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.

Erratum to "Does NSAID exacerbated respiratory disease (N-ERD) accompanying severe asthma affect biological treatment response? Efficacy of omalizumab and mepolizumab in N-ERD" [World Allergy Organ (2023) 100817].

[This corrects the article DOI: 10.1016/j.waojou.2023.100817.].

The phenotypic heterogeneity of obese and nonobese patients with severe asthma and comparison of omalizumab-mepolizumab treatment efficiency in these patients.

In obese severe asthmatics, the degree of type 2 inflammation may vary according to their atopic status and past smoking history. In this study, we aimed to analyze the clinical and physiopathological features of obese and nonobese severe asthmatics treated with omalizumab or mepolizumab treatment. In addition we aimed to compare the clinical, spirometric outcomes and total peripheral eosinophilic count (TEC) changes after treatment with these 2 biologic agents in obese and nonobese groups. In this retrospective, cross sectional study, 121 severe asthmatic treated with biologic agents (omalizumab = 88 or mepolizumab = 33) for at least 16 weeks were included. Obese (n: 44) and nonobese severe asthmatics (n: 77) were analyzed according to whether they provided a ≥ 10 pack/years (p/y) or <10 p/y smoking history and were found to be atopic. Obese and nonobese groups were compared in terms of the change in the asthma control test, asthma attacks, TEC, and forced expiratory volume in the first second (FEV1) after treatment. In patients with ≥10 p/y smoking history, nonobese group had a significantly higher TEC compared to obese group [median (min-max) 660 cells/µL (200-1500) vs 300 cells/µL (110-770); p: 0.013]. Within the nonobese group, nonatopic patients had a significantly higher TEC compared to atopic patients [median (min-max) 1200 cells/µL (100-2100) vs 310 cells/µL (0-2730); p: 0.021]. Both biologic agents had similar effects on improving asthma control test and in reducing asthma attacks; however, mepolizumab was more effective in suppressing TEC. The improvement in FEV1 in obese group following biologic 2 agents was very similar but in nonobese group, mepolizumab was found to be superior (510 mL vs. 295 mL; p: 0.034). In our real-life study, nonobese severe asthmatics with ≥10 p/y smoking history and those that were nonatopic had higher TEC. Compared to omalizumab, mepolizumab was superior at reducing TEC in all asthmatics and in improving FEV1 in nonobese group.

Does NSAID exacerbated respiratory disease (N-ERD) accompanying severe asthma affect biological treatment response? Efficacy of omalizumab and mepolizumab in N-ERD.

Introduction: Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) accompanies severe asthma in about 15% of the patients and may adversely affect the prognosis. Omalizumab and mepolizumab are biologics used in patients with severe asthma. The objective of this study is to assess the respiratory improvements, after these biologics in severe asthmatic patients stratifed by the presence of concomitant Non-erosive reflux disease (N-ERD) and the effect of omalizumab and mepolizumab in severe asthmatics with N-ERD. Material & method: The population of this three-center, retrospective, cross-sectional, observational study comprised patients using omalizumab or mepolizumab for severe asthma. Patients administered these biologics for severe asthma were comparatively analyzed for the presence of N-ERD; asthma control test (ACT) scores, number of attacks, and the changes in forced expiratory volume in 1 s (FEV1) were assessed. Subsequently, patients who were found to have N-ERD were analyzed using visual analog scale (VAS) in terms of the changes in their nasal parameters (ie, nasal obstruction, facial pain, anterior-posterior rhinitis, and hyposmia), according to whether they use omalizumab or mepolizumab. Results: The use of biologics resulted in a significant improvement in ACT and FEV1 and reduction in attacks in 28 severe asthmatics with N-ERD and 125 without N-ERD. Although both biologics resulted in a significant improvement in the respiratory parameters, omalizumab treatment resulted in a significant improvement in nasal parameters except hyposmia, mepolizumab treatment resulted in a significant improvement only in posterior rhinitis, and nasal obstruction among the nasal parameters. Conclusion: This study is the first to address both omalizumab and mepolizumab treatments in severe asthmatics with N-ERD. The improvement in nasal parameters was more pronounced in patients who were administered omalizumab. Large-scale randomized controlled studies are needed to corroborate the findings of this study.

Can development of asthma and bronchial hyperreactivity be reduced by subcutaneous immunotherapy in adult patients with allergic rhinitis?

BACKGROUND: Allergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis. METHODS: The retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment. RESULTS: A total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled.Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30-35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046). DISCUSSION: In our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma developmen.

[Effectiveness of mepolizumab in patients with severe eosinophilic asthma: In a real life study]. / Agir eozinofilik astimli hastalarda mepolizumab etkinligi: Bir gerçek yasam çalismasi.

