Impact of climate change-related environmental factors on the allergens production and the epidemiology and severity of allergic pathologies.

BACKGROUND: Allergic disease affects up to 40% of the global adult population, a proportion that is increasing with environmental changes related to global warming. METHODS: We undertook a systematic review of the literature to identify and evaluate the current evidence of the impact of climate change-related environmental factors on the allergen production and the epidemiology and severity of allergic pathologies. PECO criteria were established and guided the literature searches of the PubMed and Cochrane databases (Jan 1, 2016 to Dec 31, 2021). Study outcomes were categorized and grouped to facilitate data synthesis. Outcomes were classified as significant (statistical significance <0.05), non-significant (p>0.05) or undetermined (p value not reported). Study quality was assessed using MMAT analysis. RESULTS: Of 195 studies, 40 were considered relevant and 9 of them provided data to be included in the data quantitative synthesis. Environmental factors, including the presence of pollutants, temperature, and drought, influenced the type, volume, and timing of exposure to local aeroallergens. The most relevant environmental factor was the presence of environmental pollutants, of which tropospheric ozone was the most frequently associated to changes in allergen production, prevalence, and severity of allergic disease. Also, several publications demonstrated the impact of environmental factors on the healthcare burden. CONCLUSIONS: Climate-change related environmental factors increased allergic disease in terms of prevalence, severity, and healthcare burden due to alterations in allergen exposure (volume and type) with the presence of pollutants such as ozone being the most commonly reported driver of such increase.

Impact of Asthma Inhalers on Global Climate: A Systematic Review of Their Carbon Footprint and Clinical Outcomes in Spain.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) exert an environmental impact resulting from CO2 emissions. Therapeutic alternatives with less environmental impact are widely used. Nevertheless, the choice of device and appropriate therapy should meet the clinical needs and the characteristics of the patient. OBJECTIVE: The primary objective was to estimate the impact of pMDIs prescribed for any indication on annual CO2 emissions in Spain.The secondary objective was to evaluate the potential impact of switching pMDIs to dry-powder inhalers (DPIs) in patients with asthma. METHODS: A systematic review of the evidence published during 2010-2021 was carried out. Average annual CO2 emissions of DPIs and pMDIs were calculated in 2 scenarios: the current situation and a hypothetical situation involving a switch from all pMDIs to DPIs. The impact of the switch on clinical outcomes was also evaluated. RESULTS: The total value of CO2-eq/year due to DPIs and pMDIs accounted for 0.0056% and 0.0909%, respectively, of total emissions in Spain. In the event of switching pMDIs to DPIs, except those used for rescue medication, the percentages were 0.0076% and 0.0579%. The evaluation of efficacy, handling, satisfaction, safety, and use of health care resources was not conclusive. CONCLUSIONS: Current CO2 emissions by pMDIs account for a small percentage of the total CO2 footprint in Spain. Nevertheless, there is a need for research into new and more sustainable devices. Suitability and patient clinical criteria such as age and inspiratory flow should be prioritized when prescribing an inhaler.

Severity and duration of allergic conjunctivitis: are they associated with severity and duration of allergic rhinitis and asthma?

Summary: Objective. The association of allergic conjunctivitis (AC) with rhinitis and/or asthma is poorly understood. The objective of this study was to apply the Consensus Document for Allergic Conjunctivitis (DECA) criteria for the classification of AC to a population of patients with AC to assess the association between the severity and duration of AC and rhinitis and/or asthma. Methods. Patients with ocular symptoms of AC who participated in the 'Alergológica 2015' study were included. The demographics, classification according to the DECA criteria, etiology, and comorbidities were evaluated by age groups (less or equal than 14 and greater than 14 years). Results. A total of 2,914 patients (age range, 1-90 years) were included in the "Alergológica 2015" study. Of these, 965 patients (33.1%) were diagnosed with AC (77.5% > 14 years). AC was classified as severe, moderate, or mild in 1.8%, 46.4%, and 51.8%, respectively; and as intermittent or persistent in 51.6% and 48.4% of the patients. AC alone occurred in 4% of patients. AC was mainly associated with rhinitis (88.4%), asthma (38.2%), food allergy (8.3%) and atopic dermatitis (3.5%). In allergic respiratory disease rhinitis preceded AC and asthma developed later. The severity and duration of AC was significantly associated with severity and duration of rhinitis (p less than 0.001 for both age groups) and asthma (p less than 0.001 only in adults). Conclusions. The application of the new DECA classification for AC reveals a direct relationship between AC, rhinitis and asthma respect to severity and duration. These relationships suggest that AC should be considered an integral part of the "one airway, one disease" hypothesis.

