Results of omalizumab treatment in chronic eosinophilic pneumonia: Real-life data.

Introduction: Recurrences occur when corticosteroid therapy is discontinued or reduced during the treatment of chronic eosinophilic pneumonia (CEP). The probability of recurrence is once in 50% of patients and twice or more in 25%. In such instances, new treatment options are deemed necessary. This study aims to assess the efficacy of omalizumab treatment as a steroid-sparing drug in patients with CEP. Materials and Methods: The clinical features of patients treated with omalizumab for recurrent CEP were evaluated retrospectively before and after treatment. All data from patients and diagnoses were reviewed. The effects of treatment on recurrence rate, oral corticosteroid (OCS) use and lung functions, peripheral eosinophil values, and symptom scores were evaluated. Radiological regression was also evaluated. Result: In the final analysis, we included ten patients with a median follow-up of 22 months after initiation of omalizumab. During this follow-up period, the results were associated with a significant reduction in the number of asthma attacks per year, the number of CEP relapses, the rate of hospitalization, the amount of corticosteroids consumed daily, and the total corticosteroid dose. In addition, improvement was observed in the symptom scores and lung functions of the patients. Systemic steroids were completely discontinued in two patients receiving omalizumab treatment. In other patients, the mean steroid dose was reduced by 77.2 percent in the first year of omalizumab treatment and 82 percent in the second year, respectively. Nevertheless, there was no elevation in peripheral eosinophil count, and radiological regression was observed. Conclusions: Omalizumab can be an effective treatment for CEP and can be used as a steroid-sparing agent.

What is the Best Way to Diagnose Possible Asthma Patients with Negative Bronchodilator Reversibility Tests?

Objective: The best method and strategy for the diagnosis of asthma remains unclear, especially in patients with negative bronchodilator reversibility test (BDRT). In our study, we aimed to investigate the diagnostic yield of peak expiratory flow (PEF) variability for this patient group. Methods: A total of 50 patients with suspected asthma, all with negative BDR test, were included in the study. Demographic information and symptoms were recorded and PEF variability was monitored for 2 weeks. Metacolinbronchial provocation test (mBPT) was performed. Asthma was diagnosed when PEF variability ≥20% and/or positive mBPT was observed. Results: 30 of 50 patients were diagnosed with asthma. After 1 month, 17 patients were evaluated for treatment outcomes. The sensitivity and specificity of PEF variability for different cut-off values (≥20%, >15% and >10%) were 61.5-83.3, 88.5-62.5 and 100-16.7, respectively. One of the most important findings of our study was the absence of variable airflow limitation or airway hyper reactivity in 39% patients with a previous diagnosis of asthma. Multiple logistic regression analysis revealed that a low baseline FEF25-75 value was an independent predictive factor for the diagnosis of asthma (p= 0.05). Conclusion: The most efficient diagnostic test for asthma is still unclear due to many factors. Our study is one of the few studies on this subject. Although current diagnostic recommendations generally recommend a PEF variability of 10% for the diagnosis of asthma, this threshold may not be appropriate for the BDR-negative patient group. Our results suggest using a threshold value of <15% for PEF variability when excluding asthma and ≥20% when confirming the diagnosis of asthma in patients with clinically suspected but unproven reversibility. Furthermore, FEF25-75 is considered to be an important diagnostic parameter that should be included in diagnostic recommendations for asthma.

Hypersensitivity reactions with first-line antituberculosis drugs and outcomes of rapid desensitizations.

Background: Data about drug hypersensitivity reactions with first-line antituberculosis drugs and their management is limited. Rapid drug desensitization seems to be an appropriate management. Objective: Evaluate the efficacy of the rapid desensitization protocols in patients who had a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs and identify possible risk factors of breakthrough reactions during the protocols. Methods: This is a retrospective study of active tuberculosis patients who had a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs and underwent desensitization with the drugs used during the reaction. Characteristics of drug hypersensitivity and breakthrough reactions, and outcomes of rapid desensitizations were recorded. Results: One hundred and seventy-nine patients were included in the study. Most of the initial reactions (n = 132, 73.7%) occurred within the first week of treatment and were mild (n = 146, 81.6%). A total of 690 desensitizations were performed. Desensitizations were successfully completed without any breakthrough reaction in 103 (57.5%) patients and in 29 of 36 (80.6%) patients after a breakthrough reaction. The overall success of desensitizations were found to be 95% (132 of 139 patients). Most of the breakthrough reactions (84%) were mild. Sixteen patients had breakthrough reactions with multiple drugs. Although pyrazinamide was the most common culprit of breakthrough reactions and had the lowest desensitization success, it had the highest rate of a single breakthrough reaction (p < 0.001). Timing of the initial reaction and concomitant breakthrough reaction with ethambutol were found to have increased the risk for breakthrough reaction caused by rifampicin (p = 0.017 and p = 0.010 respectively). Conclusion: The rapid desensitization protocols used in this study provide a successful and effective management of the patients with a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs.

Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

Introduction: The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. Materials and Methods: A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Result: Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. Conclusions: The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.

Rapid drug desensitization to taxanes: a descriptive study from Turkey.

AIM: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD). METHODS: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards. RESULTS: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male. CONCLUSION: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Real-world patient-level cost-effectiveness analysis of omalizumab in patients with severe allergic asthma treated in four major medical centers in Turkey.

AIMS: To evaluate the cost-effectiveness of standard-of-care treatment (SoC) to SoC in combination with omalizumab (OML + Soc) in patients with severe asthma using real-world prospective clinical data from four major medical centers in Turkey. MATERIALS AND METHODS: Between February 2018 and November 2019, a total of 206 patients with severe asthma, including 126 of whom were in the OML + SoC group and 80 in the SoC group, were followed for 12 months to evaluate their asthma status and quality of life. Cost data for this patient-level economic evaluation were sourced from the MEDULA database of the hospitals and expressed in Turkish Lira (₺). Efficacy data were obtained by means of Turkish versions of the Asthma Control Test for asthma status, the 5-level EQ-5D-5L version (EQ-5D-5L), and the Asthma Quality of Life Scale for quality of life. A Markov model with 2-week cycles was specified, comparing costs and treatment effects of SoC vs. OML + SoC over a lifetime from the Turkish payer perspective. RESULTS: Per-patient costs were ₺23,607.08 in the SoC arm and ₺425,329.81 in the OML + Soc arm, for a difference of ₺401,722.74. Life years (LY) and quality-adjusted life years (QALY) were 13.60 and 10.08, respectively, in the SoC group; and 21.26 and 13.35, respectively, in the OML + SoC group, for differences of 7.66 LYs and 3.27 QALYs. This yielded an incremental cost-effectiveness ratio of an additional ₺52,427.04 to gain 1 LY and an incremental cost-utility ratio of an incremental ₺122,675.57 to gain 1 QALY; the latter being below the ₺156,948 willingness-to-pay threshold for Turkey referenced by WHO. One-way and multivariate sensitivity analyses confirmed the base-case results. CONCLUSION: Whereas most economic evaluations are based on aggregate data, this independent cost-effectiveness analysis using prospective real-world patient-level data suggests that omalizumab in combination with standard of care is cost-effective for severe asthma from the Turkish public payer perspective.

What is the context? Severe asthma, a subset of difficult-to-treat asthma, refers to asthma that cannot be controlled despite adherence to optimized maximal therapy and treatment of contributing factors, or asthma that worsens when high-dose therapy is reduced.Omalizumab is the first biologic therapy approved for the treatment of allergic asthma. Its main role is to prevent the release of various inflammation factors that cause severe asthma episodes.Cost-effectiveness analysis is an economic method of determining how much more a new and better treatment costs relative to the current treatment in terms of how many life years (LY) and how many quality-adjusted life years (QALY) are gained with the new treatment. Cost-effectiveness results tell us how much more money is needed over the cost of the current treatment to achieve one additional LY, regardless of the quality of life, or one additional LY with good quality of life.No cost-effectiveness data obtained from actual clinical patient data are available for Turkey. What is new? Our study found that the addition of omalizumab to the current standard of care for severe asthma increases costs but also increases life years and quality-adjusted life years. The additional cost was less than what the World Health Organization assumes is reasonable for Turkey.This study used actual clinical patient data and noted that asthma patients in the omalizumab group used fewer health services, had a better clinical course, had a better quality of life, and lived longer with their disease under control.What is the impact? In severe asthmatic patients, adding omalizumab to standard-of-care, while more costly, yields better outcomes and is therefore cost-effective.The cost-effectiveness estimates fall within the margins of being cost-responsible. The Turkish public payer should strongly consider making omalizumab available to all eligible patients. This will enable working-age patients to work, and contribute to their families, while also strengthening the Turkish economy.

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.

Successful desensitization under antihistamine suppression in a case with urticaria due to osimertinib.

