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Abstract Introduction Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. Methods In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. Results Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4–6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. Conclusions In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

Abstract Background While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (− 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (− 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. Methods Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (− 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. Results In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p

Abstract Background A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. Methods A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. Results Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease’s pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

Abstract Background The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study’s primary objective was to evaluate dupilumab treatment’s effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT). Methods A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score. Results Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups. Conclusion Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control.

Abstract Asthma is associated with a significant burden of disease, especially for patients with severe or uncontrolled asthma. Many patients with severe asthma still receive treatment in primary care settings and despite the availability of effective options, inadequate asthma treatment remains a concern, particularly the use of systemic corticosteroids to treat exacerbations and severe asthma. Around the world, many patients are stuck in a vicious circle of misdiagnosis, undertreatment, and poor understanding of disease severity and management. In this manuscript, we describe the development of The Asthma Referral Identifier (ReferID) tool, a simple, 4-item questionnaire that healthcare providers can use to help identify patients with uncontrolled and/or potentially severe asthma. ReferID was developed specifically for use in primary care clinics in low- and middle-income countries and other clinics, where the optimisation of asthma assessments and treatment recommended for countries with well-established healthcare systems, are not possible. ReferID was developed through an informal collaborative process involving international asthma experts as well as general practitioners, nurses, and specialists throughout the Asia Pacific, Latin America and Middle East regions, in conjunction with current evidence and treatment guidelines. In collaboration with local and regional partners around the world, the developers have adapted ReferID and translated it into 21 languages, and implementation is ongoing in 30 countries. ReferID has the potential to help break the vicious circle, improving disease outcomes and health-related quality of life for patients with asthma.

IntroductionDespite well-defined clinical phenotypes of chronic rhinitis, the underlying in-depth pathophysiological mechanism, particularly with reference to the involvement of immune mediators, genetic, and environmental factors, are still not fully understood. Therefore, our aim was to give updated information on the pathogenesis of allergic rhinitis (AR), with an emphasis on the role of cytokines in adults aged 18 years and above. Additionally, we investigated the impact of genetic and environmental factors in the pathogenesis of AR.ResultsA search in various databases identified 1,178 records, and 18 studies were ultimately selected from January 2018 to April 2023. The total sample size in our studies was 4,317, with 2,186 in the experimental and 2,131 in control groups, respectively. The mean age was 33.4 years, with 43% were male, while 57% were female. According to the selected studies, various factors, including immune mediators, particularly cytokines, genetic, and environmental factors, were identified in the development of AR.ConclusionThe selected studies presented findings on different factors and sub-factors in the pathogenesis of AR, making it a challenge for us to compare their results. However, based on our findings, researchers can link our identified factors to potential therapies for AR.

Background: Hereditary angioedema (HAE), a potentially life-threatening genetic disorder due to C1 inhibitor deficiency in most cases, is characterized by sudden and/or recurrent attacks of angioedema (subcutaneous/submucosal swellings). The global World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) International guideline for HAE management is comprehensive, but the implementation of this guideline may require regional adaptation considering the diversity in disease awareness, type of medical care systems, and access to diagnostics and treatment. The aim of this Delphi initiative was to build on the global guideline and provide regional adaptation to address the concerns and specific needs in the Middle East. Methods: The Consensus panel comprised 13 experts from the Middle East (3 from the United Arab Emirates, 3 from Saudi Arabia, 2 from Lebanon, 2 from Kuwait, 2 from Oman and 1 from Qatar) who have more than 2 decades of experience in allergy and immunology and are actively involved in managing HAE patients. The process that was carried out to reach the consensus recommendation included: 1.) A systematic literature review for articles related to HAE management using Ovid MEDLINE. 2.) The development of a questionnaire by an internationally acclaimed expert, with 10 questions specific to HAE management in the Middle East. 3.) Experts received the questionnaire via email individually and their answers were recorded (email/interview). 4.) A virtual consensus meeting was organized to discuss the questionnaire, make amends if needed, vote, and achieve consensus. Results: The questionnaire comprised 10 questions, each with 2 or more statements/recommendations on which the regional experts voted. A consensus was reached based on a 70% agreement between the participants. The key highlights include: 1) HAE experts in the Middle East emphasized the importance of a positive family history for arriving at a diagnosis of HAE. 2) The number of episodes per month or per 6-month period and severity should be used, together with other markers, to determine the need for prophylaxis. 3) Disease status should be monitored by periodic visits and the use of patient-reported outcome measures such as the angioedema activity score and the angioedema control test. 4) Attenuated androgens and tranexamic acid may be considered for long-term prophylaxis, if lanadelumab, C1-Inhibitor or berotralstat are not available. Conclusion: This consensus recommendation may help to educate healthcare practitioners in the Middle East and unify their approach to the diagnosis and management of HAE.

