ARIA masterclass 2018: From guidelines to real-life implementation.

Over the past 20 years, ARIA (Allergic Rhinitis and its Impact on Asthma) has developed various guidelines for the treatment of allergic rhinitis (AR) and asthma multimorbidity. Over time, the ARIA initiative has evolved to ensure the highest level of bestpractices adoption in real life settings. It has evolved towards Integrated Care Pathways (ICPs) using mobile technology, and has now entered a new phase in which change management is key to provide an active and healthy life to all AR patients. With that in mind, the first ARIA masterclass was held on 12th September 2018 in Brussels, Belgium. The masterclass aimed at informing clinicians about the principles of change management, providing unbiased education on diagnosis and treatments, sharing the most recent research data on AR and multimorbidities, and creating a snowball effect to increase the adoption of best practices around the globe. This report provides an overview of the ARIA masterclass concept, summarizes the key lectures and discussions, and gives an outline of the future key development.

Angioedema in chronic spontaneous urticaria is underdiagnosed and has a substantial impact: Analyses from ASSURE-CSU.

BACKGROUND: ASSURE-CSU revealed differences in physician and patient reporting of angioedema. This post hoc analysis was conducted to evaluate the actual rate of angioedema in the study population and explore differences between patients with and without angioedema. METHODS: This international observational study assessed 673 patients with inadequately controlled chronic spontaneous urticaria (CSU). Physicians abstracted angioedema data from medical records, which were compared with patient-reported data. Patients in the Yes-angioedema category had angioedema reported in the medical record and a patient-reported source. For those in the No-angioedema category, angioedema was reported in neither the medical record nor a patient-reported source. Those in the Misaligned category had angioedema reported in only one source. Statistical comparisons between Yes-angioedema and No-angioedema categories were conducted for measures of CSU activity, health-related quality of life (HRQoL), productivity and healthcare resource utilization (HCRU). Regression analyses explored the relationship between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for important covariates. RESULTS: Among evaluable patients, 259 (40.3%), 173 (26.9%) and 211 (32.8%) were in the Yes-angioedema, No-angioedema and Misaligned category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU was greater for Yes-angioedema patients than No-angioedema patients. After covariate adjustment, mean DLQI score was significantly higher (indicating worse HRQoL) for patients with angioedema versus no angioedema (9.88 vs 7.27, P < .001). The Misaligned category had similar results with Yes-angioedema on all outcomes. CONCLUSIONS: Angioedema in CSU seems to be under-reported but has significant negative impacts on HRQoL, daily activities, HCRU and work compared with no angioedema.

The burden of chronic spontaneous urticaria is substantial: Real-world evidence from ASSURE-CSU.

BACKGROUND: Chronic spontaneous urticaria (CSU) can be debilitating, difficult to treat, and frustrating for patients and physicians. Real-world evidence for the burden of CSU is limited. The objective of this study was to document disease duration, treatment history, and disease activity, as well as impact on health-related quality of life (HRQoL) and work among patients with inadequately controlled CSU, and to describe its humanistic, societal, and economic burden. METHODS: This international observational study assessed a cohort of 673 adult patients with CSU whose symptoms persisted for ≥12 months despite treatment. Demographics, disease characteristics, and healthcare resource use in the previous 12 months were collected from medical records. Patient-reported data on urticaria and angioedema symptoms, HRQoL, and work productivity and activity impairment were collected from a survey and a diary. RESULTS: Almost 50% of patients had moderate-to-severe disease activity as reported by Urticaria Activity Score. Mean (SD) Dermatology Life Quality Index and Chronic Urticaria Quality of Life Questionnaire scores were 9.1 (6.62) and 33.6 (20.99), respectively. Chronic spontaneous urticaria markedly interfered with sleep and daily activities. Angioedema in the previous 12 months was reported by 66% of enrolled patients and significantly affected HRQoL. More than 20% of patients reported ≥1 hour per week of missed work; productivity impairment was 27%. These effects increased with increasing disease activity. Significant healthcare resources and costs were incurred to treat CSU. CONCLUSIONS: Chronic spontaneous urticaria has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater HRQoL impairments.

