Consensus on diagnosis and management of Hereditary Angioedema in the Middle East: A Delphi initiative.

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.

PRevalence of the Eosinophilic Phenotype Among SeveRE asthma patients in Lebanon: results of the PREPARE study.

BACKGROUND: The prevalence of eosinophilic asthma in Lebanon, one of the most severe phenotypes among severe asthma, is not known. This study aimed at determining the prevalence of the eosinophilic phenotype defined as an eosinophil count ≥ 300 cells/mm3 among severe asthma patients in Lebanon. METHODS: The Lebanese Chapter of the PREPARE study was a national, multicenter, cross-sectional observational study. Patients aged ≥ 12 years with severe asthma were identified and prospectively enrolled during clinic visits and completed the Global Initiative for Asthma (GINA) assessment of asthma control questionnaire. Patients' health characteristics were collected from medical records and blood samples were obtained for measurement of serum IgE levels and blood eosinophils count. RESULTS: Overall, 101 patients (with mean age of 46.3 ± 17.0 years and 73.27% females) with severe asthma were included and, among them, 37% had eosinophilic phenotype, 67.3% had atopic phenotype with IgE > 100 IU/mL and 25.7% patients had overlapping atopic and eosinophilic phenotypes. Close to 80% had late-onset asthma, beyond 12 years of age, and around 85% had at least one severe exacerbation in the 12 months prior to study enrolment. The majority of participants [64.4%] had uncontrolled asthma, 24.7% had partially controlled symptoms and 10.9% had controlled symptoms. 19.8% of participants were on chronic oral corticosteroids, 78.2% had short course treatment of corticosteroids and all were prescribed a combination of inhaled corticosteroids and long-acting beta-agonist. CONCLUSIONS: The majority of patients with severe asthma were uncontrolled of which 37% present with an eosinophilic phenotype, which should be taken into consideration for better management of these patients in view of the novel phenotype-specific therapeutic options.

Digital tools in allergy and respiratory care.

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.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.

BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Clinical characteristics and management of chronic spontaneous urticaria in patients refractory to H1-Antihistamines in Asia, Middle-East and Africa: Results from the AWARE-AMAC study.

BACKGROUND: Chronic urticaria (CU) is a condition characterized by recurrent itchy hives and/or angioedema for ≥6 weeks. Most of the data about CU come from western countries with very little information available about CU in Asia, Africa, and the Middle East. METHODS: AWARE-AMAC is a 24-month prospective, observational, real-world, non-interventional study in patients aged ≥18 years from Asia, the Middle East, and Africa (AMAC) with CU refractory to H1-antihistamines (H1-AH). The main objective was to describe the real-world experience with CU, including clinical characteristics, presence of angioedema, treatment patterns (shifts between treatment classes and changes within a treatment class), investigator-assessed disease control, and the impact on quality of life. Subgroups of interest were type of CU at Baseline and treatment class (based on 2013 urticaria guidelines). There were no mandatory visits and diagnostic/monitoring procedures additional to routine practice, except the patient diary (7-day Urticaria Activity Score) and patient reported outcome assessments. RESULTS: The focus of the current manuscript is on patients with chronic spontaneous urticaria (CSU), who formed 98% of the sample. Patients were predominantly female (69.6% female, mean age ± SD 39.8 ± 13.29 years). Time since current diagnosis (Mean ± SD) was 28.6 ± 49.06 months. Amongst patients with CSU, 31.0% had comorbid chronic inducible urticaria (CINDU) and 46.4% had a history of angioedema. 91.9% received H1-AH therapy (±other treatments). The most frequently prescribed treatment classes at Baseline were any/combination of medications, not classified under the other 7 treatment classes, named "Others" (30.5%) followed by, omalizumab (OMA; 23.6%) and second-generation H1-AH monotherapy (sgAH; 15.1%). At Month 12, the most prescribed treatment classes (>15%) for patients were OMA (23.5%) and "Other" (21.3%); 19.7% received "No drug". At Month 24, OMA (22.5%), and "Other" (17.9%) were most frequently prescribed; 28.6% received "No drug". Overall, 79.5% of patients had some type of change in treatment. Over the study period, improvement in self-reported QoL increased, which was mirrored by better disease control. CONCLUSION: In AMAC countries, the non-recommended "Other" treatment class played a major role in the initial management of CU patients. High usage of H1-AH (±other treatments) and OMA was observed. Treatment changes were observed in a majority of patients. Treatment escalation from sgAH was mostly via OMA. Improvement of disease control and QoL was achieved during the study period. TRIAL REGISTRATION: Observational study (NA).

Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).

Air pollution causes significant morbidity and mortality in patients with inflammatory airway diseases (IAD) such as allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma, and chronic obstructive pulmonary disease (COPD). Oxidative stress in patients with IAD can induce eosinophilic inflammation in the airways, augment atopic allergic sensitization, and increase susceptibility to infection. We reviewed emerging data depicting the involvement of oxidative stress in IAD patients. We evaluated biomarkers, outcome measures and immunopathological alterations across the airway mucosal barrier following exposure, particularly when accentuated by an infectious insult.

Prevalence of asthma, allergic rhinitis and eczema among Lebanese adolescents.

OBJECTIVE: Studies on allergic diseases remain scarce in Lebanon. The aim of the present study was to determine prevalence and characteristics of asthma, allergic rhinitis and eczema among Lebanese school children. METHODS: The study was cross-sectional in design performed on a convenient sample of 3,115 students (13-14 yr) selected from 13 schools in 5 Lebanese provinces. Students were asked to complete the Arabic version of the International Study of Asthma and Allergies in Childhood questionnaire. Logistic regression was performed to assess the characteristics of having asthma, allergic rhinitis and eczema in the past year. RESULTS: The prevalence of ever having asthma, rhinitis and eczema was 8.3%, 45.2% and 12.8% respectively, while the prevalence of the symptoms of these diseases in the past year was 24.1%, 38.6% and 20.9%, respectively. Residing in the South and the North provinces of Lebanon and living in a busy area increased the likelihood of developing asthma and rhinitis. Higher rates of asthma and eczema, however, was noted among students going to private schools (Odds Ratio (OR) = 1.6, 95% confidence interval (CI): 1.3-2.1 and OR = 1.3, 95% CI: 1.0-1.7, respectively). Passive smoking was significantly associated with asthma only (OR = 1.3, 95% CI: 1.1-1.7). In addition to the above, the odds of having any of the three outcomes increases to at least 2.4-fold when accompanied by another allergic disease. CONCLUSIONS: Allergic diseases are highly prevalent in Lebanon and are catching up with the rates of developed countries. Moreover, the role of each of the three diseases in the existence of the other two had the greatest impact on their prevalence.

Worldwide perspectives on venom allergy.

Venom immunotherapy is the standard of care for people with severe reactions and has been proven to reduce risk of future anaphylactic events. There is a moral imperative to ensure production, supply and worldwide availability of locally relevant, registered, standardized commercial venom extracts for diagnosis and treatment. Insects causing severe immediate allergic reactions vary by region worldwide. The most common culprits include honeybees (Apis mellifera), social wasps including yellow jackets (Vespula and Dolichovespula), paper wasps (Polistes) and hornets (Vespa), stinging ants (Solenopsis, Myrmecia, Pachycondyla, and Pogonomyrmex), and bumblebees (Bombus). Insects with importance in specific areas of the world include the Australian tick (Ixodes holocyclus), the kissing bug (Triatoma spp), horseflies (Tabanus spp), and mosquitoes (Aedes, Culex, Anopheles). Reliable access to high quality venom immunotherapy to locally relevant allergens is not available throughout the world. Many current commercially available therapeutic vaccines have deficiencies, are not suitable for, or are unavailable in vast areas of the globe. New products are required to replace products that are unstandardized or inadequate, particularly whole-body extract products. New products are required for insects in which no current treatment options exist. Venom immunotherapy should be promoted throughout the world and the provision thereof be supported by health authorities, regulatory authorities and all sectors of the health care service.

The use of a screening questionnaire to determine the incidence of allergic rhinitis in singers with dysphonia.