Systemic corticosteroids (SCS) are a highly effective treatment for acute exacerbations and long-term symptom control in asthma. Long-term SCS use is highly prevalent across all asthma severities, occurring in over 20% of patients with severe or uncontrolled disease globally. It is now well known that exposure to both long-term and repeated acute courses of SCS is associated with a high risk of serious adverse effects (AEs), such as osteoporosis, and metabolic and cardiovascular complications, especially when prescribed onto a background of other corticosteroids. The aim of this call-to-action article, endorsed by the World Allergy Organization and the Respiratory Effectiveness Group, is to review the accumulating evidence on the burden of SCS on patients with asthma and provide an overview of potential strategies for implementing SCS Stewardship.Primary prevention of exacerbations and improvement of asthma control is a key first step in achieving SCS Stewardship, by optimizing maintenance asthma medications and addressing modifiable risk factors, such as adherence and inhaler technique. Other key elements of SCS Stewardship include increasing appropriate specialist referrals for multidisciplinary review, assessment of biomarkers, and consideration of oral corticosteroid-sparing add-on therapies (eg, biologics). In cases where SCS use is deemed clinically justified, it should be tapered to the lowest possible dose. In addition, patients receiving long-term SCS or frequent acute courses should be closely monitored for emergence of SCS-related AEs.Because of the extensive data available on the costly and burdensome AEs associated with SCS use, as well as the range of treatment options now available, there is a need for healthcare providers (HCPs) to carefully evaluate whether the benefits of SCS outweigh the potential harms, to adopt SCS-sparing and Stewardship strategies, and to consider alternative therapies where possible. Development of a structured and collaborative SCS Stewardship approach is urgently required to protect patients from the potential harm of SCS use.

Chronic inflammatory airway diseases, including asthma, chronic rhinosinusitis, eosinophilic COPD and allergic rhinitis are a global health concern. Despite the coexistence of these diseases and their common pathophysiology, they are often managed independently, resulting in poor asthma control, continued symptoms and poor quality of life. Understanding disease pathophysiology is important for best treatment practice, reduced disease burden and improved patient outcomes. The pathophysiology of type 2 inflammation is driven by both the innate immune system triggered by pollutants, viral or fungal infections involving type 2 innate lymphoid cells (ILC2) and the adaptive immune system, triggered by contact with an allergen involving type 2 T-helper (Th2) cells. Both ILC2 and Th2 cells produce the type-2 cytokines (interleukin (IL)-4, IL-5 and IL-13), each with several roles in the inflammation cascade. IL-4 and IL-13 cause B-cell class switching and IgE production, release of pro-inflammatory mediators, barrier disruption and tissue remodelling. In addition, IL-13 causes goblet-cell hyperplasia and mucus production. All three interleukins are involved in trafficking eosinophils to tissues, producing clinical symptoms characteristic of chronic inflammatory airway diseases. Asthma is a heterogenous disease; therefore, identification of biomarkers and early targeted treatment is critical for patients inadequately managed by inhaled corticosteroids and long-acting β-agonists alone. The Global Initiative for Asthma guidelines recommend add-on biological (anti IgE, IL-5/5R, IL-4R) treatments for those not responding to standard of care. Targeted therapies, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab, were developed on current understanding of the pathophysiology of type 2 inflammation. These therapies offer hope for improved management of type 2 inflammatory airway diseases.

Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria. Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care.

Background: While crucial to the assessment and improvement of asthma control, insights on treatment practices in patients with severe diseases across Gulf nations are lacking. This observational study describes the treatment patterns of adolescents and adults with severe asthma across four countries of the Gulf region and evaluates current levels of asthma control; quality of life (QoL); exacerbation frequency; and the application of cellular, protein, and respiratory biomarkers in assessing asthma severity and inflammation. Methods: Patients (aged >12 years, body weight ≥40 kg) with clinician-diagnosed, severe asthma (guided by the 2018 Global Initiative for Asthma definition) were included in this cross-sectional, multicenter, observational study conducted in the four Gulf countries of Kuwait, Oman, Qatar, and the United Arab Emirates. Data on demographics, treatment patterns, and laboratory parameters (blood eosinophil count [BEC], levels of serum immunoglobulin E [IgE], and fractional exhaled nitric oxide [FeNO]) were extracted from the medical records of patients during a 12-month retrospective period and transcribed onto case report forms. At the Enrollment visit, patients assessed their asthma control and QoL with the self-administered Asthma Control Questionnaire (ACQ) and a standardized version of the Asthma Quality of Life Questionnaire (AQLQ(S)), respectively. Results: Among the 243 patients analyzed, (mean [standard deviation (SD)] age, 48.4 [13.9] years; female, 67.5%), the inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combination was the most prescribed asthma medication (n = 240; 98.8%). Most patients were classified as “uncontrolled,” (n = 173; 71.2%) and the majority (n = 206; 84.8%) experienced ≥1 exacerbation(s) in the preceding 12 months. The mean (SD) ACQ score was 2.1 (1.2), which indicated uncontrolled asthma, and the mean (SD) total AQLQ(S) score was 4.7 (1.4), suggesting “some limitation” in overall QoL. BECs during the 12-month period were elevated in most patients (>300 cells/μL [n = 183; 41.7%], 150–300 cells/μL [n = 138; 31.4%],

Abstract Acquired thrombotic thrombocytopenic purpura is characterized by the microvascular aggregation of platelets and microangiopathic hemolytic anemia causing ischemia of multiple organs including the brain mainly and less likely the kidney and the heart. The disease is caused by severe reduction in the activity of ADAMTS 13 due to presence of inhibitory antibodies.

Abstract Background Sensitization to airborne molds may be a risk factor for severe asthma and direct cause of asthma exacerbation (AE). Methods A prospective, 1-year (April 2016–March 2017) study, done in Kuwait Allergy Centre, investigated the link between AEs with exposure to outdoor molds and the role of meteorological parameters in mold sensitized patients and compared with non-allergic asthma patients who had asthma deterioration. The total of 676 adult asthmatics with moderate-severe AEs were included and divided into atopic (85.65%) and non-atopic group. Atopy was defined by positive skin prick test (SPT) to at least one inhalant allergen. Data regarding atopy and asthma severity were collected from patient’s records. Patients with symptoms and signs of acute respiratory infection and patient sensitized to indoor allergens only were excluded. Daily count of local pollens (Salsola kali, Bermuda grass) and molds (Aspergillus, Alternaria and Cladosporium) were obtained from the Aerobiology department. Daily metrological parameters (atmospheric pressure-AP, temperature-T and relative humidity-RH) were provided by Kuwait Environment Public Authority. Count of spores/m3 and weather variable are shown on weekly basis. The year circle was divided into 4 Seasons (1, 2, 3, 4) accordingly to typical desert climate. Results Sensitization to molds was relatively high but significantly less (25.0%) if compared to the pollens sensitization. The highest number of AEs was in season 4 for both molds and pollens sensitized patients. Seasonal patterns for both allergens were significant and positively correlated with RH and AP. In season 1 only, mold sensitized patients showed higher rate of AEs. Non-atopic patients have been less sensitive to increased RH than atopic. Negative correlation with T was similar in both atopic and non-atopic patients. Conclusion Despite of high rate of sensitization to molds, their significant role in triggering AE was not found in desert environment. Typical desert climate and high allergencity of local weeds outweigh the influence of the molds.