A valid option for asthma control: Clinical evidence on efficacy and safety of fluticasone propionate/formoterol combination in a single inhaler.

A good level of asthma control improves the quality of life of asthmatic patients and may prevent future risk in term of exacerbations and decline of pulmonary function. However, in a real-life setting, several factors contribute to generally low compliance to the treatment. A rapid-onset, long-lasting medication with few adverse effects may contribute to improve adherence to therapy, along with an effective patient education and a good physician-patient communication. Many clinical studies demonstrated the comparable efficacy of the new fluticasone propionate/formoterol (FP/F) combination in a single inhaler to other combinations of inhaled corticosteroids and ß2agonists and the superiority of FP/F as compared to its individual components. Also the safety profile of this combination was encouraging in all studies, even at higher doses. By effectively and safely targeting both airway inflammation and smooth muscle dysfunction, the two pathological facets of asthma, and allowing the patient to adapt dose strength, FP/F combination in a single device represents a valid option to improve asthma control in patients with different levels of asthma severity.

Impact of ocular symptoms on quality of life (QoL), work productivity and resource utilisation in allergic rhinitis patients--an observational, cross sectional study in four countries in Europe.

OBJECTIVE: It is hypothesised that the presence of ocular, in addition to nasal, symptoms among patients with allergic rhinitis (AR) results in poorer quality of life, reduced work productivity and increased resource utilisation. This study investigated the impact on quality of life, burden of illness and healthcare resources among 1640 AR patients. METHODS: Data were drawn from an observational cross-sectional study of consulting patients undertaken in May/June 2008 in four European countries. Doctors provided records for the next four to five patients presenting with AR who filled out a self-completion survey which included the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ) and the Pittsburgh Sleep Quality Index (PSQI). Propensity scoring allied to regression-type analysis was used to assess the extra burden associated with ocular symptoms utilising two comparison groups (patients with nasal-only symptoms versus those with nasal and ocular symptoms). The analysis controlled for differences between the groups on confounding variables age, gender, smoking status and co-morbidities. The analysis was conducted twice, once controlling for differences between the groups in nasal severity and once without, recognising that it is not clear whether or not increased nasal severity symptoms are naturally associated with ocular symptoms. The severity of ocular symptoms as opposed to their presence alone was also assessed on outcome measures using regression type methods. RESULTS: A total of 1009 patient records met the inclusion criteria, of whom 69% presented with both ocular and nasal symptoms. The results show that the presence of ocular symptoms reduces quality of life, reduces work productivity and increases resource utilisation irrespective of whether differences in severity of nasal symptoms are accounted for between the comparison groups. Patients with nasal and ocular symptoms require more healthcare consultations. All work-related domains were statistically different, with the presence of ocular symptoms associated with greater impact on work hours missed and impairment while working. For each of the above this was the case regardless of whether or not adjustment was made for nasal severity (both p < 0.05). Patients with nasal and ocular symptoms also record an additional half a day more time off work in the last 3 months as a result of AR (nasal severity unadjusted or adjusted, both p < 0.05). Clinically meaningful differences were found in overall quality of life score as represented by RQLQ, with a mean score increase of 0.6 (nasal severity unadjusted) and 0.5 (nasal severity adjusted) associated with the presence of ocular symptoms (both p < 0.05). With regard to sleep quality, the presence of ocular symptoms was associated with a mean increase in PSQI of 1 when no adjustment was made for nasal severity (p < 0.05). When nasal severity was adjusted for, no significant difference was observed. Similarly, for the number of prescribed medications, when no adjustment was made for nasal severity, patients with ocular symptoms were observed to receive a significantly higher number of AR drugs (+0.19, p < 0.05) whereas with nasal severity adjusted for the difference was +0.17 which was not significant. In addition, with the exception of the number of AR drugs prescribed, for all outcome variables, the severity of ocular symptoms, and not just their presence, had a detrimental impact on the outcome. LIMITATIONS: Since patients were recruited via the physician, the study aim was to represent the consulting population. In addition, it cannot be fully excluded that the likelihood for an individual patient to complete a questionnaire is influenced by differences in patient typology compared with those patients who chose not to complete. Given the geographical dispersion of the sample patients, it may be reasonable to assume possible differences in the intensity of the AR season based on latitude. CONCLUSION: The added presence of ocular symptoms in AR patients suffering with nasal symptoms deteriorates patients' quality of life, leads to greater lost productivity and places higher burden on resource utilisation. Studies are therefore needed to test whether treatment options that address ocular in addition to nasal symptoms will improve quality of life and reduce both direct and indirect resource use associated with AR.

