Immunoglobulin free light chains in severe asthma patient: Could they be a new biomarker?

BACKGROUND: Increasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease. METHODS: We analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein) was detectable. RESULTS: FLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-λ levels, the FLC-k/FLC-λ ratio displayed remarkable differences between the two groups. A positive correlation between FLC-κ and FLC-λ levels was found. FLC- λ level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-κ /FLC- λ ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization. CONCLUSIONS: Our findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-κ and FLC-k/FLC-λ ratio could be a qualitative indicator for asthma, while FLC-λ levels could be a quantitative indicator for clinical severity parameters.

Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

Cross-cultural adaptation and validation of the RhinAsthma Patient Perspective (RAPP) in Spanish.

OBJECTIVE: the RhinAsthma Patient Perspective (RAPP) is the only available tool to assess HRQoL in daily practice. The aim of this study is to cross-culturally validate the RAPP in Spanish. METHODS: The RAPP was translated into Spanish. Adult patients receiving usual care for asthma and allergic rhinitis (AR) were recruited consecutively and assessed twice with a four-week interval between visits to test the psychometric properties of the questionnaire. RESULTS: 149 patients (62.8% female) with a mean age of 37.7 years completed the study. Exploratory and confirmatory factor analysis confirmed the uni-dimensional structure of the questionnaire. Internal consistency (0.73 at visit 1; 0.87 at visit 2), convergent and discriminant validity (p<.05 at both visits) were satisfactory. Reliability was confirmed by an ICC of 0.69 and a CCC of 0.74. Responsiveness was supported by a significant association with VAS (r=0.28, p<0.003) and ACT (r=-0.35, p<0.01). The minimal clinical difference (MID) value in the analyzed population was 2. CONCLUSIONS: The Spanish version of RAPP was demonstrated to have satisfactory psychometric properties and is a valid, reliable and responsive tool for the assessment of asthma and AR HRQoL in clinical practice.

Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined. OBJECTIVES: To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal. METHODS: In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively. RESULTS: bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P = 0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023). CONCLUSIONS: Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Is aclidinium alone or combined with a LABA a rational choice for symptomatic COPD patients?

BACKGROUND: As emphasized by international recommendations and largely confirmed by clinical experience, long-acting bronchodilators play a central role in the maintenance treatment of chronic obstructive pulmonary disease (COPD) due to their proven efficacy in reducing airflow obstruction and improving symptoms. MAIN BODY: There are some important aspects to define with regard to inhalation therapy for COPD, particularly those concerning the selection criteria and the optimal use of long-acting bronchodilators. First of all, it needs to be determined in which patients and clinical situations monotherapy with one bronchodilator, such as a long-acting muscarinic antagonist (LAMA), should be considered adequate, and in which cases the use of combination therapies, such as the "double bronchodilation" with a LAMA and a long-acting ß2-agonist (LABA), should be preferred. Another critical issue concerns the effect of the frequency of daily administration of inhaled agents on the control of symptoms during the 24 h. COPD symptoms are known to exhibit considerable circadian variability with worsening in the early morning, and a significant proportion of patients have disease-related sleep disorders which can adversely affect their quality of life. The worsening of symptoms in the early morning may be due, at least in part, to a reduction in airway caliber caused by an increased "cholinergic tone" at night. As such, the coverage of nighttime and early morning symptoms is a reasonable therapeutic goal, which can be achieved by many patients using LAMAs such as aclidinium bromide twice daily (BID). Therapeutic adherence is known to be a multifactorial phenomenon that is frequently affected by other aspects than dosing frequency, including the technical features and ease of use of the inhalers. To this end, it should be mentioned that certain new-generation inhalers such as Genuair® have been associated in clinical trials with higher patient preference. CONCLUSION: In this work, in addition to presenting an overview of the main evidence on the efficacy of COPD treatment with the LAMA aclidinium bromide BID, we suggest some selection criteria for the monotherapy with one long-acting bronchodilator or the combination therapy with LAMA and LABA in COPD patients, with particular reference to specific clinical scenarios.

Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement.

Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.

Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

BACKGROUND: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms). AIMS: To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions. METHODS: The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1-2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms. RESULTS: By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction. CONCLUSIONS: This is the first App (iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods.

Work productivity in rhinitis using cell phones: The MASK pilot study.

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.

Asthma management among allergists in Italy: results from a survey.

BACKGROUND: In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy. AIMS AND OBJECTIVES: The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management. METHODS: An anonymous 16 item web questionnaire was available (April-October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy. RESULTS: One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence. CONCLUSIONS: Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.

SANI-Severe Asthma Network in Italy: a way forward to monitor severe asthma.