Posttransplant monomorphic Burkitt's lymphoma: clinical characteristics and outcome of a multicenter series.

Burkitt's monomorphic posttransplant lymphoproliferative disorder (B-PTLD) is an uncommon subtype of PTLD. Owing to the paucity of this complication, clinical characteristics and outcome has not been fully described. Clinical characteristics and outcomes of 20 patients diagnosed with B-PTLD from 10 transplant centers belonging to the GEL/TAMO group were reviewed. Median time from transplant to B-PTLD was 7.2 years. All the cases fulfill the morphologic and genetic criteria of B-PTLD, whereas Epstein-Barr virus (EBV) was detected in 70% of cases. Patients were treated with different chemotherapy combinations, and three patients received upfront rituximab monotherapy. The great majority of patients receiving CHOP-like regimens attained a complete response (CR) (73%), similar to that obtained with dose-intensive chemotherapy (83% CR). In contrast, patients receiving upfront rituximab monotherapy required subsequent chemotherapy. Two patients (10%) died during treatment due to infection. The median progression-free survival and overall survival (OS) were 16 months and 139 months, respectively. When analyzing variables predicting for OS, we found that patients with bone marrow involvement had an adverse prognosis, with a median OS of 6 months (p = 0.008). In conclusion, B-PTLD is an uncommon complication usually associated with EBV infection and with an aggressive clinical course, particularly in patients with bone marrow involvement. High-dose chemoimmunotherapy obtained similar responses to R-CHOP, suggesting that R-CHOP could be an adequate alternative for these patients. In contrast, rituximab monotherapy does not seem to be effective enough to control the disease.

Estimate of the total costs of allergic rhinitis in specialized care based on real-world data: the FERIN Study.

BACKGROUND: Despite the socioeconomic importance of allergic rhinitis (AR), very few prospective studies have been performed under conditions of clinical practice and with a sufficiently long observation period outside the clinical trial scenario. We prospectively estimated the direct and indirect costs of AR in patients attending specialized clinics in Spain. METHODS: Patients were recruited at random from allergy outpatient clinics in 101 health centers throughout Spain over 12 months. We performed a multicenter, observational, prospective study under conditions of clinical practice. We analyzed direct costs from a funder perspective (healthcare costs) and from a societal perspective (healthcare and non-healthcare costs). Indirect costs (absenteeism and presenteeism [productivity lost in the workplace]) were also calculated. The cost of treating conjunctivitis was evaluated alongside that of AR. RESULTS: The total mean cost of AR per patient-year (n = 498) was €2326.70 (direct, €553.80; indirect, €1772.90). Direct costs were significantly higher in women (€600.34 vs €484.46, P = 0.02). Total costs for intermittent AR were significantly lower than for persistent AR (€1484.98 vs €2655.86, P < 0.001). Total indirect costs reached €1772.90 (presenteeism, €1682.71; absenteeism, €90.19). The direct costs of AR in patients with intermittent asthma (€507.35) were lower than in patients with mild-persistent asthma (€719.07) and moderate-persistent asthma (€798.71) (P = 0.006). CONCLUSIONS: The total cost of AR for society is considerable. Greater frequency of symptoms and more severe AR are associated with higher costs. Indirect costs are almost threefold direct costs, especially in presenteeism. A reduction in presenteeism would generate considerable savings for society.

Allergy rhinitis: similarities and differences between children and adults.