Feasibility and validation of telespirometry in general practice: The Italian "Alliance" study.

INTRODUCTION: At variance from office spirometry, telespirometry has not been tested as a tool for improving the ability of general practitioners (GPs) to manage chronic airway diseases. METHODS: After adequate training, 937 Italian GPs agreed to perform telespirometry in subjects attending their clinics who had risk factors, persistent respiratory symptoms, or a previous diagnosis of asthma or COPD. Each subject performed at least three forced expiratory manoeuvres using a turbine spirometer. Traces were sent by telephone to a Telespirometry Central Office, where they were interpreted by a pulmonary specialist, according to defined criteria. The result was sent in real time to the GP to assist the management of the patient. RESULTS: During 2 years, 20,757 telespirometries were performed, with a mean of 22.2+/-25.2 examinations for each GP. 70% of the tests met the criteria for good or partial co-operation, allowing spirometric abnormalities to be detected in more than 40% of the tracings. The rate of telespirometries that could not be evaluated at all was reasonably low (9.2%). For a subset of the telespirometries, a comparison between acceptability criteria for telespirometry and those recommended for laboratory (ATS) or office spirometry showed that the majority of telespirometries with good co-operation satisfied completely, or with minor deviations, the ATS and Office criteria. CONCLUSIONS: Telespirometry was well accepted by Italian GPs, who obtained acceptable screening traces in a large percentage of subjects. Therefore it might be considered a useful alternative to office spirometry in improving the management of chronic airway diseases by GPs.

Rupatadine in allergic rhinitis and chronic urticaria.

Histamine is the primary mediator involved the pathophysiology of allergic rhinitis and chronic urticaria, and this explains the prominent role that histamine H(1)-receptor antagonists have in the treatment of these disorders. However, histamine is clearly not the only mediator involved in the inflammatory cascade. There is an emerging view that drugs which can inhibit a broader range of inflammatory processes may prove to be more effective in providing symptomatic relief in both allergic rhinitis and chronic urticaria. This is an important consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative which provides a scientific basis for defining what are the desirable properties of an 'ideal' antihistamine. In this review of rupatadine, a newer dual inhibitor of histamine H(1)- and PAF-receptors, we evaluate the evidence for a mechanism of action which includes anti-inflammatory effects in addition to a powerful inhibition of H(1)- and PAF-receptors. We assess this in relation to the clinical efficacy (particularly the speed of onset of action) and safety of rupatadine, and importantly its longer term utility in everyday life. In clinical trials, rupatadine has been shown to be an effective and well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once-daily administration. In comparative clinical trials rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects in preclinical or extensive clinical testing, nor negative significant effects on cognition or psychomotor performance (including a practical driving study). It improved the overall well-being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of histamine H(1)- and PAF-receptors, which has been shown to be an effective and generally well-tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti-inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early- and late-phase inflammatory response, but the clinical relevance of these effects remain to be clarified.

Treatment of exercise-induced asthma, respiratory and allergic disorders in sports and the relationship to doping: Part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN.

AIM: The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. METHODS: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73-88) during the work of the Task Force. To assess the evidence of the literature regarding use of beta(2)-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and beta(2)-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. RESULTS: Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled beta(2)-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled beta(2)-agonists with relationship to sports in healthy individuals is of high evidence, level (1+). CONCLUSIONS: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled beta2-agonists.

Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN.