Aim To assess efficacy of omalizumab in moderate to severe asthma and notable factors affecting it, such as treatment compliance during the period of ten years. This retrospective, observational real life study is the first of this kind in the Gulf region and one of the worldwide rare long term omalizumab treatment studies. Methods The treatment for 35 patients started in 2008. Twenty patients (ongoing group) proceeded with treatment and were assessed annually until 2017. Reasons for treatment discontinuation in 15 patients (drop-out group) were also assessed. Results Before starting omalizumab the ongoing group of patients had history of ≥2 asthma exacerbations per year, which significantly decreased during the first year of the treatment (p

Background: Drug hypersensitivity reactions (DHRs) are among the most frequent reasons for consultation in allergy departments and are becoming more common due to increasing prevalence and case complexity.Objective: To describe the most common drugs associated with clinical reactions, diagnostic methods used, and outcomes of allergic evaluations of a national drug allergy registry over a 12-year period were used.Methods: An observational, prospective, patient’s data registry-based study was conducted to analyze all referrals to the drug allergy outpatient clinics at Al-Rashed Allergy Center, Kuwait, between 2007 and 2019. Demographics, description of DHRs, and results of allergy tests to potential causative medications were reviewed. Diagnostic methods were focused mainly on skin tests (STs) and drug provocation test (DPT), when indicated.Results: We evaluated 1,553 patients with reported DHRs. The mean age of the population was 41.52 ± 16.93 years, and the study population consisted of 63.7% female patients. Hypersensitivity was finally confirmed in 645 (41.5%) of patients, probable in 199 (12.8%), and not confirmed/nonallergic in 709 (45.6%) patients. Anti-inflammatory drugs and analgesics contributed to 39.22% of all confirmed drug allergies, followed by antibiotics 38.1% (β-lactam antibiotics (BLs) constituted 73.98% of all antibiotics and 28.21% of all drugs), anesthetics 1.8%, and radio-contrast media 0.31%. The majority of reactions were non-immediate 51.44%. The most commonly presenting symptoms among confirmed patients were urticaria 57.80%, angioedema 42.50%, respiratory symptoms 47.60%, and erythema 33.60%. Symptoms of anaphylaxis/anaphylactic shock were reported by 284 patients (44.00%) among confirmed cases. The most common method of diagnosis was a positive clinical history (54.4% in BLs and 90.45% in nonsteroidal anti-inflammatory drugs (NSAIDs). Among confirmed allergy to BLs, a positive ST was obtained in 31.9% of patients and positive DPT in 13.7%.Conclusion: NSAIDs and antibiotics, mainly BLs, are the most commonly implicated in confirmed allergy. In both confirmed and not confirmed/nonallergic cases, BLs are the most frequently involved DHRs which are mainly immediate, and the most commonly presenting symptoms were urticaria, angioedema, and respiratory symptoms. Diagnosis was confirmed mainly by a positive clinical history and when indicated, by positive STs or a DPT.