INTRODUCTION: Osimertinib is an approved therapy for patients with a Thr790met (T790M) mutation diagnosed with non-small cell lung cancer (NSCLC) that progresses during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. However, in 7-13% of patients, drug-related side effects lead to discontinuation of osimertinib treatment. In such cases, osimertinib desensitization is a treatment option that can be considered. CASE REPORT: A 59-year-old female patient, who was followed up with the diagnosis of stage 4 NSCLC, was consulted to the allergy clinic because of urticaria. The patient developed urticaria plaques 20 h after the third dose of osimertinib tablet. MANAGEMENT & OUTCOME: With the diagnosis of osimertinib-induced urticaria, desensitization was planned for the patient. Treatment was started with a dose of 0.1 mg/day osimertinib. The procedure was completed in approximately 50 days, and a dose of 80 mg/day was reached with antihistamine suppression. DISCUSSION: Here, a successful osimertinib desensitization in a patient with a history of osimertinib-related type 1 allergic reaction is reported. Osimertinib desensitization is a treatment option that should be considered in cases where treatment has to be ceased due to drug-related side effects.

[Mycobacterium abscessus infection management: Macrolide and quinolone desensitization]. / Mycobacterium abscessus enfeksiyonu yönetimi: Makrolid ve kinolon desensitizasyonu.

Antibiotic hypersensitivity reactions can lead to marked morbidity, mortality and inadequate treatment options. Mycobacterium abscessus infection is a difficult management system for clinicians since it most commonly involves the lungs, progresses if untreated, and the organism is resistant to many antibiotics, as well as the agents used in treatment can cause undesirable side effects. Although macrolides are one of the most reliable antibiotic groups in terms of allergic reactions, early type hypersensitivity reactions against macrolides, one of the main antibiotics used in the treatment of Mycobacterium abscessus lung disease, may make the treatment management of the disease difficult. Due to the rapid increase in the use of quinolone in recent years, the frequency of developing allergic reactions with these agents also increases. In cases where antibiotic hypersensitivity is detected, the use of the responsible agent should be avoided, but desensitization may be necessary in cases without different treatment options. In this study, it was aimed to present a case of successful desensitization with clarithromycin and moxifloxacin in a patient who was diagnosed with Mycobacterium abscessus lung disease and developed anaphylaxis with clarithromycin and moxifloxacin after treatment was initiated.

COVID-19 in patients with severe asthma using biological agents.

As the COVID-19 pandemic continues, case reports have been published where patients with severe asthma using biological agents survived with a mild course of illness and encouraged the continuation of biological therapies in patients with severe asthma. However, contrary to previous information, a more severe course of COVID-19 has recently been reported in severe asthmatics using biological therapy compared to the general population. To evaluate the COVID-19 rate and disease severity in severe asthmatics using biological agents. A retrospective study was conducted in patients with severe asthma treated with biological agents. Data concerning whether the subjects had contracted COVID-19 and the severity of the disease were evaluated. Eihgty-four severe asthmatics using biological agents (omalizumab or mepolizumab) aged 48.3 ± 10.6 years (mean ± standard deviation) with female/male ratio: 53 (63.1%)/31 (36.9%) were included in the study. Among participants 13 (15.5%) had contracted COVID-19. The course of COVID-19 was mild in five (38.5%) and moderate in eight patients (61.5%), while none of the patients had a severe course of COVID-19. Mechanical ventilation or intensive care follow-up was not required in any of the six patients (46.2%) who were treated as inpatients. All participants survived COVID-19 in full recovery and no deaths occurred in the cases. A higher rate of COVID-19 was found in patients with severe asthma using biologics compared to those reported in previous reports. However, all patients with COVID-19 have a mild to moderate disease course.

Real-life adherence to subcutaneous immunotherapy: What has changed in the era of the COVID-19 pandemic.