OBJECTIVES: To report the incidence of allergic rhinitis in singers with nonspecific laryngeal examination findings and to correlate the incidence of allergic rhinitis with their vocal symptoms when present. DESIGN: A retrospective review of all the medical records of singers with nonspecific laryngeal findings who presented to a specialty voice center for either vocal training or therapy between June 2002 and September 2005. SETTING: Specialty voice center. PARTICIPANTS: Forty-five singers with nonspecific laryngeal findings who presented to a specialty voice center for either vocal training or therapy. MAIN OUTCOME MEASURES: A standardized validated questionnaire for evaluation of allergic rhinitis was filled out by all the subjects. A score above 0 was considered positive. RESULTS: The total prevalence of allergic rhinitis was 87% (39 of 45 subjects). The singers with vocal symptoms were approximately 15% more likely to have allergic rhinitis than those with no vocal symptoms (92% vs 84%). Singers with more than 2 vocal symptoms had a 25% higher likelihood of having allergic rhinitis. CONCLUSIONS: The incidence of allergic rhinitis in singers is extremely high. Hidden respiratory allergies may affect the professional voice. Proper awareness and a multidisciplinary approach are indispensable for proper diagnosis and treatment.

Successful retreatment with infliximab in patients with prior severe infusion reactions.

Infusion of the antitumor necrosis factor-alpha chimeric monoclonal antibody infliximab can be associated with the development of severe infusion reactions (IR) during retreatment. We present the case of two rheumatoid arthritis patients with a history of severe acute IR to infliximab who subsequently underwent successful infusion using a prophylactic treatment with a combination of H1 and H2 receptor blockers, hydrocortisone, and diphenhydramine.

Acute allergic reactions in the emergency department: characteristics and management practices.

OBJECTIVE: The objective of this study is to determine the incidence of emergency department (ED) visits for acute allergic reactions, identify the triggers, assess the severity, evaluate the management practices, and examine patient outcomes at a single-center ED in Lebanon. PATIENTS AND METHODS: A retrospective review of all patient charts presenting with a final diagnosis of acute allergic reaction to a single ED within a 6-month period (July-December 2009) was carried out. Age, sex, triggers, management in the ED and at discharge, disposition, and return visit were determined. RESULTS: Two hundred and forty-five patients were identified (82.4% mild, 15.1% moderate, and 2.6% severe, respectively). This accounted for 0.96% of all ED visits. Drugs were the most commonly identified trigger (23.7%). In the ED, 72.7% of patients received H1-antihistamines, 51.8% received corticosteroids, 7.3% received H2-antihistamines, and 7.3% received inhaled B2 agonists. Only 15.9% of anaphylaxis cases received epinephrine in the ED. Similarly, the majority of patients were discharged on H1-antihistamines (93.9%), with only 4.5% of patients with anaphylaxis receiving prescriptions for epinephrine injections. All patients except one were discharged home. No fatalities were noted and the return visit rate within 1 week was 9.8%. CONCLUSION: The incidence of ED visits for acute allergic reaction was high compared with other studies, although the majority of cases were mild. Deviations from published guidelines on the treatment of anaphylaxis are common, with rare use of epinephrine and heavy reliance on H1-antihistamines both in the ED and at discharge. This did not seem to result in any measurable impact on mortality.

Epidemiology of eczema among Lebanese adolescents.

OBJECTIVE: The study aims to determine the prevalence of eczema among Lebanese adolescents and identify demographic, nutritional and environmental characteristics associated with eczema. METHODS: A cross-sectional study conducted on a convenient sample of 3 153 students (13-14 years) selected from five different provinces in Lebanon. Significant unadjusted demographic, nutritional and environmental variables were considered in a stepwise regression model. RESULTS: Ever having an itchy rash that lasted for a period more than six months was reported by 788 (25.0%) adolescents, while 404 (12.8%) reported ever having eczema. Females and passive smokers were at 1.5 increased risk of having eczema than their counterparts. Exercising regularly, living near a busy area, and frequent eating of eggs were positively associated with eczema. Finally, adolescents who suffered from allergic diseases, asthma (Odds ratio (OR): 1.64, 95% CI: 1.16-2.32), rhinitis (OR: 1.35, 95% CI: 1.07-1.70) and hay fever (OR: 2.77; 95% CI: 2.12-3.62) also reported having had eczema. CONCLUSION: Environmental factors were found to play an important role in the prevalence of eczema among adolescents.