BACKGROUND: Allergic rhinitis (AR) is a highly prevalent disease worldwide. Although a number of studies have described AR, no studies compared children and adult AR populations. The objective was to compare the AR characteristics between two AR cohorts of children and adults. METHODS: Two AR cohorts (children and adults) from Spain were studied through observational cross-sectional multicentre studies. AR was classified based on classical (allergen exposure), original (o-ARIA), and modified (m-ARIA) ARIA criteria. AR was evaluated by Total 4-Symptoms Score (T4SS), and disease severity by Visual Analogue Scale (VAS, 0-100 mm). AR comorbidities were also evaluated. RESULTS: A total of 5,405 patients (1,275 children, 4,130 adults) were studied. According to symptoms duration, intermittent AR was more frequent in children than in adults. Using o-ARIA severity, more children than adults had moderate/severe AR while, using m-ARIA, more children than adults had severe AR. T4SS was higher in adults than in children. Moreover, VAS was also higher in adults than in children. In addition, asthma atopic dermatitis and conjunctivitis were more associated to children than adults with AR, the frequency of this comorbidities increasing according to higher severity. CONCLUSIONS: AR in children was more intermittent, severe, with less symptoms but with more comorbidities than in adults. These results suggest AR has similarities but also significant differences between children and adults.

Allergic rhinitis severity can be assessed using a visual analogue scale in mild, moderate and severe.

BACKGROUND: Allergic rhinitis is a global healthcare problem due to its high prevalence, impact on individuals and socioeconomic burden for the nations. Allergic rhinitis severity evaluation is the key to a correct treatment, prevention of comorbidities and improving the quality of life of patients. This evaluation should be made with a simple, easy, fast but accurate and reliable methodology, both in a primary care and specialist setting. The visual analogue scale (VAS) meets all requirements to be the ideal tool to assess allergic rhinitis severity and has already been validated by using a single cut-off point, but this classification in two degrees of severity suffer from not allocating the patients uniformly and from giving a blind interval to classify the patients when the score is between 5 to 6 cm. METHODOLOGY: The main objective of our study is to describe the optimal cut-off points by using a VAS to discriminate between three degrees of allergic rhinitis severity (mild, moderate, and severe) following the ARIA modified severity criteria that has been previously validated. Sensitivity, specificity, positive and negative predictive values just like receiver operating characteristic curves were used to select the best cut-off values. RESULTS: In a cross-sectional multicentre study with 3,572 patients included we have found that VAS has a significant correlation with nasal symptom score and quality of life and that the best cut-off points to differentiate between mild, moderate an severe allergic rhinitis are a VAS score of 4 and 7, respectively. CONCLUSIONS: Allergic rhinitis severity could be assessed in three degrees by using VAS in a simple, easy, and accurate method.

Relationship between respiratory and food allergy and evaluation of preventive measures.

Food allergy and respiratory allergy are two frequently associated diseases and with an increasing prevalence. Several reports show the presence of respiratory symptoms in patients with food allergy, while certain foods may be related to the development or exacerbation of allergic rhinitis and asthma. The present update focuses on this relationship, revealing a pathogenic and clinical association between food and respiratory allergy. This association is even more intense when the food hypersensitivity is persistent or starts in the early years of life. Food allergy usually precedes respiratory allergy and may be a risk factor for allergic rhinitis and asthma, becoming a relevant clinical marker for severe atopic asthma. Furthermore, the presence of co-existing asthma may enhance life-threatening symptoms occurring during a food allergic reaction. Recommendations for dietary restrictions during pregnancy and breastfeeding to prevent the development of respiratory allergy are controversial and not supported by consistent scientific data. Current recommendations from medical societies propose exclusive breastfeeding during the first four months of life, with the introduction of solid food in the fourth to the seventh month period of life. A delayed introduction of solid food after this period may increase the risk of developing subsequent allergic conditions. Further studies are encouraged to avoid unjustified recommendations involving useless dietary restrictions.

