11(6):505-512. Epub 2017 May 10.

b Division of Immunology and Allergy, Department of Chest Diseases , Ankara University School of Medicine , Ankara , Turkey.

Introduction: Asthma is a common and heterogeneous disease. While current conventional therapies are effective in the majority of the patients, a significant subgroup remain uncontrolled despite these treatments. Different biological agents are currently approved or undergoing development for treatment of asthma, including anti-IgE, anti-interleukin (IL)-5, anti-IL-13, anti-IL-4 and anti-thymic stromal lymphopoietin agents. This review will focus on the currently available evidence regarding the new and emerging biological agents in severe asthma. Areas covered: A non-systematic review of the available English-language literature regarding severe asthma and biological agents was performed. We summarized and discussed the current evidence about the use of new and emerging biological agents in severe asthma. Expert commentary: Because of the heterogeneity of response to therapy in refractory asthma it is of utmost importance to correctly estimate patient outcomes before starting biological therapy to make patient selection more effective. Currently, the decision of which biologic to initiate in patients with uncontrolled severe asthma should be made based on the atopic status, blood eosinophil and total IgE levels, exacerbation history, safety profile, cost, frequency and route of administration.
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http://dx.doi.org/10.1080/17476348.2017.1326821DOI Listing
June 2017

Does the medical diagnosis of occupational asthma coincide with the legal diagnosis?

J Asthma 2017 Nov 5;54(9):930-937. Epub 2017 Jan 5.

a Department of Chest Diseases, Division of Allergy and Clinical Immunology , Ankara University School of Medicine , Ankara , Turkey.

Objective: The incidence of occupational asthma (OA) is increasing worldwide. In this study, we first aimed to document the rate of diagnosis of OA among patients who were referred to our clinic from the Social Security Institution and the factors that affected diagnosis; secondly, we aimed to assess the consistency of the medical and legal diagnoses.

Methods: The study involved 132 consecutive patients who were referred to our clinic for the evaluation of OA between 2010 and 2015. Detailed workplace history, the tools used in the diagnosis such as peak expiratory flow (PEF) monitoring and bronchial provocation tests, and the final medical diagnosis were recorded from case files.

Results: Asthma was diagnosed in 75% (n = 99) of the patients. Among them, 22.2% were diagnosed as having OA. The diagnosis was confirmed by serial PEF measurements, non-specific bronchial hyperreactivity assessment or both of the tests both at work and off-work periods. OA diagnosis was mostly established in active workers (72.7%). The legal diagnosis period was completed in 54.5% of these 22 patients, and 50% (n = 11) were officially diagnosed as having OA with a 91.6% concordance with medical diagnosis.

Conclusion: This study verifies the importance of diagnosing asthma correctly as a first step in the evaluation of OA. Diagnostic tests other than specific provocation tests could be preferential in patients who still work in the same field. We believe that cooperation with the patient's occupational physician and adequate recognition of the work environment will improve the consistency of legal and medical diagnoses.
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http://dx.doi.org/10.1080/02770903.2016.1277541DOI Listing
November 2017

Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics.

Int Arch Allergy Immunol 2016 4;171(3-4):227-233. Epub 2017 Jan 4.

Division of Immunology and Allergy, Department of Chest Diseases, School of Medicine, Ankara University, Ankara, Turkey.

Background: Rapid drug desensitization (RDD) induces a temporary tolerance to biologics which induce hypersensitivity reactions (HSRs). Data are limited regarding the use of RDD outside the USA. Our purpose was to report our data on RDD to rituximab, infliximab, cetuximab, and trastuzumab.

Methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biologics. HSRs were classified as grades I, II, and III, based on their severity. Skin-prick tests/intradermal tests (IDTs) were performed with the implicated biologics. The 12-step RDD protocol was used.

Results: The study group comprised 11 women and 6 men (mean age: 47 ± 11.7 years). Fourteen patients experienced HSRs to rituximab; 3 had HSRs to cetuximab, infliximab, and trastuzumab, respectively. HSRs to cetuximab, infliximab, and trastuzumab occurred during the first infusion and were all grade III. Twelve of the 14 patients with rituximab hypersensitivity had a reaction during the first infusion; 10 patients had grade II reactions and 4 had grade III reactions. Respiratory symptoms were the most frequent presentation of HSR. Skin tests with rituximab were performed on 10 patients; only 3 resulted in positive IDTs (with 1:100 dilutions) and the other tests were negative as were those performed with the other biologics. Of 96 RDDs, 89 desensitizations were performed with rituximab, 5 with cetuximab, 1 with infliximab, and 1 with trastuzumab. There were 12 (13.5%) breakthrough reactions, all of which were associated with rituximab and were less severe than the initial reactions.

Conclusion: RDD was found to be safe and effective in the largest case series of RDDs with biologics in our country, Turkey.
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http://dx.doi.org/10.1159/000454808DOI Listing
February 2017