Background: Severe asthma is a subtype of asthma that can be hard to control, resulting in an exceptional impact on an individual's quality of life. The aim of this review article is to explore the misalignment of perceptions of severe asthma among different stakeholders to identify how to reduce burden and improve delivery of care. Results: The misalignment of perspectives is best reflected in randomised controlled trials (RCTs) in asthma treatments, which are often designed for regulatory approval with a focus on exacerbations with no direct input from the individuals that the treatments are designed for. Based on a literature review and the clinical experience of the authors to overcome this disparity, the goals of people with severe asthma need to be incorporated throughout their care, from study design to the day-to-day management of their condition. Improved education for individuals and their support network will provide them with resources and knowledge so that they can effectively communicate their needs to other stakeholders involved in their care. Conclusion/recommendation: A collaborative effort from all stakeholders is essential to ensure efficient management of asthma and a reduction in asthma burden on individuals and society.

Background: Allergen-specific immunotherapy (AIT) is safe and effective for the treatment of allergic rhinitis and allergic asthma. However, patient non-compliance is a major barrier to achieving optimal outcomes Objective: To determine the level of compliance among patients using AIT and to identify factors associated with non-compliance Methods: A retrospective analysis using questionnaires was conducted to study compliance among 236 patients with allergic rhinitis with or without asthma who began AIT in 2009 or 2010 Results: The compliance rates at 3 y were 58.7% among patients on subcutaneous immunotherapy (SCIT) and 11.6% among those on sublingual immunotherapy (SLIT). The mean durations of treatment with SCIT and SLIT were 31 (+/−18.3) and 15.9 (+/−14.7) months, respectively. The most common causes of non-compliance among patients on SCIT were the frequency of injections (82.2%), the duration of treatment (70.9%), and commuting to the Allergy Center (67.7%). Reasons for non-compliance among patients on SLIT were related to inconvenience (43.4%), improvement without treatment (30.2%) and perception of poor efficacy (25.0%) Conclusion: Compliance with AIT is low, but at 3 years, it was higher among patients on SCIT than among patients on SLIT. Reasons for non-compliance include difficulty adjusting to treatment protocols and a perception that the efficacy is low. Patient education regarding the treatment course and the slow effect, as well as the need for close follow up to effectively prevent and treat adverse reactions, are important factors for improving compliance and treatment outcomes.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency disease (PID) among adults. CVID consists of two phenotypes – one in which infections are the characteristic and another in which impressive inflammatory and/or hematological complications also develop, including lymphadenopathy, splenomegaly, autoimmune cytopenias, enteropathy, and granulomatous disease. These phenotypes appear to be stable, are related to immunological and inflammatory markers, and are predictive of outcomes. Both subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) are equally effective for replacement therapy. No data are available about specific factors affecting the quality of life related to switching from IVIG to SCIG in the Arabian Gulf area. We present the case reports of three adult CVID patients, who were shifted from IVIG to SCIG by the US conversion method (1 : 1.5). We followed-up patients for clinical outcomes, side-effects, immunoglobulin G (IgG) trough levels, annual infection rate, and quality of life using questionnaires (RAND-36) over a 3-year period. Three patients (two females and one male), with a mean age of 26 years, had received IVIG [Gamunex-C (Grifols Therapeutics Inc., NC, 27709 USA) 10%; Grifols] treatment for an average duration of 4 years and had average IgG trough levels of 7.7±2.9 g/dl. Patients were shifted to SCIG [Subcuvia (Baxalta Innovation GmbH, Vienna, Austria) 10%; Baxter] for different reasons. SCIG was administered, using an infusion pump, under medical supervision at the hospital, on a weekly basis. The average IgG trough level on SCIG was 10.4±1.5 g/dl. The annual infection rate of pneumonias, sinusitis, otitis media, and others significantly declined after switching to SCIG in all three patients. However, while on IVIG treatment, some patients reported headache and malaise, but when on the SCIG treatment the reactions were mild and infusion site-related such as erythema, swelling, and itching. Remarkably, all patients were successfully switched to SCIG with significant decrease in the annual rate of infections and a favorable steady-state of serum trough levels of IgG. The use of SCIG was generally associated with notable improvement in physical, emotional, and social health.