Clinical Management and Use of Health Care Resources in the Treatment of Nasal Polyposis in Spanish Allergy Centers: The POLAR Study.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease that constitutes a major health problem with significant comorbidities and a considerable associated socioeconomic burden. OBJECTIVE: To describe the clinical features and management of patients with NP attending Spanish allergy centers, the use of health care resources, and the degree of compliance with the diagnostic and therapeutic recommendations of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS). METHODS: We performed a multicenter, observational, and cross-sectional epidemiologic study of 671 patients consulting for NP in 67 Spanish allergy departments. We used sociodemographic and clinical questionnaires to evaluate clinical characteristics, use of health care resources, diagnostic methods, and treatment administered. RESULTS: NP was closely associated with asthma (66%), allergic rhinitis (45.9%), and hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) (26%). Atopy was present in the 50% of cases, with Dermatophagoides pteronyssinus as the most frequent sensitizing allergen. Eleven percent of NP patients visited the emergency department during the previous year, and more than 58% used primary care, allergy, or otorhinolaryngology services. The most frequently used diagnostic tests were skin prick tests (93.6%) and anterior rhinoscopy (79.4%). Intranasal corticosteroids were the drug class most frequently prescribed by allergists (74.6%). Specific immunotherapy was prescribed in 21% of patients. CONCLUSIONS: NP is a chronic inflammatory disease that generates considerable use of health care resources. The close association with atopy, asthma, and NSAID hypersensitivity highlights the usefulness of an allergy workup in all patients with NP. Analysis of the clinical management of NP by allergists in Spain revealed a high degree of compliance with EPOS diagnostic and therapeutic recommendations.

Nasal Hyperreactivity: Nonspecific Nasal Provocation Tests. Review by the Rhinoconjunctivitis Committee of the Spanish Society of Allergy and Clinical Immunology.

Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5'-monophosphate, cold air, mannitol, rapsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity.

Consensus document on allergic conjunctivitis (DECA).

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms.

Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study.

BACKGROUND: Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population. METHODS: Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality. RESULTS: A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events. CONCLUSIONS: If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

Incidence, risk factors and therapy response of acute graft-versus-host disease after myeloablative hematopoietic stem cell transplantation with posttransplant cyclophosphamide.

Posttransplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. This study prospectively registered all consecutive adult patients with hematologic malignancies who received a myeloablative allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 385 patients were included, of whom 44%, 34% and 22% were transplanted from matched sibiling, matched unrelated and haploidentical donors, respectively. The 180-day cumulative incidence of aGVHD was 21% (95% confidence interval [CI] 17-25%) for grade II-IV and 11% (95% CI 8-14%) grade III-IV aGVHD. The use of haploidentical donors was associated with an increased risk of severe aGVHD. Among 75 patients receiving first-line systemic corticosteroids, 49% achieved a sustained complete response, while 23% and 24% developed steroid-dependent (SD-aGVHD) and steroid-refractory aGVHD (SR-aGVHD), respectively. SR-aGVHD was associated with worse salvage treatment response and overall survival compared to SD-aGVHD. The 1-year cumulative incidence of aGVHD-related mortality was 5.4% (95% CI, 3.3-8.1). Risk factors for aGVHD-related mortality included haploidentical donors, older donors, diagnosis of myeldysplastic neoplasms, and grade IV aGVHD. This study confirms a low incidence aGVHD with PTCy/siro/MMF prophylaxis. SR-aGVHD showed poorer response to salvage therapies and worse survival, while haploidentical donors and older donor age were negative predictors for aGVHD-related deaths.

Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.

BACKGROUND: Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. OBJECTIVE: The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications. DESIGN: The MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients. CONCLUSIONS: The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications.

A new HLA-DPB1 allele, HLA-DPB1*142:01, identified in a Peruvian organ donor.

The new HLA-DPB1*142:01 allele differs from DPB1*26:01:02 and DPB1*56:01 at codons 65 (I65>L65) and 35 (F35>Y35), respectively.

Use of second generation H1 antihistamines in special situations.