Introduction: We analyzed the effects of mepolizumab treatment on symptoms, asthma attacks, pulmonary function test parameters peripheral blood eosinophil level, and percentage in patients with severe eosinophilic asthma receiving mepolizumab treatment as the baseline, sixth and twelfthmonth data. Materials and Methods: The medical records of patients diagnosed with severe eosinophilic asthma and treated with mepolizumab at our clinic were retrospectively reviewed for the period between January 2018 and December 2021. Demographic data of the patients, duration of asthma disease, comorbidities such as a nasal polyp, eosinophilic granulomatous polyangiitis, and nonsteroidal anti-inflammatory drug exacerbated respiratory disease were investigated. A comparison was made of various factors before initiating mepolizumab treatment, as well as at the sixth and twelfth month after treatment initiation. These factors include asthma control test scores, frequency of asthma attacks (including emergency admissions, hospitalizations, and intensive care admissions), peripheral blood eosinophil levels and percentages, and pulmonary function test parameters. Clinic and laboratory parameters that provide a prediction of being a responder and super responder were evaluated. Result: A total of 21 patients were included in the study. Their mean age was 50.7 ± 11.9 years, and four (19%) were males. The mean duration of asthma diagnosis was 17.5 ±13.7 years. 14 patients (66.7%) were atopic. 4 patients (19%) had nasal polyps and four patients (19%) had NERD. Before mepolizumab, 13 (61.9%) patients had received omalizumab. The duration of receiving mepolizumab treatment was 29.2 ± 9.9 months. A statistically significant decrease was observed in both the number and percentage of eosinophils at months six and 12 (p<0.01). There was a statistically significant increase in FEV1 values both as a percentage and in milliliters at month 12. There was an increase in both percentage and milliliters in FEF25-75 values, but this increase did not reach statistical significance. There was a decrease in service admissions, intensive care admissions, and emergency admissions due to asthma exacerbations. Out of 21 patients, 11 (52.4%) were classified as responders, while 10 (47.6%) were classified as super responders. Conclusions: Although the number of patients in our study was limited, mepolizumab improved symptom scores in severe eosinophilic asthma, reduced the number of attacks, and improved pulmonary function test values.

Comparison of omalizumab and mepolizumab treatment efficacy in patients with atopic and eosinophilic "Overlap" severe asthma: Biological agent preference in atopic-eosinophilic severe asthma.

Approximately 1-third of patients with severe asthma are candidates for both omalizumab and mepolizumab treatment. We aimed to compare the clinical, spirometric and inflammatory efficacy of these 2 biologics in atopic and eosinophilic "overlap" severe asthma patients. In our 3-center retrospective cross-sectional observational study, the data of patients who received omalizumab or mepolizumab for at least 16 weeks to treat severe asthma were examined. Atopic (perennial allergen sensitivity and total IgE level 30-1500 IU/mL) and eosinophilic (blood eosinophil counts ≥150 cells/µL in admission; or ≥300 cells/µL in the previous year) patients with asthma suitable for both biologics were included in the study. Post-treatment changes in the asthma control test (ACT) score, number of attacks, forced expiratory volume in 1 second (FEV1), and eosinophil count were compared. The rates of any biological responder patient were compared according to whether they had high eosinophil counts (≥500 cells/µL vs <500 cells/µL). Total of 181 patients data were evaluated, of the 74 atopic and eosinophilic overlap patients included in the study, 56 were receiving omalizumab and 18 were receiving mepolizumab. When omalizumab and mepolizumab treatment efficacies were compared, there was no difference in terms of the reduction in attacks and improvement in ACT. The decrease in eosinophil levels in patients in the mepolizumab arm was significantly higher than that in patients in the omalizumab arm (46.3% vs 87.8%; P < .001). The improvement in FEV1 was greater with mepolizumab treatment, although the difference was not significant (215 mL vs 380 mL; P = .053). It has been shown that having high eosinophil counts does not affect the clinical and spirometric responder patient rates for either biological condition. The success of omalizumab and mepolizumab treatment is similar in patients with atopic and eosinophilic overlap with severe asthma. However, because the baseline patient inclusion criteria are not compatible, head-to-head studies comparing both biological agents are required.

Drug hypersensitivity in drug-resistant tuberculosis.

Objective: To evaluate drug resistant tuberculosis patients who developed drug hypersensitivity to antituberculosis drug. Methods: This was a retrospective study. The primary aim of the study is to determine the demographic and clinical characteristics of patients who develop drug hypersensitivity in drug resistant tuberculosis patients. The secondary aim of the study is to examine the treatment results. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing hypersensitivity reaction, reaction time, and treatment were evaluated. Results: A total of 25 patients were included in the study. The prevalence of hypersensitivity in drug resistance patients was 11.9%. Twelve (48%) of the cases were women. Mean age (mean ± SD) was 37.24 ± 14.44 years; early type hypersensitivity reaction in 13 (52%). Three patients were isoniazid resistant; 19 patients were multidrug-resistant (MDR); 2 patients were pre-extensive drug resistant (Pre-XDR), 1 patient was extensive drug resistance (XDR) tuberculosis. The most common skin findings were maculopapular eruption and urticaria. But also we had seen isole angiodema, urticaria and angioedema, erythema multiforme, lichenoid drug eruption and drug rash with eosinophilia and systemic symptoms. In patients who developed a hypersensitivity reaction, the responsible agent was identified in 14 cases in total. Among the drugs, pyrazinamide, ethambutol, moxifloxacin, amikacin, para amino salicylic, prothionamide, and cycloserine are the responsible agents. When evaluated in terms of treatment results, 15 (60%) patients successfully completed the treatment. Conclusion: Our study is the first study in the literature that evaluated the drug hypersensitivity in drug resistance tuberculosis patients. Drug hypersensitivity that develops with tuberculosis treatment may lead to discontinuation or change in treatment. It can cause treatment failure, drug resistance, relapse, and even death. In resistant tuberculosis, the already existing resistance pattern may become more difficult to treat. Success can be achieved with the right management in these patients who have few treatment options, more drug side effects, and high treatment failure rates. The established regimen should be curative and prevent recurrence.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