Even if severe asthma (SA) accounts for 5-10% of all cases of the disease, it is currently a crucial unmet need, owing its difficult clinical management and its high social costs. For this reason several networks, focused on SA have been organized in some countries, in order to select these patients, to recognize their clinical features, to evaluate their adherence, to classify their biological/clinical phenotypes, to identify their eligibility to the new biologic therapies and to quantify the costs of the disease. Aim of the present paper is to describe the ongoing Italian Severe Asthma Network (SANI). Up today 49 centres have been selected, widespread on the national territory. Sharing the same diagnostic protocol, data regarding patients with SA will be collected and processed in a web platform. After their recruitment, SA patients will be followed in the long term in order to investigate the natural history of the disease. Besides clinical data, the cost/benefit evaluation of the new biologics will be verified as well as the search of peculiar biomarker(s) of the disease.

Evaluation of asthma control in the pharmacy: an Italian cross-sectional study.

SUMMARY: Background. In Western countries a large proportion of asthmatic patients remain uncontrolled, despite the availability of effective drugs. An involvement of pharmacies / pharmacists in asthma management has been suggested in guidelines, since this could provide a relevant support. Objective. The present cross-sectional study aimed at assessing the level of asthma control, by using ACT questionnaire, in the community pharmacies in the County of Verona, North East of Italy. Methods. A call for participation was sent by Verona Pharmacists' Association to all the pharmacies located in the Verona municipality. Patients with a medical prescription and an asthma exemption code were recruited in pharmacies. They were asked to fill the ACT questionnaire and to answer some additional questions on asthma treatment, smoke habits and comorbidities. Results. Thirty-seven community pharmacies recruited 239 patients. According to the ACT score, more than 50% of patients had a controlled asthma but 20% of them were totally uncontrolled and 12% were using oral steroid. Only 2.9% of patients had received an asthma action plan. Asthma was intermittent in 17.6% of patients, mild persistent in 13.8%, moderate persistent in 63.1% and severe in 5.4%. Discordance was observed between the self-perceived asthma control and objective parameters, when available. Of note, in the severe asthma group, most patients had an ACT > 20. Conclusion. This is the first Italian pharmacy-based study on asthma control. A better asthma control was recorded in this study in comparison with other trials, but about 50% of patients were insufficiently controlled. The community pharmacies can play a relevant role in the preliminary assessment of asthma control by using easy and not time consuming tools, such as ACT.

Definition, aims, and implementation of GA(2) LEN Urticaria Centers of Reference and Excellence.

BACKGROUND: GA²LEN, the Global Allergy and Asthma European Network, has recently launched a program for the development, interaction, and accreditation of centers of reference and excellence in special areas of allergy embedded in its overall quality management of allergy centers of excellence. The first area chosen is urticaria. Urticaria is a common and debilitating condition and can be a challenge for both patients and treating physicians, especially when chronic. Centers of reference and excellence in urticaria (UCAREs) can help to improve the management of hard-to-treat conditions such as urticaria. AIMS: Here, we describe the aims, the requirements and deliverables, the application process, and the audit and accreditation protocol for GA²LEN UCAREs. RESULTS: The main aims of GA²LEN UCAREs are to provide excellence in urticaria management, to increase the knowledge of urticaria by research and education, and to promote the awareness of urticaria by advocacy activities. To become a certified GA²LEN UCARE, urticaria centers have to apply and fulfill 32 requirements, defined by specific deliverables that are assessed during an audit visit. DISCUSSION AND CONCLUSION: The GA²LEN UCARE program will result in a strong network of urticaria specialists, promote urticaria research, and harmonize and improve urticaria management globally.

Quality-of-life issues in survivors to anaphylactic reactions to drugs.

The aim of this cross-sectional observational study was to explore quality of life and well-being in patients with drug-induced anaphylaxis. Two validated tools were used: the Drug Hypersensitivity Quality-of-Life Questionnaire (DrHy-Q) and the Psychological General Well-Being Index (PGWBI). Sixty-five patients (13 males) underwent data analysis. The mean DrHy-Q score was 62.82 ± 12.1. Mean PGWBI score was 64.03 ± 17.66. DrHy-Q score was significantly correlated with PGWBI total score (r = -0.314; P = 0.011) and with the following domains: Anxiety (r = -0.260; P = 0.036), Depressed mood (r = -0.406; P = 0.001), Positive well-being (r = -0.251; P = 0.004), and General Health (r = -0.352; P = 0.004). Compared with the Italian reference population, patients had a significantly reduced PGWBI total and domain score. Our results highlight for the first time how impaired HRQoL and distress commonly feature in survivors to anaphylactic reactions to drug.