Objective: To present the report from the Kuwait National Primary Immunodeficiency Registry between 2004 and 2018.Methods: The patients were followed prospectively between January 2004 and December 2018 and their collected data included sociodemographic, diagnosis, clinical presentation, laboratory tests, and treatment.Results: A total of 314 PID patients (165 males and 149 females) were registered during the study period. Most of the patients (n = 287, 91.4%) were Kuwaiti nationals and the prevalence among Kuwaitis was 20.27/100,000 with a cumulative incidence of 24.96/100,000 Kuwaitis. The distribution of the patients according to PID categories was as follow: immunodeficiencies affecting cellular and humoral immunity, 100 patients (31.8%); combined immunodeficiencies with associated syndromic features, 68 patients (21.7%); predominantly antibody deficiencies, 56 patients (17.8%); diseases of immune dysregulation, 47 patients (15%); congenital defects of phagocyte number or function, 20 patients (6.4%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 22 patients (7%). The mean age of the patients at onset of symptoms was 26 months while the mean age at diagnosis was 53 months and the mean delay in diagnosis was 27 months. Most of the patients (n = 272, 86%) had onset of symptoms before the age of 5 years. Parental consanguinity rate within the registered patients was 78% and a positive family history of PID was noticed in 50% of the patients. Genetic testing was performed in 69% of the patients with an overall diagnostic yield of 90%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by an autosomal recessive pattern. Intravenous immunoglobulins and stem cell transplantation were used in 58% and 25% of the patients, respectively. There were 81 deaths (26%) among the registered patients with a mean age of death of 25 months.Conclusions: PID is not infrequent in Kuwait and the reported prevalence is the highest in the literature with increased proportion of more severe forms. Collaborative efforts including introduction of newborn screening should be implemented to diagnose such cases earlier and improve the quality of life and prevent premature deaths.

Abstract One of the major concerns in the practice of allergy is related to the safety of procedures for the diagnosis and treatment of allergic disease. Management (diagnosis and treatment) of hypersensitivity disorders involves often intentional exposure to potentially allergenic substances (during skin testing), deliberate induction in the office of allergic symptoms to offending compounds (provocation tests) or intentional application of potentially dangerous substances (allergy vaccine) to sensitized patients. These situations may be associated with a significant risk of unwanted, excessive or even dangerous reactions, which in many instances cannot be completely avoided. However, adverse reactions can be minimized or even avoided if a physician is fully aware of potential risk and is prepared to appropriately handle the situation. Information on the risk of diagnostic and therapeutic procedures in allergic diseases has been accumulated in the medical literature for decades; however, except for allergen specific immunotherapy, it has never been presented in a systematic fashion. Up to now no single document addressed the risk of the most commonly used medical procedures in the allergy office nor attempted to present general requirements necessary to assure the safety of these procedures. Following review of available literature a group of allergy experts within the World Allergy Organization (WAO), representing various continents and areas of allergy expertise, presents this report on risk associated with diagnostic and therapeutic procedures in allergology and proposes a consensus on safety requirements for performing procedures in allergy offices. Optimal safety measures including appropriate location, type and required time of supervision, availability of safety equipment, access to specialized emergency services, etc. for various procedures have been recommended. This document should be useful for allergists with already established practices and experience as well as to other specialists taking care of patients with allergies.

Hypersensitivity reactions to radiocontrast media (RCM) are common and in severe cases may present a challenge for treating physician in cases when premedication fails or the patient presents with severe comorbidities. We describe two cases in need of radiocontrast media after a severe reaction on previous exposure to iohexol. One presented anaphylactic reaction to RCM despite premedication and another presented with angina. Both cases were treated with a desensitization protocol to iodixanol. In conclusion, desensitization to radiocontrast media may be considered in patients with previously unsuccessful premedication and/or severe acute comorbidities. SIMILAR CASES PUBLISHED: 14

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population.Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges.This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.