BACKGROUND: Allergen immunotherapy (AIT) must be continued for 3 years, to achieve a long-term modifying effect. Adherence is a key to ensure effectiveness. The objective of this study was, first of all, to evaluate the adherence with subcutaneous immunotherapy (SCIT) and to identify the main causes of SCIT withdrawal in real-life practice in our clinic. Secondly, we also aimed to investigate to what extent the COVID-19 pandemic altered our SCIT receiving patients' treatment adherence behaviors and the factors that affected their decisions. METHODS: Retrospective analysis of the medical records of patients ages ≥18 years, who had started SCIT in January 2014 or later until September 2020 in our department for the diagnosis of allergic rhinitis, allergic asthma or venom allergy, were included in the study. Adherence was determined as the accomplishment of 3 years of SCIT. RESULTS: A total of 124 patients (72 female [58.1%]; median age, 35 [19-77] years) were included. The adherence rate to SCIT in our tertiary center's real-life setting was 56.25% with a follow-up duration of 3 years before COVID-19 pandemic. Dose modification, defined as reducing patient's planned SCIT dose due to a systemic allergic/large local reaction or missed injection, and its frequency, which is the number of dose adjustments done throughout the SCIT, was found to be the only factor related to nonadherence. But with the pandemic only in 6 months, among 63 patients receiving SCIT, 15 patients (23.81%) dropped out, and the most common reason was fear of being infected with COVID-19 virus during receiving SCIT in hospital (93.33%). The only independent predictor of drop-out during the COVID-19 pandemic was short duration of AIT (p = 0.012). When we compare the dropped-out cases before and after the start of pandemic, AIT duration was significantly shorter in pandemic period (p = 0.005). CONCLUSION: Adherence rate to SCIT in our real-world setting study was 56.25% before the COVID-19 pandemic. Our results indicated that patients requiring dose modification were more prone to be non-adherent. Approximately one quarter of patients dropped-out with the start of pandemic, almost all due to fear of being infected during receiving SCIT in hospital. Since short SCIT follow-up time was found to be the only risk factor for drop-out during the COVID-19 pandemic, we believe that patients who are in the early phases of their treatment should be observed more closely and their concerns should be answered by their doctors.

Identification of Risk Factors and Cross-Reactivity of Local Anesthetics Hypersensitivity: Analysis of 14-Years' Experience.

PURPOSE: Local anesthetics (LA) are widely used and adverse drug reactions (ADR) occur in 2.5-10%, but hypersensitivity reactions are rare (ranging between 0% and 4.3%). Risk is so overestimated causing too many allergy clinic referrals. There are limited and also conflicting results over the management of LA allergy. We aimed to find out who should be referred to an allergy clinic for a LA allergy testing, to define the subjects with an increased risk of LA allergy and to assess the need for testing for identifying alternative LA. PATIENTS AND METHODS: We performed a retrospective study of patients referred to our clinic for diagnostic workup of LA hypersensitivity from 2006 to 2020. RESULTS: In our cohort of 398 patients, tests were positive in 14 (3.52%) of them. Personal history of ADR with LA was the only independent risk factor for positive test (RR=4.007, p=0.033). Presence of generalized cutaneous symptoms and hypotension during past reaction were independent predictors of positive test (RR=9.043, p=0.021 and RR=10.445, p=0.038, respectively). The negative predictive value of intradermal test at dilution of 1:100 for immediate-type reaction was high (97.56%). Also, we demonstrated cross-reactivity within the amide-group LAs and co-occurrence of immediate- and delayed-type reactions. CONCLUSION: Only patients with an LA-induced ADR should be referred to an allergy clinic. History of generalized cutaneous symptoms and/or hypotension during the reaction may define subjects with an increased risk of LA allergy. A stepwise test procedure may start with skin tests especially for these patients with increased risk factors. In presence of LA allergy, alternative LA should always be confirmed by performing a challenge test.

The Diagnostic and prognostic value of CXCL12 (SDF-1α) level in Mycobacterium tuberculosis infection and disease.

INTRODUCTION: New diagnostic tools are being investigated for rapid and accurate TB detection. We aimed to find out the diagnostic yield and accuracy of chemokine CXCL12 (SDF-1a) levels in diagnosing active TB (aTB) and making a differential diagnosis from other several infectious/non-infectious pulmonary conditions. METHODOLOGY: We collected demographic, clinic features and studied plasma CXCL12 levels using ELISA kit of the participants, classified into five categories: aTB (n = 30); cured TB (cTB, n = 15); close contacts of aTB (CC, n = 15); chronic obstructive pulmonary disease (COPD) with active nonspecific pulmonary infection (infCOPD, n = 15); and healthy controls (HC, n = 15). RESULTS: CXCL12 levels were highest in aTB, but no significant difference was seen between other groups. When a cut-off level for CXCL12 was determined as 2835 pg/mL, the increased CXCL12 rate was significantly more in aTB than CC and HC (p = 0.02, p = 0.05). Also, participants with an active infection (aTB and infCOPD) had significantly higher increased CXCL12 rates (p = 0.01). The sensitivity and specificity of CXCL12 for diagnosing aTB were found to be 0.56 and 0.63, respectively. We found that bacterial load, the radiological severity and the extent of chest x-ray involvement were independent factors for increased CXCL12 levels. CONCLUSIONS: Our study demonstrates that CXCL12 may be a representative of active pulmonary infection regardless of the cause but correlated with the severity of the disease; enabling this test to be used as a prognostic factor rather than a diagnostic test for aTB.