The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

The perspective of allergy and immunology specialists on the innovations of metaverse: A survey study.

BACKGROUND: New technologies have resulted in dramatic shifts in the field of medicine, and it stands to reason that metaverse will also affect the practice of allergy and immunology. This study aimed to determine the attitudes of allergists and raise awareness about metaverse applications in allergy and immunology. METHODS: A nationwide survey-based study was conducted in Turkey. First, a 28-item questionnaire was developed and sent to Turkish allergists. After completing the first questionnaire, the participants were asked to watch a 5-min informative video about the metaverse. Lastly, a second survey was conducted to evaluate the changes in the views of the participants. RESULTS: A total of 148 allergy doctors in Turkey participated in the survey. After watching a video containing updated information about the metaverse, there was a significant increase in the importance that participants attributed to the use of virtual reality and augmented reality applications in the field of immunology and allergy (P < 0.05). Additionally, there was a significant increase in the percentage of participants who thought that Metaverse applications could be integrated into the existing system and said that this possibility excited them (P < 0.05). There was also a significant increase in the percentage of participants who thought this innovative technology could be helpful in patient examination, student and physician education, allergy testing, and patient education (P < 0.05). CONCLUSIONS: Our results demonstrate that providing information to professionals working in the field can positively influence physicians' views on the potential of the metaverse, which is a valuable tool in the field of immunology and allergy.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease.

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.

Benefits of treatment with favipiravir in hospitalized patients for COVID-19: a retrospective observational case-control study.

BACKGROUND: Although more than a year past since COVID-19 was defined, there is no specific treatment yet. Since COVID-19 management differs over time, it is hard to determine which therapy is more efficacious. In this study, we aimed to evaluate the efficacy of the regimen with Favipiravir (FPV) and determine if the timing of FPV addition offers any improvement. METHODS: A retrospective observational case-controlled cohort study was performed between March and September 2020, including adults with COVID-19 in a single-center in Turkey. We categorized patients into age-sex matched three groups, group 1 (n = 48) and group 2 (n = 48) included patients treated with the combination of FPV plus Hydroxychloroquine (HQ) early and late, respectively. Group 3 (n = 48) consisted of patients on HQ monotherapy. In Group 2, if the respiratory or clinic condition had not improved sufficiently, FPV was added on or after day 3. RESULTS: We found that starting FPV early had an impact on PCR negativity and the progression of the disease. 'No progression' was defined as the absence of a new finding in the control radiological examination and the absence of accompanying clinical deterioration. Also, the decrease in C-reactive protein (CRP) was greater in Group 1 than Group 3 (p < 0.001). However, we found that early initiation of FPV treatment did not have a positive effect on the estimated survival time. CONCLUSIONS: According to this retrospective study results, we believe that for better clinical outcomes, FPV treatment should be started promptly to enhance antiviral effects and improve clinical outcomes.

The role of vitamin D receptor gene polymorphisms in the pathogenesis of Behçet's disease: A case-control study in Turkish population.

BACKGROUND: Behçet's disease (BD) is an inflammatory disorder characterized by oral aphthous lesions, uveitis, and genital ulcerations. The vitamin D receptor (VDR) has a crucial role in the pathogenesis of this disease because it mediates the functions of vitamin D in the immune system. Alterations of VDR expression related to polymorphic alleles of the VDR gene may play a pathogenic role in BD and BD's clinical presentations. METHODS: 150 BD patients and 150 healthy controls were included and genotyping was carried out by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: Significant differences between patients and controls in rs1544410, rs2228570, and rs731236 genotypes were observed (respectively, p = 0.04, p = 0.007, p = 0.012). The clinical characteristics of BD patients were evaluated and patients with ocular lesions had a higher percentage of rs1544410 A alleles (p = 0.004), and patients with oral aphthous lesions, a positive pathergy tests, and arthritis had more rs2228570 C alleles than patients without these clinical findings (respectively, p < 0.001, p = 0.021, p = 0.045). CONCLUSION: VDR gene polymorphisms may possibly have a role in the pathogenesis of BD through their effects on VDR expression and may be associated with the increased risk of several clinical findings.

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

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.

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

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.

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

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.

[Evaluation of 255 HIV/AIDS cases: Hacettepe cohort, Ankara, Turkey]. / HIV/AIDS'li 255 olgunun degerlendirmesi: Hacettepe kohortu, Ankara.