Antihistamine drugs are one of the therapeutic classes most used at world level, at all ages and in multiple situations. Although in general they have a good safety profile, only the more recent drugs (second generation antihistamines) have been studied specifically with regard to the more important safety aspects. Given the variety of antihistamine drugs, they cannot all be considered equivalent in application to various special clinical situations, so that the documented clinical experience must be assessed in each case or, in the absence of such, the particular pharmacological characteristics of each molecule for the purpose of recommendation in these special situations. In general, there are few clinical studies published for groups of patients with kidney or liver failure, with concomitant multiple pathologies (such as cardiac pathology), in extremes of age (paediatrics or geriatrics) and in natural stages such as pregnancy or lactation, but these are normal situations and it is more and more frequent (among the elderly) for antihistamine drugs to be recommended. This review sets out the more relevant details compiled on the use of antihistamines in these special situations.

H1 antihistamines and benzodiazepines. Pharmacological interactions and their impact on cerebral function.

Antihistamines (AH) have been classified into first and second generation according to their pharmacokinetic properties, structural characteristics and adverse effects. The effects on the central nervous system (CNS) are determined basically by their capacity to cross the hematoencephalic barrier and attach to central H1 receptors. Benzodiazepines (BZD) are drugs with effects on the CNS following their union to the specific location of GABA receptors type A. At low doses, the BZD have sedative and anticonvulsive effects, and as the dose increases it leads to sedation, amnesia and finally unconsciousness. Various studies have been made on the possible interaction between the BZD and the AH H1 with special attention to their effect on the CNS. In some cases these were studies to assess the safety of this association and in others, the aim was different: to see if their joint administration gives a better therapeutic result in pathology related with anxiety syndrome or insomnia. In general it can be said that first generation AH interact with the BZD increasing the sedative effects of the latter. However, second generation AH do not increase these sedative effects, which makes them the chosen drugs to treat allergic rhinitis/rhino-conjunctivitis and urticaria in patients also receiving BZD.

Antihistamines in drivers, aircrew and occupations of risk.

The most commonly occurring allergic diseases can involve a daytime drowsiness associated with the condition itself. The antihistamines used in their treatment can also have central effects and affect certain occupations concerned with risk, road safety and maritime and air navigation. Cognitive tests, experimental studies and epidemiological data recommend avoiding 1st generation antihistamines for people who must drive regularly and/or professions concerned with safety. Although there are no comparative studies on real driving between 1st and 2nd generation antihistamines, in this type of patients there should be a preference for prescribing those with least possible central effect, especially those which are a good substrate for transmembrane transporter pumps such as P-glycoprotein and therefore have a low capacity for crossing the hematoencephalic barrier, thus allowing a broader window for therapy. In this sense, bilastine is a good P-glycoprotein substrate and shows good tolerance at CNS level, in both psychometric trials and real driving test protocols, even at double the dose recommended in the technical file.

Validation of the modified allergic rhinitis and its impact on asthma (ARIA) severity classification in allergic rhinitis children: the PEDRIAL study.

BACKGROUND: A modified allergic rhinitis and its impact on asthma (ARIA) (m-ARIA) criterion to classify the severity of allergic rhinitis (AR) has recently been validated in both treated and untreated adult patients; however, such information in children is lacking. The aim of this study was to validate this m-ARIA severity criterion, which allows for discrimination between moderate and severe AR, in a large pediatric patient sample population. METHODS: The m-ARIA classification categorizes AR severity into mild (no affected items), moderate (1-3 affected items), and severe (all four affected items). We applied this modified criterion to untreated AR pediatric patients aged 6-12 years, through an observational, cross-sectional, and multicenter study. AR symptoms were assessed using the Total Four Symptom Score (T4SS), and the severity was evaluated by both ARIA severity items and visual analogue scale (VAS). RESULTS: Allergic rhinitis pediatric patients (N = 1269) from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent disease; 89.9% had moderate/severe AR using the original ARIA (o-ARIA) classification and 59.5% had moderate, while 30.5% had severe AR using the m-ARIA criterion. Using the m-ARIA, significantly higher T4SS and VAS scores were obtained when comparing severe with moderate AR. CONCLUSIONS: The m-ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among untreated pediatric patients.