AIMS: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. METHODS: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. RESULTS: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. CONCLUSIONS: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.

EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).

EAACI/GA2LEN/EDF guideline: management of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).

Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years.

BACKGROUND: The age below 5 years is considered a prudential limit for immunotherapy in view of the possible severity of side-effects. Sublingual immunotherapy (SLIT) seems to be safe, but no study in very young children is available. We performed a safety post-marketing surveillance study in children below 5 years. METHODS: Children aged 3-5 years with respiratory allergy receiving SLIT were followed-up for at least 2 years. A diary card for side-effects was filled by parents at each dose given. Local and systemic side-effects were graded as: mild (no intervention, no dose adjustment), moderate (medical treatment and/or dose reduction), severe (life-threatening/hospitalization/emergency care). The comparative safety of different allergens and regimens was also assessed. RESULTS: One hundred and twenty-six children (mean age 4.2 years, 67 male) were included. Seventy-six (60%) had rhinitis with asthma, 34 (27%) rhinitis only and 16 (13%) only asthma. Immunotherapy was prescribed for mites (62%), grasses (22.2%), Parietaria (11.9%), Alternaria (2.4%) and olive (1.5%). Eighteen children underwent an accelerated build-up. The total number of doses was about 39,000. Nine side-effects were reported in seven children (5.6% patients and 0.2/1000 doses). Two episodes of oral itching and one of abdominal pain were mild. Six gastrointestinal side-effects were controlled by reducing the dose. All side-effects occurred during up-dosing phase. No difference in terms of safety among the allergens used was observed. CONCLUSION: SLIT is safe also in children under the age of 5 years.

Effects of budesonide and fluticasone propionate in a placebo-controlled study on symptoms and quality of life in seasonal allergic rhinitis.

BACKGROUND: Intranasal glucocorticosteroids are effective in seasonal allergic rhinitis. This study compared the efficacy of budesonide (Rhinocort Turbuhaler) and fluticasone propionate (Flixonase) in this respect. METHODS: Patients (n = 280) were randomized to receive budesonide, 140 microg (delivered dose) once daily, fluticasone, 200 microg once daily, or matching placebos for 5 weeks. The primary efficacy variable was the change in combined nasal symptom (nasal blockage, runny nose, sneezing) scores. Quality of life was measured in 121 patients by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the Short-form Health Survey (SF-36). RESULTS: Both steroids significantly reduced combined nasal symptoms, compared with placebo. There was no significant difference between the two treatments. Substantial or total symptom control was achieved in 89.9% of the budesonide-treated patients, compared with 88.7% with fluticasone and 42.7% with placebo. Four of the five domains of the RQLQ were significantly improved with budesonide, whereas with fluticasone only two domains were improved. Budesonide significantly improved scores in five out of eight domains of the SF-36, whereas no domains were improved with fluticasone. CONCLUSION: There was no significant difference in efficacy between budesonide and fluticasone in this study. However, greater improvements in quality of life were seen with budesonide than with fluticasone.

A double-blind, placebo-controlled study on the diagnostic accuracy of an electrodermal test in allergic subjects.

BACKGROUND: Many unconventional diagnostic procedures based on bioelectrical skin responses are presently widely used for allergic diseases, but rigorous experimental evaluations of their accuracy are still lacking. AIM: We assessed whether an electrodermal device can correctly diagnose respiratory allergy. METHODS: The diagnostic accuracy of the electrodermal device was assessed in double-blind fashion in 72 allergic patients and 28 healthy volunteers. A random sequence of substances in sealed vials, including histamine, allergens, immunoglobulins at various dilutions and physiological saline, were tested in duplicate in each subject. RESULTS: A wide variability of the measurements was found in most patients irrespective of their allergy status and of the substance tested. Allergic patients showed more negative skin electrical response at the second trial, compared to normal controls, independent of the tested substance. No significant difference in skin electrical response between allergens and negative controls could be detected. CONCLUSION: We conclude that the studied bioelectrical method, under blind testing, cannot correctly detect respiratory allergy.