An evaluation of remission rates with first and second line treatments and indicators of antihistamine refractoriness in chronic urticaria.

BACKGROUND: Guidelines recommend standard doses of antihistamines as first-line, and updosing of antihistamines as second-line treatment for the management of chronic urticaria (CU). However, remission rates with different types of first- and second-line treatments and indicators of antihistamine response are largely lacking in the literature. OBJECTIVES: To examine response rates to first- and second-line treatments in CU, and to identify patient characteristics that can predict antihistamine treatment outcomes. METHODS: We retrospectively analyzed treatment outcomes of 657 CU (556 chronic spontaneous urticaria (CSU), 101 chronic inducible urticaria (CIndU)) patients who had at least 3-months of follow-up data. RESULTS: A standard dose of second generation antihistamines (sgAH) was effective in 43.1 % of the patients. An additional 28.8 % of patients were in remission with second-line treatments. Among patients whose disease was in remission with a standard dose of sgAHs, 14.8 % benefited from switching from their current sgAH to another sgAH. Updosing sgAHs, combination of two different sgAHs, sgAH and first generation H1-antihistamine combination, and sgAH and leukotriene receptor antagonist combination provided remission in 38.3 %, 35.8 %, 37.5 % and 25 % of patients who were given these treatments, respectively. Baseline UCT score ≤ 4, emergency referral and family history of CSU were found to be risk factors for antihistamine refractoriness in patients with CSU. CONCLUSIONS: A step-wise approach to the management of CU is practical as more patients respond to treatment at each step. The presence of baseline UCT score ≤ 4, emergency referral and family history of CSU might be helpful to determine patients who require third-line treatments in advance.

The significance of eosinophil and eosinophil lymphocyte ratio (ELR) in predicting response to omalizumab treatment in patients with severe allergic asthma.

INTRODUCTION: Th2/Th1 mix pathological pathway may be seen as a common set of low eosinophilic phenotype in severe allergic asthma. This may affect omalizumab treatment response. In our study, we aimed to investigate whether eosinophil count (EOS) and percentage (EOS%), eosinophil lymphocyte ratio (ELR) and neutrophil lymphocyte ratio (NLR) may predict omalizumab treatment. MATERIALS AND METHODS: Patients who received omalizumab treatment at least for one year in our allergy clinic were screened retrospectively. Baseline hemogram parameters, pre- and post-treatment emergency admissions, annual attacks requiring steroid use, hospitalizations, spirometric changes, and asthma control tests (ACT) were recorded. According the global efficacy assessment (phisician's GETE) scale patients was recorded as responder and nonresponder. By looking at EOS, EOS%, ELR and NLR distributions in these groups, the role of these parameters in representation of the treatment efficacy was investigated. RESULT: The study was carried out with 83 patients, 77.1% of whom were women with an average age of 50.03 ± 10.7. While ACT scores and FEV1, FEF25-75 was significantly increased, the number of emergency admissions, annual attacks and hospitalizations decreased significantly (p<0.05). The rate of patients signed as responder was 75.9%, while the rate of nonresponder was %24.1. When the two groups were compared, it was found that the EOS, EOS% and ELR were significantly higher in the responder group. The cut-off values according to the ROC curve were determined as 0.12, 310/ml and 3.1% respectively. Considering the sensitivity (58.73%); specificity (85.00%); positive predictive value (92.50%), it was determined that ELR was a more valuable test. CONCLUSIONS: Instead of expensive and invasive methods for predicting the response of omalizumab therapy in severe allergic asthma, the ELR is correlated with treatment response and giving hope to be easier way to reach.

A rare case: Congenital thoracic ectopic kidney with diaphragmatic eventration.

Thoracic ectopic kidney is a rare developmental anomaly that is the least frequent one among all forms of ectopic kidneys. The condition is generally asymptomatic. If a kidney image is missing on one side in renalor pelvic region in sonographic examination, the possibility of thoracic ectopic kidney should be taken into consideration. For final diagnosis, chest radiography and thorax computerised tomography should be obtained. We herein report a rare case of intra-thoracic kidney accompanied by diaphragm eventration.