The first HIV/AIDS case has been reported in 1985 in Turkey, and since then 8238 cases have registered until June 2014 according to the records of Turkish Ministry of Health. The aim of this retrospective study was to evaluate the epidemiological data and clinical features of HIV/AIDS patients admitted to our center. A total of 255 HIV-infected patients admitted to our clinic between January 1986 and January 2013, whose data obtained from file records, were included in the study. Most of the patients were male (193/255, 75.6%) and Turkish citizens (216/255, 84.7%), with the mean age of 38.0 ± 11.6 (age range: 19-80) years. Approximately 25.4% (46/181) were university graduates. The most frequent route of transmission was through a heterosexual intercourse (161/255, 63.1%). In our study group, there were 34 men who had sex with men, and the majority of these cases (n= 26, 76.5%) were diagnosed in or after the year 2006, while 23.5% (n= 8) before 2006. This difference was found statistically significant (p< 0.05). The reasons that led patients for diagnosis were the presence of clinical symptoms such as diarrhea, lymphadenopathy and fever in 30.7%, and personal curiosity because of unprotected/risky sexual intercourse in 21.3% of the cases. Initial CD4(+) T lymphocyte counts could be reached for 237 cases, and the median value was calculated as 260 (range: 3-1183) cells/mm(3). Among these patients, CD4(+) T cell count was below 200/mm3 in 40.1% (95/237), and above 500/mm3 in 22.8% (54/237). The mean CD4(+) lymphocyte count on first admission was 240/mm(3) for those admitted before the year 2006 (n= 107) and 375/mm3 for those admitted after 2006 (n= 130) (p< 0.005). HIV-RNA loads could be reached for 203 cases on admission, and the median value was calculated as 67.200 copies/ml. Nearly half of the cases (91/203, 44.8%) had high viral load (≥ 100.000 copies/ml). The disease could be categorized in 246 cases, 54.1% were HIV-positive and 45.9% were in AIDS stage. Patients diagnosed after 2006 had lower rate of AIDS when compared to the patients diagnosed before 2006 (33.6% vs. 60.7%, respectively; p< 0.005). Two hundred patients were followed up more than three months (median: 41 months), and 138 patients (of them 79 were HIV-positive, and 59 were in AIDS stage) were still in follow up at the end of study period. Throughout the follow-up, 29 cases (29/255, 11.4%) had died. It was concluded that, the surveillance of data from HIV/AIDS patients would be beneficial to determine and predict the complications of the disease.

[Attitudes of adult asthma patients towards influenza vaccination]. / Eriskin astimli hastanin influenza asisina yaklasimi farkli mi?

INTRODUCTION: It is known that viral infections trigger exacerbations in asthma patients.There are conflicting reports on whether influenza vaccine is preventive or not. In this study, we aimed to evaluate asthmatic patient's attitude towards influenza vaccine and to determine which factors affect this attitude. MATERIALS AND METHODS: A questionnaire involving data about demographic information, co-morbidities, frequency of viral upper respiratory tract infections, subject's influenza vaccination status and attitude towards vaccination had been filled for our outpatient clinic asthma patients and also for healthy controls. Results were evaluated separately for the two groups and then compared to each other. RESULT: For the study; 108 asthma patients (91 female, 17 male) and 110 non-asthmatic controls (64 female, 46 male) were enrolled. In asthma group, vaccination rates were significantly higher in the previous year (40.7%) and nearly half of them stated that they do regularly have influenza shots every year. Contrast to this find; half of the patients in the control group stated that they do not need to vaccinate themselves and 26.2% said that they don't believe influenza vaccine has any preventive effect. Also in the asthma group, this ratio was similar to the control group (20.3%). In asthma group, 66.7% of the patients who had side effects at their previous shots did not want to vaccinate themselves this year (p= 0.02). More than a half of the patients (53.1%) whom did not have shots had an episode of viral upper respiratory tract infection this year and this rate was significantly lower in the vaccinated group (p= 0.00). This result highlights the preventive effect of vaccination. CONCLUSIONS: We found that asthma patients' knowledge on influenza infection and vaccine were insufficient and also their belief towards the preventive features of the vaccination was low. Informing and encouraging patients about preventive medicine through various activities and meetings would be crucial.

Clinical outcomes of hereditary angioedema on multiparous women.

OBJECTIVE: Significant concerns for patients with hereditary angioedema (HAE) include hormonal fluctuations and drug safety during pregnancy. The impact of the disease on childbearing in multiparous women remains to be elucidated. We aimed to investigate the clinical course and impacts of multiparity on HAE patients. STUDY DESIGN: This observational study included 15 multiparous women with HAE; a total of 88 pregnancies were assessed using a questionnaire and the patient's medical records. RESULTS: The median age was 36 (IQR, 33-39). Of 72 resulted in healthy babies without any congenital abnormalities. In sixteen pregnancies, 12 (13.6%) ended with spontaneous abortion; three resulted in stillbirth and one neonatal death. Two-thirds of the patients (n = 10) enounced a worsening in the frequency of angioedema attacks during pregnancy. There was no statistically significant difference compared with the nonpregnant period (p = 0.283). One-fifth of the patients (n = 3) reported alleviation in attacks. While most deliveries were vaginally (n = 57 babies), 19 deliveries in six patients were by cesarean section. None of the patients were aware of the diagnosis of HAE prior to their first pregnancies. After the diagnosis was made, eight patients received 263 vials of plasma-derived C1-inhibitor concentrate during a total of 13 pregnancies. No adverse events were reported. CONCLUSION: We conclude that our results on clinical course and outcomes of HAE in multiparous patients are consistent with the literature. A greater focus on multiparous HAE patients could produce exciting findings.

The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis.

Introduction: In the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem. Objective: In this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis. Method: To reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results. Results: Exposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues. Conclusion: Dramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

Investigating the role of IL-33 in the pathogenesis of Behçet's Disease.

OBJECTIVES: Behçet's disease (BD) is an inflammatory disease, characterized by oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations. Increased release of several cytokines may play a role in the inflammatory stages of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role in inflammation. We analyzed serum IL-33 concentration in BD patients to assess its possible role in the pathophysiology of this disease. METHODS: The study included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18 matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-33 levels were 4.84 ± 2.81 pg/ml in the BD patients (6.16 ± 2.94 pg/ml in the active stage and 2.86 ± 0.54 pg/ml in the inactive stage) and 2.88 ± 0.42 pg/ml in the healthy controls. Serum IL-33 levels were significantly higher in patients with BD compared with the healthy controls (p < 0.01). In active Behçet patients with arthritis the mean serum IL-33 level was higher but this finding was not statistically significant (p = 0.122). CONCLUSION: IL-33 may play a significant role of in the pathogenesis of BD.